Volume 10, Issue 17, May 15, 2018

CDC Science Clips: Volume 10, Issue 17, May 15, 2018

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

  1. CDC Public Health Grand Rounds
    • Antibiotic Stewardship
      1. The Core Elements of Antibiotic Stewardship for Nursing HomesCdc-pdf
        Centers for Disease Control and Prevention .
        US Department of Health and Human Services, CDC, Atlanta, GA. 2015 .

        The Core Elements of Antibiotic Stewardship for Nursing Homes adapts the CDC Core Elements of Hospital Antibiotic Stewardship into practical ways to initiate or expand antibiotic stewardship activities in nursing homes. Nursing homes are encouraged to work in a step-wise fashion, implementing one or two activities to start and gradually adding new strategies from each element over time. Any action taken to improve antibiotic use is expected to reduce adverse events, prevent emergence of resistance, and lead to better outcomes for residents in this setting.

      2. Implementation of Antibiotic Stewardship Core Elements at Small and Critical Access Hospitals
        Centers for Disease Control and Prevention .
        US Department of Health and Human Services, CDC, Atlanta, GA. 2017 .

        This document provides guidance on practical strategies to implement antibiotic stewardship programs in small and critical access hospitals. It was developed as a collaboration between The Centers for Disease Control and Prevention, The American Hospital Association, The Federal Office of Rural Health Policy and The Pew Charitable Trusts. The suggestions provided here are based on discussions with staff in small and critical access hospitals, several of which have implemented all of the CDC Core Elements.

      3. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011External
        Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartoces M, Enns EA, File TM, Finkelstein JA, et al .
        Jama. 2016 May 3;315(17):1864-73.

        IMPORTANCE: The National Action Plan for Combating Antibiotic-Resistant Bacteria set a goal of reducing inappropriate outpatient antibiotic use by 50% by 2020, but the extent of inappropriate outpatient antibiotic use is unknown. OBJECTIVE: To estimate the rates of outpatient oral antibiotic prescribing by age and diagnosis, and the estimated portions of antibiotic use that may be inappropriate in adults and children in the United States. DESIGN, SETTING, AND PARTICIPANTS: Using the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, annual numbers and population-adjusted rates with 95% confidence intervals of ambulatory visits with oral antibiotic prescriptions by age, region, and diagnosis in the United States were estimated. EXPOSURES: Ambulatory care visits. MAIN OUTCOMES AND MEASURES: Based on national guidelines and regional variation in prescribing, diagnosis-specific prevalence and rates of total and appropriate antibiotic prescriptions were determined. These rates were combined to calculate an estimate of the appropriate annual rate of antibiotic prescriptions per 1000 population. RESULTS: Of the 184,032 sampled visits, 12.6% of visits (95% CI, 12.0%-13.3%) resulted in antibiotic prescriptions. Sinusitis was the single diagnosis associated with the most antibiotic prescriptions per 1000 population (56 antibiotic prescriptions [95% CI, 48-64]), followed by suppurative otitis media (47 antibiotic prescriptions [95% CI, 41-54]), and pharyngitis (43 antibiotic prescriptions [95% CI, 38-49]). Collectively, acute respiratory conditions per 1000 population led to 221 antibiotic prescriptions (95% CI, 198-245) annually, but only 111 antibiotic prescriptions were estimated to be appropriate for these conditions. Per 1000 population, among all conditions and ages combined in 2010-2011, an estimated 506 antibiotic prescriptions (95% CI, 458-554) were written annually, and, of these, 353 antibiotic prescriptions were estimated to be appropriate antibiotic prescriptions. CONCLUSIONS AND RELEVANCE: In the United States in 2010-2011, there was an estimated annual antibiotic prescription rate per 1000 population of 506, but only an estimated 353 antibiotic prescriptions were likely appropriate, supporting the need for establishing a goal for outpatient antibiotic stewardship.

      4. Frequency of first-line antibiotic selection among US ambulatory care visits for otitis media, sinusitis, and pharyngitisExternal
        Hersh AL, Fleming-Dutra KE, Shapiro DJ, Hyun DY, Hicks LA.
        JAMA Intern Med. 2016 Dec 1;176(12):1870-1872.

        [No abstract]

      5. US outpatient antibiotic prescribing variation according to geography, patient population, and provider specialty in 2011External
        Hicks LA, Bartoces MG, Roberts RM, Suda KJ, Hunkler RJ, Taylor TH, Schrag SJ.
        Clin Infect Dis. 2015 May 1;60(9):1308-16.

        BACKGROUND: Appropriate antibiotic prescribing is an essential strategy to reduce the spread of antibiotic resistance. US prescribing practices have not been thoroughly characterized. We analyzed outpatient antibiotic prescribing data to identify where appropriate antibiotic prescribing interventions could have the most impact. METHODS: Oral antibiotic prescriptions dispensed during 2011 were extracted from the IMS Health Xponent database. The number of prescriptions and census denominators were used to calculate prescribing rates. Prescription totals were calculated for each provider specialty. Regression modeling was used to examine the association between socioeconomic and population health factors and prescribing rates. RESULTS: Healthcare providers prescribed 262.5 million courses of antibiotics in 2011(842 prescriptions per 1000 persons). Penicillins and macrolides were the most common antibiotic categories prescribed. The most commonly prescribed individual antibiotic agent was azithromycin. Family practitioners prescribed the most antibiotic courses (24%). The prescribing rate was higher in the South census region (931 prescriptions per 1000 persons) than in the West (647 prescriptions per 1000 persons; P < .001); this pattern was observed among all age groups, including children </= 2 and persons >/= 65 years of age. Counties with a high proportion of obese persons, infants and children </= 2 years of age, prescribers per capita, and females were more likely to be high prescribing by multivariable analysis (adjusted odds ratio, >1.0). CONCLUSIONS: Efforts to characterize antibiotic prescribing practices should focus on the South census region and family practitioners. Further understanding of the factors leading to high prescribing among key target populations will inform appropriate prescribing interventions.

      6. Time of day and the decision to prescribe antibioticsExternal
        Linder JA, Doctor JN, Friedberg MW, Reyes Nieva H, Birks C, Meeker D, Fox CR.
        JAMA Intern Med. 2014 Dec;174(12):2029-31.

        [No abstract]

      7. Effects of behavioral interventions on inappropriate antibiotic prescribing in primary care 12 months after stopping interventionsExternal
        Linder JA, Meeker D, Fox CR, Friedberg MW, Persell SD, Goldstein NJ, Doctor JN.
        Jama. 2017 Oct 10;318(14):1391-1392.

        [No abstract]

      8. Nudging guideline-concordant antibiotic prescribing: a randomized clinical trialExternal
        Meeker D, Knight TK, Friedberg MW, Linder JA, Goldstein NJ, Fox CR, Rothfeld A, Diaz G, Doctor JN.
        JAMA Intern Med. 2014 Mar;174(3):425-31.

        IMPORTANCE: “Nudges” that influence decision making through subtle cognitive mechanisms have been shown to be highly effective in a wide range of applications, but there have been few experiments to improve clinical practice. OBJECTIVE: To investigate the use of a behavioral “nudge” based on the principle of public commitment in encouraging the judicious use of antibiotics for acute respiratory infections (ARIs). DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial in 5 outpatient primary care clinics. A total of 954 adults had ARI visits during the study timeframe: 449 patients were treated by clinicians randomized to the posted commitment letter (335 in the baseline period, 114 in the intervention period); 505 patients were treated by clinicians randomized to standard practice control (384 baseline, 121 intervention). INTERVENTIONS: The intervention consisted of displaying poster-sized commitment letters in examination rooms for 12 weeks. These letters, featuring clinician photographs and signatures, stated their commitment to avoid inappropriate antibiotic prescribing for ARIs. MAIN OUTCOMES AND MEASURES: Antibiotic prescribing rates for antibiotic-inappropriate ARI diagnoses in baseline and intervention periods, adjusted for patient age, sex, and insurance status. RESULTS: Baseline rates were 43.5% and 42.8% for control and poster, respectively. During the intervention period, inappropriate prescribing rates increased to 52.7% for controls but decreased to 33.7% in the posted commitment letter condition. Controlling for baseline prescribing rates, we found that the posted commitment letter resulted in a 19.7 absolute percentage reduction in inappropriate antibiotic prescribing rate relative to control (P = .02). There was no evidence of diagnostic coding shift, and rates of appropriate antibiotic prescriptions did not diminish over time. CONCLUSIONS AND RELEVANCE: Displaying poster-sized commitment letters in examination rooms decreased inappropriate antibiotic prescribing for ARIs. The effect of this simple, low-cost intervention is comparable in magnitude to costlier, more intensive quality-improvement efforts. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01767064.

      9. Effect of behavioral interventions on inappropriate antibiotic prescribing among primary care practices: A randomized clinical trialExternal
        Meeker D, Linder JA, Fox CR, Friedberg MW, Persell SD, Goldstein NJ, Knight TK, Hay JW, Doctor JN.
        Jama. 2016 Feb 9;315(6):562-70.

        IMPORTANCE: Interventions based on behavioral science might reduce inappropriate antibiotic prescribing. OBJECTIVE: To assess effects of behavioral interventions and rates of inappropriate (not guideline-concordant) antibiotic prescribing during ambulatory visits for acute respiratory tract infections. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized clinical trial conducted among 47 primary care practices in Boston and Los Angeles. Participants were 248 enrolled clinicians randomized to receive 0, 1, 2, or 3 interventions for 18 months. All clinicians received education on antibiotic prescribing guidelines on enrollment. Interventions began between November 1, 2011, and October 1, 2012. Follow-up for the latest-starting sites ended on April 1, 2014. Adult patients with comorbidities and concomitant infections were excluded. INTERVENTIONS: Three behavioral interventions, implemented alone or in combination: suggested alternatives presented electronic order sets suggesting nonantibiotic treatments; accountable justification prompted clinicians to enter free-text justifications for prescribing antibiotics into patients’ electronic health records; peer comparison sent emails to clinicians that compared their antibiotic prescribing rates with those of “top performers” (those with the lowest inappropriate prescribing rates). MAIN OUTCOMES AND MEASURES: Antibiotic prescribing rates for visits with antibiotic-inappropriate diagnoses (nonspecific upper respiratory tract infections, acute bronchitis, and influenza) from 18 months preintervention to 18 months afterward, adjusting each intervention’s effects for co-occurring interventions and preintervention trends, with random effects for practices and clinicians. RESULTS: There were 14,753 visits (mean patient age, 47 years; 69% women) for antibiotic-inappropriate acute respiratory tract infections during the baseline period and 16,959 visits (mean patient age, 48 years; 67% women) during the intervention period. Mean antibiotic prescribing rates decreased from 24.1% at intervention start to 13.1% at intervention month 18 (absolute difference, -11.0%) for control practices; from 22.1% to 6.1% (absolute difference, -16.0%) for suggested alternatives (difference in differences, -5.0% [95% CI, -7.8% to 0.1%]; P = .66 for differences in trajectories); from 23.2% to 5.2% (absolute difference, -18.1%) for accountable justification (difference in differences, -7.0% [95% CI, -9.1% to -2.9%]; P < .001); and from 19.9% to 3.7% (absolute difference, -16.3%) for peer comparison (difference in differences, -5.2% [95% CI, -6.9% to -1.6%]; P < .001). There were no statistically significant interactions (neither synergy nor interference) between interventions. CONCLUSIONS AND RELEVANCE: Among primary care practices, the use of accountable justification and peer comparison as behavioral interventions resulted in lower rates of inappropriate antibiotic prescribing for acute respiratory tract infections. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01454947.

      10. Tipping the balance toward fewer antibioticsExternal
        Mehrotra A, Linder JA.
        JAMA Intern Med. 2016 Nov 1;176(11):1649-1650.

        [No abstract]

      11. The proven benefits of antibiotic stewardship programs (ASPs) for optimizing antibiotic use and minimizing adverse events, such as Clostridium difficile and antibiotic resistance, have prompted the Centers for Disease Control and Prevention (CDC) to recommend that all hospitals have an ASP. This article summarizes Core Elements of Hospital Antibiotic Stewardship Programs, a recently released CDC document focused on defining the infrastructure and practices of coordinated multidisciplinary programs to improve antibiotic use and patient care in US hospitals.

      12. Core elements of outpatient antibiotic stewardshipExternal
        Sanchez GV, Fleming-Dutra KE, Roberts RM, Hicks LA.
        MMWR Recomm Rep. 2016 Nov 11;65(6):1-12.

        The Core Elements of Outpatient Antibiotic Stewardship provides a framework for antibiotic stewardship for outpatient clinicians and facilities that routinely provide antibiotic treatment. This report augments existing guidance for other clinical settings. In 2014 and 2015, respectively, CDC released the Core Elements of Hospital Antibiotic Stewardship Programs and the Core Elements of Antibiotic Stewardship for Nursing Homes. Antibiotic stewardship is the effort to measure and improve how antibiotics are prescribed by clinicians and used by patients. Improving antibiotic prescribing involves implementing effective strategies to modify prescribing practices to align them with evidence-based recommendations for diagnosis and management. The four core elements of outpatient antibiotic stewardship are commitment, action for policy and practice, tracking and reporting, and education and expertise. Outpatient clinicians and facility leaders can commit to improving antibiotic prescribing and take action by implementing at least one policy or practice aimed at improving antibiotic prescribing practices. Clinicians and leaders of outpatient clinics and health care systems can track antibiotic prescribing practices and regularly report these data back to clinicians. Clinicians can provide educational resources to patients and families on appropriate antibiotic use. Finally, leaders of outpatient clinics and health systems can provide clinicians with education aimed at improving antibiotic prescribing and with access to persons with expertise in antibiotic stewardship. Establishing effective antibiotic stewardship interventions can protect patients and improve clinical outcomes in outpatient health care settings.

  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. Bilateral choroidal osteoma associated with langerhans cell histiocytosis, a coincidence?External
        Azadi P, Khodabande A, Riazi Esfahani M, Ghassemi F, Aliabadi N.
        J Curr Ophthalmol. 2018 .

        Purpose: To describe a case of bilateral choroidal osteoma (CO) in a patient with a history of langerhans cell histiocytosis (LCH). Methods: A 24-year-old man complaining of gradually decreasing visual acuity in both eyes was presented. He had a history of lymphadenopathy, respiratory symptoms, and pathology-proven diagnosis of LCH. Results: Ophthalmic clinical and imaging studies revealed bilateral CO. Conclusion: In this patient, we suggest a possible relationship between LCH and CO.

      2. Health care provider counseling for weight loss among adults with arthritis and overweight or obesity – United States, 2002-2014External
        Guglielmo D, Hootman JM, Murphy LB, Boring MA, Theis KA, Belay B, Barbour KE, Cisternas MG, Helmick CG.
        MMWR Morb Mortal Wkly Rep. 2018 May 4;67(17):485-490.

        In the United States, 54.4 million adults report having doctor-diagnosed arthritis (1). Among adults with arthritis, 32.7% and 38.1% also have overweight and obesity, respectively (1), with obesity being more prevalent among persons with arthritis than among those who do not have arthritis (2). Furthermore, severe joint pain among adults with arthritis in 2014 was reported by 23.5% of adults with overweight and 31.7% of adults with obesity (3). The American College of Rheumatology recommends weight loss for adults with hip or knee osteoarthritis and overweight or obesity,* which can improve function and mobility while reducing pain and disability (4,5). The Healthy People 2020 target for health care provider (hereafter provider) counseling for weight loss among persons with arthritis and overweight or obesity is 45.3%.(dagger) Adults with overweight or obesity who receive weight-loss counseling from a provider are approximately four times more likely to attempt to lose weight than are those who do not receive counseling (6). To estimate changes in the prevalence of provider counseling for weight loss reported by adults with arthritis and overweight or obesity, CDC analyzed National Health Interview Survey (NHIS) data.( section sign) Overall, age-standardized estimates of provider counseling for weight loss increased by 10.4 percentage points from 2002 (35.1%; 95% confidence interval [CI] = 33.0-37.3) to 2014 (45.5%; 95% CI = 42.9-48.1) (p<0.001). Providing comprehensive behavioral counseling (including nutrition, physical activity, and self-management education) and encouraging evidence-based weight-loss program participation can result in enhanced health benefits for this population.

      3. Diabetes during pregnancy: Surveillance, preconception care, and postpartum careExternal
        Kim SY, Deputy NP, Robbins CL.
        J Womens Health (Larchmt). 2018 May 1.

        Diabetes during pregnancy can adversely affect the health of women and infants. In this report, we provide an overview of the state of the science, and highlight Centers for Disease Control and Prevention (CDC) activities related to (1) surveillance of preexisting and gestational diabetes mellitus (GDM); (2) preconception care for women with preexisting diabetes; (3) postpartum diabetes screening among women with GDM-affected pregnancies; and (4) preventing the progression to Type 2 diabetes among women with GDM-affected pregnancies through lifestyle intervention programs. Improving preconception care, increasing postpartum diabetes screening rates, and promoting lifestyle interventions in the postpartum period all provide opportunities to improve the health of women and their infants.

      4. Radon exposure is the second leading risk factor for lung cancer among smokers and the leading risk factor among non-smokers. Radon concentrated in lower levels of homes/buildings can be reduced if found, thus lowering lung cancer risk. The objective of this study was to measure radon knowledge in diverse populations, with varying radon-related laws, to inform radon-related cancer control practices and activities. A survey was mailed to 3,000 homebuyers who purchased single-family homes; 995 responses (33%) were received. Overall, 86% of respondents heard of radon-related health issues. Real estate agents (69%) or home inspectors (65%) were the most common sources of information. Respondents were more likely to test their home for radon if they reported previously hearing of radon-related health issues or understanding of how radon-related health issues affect the home buying process. Respondents in states with notification policies were twice as likely as those without policies to have heard about radon-related health issues (OR 2.01, 95% CI: 1.27-3.17). This study provides useful information for cancer control activities, including that education is positively associated with home testing for radon. It also suggests partnering with real estate agents to further radon education and testing efforts to reduce radon exposure and lung cancer risk. This article is protected by copyright. All rights reserved.

    • Communicable Diseases
      1. The predictive value of International Classification of Disease codes for chronic hepatitis C virus infection surveillance: The utility and limitations of electronic health recordsExternal
        Abara WE, Moorman AC, Zhong Y, Collier MG, Rupp LB, Gordon SC, Boscarino JA, Schmidt MA, Trinacty CM, Holmberg SD.
        Popul Health Manag. 2018 ;21(2):110-115.

        Surveillance of chronic hepatitis C virus (HCV) cases faces limitations that result in delays and underreporting. With increasing use of electronic health records (EHRs), the authors evaluated the predictive value of using International Classification of Diseases, Ninth Revision (ICD-9) codes to identify chronic HCV cases from EHR data. Longitudinal EHR data from 4 health care systems during 2006-2012 were evaluated. Using chart abstraction and review to confirm chronic HCV cases (“gold standard” definition), the authors calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 2 case definitions: (1) >/=2 ICD-9 codes separated by >/= 6 months and (2) >/=1 positive HCV RNA (ribonucleic acid) test. Among 2,718,995 patients, 20,779 (0.8%) with ICD-9 codes indicating a likely diagnosis of chronic HCV infection were identified; 13,595 (65.4%) of these were randomly selected for review. Case definition 1 (>/= 2 ICD-9 codes separated by >/= 6 months) had 70.3% sensitivity, 91.9% PPV, 99.9% specificity, and 99.9% NPV while case definition 2 (>/= 1 positive HCV RNA test) had 74.1% sensitivity, 97.4% PPV, 99.9% specificity, and 99.9% NPV. The predictive values of these alternate EHR-derived ICD-9 code-based case definitions suggest that these measures may be useful in capturing the burden of diagnosed chronic HCV infections. Their use can augment current chronic HCV case surveillance efforts; however, their accuracy may vary by length of observation and completeness of EHR data.

      2. Acceptability of oral rapid HIV testing at dental clinics in communities with high HIV prevalence in South FloridaExternal
        Bradley EL, Vidot DC, Gaul Z, Sutton MY, Pereyra M.
        PLoS One. 2018 ;13(4):e0196323.

        BACKGROUND: Expanding HIV screening for populations at risk necessitates testing in nontraditional settings. We assessed HIV testing in dental clinics in South Florida, an urban area with the highest rates of HIV diagnoses in the United States in 2015. AIMS: We explored patients’ acceptance of oral HIV rapid tests administered by dental providers and identified reasons for accepting or declining HIV testing. METHODS: During 2014 and 2015, dentists and hygienists at two federally qualified health center (FQHC) dental clinics who serve racial/ethnic minority patient populations in South Florida were trained to administer oral HIV rapid tests as a part of a routine dental visit. Patients presenting for dental services were offered a rapid HIV test and brief survey regarding their demographics, HIV testing history and behaviors. RESULTS: We enrolled 600 patients (median age = 43 years; IQR: 29-56 years), 45% non-Hispanic black and 35% Hispanic/Latino, 83% graduated high school, and 50% unemployed. Most (85%) accepted oral HIV rapid testing (none tested HIV-positive); 14% had never been tested for HIV. The most common reasons for testing were a desire to know HIV status (56%) and free testing (54%). Among 93 (15%) patients who declined testing, 58% were tested recently and 31% felt confident that they were HIV-negative; however, 74 (80%) who declined testing said they would feel comfortable discussing HIV prevention with their dentist. Additionally, 290 of 600 patients (48%) reported condomless vaginal or anal sex in the past 6 months. Further, among 119 patients who had condomless sex with an HIV-positive partner and/or one whose HIV status was unknown, 98 (82%) accepted the oral HIV test. CONCLUSION: Dental clinics may provide expanded opportunities for oral HIV rapid testing and conversations about HIV prevention in high HIV prevalence communities.

      3. Cohort profile: China respiratory illness surveillance among pregnant women (CRISP), 2015-2018External
        Chen L, Zhou S, Zhang Z, Wang Y, Bao L, Tan Y, Sheng F, Song Y, Zhang R, Danielle Iuliano A, Thompson MG, Greene CM, Zhang J.
        BMJ Open. 2018 Apr 28;8(4):e019709.

        PURPOSE: We established the China Respiratory Illness Surveillance among Pregnant women (CRISP) to conduct active surveillance for influenza-associated respiratory illness during pregnancy in China from 2015 to 2018. Among annual cohorts of pregnant women, we assess the incidence of acute respiratory illness (ARI), influenza-like illness (ILI), laboratory-confirmed influenza virus infection and the seroconversion proportion during the winter influenza season. We also plan to examine the effect of influenza virus infection on adverse pregnancy, delivery and infant health outcomes with cumulative data from the three annual cohorts. PARTICIPANTS: Cohort nurses enrol pregnant women in different trimesters of pregnancy from prenatal care facilities in Suzhou, Jiangsu Province, eastern China. Pregnant women who plan to deliver in the study facilities are eligible. Pregnant women who are seeking care for anything other than routine prenatal care, such as confirmation of low progesterone and threatened miscarriage, are excluded. At enrolment, study nurses collect baseline information on demographics, education-level attained, underlying medical conditions, seasonal influenza vaccination receipt, risk factors for influenza infection, gravidity and parity and contact information. For each participant, cohort nurses conduct twice weekly follow-up contacts, one phone call and one WeChat message (free instant messaging), from the time of enrolment until delivery or termination of pregnancy. During follow-up, study nurses ask about symptoms, timing and characteristics of ARI, healthcare-seeking behaviour and medications taken for participants reporting respiratory illness since the last contact. In addition, we collect combined nasal and throat swabs for identified ARI to test for influenza viruses. We collect paired sera before and after the influenza season. Active respiratory illness surveillance and seroinfection data during pregnancy of participants are linked to their medical record and the Suzhou Maternal Child Information System for detailed information on clinical treatment for respiratory illness, pregnancy, delivery and infant health outcomes. FINDINGS TO DATE: In 2015-2016, of 4915 pregnant women approached, 192 (4%) refused to participate, 91 (2%) were ineligible because they did not plan to deliver in one of the study hospitals or because their visit was for anything other than routine prenatal care and 4632 (94%) were enrolled, 46% during their first trimester of pregnancy (range 5-12 weeks), 48% during the second trimester (range 13-27 weeks) and 6% during the third trimester (range 28-37 weeks). The median age of the enrollees was 27 years (range 16-45) and two (0.04%, 95% CI 0.01% to 0.17%) reported influenza vaccination in the previous 12 months before pregnancy, while zero reported influenza vaccination in the previous 12 months during pregnancy. During the observation time of 648 518 person-days, 1355 ARI episodes were identified. Among 1127 swabs collected (for 83% of all ARIs), 68 (6%) tested positive for influenza virus, for a laboratory-confirmed influenza incidence of 0.31 (95% CI 0.25 to 0.40) per 100 person-months during pregnancy in the study cohort. FUTURE PLANS: Results will be used to describe influenza disease burden in this population to model potential numbers of influenza illnesses averted if influenza vaccination coverage were increased and to support enhanced influenza prevention and control strategies among pregnant women in China. We also plan to enrol and follow three cohorts of pregnant women over three influenza seasons during 2015-2018 which will allow an analysis of the effect of influenza virus infection during pregnancy on adverse pregnancy, delivery and infant outcomes.

      4. Progress toward measles elimination – Western Pacific Region, 2013-2017External
        Hagan JE, Kriss JL, Takashima Y, Mariano KM, Pastore R, Grabovac V, Dabbagh AJ, Goodson JL.
        MMWR Morb Mortal Wkly Rep. 2018 May 4;67(17):491-495.

        In 2005, the Regional Committee for the World Health Organization (WHO) Western Pacific Region (WPR)* established a goal for measles elimination(dagger) by 2012 (1). To achieve this goal, the 37 WPR countries and areas implemented the recommended strategies in the WPR Plan of Action for Measles Elimination (2) and the Field Guidelines for Measles Elimination (3). The strategies include 1) achieving and maintaining >/=95% coverage with 2 doses of measles-containing vaccine (MCV) through routine immunization services and supplementary immunization activities (SIAs), when required; 2) conducting high-quality case-based measles surveillance, including timely and accurate testing of specimens to confirm or discard suspected cases and detect measles virus for genotyping and molecular analysis; and 3) establishing and maintaining measles outbreak preparedness to ensure rapid response and appropriate case management. This report updates the previous report (4) and describes progress toward measles elimination in WPR during 2013-2017. During 2013-2016, estimated regional coverage with the first MCV dose (MCV1) decreased from 97% to 96%, and coverage with the routine second MCV dose (MCV2) increased from 91% to 93%. Eighteen (50%) countries achieved >/=95% MCV1 coverage in 2016. Seven (39%) of 18 nationwide SIAs during 2013-2017 reported achieving >/=95% administrative coverage. After a record low of 5.9 cases per million population in 2012, measles incidence increased during 2013-2016 to a high of 68.9 in 2014, because of outbreaks in the Philippines and Vietnam, as well as increased incidence in China, and then declined to 5.2 in 2017. To achieve measles elimination in WPR, additional measures are needed to strengthen immunization programs to achieve high population immunity, maintain high-quality surveillance for rapid case detection and confirmation, and ensure outbreak preparedness and prompt response to contain outbreaks.

      5. Hepatitis B virus testing and care among pregnant women using commercial claims data, United States, 2011-2014Cdc-pdfExternal
        Harris AM, Isenhour C, Schillie S, Vellozzi C.
        Infect Dis Obstet Gynecol. 2018 ;2018.

        Introduction. Pregnant women should receive hepatitis B virus (HBV) testing with hepatitis B surface antigen (HBsAg), but it is unclear whether HBV-infected pregnant women are linked to care. Methods. We analyzed MarketScancommercial insurance claims. We included pregnant women, aged 10-50 years, with 42 weeks of continuous enrollment before (predelivery) and 6 months after (postdelivery) the first delivery claim for each unique pregnancy between 1/1/2011 and 6/30/2014. We identified claims for HBsAg testing by CPT code and described the care continuum among pregnancies with an associated ICD-9 HBV diagnosis code by demographic and clinical characteristics, including HBV-directed care ([HBV DNA or hepatitis B e antigen] and ALT test codes) and antiviral treatment (claims for tenofovir, entecavir, lamivudine, adefovir, or telbivudine) pre-And postdelivery. Results. There were 870,888 unique pregnancies (819,752 women) included. Before delivery, 714,830 (82%) pregnancies had HBsAg test claims, but this proportion decreased with subsequent pregnancies (p<0.0001): second (80%), third (71%), and fourth (61%). We identified 1,190 (0.14%) pregnancies with an associated HBV diagnosis code: most were among women aged >/= 30 years (76%) residing in the Pacific (34%) or Middle Atlantic (18%) regions. Forty-Two percent of pregnancies with an HBV diagnosis received HBV-directed care (42% predelivery and 39% postdelivery). Antiviral treatment was initiated before delivery in 128 (13%) of 975 pregnancies and postdelivery in 16 (1.6%) pregnancies. Conclusions. While most of these commercially insured pregnant women received predelivery HBV screening, we identified gaps in HBV testing and the HBV care continuum which highlight potential targets for public health interventions.

      6. Epidemiology and transmission of hepatitis A virus and hepatitis E virus infections in the United StatesExternal
        Hofmeister MG, Foster MA, Teshale EH.
        Cold Spring Harb Perspect Med. 2018 Apr 30.

        There are many similarities in the epidemiology and transmission of hepatitis A virus (HAV) and hepatitis E virus (HEV) genotype (gt)3 infections in the United States. Both viruses are enterically transmitted, although specific routes of transmission are more clearly established for HAV than for HEV: HAV is restricted to humans and primarily spread through the fecal-oral route, while HEV is zoonotic with poorly understood modes of transmission in the United States. New cases of HAV infection have decreased dramatically in the United States since infant vaccination was recommended in 1996. In recent years, however, outbreaks have occurred among an increasingly susceptible adult population. Although HEV is the most common cause of acute viral hepatitis in developing countries, it is rarely diagnosed in the United States.

      7. Notes from the field: Increase in hepatitis A virus infections – Marshall Islands, 2016-2017External
        Hofmeister MG, McCready JA, Link-Gelles R, Cramer BG, Nolen LD, Garstang H, Foster MA.
        MMWR Morb Mortal Wkly Rep. 2018 May 4;67(17):504-505.

        [No abstract]

      8. Statins suppress Ebola virus infectivity by interfering with glycoprotein processingExternal
        Shrivastava-Ranjan P, Flint M, Bergeron E, McElroy AK, Chatterjee P, Albarino CG, Nichol ST, Spiropoulou CF.
        MBio. 2018 May 1;9(3).

        Ebola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments. Statins, widely used cholesterol-lowering drugs, have pleiotropic mechanisms of action and were suggested as potential adjunct therapy for Ebola virus disease (EVD) during the 2013-2016 outbreak in West Africa. Here, we evaluated the antiviral effects of statin (lovastatin) on EBOV infection in vitro Statin treatment decreased infectious EBOV production in primary human monocyte-derived macrophages and in the hepatic cell line Huh7. Statin treatment did not interfere with viral entry, but the viral particles released from treated cells showed reduced infectivity due to inhibition of viral glycoprotein processing, as evidenced by decreased ratios of the mature glycoprotein form to precursor form. Statin-induced inhibition of infectious virus production and glycoprotein processing was reversed by exogenous mevalonate, the rate-limiting product of the cholesterol biosynthesis pathway, but not by low-density lipoprotein. Finally, statin-treated cells produced EBOV particles devoid of the surface glycoproteins required for virus infectivity. Our findings demonstrate that statin treatment inhibits EBOV infection and suggest that the efficacy of statin treatment should be evaluated in appropriate animal models of EVD.IMPORTANCE Treatments targeting Ebola virus disease (EVD) are experimental, expensive, and scarce. Statins are inexpensive generic drugs that have been used for many years for the treatment of hypercholesterolemia and have a favorable safety profile. Here, we show the antiviral effects of statins on infectious Ebola virus (EBOV) production. Our study reveals a novel molecular mechanism in which statin regulates EBOV particle infectivity by preventing glycoprotein processing and incorporation into virus particles. Additionally, statins have anti-inflammatory and immunomodulatory effects. Since inflammation and dysregulation of the immune system are characteristic features of EVD, statins could be explored as part of EVD therapeutics.

    • Disease Reservoirs and Vectors
      1. Studies reporting tick infection rates for Powassan virus (POWV), an emerging zoonotic arthropod-borne pathogen responsible for POWV disease in the Commonwealth of Pennsylvania, are limited. To determine the presence and ascertain a statewide prevalence of POWV, ticks were collected from 9,912 hunter-harvested white-tailed deer (Odocoileus virginianus) heads presented to six regional Pennsylvania Game Commission Chronic Wasting Disease sampling stations in early December of 2013, 2014 and 2015. Of the 2,973 ticks recovered, 1,990 (66.9%) were identified as adult Ixodes scapularis (black-legged tick). The 1,990 I. scapularis ticks were PCR-tested for the presence of POWV. The ticks had a statewide Powassan/deer tick virus infection rate of 0.05%, providing evidence of this pathogen in Pennsylvania’s adult I. scapularis ticks and supporting the need for more comprehensive pathogen prevalence assessment strategies, as well as increased public health awareness for this emerging zoonotic arthropod-borne pathogen of public health concern.

      2. Resistance to deltamethrin in prairie dog (Cynomys ludovicianus) fleas in the field and in the laboratoryExternal
        Eads DA, Biggins DE, Bowser J, McAllister JC, Griebel RL, Childers E, Livieri TM, Painter C, Krank LS, Bly K.
        J Wildl Dis. 2018 May 3.

        Sylvatic plague poses a substantial risk to black-tailed prairie dogs ( Cynomys ludovicianus) and their obligate predator, the black-footed ferret ( Mustela nigripes). The effects of plague on prairie dogs and ferrets are mitigated using a deltamethrin pulicide dust that reduces the spread of plague by killing fleas, the vector for the plague bacterium. In portions of Conata Basin, Buffalo Gap National Grasslands, and Badlands National Park, South Dakota, 0.05% deltamethrin has been infused into prairie dog burrows on an annual basis since 2005. We aimed to determine if fleas ( Oropsylla hirsuta) in portions of the Conata Basin and Badlands National Park have evolved resistance to deltamethrin. We assessed flea prevalence, obtained by combing prairie dogs for fleas, as an indirect measure of resistance. Dusting was ineffective in two colonies treated with deltamethrin for >8 yr; flea prevalence rebounded within 1 mo of dusting. We used a bioassay that exposed fleas to deltamethrin to directly evaluate resistance. Fleas from colonies with >8 yr of exposure to deltamethrin exhibited survival rates that were 15% to 83% higher than fleas from sites that had never been dusted. All fleas were paralyzed or dead after 55 min. After removal from deltamethrin, 30% of fleas from the dusted colonies recovered, compared with 1% of fleas from the not-dusted sites. Thus, deltamethrin paralyzed fleas from colonies with long-term exposure to deltamethrin, but a substantial number of those fleas was resistant and recovered. Flea collections from live-trapped prairie dogs in Thunder Basin National Grasslands, Wyoming suggest that, in some cases, fleas might begin to develop a moderate level of resistance to deltamethrin after 5-6 yr of annual treatments. Restoration of black-footed ferrets and prairie dogs will rely on an adaptive, integrative approach to plague management, for instance involving the use of vaccines and rotating applications of insecticidal products with different active ingredients.

      3. The Egyptian rousette genome reveals unexpected features of bat antiviral immunityExternal
        Pavlovich SS, Lovett SP, Koroleva G, Guito JC, Arnold CE, Nagle ER, Kulcsar K, Lee A, Thibaud-Nissen F, Hume AJ, Muhlberger E, Uebelhoer LS, Towner JS, Rabadan R, Sanchez-Lockhart M, Kepler TB, Palacios G.
        Cell. 2018 Apr 18.

        Bats harbor many viruses asymptomatically, including several notorious for causing extreme virulence in humans. To identify differences between antiviral mechanisms in humans and bats, we sequenced, assembled, and analyzed the genome of Rousettus aegyptiacus, a natural reservoir of Marburg virus and the only known reservoir for any filovirus. We found an expanded and diversified KLRC/KLRD family of natural killer cell receptors, MHC class I genes, and type I interferons, which dramatically differ from their functional counterparts in other mammals. Such concerted evolution of key components of bat immunity is strongly suggestive of novel modes of antiviral defense. An evaluation of the theoretical function of these genes suggests that an inhibitory immune state may exist in bats. Based on our findings, we hypothesize that tolerance of viral infection, rather than enhanced potency of antiviral defenses, may be a key mechanism by which bats asymptomatically host viruses that are pathogenic in humans.

      4. Parallel evolution of vgsc mutations at domains IS6, IIS6 and IIIS6 in pyrethroid resistant Aedes aegypti from MexicoExternal
        Saavedra-Rodriguez K, Maloof FV, Campbell CL, Garcia-Rejon J, Lenhart A, Penilla P, Rodriguez A, Sandoval AA, Flores AE, Ponce G, Lozano S, Black WC.
        Sci Rep. 2018 Apr 30;8(1):6747.

        Aedes aegypti is the primary urban mosquito vector of viruses causing dengue, Zika and chikungunya fevers -for which vaccines and effective pharmaceuticals are still lacking. Current strategies to suppress arbovirus outbreaks include removal of larval-breeding sites and insecticide treatment of larval and adult populations. Insecticidal control of Ae. aegypti is challenging, due to a recent rapid global increase in knockdown-resistance (kdr) to pyrethroid insecticides. Widespread, heavy use of pyrethroid space-sprays has created an immense selection pressure for kdr, which is primarily under the control of the voltage-gated sodium channel gene (vgsc). To date, eleven replacements in vgsc have been discovered, published and shown to be associated with pyrethroid resistance to varying degrees. In Mexico, F1,534C and V1,016I have co-evolved in the last 16 years across Ae. aegypti populations. Recently, a novel replacement V410L was identified in Brazil and its effect on vgsc was confirmed by electrophysiology. Herein, we screened V410L in 25 Ae. aegypti historical collections from Mexico, the first heterozygote appeared in 2002 and frequencies have increased in the last 16 years alongside V1,016I and F1,534C. Knowledge of the specific vgsc replacements and their interaction to confer resistance is essential to predict and to develop strategies for resistance management.

      5. DNA microarray-based assessment of virulence potential of Shiga toxin gene-carrying Escherichia coli O104:H7 isolated from feedlot cattle fecesExternal
        Shridhar PB, Patel IR, Gangiredla J, Noll LW, Shi X, Bai J, Elkins CA, Strockbine N, Nagaraja TG.
        PLoS One. 2018 ;13(4):e0196490.

        Escherichia coli O104:H4, a hybrid pathotype reported in a large 2011 foodborne outbreak in Germany, has not been detected in cattle feces. However, cattle harbor and shed in the feces other O104 serotypes, particularly O104:H7, which has been associated with sporadic cases of diarrhea in humans. The objective of our study was to assess the virulence potential of Shiga toxin-producing E. coli (STEC) O104:H7 isolated from feces of feedlot cattle using DNA microarray. Six strains of STEC O104:H7 isolated from cattle feces were analyzed using FDA-E. coli Identification (ECID) DNA microarray to determine their virulence profiles and compare them to the human strains (clinical) of O104:H7, STEC O104:H4 (German outbreak strain), and O104:H21 (milk-associated Montana outbreak strain). Scatter plots were generated from the array data to visualize the gene-level differences between bovine and human O104 strains, and Pearson correlation coefficients (r) were determined. Splits tree was generated to analyze relatedness between the strains. All O104:H7 strains, both bovine and human, similar to O104:H4 and O104:H21 outbreak strains were negative for intimin (eae). The bovine strains were positive for Shiga toxin 1 subtype c (stx1c), enterohemolysin (ehxA), tellurite resistance gene (terD), IrgA homolog protein (iha), type 1 fimbriae (fimH), and negative for genes that code for effector proteins of type III secretory system. The six cattle O104 strains were closely related (r = 0.86-0.98) to each other, except for a few differences in phage related and non-annotated genes. One of the human clinical O104:H7 strains (2011C-3665) was more closely related to the bovine O104:H7 strains (r = 0.81-0.85) than the other four human clinical O104:H7 strains (r = 0.75-0.79). Montana outbreak strain (O104:H21) was more closely related to four of the human clinical O104:H7 strains than the bovine O104:H7 strains. None of the bovine E. coli O104 strains carried genes characteristic of E. coli O104:H4 German outbreak strain and unlike other human strains were also negative for Shiga toxin 2. Because cattle E. coli O104:H7 strains possess stx1c and genes that code for enterohemolysin and a variety of adhesins, the serotype has the potential to be a diarrheagenic foodborne pathogen in humans.

      6. Equine encephalosis virus in India, 2008External
        Yadav PD, Albarino CG, Nyayanit DA, Guerrero L, Jenks MH, Sarkale P, Nichol ST, Mourya DT.
        Emerg Infect Dis. 2018 May;24(5):898-901.

        A virus isolated from a sick horse from India in 2008 was confirmed by next-generation sequencing analysis to be equine encephalosis virus (EEV). EEV in India is concerning because several species of Culicoides midge, which play a major role in EEV natural maintenance and transmission, are present in this country.

    • Drug Safety
      1. Primary care provider perceptions and practices regarding dosing units for oral liquid medicationsExternal
        Lovegrove MC, Sapiano MR, Paul IM, Yin HS, Wilkins TL, Budnitz DS.
        Acad Pediatr. 2018 May – Jun;18(4):405-408.

        INTRODUCTION: To prevent errors, health care professional and safety organizations recommend using milliliters (mL) alone for oral liquid medication dosing instructions and devices. In 2018, for federal incentives under the Quality Payment Program, one requirement is for electronic health records to automatically use mL alone whenever oral liquid medications are prescribed. Current perceptions and practices of primary care providers (PCPs) regarding dosing units for oral liquid medications were assessed. METHODS: Pediatricians, family practitioners, nurse practitioners, and internists participating in the 2015 DocStyles Web-based survey were asked about their perceptions and practices regarding dosing units for oral liquid medications. RESULTS: Three fifths of PCPs (59.0%) reported that using mL alone is safest for dosing oral liquid medications; however, nearly three quarters (72.0%) thought that patients/caregivers prefer instructions that include spoon-based units. Within each specialty, fewer PCPs reported they would prescribe using mL alone than reported that using mL alone is safest (P < .0001 for all). Among PCPs who think milliliter-only dosing is safest, those who perceived patients/caregivers prefer including spoon-based units were less likely to prescribe using mL alone (odds ratio 0.45, 95% confidence interval 0.34-0.59). Pediatricians were more likely than other PCPs to report that it is safest to use mL alone (80.8% vs 54.7%) and that they would use mL alone when prescribing (56.8% vs 30.9%) (P < .0001 for both). CONCLUSIONS: Because less than two thirds of pediatricians and one third of other PCPs would use mL alone in dosing instructions, additional education to encourage prescribing and communicating with patients/caregivers using mL alone may be needed.

    • Environmental Health
      1. Changes in extreme events and the potential impacts on human healthExternal
        Bell JE, Brown CL, Conlon K, Herring S, Kunkel KE, Lawrimore J, Luber G, Schreck C, Smith A, Uejio C.
        J Air Waste Manag Assoc. 2018 Apr;68(4):265-287.

        Extreme weather and climate-related events affect human health by causing death, injury, and illness, as well as having large socioeconomic impacts. Climate change has caused changes in extreme event frequency, intensity, and geographic distribution, and will continue to be a driver for change in the future. Some of these events include heat waves, droughts, wildfires, dust storms, flooding rains, coastal flooding, storm surges, and hurricanes. The pathways connecting extreme events to health outcomes and economic losses can be diverse and complex. The difficulty in predicting these relationships comes from the local societal and environmental factors that affect disease burden. More information is needed about the impacts of climate change on public health and economies to effectively plan for and adapt to climate change. This paper describes some of the ways extreme events are changing and provides examples of the potential impacts on human health and infrastructure. It also identifies key research gaps to be addressed to improve the resilience of public health to extreme events in the future. IMPLICATIONS: Extreme weather and climate events affect human health by causing death, injury, and illness, as well as having large socioeconomic impacts. Climate change has caused changes in extreme event frequency, intensity, and geographic distribution, and will continue to be a driver for change in the future. Some of these events include heat waves, droughts, wildfires, flooding rains, coastal flooding, surges, and hurricanes. The pathways connecting extreme events to health outcomes and economic losses can be diverse and complex. The difficulty in predicting these relationships comes from the local societal and environmental factors that affect disease burden.

      2. Prenatal and childhood exposure to per- and polyfluoroalkyl substances (PFASs) and child cognitionExternal
        Harris MH, Oken E, Rifas-Shiman SL, Calafat AM, Ye X, Bellinger DC, Webster TF, White RF, Sagiv SK.
        Environ Int. 2018 Apr 26;115:358-369.

        BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) are suspected developmental toxicants, but epidemiological evidence on neurodevelopmental effects of PFAS exposure is inconsistent. We examined associations of prenatal and childhood PFAS exposure with performance on assessments of cognition in children. METHODS: We included mother-child pairs from Project Viva, a longitudinal Boston-area birth cohort enrolled during 1999-2002. We quantified concentrations of eight PFASs, including perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexane sulfonate (PFHxS), in plasma collected from women during pregnancy (median 9.7weeks gestation) and from children at a visit in mid-childhood (median age 7.7years). In early childhood (median age 3.2years) we administered standardized assessments of visual motor skills and vocabulary comprehension, and in mid-childhood we assessed visual motor skills, visual memory, and verbal and non-verbal intelligence. Using multivariable regression, we estimated associations of prenatal and childhood PFAS plasma concentrations with children’s cognitive assessment scores, adjusted for relevant covariates including breastfeeding, maternal intelligence, parental education, and household income. Samples sizes ranged from 631 to 971, depending on analysis. RESULTS: Prenatal PFAS concentrations were associated with both better and worse cognitive performance; children with top quartile prenatal concentrations of some PFASs had better visual motor abilities in early childhood and non-verbal IQ and visual memory in mid-childhood, while children with upper quartile prenatal PFOA and PFOS had lower mid-childhood visual-motor scores. In cross-sectional analyses of mid-childhood PFAS concentrations and cognitive assessments, visual-motor scores on the Wide Range Assessment of Visual Motor Abilities (WRAVMA) (standardized mean=100, standard deviation=15) were lower among children with higher PFHxS (fourth quartile (Q4) vs. Q1: -5.0, 95% confidence interval (CI): -9.1, -0.8). Upper quartiles of childhood PFOA and PFOS were also associated with somewhat lower childhood WRAVMA scores, but childhood PFASs were not associated with verbal or non-verbal IQ or visual memory. CONCLUSIONS: We present evidence suggesting associations of prenatal and childhood PFAS exposure with lower childhood visual motor abilities. Other results were inconsistent, with higher prenatal PFASs associated in some cases with better cognitive outcomes.

      3. Urinary phthalate metabolite concentrations and breast cancer incidence and survival following breast cancer: The Long Island Breast Cancer Study ProjectExternal
        Parada H, Gammon MD, Chen J, Calafat AM, Neugut AI, Santella RM, Wolff MS, Teitelbaum SL.
        Environ Health Perspect. 2018 Apr 26;126(4):047013.

        BACKGROUND: Phthalates, known endocrine disruptors, may play a role in breast carcinogenesis. Few studies have examined phthalates in relation to breast cancer (BC), and, to our knowledge, none have considered survival following BC. OBJECTIVES: We examined 11 urinary phthalate metabolites, individually and as molar sum groupings, in association with BC incidence and subsequent survival. METHODS: Our study includes 710 women diagnosed with first primary BC in 1996-1997 and 598 women without BC from Long Island, New York. Within 3 mo of diagnosis, participants provided spot urine samples. Nine phthalate metabolites were measured in all women; two [monocarboxyoctyl phthalate (MCOP) and monocarboxy-isononyl phthalate (MCNP)] were measured in 320 women with and 205 without BC. Women with BC were followed since diagnosis using the National Death Index; during follow-up (median=17.6 y), we identified 271 deaths (98 BC related). We examined creatinine-corrected metabolite concentrations in association with: BC, using logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and all-cause/BC-specific mortality, using Cox regression to estimate hazard ratios (HRs) and 95% CIs. We also examined effect modification by body mass index (BMI) and estrogen receptor (ER) status. RESULTS: The highest (vs. lowest) quintiles of mono(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP), MCNP, and MCOP were associated with BC ORs ranging from 0.71-0.73. The highest (vs. lowest) quintiles of mono(2-ethylhexyl) phthalate (MEHP) and MCOP were associated with BC-specific mortality HRs of 0.54 (95% CI: 0.28, 1.04) and 0.55 (95% CI: 0.23, 1.35), respectively. For BC-specific mortality, interactions were significant between BMI and mono(2-ethyl-5-oxyhexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), with positive associations among women with BMI<25 and inverse associations among women with BMI>/=25.0 kg/m(2). CONCLUSIONS: Consistent with laboratory evidence, we observed inverse associations between urinary concentrations of several phthalate metabolites and BC and subsequent survival; however, these results should be interpreted with caution given that biospecimen collection among women with BC occurred after diagnosis, which may be of particular concern for our case-control findings. https://doi.org/10.1289/EHP2083.

      4. Early-pregnancy plasma concentrations of perfluoroalkyl substances and birth outcomes in Project Viva: Confounded by pregnancy hemodynamics?External
        Sagiv SK, Rifas-Shiman SL, Fleisch AF, Webster TF, Calafat AM, Ye X, Gillman MW, Oken E.
        Am J Epidemiol. 2018 Apr 1;187(4):793-802.

        Associations of prenatal exposure to perfluoroalkyl substances (PFAS), ubiquitous chemicals used in stain- and water-resistant products, with adverse birth outcomes may be confounded by pregnancy hemodynamics. We measured plasma concentrations of 4 PFAS in early pregnancy (median length of gestation, 9 weeks) among 1,645 women in Project Viva, a study of a birth cohort recruited during 1999-2002 in eastern Massachusetts. We fitted multivariable models to estimate associations of PFAS with birth weight-for-gestational age z score and length of gestation, adjusting for sociodemographic confounders and 2 hemodynamic markers: 1) plasma albumin concentration, a measure of plasma volume expansion, and 2) plasma creatinine concentration, used to estimate glomerular filtration rate. Perfluorooctane sulfonate (PFOS) and perfluorononanoate (PFNA) were weakly inversely associated with birth weight-for-gestational age z scores (adjusted beta = -0.04 (95% confidence interval (CI): -0.08, 0.01) and adjusted beta = -0.06 (95% CI: -0.11, -0.01) per interquartile-range increase, respectively). PFOS and PFNA were also associated with higher odds of preterm birth (e.g., for highest PFOS quartile vs. lowest, adjusted odds ratio = 2.4, 95% CI: 1.3, 4.4). Adjusting for markers of pregnancy hemodynamics (glomerular filtration rate and plasma albumin), to the extent that they accurately reflect underlying pregnancy physiology, did not materially affect associations. These results suggest that pregnancy hemodynamics may not confound associations with birth outcomes when PFAS are measured early in pregnancy.

    • Food Safety
      1. Salmonella epidemiology: A whirlwind of changeExternal
        Besser JM.
        Food Microbiol. 2018 May;71:55-59.

        The field of infectious disease epidemiology for Salmonella and other enteric pathogens is undergoing some of the most profound changes since the time of Kauffman and White. Rapid advances in “big data” technologies such as genomics and metagenomics are making it possible to monitor and control salmonellosis in new and exciting ways. Epidemiological methods are becoming increasingly robust through the routine use of standardized hypothesis-generating questionnaires, iterative open-ended interviewing, informational trace-backs and new modeling techniques for describing the attribution of disease to food sources. In addition, Salmonella epidemiology is facing important challenges and new opportunities due to the rapid adoption of culture independent diagnostic test panels by clinical laboratories. Where is this unprecedented wave of change taking us? This chapter will examine emerging trends in Salmonella epidemiology, and take a peek into the not-so-distant future.

      2. Notes from the Field: Salmonella Oranienburg infection linked to consumption of rattlesnake pills – Kansas and Texas, 2017External
        Bottichio L, Webb LM, Leos G, Tolar B, Dowell N, Basler C.
        MMWR Morb Mortal Wkly Rep. 2018 May 4;67(17):502-503.

        [No abstract]

    • Genetics and Genomics
      1. Improved subtyping of Staphylococcus aureus clonal complex 8 strains based on whole-genome phylogenetic analysisExternal
        Bowers JR, Driebe EM, Albrecht V, McDougal LK, Granade M, Roe CC, Lemmer D, Rasheed JK, Engelthaler DM, Keim P, Limbago BM.
        mSphere. 2018 Jun 27;3(3).

        Strains of Staphylococcus aureus in clonal complex 8 (CC8), including USA300, USA500, and the Iberian clone, are prevalent pathogens in the United States, both inside and outside health care settings. Methods for typing CC8 strains are becoming obsolete as the strains evolve and diversify, and whole-genome sequencing has shown that some strain types fall into multiple sublineages within CC8. In this study, we attempt to clarify the strain nomenclature of CC8, classifying the major strain types based on whole-genome sequence phylogenetics using both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) genomes. We show that isolates of the Archaic and Iberian clones from decades ago make up the most basal clade of the main CC8 lineages and that at least one successful lineage of CC8, made up mostly of MSSA, diverged before the other well-known strain types USA500 and USA300. We also show that the USA500 type includes two clades separated by the previously described “Canadian epidemic MRSA” strain CMRSA9, that one clade containing USA500 also contains the USA300 clade, and that the USA300-0114 strain type is not a monophyletic group. Additionally, we present a rapid, simple CC8 strain-typing scheme using real-time PCR assays that target single nucleotide polymorphisms (SNPs) derived from our CC8 phylogeny and show the significant benefit of using more stable genomic markers based on evolutionary lineages over traditional S. aureus typing techniques. This more accurate and accessible S. aureus typing system may improve surveillance and better inform the epidemiology of this very important pathogen.IMPORTANCEStaphylococcus aureus is a major human pathogen worldwide in both community and health care settings. Surveillance for S. aureus strains is important to our understanding of their spread and to informing infection prevention and control. Confusion surrounding the strain nomenclature of one of the most prevalent lineages of S. aureus, clonal complex 8 (CC8), and the imprecision of current tools for typing S. aureus make surveillance and source tracing difficult and sometimes misleading. In this study, we clarify the CC8 strain designations and propose a new typing scheme for CC8 isolates that is rapid and easy to use. This typing scheme is based on relatively stable genomic markers, and we demonstrate its superiority over traditional typing techniques. This scheme has the potential to greatly improve epidemiological investigations of S. aureus.

      2. Comprehensive viral enrichment enables sensitive respiratory virus genomic identification and analysis by next generation sequencingExternal
        O’Flaherty BM, Li Y, Tao Y, Paden CR, Queen K, Zhang J, Dinwiddie DL, Gross SM, Schroth GP, Tong S.
        Genome Res. 2018 Apr 27.

        Next generation sequencing (NGS) technologies have revolutionized the genomics field and are becoming more commonplace for identification of human infectious diseases. However, due to the low abundance of viral nucleic acids (NAs) in relation to host, viral identification using direct NGS technologies often lacks sufficient sensitivity. Here, we describe an approach based on two complementary enrichment strategies that significantly improves the sensitivity of NGS-based virus identification. To start, we developed two sets of DNA probes to enrich virus NAs associated with respiratory diseases. The first set of probes spans the genomes, allowing for identification of known viruses and full genome sequencing, while the second set targets regions conserved among viral families or genera, providing the ability to detect both known and potentially novel members of those virus groups. Efficiency of enrichment was assessed by NGS testing reference virus and clinical samples with known infection. We show significant improvement in viral identification using enriched NGS compared to unenriched NGS. Without enrichment, we observed an average of 0.3% targeted viral reads per sample. However, after enrichment, 50%-99% of the reads per sample were the targeted viral reads for both the reference isolates and clinical specimens using both probe sets. Importantly, dramatic improvements on genome coverage were also observed following virus-specific probe enrichment. The methods described here provide improved sensitivity for virus identification by NGS, allowing for a more comprehensive analysis of disease etiology.

    • Health Behavior and Risk
      1. Health risks among discordant heterosexual high school studentsExternal
        Harper CR, Clayton HB, Andrzejewski J, Johns MM.
        J LGBT Youth. 2018 :1-13.

        Limited information exists on heterosexual youth with sexual contact with same-sex partners in the United States (i.e., discordant heterosexual). We compared the prevalence of health risks between discordant heterosexual, heterosexual with only opposite-sex sexual contact, lesbian/gay, and bisexual students using the 2015 national Youth Risk Behavior Survey (YRBS). Nationwide, 3.2% of students were identified as discordant heterosexuals. The prevalence of several risk behaviors was significantly higher among discordant heterosexual students than their heterosexual peers with only opposite-sex sexual contact. Clinicians should consider sexual identity and sex of sexual partners when conducting risk-assessments to ensure they appropriately target populations for intervention.

      2. Protective factors among transgender and gender variant youth: A systematic review by socioecological levelExternal
        Johns MM, Beltran O, Armstrong HL, Jayne PE, Barrios LC.
        J Prim Prev. 2018 Apr 26.

        Transgender and gender variant (GV) youth experience elevated risk for poor health and academic outcomes due mainly to social experiences of stigma and discrimination. To supplement the growing evidence on health risks encountered by transgender/GV youth, we identified factors theorized to be protective for these youth across all four levels of Bronfenbrenner’s socioecological model (individual, relationship, community, societal). We conducted a systematic search of peer-reviewed research. The articles included in this review were published in peer-reviewed journals in English or Spanish between 1999 and 2014, analyzed data from a sample or subsample of transgender or GV participants with a mean age between 10 and 24 years, and examined the relationship of at least one theorized protective factor to a health or behavioral outcome. Twenty-one articles met inclusion criteria. Transgender/GV youth in included articles ranged from 11 to 26 years of age, were racially/ethnically diverse, and represented varied gender identities. Within these articles, 27 unique protective factors across four levels of the ecological model were identified as related to positive health and well-being. Self-esteem at the individual level, healthy relationships with parents and peers at the relationship-level, and gay-straight alliances at the community level emerged as protective factors across multiple studies. Our findings underscore the relative lack of research on transgender/GV youth and protective factors. Novel recruitment strategies for transgender/GV youth and better measurement of transgender identities are needed to confirm these protective relationships and identify others. Growth in these areas will contribute to building a body of evidence to inform interventions.

    • Health Economics
      1. Although progress has been made toward the objective of increased employment for people with disabilities, the 17.2% employment rate of people with disabilities stands in distressing contrast to the 65% rate of those without disabilities. This article summarizes the results of a comparative survey of representative academic literature and industry publications related to employer policies and practices that can affect workforce participation of individuals with disabilities. Emergent themes include variance in employer perspectives on hiring of individuals with disabilities, impact of perceived versus actual cost as a hiring barrier, and the perceived mismatch of education and/or skills to job qualifications among applicants with disabilities. These themes represent key areas to probe in subsequent research. The research objective is to identify focal points in the industry literature, representative of employer and industry (demand side) points of view that differ from those generally portrayed in the academic literature (more generally, supply side). Findings from a thematic analysis of industry publications can provide (1) evidenced based background to assist in crafting targeted policy to address employer awareness, (2) informed development of industry guidance on topics that may assist employers to achieve a more inclusive workplace, and (3) insights applicable to addressing barriers to broadening participation by technical, scientific, and engineering trained individuals with disabilities.

    • Healthcare Associated Infections
      1. Invasive methicillin-resistant Staphylococcus aureus USA500 strains from the U.S. Emerging Infections Program constitute three geographically distinct lineagesExternal
        Frisch MB, Castillo-Ramirez S, Petit RA, Farley MM, Ray SM, Albrecht VS, Limbago BM, Hernandez J, See I, Satola SW, Read TD.
        mSphere. 2018 Jun 27;3(3).

        USA500 isolates are clonal complex 8 (CC8) Staphylococcus aureus strains closely related to the prominent community- and hospital-associated USA300 group. Despite being relatively understudied, USA500 strains cause a significant burden of disease and are the third most common methicillin-resistant S. aureus (MRSA) strains identified in the U.S. Emerging Infections Program (EIP) invasive S. aureus surveillance. To better understand the genetic relationships of the strains, we sequenced the genomes of 539 USA500 MRSA isolates from sterile site infections collected through the EIP between 2005 and 2013 in the United States. USA500 isolates fell into three major clades principally separated by their distribution across different U.S. regions. Clade C1 strains, found principally in the Northeast, were associated with multiple IS256 insertion elements in their genomes and higher levels of antibiotic resistance. C2 was associated with Southern states, and E1 was associated with Western states. C1 and C2 strains all shared a frameshift in the gene encoding AdsA surface-attached surface protein. We propose that the term “USA500” should be used for CC8 strains sharing a recent common ancestor with the C1, C2, and E1 strains but not in the USA300 group.IMPORTANCE In this work, we have removed some of the confusion surrounding the use of the name “USA500,” placed USA500 strains in the context of the CC8 group, and developed a strategy for assignment to subclades based on genome sequence. Our new phylogeny of USA300/USA500 will be a reference point for understanding the genetic adaptations that have allowed multiple highly virulent clonal strains to emerge from within CC8 over the past 50 years.

    • Immunity and Immunization
      1. Birth outcomes following immunization of pregnant women with pandemic H1N1 influenza vaccine 2009-2010External
        Eaton A, Lewis N, Fireman B, Hansen J, Baxter R, Gee J, Klein NP.
        Vaccine. 2018 May 3;36(19):2733-2739.

        BACKGROUND: Following the H1N1 influenza pandemic in 2009, pregnant women were recommended to receive both seasonal (TIV) and H1N1 influenza vaccines. This study presents incidence of adverse birth and pregnancy outcomes among a population of pregnant women immunized with TIV and H1N1 vaccines at Kaiser Permanente Northern California during 2009-2010. METHODS: We telephone surveyed pregnant Kaiser Permanente Northern California members to assess non-medically-attended reactions following H1N1, TIV or both vaccines during 2009-2010 (n=5365) in a separate study. Here we assessed preterm birth (<37weeks), very preterm birth (<32weeks), low birth weight (<2500 g, LBW), very low birth weight (<1500g), small for gestational age, spontaneous abortions, stillbirths and congenital anomalies among this cohort by comparing incidence and 95% confidence intervals between the following immunization groups: TIV only, H1N1 only, H1N1 prior to TIV immunization, TIV prior to H1N1 and both immunizations given at the same time. RESULTS: Results did not vary significantly between groups. Comparing H1N1 with TIV, incidence were similar for preterm births (6.37vs 6.28/100 births), very preterm births (5.30vs 8.29/1000 births), LBW (4.19vs 2.90/100 births), very LBW (4.54vs 5.52/1000 births), small for gestational age (9.99vs 9.24/1000 births), spontaneous abortion (7.10vs 6.83/1000 pregnancies), stillbirths (7.10vs 4.57/1000 pregnancies), and congenital anomalies (2.66vs 2.43/100 births). CONCLUSIONS: Although constrained by small sample size, complex vaccine groups, and differential vaccine availability during 2009-2010, this study found no difference in adverse birth outcomes between H1N1 vaccine and TIV.

      2. BACKGROUND: Pregnant women are at higher risk for complications from influenza infection. Nevertheless, seasonal influenza vaccination among pregnant women in China is low. A better understanding of perceptions of pregnant women and their physicians, and factors influencing decisions about receiving seasonal influenza vaccine could be used to develop effective strategies for improving seasonal influenza vaccine uptake during pregnancy. METHODS: We recruited pregnant women from 9 hospitals located in 5 cities across China to participate in focus group interviews. Obstetricians from the same hospitals were recruited for one on one in-depth interviews. We collected information about perceptions of barriers and motivating factors for utilizing seasonal influenza vaccine during pregnancy. We systematically analyzed the information using qualitative methods. RESULTS: We conducted 18 focus groups with 108 pregnant women and interviewed 18 obstetricians. Awareness about the use of influenza vaccine during pregnancy was minimal in both subject groups. None of the pregnant women had received influenza vaccine during pregnancy and none of the obstetricians had recommended influenza vaccine for their patients. Both groups noted insufficient knowledge about influenza infection and benefits of the vaccine, concerns about vaccine safety, and lack of local data related to vaccine use in Chinese pregnant women. Obstetricians cited the lack of a national policy as a major barrier to recommending seasonal influenza vaccine to pregnant women. Pregnant women cited not receiving a recommendation for vaccination from healthcare workers as an additional barrier. CONCLUSION: Our findings highlight the immediate need to increase awareness and knowledge about the risks of influenza infection and the benefits and safety of seasonal influenza vaccination among both pregnant women and obstetricians in China. Obstetricians interviewed stated that the development and implementation of a national policy prioritizing pregnant women for seasonal influenza vaccination would facilitate their willingness to recommend seasonal influenza vaccine to pregnant women.

      3. Prevention of pertussis, tetanus, and diphtheria with vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP)External
        Liang JL, Tiwari T, Moro P, Messonnier NE, Reingold A, Sawyer M, Clark TA.
        MMWR Recomm Rep. 2018 Apr 27;67(2):1-44.

        This report compiles and summarizes all recommendations from CDC’s Advisory Committee on Immunization Practices (ACIP) regarding prevention and control of tetanus, diphtheria, and pertussis in the United States. As a comprehensive summary of previously published recommendations, this report does not contain any new recommendations and replaces all previously published reports and policy notes; it is intended for use by clinicians and public health providers as a resource. ACIP recommends routine vaccination for tetanus, diphtheria, and pertussis. Infants and young children are recommended to receive a 5-dose series of diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccines, with one adolescent booster dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. Adults who have never received Tdap also are recommended to receive a booster dose of Tdap. Women are recommended to receive a dose of Tdap during each pregnancy, which should be administered from 27 through 36 weeks’ gestation, regardless of previous receipt of Tdap. After receipt of Tdap, adolescents and adults are recommended to receive a booster tetanus and diphtheria toxoids (Td) vaccine every 10 years to assure ongoing protection against tetanus and diphtheria.

      4. Global distribution of invasive serotype 35D Streptococcus pneumoniae post-PCV13 introductionExternal
        Lo SW, Gladstone RA, van Tonder AJ, Hawkins PA, Kwambana-Adams B, Cornick JE, Madhi SA, Nzenze SA, du Plessis M, Kandasamy R, Carter PE, Koseoglu Eser O, Ho PL, Elmdaghri N, Shakoor S, Clarke SC, Antonio M, Everett DB, von Gottberg A, Klugman KP, McGee L, Breiman RF, Bentley SD.
        J Clin Microbiol. 2018 May 2.

        A newly recognized pneumococcal serotype 35D, which differs from the 35B polysaccharide in structure and serology by not binding to factor serum 35a, was recently reported. The genetic basis for this distinctive serology is due to the presence of an inactivating mutation in wciG, which encodes an O-acetyltransferase responsible for O-acetylation of a galactofuranose. Here, we assessed the genomic data of a worldwide pneumococcal collection to identify serotype 35D isolates and understand their geographical distribution, genetic background and invasiveness potential. Of 21,980 pneumococcal isolates, 444 were originally typed as serotype 35B by PneumoCaT. Analysis of wciG revealed 23 isolates from carriage (n=4) and disease (n=19) with partial or complete loss-of-funtion mutations, including mutations resulting in pre-mature stop codons (n=22) and an in-frame mutation (n=1). These were selected for further analysis. The putative 35D isolates were geographically widespread and 65.2% (15/23) of them was recovered after PCV13 introduction. Compared with serotype 35B, putative serotype 35D isolates have higher invasive disease potentials based on odds ratio (OR) (11.58; 95% CI, 1.42-94.19 vs 0.61; 95% CI, 0.40-0.92) and a higher prevalence of macrolide resistance mediated by mefA (26.1% vs 7.6%, p=0.009). Using Quellung, 50% (10/20) of viable isolates were serotype 35D, 25% (5/20) serotype 35B, and 25% (5/20) a mixture of 35B/35D. The discrepancy between phenotype and genotype requires further investigation. These findings illustrated a global distribution of an invasive serotype 35D among young children post-PCV13 introduction and underlined the invasive potential conferred by the loss of O-acetylation in the pneumococcal capsule.

    • Laboratory Sciences
      1. Implementing a quality management system in the medical microbiology laboratoryExternal
        Carey RB, Bhattacharyya S, Kehl SC, Matukas LM, Pentella MA, Salfinger M, Schuetz AN.
        Clin Microbiol Rev. 2018 Jul;31(3).

        This document outlines a comprehensive practical approach to a laboratory quality management system (QMS) by describing how to operationalize the management and technical requirements described in the ISO 15189 international standard. It provides a crosswalk of the ISO requirements for quality and competence for medical laboratories to the 12 quality system essentials delineated by the Clinical and Laboratory Standards Institute. The quality principles are organized under three main categories: quality infrastructure, laboratory operations, and quality assurance and continual improvement. The roles and responsibilities to establish and sustain a QMS are outlined for microbiology laboratory staff, laboratory management personnel, and the institution’s leadership. Examples and forms are included to assist in the real-world implementation of this system and to allow the adaptation of the system for each laboratory’s unique environment. Errors and nonconforming events are acknowledged and embraced as an opportunity to improve the quality of the laboratory, a culture shift from blaming individuals. An effective QMS encourages “systems thinking” by providing a process to think globally of the effects of any type of change. Ultimately, a successful QMS is achieved when its principles are adopted as part of daily practice throughout the total testing process continuum.

      2. The current study has two aims. First the method of spectral reflectance was used to measure evaporation rates of thin ( approximately 25-300 mum) films of neat liquid volatile organic chemicals exposed to a well-regulated wind speed u. Gas phase evaporation mass transfer coefficient (kevap) measurements of 10 chemicals, 9 of which were measured at similar u, are predicted (slope of log-log data = 1.01; intercept = 0.08; R(2) = 0.996) by a previously proposed mass transfer correlation. For one chemical, isoamyl alcohol, the dependence of kevap on u(0.52) was measured, in support of the predicted exponent value of (1/2). Second, measured kevap of nicotine was used as an input in analytical models based on diffusion theory to estimate the absorbed fraction (Fabs) of a small dose (5 muL/cm(2)) applied to human epidermis in vitro. The measured Fabs was 0.062 +/- 0.023. Model-estimated values are 0.066 and 0.115. Spectral reflectance is a precise method of measuring kevap of liquid chemicals and the data are well-described by a simple gas phase mass transfer coefficient. For nicotine under the single exposure condition measured herein, Fabs is well-predicted from a theoretical model that requires knowledge of kevap, maximal dermal flux and membrane lag time.

      3. Does incorporating change in APRI or FIB-4 indices over time improve the accuracy of a single index for identifying liver fibrosis in persons with chronic hepatitis C virus infection?External
        Gounder PP, Haering C, Bruden DJ, Townshend-Bulson L, Simons BC, Spradling PR, McMahon BJ.
        J Clin Gastroenterol. 2018 Jan;52(1):60-66.

        BACKGROUND: The aspartate aminotransferase-to-platelet ratio index (APRI) and a fibrosis index calculated using platelets (FIB-4) have been proposed as noninvasive markers of liver fibrosis. GOALS: To determine APRI/FIB-4 accuracy for predicting histologic liver fibrosis and evaluate whether incorporating change in index improves test accuracy in hepatitis C virus (HCV)-infected Alaska Native persons. STUDY: Using liver histology as the gold standard, we determined the test characteristics of APRI to predict Metavir >/=F2 fibrosis and FIB-4 to predict Metavir >/=F3 fibrosis. Index discrimination was measured as the area under the receiver operator characteristic curve. We fit a logistic regression model to determine whether incorporating change in APRI/FIB-4 over time improved index discrimination. RESULTS: Among 283 participants, 46% were female, 48% had a body mass index >30, 11% had diabetes mellitus, 8% reported current heavy alcohol use. Participants were infected with HCV genotypes 1 (68%), 2 (17%), or 3 (15%). On liver histology, 30% of study participants had >/=F2 fibrosis and 15% had >/=F3 fibrosis. The positive predictive value of an APRI>1.5/FIB-4>3.25 for identifying fibrosis was 77%/78%. The negative predictive value of an APRI<0.5/FIB-4<1.45 was 91%/87%. The area under the receiver operator characteristic curve of an APRI/FIB-4 for identifying fibrosis was 0.82/0.84. Incorporating change in APRI/FIB-4 did not improve index discrimination. CONCLUSIONS: The accuracy of APRI/FIB-4 for identifying liver fibrosis in HCV-infected Alaska Native persons is similar to that reported in other populations and could help prioritize patients for treatment living in areas without access to liver biopsy. Change in APRI/FIB-4 was not predictive of degree of fibrosis.

      4. Differentiating gold nanorod samples using particle size and shape distributions from transmission electron microscope imagesExternal
        Grulke EA, Wu X, Ji Y, Buhr E, Yamamoto K, Woong Song N, Stefaniak AB, Schwegler-Berry D, Burchett WW, Lambert J, Stromberg AJ.
        Metrologia. 2018 ;55(2):254-267.

        Size and shape distributions of gold nanorod samples are critical to their physico-chemical properties, especially their longitudinal surface plasmon resonance. This interlaboratory comparison study developed methods for measuring and evaluating size and shape distributions for gold nanorod samples using transmission electron microscopy (TEM) images. The objective was to determine whether two different samples, which had different performance attributes in their application, were different with respect to their size and/or shape descriptor distributions. Touching particles in the captured images were identified using a ruggedness shape descriptor. Nanorods could be distinguished from nanocubes using an elongational shape descriptor. A non-parametric statistical test showed that cumulative distributions of an elongational shape descriptor, that is, the aspect ratio, were statistically different between the two samples for all laboratories. While the scale parameters of size and shape distributions were similar for both samples, the width parameters of size and shape distributions were statistically different. This protocol fulfills an important need for a standardized approach to measure gold nanorod size and shape distributions for applications in which quantitative measurements and comparisons are important. Furthermore, the validated protocol workflow can be automated, thus providing consistent and rapid measurements of nanorod size and shape distributions for researchers, regulatory agencies, and industry.

      5. Formaldehyde allergic contact dermatitis (ACD) may be due to products with free formaldehyde or formaldehyde-releasing agents, however, assessment of formaldehyde levels in such products is infrequently conducted. The present study quantifies total releasable formaldehyde from “in-use” products associated with formaldehyde ACD and tests the utility of commercially available formaldehyde spot test kits. Personal care products from 2 patients with ACD to formaldehyde were initially screened at the clinic for formaldehyde using a formaldehyde spot test kit. Formaldehyde positive products were sent to the laboratory for confirmation by gas chromatography-mass spectrometry. In addition, 4 formaldehyde spot test kits were evaluated for potential utility in a clinical setting. Nine of the 10 formaldehyde spot test kit positive products obtained from formaldehyde allergic patients had formaldehyde with total releasable formaldehyde levels ranging from 5.4 to 269.4 microg/g. Of these, only 2 shampoos tested listed a formaldehyde-releasing agent in the ingredients or product literature. Subsequently, commercially available formaldehyde spot test kits were evaluated in the laboratory for ability to identify formaldehyde in personal care products. Chemical based formaldehyde spot test were more reliable than the enzymatic based test in identifying product releasable formaldehyde content. It is concluded that product labeled ingredient lists and available information are often inadequate to confirm the potential for formaldehyde exposure and chemical based spot test kits may have utility for identification of potential formaldehyde exposure from personal care products.

      6. A microneedle patch for measles and rubella vaccination is immunogenic and protective in infant rhesus macaquesExternal
        Joyce JC, Carroll TD, Collins ML, Chen MH, Fritts L, Dutra JC, Rourke TL, Goodson JL, McChesney MB, Prausnitz MR, Rota PA.
        J Infect Dis. 2018 Apr 26.

        Background: New methods to increase measles and rubella (MR) vaccination coverage are needed to achieve global and regional MR elimination goals. Methods: Here, we developed microneedle (MN) patches designed to administer MR vaccine by minimally trained personnel, leave no biohazardous sharps waste, remove the need for vaccine reconstitution, and provide thermostability outside the cold chain. This study evaluated the immunogenicity of MN patches delivering MR vaccine to infant rhesus macaques. Results: Protective titers of measles neutralizing antibodies (>120 mIU/mL) were detected in 100% of macaques in the MN group and 75% of macaques in the subcutaneous (SC) injection group. Rubella neutralizing antibody titers were >10 IU/mL for all groups. All macaques in the MN group were protected from challenge with wild-type measles virus, whereas 75% were protected in the SC group. However, vaccination by the MN or SC route was unable to generate protective immune responses to measles in infant macaques pretreated with measles immunoglobulin to simulate maternal antibody. Conclusions: These results show, for the first time, that MR vaccine delivered by MN patch generated protective titers of neutralizing antibodies to both measles and rubella in infant rhesus macaques and afforded complete protection from measles virus challenge.

      7. Evaluation of RIDA((R))GENE norovirus GI/GII real time RT-PCR using stool specimens collected from children and adults with acute gastroenteritisExternal
        Kanwar N, Hassan F, Barclay L, Langley C, Vinje J, Bryant PW, George KS, Mosher L, Matthews-Greer JM, Rocha MA, Beenhouwer DO, Harrison CJ, Moffatt M, Shastri N, Selvarangan R.
        J Clin Virol. 2018 Apr 10;104:1-4.

        BACKGROUND: Norovirus is the leading cause of epidemic and sporadic acute gastroenteritis (AGE) in the United States. Widespread prevalence necessitates implementation of accurate norovirus detection assays in clinical diagnostic laboratories. OBJECTIVE: To evaluate RIDA((R))GENE norovirus GI/GII real-time RT-PCR assay (RGN RT-PCR) using stool samples from patients with sporadic AGE. STUDY DESIGN: Patients between 14days to 101 years of age with symptoms of AGE were enrolled prospectively at four sites across the United States during 2014-2015. Stool specimens were screened for the presence of norovirus RNA by the RGN RT-PCR assay. Results were compared with a reference method that included conventional RT-PCR and sequencing of a partial region of the 5’end of the norovirus ORF2 gene. RESULTS: A total of 259 (36.0%) of 719 specimens tested positive for norovirus by the reference method. The RGN RT-PCR assay detected norovirus in 244 (94%) of these 259 norovirus positive specimens. The sensitivity and specificity (95% confidence interval) of the RGN RT-PCR assay for detecting norovirus genogroup (G) I was 82.8% (63.5-93.5) and 99.1% (98.0-99.6) and for GII was 94.8% (90.8-97.2) and 98.6% (96.9-99.4), respectively. Seven specimens tested positive by the RGN-RT PCR that were negative by the reference method. The fifteen false negative samples were typed as GII.4 Sydney, GII.13, GI.3, GI.5, GI.2, GII.1, and GII.3 in the reference method. CONCLUSIONS: The RGN RT-PCR assay had a high sensitivity and specificity for the detection of norovirus in stool specimens from patients with sporadic AGE.

      8. As part of development of performance standards, the International Organization for Standardization (ISO) technical committee, ISO/TC 94/SC 15 Respiratory protective devices (RPD), adopted work of breathing (WOB) to evaluate airflow resistance for all designs (classes) of respiratory protective devices. The interests of the National Institute for Occupational Safety and Health’s (NIOSH) National Personal Protective Technology Laboratory (NPPTL) are to compare the proposed WOB method and results for current RPD with those for present resistance methods. The objectives here were to assemble a method to meet the ISO SC15 standards, validate operation and conformance, and assess repeatability of WOB measurements for RPD. WOB method implementation and use followed standards ISO 16900-5:2016 and ISO 16900-12:2016. Volume-averaged total work of breathing (WOBT/VT where VT is tidal volume) determined for standard orifices was analyzed for variation and bias. After fabrication and assembly, the method gave preliminary verification orifice results that met ISO requirements and were equivalent to those from other laboratories. Evaluation of additional results from RPD testing showed tidal volume and frequency determined compliance. Appropriate adjustments reduced average absolute bias to 1.7%. Average coefficient of variation for WOBT/VT was 2.3%. Over 97% of results obtained during significant use over time met specifications. WOBT/VT for as-received air-purifying and supplied-air RPD were repeatable (p<0.05). WOBT/VT for unsealed half mask air-purifying RPD was an average of 31% lower compared to sealed. When experimental parameters were appropriately adjusted, the ISO WOB method implemented by NIOSH NPPTL consistently provided ISO-compliant verification WOBT/VT. Results for appropriately sealed RPD were reproducible.

      9. Risk-based reboot for global lab biosafetyExternal
        Kojima K, Booth CM, Summermatter K, Bennett A, Heisz M, Blacksell SD, McKinney M.
        Science. 2018 Apr 20;360(6386):260-262.

        [No abstract]

      10. Quantification of carbon nanotubes by Raman analysisExternal
        Lynch JA, Birch QT, Ridgway TH, Birch ME.
        Ann Work Expo Health. 2018 Apr 27.

        The increasing prevalence of carbon nanotubes (CNTs) in manufacturing and research environments, together with the potential exposure risks, necessitates development of reliable and accurate monitoring methods for these materials. We examined quantification of CNTs by two distinct methods based on Raman spectroscopy. First, as measured by the Raman peak intensity of aqueous CNT suspensions, and second, by Raman mapping of air filter surfaces onto which CNTs were collected as aerosols or applied as small-area (0.05 cm2) deposits. Correlation (R2 = 0.97) between CNT concentration and Raman scattering intensity for suspensions in cuvettes was found over a concentration range from about 2 to 10 microg/ml, but measurement variance precludes practical determination of a calibration curve. Raman mapping of aerosol sample filter surfaces shows correlation with CNT mass when the surface density is relatively high (R2 = 0.83 and 0.95 above about 5 microg total mass on filter), while heterogeneity of CNT deposition makes obtaining representative maps of lower density samples difficult. This difficulty can be mitigated by increasing the area mapped relative to the total sample area, improving both precision and the limit of detection (LOD). For small-area deposits, detection of low masses relevant to occupational monitoring can be achieved, with an estimated LOD of about 50 ng.

      11. Taxonomy of the family Arenaviridae and the order Bunyavirales: update 2018External
        Maes P, Alkhovsky SV, Bao Y, Beer M, Birkhead M, Briese T, Buchmeier MJ, Calisher CH, Charrel RN, Choi IR, Clegg CS, de la Torre JC, Delwart E, DeRisi JL, Di Bello PL, Di Serio F, Digiaro M, Dolja VV, Drosten C, Druciarek TZ, Du J, Ebihara H, Elbeaino T, Gergerich RC, Gillis AN, Gonzalez JJ, Haenni AL, Hepojoki J, Hetzel U, Ho T, Hong N, Jain RK, Jansen van Vuren P, Jin Q, Jonson MG, Junglen S, Keller KE, Kemp A, Kipar A, Kondov NO, Koonin EV, Kormelink R, Korzyukov Y, Krupovic M, Lambert AJ, Laney AG, LeBreton M, Lukashevich IS, Marklewitz M, Markotter W, Martelli GP, Martin RR, Mielke-Ehret N, Muhlbach HP, Navarro B, Ng TF, Nunes MR, Palacios G, Paweska JT, Peters CJ, Plyusnin A, Radoshitzky SR, Romanowski V, Salmenpera P, Salvato MS, Sanfacon H, Sasaya T, Schmaljohn C, Schneider BS, Shirako Y, Siddell S, Sironen TA, Stenglein MD, Storm N, Sudini H, Tesh RB, Tzanetakis IE, Uppala M, Vapalahti O, Vasilakis N, Walker PJ, Wang G, Wang L, Wang Y, Wei T, Wiley MR, Wolf YI, Wolfe ND, Wu Z, Xu W, Yang L, Yang Z, Yeh SD, Zhang YZ, Zheng Y, Zhou X, Zhu C, Zirkel F, Kuhn JH.
        Arch Virol. 2018 Apr 21.

        In 2018, the family Arenaviridae was expanded by inclusion of 1 new genus and 5 novel species. At the same time, the recently established order Bunyavirales was expanded by 3 species. This article presents the updated taxonomy of the family Arenaviridae and the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.

    • Maternal and Child Health
      1. Prevalence of autism spectrum disorder among children aged 8 years – Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014External
        Baio J, Wiggins L, Christensen DL, Maenner MJ, Daniels J, Warren Z, Kurzius-Spencer M, Zahorodny W, Robinson Rosenberg C, White T, Durkin MS, Imm P, Nikolaou L, Yeargin-Allsopp M, Lee LC, Harrington R, Lopez M, Fitzgerald RT, Hewitt A, Pettygrove S, Constantino JN, Vehorn A, Shenouda J, Hall-Lande J, Van Naarden Braun K, Dowling NF.
        MMWR Surveill Summ. 2018 Apr 27;67(6):1-23.

        PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2014. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance system that provides estimates of the prevalence of autism spectrum disorder (ASD) among children aged 8 years whose parents or guardians reside within 11 ADDM sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). ADDM surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by professional service providers in the community. Staff completing record review and abstraction receive extensive training and supervision and are evaluated according to strict reliability standards to certify effective initial training, identify ongoing training needs, and ensure adherence to the prescribed methodology. Record review and abstraction occurs in a variety of data sources ranging from general pediatric health clinics to specialized programs serving children with developmental disabilities. In addition, most of the ADDM sites also review records for children who have received special education services in public schools. In the second phase of the study, all abstracted information is reviewed systematically by experienced clinicians to determine ASD case status. A child is considered to meet the surveillance case definition for ASD if he or she displays behaviors, as described on one or more comprehensive evaluations completed by community-based professional providers, consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for autistic disorder; pervasive developmental disorder-not otherwise specified (PDD-NOS, including atypical autism); or Asperger disorder. This report provides updated ASD prevalence estimates for children aged 8 years during the 2014 surveillance year, on the basis of DSM-IV-TR criteria, and describes characteristics of the population of children with ASD. In 2013, the American Psychiatric Association published the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which made considerable changes to ASD diagnostic criteria. The change in ASD diagnostic criteria might influence ADDM ASD prevalence estimates; therefore, most (85%) of the records used to determine prevalence estimates based on DSM-IV-TR criteria underwent additional review under a newly operationalized surveillance case definition for ASD consistent with the DSM-5 diagnostic criteria. Children meeting this new surveillance case definition could qualify on the basis of one or both of the following criteria, as documented in abstracted comprehensive evaluations: 1) behaviors consistent with the DSM-5 diagnostic features; and/or 2) an ASD diagnosis, whether based on DSM-IV-TR or DSM-5 diagnostic criteria. Stratified comparisons of the number of children meeting either of these two case definitions also are reported. RESULTS: For 2014, the overall prevalence of ASD among the 11 ADDM sites was 16.8 per 1,000 (one in 59) children aged 8 years. Overall ASD prevalence estimates varied among sites, from 13.1-29.3 per 1,000 children aged 8 years. ASD prevalence estimates also varied by sex and race/ethnicity. Males were four times more likely than females to be identified with ASD. Prevalence estimates were higher for non-Hispanic white (henceforth, white) children compared with non-Hispanic black (henceforth, black) children, and both groups were more likely to be identified with ASD compared with Hispanic children. Among the nine sites with sufficient data on intellectual ability, 31% of children with ASD were classified in the range of intellectual disability (intelligence quotient [IQ] <70), 25% were in the borderline range (IQ 71-85), and 44% had IQ scores in the average to above average range (i.e., IQ >85). The distribution of intellectual ability varied by sex and race/ethnicity. Although mention of developmental concerns by age 36 months was documented for 85% of children with ASD, only 42% had a comprehensive evaluation on record by age 36 months. The median age of earliest known ASD diagnosis was 52 months and did not differ significantly by sex or race/ethnicity. For the targeted comparison of DSM-IV-TR and DSM-5 results, the number and characteristics of children meeting the newly operationalized DSM-5 case definition for ASD were similar to those meeting the DSM-IV-TR case definition, with DSM-IV-TR case counts exceeding DSM-5 counts by less than 5% and approximately 86% overlap between the two case definitions (kappa = 0.85). INTERPRETATION: Findings from the ADDM Network, on the basis of 2014 data reported from 11 sites, provide updated population-based estimates of the prevalence of ASD among children aged 8 years in multiple communities in the United States. The overall ASD prevalence estimate of 16.8 per 1,000 children aged 8 years in 2014 is higher than previously reported estimates from the ADDM Network. Because the ADDM sites do not provide a representative sample of the entire United States, the combined prevalence estimates presented in this report cannot be generalized to all children aged 8 years in the United States. Consistent with reports from previous ADDM surveillance years, findings from 2014 were marked by variation in ASD prevalence when stratified by geographic area, sex, and level of intellectual ability. Differences in prevalence estimates between black and white children have diminished in most sites, but remained notable for Hispanic children. For 2014, results from application of the DSM-IV-TR and DSM-5 case definitions were similar, overall and when stratified by sex, race/ethnicity, DSM-IV-TR diagnostic subtype, or level of intellectual ability. PUBLIC HEALTH ACTION: Beginning with surveillance year 2016, the DSM-5 case definition will serve as the basis for ADDM estimates of ASD prevalence in future surveillance reports. Although the DSM-IV-TR case definition will eventually be phased out, it will be applied in a limited geographic area to offer additional data for comparison. Future analyses will examine trends in the continued use of DSM-IV-TR diagnoses, such as autistic disorder, PDD-NOS, and Asperger disorder in health and education records, documentation of symptoms consistent with DSM-5 terminology, and how these trends might influence estimates of ASD prevalence over time. The latest findings from the ADDM Network provide evidence that the prevalence of ASD is higher than previously reported estimates and continues to vary among certain racial/ethnic groups and communities. With prevalence of ASD ranging from 13.1 to 29.3 per 1,000 children aged 8 years in different communities throughout the United States, the need for behavioral, educational, residential, and occupational services remains high, as does the need for increased research on both genetic and nongenetic risk factors for ASD.

    • Nutritional Sciences
      1. We examined community-level characteristics associated with free drinking water access policies in U.S. municipalities using data from a nationally representative survey of city managers/officials from 2,029 local governments in 2014. Outcomes were 4 free drinking water access policies. Explanatory measures were population size, rural/urban status, census region, poverty prevalence, education, and racial/ethnic composition. We used multivariable logistic regression to test differences and presented only significant findings. Many (56.3%) local governments had at least one community plan with a written objective to provide free drinking water in outdoor areas; municipalities in the Northeast and South regions and municipalities with </= 50% of non-Hispanic whites were less likely and municipalities with larger population size were more likely to have a plan. About 59% had polices/budget provisions for free drinking water in parks/outdoor recreation areas; municipalities in the Northeast and South regions were less likely and municipalities with larger population size were more likely to have it. Only 9.3% provided development incentives for placing drinking fountains in outdoor, publicly accessible areas; municipalities with larger population size were more likely to have it. Only 7.7% had a municipal plumbing code with a drinking fountain standard that differed from the statewide plumbing code; municipalities with a lower proportion of non-Hispanic whites were more likely to have it. In conclusion, over half of municipalities had written plans or a provision for providing free drinking water in parks, but providing development incentives or having a local plumbing code provision were rare.

    • Occupational Safety and Health
      1. BACKGROUND: Commercial fishing is a global industry that has been frequently classified as high-risk. The use of detailed surveillance data is critical in identifying hazards. METHODS: The purpose of this study was to provide updated statistics for the entire US fishing industry during 2010-2014, generate fleet-specific fatality rates using a revised calculation of full-time equivalent estimates, and examine changes in the patterns of fatalities and in risk over a 15-year period (2000-2014). RESULTS: During 2010-2014, 188 commercial fishing fatalities occurred in the United States. Vessel disasters and falls overboard remain leading contributors to commercial fishing deaths. The Atlantic scallop fleet stands out for achieving substantial declines in the risk of fatalities over the 15-year study period. However, fatality rates ranged from 21 to 147 deaths per 100 000 FTEs, many times higher than the rate for all US workers. CONCLUSIONS: Although the number of fatalities among commercial fishermen in the United States has generally declined since 2000, commercial fishing continues to have one of the highest occupational fatality rates in the United States. The sustainable seafood movement could assist in improving the health and safety of fishing industry workers if worker well-being was integrated into the definition of sustainable seafood.

      2. BACKGROUND: The purpose of this study was to estimate the prevalence of hearing loss among noise-exposed US workers within the Agriculture, Forestry, Fishing, and Hunting (AFFH) sector. METHODS: Audiograms for 1.4 million workers (17 299 within AFFH) from 2003 to 2012 were examined. Prevalence, and the adjusted risk for hearing loss as compared with the reference industry (Couriers and Messengers), were estimated. RESULTS: The overall AFFH sector prevalence was 15% compared to 19% for all industries combined, but many of the AFFH sub-sectors exceeded the overall prevalence. Forestry sub-sector prevalences were highest with Forest Nurseries and Gathering of Forest Products at 36% and Timber Tract Operations at 22%. The Aquaculture sub-sector had the highest adjusted risk of all AFFH sub-sectors (PR = 1.70; CI = 1.42-2.04). CONCLUSIONS: High risk industries within the AFFH sector need continued hearing conservation efforts. Barriers to hearing loss prevention and early detection of hearing loss need to be recognized and addressed.

      3. Effects of 5-day heat acclimation on workers wearing personal protective clothingCdc-pdfExternal
        Seo Y, Quinn T, Kim J, Powell J, Roberge R, Coca A.
        J Exer Nutr. 2018 Jan;1(1):1-10.

        Introduction: Elevated ambient temperature and personal protective clothing (PPC) induce physiological strain which may be counteracted by heat acclimation. The purpose of this study was to determine if 5-day heat acclimation training (HAT) improves thermal and perceptual responses while wearing chemical, biological, radiological, and nuclear (CBRN) PPC. Methods: Nine healthy men completed a heat stress test (walking for one hour with CBRN PPC) in 35 degrees C and 50% relative humidity (RH) before and after 5-day HAT. The HAT consisted of five consecutive days of two 45-minute cycling sessions (50% VO2max) wearing athletic clothing separated by a 15 min rest in 45 degrees C and 20% RH. Results of the pre- and post- HAT heat stress tests were compared. Results: Heat acclimation was seen through 5-day HAT; however, thermoregulatory responses did not improve while wearing CBRN PPC. Improvement (p<0.05, day 1 vs. day 5 HAT) in skin temperature (38.0+/-0.5 degrees C vs. 37.6+/-0.5 degrees C), body temperature (38.6+/-0.4 degrees C vs. 38.3+/-0.4 degrees C), sweat rate (2.26+/-0.3kg vs. 2.64+/-0.3kg), RPE (15.8+/-2.4 vs. 13.9+/-3.1), and heat perception (5.7+/-0.6 vs. 4.9+/-1.0) were noted. However, no physiological or perceptual improvements (p>0.05) were found in the post-HAT heat stress test. Conclusions: Heat acclimation adaptations may be blunted by CBRN PPC, thus requiring differing or extended HAT.

    • Parasitic Diseases
      1. Malaria surveillance – United States, 2015External
        Mace KE, Arguin PM, Tan KR.
        MMWR Surveill Summ. 2018 May 4;67(7):1-28.

        PROBLEM/CONDITION: Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission. Malaria surveillance in the United States is conducted to provide information on its occurrence (e.g., temporal, geographic, and demographic), guide prevention and treatment recommendations for travelers and patients, and facilitate transmission control measures if locally acquired cases are identified. PERIOD COVERED: This report summarizes confirmed malaria cases in persons with onset of illness in 2015 and summarizes trends in previous years. DESCRIPTION OF SYSTEM: Malaria cases diagnosed by blood film microscopy, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments by health care providers or laboratory staff members. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), the National Notifiable Diseases Surveillance System (NNDSS), or direct CDC consultations. CDC reference laboratories provide diagnostic assistance and conduct antimalarial drug resistance marker testing on blood samples submitted by health care providers or local or state health departments. This report summarizes data from the integration of all NMSS and NNDSS cases, CDC reference laboratory reports, and CDC clinical consultations. RESULTS: CDC received reports of 1,517 confirmed malaria cases, including one congenital case, with an onset of symptoms in 2015 among persons who received their diagnoses in the United States. Although the number of malaria cases diagnosed in the United States has been increasing since the mid-1970s, the number of cases decreased by 208 from 2014 to 2015. Among the regions of acquisition (Africa, West Africa, Asia, Central America, the Caribbean, South America, Oceania, and the Middle East), the only region with significantly fewer imported cases in 2015 compared with 2014 was West Africa (781 versus 969). Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 67.4%, 11.7%, 4.1%, and 3.1% of cases, respectively. Less than 1% of patients were infected by two species. The infecting species was unreported or undetermined in 12.9% of cases. CDC provided diagnostic assistance for 13.1% of patients with confirmed cases and tested 15.0% of P. falciparum specimens for antimalarial resistance markers. Of the U.S. resident patients who reported purpose of travel, 68.4% were visiting friends or relatives. A lower proportion of U.S. residents with malaria reported taking any chemoprophylaxis in 2015 (26.5%) compared with 2014 (32.5%), and adherence was poor in this group. Among the U.S residents for whom information on chemoprophylaxis use and travel region were known, 95.3% of patients with malaria did not adhere to or did not take a CDC-recommended chemoprophylaxis regimen. Among women with malaria, 32 were pregnant, and none had adhered to chemoprophylaxis. A total of 23 malaria cases occurred among U.S. military personnel in 2015. Three cases of malaria were imported from the approximately 3,000 military personnel deployed to an Ebola-affected country; two of these were not P. falciparum species, and one species was unspecified. Among all reported cases in 2015, 17.1% were classified as severe illnesses and 11 persons died, compared with an average of 6.1 deaths per year during 2000-2014. In 2015, CDC received 153 P. falciparum-positive samples for surveillance of antimalarial resistance markers (although certain loci were untestable for some samples); genetic polymorphisms associated with resistance to pyrimethamine were identified in 132 (86.3%), to sulfadoxine in 112 (73.7%), to chloroquine in 48 (31.4%), to mefloquine in six (4.3%), and to artemisinin in one (<1%), and no sample had resistance to atovaquone. Completion of data elements on the malaria case report form decreased from 2014 to 2015 and remains low, with 24.2% of case report forms missing at least one key element (species, travel history, and resident status). INTERPRETATION: The decrease in malaria cases from 2014 to 2015 is associated with a decrease in imported cases from West Africa. This finding might be related to altered or curtailed travel to Ebola-affected countries in in this region. Despite progress in reducing malaria worldwide, the disease remains endemic in many regions, and the use of appropriate prevention measures by travelers is still inadequate. PUBLIC HEALTH ACTIONS: The best way to prevent malaria is to take chemoprophylaxis medication during travel to a country where malaria is endemic. As demonstrated by the U.S. military during the Ebola response, use of chemoprophylaxis and other protection measures is possible in stressful environments, and this can prevent malaria, especially P. falciparum, even in high transmission areas. Detailed recommendations for preventing malaria are available to the general public at the CDC website (https://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient’s age and medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Health care providers should consult the CDC Guidelines for Treatment of Malaria in the United States and contact the CDC’s Malaria Hotline for case management advice when needed. Malaria treatment recommendations are available online (https://www.cdc.gov/malaria/diagnosis_treatment) and from the Malaria Hotline (770-488-7788 or toll-free at 855-856-4713). Persons submitting malaria case reports (care providers, laboratories, and state and local public health officials) should provide complete information because incomplete reporting compromises case investigations and efforts to prevent infections and examine trends in malaria cases. Compliance with recommended malaria prevention strategies is low among U.S. travelers visiting friends and relatives. Evidence-based prevention strategies that effectively target travelers who are visiting friends and relatives need to be developed and implemented to reduce the numbers of imported malaria cases in the United States. Molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) has enabled CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and internationally. More samples are needed to improve the completeness of antimalarial drug resistance marker analysis; therefore, CDC requests that blood specimens be submitted for all cases diagnosed in the United States.

      2. Malaria elimination in Indonesia: halfway thereExternal
        Sitohang V, Sariwati E, Fajariyani SB, Hwang D, Kurnia B, Hapsari RK, Laihad FJ, Sumiwi ME, Pronyk P, Hawley WA.
        Lancet Glob Health. 2018 Apr 24.

        [No abstract]

    • Program Evaluation
      1. Using the contribution analysis approach to evaluate science impactExternal
        Downes A, Novicki E, Howard J.
        Am J Eval. 2018 Apr.

        Interest from Congress, executive branch leadership, and various other stakeholders for greater accountability in government continues to gain momentum today with government-wide efforts. However, measuring the impact of research programs has proven particularly difficult. Cause and effect linkages between research findings and changes to morbidity and mortality are difficult to prove. To address this challenge, the National Institute for Occupational Safety and Health program evaluators used a modified version of contribution analysis (CA) to evaluate two research programs. CA proved to be a useful framework for assessing research impact, and both programs received valuable, actionable feedback. Although there is room to further refine our approach, this was a promising step toward moving beyond bibiliometrics to more robust assessment of research impact.

    • Reproductive Health
      1. Surgically acquired sperm use for assisted reproductive technology: trends and perinatal outcomes, USA, 2004-2015External
        Kawwass JF, Chang J, Boulet SL, Nangia A, Mehta A, Kissin DM.
        J Assist Reprod Genet. 2018 Apr 26.

        PURPOSE: To compare national trends and perinatal outcomes following the use of ejaculated versus surgically acquired sperm among IVF cycles with male factor infertility. METHODS: This retrospective cohort includes US fertility clinics reporting to the National ART Surveillance System between 2004 and 2015. Fresh, non-donor IVF male factor cycles (n = 369,426 cycles) were included. We report the following outcomes: (1) Trends in surgically acquired and ejaculated sperm. (2) Adjusted risk ratios comparing outcomes for intracytoplasmic sperm injection (ICSI) cycles using surgically acquired (epididymal or testicular) versus ejaculated sperm. (3) Outcomes per non-canceled cycle: biochemical pregnancy, intrauterine pregnancy, and live birth (>/= 20 weeks). (4) Outcomes per pregnancy: miscarriage (< 20 weeks) and singleton pregnancy. (5) Outcomes per singleton pregnancy: normal birthweight (>/= 2500 g) and full-term delivery (>/= 37 weeks). RESULTS: Percentage of male factor infertility cycles that used surgically acquired sperm increased over the study period, 9.8 (2004) to 11.6% (2015), p < 0.05. The proportion of cycles using testicular sperm increased significantly over the study period, 4.9 (2004) to 6.5% (2015), p < 0.05. Among fresh, non-donor male factor ART cycles which used ICSI (n = 347,078 cycles), cycle, pregnancy, and perinatal outcomes were statistically significant but clinically similar with confidence intervals approaching one between cycles involving epididymal versus ejaculated sperm and between testicular versus ejaculated sperm. Results were similar among cycles with a sole diagnosis of male factor (no female factors), and for the subset in which the female partner was < 35 years old. CONCLUSION: Among couples undergoing ART for treatment of male factor infertility, pregnancy and perinatal outcomes were similar between cycles utilizing ejaculated sperm or surgically acquired testicular and epididymal sperm.

      2. Spatiotemporal trends in teen birth rates in the USA, 2003-2012External
        Khan D, Rossen LM, Hamilton B, Dienes E, He Y, Wei R.
        J R Stat Soc Ser A Stat Soc. 2018 Jan;181(1):35-58.

        The objective of this analysis was to explore temporal and spatial variation in teen birth rates TBRs across counties in the USA, from 2003 to 2012, by using hierarchical Bayesian models. Prior examination of spatiotemporal variation in TBRs has been limited by the reliance on large-scale geographies such as states, because of the potential instability in TBRs at smaller geographical scales such as counties. We implemented hierarchical Bayesian models with space-time interaction terms and spatially structured and unstructured random effects to produce smoothed county level TBR estimates, allowing for examination of spatiotemporal patterns and trends in TBRs at a smaller geographic scale across the USA. The results may help to highlight US counties where TBRs are higher or lower and to inform efforts to reduce birth rates to adolescents in the USA further.

    • Substance Use and Abuse
      1. Maternal smoking during pregnancy and offspring overweight: is there a dose-response relationship? An individual patient data meta-analysisExternal
        Albers L, Sobotzki C, Kuss O, Ajslev T, Batista RF, Bettiol H, Brabin B, Buka SL, Cardoso VC, Clifton VL, Devereux G, Gilman SE, Grzeskowiak LE, Heinrich J, Hummel S, Jacobsen GW, Jones G, Koshy G, Morgen CS, Oken E, Paus T, Pausova Z, Rifas-Shiman SL, Sharma AJ, da Silva AA, Sorensen TI, Thiering E, Turner S, Vik T, von Kries R.
        Int J Obes (Lond). 2018 Feb 28.

        BACKGROUND/OBJECTIVES: A number of meta-analyses suggest an association between any maternal smoking in pregnancy and offspring overweight obesity. Whether there is a dose-response relationship across number of cigarettes and whether this differs by sex remains unclear. SUBJECT/METHODS: Studies reporting number of cigarettes smoked during pregnancy and offspring BMI published up to May 2015 were searched. An individual patient data meta-analysis of association between the number of cigarettes smoked during pregnancy and offspring overweight (defined according to the International Obesity Task Force reference) was computed using a generalized additive mixed model with non-linear effects and adjustment for confounders (maternal weight status, breastfeeding, and maternal education) and stratification for sex. RESULTS: Of 26 identified studies, 16 authors provided data on a total of 238,340 mother-child-pairs. A linear positive association was observed between the number of cigarettes smoked and offspring overweight for up to 15 cigarettes per day with an OR increase per cigarette of 1.03, 95% CI = [1.02-1.03]. The OR flattened with higher cigarette use. Associations were similar in males and females. Sensitivity analyses supported these results. CONCLUSIONS: A linear dose-response relationship of maternal smoking was observed in the range of 1-15 cigarettes per day equally in boys and girls with no further risk increase for doses above 15 cigarettes.

    • Zoonotic and Vectorborne Diseases
      1. Heartland virus and hemophagocytic lymphohistiocytosis in immunocompromised patient, Missouri, USAExternal
        Carlson AL, Pastula DM, Lambert AJ, Staples JE, Muehlenbachs A, Turabelidze G, Eby CS, Keller J, Hess B, Buller RS, Storch GA, Byrnes K, Dehner L, Kirmani N, Kuhlmann FM.
        Emerg Infect Dis. 2018 May;24(5):893-897.

        Heartland virus is a suspected tickborne pathogen in the United States. We describe a case of hemophagocytic lymphohistiocytosis, then death, in an immunosuppressed elderly man in Missouri, USA, who was infected with Heartland virus.

      2. Prevalence and risk factors of Rift Valley fever in humans and animals from Kabale district in Southwestern Uganda, 2016External
        Nyakarahuka L, de St Maurice A, Purpura L, Ervin E, Balinandi S, Tumusiime A, Kyondo J, Mulei S, Tusiime P, Lutwama J, Klena J, Brown S, Knust B, Rollin PE, Nichol ST, Shoemaker TR.
        PLoS Negl Trop Dis. 2018 May 3;12(5):e0006412.

        BACKGROUND: Rift Valley fever (RVF) is a zoonotic disease caused by Rift Valley fever virus (RVFV) found in Africa and the Middle East. Outbreaks can cause extensive morbidity and mortality in humans and livestock. Following the diagnosis of two acute human RVF cases in Kabale district, Uganda, we conducted a serosurvey to estimate RVFV seroprevalence in humans and livestock and to identify associated risk factors. METHODS: Humans and animals at abattoirs and villages in Kabale district were sampled. Persons were interviewed about RVFV exposure risk factors. Human blood was tested for anti-RVFV IgM and IgG, and animal blood for anti-RVFV IgG. PRINCIPAL FINDINGS: 655 human and 1051 animal blood samples were collected. Anti-RVFV IgG was detected in 78 (12%) human samples; 3 human samples (0.5%) had detectable IgM only, and 7 (1%) had both IgM and IgG. Of the 10 IgM-positive persons, 2 samples were positive for RVFV by PCR, confirming recent infection. Odds of RVFV seropositivity were greater in participants who were butchers (odds ratio [OR] 5.1; 95% confidence interval [95% CI]: 1.7-15.1) and those who reported handling raw meat (OR 3.4; 95% CI 1.2-9.8). No persons under age 20 were RVFV seropositive. The overall animal seropositivity was 13%, with 27% of cattle, 7% of goats, and 4% of sheep seropositive. In a multivariate logistic regression, cattle species (OR 9.1; 95% CI 4.1-20.5), adult age (OR 3.0; 95% CI 1.6-5.6), and female sex (OR 2.1; 95%CI 1.0-4.3) were significantly associated with animal seropositivity. Individual human seropositivity was significantly associated with animal seropositivity by subcounty after adjusting for sex, age, and occupation (p < 0.05). CONCLUSIONS: Although no RVF cases had been detected in Uganda from 1968 to March 2016, our study suggests that RVFV has been circulating undetected in both humans and animals living in and around Kabale district. RVFV seropositivity in humans was associated with occupation, suggesting that the primary mode of RVFV transmission to humans in Kabale district could be through contact with animal blood or body fluids.

      3. [No abstract]

      4. Vital Signs: Trends in reported vectorborne disease cases – United States and Territories, 2004-2016External
        Rosenberg R, Lindsey NP, Fischer M, Gregory CJ, Hinckley AF, Mead PS, Paz-Bailey G, Waterman SH, Drexler NA, Kersh GJ, Hooks H, Partridge SK, Visser SN, Beard CB, Petersen LR.
        MMWR Morb Mortal Wkly Rep. 2018 May 4;67(17):496-501.

        INTRODUCTION: Vectorborne diseases are major causes of death and illness worldwide. In the United States, the most common vectorborne pathogens are transmitted by ticks or mosquitoes, including those causing Lyme disease; Rocky Mountain spotted fever; and West Nile, dengue, and Zika virus diseases. This report examines trends in occurrence of nationally reportable vectorborne diseases during 2004-2016. METHODS: Data reported to the National Notifiable Diseases Surveillance System for 16 notifiable vectorborne diseases during 2004-2016 were analyzed; findings were tabulated by disease, vector type, location, and year. RESULTS: A total 642,602 cases were reported. The number of annual reports of tickborne bacterial and protozoan diseases more than doubled during this period, from >22,000 in 2004 to >48,000 in 2016. Lyme disease accounted for 82% of all tickborne disease reports during 2004-2016. The occurrence of mosquitoborne diseases was marked by virus epidemics. Transmission in Puerto Rico, the U.S. Virgin Islands, and American Samoa accounted for most reports of dengue, chikungunya, and Zika virus diseases; West Nile virus was endemic, and periodically epidemic, in the continental United States. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Vectorborne diseases are a large and growing public health problem in the United States, characterized by geographic specificity and frequent pathogen emergence and introduction. Differences in distribution and transmission dynamics of tickborne and mosquitoborne diseases are often rooted in biologic differences of the vectors. To effectively reduce transmission and respond to outbreaks will require major national improvement of surveillance, diagnostics, reporting, and vector control, as well as new tools, including vaccines.

      5. Multisectoral prioritization of zoonotic diseases in Uganda, 2017: A One Health perspectiveExternal
        Sekamatte M, Krishnasamy V, Bulage L, Kihembo C, Nantima N, Monje F, Ndumu D, Sentumbwe J, Mbolanyi B, Aruho R, Kaboyo W, Mutonga D, Basler C, Paige S, Barton Behravesh C.
        PLoS One. 2018 ;13(5):e0196799.

        BACKGROUND: Zoonotic diseases continue to be a public health burden globally. Uganda is especially vulnerable due to its location, biodiversity, and population. Given these concerns, the Ugandan government in collaboration with the Global Health Security Agenda conducted a One Health Zoonotic Disease Prioritization Workshop to identify zoonotic diseases of greatest national concern to the Ugandan government. MATERIALS AND METHODS: The One Health Zoonotic Disease Prioritization tool, a semi-quantitative tool developed by the U.S. Centers for Disease Control and Prevention, was used for the prioritization of zoonoses. Workshop participants included voting members and observers representing multiple government and non-governmental sectors. During the workshop, criteria for prioritization were selected, and questions and weights relevant to each criterion were determined. We used a decision tree to provide a ranked list of zoonoses. Participants then established next steps for multisectoral engagement for the prioritized zoonoses. A sensitivity analysis demonstrated how criteria weights impacted disease prioritization. RESULTS: Forty-eight zoonoses were considered during the workshop. Criteria selected to prioritize zoonotic diseases were (1) severity of disease in humans in Uganda, (2) availability of effective control strategies, (3) potential to cause an epidemic or pandemic in humans or animals, (4) social and economic impacts, and (5) bioterrorism potential. Seven zoonotic diseases were identified as priorities for Uganda: anthrax, zoonotic influenza viruses, viral hemorrhagic fevers, brucellosis, African trypanosomiasis, plague, and rabies. Sensitivity analysis did not indicate significant changes in zoonotic disease prioritization based on criteria weights. DISCUSSION: One Health approaches and multisectoral collaborations are crucial to the surveillance, prevention, and control strategies for zoonotic diseases. Uganda used such an approach to identify zoonoses of national concern. Identifying these priority diseases enables Uganda’s National One Health Platform and Zoonotic Disease Coordination Office to address these zoonoses in the future with a targeted allocation of resources.

      6. Congenital Chagas disease in the United States: Cost savings through maternal screeningExternal
        Stillwaggon E, Perez-Zetune V, Bialek SR, Montgomery SP.
        Am J Trop Med Hyg. 2018 Apr 30.

        Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors through transfusions, transplants, insect feces in food, and from mother to child during gestation. Congenital infection could perpetuate Chagas disease indefinitely, even in countries without vector transmission. An estimated 30% of infected persons will develop lifelong, potentially fatal, cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment of Chagas disease in the United States. We constructed a decision-analytic model to find the lower cost option, comparing costs of testing and treatment, as needed, for mothers and infants with the lifetime societal costs without testing and the consequent morbidity and mortality due to lack of treatment or late treatment. We found that maternal screening, infant testing, and treatment of Chagas disease in the United States are cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence above 0.06% compared with no screening program. Newly approved diagnostics make universal screening cost saving with maternal prevalence as low as 0.008%. The present value of lifetime societal savings due to screening and treatment is about $634 million saved for every birth year cohort. The benefits of universal screening for T. cruzi as part of routine prenatal testing far outweigh the program costs for all U.S. births.

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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.

Page last reviewed: January 31, 2019