Volume 12, Issue 15, May 15, 2020

CDC Science Clips: Volume 12, Issue 15, May 15, 2020

Science Clips is produced weekly to enhance awareness of emerging scientific knowledge for the public health community. Each article features an Altmetric Attention scoreexternal icon to track social and mainstream media mentions!

This week, Science Clips is pleased to collaborate with CDC Vital Signs by featuring scientific articles from the latest issue on Postpartum Depressive Symptoms and Provider Discussions About Perinatal Depression — United States, 2018. The articles marked with an asterisk are general review articles which may be of particular interest to clinicians and public health professionals seeking background information in this area.

  1. CDC Vital Signs
    • Reproductive Health - Postpartum Depression
      1. *Postpartum depression: current status and future directionsexternal icon
        O'Hara MW, McCabe JE.
        Annu Rev Clin Psychol. 2013 ;9:379-407.
        Postpartum depression (PPD) is a common and serious mental health problem that is associated with maternal suffering and numerous negative consequences for offspring. The first six months after delivery may represent a high-risk time for depression. Estimates of prevalence range from 13% to 19%. Risk factors mirror those typically found with major depression, with the exception of postpartum-specific factors such as sensitivity to hormone changes. Controlled trials of psychological interventions have validated a variety of individual and group interventions. Medication often leads to depression improvement, but in controlled trials there are often no significant differences in outcomes between patients in the medication condition and those in placebo or active control conditions. Reviews converge on recommendations for particular antidepressant medications for use while breastfeeding. Prevention of PPD appears to be feasible and effective. Finally, there is a growing movement to integrate mental health screening into routine primary care for pregnant and postpartum women and to follow up this screening with treatment or referral and with follow-up care. Research and clinical recommendations are made throughout this review.

      2. Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is vital to identify best treatments for optimal maternal, infant, and family outcomes. New understanding of PPD pathophysiology and emerging therapeutics offer the potential for new ways to add to current medications, somatic treatments, and evidence-based psychotherapy. The benefits and potential harms of treatment, including during breastfeeding, are presented.

      3. ACOG Committee Opinion No. 757: Screening for perinatal depressionexternal icon
        American College of Obstetricians and Gynecologists .
        Obstet Gynecol. 2018 Nov;132(5):e208-e212.
        Perinatal depression, which includes major and minor depressive episodes that occur during pregnancy or in the first 12 months after delivery, is one of the most common medical complications during pregnancy and the postpartum period, affecting one in seven women. It is important to identify pregnant and postpartum women with depression because untreated perinatal depression and other mood disorders can have devastating effects. Several screening instruments have been validated for use during pregnancy and the postpartum period. The American College of Obstetricians and Gynecologists recommends that obstetrician-gynecologists and other obstetric care providers screen patients at least once during the perinatal period for depression and anxiety symptoms using a standardized, validated tool. It is recommended that all obstetrician-gynecologists and other obstetric care providers complete a full assessment of mood and emotional well-being (including screening for postpartum depression and anxiety with a validated instrument) during the comprehensive postpartum visit for each patient. If a patient is screened for depression and anxiety during pregnancy, additional screening should then occur during the comprehensive postpartum visit. There is evidence that screening alone can have clinical benefits, although initiation of treatment or referral to mental health care providers offers maximum benefit. Therefore, clinical staff in obstetrics and gynecology practices should be prepared to initiate medical therapy, refer patients to appropriate behavioral health resources when indicated, or both.

      4. Massachusetts Child Psychiatry Access Program for Moms: Utilization and quality assessmentexternal icon
        Byatt N, Straus J, Stopa A, Biebel K, Mittal L, Moore Simas TA.
        Obstet Gynecol. 2018 Aug;132(2):345-353.
        OBJECTIVE: To describe the utilization and quality assessment of a population-based program to help health care providers address mental health and substance use disorders among pregnant and postpartum women, the Massachusetts Child Psychiatry Access Program for Moms (MCPAP for Moms). METHODS: The Massachusetts Child Psychiatry Access Program for Moms builds health care providers' capacity to address perinatal mental health and substance use disorders through 1) trainings and toolkits, 2) telephonic access to perinatal psychiatric consultation, and 3) facilitating referral to community resources. Clinical encounter data were collected during telephone consultations. Focus groups were conducted with health care providers and staff from enrolled practices. In-depth interviews were conducted with patients served by the practices that participated in the focus groups. Transcribed interviews were analyzed by two researchers using an iterative, interpretive process with a grounded theory framework. RESULTS: In the first 3.5 years, MCPAP for Moms enrolled 145 obstetric practices, conducted 145 trainings for 1,174 health care providers, and served 3,699 women. Of telephone consultations provided, 42% were with obstetric care providers-midwives and 16% with psychiatrists. Health care providers perceived that MCPAP for Moms facilitates health care providers detecting and addressing depression and women disclosing symptoms, seeking help, and initiating treatment. Obstetric practices reported that they need additional support to more proactively address and further improve depression care. CONCLUSION: The high volume of encounters, sustained utilization over 3.5 years, and qualitative themes identified from health care providers and patients demonstrate that MCPAP for Moms is a feasible, acceptable, and sustainable approach to increasing access to evidence-based treatments for perinatal mental health and substance use disorders on a population-based level.

      5. Interventions to prevent perinatal depression: US Preventive Services Task Force Recommendation Statementexternal icon
        Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, Davidson KW, Doubeni CA, Epling JW, Grossman DC, Kemper AR, Kubik M, Landefeld CS, Mangione CM, Silverstein M, Simon MA, Tseng CW, Wong JB.
        Jama. 2019 Feb 12;321(6):580-587.
        Importance: Perinatal depression, which is the occurrence of a depressive disorder during pregnancy or following childbirth, affects as many as 1 in 7 women and is one of the most common complications of pregnancy and the postpartum period. It is well established that perinatal depression can result in adverse short- and long-term effects on both the woman and child. Objective: To issue a new US Preventive Services Task Force (USPSTF) recommendation on interventions to prevent perinatal depression. Evidence Review: The USPSTF reviewed the evidence on the benefits and harms of preventive interventions for perinatal depression in pregnant or postpartum women or their children. The USPSTF reviewed contextual information on the accuracy of tools used to identify women at increased risk of perinatal depression and the most effective timing for preventive interventions. Interventions reviewed included counseling, health system interventions, physical activity, education, supportive interventions, and other behavioral interventions, such as infant sleep training and expressive writing. Pharmacological approaches included the use of nortriptyline, sertraline, and omega-3 fatty acids. Findings: The USPSTF found convincing evidence that counseling interventions, such as cognitive behavioral therapy and interpersonal therapy, are effective in preventing perinatal depression. Women with a history of depression, current depressive symptoms, or certain socioeconomic risk factors (eg, low income or young or single parenthood) would benefit from counseling interventions and could be considered at increased risk. The USPSTF found adequate evidence to bound the potential harms of counseling interventions as no greater than small, based on the nature of the intervention and the low likelihood of serious harms. The USPSTF found inadequate evidence to assess the benefits and harms of other noncounseling interventions. The USPSTF concludes with moderate certainty that providing or referring pregnant or postpartum women at increased risk to counseling interventions has a moderate net benefit in preventing perinatal depression. Conclusions and Recommendation: The USPSTF recommends that clinicians provide or refer pregnant and postpartum persons who are at increased risk of perinatal depression to counseling interventions. (B recommendation).

      6. Incorporating recognition and management of perinatal depression into pediatric practiceexternal icon
        Earls MF, Yogman MW, Mattson G, Rafferty J.
        Pediatrics. 2019 Jan;143(1).
        Perinatal depression (PND) is the most common obstetric complication in the United States. Even when screening results are positive, mothers often do not receive further evaluation, and even when PND is diagnosed, mothers do not receive evidence-based treatments. Studies reveal that postpartum depression (PPD), a subset of PND, leads to increased costs of medical care, inappropriate medical treatment of the infant, discontinuation of breastfeeding, family dysfunction, and an increased risk of abuse and neglect. PPD, specifically, adversely affects this critical early period of infant brain development. PND is an example of an adverse childhood experience that has potential long-term adverse health complications for the mother, her partner, the infant, and the mother-infant dyad. However, PND can be treated effectively, and the stress on the infant can be buffered. Pediatric medical homes should coordinate care more effectively with prenatal providers for women with prenatally diagnosed maternal depression; establish a system to implement PPD screening at the 1-, 2-, 4-, and 6-month well-child visits; use community resources for the treatment and referral of the mother with depression; and provide support for the maternal-child (dyad) relationship, including breastfeeding support. State chapters of the American Academy of Pediatrics, working with state departments of public health, public and private payers, and maternal and child health programs, should advocate for payment and for increased training for PND screening and treatment. American Academy of Pediatrics recommends advocacy for workforce development for mental health professionals who care for young children and mother-infant dyads, and for promotion of evidence-based interventions focused on healthy attachment and parent-child relationships.

      7. Depression and treatment among U.S. pregnant and nonpregnant women of reproductive age, 2005-2009external icon
        Ko JY, Farr SL, Dietz PM, Robbins CL.
        J Womens Health (Larchmt). 2012 Aug;21(8):830-6.
        BACKGROUND: Depression is often undiagnosed and untreated. It is not clear if differences exist in the diagnosis and treatment of depression among pregnant and nonpregnant women. We sought to estimate the prevalence of undiagnosed depression, treatment by modality, and treatment barriers by pregnancy status among U.S. reproductive-aged women. METHODS: We identified 375 pregnant and 8,657 nonpregnant women 18-44 years of age who met criteria for past-year major depressive episode (MDE) from 2005-2009 nationally representative data. Chi-square statistics and adjusted prevalence ratios (aPR) were calculated. RESULTS: MDE in pregnant women (65.9%) went undiagnosed more often than in nonpregnant women (58.6%) (aPR 1.1, 95% confidence interval [CI] 1.0-1.3). Half of depressed pregnant (49.6%) and nonpregnant (53.7%) women received treatment (aPR 1.0, 95% CI 0.90-1.1), with prescription medication the most common form for both pregnant (39.6%) and nonpregnant (47.4%) women. Treatment barriers did not differ by pregnancy status and were cost (54.8%), opposition to treatment (41.7%), and stigma (26.3%). CONCLUSIONS: Pregnant women with MDE were no more likely than nonpregnant women to be diagnosed with or treated for their depression.

      8. Trends in postpartum depressive symptoms - 27 states, 2004, 2008, and 2012external icon
        Ko JY, Rockhill KM, Tong VT, Morrow B, Farr SL.
        MMWR Morb Mortal Wkly Rep. 2017 Feb 17;66(6):153-158.
        Postpartum depression is common and associated with adverse infant and maternal outcomes (e.g., lower breastfeeding initiation and duration and poor maternal and infant bonding) (1-3). A developmental Healthy People 2020 objective is to decrease the proportion of women delivering a live birth who experience postpartum depressive symptoms (PDS).* To provide a baseline for this objective, CDC sought to describe self-reported PDS overall, by reporting state, and by selected sociodemographic factors, using 2004, 2008, and 2012 data from the Pregnancy Risk Assessment Monitoring System (PRAMS). A decline in the prevalence of PDS was observed from 2004 (14.8%) to 2012 (9.8%) among 13 states with data for all three periods (p<0.01). Statistically significant (p<0.05) declines in PDS prevalence were observed for eight states, and no significant changes were observed for five states. In 2012, the overall PDS prevalence was 11.5% for 27 states and ranged from 8.0% (Georgia) to 20.1% (Arkansas). By selected characteristics, PDS prevalence was highest among new mothers who 1) were aged </=19 years or 20-24 years, 2) were of American Indian/Alaska Native or Asian/Pacific Islander race/ethnicity, 3) had </=12 years of education, 4) were unmarried, 5) were postpartum smokers, 6) had three or more stressful life events in the year before birth, 7) gave birth to term, low-birthweight infants, and 8) had infants requiring neonatal intensive care unit admission at birth. Although the study did not investigate reasons for the decline, better recognition of risk factors for depression and improved screening and treatment before and during pregnancy, including increased use of antidepressants, might have contributed to the decline. However, more efforts are needed to reduce PDS prevalence in certain states and subpopulations of women. Ongoing surveillance and activities to promote appropriate screening, referral, and treatment are needed to reduce PDS among U.S. women.

      9. IMPORTANCE: Depression is a source of substantial burden for individuals and their families, including women during the pregnant and postpartum period. OBJECTIVE: To systematically review the benefits and harms of depression screening and treatment, and accuracy of selected screening instruments, for pregnant and postpartum women. Evidence for depression screening in adults in general is available in the full report. DATA SOURCES: MEDLINE, PubMed, PsycINFO, and the Cochrane Collaboration Registry of Controlled Trials through January 20, 2015; references; and government websites. STUDY SELECTION: English-language trials of benefits and harms of depression screening, depression treatment in pregnant and postpartum women with screen-detected depression, and diagnostic accuracy studies of depression screening instruments in pregnant and postpartum women. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles and extracted data from fair- and good-quality studies. Random-effects meta-analysis was used to estimate the benefit of cognitive behavioral therapy (CBT) in pregnant and postpartum women. MAIN OUTCOMES AND MEASURES: Depression remission, prevalence, symptoms, and related measures of depression recovery or response; sensitivity and specificity of selected screening measures to detect depression; and serious adverse effects of antidepressant treatment. RESULTS: Among pregnant and postpartum women 18 years and older, 6 trials (n = 11,869) showed 18% to 59% relative reductions with screening programs, or 2.1% to 9.1% absolute reductions, in the risk of depression at follow-up (3-5 months) after participation in programs involving depression screening, with or without additional treatment components, compared with usual care. Based on 23 studies (n = 5398), a cutoff of 13 on the English-language Edinburgh Postnatal Depression Scale demonstrated sensitivity ranging from 0.67 (95% CI, 0.18-0.96) to 1.00 (95% CI, 0.67-1.00) and specificity consistently 0.87 or higher. Data were sparse for Patient Health Questionnaire instruments. Pooled results for the benefit of CBT for pregnant and postpartum women with screen-detected depression showed an increase in the likelihood of remission (pooled relative risk, 1.34 [95% CI, 1.19-1.50]; No. of studies [K] = 10, I2 = 7.9%) compared with usual care, with absolute increases ranging from 6.2% to 34.6%. Observational evidence showed that second-generation antidepressant use during pregnancy may be associated with small increases in the risks of potentially serious harms. CONCLUSIONS AND RELEVANCE: Direct and indirect evidence suggested that screening pregnant and postpartum women for depression may reduce depressive symptoms in women with depression and reduce the prevalence of depression in a given population. Evidence for pregnant women was sparser but was consistent with the evidence for postpartum women regarding the benefits of screening, the benefits of treatment, and screening instrument accuracy.

      10. Consequences of maternal postpartum depression: A systematic review of maternal and infant outcomesexternal icon
        Slomian J, Honvo G, Emonts P, Reginster JY, Bruyere O.
        Womens Health (Lond). 2019 Jan-Dec;15:1745506519844044.
        INTRODUCTION: The postpartum period represents the time of risk for the emergence of maternal postpartum depression. There are no systematic reviews of the overall maternal outcomes of maternal postpartum depression. The aim of this study was to evaluate both the infant and the maternal consequences of untreated maternal postpartum depression. METHODS: We searched for studies published between 1 January 2005 and 17 August 2016, using the following databases: MEDLINE via Ovid, PsycINFO, and the Cochrane Pregnancy and Childbirth Group trials registry. RESULTS: A total of 122 studies (out of 3712 references retrieved from bibliographic databases) were included in this systematic review. The results of the studies were synthetized into three categories: (a) the maternal consequences of postpartum depression, including physical health, psychological health, relationship, and risky behaviors; (b) the infant consequences of postpartum depression, including anthropometry, physical health, sleep, and motor, cognitive, language, emotional, social, and behavioral development; and (c) mother-child interactions, including bonding, breastfeeding, and the maternal role. DISCUSSION: The results suggest that postpartum depression creates an environment that is not conducive to the personal development of mothers or the optimal development of a child. It therefore seems important to detect and treat depression during the postnatal period as early as possible to avoid harmful consequences.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Use of national asthma guidelines by allergists and pulmonologists: A national surveyexternal icon
        Cloutier MM, Akinbami LJ, Salo PM, Schatz M, Simoneau T, Wilkerson JC, Diette G, Elward KS, Fuhlbrigge A, Mazurek JM, Feinstein L, Williams S, Zeldin DC.
        J Allergy Clin Immunol Pract. 2020 Apr 25.
        BACKGROUND: Little is known about specialist-specific variations in guideline agreement and adoption. OBJECTIVE: To assess similarities and differences between allergists and pulmonologists in adherence to cornerstone components of the National Asthma Education and Prevention Program's Third Expert Panel Report (EPR-3). METHODS: Self-reported guideline agreement, self-efficacy and adherence were assessed in allergists (n=134) and pulmonologists (n=99) in the 2012 National Asthma Survey of Physicians. Multivariate models were used to assess if physician and practice characteristics explained bivariate associations between specialty and "almost always" adhering to recommendations (i.e., >/=75% of the time). RESULTS: Allergists and pulmonologists reported high guideline self-efficacy and moderate guideline agreement. Both groups "almost always" assessed asthma control (66.2%, SE 4.3), assessed school/work asthma triggers (71.3%, SE 3.9), and endorsed inhaled corticosteroids use (95.5%, SE 2.0). Repeated assessment of inhaler technique, use of asthma action/treatment plans and spirometry were lower (39.7%, SE 4.0, 30.6%, SE 3.6, 44.7%, SE 4.1, respectively). Compared to pulmonologists, more allergists almost always performed spirometry (56.6% vs 38.6%, P=.06), asked about nighttime awakening (91.9% vs 76.5%, P=.03) and ED visits (92.2% vs 76.5%, P=0.03), assessed home triggers (70.5% vs 52.6%, P=.06) and performed allergy testing (61.8% vs 21.3%, P<0.001). In multivariate analyses, practice-specific characteristics explained differences except for allergy testing. CONCLUSIONS: Overall, allergists and pulmonologists adhere to the asthma guidelines with notable exceptions, including asthma action plan use and inhaler technique assessment. Recommendations with low implementation offer opportunities for further exploration and could serve as targets for increasing guideline uptake.

      2. Ocular melanoma incidence rates and trends in the United States, 2001-2016external icon
        Culp MB, Benard V, Dowling NF, King J, Lu H, Rao C, Scott LC, Wilson R, Wu M.
        Eye (Lond). 2020 Apr 29.

      3. Prevalence of cigarette smoking among patients with different histological types of kidney cancerexternal icon
        Gansler T, Fedewa SA, Flanders WD, Pollack LA, Siegel DA, Jemal A.
        Cancer Epidemiol Biomarkers Prev. 2020 May 1.
        BACKGROUND: Cigarette smoking is causally linked to renal cell carcinoma (RCC). However, associations for individual RCC histologies are not well-described. Newly-available data on tobacco use from population-based cancer registries allow characterization of associations with individual RCC types. METHODS: We analyzed data for 30,282 RCC cases from 8 states that collected tobacco use information for a National Program of Cancer Registry project. We compared the prevalence and adjusted prevalence ratios (aPR) of cigarette smoking (current vs never, former vs never) among individuals diagnosed between 2011 and 2016 with clear cell RCC, papillary RCC, chromophobe RCC, renal collecting duct/medullary carcinoma, cyst-associated RCC, and unclassified RCC. RESULTS: Of 30,282 RCC patients, 50.2% were current or former cigarette smokers. By histology, proportions of current or formers smokers ranged from 38% in patients with chromophobe carcinoma to 61.9% in those with collecting duct/medullary carcinoma. The aPRs (with the most common histology, clear cell RCC, as referent group) for current and former cigarette smoking among chromophobe RCC cases (4.9% of our analytic sample) were 0.58 (95% CI, 0.50-0.67) and 0.88 (95% CI, 0.81-0.95), respectively. Other aPRs were slightly increased (papillary RCC and unclassified RCC, current smoking only), slightly decreased (unclassified RCC, former smoking only) or not significantly different from 1.0 (collecting duct/medullary carcinoma and cyst-associated RCC). CONCLUSIONS: Compared with other RCC histological types, chromophobe RCC has a weaker (if any) association with smoking. IMPACT: This study shows the value of population-based cancer registries' collection of smoking data, especially for epidemiological investigation of rare cancers.

      4. Access to cardiovascular disease and hypertension medicines in developing countries: An analysis of essential medicine lists, price, availability, and affordabilityexternal icon
        Husain MJ, Datta BK, Kostova D, Joseph KT, Asma S, Richter P, Jaffe MG, Kishore SP.
        J Am Heart Assoc. 2020 Apr 25:e015302.
        Background Access to medicines is important for long-term care of cardiovascular diseases and hypertension. This study provides a cross-country assessment of availability, prices, and affordability of cardiovascular disease and hypertension medicines to identify areas for improvement in access to medication treatment. Methods and Results We used the World Health Organization online repository of national essential medicines lists (EMLs) for 53 countries to transcribe the information on the inclusion of 12 cardiovascular disease/hypertension medications within each country's essential medicines list. Data on availability, price, and affordability were obtained from 84 surveys in 59 countries that used the World Health Organization's Health Action International survey methodology. We summarized and compared the indicators across lowest-price generic and originator brand medicines in the public and private sectors and by country income groups. The average availability of the select medications was 54% in low- and lower-middle-income countries and 60% in high- and upper-middle-income countries, and was higher for generic (61%) than brand medicines (41%). The average patient median price ratio was 80.3 for brand and 16.7 for generic medicines and was higher for patients in low- and lower-middle-income countries compared with high- and upper-middle-income countries across all medicine categories. The costs of 1 month's antihypertensive medications were, on average, 6.0 days' wage for brand medicine and 1.8 days' wage for generics. Affordability was lower in low- and lower-middle-income countries than high- and upper-middle-income countries for both brand and generic medications. Conclusions The availability and accessibility of pharmaceuticals is an ongoing challenge for health systems. Low availability and high costs are major barriers to the use of and adherence to essential cardiovascular disease and antihypertensive medications worldwide, particularly in low- and lower-middle-income countries.

      5. Short self-reported sleep duration among caregivers and non-caregivers in 2016external icon
        Liu Y, Wheaton AG, Edwards VJ, Xu F, Greenlund KJ, Croft JB.
        Sleep Health. 2020 Apr 21.
        INTRODUCTION: Caregiving, providing regular care or assistance to family members or friends with health problems or disabilities, may affect caregivers' sleep. This study examined self-reported short sleep duration by caregiving status among US adults. METHODS: Data of 114,496 respondents aged >/=18 years in 19 states, the District of Columbia, and Puerto Rico from the 2016 Behavioral Risk Factor Surveillance System were analyzed. Prevalence of short sleep duration (<7 hours per 24-hour period) by caregiving status was calculated, and adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) were derived from a multivariable logistic regression model with adjustment for potential covariates. RESULTS: Nearly 1 of 5 adults reported caregiving within the past month. A higher prevalence of short sleep duration was reported among caregivers (39.5%) than among non-caregivers (34.2%, adjusted PR [95% CI] = 1.12 [1.06-1.19]). Caregivers who reported prolonged caregiving (>/=5 years) reported a higher prevalence of short sleep duration than those with <2 years of caregiving. Similarly, caregivers who provided 20-39 hours of caregiving per week reported a higher prevalence of short sleep duration than those with <20 hours caregiving per week. CONCLUSIONS: Caregivers had a higher prevalence of short sleep duration than noncaregivers. Providing information and community-based resources and supports for caregiving may minimize caregiver stress and improve sleep particularly for those with prolonged or more intense caregiving.

      6. Prevalence of self-reported hypertension and antihypertensive medication use by county and rural-urban classification - United States, 2017external icon
        Samanic CM, Barbour KE, Liu Y, Wang Y, Fang J, Lu H, Schieb L, Greenlund KJ.
        MMWR Morb Mortal Wkly Rep. 2020 May 8;69(18):533-539.
        In 2017, approximately one in three U.S. adults reported having been told by a health care professional that they had high blood pressure (hypertension) (1). Although hypertension prevalence is well documented at national and state levels, less is known about rural-urban variation and county-level prevalence. To examine prevalence of self-reported hypertension and antihypertensive medication use by rural-urban classification and county, CDC analyzed data reported by 442,641 adults aged >/=18 years who participated in the 2017 Behavioral Risk Factor Surveillance System (BRFSS). In rural (noncore) areas, 40.0% (unadjusted prevalence) of adults reported having hypertension, whereas in the most urban (large central metro) areas, 29.4% reported having hypertension. Age-standardized hypertension prevalence was significantly higher in the most rural areas, compared with the most urban areas within nearly all categories of age, sex, and other demographic characteristics. Model-based hypertension prevalence across counties ranged from 18.0% to 55.0% and was highest in Southeastern* and Appalachian(dagger) counties. Model-based county-level prevalence of antihypertensive medication use among adults with hypertension ranged from 54.3% to 84.7%. Medication use also was higher in rural areas compared with use in most urban areas, with prevalence highest in Southeastern and Appalachian counties as well as counties in the Dakotas and Nebraska. CDC is working with states to enhance hypertension awareness and management through a strategy of team-based care that involves physicians, nurses, pharmacists, dietitians, and community health workers. The increased use of telemedicine to support this strategy might improve access to care among underserved populations.

      7. INTRODUCTION: Estimates of the size and characteristics of the US haemophilia population are needed for healthcare planning and resource needs assessment. A network of comprehensive haemophilia treatment centres (HTCs) located throughout the United States receives federal support for diagnosis and management of haemophilia and other rare bleeding disorders. AIM: Estimate the incidence and prevalence of haemophilia among US males using the HTC network. METHODS: During the period 2012-2018, de-identified surveillance data were collected on all males who visited an HTC that included year of birth, gender, race, Hispanic ethnicity, residence zip code, haemophilia type and severity. Data from all patients were used to calculate period prevalence by haemophilia type, severity and state of residence. Data from a subset of patients born 1995-2014 were used to estimate incidence rates over the 20-year period. RESULTS: During the period, 21 748 males with haemophilia visited the HTCs resulting in an age-adjusted prevalence of 15.7 cases per 100 000 males (12 for haemophilia A and 3.7 for haemophilia B). Prevalence was higher among whites (15.1) than blacks (12.4) or Hispanics of either race (12.4). State-specific prevalence varied from 1.6 to 23.3 cases per 100 000. Based on 9587 males born during the index period, the average haemophilia incidence was 1 case per 4334 live male births. CONCLUSION: Based on these data, we estimate that there are between 29 761 and 32 985 males with haemophilia living in the United States today, the majority of whom receive comprehensive care in specialized clinical centres.

      8. AIMS: To examine the association of HbA(1c) and glucose levels with incident diabetic retinopathy according to black African or white European ancestry. METHODS: In this retrospective cohort study of 202 500 US Veterans with diabetes (2000-2014), measures included HbA(1c) , outpatient random serum/plasma glucose, and incident retinopathy [conversion from negative to ≥2 positive evaluations (ICD-9 codes), without a subsequent negative]. RESULTS: At baseline, the study population had a mean age of 59.3 years, their mean BMI was 31.9 kg/m(2) , HbA(1c) level was 57 mmol/mol (7.4%) and glucose level was 8.8 mmol/l, and 77% were of white European ancestry (white individuals) and 21% of black African ancestry (black individuals). HbA(1c) was 0.3% higher in black vs white individuals (P < 0.001), adjusting for baseline age, sex, BMI, estimated glomerular filtration rate (eGFR), haemoglobin, and average systolic blood pressure and glucose. Over 11 years, incident retinopathy occurred in 9% of black and 7% of white individuals, but black individuals had higher HbA(1c) , glucose, and systolic blood pressure (all P < 0.001); adjusted for these factors, incident retinopathy was reduced in black vs white individuals (P < 0.001). The population incidence of retinopathy (7%) was associated with higher mean baseline HbA(1c) in individuals with black vs white ancestry [63 mmol/mol (7.9%) vs 58 mmol/mol (7.5%); P < 0.001)], but with similar baseline glucose levels (9.0 vs 9.0 mmol/l; P = 0.660, all adjusted for baseline age, sex and BMI). CONCLUSIONS: Since retinopathy occurs at higher HbA(1c) levels in black people for a given level of average plasma glucose, strategies may be needed to individualize the interpretation of HbA(1c) measurements.

      9. Screening for colorectal cancer in asymptomatic average-risk adultsexternal icon
        Wilt TJ, Crandall CJ, Hicks LA, Mustafa RA, Qaseem A.
        Ann Intern Med. 2020 Apr 7;172(7):508-509.

    • Communicable Diseases
      1. Distinct cellular immune properties in cerebrospinal fluid are associated with cognition in HIV-infected individuals initiating antiretroviral therapyexternal icon
        Amundson B, Lai L, Mulligan MJ, Xu Y, Zheng Z, Kundu S, Lennox JL, Waldrop-Valverde D, Franklin D, Swaims-Kohlmeier A, Letendre SL, Anderson AM.
        J Neuroimmunol. 2020 Apr 27;344:577246.
        We examined the relationship between CSF immune cells and neurocognition and neuronal damage in HIV+ individuals before and after initiating antiretroviral therapy. Multivariate analysis at baseline indicated that greater CD4+ T cell abundance was associated with better cognition (p = .017), while higher CSF HIV RNA was associated with increased neuronal damage (p = .014). Following 24 weeks of antiretroviral therapy, CD8+ T cells, HLA-DR expressing CD4+ and CD8+ T cells, B cells, NK cells, and non-classical monocyte percentage decreased in CSF. Female gender was negatively associated with cognitive performance over time, as was higher percentage of HLA-DR expressing CD8+ T cells at baseline.

      2. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facilityexternal icon
        Arons MM, Hatfield KM, Reddy SC, Kimball A, James A, Jacobs JR, Taylor J, Spicer K, Bardossy AC, Oakley LP, Tanwar S, Dyal JW, Harney J, Chisty Z, Bell JM, Methner M, Paul P, Carlson CM, McLaughlin HP, Thornburg N, Tong S, Tamin A, Tao Y, Uehara A, Harcourt J, Clark S, Brostrom-Smith C, Page LC, Kay M, Lewis J, Montgomery P, Stone ND, Clark TA, Honein MA, Duchin JS, Jernigan JA.
        N Engl J Med. 2020 Apr 24.
        BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents. METHODS: We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic. RESULTS: Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide. CONCLUSIONS: Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.

      3. Mortality among patients with chronic hepatitis B infection: The Chronic Hepatitis Cohort Study (CHeCS)external icon
        Bixler D, Zhong Y, Ly KN, Moorman AC, Spradling PR, Teshale EH, Rupp LB, Gordon SC, Boscarino JA, Schmidt MA, Daida YG, Holmberg SD.
        Clin Infect Dis. 2019 Mar 5;68(6):956-963.
        BACKGROUND: According to death certificates, approximately 1800 persons die from hepatitis B annually in the United States; however, this figure may underestimate true mortality from chronic hepatitis B (CHB). METHODS: We analyzed data from CHB patients seen in the Chronic Hepatitis Cohort Study (CHeCS) between 1 January 2006 and 31 December 2013. We compared overall and cause-specific death rates and mean ages at death between CHeCS CHB decedents and U.S. decedents from the Multiple Cause of Death (MCOD) file. RESULTS: Of 4389 CHB patients followed for a mean of 5.38 years, 492 (11%) CHB patients died after a mean follow-up of 3.00 years. Compared to survivors, decedents were older, more likely to be White (40.6%), African-American (27.1%), or male (74.2%); and more likely to have had cirrhosis (59.8%), diabetes (27.2%), alcohol abuse (17.7%), hepatocellular carcinoma (17.5%), or a liver transplant (5.7%); whereas survivors were more likely to be Asian (48.8%; all P < .001). CHB patients died at an average age of 59.8 years-14 years younger than the general U.S. population-and at higher rates for all causes (relative risk [RR] = 1.85, 95% confidence interval [CI], 1.851-1.857) and liver-related causes (RR = 15.91, 95% CI, 15.81-16.01). Only 19% of CHB decedents and 40% of those dying of liver disease had hepatitis B reported on their death certificates. CONCLUSIONS: Compared to the general population, CHB patients die at younger ages and higher rates from all causes and liver-related causes. Death certificates underrepresent the true mortality from CHB.

      4. The rollout of Community ART Refill Groups in Zimbabwe: a qualitative evaluationexternal icon
        Bochner AF, Meacham E, Mhungu N, Manyanga P, Petracca F, Muserere C, Gonese G, Makunike B, Wazara B, Gwanzura C, Nyika P, Levine R, Mutasa-Apollo T, Balachandra S, Wiktor SZ.
        J Int AIDS Soc. 2019 Aug;22(8):e25393.
        INTRODUCTION: Community ART Refill Groups (CARGs) are an antiretroviral therapy (ART) delivery model where clients voluntarily form into groups, and a group member visits the clinic to collect ART for all group members. In late 2016, Zimbabwe began a nationwide rollout of the CARG model. We conducted a qualitative evaluation to assess the perceived effects of this new national service delivery model. METHODS: In March-June 2018, we visited ten clinics implementing the CARG model across five provinces of Zimbabwe and conducted a focus group discussion with healthcare workers and in-depth interviews with three ART clients per clinic. Clinics had implemented the CARG model for approximately one year. All discussions were audio recorded, transcribed, and translated into English, and thematic coding was performed by two independent analysts. RESULTS: In focus groups, healthcare workers described that CARGs made ART distribution faster and facilitated client tracking in the community. They explained that their reduced workload allowed them to provide better care to those clients who did visit the clinic, and they felt that the CARG model should be sustained in the future. CARG members reported that by decreasing the frequency of clinic visits, CARGs saved them time and money, reducing previous barriers to collecting ART and improving adherence. CARG members also valued the emotional and informational support that they received from other members of their CARG, further improving adherence. Multiple healthcare workers did express concern that CARG members with diseases that begin with minor symptoms, such as tuberculosis, may not seek treatment at the clinic until the disease has progressed. CONCLUSIONS: We found that healthcare workers and clients overwhelmingly perceive CARGs as beneficial. This evaluation demonstrates that the CARG model can be successfully implemented on a national scale. These early results suggest that CARGs may be able to simultaneously improve clinical outcomes and reduce the workload of healthcare workers distributing ART.

      5. Transplacental respiratory syncytial virus and influenza virus antibody transfer in Alaska Native and Seattle mother-infant pairsexternal icon
        Chu HY, Newman KL, Englund JA, Cho S, Bull C, Lacombe K, Carlin K, Bulkow LR, Rudolph K, DeByle C, Berner J, Klejka J, Singleton R.
        J Pediatric Infect Dis Soc. 2020 May 5.
        BACKGROUND: Alaska Native (AN) infants are at risk for severe disease due to respiratory syncytial virus (RSV) and influenza. Maternal immunization protects young infants through transplacental antibody transfer. RSV- and influenza-specific transplacental antibody transfer in mother-infant pairs has not previously been evaluated in the AN population. METHODS: Serum samples collected during pregnancy and at birth from AN mother-infant pairs in the Yukon-Kuskokwim Delta region (YKD) of Alaska (2000-2011; n = 75) and predominantly white pairs in Seattle, Washington (2014-2016; n = 57), were tested for RSV and influenza antibody using a microneutralization and hemagglutination inhibition assay, respectively, and compared between sites. RESULTS: Mean RSV antibody concentrations in pregnant women in YKD and Seattle were similar (log2 RSV antibody 10.6 vs 10.7, P = .86), but cord blood RSV antibody concentrations were significantly lower in infants born to mothers in YKD compared with Seattle (log2 RSV antibody 11.0 vs 12.2, P < .001). Maternal and cord blood influenza antibody concentrations were lower for women and infants in YKD compared with Seattle for all 4 influenza antigens tested (all P < .05). The mean cord to maternal RSV antibody transfer ratio was 1.15 (standard deviation [SD], 0.13) in mother-infant pairs in Seattle compared with 1.04 (SD, 0.08) in YKD. Mean cord blood to maternal antibody transfer ratios for influenza antigens ranged from 1.22 to 1.42 in Seattle and from 1.05 to 1.59 in YKD. CONCLUSIONS: Though the transplacental antibody transfer ratio was high (>1.0) for both groups, transfer ratios for RSV antibody were significantly lower in AN mother-infant pairs. Further studies are needed to elucidate the impact of lower transplacental antibody transfer on infant disease risk in rural Alaska.Alaska Native and continental US mother-infant pairs have high transplacental antibody transfer ratios (>1.0) for influenza and respiratory syncytial virus, but anti-respiratory syncytial virus antibody levels are significantly lower in Alaska Native pairs than in those from the continental US.

      6. Evidence of failure of oral third-generation cephalosporin treatment for Shigella sonnei infectionexternal icon
        Collins JP, Friedman CR, Birhane MG, Karp BE, Osinski A, Montgomery MW, Thomas D, Barkley J, Sanchez MC, Hanna S, Adediran AA, Chen JC, Caidi H, Francois Watkins L.
        Open Forum Infect Dis. 2020 Apr;7(4):ofaa113.
        In 2017, state health departments notified the Centers for Disease Control and Prevention about 4 patients with shigellosis who experienced persistent illness after treatment with oral third-generation cephalosporins. Given increasing antibiotic resistance among Shigella, these cases highlight the need to evaluate the efficacy of oral cephalosporins for shigellosis.

      7. BACKGROUND: Since 2012, treatment guidelines have recommended initiating antiretroviral therapy for all persons as soon as possible after HIV diagnosis, irrespective of CD4 count. If clinicians adopted the treatment guidelines, a shortened interval between diagnosis and first viral suppression (Dx-to-VS) would be expected, with greater declines among those with CD4 counts >/=500 cells/microL at diagnosis. METHODS: Using the National HIV Surveillance System data, we examined Dx-to-VS intervals among persons aged >/=13 years with HIV infection diagnosed during 2012-2017. Analyses were stratified by first CD4 count: CD4 >/=500, 200-499, <200, and no CD4 value within 3 months after diagnosis. RESULTS: During 2012-2017 in the 27 U.S. jurisdictions with complete laboratory reporting, 138,759 HIV diagnoses occurred. The median Dx-to-VS interval shortened overall for persons with HIV diagnosed in 2012 vs. 2017 from 9 to 5 months, a 12.3% annual decrease (P <0.001) and in all CD4 groups. In 2012, Dx-to-VS interval was longer for persons with CD4 >/=500 than 200-499 and <200 (median, 9, 7, and 6 months, respectively). By 2017, the median interval was 4 months for these groups, compared with 25 months for those without a CD4 value within 3 months after diagnosis. CONCLUSION: Decreases in Dx-to-VS intervals across all CD4 groups with a greater decrease among those with CD4 >/=500 is consistent with implementation of treatment recommendations. The Dx-to-VS interval was longest among persons not linked to care within 3 months after diagnosis, underscoring the importance of addressing barriers to linkage to care for ending the HIV epidemic.

      8. BACKGROUND: Guidelines recommend that sexually active men who have sex with men (MSM) including human immunodeficiency virus (HIV)-positive MSM be tested at least annually for syphilis, with testing every 3-6 months for MSM at elevated risk. We examined the proportion of HIV-positive MSM tested for syphilis in the past 3, 6, and 12 months by their HIV care provider during 2013-2014. METHODS: Using data from the Medical Monitoring Project, a population-based HIV surveillance system, we evaluated the proportion of MSM who had documentation of being tested for syphilis by their HIV care provider in the past 3, 6, and 12 months. RESULTS: During 2013-2014, 71% (95% confidence interval [CI]: 69%-73%) of sexually active HIV-positive MSM were tested for syphilis in the past year. This proportion was higher among MSM reporting condomless sex: (75%; 95% CI: 72%-78%), and among MSM reporting >/= 2 sex partners (77%; 95% CI: 74%-79%), in the past 12 months. Among MSM reporting condomless sex, 49% (95% CI: 45%-53%) were tested in the past 6 months, and 26% (95% CI: 22%-30%) in the past 3 months. Among MSM reporting >/= 2 sex partners, 49% (95% CI: 44%-54%) were tested in the past 6 months and 26% (95% CI: 22%-29%) in the past 3 months. CONCLUSIONS: Nearly one-third of sexually active HIV-positive MSM were not tested annually, and many at increased risk were not tested at recommended frequencies. Efforts to improve compliance with screening guidelines for high-risk HIV-positive MSM are warranted.

      9. COVID-19 among workers in meat and poultry processing facilities - 19 states, April 2020external icon
        Dyal JW, Grant MP, Broadwater K, Bjork A, Waltenburg MA, Gibbins JD, Hale C, Silver M, Fischer M, Steinberg J, Basler CA, Jacobs JR, Kennedy ED, Tomasi S, Trout D, Hornsby-Myers J, Oussayef NL, Delaney LJ, Patel K, Shetty V, Kline KE, Schroeder B, Herlihy RK, House J, Jervis R, Clayton JL, Ortbahn D, Austin C, Berl E, Moore Z, Buss BF, Stover D, Westergaard R, Pray I, DeBolt M, Person A, Gabel J, Kittle TS, Hendren P, Rhea C, Holsinger C, Dunn J, Turabelidze G, Ahmed FS, deFijter S, Pedati CS, Rattay K, Smith EE, Luna-Pinto C, Cooley LA, Saydah S, Preacely ND, Maddox RA, Lundeen E, Goodwin B, Karpathy SE, Griffing S, Jenkins MM, Lowry G, Schwarz RD, Yoder J, Peacock G, Walke HT, Rose DA, Honein MA.
        MMWR Morb Mortal Wkly Rep. 2020 May 8;69(18).
        Congregate work and residential locations are at increased risk for infectious disease transmission including respiratory illness outbreaks. SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is primarily spread person to person through respiratory droplets. Nationwide, the meat and poultry processing industry, an essential component of the U.S. food infrastructure, employs approximately 500,000 persons, many of whom work in proximity to other workers (1). Because of reports of initial cases of COVID-19, in some meat processing facilities, states were asked to provide aggregated data concerning the number of meat and poultry processing facilities affected by COVID-19 and the number of workers with COVID-19 in these facilities, including COVID-19-related deaths. Qualitative data gathered by CDC during on-site and remote assessments were analyzed and summarized. During April 9-27, aggregate data on COVID-19 cases among 115 meat or poultry processing facilities in 19 states were reported to CDC. Among these facilities, COVID-19 was diagnosed in 4,913 (approximately 3%) workers, and 20 COVID-19-related deaths were reported. Facility barriers to effective prevention and control of COVID-19 included difficulty distancing workers at least 6 feet (2 meters) from one another (2) and in implementing COVID-19-specific disinfection guidelines.* Among workers, socioeconomic challenges might contribute to working while feeling ill, particularly if there are management practices such as bonuses that incentivize attendance. Methods to decrease transmission within the facility include worker symptom screening programs, policies to discourage working while experiencing symptoms compatible with COVID-19, and social distancing by workers. Source control measures (e.g., the use of cloth face covers) as well as increased disinfection of high-touch surfaces are also important means of preventing SARS-CoV-2 exposure. Mitigation efforts to reduce transmission in the community should also be considered. Many of these measures might also reduce asymptomatic and presymptomatic transmission (3). Implementation of these public health strategies will help protect workers from COVID-19 in this industry and assist in preserving the critical meat and poultry production infrastructure (4).

      10. Population-level benefits of extragenital gonorrhea screening among men who have sex with men: An exploratory modeling analysisexternal icon
        Earnest R, Ronn MM, Bellerose M, Gift TL, Berruti AA, Hsu KK, Testa C, Zhu L, Malyuta Y, Menzies NA, Salomon JA.
        Sex Transm Dis. 2020 Apr 29.
        BACKGROUND: Men who have sex with men (MSM) are disproportionately burdened by gonorrhea and face high rates of extragenital (rectal and pharyngeal) infection, which is mostly asymptomatic and often missed by urogenital-only screening. Extragenital screening likely remains below CDC-recommended levels. Since increasing screening coverage is often resource-intensive, we assessed whether improved extragenital screening among men already presenting at clinics could lead to substantial reductions in prevalence and incidence. METHODS: We calibrated an agent-based model of site- and race-specific gonorrhea infection in MSM to explicitly model multi-site infection within an individual and transmission via anal, orogenital, and ororectal sex. Compared to current screening levels, we assessed the impact of increasing screening at 1) both extragenital sites, 2) only the rectal site, and 3) only the pharyngeal site among men already being urogenitally screened. RESULTS: All scenarios reduced prevalence and incidence, with improved screening at both extragenital sites having the largest effect across outcomes. Extragenitally screening 100% of men being urogenitally screened reduced site-specific prevalence by an average of 42% (black MSM) and 50% (white MSM), with these values dropping by approximately 10% and 20% for each race group when targeting only the rectum and only the pharynx, respectively. However, increasing only rectal screening was more efficient in terms of the number of screens needed to avert an infection as this avoided duplicative screens due to rectum/pharynx multi-site infection. CONCLUSIONS: Improved extragenital screening substantially reduced site-specific gonorrhea prevalence and incidence, with strategies aimed at increasing rectal screening proving the most efficient.

      11. Estimating the population size of female sex workers in Zimbabwe: comparison of estimates obtained using different methods in twenty sites and development of a national-level estimateexternal icon
        Fearon E, Chabata ST, Magutshwa S, Ndori-Mharadze T, Musemburi S, Chidawanyika H, Masendeke A, Napierala S, Gonese E, Herman Roloff A, Tippett Barr BA, Kilmarx PH, Wong-Gruenwald R, Chidiya S, Mhangara M, Hanisch D, Edwards JK, Rice B, Taramusi I, Mbengeranwa T, Manangazira P, Mugurungi O, Hargreaves JR, Cowan FM.
        J Acquir Immune Defic Syndr. 2020 May 5.
        BACKGROUND: National-level population size estimates (PSEs) for hidden populations are required for HIV programming and modelling. Various estimation methods are available at the site-level, but it remains unclear which are optimal and how best to obtain national-level estimates. SETTING: Zimbabwe METHODS:: Using 2015-2017 data from respondent-driven sampling surveys (RDS) among female sex workers (FSW) aged 18+ years, mappings, and programme records, we calculated PSEs for each of 20 sites across Zimbabwe, using up to three methods per site (service and unique object multipliers, census, and capture-recapture). We compared estimates from different methods, and calculated site medians. We estimated prevalence of sex work at each site using census data available on the number of 15-49 year-old women, generated a list of all 'hotspot' sites for sex work nationally, and matched sites into strata in which the prevalence of sex work from sites with PSEs was applied to those without. Directly and indirectly estimated PSEs for all hotspot sites were summed to provide a national-level PSE, incorporating an adjustment accounting for sex work outside hotspots. RESULTS: Median site PSEs ranged from 12,863 in Harare to 247 in a rural growth-point. Multiplier methods produced the highest PSEs. We identified 55 hotspots estimated to include 95% of all FSW. FSW nationally were estimated to number 40,491, 1.23% of women aged 15-49 years, (plausibility bounds 28,177-58,797, 0.86-1.79%, those under 18 considered sexually exploited minors). CONCLUSION: There are large numbers of FSW estimated in Zimbabwe. Uncertainty in population size estimation should be reflected in policy-making.

      12. INTRODUCTION: Stigma impairs access to health care by gay, bisexual, and other men who have sex with men. Gay, bisexual, and other men who have sex with men who are open about their sexuality, or out, are more resilient to stigma than those who are not out. Outness may influence healthcare utilization and prescription of HIV pre-exposure prophylaxis to HIV-negative gay, bisexual, and other men who have sex with men. METHODS: Analyzing the 2018 American Men's Internet Survey during 2019, the adjusted prevalence ratios of healthcare stigmas and outness to healthcare providers were calculated. The effect of outness on annual healthcare visits and stigma was measured. Pre-exposure prophylaxis seeking and denial by providers was quantified and stratified by outness. RESULTS: Of 5,794 respondents, 3,402 (58.7%) were out to their provider. Out gay, bisexual, and other men who have sex with men were less likely to experience anticipated stigma (adjusted prevalence ratio=0.75, 95% CI=0.72, 0.80) but more likely to experience enacted stigma or discrimination (adjusted prevalence ratio=1.23, 95% CI=1.18, 1.28). In a subsample of out gay, bisexual, and other men who have sex with men, recently experienced discrimination was associated with higher healthcare utilization (adjusted prevalence ratio=1.51, 95% CI=1.14, 1.51). Conversely, recent experienced discrimination was associated with lower healthcare utilization in not out gay, bisexual, and other men who have sex with men (adjusted prevalence ratio=0.67, 95% CI=0.54, 0.82). Of 3,104 out gay, bisexual, and other men who have sex with men, 1,417 (45.7%) discussed pre-exposure prophylaxis with their providers, compared with 120 of 1,711 (7.0%) gay, bisexual, and other men who have sex with men who were not out (p<0.001). Pre-exposure prophylaxis denials were less common among out (116/793, 14.6%) than not out (14/55, 25.5%) gay, bisexual, and other men who have sex with men (p=0.044). CONCLUSIONS: Healthcare provider-related stigmas impair healthcare engagement among not out gay, bisexual, and other men who have sex with men who were also more commonly denied pre-exposure prophylaxis. Ending the HIV epidemic necessitates creating safe environments for disclosure of sexual preferences and practices to facilitate access to HIV prevention.

      13. High prevalence of hepatitis C infection among adult patients at four urban emergency departments - Birmingham, Oakland, Baltimore, and Boston, 2015-2017external icon
        Galbraith JW, Anderson ES, Hsieh YH, Franco RA, Donnelly JP, Rodgers JB, Schechter-Perkins EM, Thompson WW, Nelson NP, Rothman RE, White DA.
        MMWR Morb Mortal Wkly Rep. 2020 May 15;69(19):569-574.
        Identifying persons with hepatitis C virus (HCV) infection has become an urgent public health challenge because of increasing HCV-related morbidity and mortality, low rates of awareness among infected persons, and the advent of curative therapies (1). Since 2012, CDC has recommended testing of all persons born during 1945-1965 (baby boomers) for identification of chronic HCV infection (1); urban emergency departments (EDs) are well positioned venues for detecting HCV infection among these persons. The United States has witnessed an unprecedented opioid overdose epidemic since 2013 that derives primarily from commonly injected illicit opioids (e.g., heroin and fentanyl) (2). This injection drug use behavior has led to an increase in HCV infections among persons who inject drugs and heightened concern about increases in human immunodeficiency virus (HIV) and HCV infection within communities disproportionately affected by the opioid crisis (3,4). However, targeted strategies for identifying HCV infection among persons who inject drugs is challenging (5,6). During 2015-2016, EDs at the University of Alabama at Birmingham; Highland Hospital, Oakland, California; Johns Hopkins Hospital, Baltimore, Maryland; and Boston University Medical Center, Massachusetts, adopted opt-out (i.e., patients can implicitly accept or explicitly decline testing), universal hepatitis C screening for all adult patients. ED staff members offered HCV antibody (anti-HCV) screening to patients who were unaware of their status.* During similar observation periods at each site, ED staff members tested 14,252 patients and identified an overall 9.2% prevalence of positive results for anti-HCV among the adult patient population. Among the 1945-1965 birth cohort, prevalence of positive results for anti-HCV (13.9%) was significantly higher among non-Hispanic blacks (blacks) (16.0%) than among non-Hispanic whites (whites) (12.2%) (p<0.001). Among persons born after 1965, overall prevalence of positive results for anti-HCV was 6.7% and was significantly higher among whites (15.3%) than among blacks (3.2%) (p<0.001). These findings highlight age-associated differences in racial/ethnic prevalences and the potential for ED venues and opt-out, universal testing strategies to improve HCV infection awareness and surveillance for hard-to-reach populations. This opt-out, universal testing approach is supported by new recommendations for hepatitis C screening at least once in a lifetime for all adults aged >/=18 years, except in settings where the prevalence of positive results for HCV infection is <0.1% (7).

      14. BACKGROUND: Primary amebic meningoencephalitis (PAM) is a rapidly progressive and often fatal condition caused by the free-living ameba Naegleria fowleri. To estimate the global occurrence, characterize the epidemiology, and describe the clinical features of PAM, we report a series of PAM cases published in the international literature and reported to CDC. METHODS: We performed a literature search of PAM case reports published through 2018. Additionally, we included cases reported through CDC's Free-Living Ameba surveillance or diagnosed via CDC's Free-Living and Intestinal Amebas Laboratory. Cases were classified as confirmed, probable, or suspect on the basis of confirmatory testing, presentation, exposure, and disease course. RESULTS: A total of 381 PAM cases were identified. From 1965 to 2016, the number of reported cases increased an average of 1.6% per year. Seven reported survivors were classified as confirmed.The most commonly reported exposure associated with PAM was swimming/diving, and the most common class of water source was lakes/ponds/reservoirs. Patients were predominantly male (75%), with a median age of 14 years. Confirmed and probable cases were similar in their survival, course of illness, and CSF findings. CONCLUSIONS: PAM is a rare but deadly disease with worldwide occurrence. Improved clinician awareness, resulting in earlier diagnosis and treatment, may contribute to increased survival among PAM patients. The probable case definition used in this study appears to capture cases of PAM, as evidenced by similarities in outcomes, clinical course, and CSF profile to confirmed cases. In the absence of confirmatory testing, clinicians could use this case definition to identify cases of PAM.

      15. Visualizing variation within Global Pneumococcal Sequence Clusters (GPSCs) and country population snapshots to contextualize pneumococcal isolatesexternal icon
        Gladstone RA, Lo SW, Goater R, Yeats C, Taylor B, Hadfield J, Lees JA, Croucher NJ, van Tonder AJ, Bentley LJ, Quah FX, Blaschke AJ, Pershing NL, Byington CL, Balaji V, Hryniewicz W, Sigauque B, Ravikumar KL, Almeida SC, Ochoa TJ, Ho PL, du Plessis M, Ndlangisa KM, Cornick JE, Kwambana-Adams B, Benisty R, Nzenze SA, Madhi SA, Hawkins PA, Pollard AJ, Everett DB, Antonio M, Dagan R, Klugman KP, von Gottberg A, Metcalf BJ, Li Y, Beall BW, McGee L, Breiman RF, Aanensen DM, Bentley SD.
        Microb Genom. 2020 Apr 30.
        Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact. Gene presence and absence defined using Roary, and recombination profiles derived from Gubbins are presented in Phandango for each GPSC. Temporal phylogenetic signal was assessed for each GPSC using BactDating. We provide examples of how such resources can be used. In our example use of a country-specific phylogenetic snapshot we determined that serotype 14 was observed in nine unrelated genetic backgrounds in South Africa. The international phylogenetic snapshot of GPSC9, in which most serotype 14 isolates from South Africa were observed, highlights that there were three independent sub-clusters represented by South African serotype 14 isolates. We estimated from the GPSC9-dated tree that the sub-clusters were each established in South Africa during the 1980s. We show how recombination plots allowed the identification of a 20 kb recombination spanning the capsular polysaccharide locus within GPSC97. This was consistent with a switch from serotype 6A to 19A estimated to have occured in the 1990s from the GPSC97-dated tree. Plots of gene presence/absence of resistance genes (tet, erm, cat) across the GPSC23 phylogeny were consistent with acquisition of a composite transposon. We estimated from the GPSC23-dated tree that the acquisition occurred between 1953 and 1975. Finally, we demonstrate the assignment of GPSC31 to 17 externally generated pneumococcal serotype 1 assemblies from Utah via Pathogenwatch. Most of the Utah isolates clustered within GPSC31 in a USA-specific clade with the most recent common ancestor estimated between 1958 and 1981. The resources we have provided can be used to explore to data, test hypothesis and generate new hypotheses. The accessible assignment of GPSCs allows others to contextualize their own collections beyond the data presented here.

      16. Characteristics and clinical outcomes of adult patients hospitalized with COVID-19 - Georgia, March 2020external icon
        Gold JA, Wong KK, Szablewski CM, Patel PR, Rossow J, da Silva J, Natarajan P, Morris SB, Fanfair RN, Rogers-Brown J, Bruce BB, Browning SD, Hernandez-Romieu AC, Furukawa NW, Kang M, Evans ME, Oosmanally N, Tobin-D'Angelo M, Drenzek C, Murphy DJ, Hollberg J, Blum JM, Jansen R, Wright DW, Sewell WM, Owens JD, Lefkove B, Brown FW, Burton DC, Uyeki TM, Bialek SR, Jackson BR.
        MMWR Morb Mortal Wkly Rep. 2020 May 8;69(18):545-550.
        SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in the United States during January 2020 (1). Since then, >980,000 cases have been reported in the United States, including >55,000 associated deaths as of April 28, 2020 (2). Detailed data on demographic characteristics, underlying medical conditions, and clinical outcomes for persons hospitalized with COVID-19 are needed to inform prevention strategies and community-specific intervention messages. For this report, CDC, the Georgia Department of Public Health, and eight Georgia hospitals (seven in metropolitan Atlanta and one in southern Georgia) summarized medical record-abstracted data for hospitalized adult patients with laboratory-confirmed* COVID-19 who were admitted during March 2020. Among 305 hospitalized patients with COVID-19, 61.6% were aged <65 years, 50.5% were female, and 83.2% with known race/ethnicity were non-Hispanic black (black). Over a quarter of patients (26.2%) did not have conditions thought to put them at higher risk for severe disease, including being aged >/=65 years. The proportion of hospitalized patients who were black was higher than expected based on overall hospital admissions. In an adjusted time-to-event analysis, black patients were not more likely than were nonblack patients to receive invasive mechanical ventilation(dagger) (IMV) or to die during hospitalization (hazard ratio [HR] = 0.63; 95% confidence interval [CI] = 0.35-1.13). Given the overrepresentation of black patients within this hospitalized cohort, it is important for public health officials to ensure that prevention activities prioritize communities and racial/ethnic groups most affected by COVID-19. Clinicians and public officials should be aware that all adults, regardless of underlying conditions or age, are at risk for serious illness from COVID-19.

      17. Improving detection and response to respiratory events - Kenya, April 2016-April 2020external icon
        Idubor OI, Kobayashi M, Ndegwa L, Okeyo M, Galgalo T, Kalani R, Githii S, Hunsperger E, Balajee A, Verani JR, da Gloria Carvalho M, Winchell J, Van Beneden CA, Widdowson MA, Makayotto L, Chaves SS.
        MMWR Morb Mortal Wkly Rep. 2020 May 8;69(18):540-544.
        Respiratory pathogens, such as novel influenza A viruses, Middle East respiratory syndrome coronavirus (MERS-CoV), and now, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are of particular concern because of their high transmissibility and history of global spread (1). Clusters of severe respiratory disease are challenging to investigate, especially in resource-limited settings, and disease etiology often is not well understood. In 2014, endorsed by the Group of Seven (G7),* the Global Health Security Agenda (GHSA) was established to help build country capacity to prevent, detect, and respond to infectious disease threats.(dagger) GHSA is a multinational, multisectoral collaboration to support countries towards full implementation of the World Health Organization's International Health Regulations (IHR).( section sign) Initially, 11 technical areas for collaborator participation were identified to meet GHSA goals. CDC developed the Detection and Response to Respiratory Events (DaRRE) strategy in 2014 to enhance country capacity to identify and control respiratory disease outbreaks. DaRRE initiatives support the four of 11 GHSA technical areas that CDC focuses on: surveillance, laboratory capacity, emergency operations, and workforce development.( paragraph sign) In 2016, Kenya was selected to pilot DaRRE because of its existing respiratory disease surveillance and laboratory platforms and well-developed Field Epidemiology and Laboratory Training Program (FELTP) (2). During 2016-2020, Kenya's DaRRE partners (CDC, the Kenya Ministry of Health [MoH], and Kenya's county public health officials) conceptualized, planned, and implemented key components of DaRRE. Activities were selected based on existing capacity and determined by the Kenya MoH and included 1) expansion of severe acute respiratory illness (SARI) surveillance sites; 2) piloting of community event-based surveillance; 3) expansion of laboratory diagnostic capacity; 4) training of public health practitioners in detection, investigation, and response to respiratory threats; and 5) improvement of response capacity by the national emergency operations center (EOC). Progress on DaRRE activity implementation was assessed throughout the process. This pilot in Kenya demonstrated that DaRRE can support IHR requirements and can capitalize on a country's existing resources by tailoring tools to improve public health preparedness based on countries' needs.

      18. Survival and HIV-free survival among children aged </=3 years - eight Sub-Saharan African countries, 2015-2017external icon
        Jonnalagadda S, Yuengling K, Abrams E, Stupp P, Voetsch A, Patel M, Minisi Z, Eliya M, Hamunime N, Rwebembera A, Kirungi W, Mulenga L, Mushavi A, Ryan C, Ts'oeu M, Kim E, Dziuban EJ, Hageman K, Galbraith J, Mweebo K, Mwila A, Gonese E, Patel H, Modi S, Saito S.
        MMWR Morb Mortal Wkly Rep. 2020 May 15;69(19):582-586.
        Although mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) is preventable through antiretroviral treatment (ART) during pregnancy and postpartum, the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that 160,000 new HIV infections occurred among children in 2018 (1). Child survival and HIV-free survival rates* are standard measures of progress toward eliminating MTCT(dagger) (2). Nationally representative Population-based HIV Impact Assessment (PHIA)( section sign) survey data, pooled from eight sub-Saharan African countries( paragraph sign) were used to calculate survival probability among children aged </=3 years by maternal HIV status during pregnancy and HIV-free survival probability among children aged </=3 years born to women with HIV infection, stratified by maternal ART** status during pregnancy. Survival probability was significantly lower among children born to women with HIV infection (94.7%) than among those born to women without HIV infection (97.6%). HIV-free survival probability of children born to women with HIV infection differed significantly by the timing of initiation of maternal ART: 93.0% among children whose mothers received ART before pregnancy, 87.8% among those whose mothers initiated ART during pregnancy, and 53.4% among children whose mothers did not receive ART during pregnancy. Focusing on prevention of HIV acquisition and, among women of reproductive age with HIV infection, on early diagnosis of HIV infection and ART initiation when applicable, especially before pregnancy, can improve child survival and HIV-free survival.

      19. Modeling poliovirus transmission in Borno and Yobe, Northeast Nigeriaexternal icon
        Kalkowska DA, Franka R, Higgins J, Kovacs SD, Forbi JC, Wassilak SG, Pallansch MA, Thompson KM.
        Risk Anal. 2020 Apr 29.
        Beginning in 2013, multiple local government areas (LGAs) in Borno and Yobe in northeast Nigeria and other parts of the Lake Chad basin experienced a violent insurgency that resulted in substantial numbers of isolated and displaced people. Northeast Nigeria represents the last known reservoir country of wild poliovirus (WPV) transmission in Africa, with detection of paralytic cases caused by serotype 1 WPV in 2016 in Borno and serotype 3 WPV in late 2012. Parts of Borno and Yobe are also problematic areas for transmission of serotype 2 circulating vaccine-derived polioviruses, and they continue to face challenges associated with conflict and inadequate health services in security-compromised areas that limit both immunization and surveillance activities. We model poliovirus transmission of all three serotypes for Borno and Yobe using a deterministic differential equation-based model that includes four subpopulations to account for limitations in access to immunization services and dynamic restrictions in population mixing. We find that accessibility issues and insufficient immunization allow for prolonged poliovirus transmission and potential undetected paralytic cases, although as of the end of 2019, including responsive program activities in the modeling suggest die out of indigenous serotypes 1 and 3 WPVs prior to 2020. Specifically, recent and current efforts to access isolated populations and provide oral poliovirus vaccine continue to reduce the risks of sustained and undetected transmission, although some uncertainty remains. Continued improvement in immunization and surveillance in the isolated subpopulations should minimize these risks. Stochastic modeling can build on this analysis to characterize the implications for undetected transmission and confidence about no circulation.

      20. Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United Statesexternal icon
        Kujawski SA, Wong KK, Collins JP, Epstein L, Killerby ME, Midgley CM, Abedi GR, Ahmed NS, Almendares O, Alvarez FN, Anderson KN, Balter S, Barry V, Bartlett K, Beer K, Ben-Aderet MA, Benowitz I, Biggs HM, Binder AM, Black SR, Bonin B, Bozio CH, Brown CM, Bruce H, Bryant-Genevier J, Budd A, Buell D, Bystritsky R, Cates J, Charles EM, Chatham-Stephens K, Chea N, Chiou H, Christiansen D, Chu V, Cody S, Cohen M, Conners EE, Curns AT, Dasari V, Dawson P, DeSalvo T, Diaz G, Donahue M, Donovan S, Duca LM, Erickson K, Esona MD, Evans S, Falk J, Feldstein LR, Fenstersheib M, Fischer M, Fisher R, Foo C, Fricchione MJ, Friedman O, Fry A, Galang RR, Garcia MM, Gerber SI, Gerrard G, Ghinai I, Gounder P, Grein J, Grigg C, Gunzenhauser JD, Gutkin GI, Haddix M, Hall AJ, Han GS, Harcourt J, Harriman K, Haupt T, Haynes AK, Holshue M, Hoover C, Hunter JC, Jacobs MW, Jarashow C, Joshi K, Kamali T, Kamili S, Kim L, Kim M, King J, Kirking HL, Kita-Yarbro A, Klos R, Kobayashi M, Kocharian A, Komatsu KK, Koppaka R, Layden JE, Li Y, Lindquist S, Lindstrom S, Link-Gelles R, Lively J, Livingston M, Lo K, Lo J, Lu X, Lynch B, Madoff L, Malapati L, Marks G, Marlow M, Mathisen GE, McClung N, McGovern O, McPherson TD, Mehta M, Meier A, Mello L, Moon SS, Morgan M, Moro RN, Murray J, Murthy R, Novosad S, Oliver SE, O’Shea J, Pacilli M, Paden CR, Pallansch MA, Patel M, Patel S, Pedraza I, Pillai SK, Pindyck T, Pray I, Queen K, Quick N, Reese H, Reporter R, Rha B, Rhodes H, Robinson S, Robinson P, Rolfes MA, Routh JA, Rubin R, Rudman SL, Sakthivel SK, Scott S, Shepherd C, Shetty V, Smith EA, Smith S, Stierman B, Stoecker W, Sunenshine R, Sy-Santos R, Tamin A, Tao Y, Terashita D, Thornburg NJ, Tong S, Traub E, Tural A, Uehara A, Uyeki TM, Vahey G, Verani JR, Villarino E, Wallace M, Wang L, Watson JT, Westercamp M, Whitaker B, Wilkerson S, Woodruff RC, Wortham JM, Wu T, Xie A, Yousaf A, Zahn M, Zhang J.
        Nat Med. 2020 Apr 23.
        Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously(1-3). Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21-68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness.

      21. Influenza-related parotitis during a large mumps outbreak - Arkansas, 2016-2017external icon
        Labuda SM, Yang C, Daniels C, Young SR, Safi H, Haselow D.
        Arch Clin Case Rep. 2019 May;2(2):6-8.
        During August 2016-July 2017, Arkansas experienced a large mumps (parotitis) outbreak; however, mumps-negative cases of parotitis were also identified in this period. Nineteen of 215 samples (9%) randomly selected for influenza PCR testing were positive for influenza A virus. Practitioners should consider influenza as a cause of nonmumps parotitis.

      22. M1UK lineage in invasive group A streptococcus isolates from the USAexternal icon
        Li Y, Nanduri SA, Van Beneden CA, Beall BW.
        Lancet Infect Dis. 2020 May;20(5):538-539.

      23. Case series of glans injuries during voluntary medical male circumcision for HIV prevention - eastern and southern Africa, 2015-2018external icon
        Lucas TJ, Toledo C, Davis SM, Watts DH, Cavanaugh JS, Kiggundu V, Thomas AG, Odoyo-June E, Bonnecwe C, Maringa TH, Martin E, Juma AW, Xaba S, Balachandra S, Come J, Canda M, Nyirenda R, Msungama W, Odek J, Lija GJ, Mlanga E, Zulu JE, O'Bra H, Chituwo O, Aupokolo M, Mali DA, Zemburuka B, Malaba KD, Ntsuape OC, Hines JZ.
        BMC Urol. 2020 Apr 25;20(1):45.
        BACKGROUND: Male circumcision confers partial protection against heterosexual HIV acquisition among men. The President's Emergency Plan for AIDS Relief (PEPFAR) has supported > 18,900,000 voluntary medical male circumcisions (VMMC). Glans injuries (GIs) are rare but devastating adverse events (AEs) that can occur during circumcision. To address this issue, PEPFAR has supported multiple interventions in the areas of surveillance, policy, education, training, supply chain, and AE management. METHODS: Since 2015, PEPFAR has conducted surveillance of GIs including rapid investigation by the in-country PEPFAR team. This information is collected on standardized forms, which were reviewed for this analysis. RESULTS: Thirty-six GIs were reported from 2015 to 2018; all patients were < 15 years old (~ 0.7 per 100,000 VMMCs in this age group) with a decreasing annual rate (2015: 0.7 per 100,000 VMMCs; 2018: 0.4 per 100,000 VMMC; p = 0.02). Most (64%) GIs were partial or complete amputations. All amputations among 10-14 year-olds occurred using the forceps-guided (FG) method, as opposed to the dorsal-slit (DS) method, and three GIs among infants occurred using a Mogen clamp. Of 19 attempted amputation repairs, reattached tissue was viable in four (21%) in the short term. In some cases, inadequate DS method training and being overworked, were found. CONCLUSION: Following numerous interventions by PEPFAR and other stakeholders, GIs are decreasing; however, they have not been eliminated and remain a challenge for the VMMC program. Preventing further cases of complete and partial amputation will likely require additional interventions that prevent use of the FG method in young patients and the Mogen clamp in infants. Improving management of GIs is critical to optimizing outcomes.

      24. Rates and correlates of HIV incidence in Namibia's Zambezi region: Sentinel, community-based cohort study, 2014 to 2016external icon
        Maher AD, Nakanyala T, Mutenda N, Banda KM, Prybylski D, Wolkon A, Jonas A, Sawadogo S, Ntema C, Chipadze MR, Sinvula G, Tizora A, Mwandambele A, Chaturvedi S, Agovi AM, Agolory S, Hamunime N, Lowrance DW, McFarland W, Patel SV.
        JMIR Public Health Surveill. 2020 Mar 6.
        BACKGROUND: Direct measures of HIV incidence are needed to assess the population-level impact of prevention programs but are scarcely available in subnational epidemic hotspots of sub-Saharan Africa. We created a sentinel HIV incidence cohort within a community-based program that provided home-based HIV testing to all residents of Namibia's Zambezi region, where approximately 24% of the adult population was estimated to be living with HIV. OBJECTIVE: The aim of this study was to estimate HIV incidence, detect correlates of HIV acquisition, and assess the feasibility of the sentinel, community-based approach to HIV incidence surveillance in a subnational epidemic hotspot. METHODS: Following the program's initial home-based testing (December 2014-July 2015), we purposefully selected 10 clusters of 60 to 70 households each and invited residents who were HIV negative and aged >/=15 years to participate in the cohort. Consenting participants completed behavioral interviews and a second HIV test approximately 1 year later (March-September 2016). We used Poisson models to calculate HIV incidence rates between baseline and follow-up and multivariable Cox proportional hazard models to assess the correlates of seroconversion. RESULTS: Among 1742 HIV-negative participants, 1624 (93.23%) completed follow-up. We observed 26 seroconversions in 1954 person-years (PY) of follow-up, equating to an overall incidence rate of 1.33 per 100 PY (95% CI 0.91-1.95). Among women, the incidence was 1.55 per 100 PY (95% CI 1.12-2.17) and significantly higher among those aged 15 to 24 years and residing in rural areas (adjusted hazard ratio [aHR] 4.26, 95% CI 1.39-13.13; P=.01), residing in the Ngweze suburb of Katima Mulilo city (aHR 2.34, 95% CI 1.25-4.40; P=.01), who had no prior HIV testing in the year before cohort enrollment (aHR 3.38, 95% CI 1.04-10.95; P=.05), and who had engaged in transactional sex (aHR 17.64, 95% CI 2.88-108.14; P=.02). Among men, HIV incidence was 1.05 per 100 PY (95% CI 0.54-2.31) and significantly higher among those aged 40 to 44 years (aHR 13.04, 95% CI 5.98-28.41; P<.001) and had sought HIV testing outside the study between baseline and follow-up (aHR 8.28, 95% CI 1.39-49.38; P=.02). No seroconversions occurred among persons with HIV-positive partners on antiretroviral treatment. CONCLUSIONS: Nearly three decades into Namibia's generalized HIV epidemic, these are the first estimates of HIV incidence for its highest prevalence region. By creating a sentinel incidence cohort from the infrastructure of an existing community-based testing program, we were able to characterize current transmission patterns, corroborate known risk factors for HIV acquisition, and provide insight into the efficacy of prevention interventions in a subnational epidemic hotspot. This study demonstrates an efficient and scalable framework for longitudinal HIV incidence surveillance that can be implemented in diverse sentinel sites and populations.

      25. Improving sputum collection processes to increase tuberculosis case finding among HIV-positive persons in Botswanaexternal icon
        Mathebula U, Emerson C, Agizew T, Pals S, Boyd R, Mathoma A, Basotli J, Rankgoane-Pono G, Serumola C, Date A, Auld AF, Finlay A.
        Public Health Action. 2020 Mar 21;10(1):11-16.
        Setting: Twenty-two human immunodeficiency virus (HIV) clinics in Botswana. Objective: To compare sputum collection rates, sputum quality and volume, and tuberculosis (TB) diagnosis rates before and after field efforts to improve sputum collection among individuals newly diagnosed with HIV with TB symptoms. Design: Newly diagnosed individuals living with HIV attending 22 HIV clinics in Botswana were screened for TB from August 2012 to March 2014. Starting in May 2013, a field intervention composed of the introduction of a tracking log for presumed TB patients, and patient instructions and sputum induction to improve sputum collection rates was implemented. Results: Prior to the intervention, sputum collection rates were 44.1% (384/870). Subsequently, sputum collection increased to 58.3% (579/993) (P < 0.001). Sputum quality and volume also improved. Although rates of TB diagnosis increased from 9.7% (84/870) to 12.5% (120/993), this difference was not significant (P = 0.143). Conclusion: Sputum collection rates among presumptive TB cases, as well as sputum quality and volume improved after implementation of the field intervention. To improve sputum collection rates, efforts at the program level should be ongoing.

      26. Estimating acute human leptospirosis incidence in northern Tanzania using sentinel site and community behavioural surveillanceexternal icon
        Maze MJ, Sharples KJ, Allan KJ, Biggs HM, Cash-Goldwasser S, Galloway RL, de Glanville WA, Halliday JE, Kazwala RR, Kibona T, Mmbaga BT, Maro VP, Rubach MP, Cleaveland S, Crump JA.
        Zoonoses Public Health. 2020 May 6.
        Many infectious diseases lack robust estimates of incidence from endemic areas, and extrapolating incidence when there are few locations with data remains a major challenge in burden of disease estimation. We sought to combine sentinel surveillance with community behavioural surveillance to estimate leptospirosis incidence. We administered a questionnaire gathering responses on established locally relevant leptospirosis risk factors and recent fever to livestock-owning community members across six districts in northern Tanzania and applied a logistic regression model predicting leptospirosis risk on the basis of behavioural factors that had been previously developed among patients with fever in Moshi Municipal and Moshi Rural Districts. We aggregated probability of leptospirosis by district and estimated incidence in each district by standardizing probabilities to those previously estimated for Moshi Districts. We recruited 286 community participants: Hai District (n = 11), Longido District (59), Monduli District (56), Moshi Municipal District (103), Moshi Rural District (44) and Rombo District (13). The mean predicted probability of leptospirosis by district was Hai 0.029 (0.005, 0.095), Longido 0.071 (0.009, 0.235), Monduli 0.055 (0.009, 0.206), Moshi Rural 0.014 (0.002, 0.049), Moshi Municipal 0.015 (0.004, 0.048) and Rombo 0.031 (0.006, 0.121). We estimated the annual incidence (upper and lower bounds of estimate) per 100,000 people of human leptospirosis among livestock owners by district as Hai 35 (6, 114), Longido 85 (11, 282), Monduli 66 (11, 247), Moshi Rural 17 (2, 59), Moshi Municipal 18 (5, 58) and Rombo 47 (7, 145). Use of community behavioural surveillance may be a useful tool for extrapolating disease incidence beyond sentinel surveillance sites.

      27. Assessment of SARS-CoV-2 infection prevalence in homeless shelters - four U.S. cities, March 27-April 15, 2020external icon
        Mosites E, Parker EM, Clarke KE, Gaeta JM, Baggett TP, Imbert E, Sankaran M, Scarborough A, Huster K, Hanson M, Gonzales E, Rauch J, Page L, McMichael TM, Keating R, Marx GE, Andrews T, Schmit K, Morris SB, Dowling NF, Peacock G.
        MMWR Morb Mortal Wkly Rep. 2020 May 1;69(17):521-522.
        In the United States, approximately 1.4 million persons access emergency shelter or transitional housing each year (1). These settings can pose risks for communicable disease spread. In late March and early April 2020, public health teams responded to clusters (two or more cases in the preceding 2 weeks) of coronavirus disease 2019 (COVID-19) in residents and staff members from five homeless shelters in Boston, Massachusetts (one shelter); San Francisco, California (one); and Seattle, Washington (three). The investigations were performed in coordination with academic partners, health care providers, and homeless service providers. Investigations included reverse transcription-polymerase chain reaction testing at commercial and public health laboratories for SARS-CoV-2, the virus that causes COVID-19, over approximately 1-2 weeks for residents and staff members at the five shelters. During the same period, the team in Seattle, Washington, also tested residents and staff members at 12 shelters where a single case in each had been identified. In Atlanta, Georgia, a team proactively tested residents and staff members at two shelters with no known COVID-19 cases in the preceding 2 weeks. In each city, the objective was to test all shelter residents and staff members at each assessed facility, irrespective of symptoms. Persons who tested positive were transported to hospitals or predesignated community isolation areas.

      28. Identification and monitoring of international travelers during the initial phase of an outbreak of COVID-19 - California, February 3-March 17, 2020external icon
        Myers JF, Snyder RE, Porse CC, Tecle S, Lowenthal P, Danforth ME, Powers E, Kamali A, Jain S, Fritz CL, Chai SJ.
        MMWR Morb Mortal Wkly Rep. 2020 May 15;69(19):599-602.
        The threat of introduction of coronavirus disease 2019 (COVID-19) into the United States with the potential for community transmission prompted U.S. federal officials in February 2020 to screen travelers from China, and later Iran, and collect and transmit their demographic and contact information to states for follow-up. During February 5-March 17, 2020, the California Department of Public Health (CDPH) received and transmitted contact information for 11,574 international travelers to 51 of 61 local health jurisdictions at a cost of 1,694 hours of CDPH personnel time. If resources permitted, local health jurisdictions contacted travelers, interviewed them, and oversaw 14 days of quarantine, self-monitoring, or both, based on CDC risk assessment criteria for COVID-19. Challenges encountered during follow-up included errors in the recording of contact information and variation in the availability of resources in local health jurisdictions to address the substantial workload. Among COVID-19 patients reported to CDPH, three matched persons previously reported as travelers to CDPH. Despite intensive effort, the traveler screening system did not effectively prevent introduction of COVID-19 into California. Effectiveness of COVID-19 screening and monitoring in travelers to California was limited by incomplete traveler information received by federal officials and transmitted to states, the number of travelers needing follow-up, and the potential for presymptomatic and asymptomatic transmission. More efficient methods of collecting and transmitting passenger data, including electronic provision of flight manifests by airlines to federal officials and flexible text-messaging tools, would help local health jurisdictions reach out to all at-risk travelers quickly, thereby facilitating timely testing, case identification, and contact investigations. State and local health departments should weigh the resources needed to implement incoming traveler monitoring against community mitigation activities, understanding that the priorities of each might shift during the COVID-19 pandemic.

      29. Qualitative exploration of perceived benefits of care and barriers influencing HIV care in trans Nzoia, Kenyaexternal icon
        Naanyu V, Ruff J, Goodrich S, Spira T, Bateganya M, Toroitich-Ruto C, Otieno-Nyunya B, Siika AM, Wools-Kaloustian K.
        BMC Health Serv Res. 2020 Apr 25;20(1):355.
        BACKGROUND: Substantial efforts have been made to ensure people living with HIV (PLHIV) are linked to and retained in care but many challenges deter care utilization. We report perceived benefits of seeking HIV care and barriers to HIV care that were identified through a formative assessment conducted to advise the development of an alternative care model to deliver antiretroviral treatment therapy (ART) in Trans Nzoia County, Kenya. METHODS: Data were collected in 2015 through key informant interviews (KIIs), in-depth interviews (IDIs), and focus group discussions (FGDs). The study involved 55 participants of whom 53% were female. Ten KIIs provided community contextual information and viewpoints on the HIV epidemic in Trans Nzoia County while 20 PLHIV (10 male and 10 female) participated in IDIs. Twenty-five individuals living with HIV participated in four FGDs - two groups for men and two for women. Key informants were purposively selected, while every third patient above 18 years at the Kitale HIV Clinic was invited to share their HIV care experience through IDIs or FGDs. Trained research assistants moderated all sessions and audio recordings were transcribed and analyzed thematically. RESULTS: Findings showed that PLHIV in Trans Nzoia County used both conventional and complementary alternative care for HIV; however, public health facilities were preferred. Popular perceived benefits of adopting care were relief from symptoms and the chance to live longer. Benefits of care uptake included weight gain, renewed energy, and positive behavior change. Individual-level barriers to HIV care included lack of money and food, use of alternative care, negative side effects of ART, denial, and disclosure difficulties. At the community level, stigma, limited social support for conventional HIV treatment, and poor means of transport were reported. The health system barriers were limited supplies and staff, long distance to conventional HIV care, and unprofessional providers. CONCLUSIONS: Diverse individual, community and health system barriers continue to affect HIV care-seeking efforts in Kenya. Appreciation of context and lived experiences allows for development of realistic care models.

      30. Burden of influenza-associated respiratory and circulatory mortality in India, 2010-2013external icon
        Narayan VV, Iuliano AD, Roguski K, Bhardwaj R, Chadha M, Saha S, Haldar P, Kumar R, Sreenivas V, Kant S, Bresee J, Jain S, Krishnan A.
        J Glob Health. 2020 Jun;10(1):010402.
        Background: Influenza causes substantial morbidity and mortality worldwide, however, reliable burden estimates from developing countries are limited, including India. We aimed to quantify influenza-associated mortality for India utilizing 2010-2013 nationally representative data sources for influenza virus circulation and deaths. Methods: Virological data were obtained from the influenza surveillance network of 10 laboratories led by National Institute of Virology, Pune covering eight states from 2010-2013. Death data were obtained from the nationally representative Sample Registration System for the same time period. Generalized linear regression with negative binomial distribution was used to model weekly respiratory and circulatory deaths by age group and proportion of specimens positive for influenza by subtype; excess deaths above the seasonal baseline were taken as an estimate of influenza-associated mortality counts and rates. Annual excess death rates and the 2011 India Census data were used to estimate national influenza-associated deaths. Results: Estimated annual influenza-associated respiratory mortality rates were highest for those >/=65 years (51.1, 95% confidence interval (CI) = 9.2-93.0 deaths/100 000 population) followed by those <5 years (9.8, 95% CI = 0-21.8/100 000). Influenza-associated circulatory death rates were also higher among those >/=65 years (71.8, 95% CI = 7.9-135.8/100 000) as compared to those aged <65 years (1.9, 95% CI = 0-4.6/100 000). Across all age groups, a mean of 127 092 (95% CI = 64 046-190,139) annual influenza-associated respiratory and circulatory deaths may occur in India. Conclusions: Estimated influenza-associated mortality in India was high among children <5 years and adults >/=65 years. These estimates may inform strategies for influenza prevention and control in India, such as possible vaccine introduction.

      31. Between October 2015 and March 2018, we conducted the Modified Antiretroviral Treatment Access Study (MARTAS), a nurse-delivered case management intervention to improve linkage-to-care for persons recently tested HIV positive. Adult participants from nine urban clinics in three regions of Ukraine were randomized to either MARTAS or standard of care (SOC) using individual, parallel, two-arm design. The main study outcome was linkage-to-care (defined as registration at an HIV clinic) within a 3-month period from enrollment in the study. Intention-to-treat analysis of MARTAS (n = 135) versus SOC (n = 139) showed intervention efficacy in linkage to HIV care (84.4% vs. 33.8%; adjusted RR 2.45; 95% CI 1.72, 3.47; p < 0.001). MARTAS is recommended for implementation in Ukraine and may be helpful in other countries with similar gaps in linkage-to-care. registration number: NCT02338024.

      32. The second national tuberculosis prevalence survey in Vietnamexternal icon
        Nguyen HV, Tiemersma EW, Nguyen HB, Cobelens FG, Finlay A, Glaziou P, Dao CH, Mirtskhulava V, Nguyen HV, Pham HT, Khieu NT, de Haas P, Do NH, Nguyen PD, Cung CV, Nguyen NV.
        PLoS One. 2020 ;15(4):e0232142.
        INTRODUCTION: Tuberculosis (TB) remains a significant cause of morbidity and mortality in Vietnam. The current TB burden is unknown as not all individuals with TB are diagnosed, recorded and notified. The second national TB prevalence survey was conducted in 2017-2018 to assess the current burden of TB disease in the country. METHOD: Eighty-two clusters were selected using a multistage cluster sampling design. Adult (≥15 years of age) residents having lived for 2 weeks or more in the households of the selected clusters were invited to participate in the survey. The survey participants were screened for TB by a questionnaire and digital chest X-ray after providing written informed consent. Individuals with a positive symptom screen and/or chest X-ray suggestive of TB were asked to provide sputum samples to test for Mycobacterium tuberculosis by Ziehl-Neelsen direct light microscopy, Xpert MTB/RIF G4, BACTEC MGIT960 liquid culture and Löwenstein-Jensen solid culture. Bacteriologically confirmed TB cases were defined by an expert panel following a standard decision tree. RESULT: Of 87,207 eligible residents, 61,763 (70.8%) participated, and 4,738 (7.7%) screened positive for TB. Among these, 221 participants were defined as bacteriologically confirmed TB cases. The estimated prevalence of bacteriologically confirmed adult pulmonary TB was 322 (95% CI: 260-399) per 100,000, and the male-to-female ratio was 4.0 (2.8-5.8, p<0.001). In-depth interviews with the participants with TB disease showed that only 57.9% (95% CI: 51.3-64.3%) reported cough for 2 weeks or more and 32.1% (26.3-38.6%) did not report any symptom consistent with TB, while their chest X-ray results showed that 97.7% (95% CI: 94.6-99.1) had abnormal chest X-ray images suggesting TB. CONCLUSION: With highly sensitive diagnostics applied, this survey showed that the TB burden in Vietnam remains high. Half of the TB cases were not picked up by general symptom-based screening and were identified by chest X-ray only. Our results indicate that improving TB diagnostic capacity and access to care, along with reducing TB stigma, need to be top priorities for TB control and elimination in Vietnam.

      33. Respiratory syncytial virus and influenza hospitalizations in Alaska native adultsexternal icon
        Nolen LD, Seeman S, Desnoyers C, DeByle C, Klejka J, Bruden D, Rudolph K, Gerber SI, Kim L, Langley G, Patel M, Englund J, Chu HY, Tiesinga J, Singleton R.
        J Clin Virol. 2020 Apr 18;127:104347.
        BACKGROUND: Alaska Native (AN) infants from Yukon Kuskokwim Delta (YKD) have the highest U.S. infant hospitalization rate for respiratory syncytial virus (RSV). RSV can cause significant morbidity and mortality in adult populations, although the RSV burden in AN adults is unknown. Here we investigate RSV, influenza, and human metapneumovirus (hMPV) in hospitalized rural AN adults. METHODS: YKD AN adults, hospitalized with acute respiratory illness between November 2016 and October 2018 were enrolled prospectively. Nasopharyngeal (NP) swabs were tested for RSV, influenza and hMPV using polymerase chain reaction. Hospitalization rates were calculated. RESULTS: Of 251 patients who had an NP swab, RSV was detected in 8 (3.2 %), influenza in 31 (12.4 %), and hMPV in no patients. Weighted annual rates of lower respiratory tract infection (LRTI), RSV and influenza hospitalization were 192.0 (95 % CI: 176.5-208.4), 9.1 (6.0-13.3), and 42.2 (35.1-50.2) per 10,000. The most common discharge diagnosis was pneumonia (57.0 %), followed by chronic obstructive pulmonary disease (51.4 %). Ninety-eight percent (246/251) had a medical co-morbidity and 49.8 % (125/251) lived in a house with a smoker. Overall, 6.4 % (16/251) required mechanical ventilation, and 3.6 % (9/251) died during hospitalization. Only 35.7 % (66/185) of patients admitted during influenza season had received the annual influenza vaccine. DISCUSSION: We examined adult LRTI, influenza, and RSV hospitalization rates in an AN population with high infant RSV hospitalization rates. While we confirmed a high rate of hospitalization from LRTIs and influenza, we did not find a high rate due to RSV or hMPV. Improving influenza vaccination rates, and addressing co-morbidities could reduce respiratory hospitalizations.

      34. Taking tuberculosis preventive therapy implementation to national scale: the Nigerian PEPFAR Program experienceexternal icon
        Odume B, Meribe SC, Odusote T, Ifunanya M, Debem H, Amazue-Ezeuko I, Ogbanufe O, Adamu Y, Onotu D.
        Public Health Action. 2020 Mar 21;10(1):7-10.
        Background: Tuberculosis (TB) preventive therapy (TPT), including isoniazid preventive therapy (IPT), has been implemented within the Nigerian human immunodeficiency virus (HIV) programme since 2014. However, drug procurement and logistic support has remained the responsibility of the National Tuberculosis and Leprosy Control Programme. The US President's Emergency Plan for AIDS Relief-Nigeria (PEPFAR Nigeria) reviewed the key bottlenecks to TPT implementation in 2016. Method: The logistics of delivery of isoniazid (INH) were integrated with the antiretroviral (ARV) logistics management and information system (LMIS). Drug order and requisition forms at the facility level were revised to include INH, along with training on appropriate quantification and requisition of INH with ARVs. Support was provided for last mile delivery of INH directly to every implementing site, alongside ARV. Reults: We observed an increasing trend in TPT uptake between the pre-and-post intervention periods: 6% in fiscal year (FY) 2015, 7% in FY2016 and 12% in FY2017. Overall, the logistical changes in the LMIS to include INH in 2016 led to a 69% increase in TPT by the end of FY2017; this was statistically significant. Conclusion: Addressing logistical challenges to TPT implementation will ensure that the TB and HIV programmes can tackle the increasing burden of TB infection in people living with HIV. We recommended that the provider-to-client stage of TPT implementation be driven by the HIV programme and that cross-communication between the two programmes be improved.

      35. Pneumococcal colonization prevalence and density among Thai children with severe pneumonia and community controlsexternal icon
        Piralam B, Prosperi C, Thamthitiwat S, Bunthi C, Sawatwong P, Sangwichian O, Higdon MM, Watson NL, Deloria Knoll M, Paveenkittiporn W, Chara C, Hurst CP, Akarasewi P, Rhodes J, Maloney SA, O'Brien KL, Baggett HC.
        PLoS One. 2020 ;15(4):e0232151.
        BACKGROUND: Pneumococcal colonization prevalence and colonization density, which has been associated with invasive disease, can offer insight into local pneumococcal ecology and help inform vaccine policy discussions. METHODS: The Pneumonia Etiology Research for Child Health Project (PERCH), a multi-country case-control study, evaluated the etiology of hospitalized cases of severe and very severe pneumonia among children aged 1-59 months. The PERCH Thailand site enrolled children during January 2012-February 2014. We determined pneumococcal colonization prevalence and density, and serotype distribution of colonizing isolates. RESULTS: We enrolled 224 severe/very severe pneumonia cases and 659 community controls in Thailand. Compared to controls, cases had lower colonization prevalence (54.5% vs. 62.5%, p = 0.12) and lower median colonization density (42.1 vs. 210.2 x 103 copies/mL, p <0.0001); 42% of cases had documented antibiotic pretreatment vs. 0.8% of controls. In no sub-group of assessed cases did pneumococcal colonization density exceed the median for controls, including cases with no prior antibiotics (63.9x103 copies/mL), with consolidation on chest x-ray (76.5x103 copies/mL) or with pneumococcus detected in whole blood by PCR (9.3x103 copies/mL). Serotype distribution was similar among cases and controls, and a high percentage of colonizing isolates from cases and controls were serotypes included in PCV10 (70.0% and 61.8%, respectively) and PCV13 (76.7% and 67.9%, respectively). CONCLUSIONS: Pneumococcal colonization is common among children aged <5 years in Thailand. However, colonization density was not higher among children with severe pneumonia compared to controls. These results can inform discussions about PCV introduction and provide baseline data to monitor PCV impact after introduction in Thailand.

      36. From January 21 through February 23, 2020, a total of 14 cases of coronavirus disease 2019 (COVID-19) were diagnosed in six U.S. states, including 12 cases in travelers arriving from China and two in household contacts of persons with confirmed infections. An additional 39 cases were identified in persons repatriated from affected areas outside the United States (1). Starting in late February, reports of cases with no recent travel to affected areas or links to known cases signaled the initiation of pandemic spread in the United States (2). By mid-March, transmission of SARS-CoV-2, the virus that causes COVID-19, had accelerated, with rapidly increasing case counts indicating established transmission in the United States. Ongoing traveler importation of SARS-CoV-2, attendance at professional and social events, introduction into facilities or settings prone to amplification, and challenges in virus detection all contributed to rapid acceleration of transmission during March. Public health responses included intensive efforts to detect cases and trace contacts, and implementation of multiple community mitigation strategies. Because most of the population remains susceptible to infection, recognition of factors associated with amplified spread during the early acceleration period will help inform future decisions as locations in the United States scale back some components of mitigation and strengthen systems to detect a potential transmission resurgence. U.S. circulation of SARS-CoV-2 continues, and sustained efforts will be needed to prevent future spread within the United States.

      37. Spatial and temporal clustering of patients hospitalized with laboratory-confirmed influenza in the United Statesexternal icon
        Sloan C, Chandrasekhar R, Mitchel E, Ndi D, Miller L, Thomas A, Bennett NM, Chai S, Spencer M, Eckel S, Spina N, Monroe M, Anderson EJ, Lynfield R, Yousey-Hindes K, Bargsten M, Zansky S, Lung K, Schroeder M, Cummings C, Garg S, Schaffner W, Lindegren ML.
        Epidemics. 2020 Feb 10;31:100387.
        BACKGROUND: Timing of influenza spread across the United States is dependent on factors including local and national travel patterns and climate. Local epidemic intensity may be influenced by social, economic and demographic patterns. Data are needed to better explain how local socioeconomic factors influence both the timing and intensity of influenza seasons to result in national patterns. METHODS: To determine the spatial and temporal impacts of socioeconomics on influenza hospitalization burden and timing, we used population-based laboratory-confirmed influenza hospitalization surveillance data from the CDC-sponsored Influenza Hospitalization Surveillance Network (FluSurv-NET) at up to 14 sites from the 2009/2010 through 2013/2014 seasons (n = 35,493 hospitalizations). We used a spatial scan statistic and spatiotemporal wavelet analysis, to compare temporal patterns of influenza spread between counties and across the country. RESULTS: There were 56 spatial clusters identified in the unadjusted scan statistic analysis using data from the 2010/2011 through the 2013/2014 seasons, with relative risks (RRs) ranging from 0.09 to 4.20. After adjustment for socioeconomic factors, there were five clusters identified with RRs ranging from 0.21 to 1.20. In the wavelet analysis, most sites were in phase synchrony with one another for most years, except for the H1N1 pandemic year (2009-2010), wherein most sites had differential epidemic timing from the referent site in Georgia. CONCLUSIONS: Socioeconomic factors strongly impact local influenza hospitalization burden. Influenza phase synchrony varies by year and by socioeconomics, but is less influenced by socioeconomics than is disease burden.

      38. COVID-19 outbreak among three affiliated homeless service sites - King County, Washington, 2020external icon
        Tobolowsky FA, Gonzales E, Self JL, Rao CY, Keating R, Marx GE, McMichael TM, Lukoff MD, Duchin JS, Huster K, Rauch J, McLendon H, Hanson M, Nichols D, Pogosjans S, Fagalde M, Lenahan J, Maier E, Whitney H, Sugg N, Chu H, Rogers J, Mosites E, Kay M.
        MMWR Morb Mortal Wkly Rep. 2020 May 1;69(17):523-526.
        On March 30, 2020, Public Health - Seattle and King County (PHSKC) was notified of a confirmed case of coronavirus disease 2019 (COVID-19) in a resident of a homeless shelter and day center (shelter A). Residents from two other homeless shelters (B and C) used shelter A's day center services. Testing for SARS-CoV-2, the virus that causes COVID-19, was offered to available residents and staff members at the three shelters during March 30-April 1, 2020. Among the 181 persons tested, 19 (10.5%) had positive test results (15 residents and four staff members). On April 1, PHSKC and CDC collaborated to conduct site assessments and symptom screening, isolate ill residents and staff members, reinforce infection prevention and control practices, provide face masks, and advise on sheltering-in-place. Repeat testing was offered April 7-8 to all residents and staff members who were not tested initially or who had negative test results. Among the 118 persons tested in the second round of testing, 18 (15.3%) had positive test results (16 residents and two staff members). In addition to the 31 residents and six staff members identified through testing at the shelters, two additional cases in residents were identified during separate symptom screening events, and four were identified after two residents and two staff members independently sought health care. In total, COVID-19 was diagnosed in 35 of 195 (18%) residents and eight of 38 (21%) staff members who received testing at the shelter or were evaluated elsewhere. COVID-19 can spread quickly in homeless shelters; rapid interventions including testing and isolation to identify cases and minimize transmission are necessary. CDC recommends that homeless service providers implement appropriate infection control practices, apply physical distancing measures including ensuring resident's heads are at least 6 feet (2 meters) apart while sleeping, and promote use of cloth face coverings among all residents (1).

      39. COVID-19 in correctional and detention facilities - United States, February-April 2020external icon
        Wallace M, Hagan L, Curran KG, Williams SP, Handanagic S, Bjork A, Davidson SL, Lawrence RT, McLaughlin J, Butterfield M, James AE, Patil N, Lucas K, Hutchinson J, Sosa L, Jara A, Griffin P, Simonson S, Brown CM, Smoyer S, Weinberg M, Pattee B, Howell M, Donahue M, Hesham S, Shelley E, Philips G, Selvage D, Staley EM, Lee A, Mannell M, McCotter O, Villalobos R, Bell L, Diedhiou A, Ortbahn D, Clayton JL, Sanders K, Cranford H, Barbeau B, McCombs KG, Holsinger C, Kwit NA, Pringle JC, Kariko S, Strick L, Allord M, Tillman C, Morrison A, Rowe D, Marlow M.
        MMWR Morb Mortal Wkly Rep. 2020 May 15;69(19):587-590.
        An estimated 2.1 million U.S. adults are housed within approximately 5,000 correctional and detention facilities(dagger) on any given day (1). Many facilities face significant challenges in controlling the spread of highly infectious pathogens such as SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Such challenges include crowded dormitories, shared lavatories, limited medical and isolation resources, daily entry and exit of staff members and visitors, continual introduction of newly incarcerated or detained persons, and transport of incarcerated or detained persons in multiperson vehicles for court-related, medical, or security reasons (2,3). During April 22-28, 2020, aggregate data on COVID-19 cases were reported to CDC by 37 of 54 state and territorial health department jurisdictions. Thirty-two (86%) jurisdictions reported at least one laboratory-confirmed case from a total of 420 correctional and detention facilities. Among these facilities, COVID-19 was diagnosed in 4,893 incarcerated or detained persons and 2,778 facility staff members, resulting in 88 deaths in incarcerated or detained persons and 15 deaths among staff members. Prompt identification of COVID-19 cases and consistent application of prevention measures, such as symptom screening and quarantine, are critical to protecting incarcerated and detained persons and staff members.

      40. Public health response to COVID-19 cases in correctional and detention facilities - Louisiana, March-April 2020external icon
        Wallace M, Marlow M, Simonson S, Walker M, Christophe N, Dominguez O, Kleamenakis L, Orellana A, Pagan-Pena D, Singh C, Pogue M, Saucier L, Lo T, Benson K, Sokol T.
        MMWR Morb Mortal Wkly Rep. 2020 May 15;69(19):594-598.
        Correctional and detention facilities face unique challenges in the control of infectious diseases, including coronavirus disease 2019 (COVID-19) (1-3). Among >10 million annual admissions to U.S. jails, approximately 55% of detainees are released back into their communities each week (4); in addition, staff members at correctional and detention facilities are members of their local communities. Thus, high rates of COVID-19 in correctional and detention facilities also have the potential to influence broader community transmission. In March 2020, the Louisiana Department of Health (LDH) began implementing surveillance for COVID-19 among correctional and detention facilities in Louisiana and identified cases and outbreaks in many facilities. In response, LDH and CDC developed and deployed the COVID-19 Management Assessment and Response (CMAR) tool to guide technical assistance focused on infection prevention and control policies and case management with correctional and detention facilities. This report describes COVID-19 prevalence in correctional and detention facilities detected through surveillance and findings of the CMAR assessment. During March 25-April 22, 489 laboratory-confirmed COVID-19 cases, including 37 (7.6%) hospitalizations and 10 (2.0%) deaths among incarcerated or detained persons, and 253 cases, including 19 (7.5%) hospitalizations and four (1.6%) deaths among staff members were reported. During April 8-22, CMAR telephone-based assessments were conducted with 13 of 31 (42%) facilities with laboratory-confirmed cases and 11 of 113 (10%) facilities without known cases. Administrators had awareness and overall understanding of CDC guidance for prevention of transmission in these facilities but reported challenges in implementation, related to limited space to quarantine close contacts of COVID-19 patients and inability of incarcerated and detained persons to engage in social distancing, particularly in dormitory-style housing. CMAR was a useful tool that helped state and federal public health officials assist multiple correctional and detention facilities to better manage COVID-19 patients and guide control activities to prevent or mitigate transmission.

      41. COVID-19 and risks posed to personnel during endotracheal intubationexternal icon
        Weissman DN, de Perio MA, Radonovich LJ.
        Jama. 2020 Apr 27.

      42. Notes from the Field: Cholera outbreak - Zimbabwe, September 2018-March 2019external icon
        Winstead A, Strysko J, Relan P, Conners EE, Martinsen AL, Lopez V, Arons M, Masunda KP, Mukeredzi I, Manyara J, Duri C, Mashe T, Phiri I, Poncin M, Sreenivasan N, Aubert RD, Fuller L, Balachandra S, Mintz E, Manangazira P.
        MMWR Morb Mortal Wkly Rep. 2020 May 1;69(17):527-528.

      43. Consistent and correct use of condoms can reduce the risk for sexually transmitted diseases, including HIV/AIDS. Studies have reported that condomless sex among men who have sex with men (MSM) has steadily increased in recent years. We analyzed data reported by 51 health departments regarding 82 556 HIV-positive and HIV-negative MSM 13 years or older and participated in Centers for Disease Control and Prevention-funded behavioral risk-reduction intervention programs during 2012-2017. The percentages of condomless sex increased from 56.3% to 72.0% (estimated annual percent change [EAPC] = 7.1%) among HIV-positive MSM and from 46.0% to 70.5% (EAPC = 4.1%) among HIV-negative MSM. Continued increases in condomless sex might disrupt progress in ending the HIV/AIDS epidemic. Transmission risk associated with condomless sex can be reduced by ensuring that HIV-positive persons know their status early and are linked to care to achieve viral suppression and those at risk for acquiring HIV/AIDS can readily access preexposure prophylaxis.

    • Disease Reservoirs and Vectors
      1. Impact of deltamethrin selection on kdr mutations and insecticide detoxifying enzymes in Aedes aegypti from Mexicoexternal icon
        Contreras-Perera Y, Ponce-Garcia G, Villanueva-Segura K, Lopez-Monroy B, Rodriguez-Sanchez IP, Lenhart A, Manrique-Saide P, Flores AE.
        Parasit Vectors. 2020 May 6;13(1):224.
        BACKGROUND: Insecticide resistance is a serious problem for vector control programmes worldwide. Resistance is commonly attributed to mutations at the insecticide's target site or increased activity of detoxification enzymes. METHODS: We determined the knockdown concentration (KC50) and lethal concentration (LC50) of deltamethrin in six natural populations of adult Aedes aegypti from southeastern Mexico. These populations were then selected over five generations using the LC50 from the preceding generation that underwent selection, and the heritability of deltamethrin resistance was quantified. For each generation, we also determined the frequency of the kdr alleles L410, I1016 and C1534, and the levels of activity of three enzyme families (alpha- and beta-esterases, mixed-function oxidases and glutathione S-transferases (GST)) associated with insecticide detoxification. RESULTS: There was an increase in KC50 and LC50 values in the subsequent generations of selection with deltamethrin (FS5vs FS0). According to the resistance ratios (RRs), we detected increases in LC50 ranging from 1.5 to 5.6 times the values of the parental generation and in KC50 ranging from 1.3-3.8 times the values of the parental generation. Triple homozygous mutant individuals (tri-locus, LL/II/CC) were present in the parental generations and increased in frequency after selection. The frequency of L410 increased from 1.18-fold to 2.63-fold after selection with deltamethrin (FS5vs FS0) in the populations analyzed; for I1016 an increase between 1.19-fold to 2.79-fold was observed, and C1534 was fixed in all populations after deltamethrin selection. Enzymatic activity varied significantly over the generations of selection. However, only alpha- esterase activity remained elevated in multiple populations after five generations of deltamethrin selection. We observed an increase in the mean activity levels of GSTs in two of the six populations analyzed. CONCLUSIONS: The high levels of resistance and their association with high frequencies of kdr mutations (V410L, V1016I and F1534C) obtained through artificial selection, suggest an important role of these mutations in conferring resistance to deltamethrin. We highlight the need to implement strategies that involve the monitoring of kdr frequencies in insecticide resistance monitoring and management programmes.

      2. Lyme and other tick-borne diseases are increasing in the United States. Development of tick control tools have focused primarily on the blacklegged tick, Ixodes scapularis Say. Application of acaricides or entomopathogenic fungal agents to kill host-seeking ticks or ticks on rodents can suppress I. scapularis abundance in residential landscapes, but evidence is lacking for impact on human tick bites or tick-borne disease. Similar studies remain limited for the lone star tick, Amblyomma americanum (L.). Other knowledge gaps include how well homeowners and pest control companies perform in the broadcast application of tick-killing products, relative to high efficacy reported in research studies, and the tick-killing potential of natural product formulations exempt from Environmental Protection Agency registration. Area-wide control based on preventing ticks from feeding on their main reproductive host, the white-tailed deer, can suppress populations of both I. scapularis and A. americanum. Some studies also suggest an impact on Lyme disease cases, but this needs to be further validated in larger-scale intervention studies. The effectiveness, scale, cost, and implementation of various tick management strategies are important considerations in efforts to reduce human tick encounters and tick-borne disease. Additional barriers include weak incentives for industry and academia to develop, test, and register new tick and pathogen control technologies, including vaccines targeting humans, tick reproductive hosts, or wildlife pathogen reservoirs. Solutions will need to be 'two-pronged': improving the tick and pathogen control toolbox and strengthening the public health workforce engaging in tick control at local and state levels.

      3. The invasive Asian longhorned tick, Haemaphysalis longicornis Neumann, was first detected in the United States in 2017. It has since been found in 12 states, and there is concern that the tick's parthenogenetic ability and wide variety of host species may allow for broader dissemination. Of the tick-borne diseases endemic to the United States, Rocky Mountain spotted fever (RMSF), a rapidly progressive and potentially fatal disease caused by Rickettsia rickettsii, is the most severe. There is considerable geographical overlap between spotted fever rickettsioses cases, which include RMSF, and the currently known distribution of H. longicornis, providing the potential for this tick to encounter this pathogen. We have evaluated the ability of H. longicornis to acquire and transmit R. rickettsii under laboratory conditions. Haemaphysalis longicornis as larvae and nymphs acquired the pathogen while feeding on infected guinea pigs. The infection persisted through every life stage, all of which were able to transmit R. rickettsii to naive hosts. The pathogen was also transmitted at a low frequency between generations of H. longicornis through the ova. While H. longicornis was demonstrated to be a competent vector for R. rickettsii under laboratory conditions, the probability of its involvement in the maintenance and transmission of this pathogen in nature, as well as its potential impact on human health, requires further study.

    • Environmental Health
      1. Keratinous biomarker of mercury exposure associated with amyotrophic lateral sclerosis risk in a nationwide U.S. studyexternal icon
        Andrew AS, O'Brien KM, Jackson BP, Sandler DP, Kaye WE, Wagner L, Stommel EW, Horton DK, Mehta P, Weinberg CR.
        Amyotroph Lateral Scler Frontotemporal Degener. 2020 Apr 24:1-8.
        Objective: The majority of cases of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are of unknown etiology. A proportion of these cases are likely to be attributable to contaminant exposures, although the specific environmental etiology of ALS remains largely a mystery. Certain forms of the neurotoxic metal mercury readily cross into the central nervous system. Fish is a dietary source of methylmercury, but also of beneficial components, such as omega-3 polyunsaturated fatty acids. Prior work using clinic-based studies of toenails and hair as keratinous biomarkers of exposure suggest elevated mercury levels in ALS patients compared with controls. We sought to validate this relationship in a U.S. case-control comparison of mercury levels in nail clippings. Methods: We performed trace element analysis using inductively coupled plasma mass spectrometry (ICP-MS) on the nail clippings of n = 70 female, geographically representative ALS patients from the National ALS Biorepository and compared them to n = 210 age-matched controls from a set of n = 1216 nationally distributed controls from the Sister and Two Sister Studies. Results: Compared to the lowest quartile of nail mercury, moderate levels were associated with decreased risk of ALS (P = 4.18e-6). However, the odds of having nail mercury levels above the 90th percentile were 2.3-fold higher among ALS patients compared with controls (odds ratio (OR) = 2.3, 95% confidence interval 1.10-4.58, adjusted for age and smoking status). Conclusion: This finding suggests that excessive mercury exposure may be associated with the neurodegenerative health of aging populations.

      2. Background: Local, state, and national childhood blood lead surveillance is based on healthcare providers and clinical laboratories reporting test results to public health departments. Increased interest in detecting blood lead level (BLL) patterns and changes of potential public health significance in a timely manner has highlighted the need for surveillance systems to rapidly detect and investigate these events. Objective(s): Decrease the time to detect changes in surveillance patterns by using an alerting algorithm developed and assessed through historical child blood lead surveillance data analysis. Method(s): We applied geographic and temporal data-aggregation strategies on childhood blood lead surveillance data and developed a novel alerting algorithm. The alerting algorithm employed a modified cumulative summary/Shewhart algorithm, initially applied on 113 months of data from two jurisdictions with a known increase in the proportion of children <6 years of age with BLLs >=5 micro g/dl. Result(s): Alert signals retrospectively identified time periods in two jurisdictions where a known change in the proportion of children <6 years of age with BLLs >=5 micro g/dl occurred. Additionally, we identified alert signals among six of the 18 (33%) randomly selected counties assessed where no previously known or suspected pattern changes existed. Conclusion(s): The modified cumulative summary/Shewhart algorithm provides a framework for enhanced blood lead surveillance by identifying changes in the proportion of children with BLLs >=5 micro g/dl. The algorithm has the potential to alert public health officials to changes requiring further important public health investigation.

      3. Temporal trends and demographic risk factors for hospital admissions due to carbon monoxide poisoning in Englandexternal icon
        Roca-Barcelo A, Crabbe H, Ghosh R, Freni-Sterrantino A, Fletcher T, Leonardi G, Hoge C, Hansell AL, Piel FB.
        Prev Med. 2020 Apr 27:106104.
        Unintentional non-fire related (UNFR) carbon monoxide (CO) poisoning is a preventable cause of morbidity and mortality. Epidemiological data on UNFR CO poisoning can help monitor changes in the magnitude of this burden, particularly through comparisons of multiple countries, and to identify vulnerable sub-groups of the population which may be more at risk. Here, we collected data on age- and sex- specific number of hospital admissions with a primary diagnosis of UNFR CO poisoning in England (2002-2016), aggregated to small areas, alongside area-level characteristics (i.e. deprivation, rurality and ethnicity). We analysed temporal trends using piecewise log-linear models and compared them to analogous data obtained for Canada, France, Spain and the US. We estimated age-standardized rates per 100,000 inhabitants by area-level characteristics using the WHO standard population (2000-2025). We then fitted the Besag York Mollie (BYM) model, a Bayesian hierarchical spatial model, to assess the independent effect of each area-level characteristic on the standardized risk of hospitalization. Temporal trends showed significant decreases after 2010. Decreasing trends were also observed across all countries studied, yet France had a 5-fold higher risk. Based on 3399 UNFR CO poisoning hospitalizations, we found an increased risk in areas classified as rural (0.69, 95% CrI: 0.67; 0.80), highly deprived (1.77, 95% CrI: 1.66; 2.10) or with the largest proportion of Asian (1.15, 95% CrI: 1.03; 1.49) or Black population (1.35, 95% CrI: 1.20; 1.80). Our multivariate approach provides strong evidence for the identification of vulnerable populations which can inform prevention policies and targeted interventions.

      4. Modeled prenatal exposure to per- and polyfluoroalkyl substances in association with child autism spectrum disorder: A case-control studyexternal icon
        Shin HM, Bennett DH, Calafat AM, Tancredi D, Hertz-Picciotto I.
        Environ Res. 2020 Apr 14;186:109514.
        BACKGROUND/OBJECTIVE: Per- and polyfluoroalkyl substances (PFAS) display neurobehavioral toxicity in laboratory animal studies. We examined associations of modeled prenatal maternal exposure to PFAS with child diagnosis of autism spectrum disorder (ASD). METHODS: Participants were 453 mother-child pairs from CHARGE (CHildhood Autism Risk from Genetics and Environment), a population-based case-control study. Children underwent psychometric testing and were clinically confirmed for ASD (n = 239) or typical development (TD, n = 214). At the end of the clinic visit, maternal blood specimens were collected. We quantified nine PFAS in maternal serum samples collected when their child was 2-5 years old. As surrogate in utero exposure, we used a model built from external prospective data in pregnancy and 24 months post-partum and then reconstructed maternal PFAS serum concentrations during pregnancy in this case-control sample. We used logistic regression to evaluate associations of modeled prenatal maternal PFAS concentrations with child ASD. RESULTS: Modeled prenatal maternal perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) were borderline associated with increased odds of child diagnosis of ASD (per nanogram per milliliter increase: odds ratio [OR] = 1.46; 95% confidence interval [CI]: 0.98, 2.18 for PFHxS, OR = 1.03; 95% CI: 0.99, 1.08 for PFOS). When compared to the lowest quartile (reference category), the highest quartile of modeled prenatal maternal PFHxS was associated with increased odds of child diagnosis of ASD (OR = 1.95; 95% CI: 1.02, 3.72). CONCLUSIONS: In analyses where modeled prenatal maternal PFAS serum concentrations served as in utero exposure, we observed that prenatal PFHxS and PFOS exposure, but not other PFAS, were borderline associated with increased odds of child diagnosis of ASD. Further studies in which PFAS concentrations are prospectively measured in mothers and children at a range of developmental stages are needed to confirm these findings.

      5. Co-occurrence of antibiotic, biocide, and heavy metal resistance genes in bacteria from metal and radionuclide contaminated soils at the Savannah River Siteexternal icon
        Thomas JC, Oladeinde A, Kieran TJ, Finger JW, Bayona-Vasquez NJ, Cartee JC, Beasley JC, Seaman JC, McArthur JV, Rhodes OE, Glenn TC.
        Microb Biotechnol. 2020 May 3.
        Contaminants such as heavy metals may contribute to the dissemination of antimicrobial resistance (AMR) by enriching resistance gene determinants via co-selection mechanisms. In the present study, a survey was performed on soils collected from four areas at the Savannah River Site (SRS), South Carolina, USA, with varying contaminant profiles: relatively pristine (Upper Three Runs), heavy metals (Ash Basins), radionuclides (Pond B) and heavy metal and radionuclides (Tim's Branch). Using 16S rRNA gene amplicon sequencing, we explored the structure and diversity of soil bacterial communities. Sites with legacies of metal and/or radionuclide contamination displayed significantly lower bacterial diversity compared to the reference site. Metagenomic analysis indicated that multidrug and vancomycin antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) including those associated with copper, arsenic, iron, nickel and zinc were prominent in all soils including the reference site. However, significant differences were found in the relative abundance and diversity of certain ARGs and MRGs in soils with metal/radionuclide contaminated soils compared to the reference site. Co-occurrence patterns revealed significant ARG/MRG subtypes in predominant soil taxa including Acidobacteriaceae, Bradyrhizobium, Mycobacterium, Streptomyces, Verrumicrobium, Actinomadura and Solirubacterales. Overall, the study emphasizes the potential risk of human activities on the dissemination of AMR in the environment.

      6. Perinatal urinary benzophenone-3 concentrations and glucose levels among women from a fertility clinicexternal icon
        Wang Z, Minguez-Alarcon L, Williams PL, Bellavia A, Ford JB, Keller M, Petrozza JC, Calafat AM, Hauser R, James-Todd T.
        Environ Health. 2020 Apr 28;19(1):45.
        BACKGROUND: Subfertile women have higher risk of glucose intolerance during pregnancy. Studies suggest associations between several endocrine disrupting chemicals (EDCs) and pregnancy glucose levels. However, the association between benzophenone-3 (BP-3), an EDC widely found in sunscreen, and pregnancy glucose levels remains unclear. We aimed to assess the association between perinatal exposures to BP-3 and pregnancy glucose levels in subfertile women. METHODS: We evaluated 217 women from a prospective cohort based at a fertility clinic who had urinary BP-3 concentrations measured during 3-month preconception, first and/or second trimesters, and blood glucose measured at glucose load tests (GLTs) during late pregnancy. Multivariable linear and logistic regression models were used to assess associations between time-specific BP-3 in quartiles (Q1 - Q4) and mean glucose levels, as well as odds of abnormal GLT (glucose level >/= 140 mg/dL), adjusting for potential confounders. Effect modification was assessed by age, season, BMI, infertility diagnosis, sex of fetus (es) and physical activity. RESULTS: Women with higher first trimester BP-3 concentrations had lower mean glucose levels [mean glucose (95% CI) for Q4 vs Q1 = 103.4 (95.0, 112.5) vs. 114.6 (105.8, 124.2) mg/dL]. Women with higher second trimester BP-3 concentrations had lower odds of abnormal GLT [OR (95% CI) for Q3 vs. Q1 = 0.12 (0.01, 0.94)]. The associations between BP-3 and glucose levels were modified by several factors: women with female-factor infertility, urine collected during summer, older age, lower BMI, or carried female fetus (es) had the strongest inverse associations between BP-3 and glucose levels, while no associations were observed in the remaining subgroups. CONCLUSIONS: Time-specific inverse associations between BP-3 and pregnancy glucose levels existed in subfertile women, and especially among certain subgroups of this high-risk-population.

    • Epidemiology and Surveillance
      1. Developing monitoring and evaluation tools for event-based surveillance: experience from Vietnamexternal icon
        Clara A, Dao AT, Mounts AW, Bernadotte C, Nguyen HT, Tran QM, Tran QD, Dang TQ, Merali S, Balajee SA, Do TT.
        Global Health. 2020 Apr 30;16(1):38.
        BACKGROUND: In 2016-2017, Vietnam's Ministry of Health (MoH) implemented an event-based surveillance (EBS) pilot project in six provinces as part of Global Health Security Agenda (GHSA) efforts. This manuscript describes development and design of tools for monitoring and evaluation (M&E) of EBS in Vietnam. METHODS: A strategic EBS framework was developed based on the EBS implementation pilot project's goals and objectives. The main process and outcome components were identified and included input, activities, outputs, and outcome indicators. M&E tools were developed to collect quantitative and qualitative data. The tools included a supervisory checklist, a desk review tool, a key informant interview guide, a focus group discussion guide, a timeliness form, and an online acceptability survey. An evaluation team conducted field visits for assessment of EBS 5-9 months after implementation. RESULTS: The quantitative data collected provided evidence on the number and type of events that were being reported, the timeliness of the system, and the event-to-signal ratio. The qualitative and subjective data collected helped to increase understanding of the system's field utility and acceptance by field staff, reasons for non-compliance with established guidelines, and other factors influencing implementation. CONCLUSIONS: The use of M&E tools for the EBS pilot project in Vietnam provided data on signals and events reported, timeliness of reporting and response, perceptions and opinions of implementers, and fidelity of EBS implementation. These data were valuable for Vietnam's MoH to understand the function of the EBS program, and the success and challenges of implementing this project in Vietnam.

    • Food Safety
      1. Preliminary incidence and trends of infections with pathogens transmitted commonly through food - Foodborne Diseases Active Surveillance Network, 10 U.S. sites, 2016-2019external icon
        Tack DM, Ray L, Griffin PM, Cieslak PR, Dunn J, Rissman T, Jervis R, Lathrop S, Muse A, Duwell M, Smith K, Tobin-D'Angelo M, Vugia DJ, Zablotsky Kufel J, Wolpert BJ, Tauxe R, Payne DC.
        MMWR Morb Mortal Wkly Rep. 2020 May 1;69(17):509-514.
        To evaluate progress toward prevention of enteric illnesses, the Foodborne Diseases Active Surveillance Network (FoodNet) of CDC's Emerging Infections Program monitors the incidence of laboratory-diagnosed infections caused by eight pathogens transmitted commonly through food at 10 U.S. sites.* This report summarizes preliminary 2019 data and describes changes in incidence compared with that during 2016-2018. The incidence of enteric infections caused by these eight pathogens reported by FoodNet sites in 2019 continued to increase or remained unchanged, indicating progress in controlling major foodborne pathogens in the United States has stalled. Campylobacter and Salmonella caused the largest proportion of illnesses; trends in incidence varied by Salmonella serotype. Widespread adoption of whole genome sequencing (WGS) of bacteria has improved the ability to identify outbreaks, emerging strains, and sources of pathogens. To maximize the potential of WGS to link illnesses to particular sources, testing of isolates by clinical and public health laboratories is needed. Reductions in Salmonella serotype Typhimurium suggest that targeted interventions (e.g., vaccinating chickens and other food animals) might decrease human infections. Reducing contamination during food production, processing, and preparation will require more widespread implementation of known prevention measures and of new strategies that target particular pathogens and serotypes.

    • Health Behavior and Risk
      1. A triadic intervention for adolescent sexual health: A randomized clinical trialexternal icon
        Guilamo-Ramos V, Benzekri A, Thimm-Kaiser M, Dittus P, Ruiz Y, Cleland CM, McCoy W.
        Pediatrics. 2020 Apr 28.
        OBJECTIVES: In this study, we evaluate the efficacy of Families Talking Together (FTT), a triadic intervention to reduce adolescent sexual risk behavior. METHODS: Adolescents aged 11 to 14 and their female caregivers were recruited from a pediatric clinic; 900 families were enrolled; 84 declined. Families were randomly assigned to FTT or 1 of 2 control conditions. The FTT triadic intervention consisted of a 45-minute face-to-face session for mothers, health care provider endorsement of intervention content, printed materials for families, and a booster call for mothers. The primary outcomes were ever having had vaginal intercourse, sexual debut within the past 12 months, and condom use at last sexual intercourse. Assessments occurred at baseline, 3 months post baseline, and 12 months post baseline. RESULTS: Of enrolled families, 73.4% identified as Hispanic, 20.4% as African American, and 6.2% as mixed race. Mean maternal age was 38.8 years, and mean adolescent grade was seventh grade. At the 12-month follow-up, 5.2% of adolescents in the experimental group reported having had sexual intercourse, compared with 18% of adolescents in the control groups (P < .05). In the experimental group, 4.7% of adolescents reported sexual debut within the past 12 months, compared with 14.7% of adolescents in the control group (P < .05). In the experimental group, 74.2% of sexually active adolescents indicated using a condom at last sexual intercourse, compared with 49.1% of adolescents in the control group (P < .05). CONCLUSIONS: This research suggests that the FTT triadic intervention is efficacious in delaying sexual debut and reducing sexual risk behavior among adolescents.

    • Health Disparities
      1. Racial disparities in mortality in the adult hispanic populationexternal icon
        Arias E, Johnson NJ, Vera BT.
        SSM Popul Health. 2020 Aug;11:100583.
        Objective: We addressed three research questions: (1) Are there racial mortality disparities in the adult Hispanic population that resemble those observed in the non-Hispanic population in the US? (2) Does nativity mediate the race-mortality relationship in the Hispanic population? and (3) What does the Hispanic mortality advantage relative to the non-Hispanic white population look like when Hispanic race is considered? Methods: We estimated a series of parametric hazard models on eight years of mortality follow-up data and calculated life expectancy estimates using the Mortality Disparities in American Communities database. Results: Hispanic white adults experience lower mortality than their Hispanic black, American Indian and Alaska Native, Some Other Race, and multiple race counterparts. This Hispanic white advantage is found mostly among the US born. The Hispanic advantage relative to the non-Hispanic white population operates for most Hispanic race groups among the foreign born but either disappears or converts to a disadvantage for most of the non-white Hispanic groups among the US born. Contribution: Our study extends the literature on the Hispanic Mortality Paradox by revealing that the adult Hispanic population experiences racial mortality disparities that closely resemble those observed in the non-Hispanic population. The Hispanic mortality advantage is mediated not only by nativity but by race. These results indicate that race is a critical factor that should be considered in any study with the goal of understanding the health and mortality profiles of the Hispanic population in the US.

    • Health Economics
      1. BACKGROUND: Medication nonadherence is an important element of uncontrolled hypertension. Financial factors are frequently contributor to nonadherence. The objective of this study was to examine the association between cost-related medication nonadherence and self-reported antihypertensive medication use and self-reported normal blood pressure among US adults with self-reported hypertension. METHODS: Participants with self-reported hypertension from the 2017 National Health Interview Survey were included (n=7,498). Cost-related medication nonadherence was defined using standard questions. Hypertension management included: 1) self-reported current antihypertensive medication use, and 2) self-reported normal blood pressure within the past 12 months. Adjusted prevalence and prevalence ratios of hypertension management indicators among those with and without cost-related medication non-adherence were estimated. RESULTS: Overall, 10.7% reported cost-related medication nonadherence, 83.6% reported current antihypertensive medication use, and 67.4% reported normal blood pressure within past 12 months. Adjusted percentages of current antihypertensive medication use (88.6% vs 82.9%, p<0.001) and self-reported normal blood pressure (69.8% vs 59.5%, p=0.002) were higher among those without cost-related medication nonadherence compared to those with cost-related medication nonadherence. Adjusted prevalence ratios showed that, compared to those with cost-related medication non-adherence, those without cost-related medication non-adherence were more likely to report current antihypertensive medication use (OR=1.08, 95% confidence interval 1.04-1.12) and self-reported normal blood pressure (1.15 (1.07-1.23)). CONCLUSIONS: Among US adults with self-reported hypertension, those without cost-related medication nonadherence were more likely to report current antihypertensive medication use and normal blood pressure within the past 12 months. Financial barriers to medication adherence persist and impact hypertension management.

      2. Budgetary impact from multiple perspectives of sustained antitobacco national media campaigns to reduce the harms of cigarette smokingexternal icon
        Maciosek MV, Armour BS, Babb SD, Dhemer SP, Grossman ES, Homa DM, LaFrance AB, Rodes R, Wang X, Xu Z, Yang Z, Roy K.
        Tob Control. 2020 Apr 27.
        BACKGROUND: High-intensity antitobacco media campaigns are a proven strategy to reduce the harms of cigarette smoking. While buy-in from multiple stakeholders is needed to launch meaningful health policy, the budgetary impact of sustained media campaigns from multiple payer perspectives is unknown. METHODS: We estimated the budgetary impact and time to breakeven from societal, all-payer, Medicare, Medicaid and private insurer perspectives of national antitobacco media campaigns in the USA. Campaigns of 1, 5 and 10 years of durations were assessed in a microsimulation model to estimate the 10 and 20-year health and budgetary impact. Simulation model inputs were obtained from literature and both pubic use and proprietary data sets. RESULTS: The microsimulation predicts that a 10-year national smoking cessation campaign would produce net savings of $10.4, $5.1, $1.4, $3.6 and $0.2 billion from the societal, all-payer, Medicare, Medicaid and private insurer perspectives, respectively. National antitobacco media campaigns of 1, 5 and 10-year durations could produce net savings for Medicaid and Medicare within 2 years, and for private insurers within 6-9 years. A 10-year campaign would reduce adult cigarette smoking prevalence by 1.2 percentage points, prevent 23 500 smoking-attributable deaths over the first 10 years. In sensitivity analysis, media campaign costs would be offset by reductions in medical care spending of smoking among all payers combined within 6 years in all tested scenarios. CONCLUSIONS: 1, 5 and 10-year antitobacco media campaigns all yield net savings within 10 years from all perspectives. Multiyear campaigns yield substantially higher savings than a 1-year campaign.

      3. In 2017, the Virginia Department of Health (VDH) implemented billing of insurance in local health department sexually transmitted disease (STD) clinics. We examined data collected by VDH related to clinic encounters, billing, and revenue from STD clinics statewide. Implementing insurance billing created a new revenue stream for local health departments.

      4. OBJECTIVE: To estimate the average lost work productivity due to non-fatal injuries in the USA comprehensively by injury type. METHODS: The attributable average number and value of lost work days in the year following non-fatal emergency department (ED)-treated injuries were estimated by injury mechanism (eg, fall) and body region (eg, head and neck) among individuals age 18-64 with employer health insurance injured 1 October 2014 through 30 September 2015 as reported in MarketScan medical claims and Health and Productivity Management databases. Workplace, short-term disability and workers' compensation absences were assessed. Multivariable regression models compared lost work days among injury patients and matched controls during the year following injured patients' ED visit, controlling for demographic, clinical and health insurance factors. Lost work days were valued using an average US daily market production estimate. Costs are 2015 USD. RESULTS: The 1-year per-person average number and value of lost work days due to all types of non-fatal injuries combined were approximately 11 days and US$1590. The range by injury mechanism was 1.5 days (US$210) for bites and stings to 44.1 days (US$6196) for motorcycle injuries. The range by body region was 4.0 days (US$567) for other head, face and neck injuries to 19.8 days (US$2787) for traumatic brain injuries. CONCLUSIONS AND RELEVANCE: Injuries are costly and preventable. Accurate estimates of attributable lost work productivity are important to monitor the economic burden of injuries and help to prioritise cost-effective public health prevention activities.

      5. Medical costs associated with metastatic breast cancer in younger, midlife, and older womenexternal icon
        Trogdon JG, Baggett CD, Gogate A, Reeder-Hayes KE, Rotter J, Zhou X, Ekwueme DU, Fairley TL, Wheeler SB.
        Breast Cancer Res Treat. 2020 Apr 28.
        PURPOSE: We estimated average medical costs due to metastatic breast cancer (mBC) among younger (aged 18-44), midlife (aged 45-64), and older women (aged 65 and older) by phase of care: initial, continuing, and terminal. METHODS: We used 2003-2014 North Carolina cancer registry data linked with administrative claims from public and private payers. We developed a claims-based algorithm to identify breast cancer patients who progressed to metastatic disease. We matched breast cancer patients (mBC and earlier stage) to non-cancer patients on age group, county of residence, and insurance plan. Outcomes were average monthly medical expenditures and expected medical expenditures by phase. We used regression to estimate excess costs attributed to mBC as the difference in mean payments between patients with mBC (N = 4806) and patients with each earlier-stage breast cancer (stage 1, stage 2, stage 3, and unknown stage; N = 21,772) and non-cancer controls (N = 109,631) by treatment phase and age group. RESULTS: Adjusted monthly costs for women with mBC were significantly higher than for women with earlier-stage breast cancer and non-cancer controls for all age groups and treatment phases except the initial treatment among women with stage 3 breast cancer at diagnosis. The largest expected total costs were for women aged 18-44 with mBC during the continuing phase ($209,961 95% Confidence Interval $165,736-254,186). CONCLUSIONS: We found substantial excess costs for mBC among younger women and during the continuing and terminal phases of survivorship. It is important to assess whether this care is high value for these women.

    • Healthcare Associated Infections
      1. Bloodstream infections with Candida auris among children in Colombia: Clinical characteristics and outcomes of 34 casesexternal icon
        Berrio I, Caceres DH, Coronell RW, Salcedo S, Mora L, Marin A, Varon C, Lockhart SR, Escandon P, Berkow EL, Rivera S, Chiller T, Vallabhaneni S.
        J Pediatric Infect Dis Soc. 2020 May 6.
        BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and healthcare-associated outbreaks. Here, we describe 34 cases of pediatric C. auris bloodstream infections (BSIs) identified during July 2014-October 2017 in 2 hospitals in Colombia. METHODS: We conducted a retrospective review of microbiology records for possible C. auris cases in 2 hospitals in Barranquilla and Cartagena. BSIs that occurred in patients aged <18 years confirmed as C. auris were included in this analysis. RESULTS: We identified 34 children with C. auris BSIs. Twenty-two (65%) patients were male, 21% were aged <28 days, 47% were aged 29-365 days, and 32% were aged >1 year. Underlying conditions included preterm birth (26%), being malnourished (59%), cancer (12%), solid-organ transplant (3%), and renal disease (3%). Eighty-two percent had a central venous catheter (CVC), 82% were on respiratory support, 56% received total parenteral nutrition (TPN), 15% had a surgical procedure, and 9% received hemodialysis. Preinfection inpatient stay was 22 days (interquartile range, 19-33 days), and in-hospital mortality was 41%. CONCLUSIONS: Candida auris affects children with a variety of medical conditions including prematurity and malignancy, as well as children with CVCs and those who receive TPN. Mortality was high, with nearly half of patients dying before discharge. However, unlike most other Candida species, C. auris can be transmitted in healthcare settings, as suggested by the close clustering of cases in time at each of the hospitals.Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and healthcare-associated outbreaks. This report describes 34 cases of pediatric C. auris bloodstream infections, identified in two hospitals in Colombia, South America.

      2. Use of whole-genome sequencing to detect an outbreak of Malassezia pachydermatis infection and colonization in a neonatal intensive care unit-California, 2015-2016external icon
        Chow NA, Chinn R, Pong A, Schultz K, Kim J, Gade L, Jackson BR, Beer KD, Litvintseva AP.
        Infect Control Hosp Epidemiol. 2020 May 6:1-3.
        Whole-genome sequencing confirmed the presence of a Malassezia pachydermatis outbreak among neonates in a neonatal intensive care unit. This technology supports the importance of adhering to infection prevention measures.

      3. Tracing the evolutionary history and global expansion of Candida auris using population genomic analysesexternal icon
        Chow NA, Munoz JF, Gade L, Berkow EL, Li X, Welsh RM, Forsberg K, Lockhart SR, Adam R, Alanio A, Alastruey-Izquierdo A, Althawadi S, Arauz AB, Ben-Ami R, Bharat A, Calvo B, Desnos-Ollivier M, Escandon P, Gardam D, Gunturu R, Heath CH, Kurzai O, Martin R, Litvintseva AP, Cuomo CA.
        mBio. 2020 Apr 28;11(2).
        Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris IMPORTANCE In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.

      4. CONTEXT: The Centers for Disease Control and Prevention awarded $85 million to health care-associated infection and antibiotic resistance (HAI/AR) programs in March 2015 as part of Infection Control Assessment and Response (ICAR) activities in the Epidemiology and Laboratory Capacity cooperative agreement Domestic Ebola Supplement. PROGRAM: One goal of this funding was to assess and improve program capacity to respond to potential health care outbreaks (eg, HAI clusters). All 55 funded programs (in 49 state and 6 local health departments) participated. IMPLEMENTATION: The Centers for Disease Control and Prevention developed guidance and tools for HAI/AR programs to document relevant response capacities, assess policies, and measure progress. HAI/AR programs completed an interim assessment in 2016 and a final progress report in 2017. EVALUATION: During the project period, 78% (n = 43) of the programs developed new investigation tools, 85% (n = 47) trained staff on outbreak response, and 96% (n = 53) of the programs reported hiring staff to assist with outbreak response activities. Staffing and expertise to support HAI outbreak response increased substantially among awardees reporting staffing limitations on the interim assessment, including in domains such as on-site infection control assessment (n = 20; 83%), laboratory capacity (n = 20; 91%), and data management/analytics (n = 14; 67%). By 2017, reporting requirements in 100% of the programs addressed possible HAI/AR outbreaks; 93% (n = 51) also addressed sentinel events such as identification of novel AR threats. More than 90% (n = 50) of programs enhanced capacities for tracking response activities; in 2016, these systems captured 6665 events (range, 3-1379; median = 46). Health departments also reported wide-ranging efforts to engage regulatory, public health, and health care partners to improve HAI/AR outbreak reporting and investigation. DISCUSSION: Broad capacity for responding to HAI/AR outbreaks was enhanced using Ebola ICAR supplemental funding. As response activities expand, health department programs will be challenged to continue building expertise, reporting infrastructure, investigation resources, and effective relations with health care partners.

      5. Vascular access and risk of bloodstream infection among older incident hemodialysis patientsexternal icon
        Kazakova SV, Baggs J, Apata IW, Yi SH, Jernigan JA, Nguyen D, Patel PR.
        Kidney Medicine. 2020 .
        Rationale & Objective: Most new patients with end-stage renal disease (ESRD) initiate hemodialysis (HD) with a central venous catheter (CVC) and later transition to a permanent vascular access with lower infection risk. The benefit of early fistula use in preventing severe infections is incompletely understood. We examined patients’ first access and subsequent transitions between accesses during the first year of HD to estimate the risk for bloodstream infection (BSI) associated with incident and time-dependent use of HD access. Study Design: A retrospective cohort study using enhanced 5% Medicare claims data. Setting & Participants: New patients with ESRD initiating HD between January 1, 2011, and December 31, 2012, and having complete pre-ESRD Medicare fee-for-service coverage for 2 years. Exposure: The incident and prevalent use of CVC, graft, or fistula as determined from monthly reports to the Centers for Medicare & Medicaid Services by HD providers. Outcome: Incident hospitalization with a primary/secondary diagnosis of BSI (International Classification of Diseases, Ninth Revision, Clinical Modification code 038.xx or 790.7). Analytical Approach: Extended survival analysis accounting for patient confounders. Results: Of 2,352 study participants, 1,870 (79.5%), 77 (3.3%), and 405 (17.2%) initiated HD with a CVC, graft, and fistula, respectively. During the first year, the incident BSI hospitalization rates per 1,000 person-days were 1.3, 0.8, and 0.3 (P<0.001) in patients initiating with a CVC, graft, and fistula, respectively. After adjusting for confounders, incident fistula use was associated with 61% lower risk for BSI (HR, 0.39; 95% CI, 0.28-0.54; P<0.001) compared with incident CVC or graft use. The prevalent fistula or graft use was associated with lower risk for BSI compared with prevalent CVC use (HRs of 0.30 [95% CI, 0.22-0.42] and 0.47 [95% CI, 0.31-0.73], respectively). Limitations: Restricted to an elderly population; potential residual confounding. Conclusions: Incident fistula use was associated with lowest rates of BSI, but the majority of beneficiaries with pre-ESRD insurance initiated HD with a CVC. Strategies are needed to improve pre-ESRD fistula placement.

      6. Documentation of acute change in mental status in nursing homes highlights opportunity to augment infection surveillance criteriaexternal icon
        Penna AR, Sancken CL, Stone ND, Eure TR, Bamberg W, Barney G, Barter D, Carswell S, Clogher P, Dumyati G, Felsen CB, Frank L, Godine D, Johnston H, Kainer MA, Li L, Lynfield R, Mahoehney JP, Nadle J, Pierce R, Ray SM, Davis SS, Sievers M, Wilson LE, Zhang AY, Magill SS, Thompson ND.
        Infect Control Hosp Epidemiol. 2020 Apr 28:1-3.
        Acute change in mental status (ACMS), defined by the Confusion Assessment Method, is used to identify infections in nursing home residents. A medical record review revealed that none of 15,276 residents had an ACMS documented. Using the revised McGeer criteria with a possible ACMS definition, we identified 296 residents and 21 additional infections. The use of a possible ACMS definition should be considered for retrospective nursing home infection surveillance.

      7. Genomic characterization of Neisseria gonorrhoeae strains from 2016 U.S. sentinel surveillance displaying reduced susceptibility to azithromycinexternal icon
        Schmerer MW, Abrams AJ, Seby S, Thomas IV JC, Cartee J, Lucking S, Vidyaprakash E, Pham CD, Sharpe S, Pettus K, St Cyr SB, Torrone EA, Kersh EN, Gernert KM.
        Antimicrob Agents Chemother. 2020 Apr 21;64(5).
        In 2016, the proportion of Neisseria gonorrhoeae isolates with reduced susceptibility to azithromycin rose to 3.6%. A phylogenetic analysis of 334 N. gonorrhoeae isolates collected in 2016 revealed a single, geographically diverse lineage of isolates with MICs of 2 to 16 mug/ml that carried a mosaic-like mtr locus, whereas the majority of isolates with MICs of >/=16 mug/ml appeared sporadically and carried 23S rRNA mutations. Continued molecular surveillance of N. gonorrhoeae isolates will identify new resistance mechanisms.

    • Immunity and Immunization
      1. BACKGROUND: Rotavirus disease rates dramatically declined among children <5 years of age since the rotavirus vaccine was introduced in 2006; population-level impacts remain to be fully elucidated. METHODS: Data from the Healthcare Cost and Utilization Project State Inpatient Databases were used to conduct a time-series analysis of monthly hospital discharges across age groups for acute gastroenteritis and rotavirus from 2000 to 2013. Rate ratios were calculated comparing prevaccine and postvaccine eras. RESULTS: Following vaccine introduction, a decrease in rotavirus hospitalizations occurred with a shift toward biennial patterns across all ages. The 0-4-year age group experienced the largest decrease in rotavirus hospitalizations (rate ratio, 0.14; 95% confidence interval, .09-.23). The 5-19-year and 20-59-year age groups experienced significant declines in rotavirus hospitalization rates overall; the even postvaccine calendar years were characterized by progressively lower rates, and the odd postvaccine years were associated with reductions in rates that diminished over time. Those aged >/=60 years experienced the smallest change in rotavirus hospitalization rates overall, with significant reductions in even postvaccine years compared with prevaccine years (rate ratio, 0.51; 95% confidence interval, .39-.66). CONCLUSIONS: Indirect impacts of infant rotavirus vaccination are apparent in the emergence of biennial patterns in rotavirus hospitalizations that extend to all age groups ineligible for vaccination. These observations are consistent with the notion that young children are of primary importance in disease transmission and that the initial postvaccine period of dramatic population-wide impacts will be followed by more complex incidence patterns across the age range in the long term.

      2. Use of standing orders for vaccination among pediatriciansexternal icon
        Cataldi J, O'Leary ST, Lindley MC, Allison MA, Hurley LP, Crane LA, Brtnikova M, Beaty B, McBurney E, Kempe A.
        Pediatrics. 2020 Apr 29.
        OBJECTIVES: Standing orders are an effective way to increase vaccination rates, yet little is known about how pediatricians use this strategy for childhood immunizations. We assessed current use of, barriers to using, and factors associated with use of standing orders for vaccination among pediatricians. METHODS: Internet and mail survey from June 2017 to September 2017 among a nationally representative sample of pediatricians. In the principal component analysis of barrier items, we identified 2 factors: physician responsibility and concerns about office processes. A multivariable analysis that included barrier scales and physician and/or practice characteristics was used to identify factors associated with use of standing orders. RESULTS: The response rate was 79% (372 of 471); 59% of respondents reported using standing orders. The most commonly identified barriers among nonusers were concern that patients may mistakenly receive the wrong vaccine (68%), concern that patients prefer to speak with the physician about a vaccine before receiving it (62%), and belief that it is important for the physician to be the person who recommends a vaccine to patients (57%). These 3 items also made up the physician responsibility barrier factor. Respondents with higher physician responsibility scores were less likely to use standing orders (risk ratio: 0.59 [95% confidence interval: 0.53-0.66] per point increase). System-level decision-making about vaccines, suburban or rural location, and lower concerns about office processes scores were each associated with use of standing orders in the bivariate, but not the multivariable, analysis. CONCLUSIONS: Among pediatricians, use of standing orders for vaccination is far from universal. Interventions to increase use of standing orders should address physicians' attitudinal barriers as well as organizational factors.

      3. Patterns of influenza vaccination and vaccine effectiveness among young US children who receive outpatient care for acute respiratory tract illnessexternal icon
        Chung JR, Flannery B, Gaglani M, Smith ME, Reis EC, Hickey RW, Jackson ML, Jackson LA, Belongia EA, McLean HQ, Martin ET, Segaloff HE, Kim SS, Patel MM.
        JAMA Pediatr. 2020 May 4.
        Importance: The burden of influenza among young children is high, and influenza vaccination is the primary strategy to prevent the virus and its complications. Less is known about differences in clinical protection following 1 vs 2 doses of initial influenza vaccination. Objectives: To describe patterns of influenza vaccination among young children who receive outpatient care for acute respiratory tract illness in the US and compare vaccine effectiveness (VE) against medically attended laboratory-confirmed influenza by number of influenza vaccine doses received. Design: This test-negative case-control study was conducted in outpatient clinics, including emergency departments, at 5 sites of the US Influenza Vaccine Effectiveness Network during the 2014-2015 through 2017-2018 influenza seasons. The present study was performed from November 5, 2014, to April 12, 2018, during periods of local influenza circulation. Children aged 6 months to 8 years with an acute respiratory tract illness with cough who presented for outpatient care within 7 days of illness onset were included. All children were tested using real-time, reverse-transcriptase polymerase chain reaction for influenza for research purposes. Exposures: Vaccination in the enrollment season with either 1 or 2 doses of inactivated influenza vaccine as documented from electronic medical records, including state immunization information systems. Main Outcomes and Measures: Medically attended acute respiratory tract infection with real-time, reverse-transcriptase polymerase chain reaction testing for influenza. Results: Of 7533 children, 3480 children (46%) were girls, 4687 children (62%) were non-Hispanic white, and 4871 children (65%) were younger than 5 years. A total of 3912 children (52%) were unvaccinated in the enrollment season, 2924 children (39%) were fully vaccinated, and 697 children (9%) were partially vaccinated. Adjusted VE against any influenza was 51% (95% CI, 44%-57%) among fully vaccinated children and 41% (95% CI, 25%-54%) among partially vaccinated children. Among 1519 vaccine-naive children aged 6 months to 2 years, the VE of 2 doses in the enrollment season was 53% (95% CI, 28%-70%), and the VE of 1 dose was 23% (95% CI, -11% to 47%); those who received 2 doses were less likely to test positive for influenza compared with children who received only 1 dose (adjusted odds ratio, 0.57; 95% CI, 0.35-0.93). Conclusions and Relevance: Consistent with US influenza vaccine policy, receipt of the recommended number of doses resulted in higher VE than partial vaccination in 4 influenza seasons. Efforts to improve 2-dose coverage for previously unvaccinated children may reduce the burden of influenza in this population.

      4. The recent setbacks in efforts to achieve measles elimination goals are alarming. To reverse the current trends, it is imperative that the global health community urgently intensify efforts and make resource commitments to implement evidence-based elimination strategies fully, including supporting research and innovations. The Immunization Agenda 2030: A Global Strategy to Leave No One Behind (IA2030) is the new global guidance document that builds on lessons learned and progress made toward the GVAP goals, includes research and innovation as a core strategic priority, and identifies measles as a "tracer" for improving immunisation services and strengthening primary health care systems. To achieve vaccination coverage and equity targets that leave no one behind, and accelerate progress toward disease eradication and elimination goals, sustained and predictable investments are needed for the identified research and innovations priorities for the new decade.

      5. State policies on access to vaccination services for low-income adultsexternal icon
        Granade CJ, McCord RF, Bhatti AA, Lindley MC.
        JAMA Netw Open. 2020 Apr 1;3(4):e203316.
        Importance: State vaccination benefits coverage and access for adult Medicaid beneficiaries vary substantially. Multiple studies have documented lower vaccination uptake in publicly insured adults compared with privately insured adults. Objective: To evaluate adult Medicaid beneficiaries' access to adult immunization services through review of vaccination benefits coverage in Medicaid programs across the 50 states and the District of Columbia. Design, Setting, and Participants: A public domain document review with supplemental semistructured telephone survey was conducted between June 1, 2018, and June 14, 2019, to evaluate vaccination services benefits in fee-for-service and managed care organization arrangements for adult Medicaid beneficiaries in the 50 states and the District of Columbia (total, 51 Medicaid programs). Exposures: Document review of benefits coverage for adult immunization services and supplemental survey with validation of document review findings. Main Outcomes and Measures: Benefits coverage for adult Medicaid beneficiaries and reimbursement amounts for vaccine purchase and administration. Results: Public domain document review was completed for all 51 jurisdictions. Among these, 44 Medicaid programs (86%) validated document review findings and completed the survey. Only 22 Medicaid programs (43%) covered all 13 Advisory Committee on Immunization Practices-recommended adult immunizations under both fee-for-service and managed care organization arrangements. Most fee-for-service arrangements (37 of 49) reimbursed health care professionals using any of the 4 approved vaccine administration codes; however, 8 of 49 programs did not separately reimburse for vaccine administration to adult Medicaid beneficiaries. Depending on administration route, median reimbursement for adult vaccine administration ranged from $9.81 to $13.98 per dose. Median per-dose reimbursement for adult vaccine purchase was highest for 9-valent human papillomavirus vaccine ($204.87) and lowest for Haemophilus influenzae type b vaccine ($18.09). Median reimbursement was below the private sector price for 7 of the 13 included vaccines. Conclusions and Relevance: Even in programs with complete vaccination benefits coverage, reimbursement amounts to health care professionals for vaccine purchase and administration may not fully cover vaccination provision costs. Reimbursement amounts below costs may reduce incentives for health care professionals to vaccinate low-income adults and thereby limit Medicaid adult beneficiary access to vaccination.

      6. BACKGROUND: Group A Streptococcus (GAS) is a leading cause of acute respiratory infections frequently resulting in antibiotic prescribing. Vaccines against GAS are currently in development. METHODS: We estimated the incidence of healthcare visits and antibiotic prescribing for pharyngitis, sinusitis, and acute otitis media (AOM) in the United States using nationally-representative surveys of outpatient care provision, supplemented by insurance claims data. We estimated the proportion of these episodes attributable to GAS, and to GAS emm types included in a proposed 30-valent vaccine. We used these outputs to estimate the incidence of outpatient visits and antibiotic prescribing preventable by GAS vaccines with various efficacy profiles under infant and school-age dosing schedules. RESULTS: GAS pharyngitis causes 19.1 (95%CI: 17.3-21.1) outpatient visits and 10.2 (9.0-11.5) antibiotic prescriptions per 1,000 US persons aged 0-64 years, annually. GAS pharyngitis causes 93.2 (82.3-105.3) visits and 53.2 (45.2-62.5) antibiotic prescriptions per 1,000 children ages 3-9 years, annually, representing 5.9% (5.1-7.0%) of all outpatient antibiotic prescribing in this age group. Collectively, GAS-attributable pharyngitis, sinusitis, and AOM cause 26.9 (23.9-30.8) and 16.1 (14.0-18.7) outpatient visits and antibiotic prescriptions per 1,000 population, annually. A 30-valent GAS vaccine meeting the WHO 80% efficacy target could prevent 5.4% (4.6-6.4%) of outpatient antibiotic prescriptions among children aged 3-9 years. If vaccine prevention of GAS pharyngitis made routine antibiotic treatment of pharyngitis unnecessary, up to 17.1% (15.0-19.6%) of outpatient antibiotic prescriptions among children aged 3-9 years could be prevented. CONCLUSIONS: An efficacious GAS vaccine could prevent substantial incidence of pharyngitis infections and associated antibiotic prescribing in the United States.

      7. Theoretical risk of genetic reassortment should not impede development of live, attenuated Rift Valley fever (RVF) vaccines commentary on the draft WHO RVF Target Product Profileexternal icon
        Monath TP, Kortekaas J, Watts DM, Christofferson RC, Desiree LaBeaud A, Gowen B, Peters CJ, Smith DR, Swanepoel R, Morrill JC, Ksiazek TG, Pittman PR, Bird BH, Bettinger G.
        Vaccine X. 2020 Aug 7;5:100060.
        In November 2019, The World Health Organization (WHO) issued a draft set of Target Product Profiles (TPPs) describing optimal and minimally acceptable targets for vaccines against Rift Valley fever (RVF), a Phlebovirus with a three segmented genome, in both humans and ruminants. The TPPs contained rigid requirements to protect against genomic reassortment of live, attenuated vaccines (LAVs) with wild-type RVF virus (RVFV), which place undue constraints on development and regulatory approval of LAVs. We review the current LAVs in use and in development, and conclude that there is no evidence that reassortment between LAVs and wild-type RVFV has occurred during field use, that such a reassortment event if it occurred would have no untoward consequence, and that the TPPs should be revised to provide a more balanced assessment of the benefits versus the theoretical risks of reassortment.

      8. Progress toward maternal and neonatal tetanus elimination - worldwide, 2000-2018external icon
        Njuguna HN, Yusuf N, Raza AA, Ahmed B, Tohme RA.
        MMWR Morb Mortal Wkly Rep. 2020 May 1;69(17):515-520.
        Maternal and neonatal tetanus* (MNT) remains a major public health problem, with an 80%-100% case-fatality rate among neonates, especially in areas with poor immunization coverage and limited access to clean deliveries (i.e., delivery in a health facility or assisted by medically trained attendants in sanitary conditions) and umbilical cord care (1). In 1989, the World Health Assembly endorsed the elimination(dagger) of neonatal tetanus (NT), and in 1999, the initiative was relaunched and renamed the MNT elimination( section sign) initiative, targeting 59( paragraph sign) priority countries (1). Elimination strategies include 1) achieving >/=80% coverage with >/=2 doses of tetanus toxoid-containing vaccine (TTCV) among women of reproductive age through routine immunization of pregnant women and supplementary immunization activities (SIAs)** in high-risk areas and districts(daggerdagger); 2) achieving care at >/=70% of deliveries by a skilled birth attendant (SBA)( section sign section sign); and 3) enhancing surveillance for NT cases (1). This report summarizes progress toward achieving MNT elimination during 2000-2018. Coverage with >/=2 doses of TTCV (2 doses of tetanus toxoid [TT2+] or 2 doses of tetanus-diphtheria toxoid [Td2+]) among women of reproductive age increased by 16%, from 62% in 2000 to 72% in 2018. By December 2018, 52 (88%) of 59 priority countries had conducted TTCV SIAs, vaccinating 154 million (77%) of 201 million targeted women of reproductive age with TT2+/Td2+. Globally, the percentage of deliveries assisted by SBAs increased from 62% during 2000-2005 to 81% during 2013-2018, and estimated neonatal tetanus deaths decreased by 85%, from 170,829 in 2000 to 25,000 in 2018. By December 2018, 45 (76%) of 59 priority countries were validated by WHO as having achieved MNT elimination. To achieve elimination in the remaining 14 countries and sustain elimination in countries that have achieved it, implementation of MNT elimination strategies needs to be maintained and strengthened, and TTCV booster doses need to be included in country immunization schedules as recommended by the World Health Organization (WHO) (2). In addition, integration of maternal, newborn, and child health services with vaccination services is needed, as well as innovative approaches to target hard-to-reach areas for tetanus vaccination and community engagement to strengthen surveillance.

      9. Characterization of pneumococcal meningitis before and after introduction of 13-valent pneumococcal conjugate vaccine in Niger, 2010-2018external icon
        Ousmane S, Kobayashi M, Seidou I, Issaka B, Sharpley S, Farrar JL, Whitney CG, Ouattara M.
        Vaccine. 2020 Apr 20.
        Pneumococcal meningitis in the African meningitis belt is primarily caused by Streptococcus pneumoniae serotype 1, a serotype contained in the 13-valent pneumococcal conjugate vaccine (PCV13). In 2014, Niger introduced PCV13 with doses given at 6, 10, and 14 weeks of age. We leveraged existing meningitis surveillance data to describe pneumococcal meningitis trends in Niger. As a national reference laboratory for meningitis, Centre de Recherche Medicale et Sanitaire (CERMES) receives cerebrospinal fluid specimens from suspected bacterial meningitis cases and performs confirmatory testing for an etiology by culture or polymerase chain reaction (PCR). Specimens with S. pneumoniae detection during 2010-2018 were sent to the Centers for Disease Control and Prevention for serotyping by sequential triplex real-time PCR. Specimens that were non-typeable by real-time PCR underwent serotyping by conventional multiplex PCR. We tested differences in the distribution of pneumococcal serotypes before (2010-2012) and after (2016-2018) PCV13 introduction. During January 2010 to December 2018, CERMES received 16,155 specimens; 5,651 (35%) had bacterial etiology confirmed. S. pneumoniae accounted for 13.2% (744/5,651); 53.1% (395/744) were serotyped. During 2010-12, PCV13-associated serotypes (VT) constituted three-fourths of serotyped pneumococcus-positive specimens; this proportion declined in all age groups in 2016-18, most substantially in children aged < 5 years (74.0% to 28.1%; P < 0.05). Among persons aged >/= 5 years, VT constituted > 50% of pneumococcal meningitis after PCV13 introduction; serotype 1 remained the most common VT among persons aged >/= 5 years, but not among those < 5 years. VT as a group caused a smaller proportion of reported pneumococcal meningitis cases after PCV13 introduction in Niger. Serotype 1, however, remains the major cause of pneumococcal meningitis in older children and adults. Different vaccination strategies, such as changing the infant vaccination schedule or extending vaccine coverage to older children and adults, are needed, in addition to stronger surveillance.

      10. Effects of the COVID-19 pandemic on routine pediatric vaccine ordering and administration - United States, 2020external icon
        Santoli JM, Lindley MC, DeSilva MB, Kharbanda EO, Daley MF, Galloway L, Gee J, Glover M, Herring B, Kang Y, Lucas P, Noblit C, Tropper J, Vogt T, Weintraub E.
        MMWR Morb Mortal Wkly Rep. 2020 May 15;69(19):591-593.
        On March 13, 2020, the president of the United States declared a national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic (1). With reports of laboratory-confirmed cases in all 50 states by that time (2), disruptions were anticipated in the U.S. health care system's ability to continue providing routine preventive and other nonemergency care. In addition, many states and localities issued shelter-in-place or stay-at-home orders to reduce the spread of COVID-19, limiting movement outside the home to essential activities (3). On March 24, CDC posted guidance emphasizing the importance of routine well child care and immunization, particularly for children aged </=24 months, when many childhood vaccines are recommended.

      11. Impact of 13-valent pneumococcal conjugate vaccine on colonization and invasive disease in Cambodian childrenexternal icon
        Turner P, Leab P, Ly S, Sao S, Miliya T, Heffelfinger JD, Batmunkh N, Lessa FC, Walldorf JA, Hyde TB, Ork V, Hossain MS, Gould KA, Hinds J, Cooper BS, Ngoun C, Turner C, Day NP.
        Clin Infect Dis. 2020 Apr 10;70(8):1580-1588.
        BACKGROUND: Cambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3 + 0 dosing schedule and no catch-up campaign. We investigated the effects of this introduction on pneumococcal colonization and invasive disease in children aged <5 years. METHODS: There were 6 colonization surveys done between January 2014 and January 2018 in children attending the outpatient department of a nongovernmental pediatric hospital in Siem Reap. Nasopharyngeal swabs were analyzed by phenotypic and genotypic methods to detect pneumococcal serotypes and antimicrobial resistance. Invasive pneumococcal disease (IPD) data for January 2012-December 2018 were retrieved from hospital databases. Pre-PCV IPD data and pre-/post-PCV colonization data were modelled to estimate vaccine effectiveness (VE). RESULTS: Comparing 2014 with 2016-2018, and using adjusted prevalence ratios, VE estimates for colonization were 16.6% (95% confidence interval [CI] 10.6-21.8) for all pneumococci and 39.2% (95% CI 26.7-46.1) for vaccine serotype (VT) pneumococci. There was a 26.0% (95% CI 17.7-33.0) decrease in multidrug-resistant pneumococcal colonization. The IPD incidence was estimated to have declined by 26.4% (95% CI 14.4-35.8) by 2018, with a decrease of 36.3% (95% CI 23.8-46.9) for VT IPD and an increase of 101.4% (95% CI 62.0-145.4) for non-VT IPD. CONCLUSIONS: Following PCV13 introduction into the Cambodian immunization schedule, there have been declines in VT pneumococcal colonization and disease in children aged <5 years. Modelling of dominant serotype colonization data produced plausible VE estimates.

    • Informatics
      1. Building HIV healthcare worker capacity through telehealth in Vietnamexternal icon
        Pollack TM, Nhung VT, Vinh DT, Hao DT, Trang LT, Duc PA, Kinh NV, Dung NT, Dung DL, Ninh NT, Huyen HT, Huy VX, Hai DM, Khanh TH, Hien NT, Khuong PT, Trong NT, Lam NV, Phinh VN, Phuong DT, Duat ND, Liem NT, Binh NT, Chi NK, Yen LN, Cosimi L.
        BMJ Glob Health. 2020 ;5(4):e002166.
        Development of a robust technical assistance system is an essential component of a sustainable HIV response. Vietnam's National HIV Program is transitioning from a largely donor-funded programme to one primarily supported by domestic resources. Telehealth interventions are increasingly being used for training, mentoring and expert consultation in high-resource settings and hold significant potential for use as a tool to build HIV health worker capacity in low and middle-income countries. We designed, implemented and scaled up a novel HIV telehealth programme for Vietnam, with the goal of building a sustainable training model to support the country's HIV workforce needs. Over a 4-year period, HIV telehealth programmes were initiated in 17 public institutions with participation of nearly 700 clinical sites across 62 of the 63 provinces in the country. The telehealth programme was used to deliver certificate training courses, provide clinical mentoring and case-based learning, support programme implementation, provide coaching in quality improvement and disseminate new guidelines and policies. Programme evaluation demonstrated improved health worker self-reported competence in HIV care and treatment and high satisfaction among the programme participants. Lessons learnt from Vietnam's experience with telehealth can inform country programmes looking to develop a sustainable approach to HIV technical assistance and health worker capacity building.

    • Injury and Violence
      1. BACKGROUND: Sports- and recreation-related (SRR) activities are a major cause of adolescent concussions. Most adolescent SRR concussion research has been conducted among public school students. As private schools are qualitatively different from public schools (eg, location, socioeconomic status, sports played), this study explores the concussion experiences of a large group of private high school students. METHODS: We surveyed 2047 New England private preparatory high school students who played sports or engaged in a recreational activity in 2018 about the sports they played, and their self-reported concussion experiences (eg, age at first concussion, if concussions were sports- or recreation-related). Descriptive, bivariate, and multivariate statistics are presented. RESULTS: One-third (33.0%) of students who reported engaging in sport- or recreation-related activities self-reported experiencing a concussion in their lifetime. A higher percentage of boys, students who played contact sports, and those who played multiple seasons of school sports reported a concussion. Sex, contact level of primary sport played, and age of first concussion were also significantly associated with reporting a sports- or recreation-related concussion. CONCLUSIONS: A sizeable proportion of private preparatory high school students reported experiencing a concussion, with some students at higher risk. Private preparatory high school-specific concussion prevention strategies may be needed.

      2. BACKGROUND: School policies and practices designed to educate athletes, parents, and coaches about youth sports concussions may be a way to reduce concussion risk and improve both the recognition and management of concussions. METHODS: Nationally representative data from the 2014 School Health Policies and Practices Study (SHPPS) were used to assess associations between school demographic characteristics (eg, school level, metropolitan status, and school type) and school policies and practices addressing youth sports concussion-related education for athletes, parents, and coaches. RESULTS: Overall, many schools had policies and practices that addressed youth sports concussion-related education for athletes, parents, and coaches. There was significant variability in the adoption of policies and practices by some school demographic characteristics. Middle schools, private schools, and urban schools were less likely to adopt many of the policies and practices than high schools, public schools, and rural schools, respectively. For other school characteristics, no consistent patterns of associations emerged. CONCLUSIONS: These findings suggest that middle, private, and urban schools, in particular, are more likely to lack youth sports concussion-related educational policies and practices and may need information or resources about the importance of education related to preventing, recognizing, and responding to concussions.

      3. Public health addresses child maltreatment and other adverse childhood experiences by focusing primarily on preventing them from happening in the first place; understanding and addressing their individual, relational, community, and societal causes using the best available scientific evidence; and engaging in large-scale, multi-sector partnerships. Such large scale efforts require bringing together a compelling narrative, relationships, and strategy. This article describes how the Centers for Disease Control and Prevention used a public health approach to develop a narrative, relationships, and strategy to prevent child maltreatment.

    • Laboratory Sciences
      1. Massively multiplexed nucleic acid detection using Cas13external icon
        Ackerman CM, Myhrvold C, Thakku SG, Freije CA, Metsky HC, Yang DK, Ye SH, Boehm CK, Kosoko-Thoroddsen TF, Kehe J, Nguyen TG, Carter A, Kulesa A, Barnes JR, Dugan VG, Hung DT, Blainey PC, Sabeti PC.
        Nature. 2020 Apr 29.
        The overwhelming majority of globally circulating pathogens go undetected, undermining patient care and hindering outbreak preparedness and response. To enable routine surveillance and comprehensive diagnostic applications, there is a need for detection technologies that can scale to test many samples(1-3) while simultaneously testing for many pathogens(4-6). Here, we develop Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN), a platform for scalable, multiplexed pathogen detection. In the CARMEN platform, nanoliter droplets containing CRISPR-based nucleic acid detection reagents(7) self-organize in a microwell array(8) to pair with droplets of amplified samples, testing each sample against each CRISPR RNA (crRNA) in replicate. The combination of CARMEN and Cas13 detection (CARMEN-Cas13) enables robust testing of >4,500 crRNA-target pairs on a single array. Using CARMEN-Cas13, we developed a multiplexed assay that simultaneously differentiates all 169 human-associated viruses with >/=10 published genome sequences and rapidly incorporated an additional crRNA to detect the causative agent of the 2020 COVID-19 pandemic. CARMEN-Cas13 further enables comprehensive subtyping of influenza A strains and multiplexed identification of dozens of HIV drug-resistance mutations. CARMEN's intrinsic multiplexing and throughput capabilities make it practical to scale, as miniaturization decreases reagent cost per test >300-fold. Scalable, highly-multiplexed CRISPR-based nucleic acid detection shifts diagnostic and surveillance efforts from targeted testing of high-priority samples to comprehensive testing of large sample sets, greatly benefiting patients and public health(9-11).

      2. Antifungal susceptibility testing: Current approachesexternal icon
        Berkow EL, Lockhart SR, Ostrosky-Zeichner L.
        Clin Microbiol Rev. 2020 Jun 17;33(3).
        SUMMARYAlthough not as ubiquitous as antibacterial susceptibility testing, antifungal susceptibility testing (AFST) is a tool of increasing importance in clinical microbiology laboratories. The goal of AFST is to reliably produce MIC values that may be used to guide patient therapy, inform epidemiological studies, and track rates of antifungal drug resistance. There are three methods that have been standardized by standards development organizations: broth dilution, disk diffusion, and azole agar screening for Aspergillus Other commonly used methods include gradient diffusion and the use of rapid automated instruments. Novel methodologies for susceptibility testing are in development. It is important for laboratories to consider not only the method of testing but also the interpretation (or lack thereof) of in vitro data.

      3. IFCC Working Group recommendations for correction of bias caused by noncommutability of a certified reference material used in the calibration hierarchy of an end-user measurement procedureexternal icon
        Miller WG, Budd J, Greenberg N, Weykamp C, Althaus H, Schimmel H, Panteghini M, Delatour V, Ceriotti F, Keller T, Hawkins D, Burns C, Rej R, Camara JE, MacKenzie F, van der Hagen E, Vesper H.
        Clin Chem. 2020 Apr 25.
        Establishing metrological traceability to an assigned value of a matrix-based certified reference material (CRM) that has been validated to be commutable among available end-user measurement procedures (MPs) is central to producing equivalent results for the measurand in clinical samples (CSs) irrespective of the clinical laboratory MPs used. When a CRM is not commutable with CSs, the bias due to noncommutability will be propagated to the CS results causing incorrect metrological traceability to the CRM and nonequivalent CS results among different MPs. In a commutability assessment, a conclusion that a CRM is commutable or noncommutable for use with a specific MP is made when the difference in bias between the CRM and CSs meets or does not meet a criterion for that specific MP when compared to other MPs. A conclusion regarding commutability or noncommutability requires that the magnitude of the difference in bias observed in the commutability assessment remains unchanged over time. This conclusion requires the CRM to be stable and no substantive changes in the MPs. These conditions should be periodically reverified. If an available CRM is determined to be noncommutable for a specific MP, that CRM can be used in the calibration hierarchy for that MP when an appropriately validated MP-specific correction for the noncommutability bias is included. We describe with examples how a MP-specific correction and its uncertainty can be developed and applied in a calibration hierarchy to achieve metrological traceability of results for CSs to the CRM's assigned value.

      4. Recommendations for clinical warfarin sensitivity genotyping allele selection: A report of the Association for Molecular Pathology and College of American Pathologistsexternal icon
        Pratt VM, Cavallari LH, Del Tredici AL, Hachad H, Ji Y, Kalman LV, Ly RC, Moyer AM, Scott SA, Whirl-Carrillo M, Weck KE.
        J Mol Diagn. 2020 May 4.
        The goals of the Association for Molecular Pathology (AMP) Clinical Practice Committee's AMP Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic (PGx) alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document series provide recommendations for a minimum panel of variant alleles ("Tier 1") and an extended panel of variant alleles ("Tier 2") that will aid clinical laboratories when designing assays for PGx testing. The AMP PGx Working Group considered functional impact of the variants, allele frequencies in multiethnic populations, the availability of reference materials (RMs), as well as other technical considerations for PGx testing when developing these recommendations. Our ultimate goal is to promote standardization of PGx gene/allele testing across clinical laboratories. These recommendations are not to be interpreted as prescriptive but to provide a reference guide. Of note, a separate article with recommendations for CYP2C9 allele selection was previously developed by the PGx Working Group that can be applied broadly to CYP2C9-related medications. The warfarin sensitivity allele recommendations in this report incorporate the previous CYP2C9 allele recommendations and additional genes and alleles that are specific to warfarin sensitivity testing.

      5. In vitro intestinal toxicity of commercially available spray disinfectant products advertised to contain colloidal silverexternal icon
        Rogers KR, Henson TE, Navratilova J, Surette M, Hughes MF, Bradham KD, Stefaniak AB, Knepp AK, Bowers L.
        Sci Total Environ. 2020 Apr 14;728:138611.
        The use of colloidal silver-containing products as dietary supplements, immune boosters and surface disinfectants has increased in recent years which has elevated the potential for human exposure to silver nanoparticles and ions. Product mislabeling and long-term use of these products may put consumers at risk for adverse health outcomes including argyria. This study assessed several physical and chemical characteristics of five commercial products as well as their cytotoxicity using a rat intestinal epithelial cell (IEC-6) model. Concentrations of silver were determined for both the soluble and particulate fractions of the products. Primary particle size distribution and elemental composition were determined by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. Hydrodynamic diameters were measured using nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS). The effect of gastrointestinal (GI) simulation on the colloidal silver products was determined using two systems. First, physical and chemical changes of the silver nanoparticles in these products was assessed after exposure to Synthetic Stomach Fluid (SSF) resulting in particle agglomeration, and the appearance of AgCl on the surfaces and between particles. IEC-6 cells were exposed for 24 h to dilutions of the products and assessed for cell viability. The products were also treated with a three-stage simulated GI system (stomach and intestinal fluids) prior to exposure of the IEC-6 cells to the isolated silver nanoparticles. Cell viability was affected by each of the consumer products. Based on the silver nitrate and commercial silver nanoparticle dose response, the cytotoxicity for each of the colloidal silver products was attributed to the particulate silver, soluble silver or nonsilver matrix constituents.

      6. Potential for point-of-care tests to reduce chlamydia-associated burden in the United States: A mathematical modeling analysisexternal icon
        Ronn MM, Menzies NA, Gift TL, Chesson HW, Trikalinos TA, Bellerose M, Malyuta Y, Berruti A, Gaydos CA, Hsu KK, Salomon JA.
        Clin Infect Dis. 2020 Apr 15;70(9):1816-1823.
        BACKGROUND: Point-of-care testing (POCT) assays for chlamydia are being developed. Their potential impact on the burden of chlamydial infection in the United States, in light of suboptimal screening coverage, remains unclear. METHODS: Using a transmission model calibrated to data in the United States, we estimated the impact of POCT on chlamydia prevalence, incidence, and chlamydia-attributable pelvic inflammatory disease (PID) incidence, assuming status quo (Analysis 1) and improved (Analysis 2) screening frequencies. We tested the robustness of results to changes in POCT sensitivity, the proportion of patients getting treated immediately, the baseline proportion lost to follow-up (LTFU), and the average treatment delay. RESULTS: In Analysis 1, high POCT sensitivity was needed to reduce the chlamydia-associated burden. With a POCT sensitivity of 90%, reductions from the baseline burden only occurred in scenarios in which over 60% of the screened individuals would get immediate treatment and the baseline LTFU proportion was 20%. With a POCT sensitivity of 99% (baseline LTFU 10%, 2-week treatment delay), if everyone were treated immediately, the prevalence reduction was estimated at 5.7% (95% credible interval [CrI] 3.9-8.2%). If only 30% of tested persons would wait for results, the prevalence reduction was only 1.6% (95% CrI 1.1-2.3). POCT with 99% sensitivity could avert up to 12 700 (95% CrI 5000-22 200) PID cases per year, if 100% were treated immediately (baseline LTFU 20% and 3-week treatment delay). In Analysis 2, when POCT was coupled with increasing screening coverage, reductions in the chlamydia burden could be realized with a POCT sensitivity of 90%. CONCLUSIONS: POCT could improve chlamydia prevention efforts if test performance characteristics are significantly improved over currently available options.

      7. Building a public-private partnership to enhance laboratory preparedness and response in the United Statesexternal icon
        Salerno R, Chaitram J, Andreadis J.
        Disaster Med Public Health Prep. 2020 May 4:1-9.

      8. Adapting microarray gene expression signatures for early melioidosis diagnosisexternal icon
        Sangwichian O, Whistler T, Nithichanon A, Kewcharoenwong C, Sein MM, Arayanuphum C, Chantratita N, Lertmemongkolchai G.
        J Clin Microbiol. 2020 Apr 29.
        Melioidosis is caused by Burkholderia pseudomallei and is predominantly seen in tropical regions. The clinical signs and symptoms of the disease are non-specific often resulting in misdiagnosis, failure of treatment, and poor clinical outcome. Septicemia with septic shock is the most common cause of death with mortality rates above 40%. Bacterial culture is the gold standard for diagnosis but it has low sensitivity and takes days to produce definitive results. Early laboratory diagnosis can help guide physicians to provide treatment specific to B. pseudomallei In our study, we adapted host gene expression signatures obtained from microarray data of B. pseudomallei infected cases to develop a real-time PCR diagnostic test using two differentially expressed genes, AIM2 (Absent in Melanoma 2) and FAM26F (Family with sequence similarity 26, member F). We tested blood from 33 patients with B. pseudomallei and 29 patients with other bacterial infections to validate the test and determine cutoff values for use in a cascading diagnostic algorithm. Differentiation of septicemic melioidosis from other sepsis cases had a sensitivity of 82%, specificity of 93%, and negative and positive predictive values (NPV and PPV) of 82% and 93% respectively. Separation of cases likely to be melioidosis from unlikely cases in non-bacteremic situations showed a sensitivity of 40%, specificity of 54%, and NPV and PPV of 44% and 50% respectively. We suggest that our AIM2 and FAM26F expression combination algorithm could be beneficial for early melioidosis diagnosis offering a result within 24 hours of admission.

      9. OBJECTIVES: Serological tests of non-treponemal and treponemal types are the most frequently used for syphilis diagnosis. Treponemal tests are available in wide variety of assay formats; however, limited advances have been made for the improvement of conventional non-treponemal tests. The objective of this work was to develop a novel non-treponemal magnetic particle-based agglutination assay (NT-MAA) and evaluate its feasibility for syphilis testing. METHODS: Cardiolipin was modified and coupled to magnetic microbeads. Serum diluted in phosphate-buffered saline was mixed with cardiolipin-coupled beads and incubated in a round bottom microplate for 90-120 min followed by visual inspection. A panel of reported syphilis (n=127) and non-reactive (n=244) specimens was prepared to evaluate the NT-MAA performance in comparison to conventional rapid plasma reagin (RPR). Treponema pallidum particle agglutination (TP-PA) assay and enzyme immunoassay (EIA) were included. Analytical sensitivity and reproducibility of NT-MAA were also determined. RESULTS: The non-treponemal NT-MAA and RPR showed sensitivity of 90.6% and 88.2% and specificity of 96.7% and 100%, respectively. The treponemal TP-PA and EIA yielded sensitivity of 100% and 99.2%, respectively, and 100% specificity by both assays. The per cent agreement between NT-MAA and RPR was 97% (kappa=0.931, 95% CI 0.891 to 0.971). Analytical sensitivity determined with IgM anticardiolipin antibody (ACA) was 2.6 microg/mL for both NT-MAA and RPR, while IgG ACA yielded 0.9 microg/mL and 1.7 microg/mL for NT-MAA and RPR, respectively. Qualitative results of intra-assay and interassay reproducibility revealed 100% consistency for NT-MAA. CONCLUSION: Preliminary evaluation of the novel NT-MAA validated proof of concept using laboratory-characterised syphilis sera and demonstrated performance comparable to RPR. Further validation of NT-MAA using additional specimens with better clinical staging may broaden the scope of developed test for syphilis diagnosis.

      10. Routine HIV test results in 6 US clinical laboratories using the recommended laboratory HIV testing algorithm with Geenius HIV 1/2 supplemental assayexternal icon
        Wesolowski LG, Chavez PR, Cardenas AM, Katayev A, Slev P, Valsamakis A, Wang YF, Yao JD, Dougherty C, Gillim-Ross L, Harmon C, Delaney KP.
        Sex Transm Dis. 2020 May;47(5S Suppl 1):S13-s17.
        BACKGROUND: Geenius HIV 1/2 Supplemental Assay (Geenius; Bio-Rad Laboratories) is the only Food and Drug Administration-approved HIV-1/HIV-2 antibody differentiation test for the second step in the HIV laboratory testing algorithm. We characterized the occurrence of true HIV-1 and HIV-2 infections as well as false results in 6 US clinical laboratories using Geenius. METHODS: We examined routine HIV testing outcome data from the time the laboratories began using the algorithm with Geenius until September 30, 2017. We calculated the positive predictive value for Geenius HIV-1 and HIV-2 reactivity separately. RESULTS: Of 5,046,684 specimens tested, 41,791 had reactive antigen/antibody test results. Most specimens with reactive antigen/antibody results were HIV-1 antibody-positive established infections (n = 32,421), 1,865 of which also had indeterminate HIV-2 bands present. Ninety-three specimens were HIV-2 antibody positive or untypable for HIV-1/HIV-2 antibody. Acute HIV-1 infections were found in 528 specimens; 881 specimens lacked the nucleic acid test to determine the possibility of acute HIV-1 infection. False-positive antigen/antibody test results were present in 7505 specimens. Few specimens (n = 363) had false-positive antigen/antibody results with indeterminate Geenius and negative HIV-1 nucleic acid test results. The positive predictive values of Geenius reactivity were 99.4% for HIV-1 and 4.3% for HIV-2. CONCLUSIONS: Routine testing using the laboratory testing algorithm with Geenius resulted in most specimens resolving as HIV negative or HIV-1 positive. The occurrence of indeterminate HIV-2 bands with a Geenius final assay interpretation of HIV-1 positive was more common than true HIV-2 infections. Reporting indeterminate HIV-2 results in this situation may cause confusion with interpreting HIV infection status.

      11. Measuring 237Np and 239Pu in urine at low levels is important for both biomonitoring and radiological emergency response. Here we report a newly developed and validated analytical method used to determine 237Np and 239Pu in urine by selective retention of Np and Pu from 2 mL of urine directly onto TEVA® resin followed by SF-ICP-MS (coupled to a membrane desolvating introduction system) detection. The method provides solid phase extraction of Np/Pu with observed recovery ratios ranging from 89 to 113% and rapid results with limits of detection well below recommended detection guidelines for children and pregnant women (NCRP 161 reference).

    • Maternal and Child Health
      1. Using supervised learning methods to develop a list of prescription medications of greatest concern during pregnancyexternal icon
        Ailes EC, Zimmerman J, Lind JN, Fan F, Shi K, Reefhuis J, Broussard CS, Frey MT, Cragan JD, Petersen EE, Polen KD, Honein MA, Gilboa SM.
        Matern Child Health J. 2020 May 6.
        INTRODUCTION: Women and healthcare providers lack adequate information on medication safety during pregnancy. While resources describing fetal risk are available, information is provided in multiple locations, often with subjective assessments of available data. We developed a list of medications of greatest concern during pregnancy to help healthcare providers counsel reproductive-aged and pregnant women. METHODS: Prescription drug labels submitted to the U.S. Food and Drug Administration with information in the Teratogen Information System (TERIS) and/or Drugs in Pregnancy and Lactation by Briggs & Freeman were included (N = 1,186 medications; 766 from three data sources, 420 from two). We used two supervised learning methods ('support vector machine' and 'sentiment analysis') to create prediction models based on narrative descriptions of fetal risk. Two models were created per data source. Our final list included medications categorized as 'high' risk in at least four of six models (if three data sources) or three of four models (if two data sources). RESULTS: We classified 80 prescription medications as being of greatest concern during pregnancy; over half were antineoplastic agents (n = 24), angiotensin converting enzyme inhibitors (n = 10), angiotensin II receptor antagonists (n = 8), and anticonvulsants (n = 7). DISCUSSION: This evidence-based list could be a useful tool for healthcare providers counseling reproductive-aged and pregnant women about medication use during pregnancy. However, providers and patients may find it helpful to weigh the risks and benefits of any pharmacologic treatment for both pregnant women and the fetus when managing medical conditions before and during pregnancy.

      2. Vital Signs: Postpartum depressive symptoms and provider discussions about perinatal depression - United States, 2018external icon
        Bauman BL, Ko JY, Cox S, D'Angelo DV, Warner L, Folger S, Tevendale HD, Coy KC, Harrison L, Barfield WD.
        MMWR Morb Mortal Wkly Rep. 2020 May 15;69(19):575-581.
        INTRODUCTION: Perinatal depression is a complication of pregnancy that can result in adverse maternal and infant outcomes. Screening to identify pregnant and postpartum women with depressive symptoms is recommended to provide diagnosis, treatment, and follow-up care to reduce poor outcomes. METHODS: CDC analyzed 2018 data from the Pregnancy Risk Assessment Monitoring System to describe postpartum depressive symptoms (PDS) among women with a recent live birth and to assess whether health care providers asked women about depression during prenatal and postpartum health care visits, by site and maternal and infant characteristics. RESULTS: Among respondents from 31 sites, the prevalence of PDS was 13.2%, ranging from 9.7% in Illinois to 23.5% in Mississippi. The prevalence of PDS exceeded 20% among women who were aged </=19 years, were American Indian/Alaska Native, smoked during or after pregnancy, experienced intimate partner violence before or during pregnancy, self-reported depression before or during pregnancy, or whose infant had died since birth. The prevalence of women reporting that a health care provider asked about depression during prenatal care visits was 79.1% overall, ranging from 51.3% in Puerto Rico to 90.7% in Alaska. The prevalence of women reporting that a provider asked about depression during postpartum visits was 87.4% overall, ranging from 50.7% in Puerto Rico to 96.2% in Vermont. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: The prevalence of self-reported PDS varied by site and maternal and infant characteristics. Whether providers asked women about perinatal depression was not consistent across sites. Provision of recommended screenings and appropriate referrals for diagnosis, treatment, and follow-up care can ensure early and effective management of depression to reduce adverse maternal and infant outcomes.

      3. Addressing perinatal mental health and opportunities for public healthexternal icon
        Ko JY, Haight SC.
        Am J Public Health. 2020 Jun;110(6):765-767.

      4. Early-onset neonatal sepsis 2015 to 2017, the rise of Escherichia coli, and the need for novel prevention strategiesexternal icon
        Stoll BJ, Puopolo KM, Hansen NI, Sanchez PJ, Bell EF, Carlo WA, Cotten CM, D'Angio CT, Kazzi SN, Poindexter BB, Van Meurs KP, Hale EC, Collins MV, Das A, Baker CJ, Wyckoff MH, Yoder BA, Watterberg KL, Walsh MC, Devaskar U, Laptook AR, Sokol GM, Schrag SJ, Higgins RD.
        JAMA Pediatr. 2020 May 4:e200593.
        Importance: Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. Objective: To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. Design, Setting, and Participants: This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Main Outcomes and Measures: Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. Results: A total of 235 EOS cases (127 male [54.0%]) were identified among 217480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008). Conclusions and Relevance: In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.

      5. Specific birth defects in pregnancies of women with diabetes: National Birth Defects Prevention Study, 1997-2011external icon
        Tinker SC, Gilboa SM, Moore CA, Waller DK, Simeone RM, Kim SY, Jamieson DJ, Botto LD, Reefhuis J.
        Am J Obstet Gynecol. 2020 Feb;222(2):176.e1-176.e11.
        BACKGROUND: Diabetes is associated with an increased risk for many birth defects and is likely to have an increasing impact on birth defect prevalence because of the rise in diabetes in the United States in recent decades. One of the first analyses in which specific birth defects were assessed for their relationship with both pregestational and gestational diabetes used data from the initial 6 years of the National Birth Defects Prevention Study. That analysis reported strong associations for pregestational diabetes with several birth defects, but few exposures among some of the less common birth defects led to unstable estimates with wide confidence intervals. Since that analysis, the study continued to collect data for another 8 years, including information on approximately 19,000 additional cases and 6900 additional controls. OBJECTIVE: Our objective was to use data from the National Birth Defects Prevention Study, the largest population-based birth defects case-control study in the United States, to provide updated and more precise estimates of the association between diabetes and birth defects, including some defects not previously assessed. STUDY DESIGN: We analyzed data on deliveries from October 1997 through December 2011. Mothers of case and control infants were interviewed about their health conditions and exposures during pregnancy, including diagnosis of pregestational (type 1 or type 2) diabetes before the index pregnancy or gestational diabetes during the index pregnancy. Using logistic regression, we separately assessed the association between pregestational and gestational diabetes with specific categories of structural birth defects for which there were at least 3 exposed case infants. For birth defect categories for which there were at least 5 exposed case infants, we calculated odds ratios adjusted for maternal body mass index, age, education, race/ethnicity, and study site; for defect categories with 3 or 4 exposed cases, we calculated crude odds ratios. RESULTS: Pregestational diabetes was reported by 0.6% of mothers of control infants (71 of 11,447) and 2.5% of mothers of case infants (775 of 31,007). Gestational diabetes during the index pregnancy was reported by 4.7% of mothers of control infants (536 of 11,447) and 5.3% of mothers of case infants (1,653 of 31,007). Pregestational diabetes was associated with strong, statistically significant odds ratios (range, 2.5-80.2) for 46 of 50 birth defects considered. The largest odds ratio was observed for sacral agenesis (adjusted odds ratio, 80.2; 95% confidence interval, 46.1-139.3). A greater than 10-fold increased risk was also observed for holoprosencephaly (adjusted odds ratio, 13.1; 95% confidence interval, 7.0-24.5), longitudinal limb deficiency (adjusted odds ratio, 10.1; 95% confidence interval, 6.2-16.5), heterotaxy (adjusted odds ratio, 12.3; 95% confidence interval, 7.3-20.5), truncus arteriosus (adjusted odds ratio, 14.9; 95% confidence interval, 7.6-29.3), atrioventricular septal defect (adjusted odds ratio, 10.5; 95% confidence interval, 6.2-17.9), and single ventricle complex (adjusted odds ratio, 14.7; 95% confidence interval, 8.9-24.3). For gestational diabetes, statistically significant odds ratios were fewer (12 of 56) and of smaller magnitude (range, 1.3- 2.1; 0.5 for gastroschisis). CONCLUSION: Pregestational diabetes is associated with a markedly increased risk for many specific births defects. Because glycemic control before pregnancy is associated with a reduced risk for birth defects, ongoing quality care for persons with diabetes is an important opportunity for prevention.

    • Medicine
      1. Vitamin K1 treatment duration in patients with brodifacoum poisoningexternal icon
        Yip L, Stanton NV, Middleberg RA.
        N Engl J Med. 2020 Apr 30;382(18):1764-1765.

    • Nutritional Sciences
      1. An integrated infant and young child feeding and micronutrient powder intervention does not affect anemia, iron status, or vitamin a status among children aged 12-23 months in eastern Ugandaexternal icon
        Ford ND, Ruth LJ, Ngalombi S, Lubowa A, Halati S, Ahimbisibwe M, Baingana R, Whitehead RD, Mapango C, Jefferds ME.
        J Nutr. 2020 Apr 1;150(4):938-944.
        BACKGROUND: Micronutrient powders (MNP) can reduce iron deficiency and anemia in children. OBJECTIVE: We evaluated the impact of an integrated infant and young child feeding (IYCF)-MNP intervention on anemia and micronutrient status among children aged 12-23 mo in Eastern Uganda. The intervention focused on MNP distribution, IYCF education, and caregiver behavior change. METHODS: Population-based cross-sectional surveys representative of children aged 12-23 mo in Amuria (intervention) and Soroti (nonintervention) districts were collected in June/July 2015 at baseline (n = 1260) and 12 mo after implementation at endline in 2016 (n = 1490). From pooled capillary blood, we assessed hemoglobin, malaria, ferritin, retinol binding protein (RBP), C-reactive protein, and ɑ1-acid glycoprotein. Ferritin and RBP were regression-adjusted to correct for inflammation. Caregivers reported sociodemographic characteristics and MNP knowledge and practices. Linear regression estimated the difference-in-difference (DiD) effect of MNP on hemoglobin, ferritin, and RBP, and logistic regression estimated DiD effect of MNP on anemia (hemoglobin <11.0 g/dL), iron deficiency (ferritin <12.0 µg/L), iron deficiency anemia (hemoglobin <11.0 g/dL and ferritin <12.0 µg/L), and vitamin A deficiency (VAD; RBP equivalent to <0.70 µmol/L retinol: <0.79 µmol/L at baseline and RBP <0.67 µmol/L at endline). RESULTS: In Amuria, 96% of children had ever consumed MNP versus <1% of children in Soroti. Fifty-four percent of caregivers reported organoleptic changes when MNP were added to foods cooked with soda ash. Adjusting for age, sex, malaria, recent morbidity, and household-level factors, the intervention was associated with -0.83 g/dL lower hemoglobin (95% CI, -1.36, -0.30 g/dL; P = 0.003) but not with anemia, ferritin, iron deficiency, iron deficiency anemia, RBP, or VAD. CONCLUSIONS: Despite high program fidelity, the intervention was associated with reduced hemoglobin concentrations but not with change in anemia or micronutrient status among children aged 12-23 mo in Eastern Uganda. Contextual factors, such as cooking with soda ash, might explain the lack of effectiveness.

    • Occupational Safety and Health
      1. OBJECTIVES: To examine the impact of workplace injury on opioid dependence, abuse and overdose (opioid-related morbidity) and if severity of injury increases the hazard of these health effects. METHODS: We used MarketScan databases to follow injured and propensity score matched non-injured workers, both without prior opioid-related diagnoses. Using a Cox proportional hazard model, we examined the impact of workplace injury on opioid-related morbidity. RESULTS: The hazard of opioid-related morbidity for injured workers was 1.79 times than that of matched non-injured workers (95% CI 1.89 to 3.60). For medical-only and lost-time injured workers, it was respectively 1.54 (95% CI 1.02 to 2.32) and 2.91 (95% CI 1.75 to 4.84) times that of non-injured workers. CONCLUSIONS: Reducing workplace injury or severity of workplace injury, as well as efforts to ensure appropriate opioid prescribing for injured workers, may help to reduce the societal costs of opioid use.

      2. When NIOSH promulgated its Respiratory Protective Devices rule in 1995 (Title 42 code of Federal Regulations, Part 84), which specified approval standards for respirators, no test for evaluating the fitting characteristics of filtering facepiece respirators was included. The consequences of the lack of a fit test in 42 CFR 84 included the approval of devices that did not fit the general respirator-wearing population very well, higher costs for conducting the OSHA-required fit test, and the potential for wearing to pass a fit test in error. Today, the need still exists for a fit test for use by manufacturers of filtering facepiece respirators and conformity assessment organizations.

      3. In vitro toxicity assessment of respirable solid surface composite sawing particlesexternal icon
        Mandler WK, Kang S, Farcas M, Qi C, Friend SA, Qian Y.
        Toxicol Ind Health. 2020 May 7:748233720921683.
        Solid surface composites (SSCs) are a class of popular construction materials composed of aluminum trihydrate and acrylic polymers. Previous investigations have demonstrated that sawing SSC releases substantial airborne dusts, with a number-based geometric mean diameter of 1.05 microm. We reported that in mice, aspiration exposure to airborne SSC dusts induced symptoms of pulmonary inflammation at 24-h postexposure: neutrophilic influx, alveolitis, and increased lactate dehydrogenase (LDH) and pro-inflammatory cytokine levels in lavage fluid. The particles appeared to be poorly cleared, with 81% remaining at 14-day postexposure. The objective of this study was to determine the toxicity specifically of respirable particles on a model of human alveolar macrophages (THP-1). The relative toxicities of subfractions (0.07, 0.66, 1.58, 5.0, and 13.42 microm diameter) of the airborne particles were also determined. THP-1 macrophages were exposed for 24 h to respirable particles from sawing SSC (0, 12.5, 25, 50, or 100 microg/ml) or size-specific fractions (100 microg/ml). Exposure to respirable SSC particles induced THP-1 macrophage toxicity in a dose-dependent manner. Viability was decreased by 15% and 19% after exposure to 50 and 100 microg/ml SSC, respectively, which correlated with increased cell culture supernatant LDH activity by 40% and 70% when compared to control. Reactive oxygen species (ROS) production and inflammatory cytokines were increased in a dose-dependent manner. A size-dependent cytotoxic effect was observed in the cells exposed to subfractions of SSC particles. SSC particles of 0.07, 0.66, and 1.58 microm diameter killed 36%, 17%, and 22% of cells, respectively. These results indicate a potential for cytotoxicity of respirable SSC particles and a relationship between particle size and toxicity, with the smallest fractions appearing to exhibit the greatest toxicity.

      4. BACKGROUND: Previous analyses of mortality were conducted in a large cohort of ethylene oxide (EtO) exposed workers employed at 13 sterilization facilities throughout the U.S. and followed from the start of operation through 1998. Statistically significant elevated mortality was reported from hematopoietic cancer in men and breast cancer in women compared to the general population. Possible healthy worker survivor bias was not addressed. METHODS: To examine survivor bias in this cohort, employment termination was analyzed with statistical models stratified on sex and race that included age, employment duration, and cumulative EtO exposure. To reduce survivor bias employment duration was included in Poisson regression model specifications for estimating standardized mortality ratios for several cancer outcomes. RESULTS: Strong statistically significant effects of unlagged cumulative EtO exposure were observed on rate of employment termination, indicating potential healthy worker survivor effect bias. Adjustment for employment duration in analyses of mortality resulted in statistically significant and stronger associations between cumulative EtO exposure and lung cancer, female breast cancer and hematopoietic cancer. There was a striking reduction in nonmalignant respiratory disease mortality risk with increasing employment duration with a further (nonsignificant) reduction with cumulative EtO, suggesting that EtO itself is driving termination of workers with respiratory morbidity even though the average EtO exposures in this population were generally far below odor and acute irritancy thresholds. CONCLUSIONS: Important survivor bias was present in this EtO cohort and may be present in many occupational settings involving irritant exposures.

    • Occupational Safety and Health - Mining
      1. Characterization of aerosols in an underground mine during a longwall moveexternal icon
        Bugarski AD, Hummer JA, Vanderslice S, Shahan MR.
        Min Metall Explor. 2020 .
        A study was conducted in an underground mine with the objective to identify, characterize, and source apportion airborne aerosols at the setup face and recovery room during longwall move operations. The focus was on contributions of diesel- and battery-powered heavy-duty vehicles used to transfer equipment between the depleted and new longwall panels and diesel-powered light-duty vehicles used to transport personnel and materials to various locations within the mine. Aerosols at the setup face were found to be distributed among diesel combustion-generated submicrometer and mechanically generated coarse aerosols. According to the data, the submicrometer aerosols downstream of the setup face were sourced to diesel exhaust emitted by vehicles operated inside and outside of the panel. Depending on the intensity of the activities on the panel, the outby sources contributed between 12.5 and 99.6% to the average elemental carbon mass flow at the setup face and recovery room. Extensively used light-duty vehicles contributed measurably to the elemental carbon concentrations at the setup face. The number concentrations of aerosols downstream of the setup face were associated with aerosols generated by combustion in diesel engines operated in the shield haulage loop and/or outside of the longwall panels. Entrainment of road dust by diesel or battery-powered load-haul-dump vehicles operated near the measurement site appears to be the primary source of mass concentrations of aerosols. The findings of this study should help the underground mining industry in its efforts to reduce exposures of miners to diesel and coarse aerosols.

      2. Recognition of illuminated coloured markers that designate primary and secondary mine escapewaysexternal icon
        Sammarco JJ, Demich B, Macdonald BD, Rubinstein EN, Martell M.
        Light Res Technol. 2020 .
        It is critical for the safety of miners to be able to escape, unaided, during a mine emergency. Self-escape is challenging in the presence of smoke that can occur during a mine emergency. To assist self-escape, coloured markers in underground mines designate the primary/secondary escapeways, but no universal colour code exists. Ten participants were tested to recognize the colour and designation (primary/secondary) of fluorescent yellow–green (FYG), yellow (Y), white (W) and green (G) escapeway markers in both a clear and smoked-filled environment. The overall misidentification rate for all colours was 1.9% and 18.1%, respectively, in clear and smoke conditions. FYG had the highest misidentification percentage for both conditions. For the marker designation tests, participants were most accurate in clear conditions (100.0%) for the FYG + W, Y + G, G + W and W + FYG combinations, and least accurate (89.6%) for the Y + FYG combination, while for smoke conditions participants were most accurate for the G + Y combination (95.8%). The overall effect of colour combination was significant, indicating that the colour combination for primary/secondary recognition is a significant factor where the G + Y combination was best. It can be inferred from these data that the colour combination is an important factor in participants’ ability to recognize primary/secondary escapeway markers in smoke conditions.

    • Parasitic Diseases
      1. Impact of intermittent mass testing and treatment on incidence of malaria infection in a high transmission area of western Kenyaexternal icon
        Desai M, Samuels A, Odongo W, Williamson J, Odero NA, Otieno K, Shi YP, Kachur SP, Hamel MJ, Kariuki S, Lindblade KA.
        Am J Trop Med Hyg. 2020 Apr 27.
        Progress with malaria control in western Kenya has stagnated since 2007. Additional interventions to reduce the high burden of malaria in this region are urgently needed. We conducted a two-arm, community-based, cluster-randomized, controlled trial of active case detection and treatment of malaria infections in all residents mass testing and treatment (MTaT) of 10 village clusters (intervention clusters) for two consecutive years to measure differences in the incidence of clinical malaria disease and malaria infections compared with 20 control clusters where MTaT was not implemented. All residents of intervention clusters, irrespective of history of fever or other malaria-related symptoms, were tested three times per year before the peak malaria season using malaria rapid diagnostic tests. All positive cases were treated with dihydroartemisinin-piperaquine. The incidence of clinical malaria was measured through passive surveillance, whereas the cumulative incidence of malaria infection was measured using active surveillance in a cohort comprising randomly selected residents. The incidence of clinical malaria was 0.19 cases/person-year (p-y, 95% CI: 0.13-0.28) in the intervention arm and 0.24 cases/p-y (95% CI: 0.15-0.39) in the control arm (incidence rate ratio [IRR] 0.79, 95% CI: 0.61-1.02). The cumulative incidence of malaria infections was similar between the intervention (2.08 infections/p-y, 95% CI: 1.93-2.26) and control arms (2.19 infections/p-y, 95% CI: 2.02-2.37) with a crude IRR of 0.95 (95% CI: 0.87-1.04). Six rounds of MTaT over 2 years did not have a significant impact on the incidence of clinical malaria or the cumulative incidence of malaria infection in this area of high malaria transmission.

      2. Cytokine signatures of Plasmodium vivax infection during pregnancy and delivery outcomesexternal icon
        Dobano C, Bardaji A, Arevalo-Herrera M, Martinez-Espinosa FE, Botto-Menezes C, Padilla N, Menegon M, Kochar S, Kochar SK, Unger H, Ome-Kaius M, Rosanas-Urgell A, Malheiros A, Castellanos ME, Hans D, Desai M, Casellas A, Chitnis CE, Severini C, Mueller I, Rogerson S, Menendez C, Requena P.
        PLoS Negl Trop Dis. 2020 May 4;14(5):e0008155.
        Plasmodium vivax malaria is a neglected disease, particularly during pregnancy. Severe vivax malaria is associated with inflammatory responses but in pregnancy immune alterations make it uncertain as to what cytokine signatures predominate, and how the type and quantity of blood immune mediators influence delivery outcomes. We measured the plasma concentrations of a set of thirty-one biomarkers, comprising cytokines, chemokines and growth factors, in 987 plasma samples from a cohort of 572 pregnant women from five malaria-endemic tropical countries and related these concentrations to delivery outcomes (birth weight and hemoglobin levels) and malaria infection. Samples were collected at recruitment (first antenatal visit) and at delivery (periphery, cord and placenta). At recruitment, we found that P. vivax-infected pregnant women had higher plasma concentrations of proinflammatory (IL-6, IL-1beta, CCL4, CCL2, CXCL10) and TH1-related cytokines (mainly IL-12) than uninfected women. This biomarker signature was essentially lost at delivery and was not associated with birth weight nor hemoglobin levels. Antiinflammatory cytokines (IL-10) were positively associated with infection and poor delivery outcomes. CCL11 was the only biomarker to show a negative association with P. vivax infection and its concentration at recruitment was positively associated with hemoglobin levels at delivery. Birth weight was negatively associated with peripheral IL-4 levels at delivery. Our multi-biomarker multicenter study is the first comprehensive one to characterize the immunological signature of P. vivax infection in pregnancy thus far. In conclusion, data show that while TH1 and pro-inflammatory responses are dominant during P. vivax infection in pregnancy, antiinflammatory cytokines may compensate excessive inflammation avoiding poor delivery outcomes, and skewness toward a TH2 response may trigger worse delivery outcomes. CCL11, a chemokine largely neglected in the field of malaria, emerges as an important marker of exposure or mediator in this condition.

      3. Proactive community case management in Senegal 2014-2016: a case study in maximizing the impact of community case management of malariaexternal icon
        Gaye S, Kibler J, Ndiaye JL, Diouf MB, Linn A, Gueye AB, Fall FB, Ndiop M, Diallo I, Cisse M, Ba M, Thwing J.
        Malar J. 2020 Apr 25;19(1):166.
        The Senegal National Malaria Control Programme (NMCP) introduced home-based malaria management for all ages, with diagnosis by rapid diagnostic test (RDT) and treatment with artemisinin-based combination therapy (ACT) in 2008, expanding to over 2000 villages nationwide by 2014. With prise en charge a domicile (PECADOM), community health workers (CHWs) were available for community members to seek care, but did not actively visit households to find cases. A trial of a proactive model (PECADOM Plus), in which CHWs visited all households in their village weekly during transmission season to identify fever cases and offer case management, in addition to availability during the week for home-based management, found that CHWs detected and treated more cases in intervention villages, while the number of cases detected weekly decreased over the transmission season. The NMCP scaled PECADOM Plus to three districts in 2014 (132 villages), to a total of six districts in 2015 (246 villages), and to a total of 16 districts in 2016 (708 villages). A narrative case study with programmatic results is presented. During active sweeps over approximately 20 weeks, CHWs tested a mean of 77 patients per CHW in 2014, 89 patients per CHW in 2015, and 90 patients per CHW in 2016, and diagnosed a mean of 61, 61 and 43 patients with malaria per CHW in 2014, 2015 and 2016, respectively. The number of patients who sought care between sweeps increased, with a 104% increase in the number of RDTs performed and a 77% increase in the number of positive tests and patients treated with ACT during passive case detection. While the number of CHWs increased 7%, the number of patients receiving an RDT increased by 307% and the number of malaria cases detected and treated by CHWs increased 274%, from the year prior to PECADOM Plus introduction to its first year of implementation. Based on these results, approximately 700 additional CHWs in 24 new districts were added in 2017. This case study describes the process, results and lessons learned from Senegal's implementation of PECADOM Plus, as well as guidance for other programmes considering introduction of this innovative strategy.

      4. Anti-PfGARP activates programmed cell death of parasites and reduces severe malariaexternal icon
        Raj DK, Das Mohapatra A, Jnawali A, Zuromski J, Jha A, Cham-Kpu G, Sherman B, Rudlaff RM, Nixon CE, Hilton N, Oleinikov AV, Chesnokov O, Merritt J, Pond-Tor S, Burns L, Jolly G, Ben Mamoun C, Kabyemela E, Muehlenbachs A, Lambert L, Orr-Gonzalez S, Gnadig NF, Fidock DA, Park S, Dvorin JD, Pardi N, Weissman D, Mui BL, Tam YK, Friedman JF, Fried M, Duffy PE, Kurtis JD.
        Nature. 2020 .
        Malaria caused by Plasmodium falciparum remains the leading single-agent cause of mortality in children1, yet the promise of an effective vaccine has not been fulfilled. Here, using our previously described differential screening method to analyse the proteome of blood-stage P. falciparum parasites2, we identify P. falciparum glutamic-acid-rich protein (PfGARP) as a parasite antigen that is recognized by antibodies in the plasma of children who are relatively resistant—but not those who are susceptible—to malaria caused by P. falciparum. PfGARP is a parasite antigen of 80 kDa that is expressed on the exofacial surface of erythrocytes infected by early-to-late-trophozoite-stage parasites. We demonstrate that antibodies against PfGARP kill trophozoite-infected erythrocytes in culture by inducing programmed cell death in the parasites, and that vaccinating non-human primates with PfGARP partially protects against a challenge with P. falciparum. Furthermore, our longitudinal cohort studies showed that, compared to individuals who had naturally occurring anti-PfGARP antibodies, Tanzanian children without anti-PfGARP antibodies had a 2.5-fold-higher risk of severe malaria and Kenyan adolescents and adults without these antibodies had a twofold-higher parasite density. By killing trophozoite-infected erythrocytes, PfGARP could synergize with other vaccines that target parasite invasion of hepatocytes or the invasion of and egress from erythrocytes.

      5. The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRCexternal icon
        Verity R, Aydemir O, Brazeau NF, Watson OJ, Hathaway NJ, Mwandagalirwa MK, Marsh PW, Thwai K, Fulton T, Denton M, Morgan AP, Parr JB, Tumwebaze PK, Conrad M, Rosenthal PJ, Ishengoma DS, Ngondi J, Gutman J, Mulenga M, Norris DE, Moss WJ, Mensah BA, Myers-Hansen JL, Ghansah A, Tshefu AK, Ghani AC, Meshnick SR, Bailey JA, Juliano JJ.
        Nat Commun. 2020 Apr 30;11(1):2107.
        The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.

      6. Intensity of pyrethroid resistance in Anopheles gambiae before and after a mass distribution of insecticide-treated nets in Kinshasa and in 11 provinces of the Democratic Republic of Congoexternal icon
        Wat'senga F, Agossa F, Manzambi EZ, Illombe G, Mapangulu T, Muyembe T, Clark T, Niang M, Ntoya F, Sadou A, Plucinski M, Li Y, Messenger LA, Fornadel C, Oxborough RM, Irish SR.
        Malar J. 2020 Apr 30;19(1):169.
        BACKGROUND: Between 2011 and 2018, an estimated 134.8 million pyrethroid-treated long-lasting insecticidal nets (LLINs) were distributed nationwide in the Democratic Republic of Congo (DRC) for malaria control. Pyrethroid resistance has developed in DRC in recent years, but the intensity of resistance and impact on LLIN efficacy was not known. Therefore, the intensity of resistance of Anopheles gambiae sensu lato (s.l.) to permethrin and deltamethrin was monitored before and after a mass distribution of LLINs in Kinshasa in December 2016, and in 6 other sites across the country in 2017 and 11 sites in 2018. METHODS: In Kinshasa, CDC bottle bioassays using 1, 2, 5, and 10 times the diagnostic dose of permethrin and deltamethrin were conducted using An. gambiae s.l. collected as larvae and reared to adults. Bioassays were conducted in four sites in Kinshasa province 6 months before a mass distribution of deltamethrin-treated LLINs and then two, six, and 10 months after the distribution. One site in neighbouring Kongo Central province was used as a control (no mass campaign of LLIN distribution during the study). Nationwide intensity assays were conducted in six sites in 2017 using CDC bottle bioassays and in 11 sites in 2018 using WHO intensity assays. A sub-sample of An. gambiae s.l. was tested by PCR to determine species composition and frequency of kdr-1014F and 1014S alleles. RESULTS: In June 2016, before LLIN distribution, permethrin resistance intensity was high in Kinshasa; the mean mortality rate was 43% at the 5x concentration and 73% at the 10x concentration. Bioassays at 3 time points after LLIN distribution showed considerable variation by site and time and there was no consistent evidence for an increase in pyrethroid resistance intensity compared to the neighbouring control site. Tests of An. gambiae s.l. in 6 sites across the country in 2017 and 11 sites in 2018 showed all populations were resistant to the diagnostic doses of 3 pyrethroids. In 2018, the intensity of resistance varied by site, but was generally moderate for all three pyrethroids, with survivors at x5 the diagnostic dose. Anopheles gambiae sensu stricto (s.s.) was the most common species identified across 11 sites in DRC, but in Kinshasa, An. gambiae s.s. (91%) and Anopheles coluzzii (8%) were sympatric. CONCLUSIONS: Moderate or high intensity pyrethroid resistance was detected nationwide in DRC and is a serious threat to sustained malaria control with pyrethroid LLINs. Next generation nets (PBO nets or bi-treated nets) should be considered for mass distribution.

      7. Clinical sequelae associated with unresolved tropical splenomegaly in a cohort of recently resettled Congolese refugees in the United States - multiple states, 2015-2018external icon
        Zambrano LD, Jentes E, Phares C, Weinberg M, Kachur SP, Basnet MS, Klosovsky A, Mwesigwa M, Naoum M, Nsobya SL, Samson O, Goers M, McDonald R, Morawski B, Njuguna H, Peak C, Laws R, Bakhsh Y, Iverson SA, Bezold C, Allkhenfr H, Horth R, Yang J, Miller S, Kacka M, Davids A, Mortimer M, Stauffer W, Marano N.
        Am J Trop Med Hyg. 2020 May 4.
        Tropical splenomegaly is often associated with malaria and schistosomiasis. In 2014 and 2015, 145 Congolese refugees in western Uganda diagnosed with splenomegaly during predeparture medical examinations underwent enhanced screening for various etiologies. After anecdotal reports of unresolved splenomegaly and complications after U.S. arrival, patients were reassessed to describe long-term clinical progression after arrival in the United States. Post-arrival medical information was obtained through medical chart abstraction in collaboration with state health partners in nine participating states. We evaluated observed splenomegaly duration and associated clinical sequelae between 130 case patients from eastern Congo and 102 controls through adjusted hierarchical Poisson models, accounting for familial clustering. Of the 130 case patients, 95 (73.1%) had detectable splenomegaly after arrival. Of the 85 patients with records beyond 6 months, 45 (52.9%) had persistent splenomegaly, with a median persistence of 14.7 months (range 6.0-27.9 months). Of the 112 patients with available results, 65 (58.0%) patients had evidence of malaria infection, and the mean splenomegaly duration did not differ by Plasmodium species. Refugees with splenomegaly on arrival were 43% more likely to have anemia (adjusted relative risk [aRR]: 1.43, 95% CI: 1.04-1.97). Those with persistent splenomegaly were 60% more likely (adjusted relative risk [aRR]: 1.60, 95% CI: 1.15-2.23) to have a hematologic abnormality, particularly thrombocytopenia (aRR: 5.53, 95% CI: 1.73-17.62), and elevated alkaline phosphatase (aRR: 1.57, 95% CI: 1.03-2.40). Many patients experienced persistent splenomegaly, contradicting literature describing resolution after treatment and removal from an endemic setting. Other possible etiologies should be investigated and effective treatment, beyond treatment for malaria and schistosomiasis, explored.

    • Public Health Leadership and Management
      1. Background: Employee engagement, exemplified by positive perceptions of supervisors, workplace, and job, improves productivity and employee retention. We identified the extent of and barriers to employee engagement at Centers for Disease Control and Prevention's (CDC) National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP). Methods: In 2015, NCHHSTP's leadership collected baseline data through a centerwide Employee Engagement Pulse Survey (EEPS) from NCHHSTP's full-time Civil Service employees, U.S. Public Health Service Commissioned Corps officers, and Title 42 service fellows. EEPS included six demographic questions; nine Likert-type scale questions measuring 26 perceptions related to immediate supervisors, the work environment, and job satisfaction; and four open-ended questions soliciting recommendations for improvement. Findings: Among 727 of 1,171 staff (response rate = 62%), positive perceptions of supervisors ranged from a high of 94% (supervisor conducts performance reviews) to a low of 63% (supervisor assists employees with career development). Perceptions of work experience ranged from 98% (respondents were willing to put in extra effort to get a job done) to 68% (respondents' talents were used well in the workplace). Perceptions of job satisfaction ranged from 87% (support from their coworkers) to 69% (satisfaction with opportunities to learn or grow professionally). Conclusion/Application to Practice: Overall, NCHHSTP staff have positive perceptions of their work, their leaders, and the agency. Other public- and private-sector employers might be able to improve their employees' engagement and retention by listening to their opinions and needs and frequently recognizing their individual achievements. NCHHSTP's workforce development initiatives can be used as a model for assessing a baseline of their employees' engagement.

    • Reproductive Health
      1. Program fidelity and patient satisfaction among women served by the Zika contraception access network program in Puerto Ricoexternal icon
        Zapata LB, Romero L, Rivera MI, Rivera-Soto SK, Hurst S, Mendoza ZV, Clayton HB, Bracero N, Whiteman MK, Lathrop E.
        Womens Health Issues. 2020 May 3.
        BACKGROUND: The Zika Contraception Access Network (Z-CAN) was designed to provide women in Puerto Rico who chose to delay or avoid pregnancy during the 2016-2017 Zika virus outbreak access to high-quality client-centered contraceptive counseling and the full range of reversible contractive methods on the same day and at no cost through a network of trained providers. We evaluated the implementation of Z-CAN from the patient perspective. METHODS: An online survey, administered to a subset of women served by the Z-CAN program approximately 2 weeks after their initial Z-CAN visit, assessed patient satisfaction and receipt of services consistent with select program strategies: receipt of high-quality client-centered contraceptive counseling, same-day access to the contraceptive method they were most interested in after counseling, and no-cost contraception. RESULTS: Of 3,503 respondents, 85.2% reported receiving high-quality client-centered contraceptive counseling. Among women interested in a contraceptive method after counseling (n = 3,470), most reported same-day access to that method (86.8%) and most reported receiving some method of contraception at no cost (87.4%). Women who reported receiving services according to Z-CAN program strategies were more likely than those who did not to be very satisfied with services. Women who received high-quality client-centered contraceptive counseling and same-day access to the method they were most interested in after counseling were also more likely to be very satisfied with the contraceptive method received. CONCLUSIONS: A contraception access program can be rapidly implemented with high fidelity to program strategies in a fast-moving and complex public health emergency setting.

    • Social and Behavioral Sciences
      1. Daily mood reactivity to stress during childhood predicts internalizing problems three years laterexternal icon
        Bai S, Robles TF, Reynolds BM, Repetti RL.
        J Abnorm Child Psychol. 2020 Apr 23.
        The mental health toll of common school problems that many children encounter every day is not well understood. This study examined individual differences in mood reactivity to naturally occurring school problems using daily diaries, and assessed their prospective associations with youth mental health, three years later. At baseline, 47 children ages 8 to 13 years described common problems at school and mood on a daily basis, for 8 weeks. Thirty-three youth returned for follow-up three years later at ages 11 to 17 years. Children and parents also completed one-time questionnaires about youth mental health at baseline and follow-up. There were individual differences in the within-person associations between school problems and same-day and next-day mood. A greater tendency to react to school problems with more negative mood or less positive mood on the same day predicted more parent-rated internalizing and externalizing problems and child ratings of depression symptoms three years later, relative to baseline levels of symptoms. Daily diaries can help to identify specific targets of psychosocial interventions in real world settings.

    • Statistics as Topic
      1. Bayesian hierarchical regression (BHR) is often used in small area estimation (SAE). BHR conditions on the samples. Therefore, when data are from a complex sample survey, neither survey sampling design nor survey weights are used. This can introduce bias and/or cause large variance. Further, if non-informative priors are used, BHR often requires the combination of multiple years of data to produce sample sizes that yield adequate precision; this can result in poor timeliness and can obscure trends. To address bias and variance, we propose a design assisted model-based approach for SAE by integrating adjusted sample weights. To address timeliness, we use historical data to define informative priors (power prior); this allows estimates to be derived from a single year of data. Using American Community Survey data for validation, we applied the proposed method to Behavioral Risk Factor Surveillance System data. We estimated the prevalence of disability for all U.S. counties. We show that our method can produce estimates that are both more timely than those arising from widely-used alternatives and are closer to ACS' direct estimates, particularly for low-data counties. Our method can be generalized to estimate the county-level prevalence of other health related measurements.

    • Substance Use and Abuse
      1. Illicit opioid use following changes in opioids prescribed for chronic non-cancer painexternal icon
        Coffin PO, Rowe C, Oman N, Sinchek K, Santos GM, Faul M, Bagnulo R, Mohamed D, Vittinghoff E.
        PLoS One. 2020 ;15(5):e0232538.
        BACKGROUND: After decades of increased opioid pain reliever prescribing, providers are rapidly reducing prescribing. We hypothesized that reduced access to prescribed opioid pain relievers among patients previously reliant upon opioid pain relievers would result in increased illicit opioid use. METHODS AND FINDINGS: We conducted a retrospective cohort study among 602 publicly insured primary care patients who had been prescribed opioids for chronic non-cancer pain for at least three consecutive months in San Francisco, recruited through convenience sampling. We conducted a historical reconstruction interview and medical chart abstraction focused on illicit substance use and opioid pain reliever prescriptions, respectively, from 2012 through the interview date in 2017-2018. We used a nested-cohort design, in which patients were classified, based on opioid pain reliever dose change, into a series of nested cohorts starting with each follow-up quarter. Using continuation-ratio models, we estimated associations between opioid prescription discontinuation or 30% increase or decrease in dose, relative to no change, and subsequent frequency of heroin and non-prescribed opioid pain reliever use, separately. Models controlled for demographics, clinical and behavioral characteristics, and past use of heroin or non-prescribed opioid pain relievers. A total of 56,372 and 56,484 participant-quarter observations were included from the 597 and 598 participants available for analyses of heroin and non-prescribed opioid pain reliever outcomes, respectively. Participants discontinued from prescribed opioids were more likely to use heroin (Adjusted Odds Ratio (AOR) = 1.57, 95% CI: 1.25-1.97) and non-prescribed opioid pain relievers (AOR = 1.75, 1.45-2.11) more frequently in subsequent quarters compared to participants with unchanged opioid prescriptions. Participants whose opioid pain reliever dose increased were more likely to use heroin more frequently (AOR = 1.67, 1.32-2.12). Results held throughout sensitivity analyses. The main limitations were the observational nature of results and limited generalizability beyond safety-net settings. CONCLUSIONS: Discontinuation of prescribed opioid pain relievers was associated with more frequent non-prescribed opioid pain reliever and heroin use; increased dose was also associated with more frequent heroin use. Clinicians should be aware of these risks in determining pain management approaches.

      2. Free and glucuronide urine cannabinoids after controlled smoked, vaporized, and oral cannabis administration in frequent and occasional cannabis usersexternal icon
        Huestis MA, Sempio C, Newmeyer MN, Andersson M, Barnes AJ, Abulseoud OA, Blount BC, Schroeder J, Smith ML.
        J Anal Toxicol. 2020 May 5.
        BACKGROUND: Total urinary 11-nor-9-carboxy-tetrahydrocannabinol (THCCOOH) concentrations are generally reported following cannabis administration. Few data are available for glucuronide and minor cannabinoid metabolite concentrations. METHODS: All urine specimens from 11 frequent and 9 occasional cannabis users were analyzed for 11 cannabinoids for up to 85 h by LC-MS-MS following controlled smoked, vaporized or oral 50.6 mg Delta9-tetrahydrocannabinol (THC) in a randomized, placebo-controlled, within-subject dosing design. RESULTS: No cannabidiol, cannabinol, cannabigerol, tetrahydrocannabivarin (THCV), THC, 11-OH-THC, Delta9-tetrahydrocannabinolic acid were detected in urine. Median THCCOOH-glucuronide maximum concentrations (Cmax) following smoked, vaporized and oral routes were 68.0, 26.7 and 360 mug/L for occasional and 378, 248 and 485 mug/L for frequent users, respectively. Median time to specific-gravity normalized Cmax (Tmax) was 5.1-7.9 h for all routes and all users. Median Cmax for THCCOOH, THC-glucuronide and 11-nor-9-carboxy-Delta9-THCV (THCVCOOH) were less than 7.5% of THCCOOH-glucuronide Cmax concentrations. Only THC-glucuronide mean Tmax differed between routes and groups, and was often present only in occasional users' first urine void. Multiple THCCOOH-glucuronide and THCCOOH peaks were observed. We also evaluated these urinary data with published models for determining recency of cannabis use. CONCLUSIONS: These urinary cannabinoid marker concentrations from occasional and frequent cannabis users following three routes of administration provide a scientific database to assess single urine concentrations in cannabis monitoring programs. New target analytes (CBD, CBN, CBG, THCV and phase II metabolites) were not found in urine. The results are important to officials in drug treatment, workplace and criminal justice drug monitoring programs, as well as policy makers with responsibility for cannabis regulations.

      3. Flavors are a major driver of the youth e-cigarette epidemicexternal icon
        King BA.
        Am J Public Health. 2020 Jun;110(6):773-774.

      4. Trends and associations of menthol cigarette smoking among US middle and high school students - National Youth Tobacco Survey, 2011-2018external icon
        Sawdey MD, Chang JT, Cullen KA, Rass O, Jackson KJ, Ali FR, Odani S, Courtney-Long EA, Armour BS, Ambrose BK, Agaku IT.
        Nicotine Tob Res. 2020 Apr 29.
        INTRODUCTION: Youth cigarette smoking decreased significantly over the last two decades in the United States. This study provides estimates and trends from 2011 to 2018 and factors associated with youth menthol and non-menthol smoking from 2016 to 2018. METHODS: Using data from the 2011-2018 National Youth Tobacco Surveys, past 30-day (current) menthol and non-menthol cigarette smoking were estimated for all youth (prevalence) and youth smokers (proportions). Trends were examined using Joinpoint regression, calculating the annual percent change (APC). Multivariate logistic regression analyses identified factors associated with menthol smoking. RESULTS: From 2011 to 2018, menthol cigarette smoking among current youth cigarette smokers significantly decreased from 57.3% to 45.7% (APC: -3.0%), while non-menthol (38.2% to 47.3% [APC: 2.9%]) and unknown menthol status (not sure\missing) (4.5% to 7.0% [APC: 7.1%]) significantly increased. Menthol cigarette smoking among high school, male, female, and non-Hispanic white current cigarette smokers decreased, but remained unchanged among middle school, non-Hispanic black, and Hispanic smokers. Significantly higher proportions of menthol cigarette smokers smoked on >/=20 days, >/=2 cigarettes per day, and >/=100 cigarettes in their lifetime compared to non-menthol smokers. Among current cigarette smokers, non-Hispanic blacks, Hispanics, flavored non-cigarette tobacco users, frequent smokers (>/=20 days), those smoking 2-5 cigarettes per day, and those living with someone who uses tobacco had higher odds of menthol cigarette smoking. CONCLUSIONS: In 2018, nearly half of current youth cigarette smokers smoked menthol cigarettes. While menthol cigarette smoking declined from 2011 to 2018 among all youth and among youth smokers, there was no change in menthol cigarette smoking among non-Hispanic black, Hispanic, and middle school cigarette smokers. IMPLICATIONS: This study finds that overall cigarette and menthol cigarette smoking declined in youth from 2011 to 2018. However, menthol cigarette smoking among non-Hispanic black, Hispanic, and middle school youth cigarette smokers did not change. Information from this study can help inform efforts to reduce menthol cigarette smoking among US youth, particularly racial/ethnic minority populations.

      5. Advancing housing and health: Promoting smoking cessation in permanent supportive housingexternal icon
        Vijayaraghavan M, King BA.
        Public Health Rep. 2020 Apr 30:33354920922374.

    • Zoonotic and Vectorborne Diseases
      1. Zika among international travelers presenting to GeoSentinel sites, 2012-2019: implications for clinical practiceexternal icon
        Angelo KM, Stoney RJ, Brun-Cottan G, Leder K, Grobusch MP, Hochberg N, Kuhn S, Bottieau E, Schlagenhauf P, Chen L, Hynes NA, Perez CP, Mockenhaupt FP, Molina I, Crespillo-Andujar C, Malvy D, Caumes E, Plourde P, Shaw M, McCarthy AE, Piper-Jenks N, Connor BA, Hamer DH, Wilder-Smith A.
        J Travel Med. 2020 Apr 25.
        INTRODUCTION: International travellers contribute to the rapid spread of Zika virus (ZIKV) and its sentinel identification globally. We describe ZIKV infections among international travelers seen at GeoSentinel sites with a focus on ZIKV acquired in the Americas and the Caribbean, describe countries of exposure and traveler characteristics, and assess ZIKV diagnostic testing by site. METHODS: Records with an international travel-related diagnosis of confirmed or probable ZIKV from January 2012 through December 2019 reported to GeoSentinel with a recorded illness onset date, were included to show reported cases over time. Records from March 2016 through December 2019 with an exposure region of the Americas or the Caribbean were included in the descriptive analysis. A survey was conducted to assess the availability, accessibility, and utilization of ZIKV diagnostic tests at GeoSentinel sites. RESULTS: GeoSentinel sites reported 525 ZIKV cases from 2012 through 2019. Between 2012 and 2014, 8 cases were reported; all were acquired in Asia or Oceania. After 2014, most cases were acquired in the Americas or the Caribbean; a large decline in ZIKV cases occurred in 2018-19.Between March 2016 and December 2019, 423 patients acquired ZIKV in the Americas or the Caribbean; peak reporting to these regions occurred in 2016 (330 cases [78%]). The median age was 36 years (range: 3-92); 63% were female. The most frequent region of exposure was the Caribbean (60%). Thirteen travelers were pregnant during or after travel; one had a sexually-acquired ZIKV infection. There was one case of fetal anomaly and two travelers with Guillain-Barre syndrome. GeoSentinel sites reported various challenges to diagnose ZIKV effectively. CONCLUSION: ZIKV should remain a consideration for travelers returning from areas with risk of ZIKV transmission. Travelers should discuss their travel plans with their healthcare providers to ensure ZIKV prevention measures are taken.

      2. Adapting the ages and stages questionnaire to identify and quantify development among children with evidence of Zika infectionexternal icon
        Attell JE, Rose C, Bertolli J, Kotzky K, Squires J, Krishna NK, Satterfield-Nash A, Peacock G, Ornelas Pereira I, Faria E. Silva Santelli AS, Smith C.
        Infants Young Child. 2020 ;33(2):95-107.
        This article describes novel methods of applying the Ages and Stages Questionnaire-3rd edition (ASQ-3) to assess and quantify developmental delay among children following the 2015-2016 Zika virus outbreak in Brazil. Many of the children with Zika virus infection were expected to have severe developmental delay. However, administering the ASQ-3 to caregivers of these children according to standard protocol would have screened for the overall presence of delay but not the severity of delay. We adopted an amended protocol for administration of the ASQ-3 to quantify the developmental functioning of children severely affected by Zika virus infection in this investigation. Protocols for administering the ASQ-3 among this population were drafted in consultation with developmental measurement experts and are presented here. Specific developmental estimates are discussed, including developmental age equivalents, developmental quotients, and developmental quotient z scores. The calculations of these estimates are presented with examples in the context of the 2015-2016 Zika virus outbreak and associated microcephaly among prenatally infected children from 2 states in northeastern Brazil. Potential applications of these methods for estimating developmental ability among similar pediatric populations are discussed.

      3. Indirect evidence of Bourbon virus (Thogotovirus, Orthomyxoviridae) infection in North Carolinaexternal icon
        Komar N, Hamby N, Palamar MB, Staples JE, Williams C.
        N C Med J. 2020 May-Jun;81(3):214-215.

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DISCLAIMER: Articles listed in the CDC Science Clips are selected by the Stephen B. Thacker CDC Library to provide current awareness of the public health literature. An article's inclusion does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.

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