Current Issue

CDC Science Clips: Volume 11, Issue 48, December 3, 2019

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

This week, Science Clips is pleased to collaborate with CDC Vital Signs by featuring scientific articles from the latest issue on “Status of Human Immunodeficiency Virus (HIV) Testing, Viral Suppression, and Receipt of HIV Preexposure Prophylaxis — United States, 2013–2018.” The items marked with an asterisk may be of particular interest to clinicians and public health professionals seeking background information in this area.

  1. CDC Vital Signs
    • Communicable Diseases – Human Immunodeficiency Virus
      1. *Ending the HIV epidemic: A plan for the United Statesexternal icon
        Fauci AS, Redfield RR, Sigounas G, Weahkee MD, Giroir BP.
        Jama. 2019 Mar 5;321(9):844-845.

        [No abstract]

      2. *Fact Sheet: Evidence of HIV treatment and viral suppression in preventing the sexual transmission of HIV.pdf icon
        Centers for Disease Control and Prevention.
        Atlanta, GA: Centers for Disease Control and Prevention, National Center for HIV/AIDS, STD, and TB Prevention, Division of HIV/AIDS Prevention. 2018.
        HIV treatment has dramatically improved the health, quality of life, and life expectancy of people with HIV. HIV treatment has also transformed the HIV prevention landscape. Over the last decade, research has
        shown the profound impact of HIV treatment in preventing the sexual transmission of HIV, sometimes called “Treatment as Prevention” (TasP). This fact sheet summarizes the latest evidence, provides
        key communication messages, and reviews key factors needed to maximize the effectiveness of this prevention strategy.

      3. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settingsexternal icon
        Branson BM, Handsfield HH, Lampe MA, Janssen RS, Taylor AW, Lyss SB, Clark JE.
        MMWR Recomm Rep. 2006 Sep 22;55(Rr-14):1-17; quiz CE1-4.
        These recommendations for human immunodeficiency virus (HIV) testing are intended for all health-care providers in the public and private sectors, including those working in hospital emergency departments, urgent care clinics, inpatient services, substance abuse treatment clinics, public health clinics, community clinics, correctional health-care facilities, and primary care settings. The recommendations address HIV testing in health-care settings only. They do not modify existing guidelines concerning HIV counseling, testing, and referral for persons at high risk for HIV who seek or receive HIV testing in nonclinical settings (e.g., community-based organizations, outreach settings, or mobile vans). The objectives of these recommendations are to increase HIV screening of patients, including pregnant women, in health-care settings; foster earlier detection of HIV infection; identify and counsel persons with unrecognized HIV infection and link them to clinical and prevention services; and further reduce perinatal transmission of HIV in the United States. These revised recommendations update previous recommendations for HIV testing in health-care settings and for screening of pregnant women (CDC. Recommendations for HIV testing services for inpatients and outpatients in acute-care hospital settings. MMWR 1993;42[No. RR-2]:1-10; CDC. Revised guidelines for HIV counseling, testing, and referral. MMWR 2001;50[No. RR-19]:1-62; and CDC. Revised recommendations for HIV screening of pregnant women. MMWR 2001;50[No. RR-19]:63-85). Major revisions from previously published guidelines are as follows: For patients in all health-care settings HIV screening is recommended for patients in all health-care settings after the patient is notified that testing will be performed unless the patient declines (opt-out screening). Persons at high risk for HIV infection should be screened for HIV at least annually. Separate written consent for HIV testing should not be required; general consent for medical care should be considered sufficient to encompass consent for HIV testing. Prevention counseling should not be required with HIV diagnostic testing or as part of HIV screening programs in health-care settings. For pregnant women HIV screening should be included in the routine panel of prenatal screening tests for all pregnant women. HIV screening is recommended after the patient is notified that testing will be performed unless the patient declines (opt-out screening). Separate written consent for HIV testing should not be required; general consent for medical care should be considered sufficient to encompass consent for HIV testing. Repeat screening in the third trimester is recommended in certain jurisdictions with elevated rates of HIV infection among pregnant women.

      4. HIV preexposure prophylaxis, by race and ethnicity – United States, 2014-2016external icon
        Huang YA, Zhu W, Smith DK, Harris N, Hoover KW.
        MMWR Morb Mortal Wkly Rep. 2018 Oct 19;67(41):1147-1150.
        Preexposure prophylaxis (PrEP) with a daily, oral pill containing antiretroviral drugs is highly effective in preventing acquisition of human immunodeficiency virus (HIV) infection (1-4). The combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is the only medication approved by the Food and Drug Administration (FDA) for PrEP. PrEP is indicated for men and women with sexual or injection drug use behaviors that increase their risk for acquiring HIV (5). CDC analyzed 2014-2016 data from the IQVIA Real World Data – Longitudinal Prescriptions (IQVIA database) to estimate the number of persons prescribed PrEP (users) in the United States and to describe their demographic characteristics, including sex and race/ethnicity. From 2014 to 2016, the annual number of PrEP users aged >/=16 years increased by 470%, from 13,748 to 78,360. In 2016, among 32,853 (41.9%) PrEP users for whom race/ethnicity data were available, 68.7% were white, 11.2% were African American or black (black), 13.1% were Hispanic, and 4.5% were Asian. Approximately 7% of the estimated 1.1 million persons who had indications for PrEP were prescribed PrEP in 2016, including 2.1% of women with PrEP indications (6). Although black men and women accounted for approximately 40% of persons with PrEP indications (6), this study found that nearly six times as many white men and women were prescribed PrEP as were black men and women. The findings of this study highlight gaps in effective PrEP implementation efforts in the United States.

      5. Vital Signs: HIV transmission along the continuum of care – United States, 2016external icon
        Li Z, Purcell DW, Sansom SL, Hayes D, Hall HI.
        MMWR Morb Mortal Wkly Rep. 2019 Mar 22;68(11):267-272.
        BACKGROUND: In 2016, an estimated 1.1 million persons had human immunodeficiency virus (HIV) infection in the United States; 38,700 were new infections. Knowledge of HIV infection status, behavior change, and antiretroviral therapy (ART) all prevent HIV transmission. Persons who achieve and maintain viral suppression (achieved by most persons within 6 months of starting ART) can live long, healthy lives and pose effectively no risk of HIV transmission to their sexual partners. METHODS: A model was used to estimate transmission rates in 2016 along the HIV continuum of care. Data for sexual and needle-sharing behaviors were obtained from National HIV Behavioral Surveillance. Estimated HIV prevalence, incidence, receipt of care, and viral suppression were obtained from National HIV Surveillance System data. RESULTS: Overall, the HIV transmission rate was 3.5 per 100 person-years in 2016. Along the HIV continuum of care, the transmission rates from persons who were 1) acutely infected and unaware of their infection, 2) non-acutely infected and unaware, 3) aware of HIV infection but not in care, 4) receiving HIV care but not virally suppressed, and 5) taking ART and virally suppressed were 16.1, 8.4, 6.6, 6.1, and 0 per 100 person-years, respectively. The percentages of all transmissions generated by each group were 4.0%, 33.6%, 42.6%, 19.8%, and 0%, respectively. CONCLUSION: Approximately 80% of new HIV transmissions are from persons who do not know they have HIV infection or are not receiving regular care. Going forward, increasing the percentage of persons with HIV infection who have achieved viral suppression and do not transmit HIV will be critical for ending the HIV epidemic in the United States.

      6. Preexposure prophylaxis for the prevention of HIV infection: US Preventive Services Task Force Recommendation Statementexternal icon
        Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, Curry SJ, Doubeni CA, Epling JW, Kubik M, Landefeld CS, Mangione CM, Pbert L, Silverstein M, Simon MA, Tseng CW, Wong JB.
        Jama. 2019 Jun 11;321(22):2203-2213.
        Importance: An estimated 1.1 million individuals in the United States are currently living with HIV, and more than 700000 persons have died of AIDS since the first cases were reported in 1981. In 2017, there were 38281 new diagnoses of HIV infection reported in the United States; 81% of these new diagnoses were among males and 19% were among females. Although treatable, HIV infection has no cure and has significant health consequences. Objective: To issue a new US Preventive Services Task Force (USPSTF) recommendation on preexposure prophylaxis (PrEP) for the prevention of HIV infection. Evidence Review: The USPSTF reviewed the evidence on the benefits of PrEP for the prevention of HIV infection with oral tenofovir disoproxil fumarate monotherapy or combined tenofovir disoproxil fumarate and emtricitabine and whether the benefits vary by risk group, population subgroup, or regimen or dosing strategy; the diagnostic accuracy of risk assessment tools to identify persons at high risk of HIV acquisition; the rates of adherence to PrEP in primary care settings; the association between adherence and effectiveness of PrEP; and the harms of PrEP when used for HIV prevention. Findings: The USPSTF found convincing evidence that PrEP is of substantial benefit in decreasing the risk of HIV infection in persons at high risk of HIV acquisition. The USPSTF also found convincing evidence that adherence to PrEP is highly associated with its efficacy in preventing the acquisition of HIV infection; thus, adherence to PrEP is central to realizing its benefit. The USPSTF found adequate evidence that PrEP is associated with small harms, including kidney and gastrointestinal adverse effects. The USPSTF concludes with high certainty that the magnitude of benefit of PrEP with oral tenofovir disoproxil fumarate-based therapy to reduce the risk of acquisition of HIV infection in persons at high risk is substantial. Conclusions and Recommendation: The USPSTF recommends offering PrEP with effective antiretroviral therapy to persons at high risk of HIV acquisition. (A recommendation).

      7. HIV testing in 50 local jurisdictions accounting for the majority of new HIV diagnoses and seven states with disproportionate occurrence of HIV in rural areas, 2016-2017external icon
        Pitasi MA, Delaney KP, Brooks JT, DiNenno EA, Johnson SD, Prejean J.
        MMWR Morb Mortal Wkly Rep. 2019 Jun 28;68(25):561-567.
        Since 2006, CDC has recommended universal screening for human immunodeficiency virus (HIV) infection at least once in health care settings and at least annual rescreening of persons at increased risk for infection (1,2), but data from national surveys and HIV surveillance demonstrate that these recommendations have not been fully implemented (3,4). The national Ending the HIV Epidemic initiative* is intended to reduce the number of new infections by 90% from 2020 to 2030. The initiative focuses first on 50 local jurisdictions (48 counties, the District of Columbia, and San Juan, Puerto Rico) where the majority of new diagnoses of HIV infection in 2016 and 2017 were concentrated and seven states with a disproportionate occurrence of HIV in rural areas relative to other states (i.e., states with at least 75 reported HIV diagnoses in rural areas that accounted for >/=10% of all diagnoses in the state).(dagger) This initial geographic focus will be followed by wider implementation of the initiative within the United States. An important goal of the initiative is the timely identification of all persons with HIV infection as soon as possible after infection (5). CDC analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS)( section sign) to assess the percentage of adults tested for HIV in the United States nationwide (38.9%), in the 50 local jurisdictions (46.9%), and in the seven states (35.5%). Testing percentages varied widely by jurisdiction but were suboptimal and generally low in jurisdictions with low rates of diagnosis of HIV infection. To achieve national goals and end the HIV epidemic in the United States, strategies must be tailored to meet local needs. Novel screening approaches might be needed to reach segments of the population that have never been tested for HIV.

      8. PURPOSE: Effectively measuring progress in delivering HIV pre-exposure prophylaxis (PrEP) requires subnational estimates of the number of adults with indications for its use that account for differences in HIV infection rates by transmission risk (risk) group and race/ethnicity. METHODS: We applied a multiplier method with 2015 Centers for Disease Control and Prevention surveillance data on proportions of HIV diagnoses by race/ethnicity and risk group and population-based estimates of risk group sizes to derive estimated numbers of adults with indications by risk group (men who have sex with men [MSM], heterosexually active adults [HET], and persons who inject drugs [PWID]) by race/ethnicity in each jurisdiction. RESULTS: An estimated 1.1 million adults had indications for PrEP use in 2015: 813,970 MSM, 258,080 HET, and 72,510 persons who inject drugs, and 500,340 blacks, 282,260 Latinos, and 303,230 whites. Among HET, 176,670 females and 81,410 males had indications. The proportions of adults with indications in each risk and race/ethnicity group varied by jurisdiction. CONCLUSIONS: Blacks comprised the highest number of adults with indications showing that increasing PrEP use in this population must be the highest priority. MSM remain a priority because of the high number with indications. These estimates can be used as denominators to assess PrEP coverage and impact on HIV incidence at subnational levels.

      9. Using CD4 data to estimate HIV incidence, prevalence, and percent of undiagnosed infections in the United Statesexternal icon
        Song R, Hall HI, Green TA, Szwarcwald CL, Pantazis N.
        J Acquir Immune Defic Syndr. 2017 Jan 1;74(1):3-9.
        INTRODUCTION: The incidence and prevalence of HIV infection are important measures of HIV trends; however, they are difficult to estimate because of the long incubation period between infection and symptom development and the relative infrequency of HIV screening. A new method is introduced to estimate HIV incidence, prevalence, and the number of undiagnosed infections in the United States using data from the HIV case surveillance system and CD4 test results. METHODS: Persons with HIV diagnosed during 2006-2013 and their CD4 test results were used to estimate the distribution of diagnosis delay from HIV infection to diagnosis based on a well-characterized CD4 depletion model. This distribution was then used to estimate HIV incidence, prevalence, and the number of undiagnosed infections. RESULTS: Applying this method, we estimated that the annual number of new HIV infections decreased after 2007, from 48,300 (95% confidence interval [CI]: 47,300 to 49,400) to 39,000 (95% CI: 36,600 to 41,400) in 2013. Prevalence increased from 923,200 (95% CI: 914,500 to 931,800) in 2006 to 1,104,600 (95% CI: 1,084,300 to 1,124,900) in 2013, whereas the proportion of undiagnosed infections decreased from 21.0% in 2006 (95% CI: 20.2% to 21.7%) to 16.4% (95% CI: 15.7% to 17.2%) in 2013. CONCLUSIONS: HIV incidence, prevalence, and undiagnosed infections can be estimated using HIV case surveillance data and information on first CD4 test result after diagnosis. Similar to earlier findings, the decreases in incidence and undiagnosed infections are encouraging but intensified efforts for HIV testing and treatment are needed to meet the goals of the National HIV/AIDS Strategy.

  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. Using natural experimental studies to guide public health action: turning the evidence-based medicine paradigm on its headexternal icon
        Ogilvie D, Adams J, Bauman A, Gregg EW, Panter J, Siegel KR, Wareham NJ, White M.
        J Epidemiol Community Health. 2019 Nov 19.
        Despite smaller effect sizes, interventions delivered at population level to prevent non-communicable diseases generally have greater reach, impact and equity than those delivered to high-risk groups. Nevertheless, how to shift population behaviour patterns in this way remains one of the greatest uncertainties for research and policy. Evidence about behaviour change interventions that are easier to evaluate tends to overshadow that for population-wide and system-wide approaches that generate and sustain healthier behaviours. Population health interventions are often implemented as natural experiments, which makes their evaluation more complex and unpredictable than a typical randomised controlled trial (RCT). We discuss the growing importance of evaluating natural experiments and their distinctive contribution to the evidence for public health policy. We contrast the established evidence-based practice pathway, in which RCTs generate ‘definitive’ evidence for particular interventions, with a practice-based evidence pathway in which evaluation can help adjust the compass bearing of existing policy. We propose that intervention studies should focus on reducing critical uncertainties, that non-randomised study designs should be embraced rather than tolerated and that a more nuanced approach to appraising the utility of diverse types of evidence is required. The complex evidence needed to guide public health action is not necessarily the same as that which is needed to provide an unbiased effect size estimate. The practice-based evidence pathway is neither inferior nor merely the best available when all else fails. It is often the only way to generate meaningful evidence to address critical questions about investing in population health interventions.

      2. Why men with a low-risk prostate cancer select and stay on active surveillance: A qualitative studyexternal icon
        Seaman AT, Taylor KL, Davis K, Nepple KG, Lynch JH, Oberle AD, Hall IJ, Volk RJ, Reisinger HS, Hoffman RM.
        PLoS One. 2019 ;14(11):e0225134.
        OBJECTIVE: Active surveillance (AS) is an increasingly utilized strategy for monitoring men with low-risk prostate cancer (PCa) that allows them to defer active treatment (AT) in the absence of cancer progression. Studies have explored reasons for selecting AS and for then switching to AT, but less is known about men’s experiences being on AS. We interviewed men to determine the clinical and psychological factors associated with selecting and adhering to AS protocols. METHODS: We conducted semi-structured interviews with men with a low-risk PCa at two academic medical centers. Subjects had either been on AS for >/= 1 year or had opted for AT after a period of AS. We used an iterative, content-driven approach to analyze the interviews and to identify themes. RESULTS: We enrolled 21 subjects, mean age 70.4 years, 3 racial/ethnic minorities, and 16 still on AS. Men recognized the favorable prognosis of their cancer (some had sought second opinions when initially offered AT), valued avoiding treatment complications, were reassured that close monitoring would identify progression early enough to be successfully treated, and trusted their urologists. Although men reported feeling anxious around the time of surveillance testing, those who switched to AT did so based only on evidence of cancer progression. CONCLUSIONS: Our selected sample was comfortable being on AS because they understood and valued the rationale for this approach. However, this highlights the importance of ensuring that men newly diagnosed with a low-risk PCa are provided sufficient information about prognosis and treatment options to make informed decisions.

    • Communicable Diseases
      1. BACKGROUND: The Medical Monitoring Project (MMP) is a national population-based behavioral and clinical surveillance system of adults with diagnosed HIV in the United States, and it is sponsored by the Centers for Disease Control and Prevention (CDC). Its purpose is to provide locally and nationally representative estimates of factors affecting HIV transmission risk and clinical outcomes. OBJECTIVE: This study aimed to describe the rationale for and methodology of the MMP, in addition to its contribution to evaluating and monitoring HIV prevention, care, and treatment efforts in the United States. METHODS: MMP employs a stratified 2-stage sample design to select annual samples of persons living with diagnosed HIV from the National HIV Surveillance System and conducts interviews and medical record abstractions with participating persons. RESULTS: MMP data are published routinely via annual reports, conference presentations, and scientific publications. Data may be accessed upon request from the CDC, contingent on the guidelines established for the security and confidentiality of HIV surveillance data. CONCLUSIONS: MMP is the only source of annual population-based data on the behaviors and clinical care of persons with diagnosed HIV in the United States. It provides essential information for monitoring progress toward national treatment and prevention goals and guiding efforts to improve the health of persons with diagnosed HIV and prevent HIV transmission. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/15453.

      2. Factors associated with measles transmission in the United States during the postelimination eraexternal icon
        Gastanaduy PA, Funk S, Lopman BA, Rota PA, Gambhir M, Grenfell B, Paul P.
        JAMA Pediatr. 2019 Nov 18.
        Importance: Measles cases and outbreaks continue to occur in the United States after the introduction of measles from endemic settings. Objective: To discern the factors associated with measles transmission in the United States after measles had been eliminated. Design, Setting, and Participants: This cross-sectional study was conducted from January 1, 2001, to December 31, 2017, in the United States among US residents and international visitors with confirmed measles. A maximum likelihood algorithm that uses the observed dates of rash onset and the known distribution of the serial interval (time between symptom onset in related consecutive cases) was applied to outbreak notification data to estimate the effective reproduction number (R), or the mean number of new infections generated per case. Transmissibility was assessed by comparing R based on the characteristics of primary and secondary cases of measles. Exposures: Measles virus. Main Outcomes and Measures: Effective reproduction number (R), or the mean number of successful transmission events per case of measles (ie, the mean number of persons to whom each patient with measles spreads measles). Results: A total of 2218 individuals with confirmed measles cases (1025 female, 1176 male, and 17 sex not reported; median age, 15 years [range, 0-89 years]) reported from 2001 to 2017 were evaluated. Among patients who received no doses of measles vaccine, R was 0.76 (95% CI, 0.71-0.81); among patients who received 1 dose of measles vaccine, R was 0.17 (95% CI, 0.11-0.26); among patients who received 2 doses or more of measles vaccine, R was 0.27 (95% CI, 0.17-0.39); and among patients with unknown vaccination status, R was 0.52 (95% CI, 0.44-0.60). Among patients born before 1957, R was 0.35 (95% CI, 0.20-0.58), and among those born on or after 1957, R was 0.64 (95% CI, 0.61-0.68). R was higher when primary and secondary cases of measles were patients aged 5 to 17 years (0.36 [95% CI, 0.31-0.42]) compared with assortative transmission in other age groups (<1 year, 0.14 [95% CI, 0.10-0.20]; 1-4 years, 0.25 [95% CI, 0.20-0.30]; 18-29 years, 0.19 [95% CI, 0.15-0.24]; 30-49 years, 0.15 [95% CI, 0.11-0.20]; >/=50 years, 0.04 [95% CI, 0.01-0.10]). Conclusions and Relevance: The findings of this study support having high targets for 2-dose measles vaccine coverage, particularly among school-aged children in the United States.

      3. Epidemiology of tuberculosis in the United Statesexternal icon
        Langer AJ, Navin TR, Winston CA, LoBue P.
        Clin Chest Med. 2019 Dec;40(4):693-702.
        Although considerable progress has been made in reducing US tuberculosis incidence, the goal of eliminating the disease from the United States remains elusive. A continued focus on preventing new tuberculosis infections while also identifying and treating persons with existing tuberculosis infection is needed. Continued vigilance to ensure ongoing control of tuberculosis transmission remains key.

      4. Effect of internet-distributed HIV self-tests on HIV diagnosis and behavioral outcomes in men who have sex with men: A randomized clinical trialexternal icon
        MacGowan RJ, Chavez PR, Borkowf CB, Owen SM, Purcell DW, Mermin JH, Sullivan PS.
        JAMA Intern Med. 2019 Nov 18.
        Importance: Undiagnosed HIV infection results in delayed access to treatment and increased transmission. Self-tests for HIV may increase awareness of infection among men who have sex with men (MSM). Objective: To evaluate the effect of providing HIV self-tests on frequency of testing, diagnoses of HIV infection, and sexual risk behaviors. Design, Setting, and Participants: This 12-month longitudinal, 2-group randomized clinical trial recruited MSM through online banner advertisements from March through August 2015. Those recruited were at least 18 years of age, reported engaging in anal sex with men in the past year, never tested positive for HIV, and were US residents with mailing addresses. Participants completed quarterly online surveys. Telephone call notes and laboratory test results were included in the analysis, which was completed from August 2017 through December 2018. Interventions: All participants had access to online web-based HIV testing resources and telephone counseling on request. Participants were randomized in a 1:1 ratio to the control group or a self-testing (ST) group, which received 4 HIV self-tests after completing the baseline survey with the option to replenish self-tests after completing quarterly surveys. At study completion, all participants were offered 2 self-tests and 1 dried blood spot collection kit. Main Outcomes and Measures: Primary outcomes were HIV testing frequency (tested >/=3 times during the trial) and number of newly identified HIV infections among participants in both groups and social network members who used the study HIV self-tests. Secondary outcomes included sex behaviors (eg, anal sex, serosorting). Results: Of 2665 participants, the mean (SD) age was 30 (9.6) years, 1540 (57.8%) were white, and 443 (16.6%) had never tested for HIV before enrollment. Retention rates at each time point were more than 54%, and 1991 (74.7%) participants initiated 1 or more follow-up surveys. More ST participants reported testing 3 or more times during the trial than control participants (777 of 1014 [76.6%] vs 215 of 977 [22.0%]; P < .01). The cumulative number of newly identified infections during the trial was twice as high in the ST participants as the control participants (25 of 1325 [1.9%] vs 11 of 1340 [0.8%]; P = .02), with the largest difference in HIV infections identified in the first 3 months (12 of 1325 [0.9%] vs 2 of 1340 [0.1%]; P < .01). The ST participants reported 34 newly identified infections among social network members who used the self-tests. Conclusions and Relevance: Distribution of HIV self-tests provides a worthwhile mechanism to increase awareness of HIV infection and prevent transmission among MSM. Trial Registration: identifier: NCT02067039.

      5. Treatment of drug-resistant tuberculosisexternal icon
        Mase SR, Chorba T.
        Clin Chest Med. 2019 Dec;40(4):775-795.
        The treatment of drug-resistant tuberculosis (TB) is complicated and has evolved significantly in the past decade with the advent of rapid molecular tests and updated evidence-based guidelines of the World Health Organization and other organizations. The latest recommendations incorporate the use of new drugs and regimens that maximize efficacy and minimize toxicity to improve treatment outcomes for the patients. This article provides an overview of the latest published strategies for clinical and programmatic management of drug-resistant TB.

      6. Global knowledge gaps in acute febrile illness etiologic investigations: A scoping reviewexternal icon
        Rhee C, Kharod GA, Schaad N, Furukawa NW, Vora NM, Blaney DD, Crump JA, Clarke KR.
        PLoS Negl Trop Dis. 2019 Nov 15;13(11):e0007792.
        BACKGROUND: Acute febrile illness (AFI), a common reason for people seeking medical care globally, represents a spectrum of infectious disease etiologies with important variations geographically and by population. There is no standardized approach to conducting AFI etiologic investigations, limiting interpretation of data in a global context. We conducted a scoping review to characterize current AFI research methodologies, identify global research gaps, and provide methodological research standardization recommendations. METHODOLOGY/FINDINGS: Using pre-defined terms, we searched Medline, Embase, and Global Health, for publications from January 1, 2005-December 31, 2017. Publications cited in previously published systematic reviews and an online study repository of non-malarial febrile illness etiologies were also included. We screened abstracts for publications reporting on human infectious disease, aimed at determining AFI etiology using laboratory diagnostics. One-hundred ninety publications underwent full-text review, using a standardized tool to collect data on study characteristics, methodology, and laboratory diagnostics. AFI case definitions between publications varied: use of self-reported fever as part of case definitions (28%, 53/190), fever cut-off value (38.0 degrees C most commonly used: 45%, 85/190), and fever measurement site (axillary most commonly used: 19%, 36/190). Eighty-nine publications (47%) did not include exclusion criteria, and inclusion criteria in 13% (24/190) of publications did not include age group. No publications included study settings in Southern Africa, Micronesia & Polynesia, or Central Asia. We summarized standardized reporting practices, specific to AFI etiologic investigations that would increase inter-study comparability. CONCLUSIONS: Wider implementation of standardized AFI reporting methods, with multi-pathogen disease detection, could improve comparability of study findings, knowledge of the range of AFI etiologies, and their contributions to the global AFI burden. These steps can guide resource allocation, strengthen outbreak detection and response, target prevention efforts, and improve clinical care, especially in resource-limited settings where disease control often relies on empiric treatment. PROSPERO: CRD42016035666.

      7. Analysis of systematic reviews of medication adherence interventions for persons with HIV, 1996-2017external icon
        Rooks-Peck CR, Wichser ME, Adegbite AH, DeLuca JB, Barham T, Ross LW, Higa DH, Sipe TA.
        AIDS Patient Care STDS. 2019 Nov 21.
        This overview of reviews summarizes the evidence from systematic reviews (SR) on the effectiveness of antiretroviral therapy (ART) adherence interventions for people with HIV (PWH) and descriptively compares adherence interventions among key populations. Relevant articles published during 1996-2017 were identified by comprehensive searches of CDC’s HIV/acquired immunodeficiency syndrome (AIDS) Prevention Research Synthesis Database and manual searches. Included SRs examined primary interventions intended to improve ART adherence, focused on PWH, and assessed medication adherence or biologic outcomes (e.g., viral load). We synthesized the qualitative data and used the Assessment of Multiple Systematic Reviews (AMSTAR) for quality assessment. Forty-one SRs met inclusion criteria. Average quality was high. SRs that evaluated text-messaging interventions (n = 9) consistently reported statistically significant improvements in adherence and biologic outcomes. Other ART adherence strategies (e.g., behavioral, directly administered antiretroviral therapy [DAART]) reported improvements, but did not report significant effects for both outcomes, or intervention effects that did not persist postintervention. In the review focused on people who inject drugs (n = 1), DAART alone or in combination with medication-assisted therapy improved both outcomes. In SRs focused on children or adolescents aged <18 years (n = 5), regimen-related and hospital-based DAART improved biologic outcomes. ART adherence interventions (e.g., text-messaging) improved adherence and biologic outcomes; however, results differed for other intervention strategies, populations, and outcomes. Because few SRs reported evidence for populations at high risk (e.g., men who have sex with men), the results are not generalizable to all PWH. Future implementation studies are needed to examine medication adherence interventions in specific populations and address the identified gaps.

      8. HIV prevention via mobile messaging for men who have sex with men (M-Cubed): Protocol for a randomized controlled trialexternal icon
        Sullivan PS, Zahn RJ, Wiatrek S, Chandler CJ, Hirshfield S, Stephenson R, Bauermeister JA, Chiasson MA, Downing MJ, Gelaude DJ, Siegler AJ, Horvath K, Rogers E, Alas A, Olansky EJ, Saul H, Rosenberg ES, Mansergh G.
        JMIR Res Protoc. 2019 Nov 15;8(11):e16439.
        BACKGROUND: Men who have sex with men (MSM) continue to be the predominately impacted risk group in the United States HIV epidemic and are a priority group for risk reduction in national strategic goals for HIV prevention. Modeling studies have demonstrated that a comprehensive package of status-tailored HIV prevention and care interventions have the potential to substantially reduce new infections among MSM. However, uptake of basic prevention services, including HIV testing, sexually transmitted infection (STI) testing, condom distribution, condom-compatible lubricant distribution, and preexposure prophylaxis (PrEP), is suboptimal. Further, stronger public health strategies are needed to promote engagement in HIV care and viral load suppression among MSM living with HIV. Mobile health (mHealth) tools can help inform and encourage MSM regarding HIV prevention, care, and treatment, especially among men who lack access to conventional medical services. This protocol details the design and procedures of a randomized controlled trial (RCT) of a novel mHealth intervention that comprises a comprehensive HIV prevention app and brief, tailored text- and video-based messages that are systematically presented to participants based on the participants’ HIV status and level of HIV acquisition risk. OBJECTIVE: The objective of the RCT was to test the efficacy of the Mobile Messaging for Men (M-Cubed, or M3) app among at least 1200 MSM in Atlanta, Detroit, and New York. The goal was to determine its ability to increase HIV testing (HIV-negative men), STI testing (all men), condom use for anal sex (all men), evaluation for PrEP eligibility, uptake of PrEP (higher risk HIV-negative men), engagement in HIV care (men living with HIV), and uptake of and adherence to antiretroviral medications (men living with HIV). A unique benefit of this approach is the HIV serostatus-inclusiveness of the intervention, which includes both HIV-negative and HIV-positive MSM. METHODS: MSM were recruited through online and venue-based approaches in Atlanta, Detroit, and New York City. Men who were eligible and consented were randomized to the intervention (immediate access to the M3 app for a period of three months) or to the waitlist-control (delayed access) group. Outcomes were evaluated immediately postintervention or control period, and again three and six months after the intervention period. Main outcomes will be reported as period prevalence ratios or hazards, depending on the outcome. Where appropriate, serostatus/risk-specific outcomes will be evaluated in relevant subgroups. Men randomized to the control condition were offered the opportunity to use (and evaluate) the M3 app for a three-month period after the final RCT outcome assessment. RESULTS: M3 enrollment began in January 2018 and concluded in November 2018. A total of 1229 MSM were enrolled. Data collection was completed in September 2019. CONCLUSIONS: This RCT of the M3 mobile app seeks to determine the effects of an HIV serostatus-inclusive intervention on the use of multiple HIV prevention and care-related outcomes among MSM. A strength of the design is that it incorporates a large sample and broad range of MSM with differing prevention needs in three cities with high prevalence of HIV among MSM. TRIAL REGISTRATION: NCT03666247; INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16439.

      9. Seroprevalence of rubella virus antibodies among pregnant women in the Center and South-West regions of Cameroonexternal icon
        Taku NA, Ndze VN, Abernathy E, Hao L, Waku-Kouomou D, Icenogle JP, Wanji S, Akoachere JK.
        PLoS One. 2019 ;14(11):e0225594.
        Rubella infection in early pregnancy can lead to miscarriages, fetal death, or birth of an infant with congenital rubella syndrome (CRS). In Cameroon, like in many developing countries, rubella surveillance is not well-established. The aim of this study was to determine the prevalence of rubella virus specific antibodies among pregnant Cameroonians. We conducted a cross-sectional study for rubella infection among pregnant women attending antenatal clinics in the Center and South-West regions of Cameroon. Demographic data and blood were collected and tested for rubella specific antibodies (IgG and IgM), and for the IgM positive cases, IgG avidity and real time PCR was done. From December 2015 to July 2017, 522 serum samples were collected and tested from pregnant women. The seroprevalence of rubella specific IgG was 94.4%, presumably due to immunity induced by wild-type rubella virus. The seroprevalence of rubella specific IgM was 5.0%, possibly indicating rubella infection. However, IgG avidity testing of the IgM positive cases detected high avidity IgGs, ranging from 52.37% to 87.70%, indicating past rubella infection. 5.6% (29/522) of the participants had negative results for IgG to rubella virus, indicating susceptibility to rubella infection. None of the participants had received a rubella containing vaccine (RCV), but 51% (266/522) of the pregnant women lived in a house with a child with records of at least one dose of RCV. Rubella virus RNA was not detected in the urine of any IgM positive case. Findings from this study show that rubella infection is significant in Cameroon. Some pregnant women are still susceptible to rubella infection. For a better management of rubella infection in pregnancy in Cameroon, consideration should be taken to investigate for IgG-avidity test in cases with positive rubella IgM result to distinguish between recent from past rubella infection.

      10. Norovirus is the leading cause of acute gastroenteritis and foodborne disease in the United States. The Food and Drug Administration recommends that food workers infected with norovirus be excluded from the workplace while symptomatic and for 48 hours after their symptoms subside. Compliance with this recommendation is not ideal, and the population-level impacts of changes in food-worker compliance have yet to be quantified. We aimed to assess the population impacts of varying degrees of compliance with the current recommendation through the use of a compartmental model. We modeled the number and proportion of symptomatic norovirus cases averted annually in the US population (using data from 1983-2014) in specific age groups (children aged <5 years, children aged 5-17 years, adults aged 18-64 years, and adults aged >/=65 years) under various scenarios of food-worker exclusion (i.e., proportion compliant and days of postsymptomatic exclusion) in comparison with a referent scenario which assumed that 66.6 % of norovirus-symptomatic food workers and 0% of postsymptomatic food workers were excluded from work. Overall, we estimated that 6.0 million cases of norovirus have already been avoided annually under the referent scenario and that 6.7 million (28%) more cases might be avoided through 100% compliance with the current recommendations. Substantial population-level benefits were predicted from improved compliance in exclusion of norovirus-infected food workers from the workplace-benefits that may be realized through policies or programs incentivizing self-exclusion.

    • Disaster Control and Emergency Services
      1. How public health agencies use the public health emergency preparedness capabilitiesexternal icon
        Horney J, Carbone EG, Lynch M, Ji CS, Jones T.
        Disaster Med Public Health Prep. 2019 Nov 19:1-2.

        [No abstract]

    • Disease Reservoirs and Vectors
      1. State-wide survey of Aedes aegypti and Aedes albopictus (Diptera: Culicidae) in Floridaexternal icon
        Parker C, Ramirez D, Connelly CR.
        J Vector Ecol. 2019 Dec;44(2):210-215.
        Aedes aegypti and Aedes albopictus are invasive mosquito species with geographic ranges that have oscillated within Florida since their presence was first documented. Local transmission of dengue, chikungunya, and Zika viruses serves as evidence of the public health importance of these two species. It is important to have detailed knowledge of their distribution to aid in mosquito control efforts and understand the risk of arbovirus transmission to humans. Through a partnership involving the University of Florida Institute of Food and Agricultural Sciences Cooperative Extension Service and the Florida Medical Entomology Laboratory; the Florida Department of Health; and mosquito control agencies throughout Florida, a container mosquito surveillance program involving all life stages was launched in the summer of 2016 to detect the presence of Ae. aegypti and Ae. albopictus. Results from this survey were mapped to provide a picture of the current known distribution of Ae. aegypti and Ae. albopictus in Florida. Aedes aegypti and/or Ae. albopictus were detected in the 56 counties that were part of the survey. Only Aedes albopictus was detected in 26 counties, primarily in the panhandle region of Florida. The results of this work underscore the importance of maintaining container mosquito surveillance in a state where chikungunya, dengue, and Zika viruses are present and where there is continued risk for exotic arbovirus introductions.

    • Drug Safety
      1. [No abstract]

    • Environmental Health
      1. Polybrominated diphenyl ethers, polybrominated biphenyls, and risk of papillary thyroid cancer: A nested case-control studyexternal icon
        Huang H, Sjodin A, Chen Y, Ni X, Ma S, Yu H, Ward MH, Udelsman R, Rusiecki J, Zhang Y.
        Am J Epidemiol. 2019 Nov 19.
        A nested case-control study was carried out using data from the United States Department of Defense cohort between 2000 and 2013 to investigate the associations of papillary thyroid cancer (PTC) with serum concentrations of polybrominated diphenyl ethers and polybrominated biphenyls. This study included 742 (341 women and 401 men) histologically confirmed PTC cases and 742 matched controls with pre-diagnostic serum samples from the Department of Defense Serum Repository. Lipid-corrected serum concentrations of eight congeners were measured. Multivariate conditional logistic regression analyses were performed for classical PTC and follicular variant of PTC, respectively. We also examined effect modification by gender. BDE-28 was associated with significantly increased risk of classical PTC [OR=2.09; 95% CI, 1.05, 4.15, for the 3rd tertile vs. below limit of detection; Ptrend=0.02], adjusting for other congeners, body mass index, and branch of military service. This association was mainly observed for larger classical PTC (tumor size >10 mm) with a significantly stronger association among women than men (Pinteraction=0.004). No consistent associations were observed for other congeners, including those at higher concentrations. This study found a significantly increased risk of classical PTC associated with increasing levels of BDE-28. The risk varied by gender and tumor size.

      2. Functional connectivity of the reading network is associated with prenatal polybrominated diphenyl ether concentrations in a community sample of 5 year-old children: A preliminary studyexternal icon
        Margolis AE, Banker S, Pagliaccio D, De Water E, Curtin P, Bonilla A, Herbstman JB, Whyatt R, Bansal R, Sjodin A, Milham MP, Peterson BS, Factor-Litvak P, Horton MK.
        Environ Int. 2019 Nov 16;134:105212.
        Genetic factors explain 60 percent of variance in reading disorder. Exposure to neurotoxicants, including polybrominated diphenyl ethers (PBDEs), may be overlooked risk factors for reading problems. We used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between prenatal PBDE concentrations and functional connectivity of a reading-related network (RN) in a community sample of 5-year-old children (N=33). Maternal serum PBDE concentrations ( summation operatorPBDE) were measured at 12.2+/-2.8weeks gestation (mean+/-SD). The RN was defined by 12 regions identified in prior task-based fMRI meta-analyses; global efficiency (GE) was used to measure network integration. Linear regression evaluated associations between summation operatorPBDE, word reading, and GE of the RN and the default mode network (DMN); the latter to establish specificity of findings. Weighted quantile sum regression analyses evaluated the contributions of specific PBDE congeners to observed associations. Greater RN efficiency was associated with better word reading in these novice readers. Children with higher summation operatorPBDE showed reduced GE of the RN; summation operatorPBDE was not associated with DMN efficiency, demonstrating specificity of our results. Consistent with prior findings, summation operatorPBDE was not associated word reading at 5-years-old. Altered efficiency and integration of the RN may underlie associations between summation operatorPBDE concentrations and reading problems observed previously in older children.

    • Epidemiology and Surveillance
      1. The Asthma Call-back Survey (ACBS) is conducted after the Behavioral Risk Factor Surveillance System (BRFSS) survey by calling BRFSS respondents who reported ever being diagnosed with asthma. To find response patterns and increase ACBS response rates, we first examined whether obtaining consents during the BRFSS survey could increase call back response rates by reducing the refusal and break-off. Then, we assessed how the lag days between BRFSS and ACBS interviews affected response rates. BRFSS cell phone respondents agreed more often to being called back than did landline respondents (75.5 vs. 70.9 percent). However, when respondents were contacted for ACBS, the cell phone response rate was lower than landline response rate (43.4 vs. 47.0 percent), except among males aged 25-34 years, for which the cell phone response rate was 2.1 percent higher than the landline response rate. ACBS response rate for landline and cell phone response were highest if the callback was within 2 days of BRFSS interviews (92.3 vs. 88.8 percent). As lag days increased, the response rate decreased. The cell phone response rate showed a sharper drop; after 2 weeks, the response rate gap between landline and cell phone samples reached 17.3 percent.

    • Food Safety
      1. Multistate outbreak of Salmonella infections linked to raw turkey products – United States, 2017-2019external icon
        Hassan R, Buuck S, Noveroske D, Medus C, Sorenson A, Laurent J, Rotstein D, Schlater L, Freiman J, Douris A, Simmons M, Donovan D, Henderson J, Tewell M, Snyder K, Oni O, Von Stein D, Dassie K, Leeper M, Adediran A, Dowell N, Gieraltowski L, Basler C.
        MMWR Morb Mortal Wkly Rep. 2019 Nov 22;68(46):1045-1049.

        [No abstract]

      2. Short communication: Multistate outbreak of Listeria monocytogenes infections retrospectively linked to unpasteurized milk using whole-genome sequencingexternal icon
        Nichols M, Conrad A, Whitlock L, Stroika S, Strain E, Weltman A, Johnson L, DeMent J, Reporter R, Williams I.
        J Dairy Sci. 2019 Nov 13.
        Unpasteurized milk can contain harmful bacteria such as Listeria monocytogenes. In 2016, the US Food and Drug Administration notified the Centers for Disease Control and Prevention (Atlanta, GA) that L. monocytogenes isolated from unpasteurized chocolate milk from a Pennsylvania dairy was closely related, by whole-genome sequencing, to L. monocytogenes isolates collected from blood specimens of 2 patients (in California and Florida) in 2014. The California and Florida patients consumed unpasteurized milk from the Pennsylvania dairy. Both were >65 yr old and were hospitalized in 2014; the Florida patient died. Isolates from the 2 patients had indistinguishable pulsed-field gel electrophoresis patterns and were closely related by whole-genome multilocus sequence typing analysis (by 2 alleles) to the isolate from unpasteurized chocolate milk produced by the Pennsylvania dairy in 2015. Together, epidemiologic and laboratory information indicated a common origin. This is the first multistate listeriosis outbreak linked to unpasteurized milk in the United States detected using whole-genome multilocus sequence analysis.

    • Global Health
      1. The burden of anaemia among displaced women and children in refugee settings worldwide, 2013-2016external icon
        Kay A, Leidman E, Lopez V, Wilkinson C, Tondeur M, Bilukha O.
        BMJ Global Health. 2019 ;4(6).
        Introduction Displaced persons have a unique risk for developing anaemia due to often limited diets, overcrowding, new infections and inadequate sanitation and hygiene. The lack of anaemia prevalence estimates among the displaced inhibit global planning for anaemia reduction. Methods We analysed population representative, cross-sectional nutrition surveys from 2013 to 2016 conducted by the United Nations High Commissioner for Refugees and partner agencies. Included surveys measured haemoglobin concentration among children 6-59 months, non-pregnant women 15-49 years, or both groups. For each survey, we calculated mean haemoglobin and prevalence of total anaemia (<110 g/L in children, <120 g/L in women), and classified public health severity following WHO guidelines. Pearson correlations between indicators from women and children surveys were calculated where both subpopulations were measured. Results Analysis included 196 surveys among children and 184 surveys among women from 121 unique refugee settings in 24 countries. The median prevalence of total anaemia in children and women was 44% and 28%, respectively. Sixty-one per cent of child surveys indicated a problem of severe public health importance compared with 25% of surveys in women. The prevalence of total anaemia in children and women was strongly correlated (p=0.80). Median prevalence of total anaemia was approximately 55% greater and mean haemoglobin was 6 g/L lower among children age 6-23 months compared with children 24-59 months. West and Central Africa region had the highest median prevalence of anaemia both in women and children. Conclusion While the burden of anaemia is high among the displaced, it mirrors that of the general population. Haemoglobin should continue to be measured in nutrition surveys in refugee settings. Sustained, multisectoral efforts to reduce anaemia are needed, with specific focus on children under 2 years of age and refugee settings in the West and Central Africa region.

    • Health Disparities
      1. Racial/ethnic and geographic disparities in HIV diagnosis rates exist among women in the United States. Black/African American women are disproportionately affected; rates are highest in the South and Northeast. Monitoring progress towards eliminating disparities in HIV diagnosis rates among women is a national HIV prevention goal. To illustrate the performance of different measures of disparities, we compared 2012 and 2017 HIV diagnosis rates among adult and adolescent females by race/ethnicity and geographic region. We used HIV surveillance data for diagnoses and five absolute and three relative measures of disparity. The absolute disparity decreased in each region; the relative disparity decreased with the exception of one measure in the Northeast and South. Despite progress, disparities in HIV diagnosis rates among women remain. Appropriate strategies to measure progress and contextualize findings are needed.

      2. INTRODUCTION: Infant mortality rates are higher in nonmetropolitan areas versus large metropolitan areas. Variation by race/ethnicity and cause of death has not been assessed. Urban-rural infant mortality rate differences were quantified by race/ethnicity and cause of death. METHODS: National Vital Statistics System linked birth/infant death data (2014-2016) were analyzed in 2019 by 3 urban-rural county classifications: large metropolitan, medium/small metropolitan, and nonmetropolitan. Excess infant mortality rates (rate differences) by urban-rural classification were calculated relative to large metropolitan areas overall and for each racial/ethnic group. The number of excess deaths, population attributable fraction, and proportion of excess deaths attributable to underlying causes of death was calculated. RESULTS: Nonmetropolitan areas had the highest excess infant mortality rate overall. Excess infant mortality rates were substantially lower for Hispanic infants than other races/ethnicities. Overall, 7.4% of infant deaths would be prevented if all areas had the infant mortality rate of large metropolitan areas. With more than half of births occurring outside of large metropolitan areas, the population attributable fraction was highest for American Indian/Alaska Natives (20.3%) and whites, non-Hispanic (14.3%). Excess infant mortality rates in both nonmetropolitan and medium/small metropolitan areas were primarily attributable to sudden unexpected infant deaths (42.3% and 31.9%) and congenital anomalies (30.1% and 26.8%). This pattern was consistent for all racial/ethnic groups except black, non-Hispanic infants, for whom preterm-related and sudden unexpected infant deaths accounted for the largest share of excess infant mortality rates. CONCLUSIONS: Infant mortality increases with rurality, and excess infant mortality rates are predominantly attributable to sudden unexpected infant deaths and congenital anomalies, with differences by race/ethnicity regarding magnitude and cause of death.

      3. Prevalence of disability and disability types by urban-rural county classification – U.S., 2016external icon
        Zhao G, Okoro CA, Hsia J, Garvin WS, Town M.
        Am J Prev Med. 2019 ;57(6):749-756.
        Introduction: In the U.S., disability affects approximately 61.4 million (25.7%) adults, with mobility disability being the most prevalent type, affecting about 1 in 7 U.S. adults. However, little is known about the prevalence of disability and functional disability types by urbanization level. Methods: Data from the 2016 Behavioral Risk Factor Surveillance System were analyzed. The prevalences of disability, overall and by functional disability type, were estimated among U.S. adults across 6 levels of urban-rural county categories based on the 2013 National Center for Health Statistics Urban-Rural Classification Scheme for Counties. Adjusted prevalence ratios with 95% CIs were estimated by conducting log-linear regression analyses with robust variance estimator while adjusting for study covariates. Data analyses were conducted in 2018. Results: The prevalences of having any disability, functional disability type, or multiple disabilities were lowest in large metropolitan centers and fringe metropolitan counties and highest in noncore (rural) counties. After controlling for age, sex, race/ethnicity, education, and federal poverty level, adults living in noncore counties were 9% more likely to report having any disability, 24% more likely to report having 3 or more disabilities, and 7% (cognition) to 35% (hearing) more likely to report specific disability types than the adults living in large metropolitan centers. Conclusions: Results of this study suggest that significant disparities in the prevalence of disability exist by level of urbanization, with rural U.S. residents having the highest prevalence of disability. Public health interventions to reduce health disparities could include people with disabilities, particularly in rural counties.

    • Health Economics
      1. Selecting the optimal risk threshold of diabetes risk scores to identify high-risk individuals for diabetes prevention: a cost-effectiveness analysisexternal icon
        Muhlenbruch K, Zhuo X, Bardenheier B, Shao H, Laxy M, Icks A, Zhang P, Gregg EW, Schulze MB.
        Acta Diabetol. 2019 Nov 19.
        AIMS: Although risk scores to predict type 2 diabetes exist, cost-effectiveness of risk thresholds to target prevention interventions are unknown. We applied cost-effectiveness analysis to identify optimal thresholds of predicted risk to target a low-cost community-based intervention in the USA. METHODS: We used a validated Markov-based type 2 diabetes simulation model to evaluate the lifetime cost-effectiveness of alternative thresholds of diabetes risk. Population characteristics for the model were obtained from NHANES 2001-2004 and incidence rates and performance of two noninvasive diabetes risk scores (German diabetes risk score, GDRS, and ARIC 2009 score) were determined in the ARIC and Cardiovascular Health Study (CHS). Incremental cost-effectiveness ratios (ICERs) were calculated for increasing risk score thresholds. Two scenarios were assumed: 1-stage (risk score only) and 2-stage (risk score plus fasting plasma glucose (FPG) test (threshold 100 mg/dl) in the high-risk group). RESULTS: In ARIC and CHS combined, the area under the receiver operating characteristic curve for the GDRS and the ARIC 2009 score were 0.691 (0.677-0.704) and 0.720 (0.707-0.732), respectively. The optimal threshold of predicted diabetes risk (ICER < $50,000/QALY gained in case of intervention in those above the threshold) was 7% for the GDRS and 9% for the ARIC 2009 score. In the 2-stage scenario, ICERs for all cutoffs >/= 5% were below $50,000/QALY gained. CONCLUSIONS: Intervening in those with >/= 7% diabetes risk based on the GDRS or >/= 9% on the ARIC 2009 score would be cost-effective. A risk score threshold >/= 5% together with elevated FPG would also allow targeting interventions cost-effectively.

    • Immunity and Immunization
      1. [No abstract]

      2. Near real-time surveillance to assess the safety of the 9-valent human papillomavirus vaccineexternal icon
        Donahue JG, Kieke BA, Lewis EM, Weintraub ES, Hanson KE, McClure DL, Vickers ER, Gee J, Daley MF, DeStefano F, Hechter RC, Jackson LA, Klein NP, Naleway AL, Nelson JC, Belongia EA.
        Pediatrics. 2019 Nov 18.
        BACKGROUND AND OBJECTIVES: Human papillomavirus is the most common sexually transmitted infection in the United States and causes certain anogenital and oropharyngeal cancers. The 9-valent human papillomavirus vaccine (9vHPV) provides protection against additional types not included in the quadrivalent vaccine. We conducted near real-time vaccine safety surveillance for 24 months after the vaccine became available in the Vaccine Safety Datalink. METHODS: Immunizations and adverse events were extracted weekly from October 2015 to October 2017 from standardized data files for persons 9 to 26 years old at 6 Vaccine Safety Datalink sites. Prespecified adverse events included anaphylaxis, allergic reaction, appendicitis, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, injection site reaction, pancreatitis, seizure, stroke, syncope, and venous thromboembolism. The observed and expected numbers of events after 9vHPV were compared weekly by using sequential methods. Both historical and concurrent comparison groups were used to identify statistical signals for adverse events. Unexpected signals were investigated by medical record review and/or additional analyses. RESULTS: During 105 weeks of surveillance, 838 991 doses of 9vHPV were administered. We identified unexpected statistical signals for 4 adverse events: appendicitis among boys 9 to 17 years old after dose 3; pancreatitis among men 18 to 26 years old; and allergic reactions among girls 9 to 17 years old and women 18 to 26 years old after dose 2. On further evaluation, which included medical record review, temporal scan analysis, and additional epidemiological analyses, we did not confirm signals for any adverse events. CONCLUSIONS: After 2 years of near real-time surveillance of 9vHPV and several prespecified adverse events, no new safety concerns were identified.

      3. Rubella virus-specific humoral immune responses and their interrelationships before and after a third dose of measles-mumps-rubella vaccine in women of childbearing ageexternal icon
        Haralambieva IH, Ovsyannikova IG, Kennedy RB, Goergen KM, Grill DE, Chen MH, Hao L, Icenogle J, Poland GA.
        Vaccine. 2019 Nov 12.
        In the U.S., measles, mumps, and rubella vaccination is recommended as two vaccine doses. A third dose of measles-mumps-rubella (MMR) vaccine is being administered in certain situations (e.g., identified seronegativity and during outbreaks). We studied rubella-specific humoral immunity (neutralizing antibody, enzyme-linked immunosorbent assay/ELISA IgG titer and antibody avidity) and the frequencies of antigen-specific memory B cells before and after a third dose of MMR-II in 109 female participants of childbearing age (median age, 34.5years old) from Olmsted County, MN, with two documented prior MMR vaccine doses. The participants were selected from a cohort of 1117 individuals if they represented the high and the low ends of the rubella-specific antibody response spectrum. Of the 109 participants, we identified four individuals (3.67% of all study participants; 7.14% of the low-responder group) that were seronegative at Baseline (rubella-specific ELISA IgG titers <10IU/mL), suggesting a lack of protection against rubella before receipt of a third MMR vaccine dose. The peak geometric mean neutralizing antibody titer one month following the third dose of MMR vaccine for the cohort was 243 NT50 (CI; 241, 245), which is expected for a cohort with two doses of MMR, and the peak geometric mean IgG titer was 150IU/mL (CI; 148, 152) with no seronegative individuals at Day 28. One-third of all subjects (31.8% for the neutralizing antibody; 30.8% for the IgG titer) experienced a significant boost (>/=4-fold) of antibody titers one month following vaccination. Antibody titers and other tested immune-response variables were significantly higher in the high-responder group compared to the low-responder group. The frequencies of rubella-specific memory B cells were modestly associated with the antibody titers. Our study suggests the importance of yet unknown inherent biologic and immune factors for the generation and maintenance of rubella-vaccine-induced humoral immune responses.

      4. Two pneumococcal vaccines are currently licensed for use in adults in the United States: a 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Pfizer, Inc.]) and a 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax 23, Merck and Co., Inc.]). In 2014, the Advisory Committee on Immunization Practices (ACIP)* recommended routine use of PCV13 in series with PPSV23 for all adults aged >/=65 years based on demonstrated PCV13 safety and efficacy against PCV13-type pneumonia among adults aged >/=65 years (1). At that time, ACIP recognized that there would be a need to reevaluate this recommendation because it was anticipated that PCV13 use in children would continue to reduce disease burden among adults through reduced carriage and transmission of vaccine serotypes from vaccinated children (i.e., PCV13 indirect effects). On June 26, 2019, after having reviewed the evidence accrued during the preceding 3 years (, ACIP voted to remove the recommendation for routine PCV13 use among adults aged >/=65 years and to recommend administration of PCV13 based on shared clinical decision-making for adults aged >/=65 years who do not have an immunocompromising condition,(dagger) cerebrospinal fluid (CSF) leak, or cochlear implant, and who have not previously received PCV13. ACIP recognized that some adults aged >/=65 years are potentially at increased risk for exposure to PCV13 serotypes, such as persons residing in nursing homes or other long-term care facilities and persons residing in settings with low pediatric PCV13 uptake or traveling to settings with no pediatric PCV13 program, and might attain higher than average benefit from PCV13 vaccination. When patients and vaccine providers( section sign) engage in shared clinical decision-making for PCV13 use to determine whether PCV13 is right for a particular person, considerations might include both the person’s risk for exposure to PCV13 serotypes and their risk for developing pneumococcal disease as a result of underlying medical conditions. All adults aged >/=65 years should continue to receive 1 dose of PPSV23. If the decision is made to administer PCV13, it should be given at least 1 year before PPSV23. ACIP continues to recommend PCV13 in series with PPSV23 for adults aged >/=19 years with an immunocompromising condition, CSF leak, or cochlear implant (2).

      5. Priming with MF59 adjuvanted versus nonadjuvanted seasonal influenza vaccines in children – A systematic review and a meta-analysisexternal icon
        Patel MM, Davis W, Beacham L, Spencer S, Campbell AP, Lafond K, Rolfes M, Levine MZ, Azziz-Baumgartner E, Thompson MG, Fry AM.
        Vaccine. 2019 Nov 14.
        BACKGROUND: Identifying optimal priming strategies for children <2years could substantially improve the public health benefits of influenza vaccines. Adjuvanted seasonal influenza vaccines were designed to promote a better immune response among young vaccine-naive children. METHODS: We systematically reviewed randomized trials to assess hemagglutination inhibition (HAI) antibody response to MF59-adjuvanted inactivated influenza vaccine (aIIV) versus nonadjuvanted IIV among children. We estimated pooled ratios of post-vaccination HAI geometric mean titer (GMT) for aIIV versus IIV and confidence intervals (CIs) using the pooled variances derived from reported CIs. RESULTS: Mean age was 28months (range, 6-72months). Children received vaccines with either 7.5mug (6-35months) or 15mug (>/=36months) hemagglutinin of each strain depending on age. Seven of eight trials administered trivalent vaccines and one used quadrivalent vaccine. Pooled post-vaccination GMT ratios against the three influenza vaccine strains were 2.5-3.5 fold higher after 2-dose-aIIV versus 2-dose-IIV among children 6-72months, and point estimates were higher among children 6-35months compared with older children. When comparing 1-dose-aIIV to 2-dose-IIV doses, pooled GMT ratios were not significantly different against A/H1N1 (1.0; 95% CI: 0.5-1.8; p=0.90) and A/H3N2 viruses (1.0; 95% CI: 0.7-1.5; p=0.81) and were significantly lower against B viruses (0.6; 95% CI: 0.4-0.8; p<0.001) for both age groups. Notably, GMT ratios for vaccine-mismatched heterologous viruses after 2-dose-aIIV compared with 2-dose-IIV were higher against A/H1N1 (2.0; 95% CI: 1.1-3.4), A/H3N2 (2.9; 95% CI: 1.9-4.2), and B-lineage viruses (2.1; 95% CI: 1.8-2.6). CONCLUSIONS: Two doses of adjuvanted IIV consistently induced better humoral immune responses against Type A and B influenza viruses compared with nonadjuvanted IIVs in young children, particularly among those 6-35months. One adjuvanted IIV dose had a similar response to two nonadjuvanted IIV doses against Type A influenza viruses. Longer-term benefits from imprinting and cell-mediated immunity, including trials of clinical efficacy, are gaps that warrant investigation.

      6. BACKGROUND: Palivizumab, a monoclonal antibody and the only licensed immunization product for preventing respiratory syncytial virus (RSV) infection, is recommended for children with certain high-risk conditions. Other antibody products and maternal vaccines targeting young infants are in clinical development. Few studies have compared products closest to potential licensure and have primarily focused on the effects on hospitalizations only. Estimates of the impact of these products on medically-attended (MA) infections in a variety of healthcare settings are needed to assist with developing RSV immunization recommendations. METHODS: We developed a tool for practicing public health officials to estimate the impact of immunization strategies on RSV-associated MA lower respiratory tract infections (LRTIs) in various healthcare settings among infants <12months. Users input RSV burden and seasonality and examine the influence of altering product efficacy and uptake assumptions. We used the tool to evaluate candidate products’ impacts among a US birth cohort. RESULTS: We estimated without immunization, 407,360 (range: 339,650-475,980) LRTIs are attended annually in outpatient clinics, 147,240 (126,070-168,510) in emergency departments (EDs), and 33,180 (24,760-42,900) in hospitals. A passive antibody candidate targeting all infants prevented the most LRTIs: 196,470 (48% of visits without immunization) outpatient clinic visits (range: 163,810-229,650), 75,250 (51%) EDs visits (64,430-86,090), and 18,140 (55%) hospitalizations (13,770-23,160). A strategy combining maternal vaccine candidate and palivizumab prevented 58,210 (14% of visits without immunization) LRTIs in outpatient clinics (range: 48,520-67,970), 19,580 (13%) in EDs (16,760-22,400), and 8,190 (25%) hospitalizations (6,390-10,150). CONCLUSIONS: Results underscore the potential for anticipated products to reduce serious RSV illness. Our tool (provided to readers) can be used by different jurisdictions and accept updated data. Results can aid economic evaluations and public health decision-making regarding RSV immunization products.

      7. Safety of the 9-valent human papillomavirus vaccineexternal icon
        Shimabukuro TT, Su JR, Marquez PL, Mba-Jonas A, Arana JE, Cano MV.
        Pediatrics. 2019 Nov 18.
        BACKGROUND: The 9-valent human papillomavirus vaccine (9vHPV) was approved for females and males aged 9 to 26 years in 2014. We analyzed postlicensure surveillance reports to the Vaccine Adverse Event Reporting System (VAERS). METHODS: We searched VAERS data for US reports of adverse events (AEs) after 9vHPV from December 2014 through December 2017. We calculated reporting rates and conducted empirical Bayesian data mining to identify disproportional reporting. Physicians reviewed reports for selected prespecified conditions. RESULTS: VAERS received 7244 reports after 9vHPV: 31.2% among females, 21.6% among males, and for 47.2%, sex was not reported. Overall, 97.4% of reports were nonserious. Dizziness, syncope, headache, and injection site reactions were most commonly reported; the most commonly reported AEs were similar between females and males. Two reports of death after 9vHPV were verified; no information in autopsy reports or death certificates suggested a causal relationship with vaccination. Approximately 28 million 9vHPV doses were distributed during the study period; crude AE reporting rates were 259 reports per million 9vHPV doses distributed for all reports and 7 per million doses distributed for serious reports. Syncope (a known AE associated with human papillomavirus vaccination) and several types of vaccine administration errors (eg, administered at wrong age) exceeded the statistical threshold for empirical Bayesian data mining findings. CONCLUSIONS: No new or unexpected safety concerns or reporting patterns of 9vHPV with clinically important AEs were detected. The safety profile of 9vHPV is consistent with data from prelicensure trials and from postmarketing safety data of its predecessor, the quadrivalent human papillomavirus vaccine.

      8. Influenza vaccine effectiveness against hospitalizations in children and older adults – data from South America, 2013-2017. A test negative designexternal icon
        Sofia Arriola C, El Omeiri N, Azziz-Baumgartner E, Thompson MG, Sotomayor-Proschle V, Fasce RA, Von Horoch M, Enrique Carrizo Olalla J, Aparecida Ferreira de Almeida W, Palacios J, Palekar R, Couto P, Descalzo M, Maria Ropero-Alvarez A, Gonzalez C, Loayza S, Vergara N, Bustos P, Andrade W, Magda S. Domingues CD, Issac Montenegro Renoiner E, Tatiane da Silva E, Lima Palmeira S, Araujo da Silva D, Carolina de Lacerda Sousa A, Mendonca Siqueira M, Vazquez C, Battaglia S, Vizzotti C, Baumeister E, Giovacchini C, Katz N, Pacheco O, Barbosa J, Malo D, Pulido P, Garcia D, Pinzon C.
        Vaccine: X. 2019 ;3.
        Background: In 2013, the Pan American Health Organization established a multi-site, multi-country network to evaluate influenza vaccine effectiveness (VE). We pooled data from five consecutive seasons in five countries to conduct an analysis of southern hemisphere VE against laboratory-confirmed influenza hospitalizations in young children and older adults. Methods: We used a test-negative design to estimate VE against laboratory-confirmed influenza in hospitalized young children (aged 6-24 months) and older adults (aged >/= 60 years) in Argentina, Brazil, Chile, Colombia, and Paraguay. Following country-specific influenza surveillance protocol, hospitalized persons with severe acute respiratory infections (SARI) at 48 sentinel hospitals (March 2013-December 2017) were tested for influenza virus infection by rRT-PCR. VE was estimated for young children and older adults using logistic random effects models accounting for cluster (country), adjusting for sex, age (months for children, and age-in-year categories for adults), calendar year, country, preexisting conditions, month of illness onset and prior vaccination as an effect modifier for the analysis in adults. Results: We included 8426 SARI cases (2389 children and 6037 adults) in the VE analyses. Among young children, VE against SARI hospitalization associated with any influenza virus was 43% (95%CI: 33%, 51%) for children who received two doses, but was 20% (95%CI: -16%, 45%) and not statistically significant for those who received one dose in a given season. Among older adults, overall VE against SARI hospitalization associated with any influenza virus was 41% (95%CI: 28%, 52%), 45% (95%CI: 34%, 53%) against A(H3N2), 40% (95%CI: 18%, 56%) against A(H1N1)pdm09, and 20% (95%CI: -40%, 54%) against influenza B viruses. Conclusions: Our results suggest that over the five-year study period, influenza vaccination programs in five South American countries prevented more than one-third of laboratory confirmed influenza-associated hospitalizations in young children receiving the recommended two doses and vaccinated older adults.

    • Informatics
      1. Digital segmentation of priority populations in public healthexternal icon
        Evans WD, Thomas CN, Favatas D, Smyser J, Briggs J.
        Health Educ Behav. 2019 Dec;46(2_suppl):81-89.
        The rapid growth and diffusion of digital media technologies has changed the landscape of market segmentation in the last two decades, including its use in promoting prosocial and behavior change. New, population-specific and culturally appropriate prevention strategies can leverage the potential of digital media to influence health outcomes, especially for the greatest users of digital technology, including youth and young adults. Health behavior change campaigns are increasingly shifting resources to social media, creating opportunities for innovative interventions and new research methods. This article examines three case studies of digital segmentation: (1) tobacco control from the Truth Initiative, (2) community-based public health programs from the Centers for Disease Control and Prevention, and (3) substance use (including opioids) and other risk behavior prevention from Public Good Projects. These case studies of recent digital segmentation efforts in the not-for-profit, government, and academic sectors show that it increases reach and frequency of messages delivered to priority populations. The practice of digital segmentation is rapidly growing, shows early signs of effectiveness, and may enhance future public health campaigns. Additional research could optimize its use and effectiveness in promoting prosocial and behavior change campaign outcomes.

    • Injury and Violence
      1. Traumatic brain injury-related deaths by race/ethnicity, sex, intent, and mechanism of injury – United States, 2000-2017external icon
        Daugherty J, Waltzman D, Sarmiento K, Xu L.
        MMWR Morb Mortal Wkly Rep. 2019 Nov 22;68(46):1050-1056.
        Traumatic brain injury (TBI) affects the lives of millions of Americans each year (1). To describe the trends in TBI-related deaths among different racial/ethnic groups and by sex, CDC analyzed death data from the National Vital Statistics System (NVSS) over an 18-year period (2000-2017). Injuries were also categorized by intent, and unintentional injuries were further categorized by mechanism of injury. In 2017, TBI contributed to 61,131 deaths in the United States, representing 2.2% of approximately 2.8 million deaths that year. From 2015 to 2017, 44% of TBI-related deaths were categorized as intentional injuries (i.e., homicides or suicides). The leading category of TBI-related death varied over time and by race/ethnicity. For example, during the last 10 years of the study period, suicide surpassed unintentional motor vehicle crashes as the leading category of TBI-related death. This shift was in part driven by a 32% increase in TBI-related suicide deaths among non-Hispanic whites. Firearm injury was the underlying mechanism of injury in nearly all (97%) TBI-related suicides among all groups. An analysis of TBI-related death rates by sex and race/ethnicity found that TBI-related deaths were significantly higher among males and persons who were American Indians/Alaska Natives (AI/ANs) than among all other groups across all years. Other leading categories of TBI-related deaths included unintentional motor vehicle crashes, unintentional falls, and homicide. Understanding the leading contributors to TBI-related death and identifying groups at increased risk is important in preventing this injury. Broader implementation of evidence-based TBI prevention efforts for the leading categories of injury, such as those aimed at stemming the significant increase in TBI-related deaths from suicide, are warranted.

      2. Concussion and academic impairment among U.S. high school studentsexternal icon
        Lowry R, Haarbauer-Krupa JK, Breiding MJ, Thigpen S, Rasberry CN, Lee SM.
        Am J Prev Med. 2019 ;57(6):733-740.
        Introduction: Sports and physical activities are a frequent cause of traumatic brain injury, primarily concussions, among adolescents. These concussions may adversely affect students’ ability to learn and impair academic achievement in educational settings. Methods: The 2017 Youth Risk Behavior Survey, conducted among a nationally representative sample of 14,765 U.S. high school students, was analyzed in 2018 to examine associations between self-reported sports- and physical activity-related concussions and symptoms of cognitive impairment (difficulty concentrating, remembering, or making decisions) and self-reported academic grades (mostly A’s=4.0, mostly B’s=3.0, mostly C’s=2.0, mostly D’s=1.0, mostly F’s=0.0). Adjusted prevalence ratio and the difference in self-reported estimated grade point average were adjusted for sex, race/ethnicity, grade, and athlete status (participation on sports teams) and considered statistically significant if p<0.05. Results: Male students were more likely than female students (17.1% vs 13.0%), and athletes were more likely than nonathletes (21.4% vs 7.6%) to have a self-reported sports- and physical activity-related concussion in the 12 months preceding the survey. Students with a reported sports- and physical activity-related concussion were more likely than students without one to report symptoms of cognitive impairment regardless of whether they were male (adjusted prevalence ratio=1.49), female (adjusted prevalence ratio=1.37), athletes (adjusted prevalence ratio=1.45), or nonathletes (adjusted prevalence ratio=1.42). Self-reported grade point averagedecreased significantly from 3.14 among students who reported no concussions (referent), to 3.04 among students who reported a single concussion, and 2.81 among students who reported >/= 2 concussions. Conclusions: School-based programs are needed to monitor students’ academic performance and provide educational support and resources to promote academic success following a concussion.

    • Laboratory Sciences
      1. Training rhesus macaques to take daily oral antiretroviral therapy for preclinical evaluation of HIV prevention and treatment strategiesexternal icon
        Daly MB, Clayton AM, Ruone S, Mitchell J, Dinh C, Holder A, Jolly J, Garcia-Lerma JG, Weed JL.
        PLoS One. 2019 ;14(11):e0225146.
        BACKGROUND: Macaque models of simian or simian/human immunodeficiency virus (SIV or SHIV) infection are critical for the evaluation of antiretroviral (ARV)-based HIV treatment and prevention strategies. However, modelling human oral ARV administration is logistically challenging and fraught by limited adherence. Here, we developed a protocol for administering daily oral doses of ARVs to macaques with a high rate of compliance. METHODS: Parameters of positive reinforcement training (PRT), behavioral responses and optimal drug delivery foods were defined in 7 male rhesus macaques (Macaca mulatta). Animals were trained to sit in a specified cage location prior to receiving ARVs, emtricitabine (FTC) and tenofovir alafenamide (TAF), in a blended food mixture, which was followed immediately with a juice chaser. Consistency of daily oral adherence was evaluated in 4 trained macaques receiving clinically equivalent doses of FTC and TAF (20 and 1.5 mg/kg, respectively) in a short-term (1 month) and an extended (6 month) trial. Adherence was monitored using medication diaries and by quantifying intracellular FTC-triphosphate (FTC-TP) and tenofovir-diphosphate (TFV-DP) concentrations in peripheral mononuclear blood cells (PBMCs). RESULTS: Trained macaques quickly and consistently took daily oral ARVs for 1 month with an average 99.8% observed adherence. Intracellular concentrations of TFV-DP (median = 845.8 fmol/million cells [range, 620.8-1031.3]) and FTC-TP (median = 367.0 fmol/million cells [range, 289.5-413.5) in PBMCs were consistent with high adherence. Extended treatment with select subjects yielded similar observations for three months (99.5% adherence, 352/356 complete doses taken), although a sudden drop in adherence was observed after splenic biopsy surgery. CONCLUSIONS: We demonstrate that trained macaques reliably adhere to a daily oral ARV regimen, although unexpected adherence issues are possible. Our approach, using clinical doses of oral FTC and TAF daily, further refines macaque models of HIV treatment and prevention by mimicking the human route and timing of ARV administration.

      2. Alterations in blood chemistry levels associated with Nipah virus disease in the Syrian hamster modelexternal icon
        Genzer SC, Welch SR, Scholte FE, Harmon JR, Coleman-McCray JD, Lo MK, Montgomery JM, Nichol ST, Spiropoulou CF, Spengler JR.
        J Infect Dis. 2019 Nov 20.
        Nipah virus ([NiV] family Paramyxoviridae, genus Henipavirus) infection can cause severe respiratory and neurological disease in humans. The pathophysiology of disease is not fully understood, and it may vary by presentation and clinical course. In this study, we investigate changes in blood chemistry in NiV-infected Syrian hamsters that survived or succumbed to disease. Increased sodium and magnesium and decreased albumin and lactate levels were detected in animals euthanized with severe clinical disease compared with mock-infected controls. When subjects were grouped by clinical syndrome, additional trends were discernable, highlighting changes associated with either respiratory or neurological disease.

      3. Immunoproteomic analysis of Borrelia miyamotoi for the identification of serodiagnostic antigensexternal icon
        Harris EK, Harton MR, de Mello Marques MA, Belisle JT, Molins CR, Breuner N, Wormser GP, Gilmore RD.
        Sci Rep. 2019 Nov 14;9(1):16808.
        The tick-borne spirochete, Borrelia miyamotoi, is an emerging pathogen of public health significance. Current B. miyamotoi serodiagnostic testing depends on reactivity against GlpQ which is not highly sensitive on acute phase serum samples. Additionally, anti-B. miyamotoi antibodies can cross-react with C6 antigen testing for B. burgdorferi, the causative agent of Lyme disease, underscoring the need for improved serological assays that produce accurate diagnostic results. We performed an immunoproteomics analysis of B. miyamotoi proteins to identify novel serodiagnostic antigens. Sera from mice infected with B. miyamotoi by subcutaneous inoculation or tick bite were collected for immunoblotting against B. miyamotoi membrane-associated proteins separated by 2-dimensional electrophoresis (2DE). In total, 88 proteins in 40 2DE immunoreactive spots were identified via mass spectrometry. Multiple variable large proteins (Vlps) and a putative lipoprotein were among those identified and analyzed. Reactivity of anti-B. miyamotoi sera against recombinant Vlps and the putative lipoprotein confirmed their immunogenicity. Mouse anti-B. burgdorferi serum was cross-reactive to all recombinant Vlps, but not against the putative lipoprotein by IgG. Furthermore, antibodies against the recombinant putative lipoprotein were present in serum from a B. miyamotoi-infected human patient, but not a Lyme disease patient. Results presented here provide a comprehensive profile of B. miyamotoi antigens that induce the host immune response and identify a putative lipoprotein as a potentially specific antigen for B. miyamotoi serodetection.

      4. Studies in mouse and lamb models indicate important roles of reactive oxygen species (ROS) in the pathology and immune response to respiratory syncytial virus (RSV). The role of ROS in bovine RSV (BRSV) infection of calves remains unclear. BRSV naturally infects calves, leading to similar disease course, micro- and macro-lesions, and symptomology as is observed in RSV infection of human neonates. Furthermore, humans, lambs, and calves, but not mice, have an active lung oxidative system involving lactoperoxidase (LPO) and the dual oxidases (DUOX) 1 and 2. To gain insight into the role of ROS in the BRSV-infected lung, we examined gene expression in infected bovine cells using qPCR. A panel of 19 primers was used to assay ex vivo and in vitro BRSV-infected cells. The panel targeted genes involved in both production and regulation of ROS. BRSV infection significantly increased transcription of five genes in bovine respiratory tract cells in vitro and ex vivo. PTGS2 expression more than doubled in both sample types. Four transcripts varied significantly in lung lesions, but not non-lesion samples, compared with uninfected lung. This is the first report of the transcriptional profile of ROS-related genes in the airway after BRSV infection in the natural host.

      5. Insular microbiogeography: Three pathogens as exemplarsexternal icon
        Kaufman JH, Elkins CA, Davis M, Weis AM, Huang BC, Mammel MK, Patel IR, Beck KL, Edlund S, Chambliss D, Douglas J, Bianco S, Kunitomi M, Weimer BC.
        Curr Issues Mol Biol. 2019 Oct 9;36:89-108.
        Traditional taxonomy in biology assumes that life is organized in a simple tree. Attempts to classify microorganisms in this way in the genomics era led microbiologists to look for finite sets of ‘core’ genes that uniquely group taxa as clades in the tree. However, the diversity revealed by large-scale whole genome sequencing is calling into question the long-held model of a hierarchical tree of life, which leads to questioning of the definition of a species. Large-scale studies of microbial genome diversity reveal that the cumulative number of new genes discovered increases with the number of genomes studied as a power law and subsequently leads to the lack of evidence for a unique core genome within closely related organisms. Sampling ‘enough’ new genomes leads to the discovery of a replacement or alternative to any gene. This power law behaviour points to an underlying self-organizing critical process that may be guided by mutation and niche selection. Microbes in any particular niche exist within a local web of organism interdependence known as the microbiome. The same mechanism that underpins the macro-ecological scaling first observed by MacArthur and Wilson also applies to microbial communities. Recent metagenomic studies of a food microbiome demonstrate the diverse distribution of community members, but also genotypes for a single species within a more complex community. Collectively, these results suggest that traditional taxonomic classification of bacteria could be replaced with a quasispecies model. This model is commonly accepted in virology and better describes the diversity and dynamic exchange of genes that also hold true for bacteria. This model will enable microbiologists to conduct population-scale studies to describe microbial behaviour, as opposed to a single isolate as a representative.

      6. Evaluation of a single-dose nucleoside-modified messenger RNA vaccine encoding hendra virus-soluble glycoprotein against lethal Nipah virus challenge in Syrian Hamstersexternal icon
        Lo MK, Spengler JR, Welch SR, Harmon JR, Coleman-Mccray JD, Scholte FE, Shrivastava-Ranjan P, Montgomery JM, Nichol ST, Weissman D, Spiropoulou CF.
        J Infect Dis. 2019 Nov 21.
        In the absence of approved vaccines and therapeutics for use in humans, Nipah virus continues to cause fatal outbreaks of encephalitis and respiratory disease in Bangladesh and India on a near-annual basis. We determined that a single dose of a lipid nanoparticle nucleoside-modified messenger RNA vaccine encoding the soluble Hendra virus glycoprotein protected up to 70% of Syrian hamsters from lethal NiV challenge, despite animals having suboptimally primed immune responses before challenge. These data provide a foundation from which to optimize future messenger RNA vaccination studies against NiV and other highly pathogenic viruses.

      7. Genome sequence of a Salmonella enterica subsp. enterica serovar Corvallis strain isolated from human bloodexternal icon
        McCutchen EL, Galac M, Kapsak C, Hinrichs SH, Iwen PC, Abdalhamid B.
        Microbiol Resour Announc. 2019 Oct 31;8(44).
        Salmonella enterica subsp. enterica serovar Corvallis is commonly reported in avian populations and avian by-products. We report the draft genome sequence of a multidrug-resistant S. Corvallis strain (NPHL 15376). To our knowledge, this is the first reported case of this serovar isolated from human blood in the United States.

      8. Replacement of neuraminidase inhibitor-susceptible influenza A(H1N1) with resistant phenotype in 2008 and circulation of susceptible influenza A and B viruses during 2009-2013, South Africaexternal icon
        Treurnicht FK, Buys A, Tempia S, Seleka M, Cohen AL, Walaza S, Glass AJ, Rossouw I, McAnerney J, Blumberg L, Cohen C, Venter M.
        Influenza Other Respir Viruses. 2019 Jan;13(1):54-63.
        BACKGROUND: Data on the susceptibility of influenza viruses from South Africa to neuraminidase inhibitors (NAIs) are scarce, and no extensive analysis was done. OBJECTIVES: We aimed to determine oseltamivir and zanamivir susceptibility of influenza A and B virus neuraminidases (NAs), 2007-2013, South Africa. PATIENTS/METHODS: We enrolled participants through national influenza-like illness surveillance, 2007-2013. Influenza diagnosis was by virus isolation and quantitative polymerase chain reaction (qPCR). Drug susceptibility was determined by chemiluminescence-based NA-STAR/NA-XTD assay. Sanger sequencing was used to determine molecular markers of NAI resistance. RESULTS: Forty percent (6341/15 985) of participants were positive for influenza viruses using virus isolation (2007-2009) and qPCR (2009-2013) methods. A total of 1236/6341 (19.5%) virus isolates were generated of which 307/1236 (25%) were tested for drug susceptibility. During 2007-2008, the median 50% inhibitory concentration (IC50 ) of oseltamivir for seasonal influenza A(H1N1) increased from of 0.08 nmol/L (range 0.01-3.60) in 2007 to 73 nmol/L (range 1.56-305 nmol/L) in 2008. Influenza A isolates from 2009 to 2013 were susceptible to oseltamivir [A(H3N2) median IC50 = 0.05 nmol/L (range 0.01-0.08); A(H1N1)pdm09 = 0.11 nmol/L (range 0.01-0.78)] and zanamivir [A(H3N2) median IC50 = 0.56 nmol/L (range 0.47-0.66); A(H1N1)pdm09 = 0.35 nmol/L (range 0.27-0.533)]. Influenza B viruses were susceptible to both NAIs. NAI resistance-associated substitutions H275Y, E119V, and R150K (N1 numbering) were not detected in influenza A viruses that circulated in 2009-2013. CONCLUSIONS: We confirm replacement of NAI susceptible by resistant phenotype influenza A(H1N1) in 2008. Influenza A and B viruses (2009-2013) remained susceptible to NAIs; therefore, these drugs are useful for treating influenza-infected patients.

      9. Conserved patterns of symmetric inversion in the genome evolution of Bordetella respiratory pathogensexternal icon
        Weigand MR, Peng Y, Batra D, Burroughs M, Davis JK, Knipe K, Loparev VN, Johnson T, Juieng P, Rowe LA, Sheth M, Tang K, Unoarumhi Y, Williams MM, Tondella ML.
        mSystems. 2019 Nov 19;4(6).
        Whooping cough (pertussis), primarily caused by Bordetella pertussis, has resurged in the United States, and circulating strains exhibit considerable chromosome structural fluidity in the form of rearrangement and deletion. The genus Bordetella includes additional pathogenic species infecting various animals, some even causing pertussis-like respiratory disease in humans; however, investigation of their genome evolution has been limited. We studied chromosome structure in complete genome sequences from 167 Bordetella species isolates, as well as 469 B. pertussis isolates, to gain a generalized understanding of rearrangement patterns among these related pathogens. Observed changes in gene order primarily resulted from large inversions and were only detected in species with genomes harboring multicopy insertion sequence (IS) elements, most notably B. holmesii and B. parapertussis While genomes of B. pertussis contain >240 copies of IS481, IS elements appear less numerous in other species and yield less chromosome structural diversity through rearrangement. These data were further used to predict all possible rearrangements between IS element copies present in Bordetella genomes, revealing that only a subset is observed among circulating strains. Therefore, while it appears that rearrangement occurs less frequently in other species than in B. pertussis, these clinically relevant respiratory pathogens likely experience similar mutation of gene order. The resulting chromosome structural fluidity presents both challenges and opportunity for the study of Bordetella respiratory pathogens.IMPORTANCE Bordetella pertussis is the primary agent of whooping cough (pertussis). The Bordetella genus includes additional pathogens of animals and humans, including some that cause pertussis-like respiratory illness. The chromosome of B. pertussis has previously been shown to exhibit considerable structural rearrangement, but insufficient data have prevented comparable investigation in related species. In this study, we analyze chromosome structure variation in several Bordetella species to gain a generalized understanding of rearrangement patterns in this genus. Just as in B. pertussis, we observed inversions in other species that likely result from common mutational processes. We used these data to further predict additional, unobserved inversions, suggesting that specific genome structures may be preferred in each species.

    • Maternal and Child Health
      1. Protocols, practices, and needs for investigating sudden unexpected infant deathsexternal icon
        Cottengim C, Parks S, Rhoda D, Andrew T, Nolte KB, Fudenberg J, Sens MA, Brustrom J, Payn B, Shapiro-Mendoza CK.
        Forensic Sci Med Pathol. 2019 Nov 18.
        Understanding case identification practices, protocols, and training needs of medical examiners and coroners (MEC) may inform efforts to improve cause-of-death certification. We surveyed a U.S.-representative sample of MECs and described investigation practices and protocols used in certifying sudden unexpected infant deaths (SUID). We also identified MEC training and resource needs. Of the 377 respondents, use of the SUID Investigation Reporting Form or an equivalent was 89% for large, 87% for medium, and 52% for small jurisdictions. Routine completion of infant medical history, witness interviews, autopsy, photos or videos, and family social history for infant death investigations was >/=80%, but routine scene re-creation with a doll was 30% in small, 64% in medium, and 59% in large offices. Seventy percent of MECs reported infant death investigation training needs. Increased training and use of standardized practices may improve SUID cause-of-death certification, allowing us to better understand SUID.

      2. Characteristics associated with presence of pediatric mental health care policies in emergency departmentsexternal icon
        Cree RA, So M, Franks J, Richards R, Leeb R, Hashikawa A, Krug S, Ludwig L, Olson LM.
        Pediatr Emerg Care. 2019 Nov 13.
        OBJECTIVES: The majority of US children do not have access to an emergency department (ED) with a pediatric mental health care policy in place. Our objective was to understand factors associated with whether US EDs have a pediatric mental health care policy. METHODS: We analyzed data from the National Pediatric Readiness Project, a nationally representative cross-sectional survey of US EDs. Nurse managers reported whether their hospitals had a policy to care for children with social/mental health concerns (n = 3612). We calculated prevalence estimates, prevalence ratios (PRs), and confidence intervals (CIs) for regional and ED characteristics (eg, rurality and types of personnel) by whether EDs had a pediatric mental health care policy. RESULTS: Overall, 46.2% (n = 1668/3612) of EDs had a pediatric mental health care policy. Emergency departments located in remote areas were 60% less likely to have such a policy compared with EDs in urban areas (PR, 0.4; CI, 0.3-0.5). Emergency department characteristics associated with having a pediatric mental health care policy included having a policy to transfer children with social/mental health concerns (PR, 5.4; CI, 4.7-6.2), having a policy to address maltreatment (PR, 3.4; CI, 2.6-4.4), and having nurse and physician pediatric emergency care coordinators (PR, 1.6; CI, 1.5-1.8). CONCLUSIONS: Lower prevalence of pediatric mental health policies in rural EDs is concerning considering EDs are often the first point of contact for pediatric patients. This work highlights the importance of pediatric emergency care coordinators in fostering ED capacity to meet children’s mental health needs.

      3. Differences in continence rates in individuals with spina bifida based on ethnicityexternal icon
        Smith KA, Liu T, Freeman KA, Betz C, Clayton GH, Castillo H, Castillo J, Tu D, Speybroeck AV, Walker WO.
        J Pediatr Rehabil Med. 2019 Nov 8.
        BACKGROUND: Ethnic disparities in continence rates in spina bifida (SB) have been studied regionally but not nationally. National SB Patient Registry (NSBPR) data were analyzed to explore differences in prevalence of bowel and bladder continence and interventions between Hispanics/Latinos and others. METHODS: Participants 5 to 21 years were categorized into Hispanic/Latino and non-Hispanic/non-Latino. Bladder/bowel continence was defined as dry/no involuntary stool leakage during the day or none/ monthly incontinence. Chi-square test, Wilcoxon Two Sample Test, and generalized estimating equation (GEE) were used for statistical analysis. RESULTS: Twenty-five percent of the 4,364 patients were Hispanic/Latino. At their most recent clinic visit, Hispanics/Latinos demonstrated lower rates of urinary continence (38.6% vs. 44.9%; p= 0.0003), bowel continence (43.9% vs. 55.8%, p< 0.0001), private insurance (p< 0.0001), bowel (p< 0.0001) or bladder surgeries (p= 0.0054), and more vesicostomies (p= 0.0427) compared to others. In multiple GEE models, Hispanic/Latino participants demonstrated lower odds of bowel continence as compared to non-Hispanic/non-Latino participants (estimated odds ratio, 0.82, 95% CI, 0.72-0.94, p= 0.0032). CONCLUSIONS: After controlling for covariates, Hispanics/Latinos with SB are less likely to report bowel continence. Clinicians are encouraged to consider risk of negative health disparities for Hispanic patients with SB and work to mitigate this risk.

    • Nutritional Sciences
      1. Obesity negatively affects children’s health because of its associations with cardiovascular disease risk factors, type 2 diabetes, asthma, fatty liver disease, victimization stemming from social stigma and bullying, and poor mental health (e.g., anxiety and depression) (1). Children who have overweight or obesity in early childhood are approximately four times as likely to have overweight or obesity in young adulthood as their normal weight peers (2). Obesity prevalence is especially high among children from low-income families (3). In 2010, the overall upward trend in obesity prevalence turned downward among children aged 2-4 years enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), a program of the U.S. Department of Agriculture (USDA); prevalence decreased significantly in all racial/ethnic groups and in 34 of the 56 WIC state or territory agencies during 2010-2014 (4). A more recent study among young children enrolled in WIC reported that the overall obesity prevalence decreased from 15.9% in 2010 to 13.9% in 2016 and statistically significant decreases were observed in all age, sex, and racial/ethnic subgroups (3). However, this study did not provide obesity trends at the state level. In collaboration with USDA, CDC used data from the WIC Participant and Program Characteristics (WIC PC) to update state-specific trends through 2016. During 2010-2016, modest but statistically significant decreases in obesity prevalence among children aged 2-4 years enrolled in WIC occurred in 41 (73%) of 56 WIC state or territory agencies. Comprehensive approaches that create positive changes to promote healthy eating and physical activity for young children from all income levels,* strengthen nutrition education and breastfeeding support among young children enrolled in WIC, and encourage redemptions of healthy foods in WIC food packages could help maintain or accelerate these declining trends.

    • Occupational Safety and Health
      1. Are knee savers and knee pads a viable intervention to reduce lower extremity musculoskeletal disorder risk in residential roofers?external icon
        Breloff SP, Sinsel EW, Dutta A, Carey RE, Warren CM, Dai F, Ning S, Wu JZ.
        Int J Ind Ergon. 2019 ;74.
        One factor commonly associated with musculoskeletal disorder risk is extreme postures. To lessen this risk, extreme postures should be reduced using proactive and prevention-focused methods. The effect of combinations of two interventions, knee pads and knee savers, on lower extremity kinematics during deep or near full flexion kneeling on differently sloped surfaces was analyzed. Nine male subjects were requested to keep a typical resting posture while kneeling on a sloped roofing simulator with and without knee pads and knee savers. Three-dimensional peak knee kinematics were recording using a motion capture system. The kinematic data were analyzed with a two-way-4(intervention) X 3(slope)-repeated measure analysis of variance (ANOVA). It was observed that knee pads did not alter lower extremity kinematics in a way that may reduce musculoskeletal injury risk, but they do provide comfort. Knee savers did statistically significantly reduce peak lower extremity kinematics, however these changes were small and it is uncertain if the changes will reduce musculoskeletal injury risk. This study has provided initial data that supports the use of knee savers as a potential intervention to reduce musculoskeletal disorder risk due to lower extremity joint angles on a sloped surface, nonetheless, further testing involving other musculoskeletal disorder risk factors is needed prior to a conclusive recommendation.

      2. Workshop summary: Potential usefulness and feasibility of a US national mesothelioma registryexternal icon
        Cummings KJ, Becich MJ, Blackley DJ, Deapen D, Harrison R, Hassan R, Henley SJ, Hesdorffer M, Horton DK, Mazurek JM, Pass HI, Taioli E, Wu XC, Zauderer MG, Weissman DN.
        Am J Ind Med. 2019 Nov 19.
        BACKGROUND: The burden and prognosis of malignant mesothelioma in the United States have remained largely unchanged for decades, with approximately 3200 new cases and 2400 deaths reported annually. To address care and research gaps contributing to poor outcomes, in March of 2019 the Mesothelioma Applied Research Foundation convened a workshop on the potential usefulness and feasibility of a national mesothelioma registry. METHODS: The workshop included formal presentations by subject matter experts and a moderated group discussion. RESULTS: Workshop participants identified top priorities for a registry to be: (a) connecting patients with high-quality care and clinical trials soon after diagnosis and (b) making useful data and biospecimens available to researchers in a timely manner. Existing databases that capture mesothelioma cases are limited by factors such as delays in reporting, de-identification, and lack of exposure information critical to understanding as yet unrecognized causes of disease. National disease registries for amyotrophic lateral sclerosis in the United States, and for mesothelioma in other countries, provide examples of how a registry could be structured to meet the needs of patients and the scientific community. CONCLUSIONS: Small-scale pilot initiatives should be undertaken to validate methods for rapid case identification, develop procedures to facilitate patient access to guidelines-based standard care and investigational therapies, and explore approaches to data-sharing with researchers. Ultimately, federal coordination and funding will be critical to the success of a national mesothelioma registry in improving mesothelioma outcomes and preventing future cases of this devastating disease.

      3. Development of an asthma-specific job exposure matrix for use in the United Statesexternal icon
        Henneberger PK, Kurth LM, Doney B, Liang X, Andersson E.
        Ann Work Expo Health. 2019 Nov 20.
        INTRODUCTION: Existing asthma-specific job-exposure matrices (JEMs) do not necessarily reflect current working conditions in the USA and do not directly function with occupational coding systems commonly used in the USA. We initiated a project to modify an existing JEM to address these limitations, and to apply the new JEM to the entire US employed population to estimate quantitatively the extent of probable work-related asthma exposures nationwide. METHODS: We started with an asthma-specific JEM that was developed for northern Europe (the N-JEM) and modified it to function with the 2010 US Standard Occupational Classification (SOC-2010) codes and to reflect working conditions in the USA during the post-2000 period. This involved cross walking from the 1988 International Standard Classification of Occupations (ISCO-88) codes used in the N-JEM to the SOC-2010 codes, transferring the N-JEM exposure assignments to the SOC-2010 codes, and modifying those assignments to reflect working conditions in the USA. The new US asthma JEM (USA-JEM) assigns exposures to 19 agents organized into five categories. The USA-JEM and N-JEM were applied to the same sample of working adults with asthma to compare how they performed, and the USA-JEM was also applied to the entire 2015 US working population to estimate the extent of occupational asthma exposures nationally. RESULTS: The USA-JEM assigns at least one asthma-related probable exposure to 47.5% and at least one possible exposure to 14.9% of the 840 SOC-2010 detailed occupations, and 9.0% of the occupations have both probable exposure to at least one agent and possible exposure to at least one other agent. The USA-JEM has greater sensitivity for cleaning products, highly reactive disinfectants and sterilants, and irritant peak exposures than the N-JEM. When applied to the entire 2015 US working population, the USA-JEM determined that 42.6% of workers had probable exposure to at least one type of occupational asthma agent. DISCUSSION: A new asthma-specific JEM for application in the USA was developed. Additional work is needed to compare its performance to similar JEMs and, if possible, to exposure assessments generated on a case-by-case basis.

      4. Workers’ compensation claims for traumatic brain injuries among private employers-Ohio, 2001-2011external icon
        Konda S, Al-Tarawneh IS, Reichard AA, Tiesman HM, Wurzelbacher SJ, Pinkerton LE, Meyers AR, Hendricks SA, Tseng CY, Lampl MP, Robins DC.
        Am J Ind Med. 2019 Nov 19.
        BACKGROUND: The purpose of this analysis was to identify and prioritize high-risk industry groups for traumatic brain injury (TBI) prevention efforts. METHODS: Workers with TBI from 2001 to 2011 were identified from the Ohio Bureau of Workers’ Compensation data. To prioritize industry groups by claim type (lost-time (>/=8 days away from work) and total claims) and injury event categories, we used a prevention index (PI) that averaged TBI counts and rate ranks (PI = (count rank + rate rank)/2). TBI rates per 10 000 estimated full-time equivalent (FTE = 2000 h/y) workers were calculated. RESULTS: From 2001 to 2011, 12 891 TBIs were identified among private employers, resulting in a rate of 5.1 TBIs per 10 000 FTEs. Of these, 40% (n = 5171) were lost-time TBIs, at a rate of 2.0 per 10 000 FTEs. Spectator Sports had the highest lost-time TBI rate (13.5 per 10 000 FTEs), whereas General Freight Trucking had the greatest number of lost-time TBIs (n = 293). Based on PIs, General Freight Trucking ranked first for lost-time TBIs for all injury events combined. Several industry groups within Construction, General and Specialized Freight Trucking, Services to Building and Dwellings, Employment Services, and Restaurants and Other Eating Places ranked high across multiple injury event categories for lost-time TBIs. CONCLUSIONS: The high-ranking industry groups identified from our study can be used to effectively direct occupational TBI prevention efforts.

    • Occupational Safety and Health – Mining
      1. A study was conducted to examine the potential of diesel emissions control strategies based on retrofitting existing power packages with exhaust aftertreatment devices and repowering with advanced power packages. The retrofit systems, a diesel oxidation catalyst (DOC) and diesel particulate filter (DPF), were evaluated individually using a US EPA tier 2 (ter 2) engine operated under four steady-state conditions and one transient cycle. The DOC effectively curtailed emissions of CO, and to some extent organic carbon (OC), elemental carbon (EC), and aerosol number concentration. The DPF system offered substantially higher reductions in OC and EC mass and aerosol number concentrations. Both, the DOC and DPF achieved reductions in the aforementioned emissions without adversely affecting emissions of NO2 and nano-sized aerosols. The strategy of repowering with an advanced system was examined using a US EPA tier 4 final (tier 4f) engine equipped with a cooled exhaust gas recirculation system and diesel exhaust fluid-based selective catalytic reduction system, but not with a DPF system. The tier 4f engine contributed substantially less than the tier 2 engine to the EC and OC mass, aerosol number, and CO, NO, and NO2 concentrations. The tier 4f engine was very effective in reducing aerosol mass, NO, and NO2 concentrations, but it was not equally effective in reducing aerosol number concentrations. The implementation of viable exhaust after treatment systems and advanced diesel power packages could be instrumental to the underground mining industry to secure a clean, economical, and dependable source of power for mobile equipment.

    • Parasitic Diseases
      1. Schistosomiasis was not associated with higher HIV-1 plasma or genital set point viral loads among HIV seroconverters from four cohort studiesexternal icon
        Bochner AF, Secor WE, Baeten JM, van Dam GJ, Szpiro AA, Njenga SM, Corstjens P, Mackelprang RD, Mugo NR, Overbaugh J, Celum C, Mujugira A, McClelland RS, Barnabas RV.
        PLoS Negl Trop Dis. 2019 Nov;13(11).
        BACKGROUND: Many regions of sub-Saharan Africa experience a high prevalence of both schistosomiasis and HIV-1, leading to frequent coinfection. Higher plasma HIV-1 viral loads are associated with faster disease progression and genital HIV-1 loads are a primary determinant of HIV-1 transmission risk. We hypothesized that schistosome infection would be associated with higher HIV-1 viral loads in plasma and genital samples. METHODS/PRINCIPAL FINDINGS: We utilized data from individuals who HIV-1 seroconverted while enrolled in one of four prospective cohort studies. Plasma and genital viral loads collected 4-24 months after the estimated date of HIV-1 acquisition, but prior to antiretroviral therapy initiation, were included. Detection of circulating anodic antigen in archived blood samples, collected prior to HIV-1 seroconversion, identified participants with active schistosomiasis; immunoblots determined the schistosome species causing infection. Our analysis included 370 HIV-1 seroconverters with plasma viral load results, of whom 82 (22%) had schistosomiasis. We did not find a statistically significant association between schistosomiasis and higher HIV-1 set point plasma viral loads (-0.17 log10 copies/ml, 95% CI -0.38 to 0.03); S. mansoni infection was associated with a lower set point (-0.34 log10 copies/ml, 95% CI -0.58 to -0.09). We found no association between schistosomiasis and cervical (+0.07 log10 copies/swab, 95% CI -0.20 to 0.34) or vaginal (+0.11 log10 copies/swab, 95% CI -0.17 to 0.39) set point viral loads; S. haematobium infection was associated with lower cervical viral loads (-0.59 log10 copies/swab, 95% CI -1.11 to -0.06). CONCLUSIONS/SIGNIFICANCE: These results do not support the hypotheses that schistosome coinfection increases plasma or genital HIV-1 viral loads.

      2. Atovaquone-proguanil exposure in pregnancy and risk for adverse fetal and infant outcomes: A retrospective analysisexternal icon
        Gutman JR, Hall C, Khodr ZG, Bukowinski AT, Gumbs GR, Conlin AM, Wells NY, Tan KR.
        Travel Med Infect Dis. 2019 Nov 17:101519.
        BACKGROUND: Malaria in pregnancy can cause severe maternal and fetal complications. Chloroquine (CQ) and mefloquine (MQ) are recommended for chemoprophylaxis in pregnancy, but are not always suitable. Atovaquone-proguanil (AP) might be a viable option for malaria prevention in pregnancy, but more safety data are needed. METHODS: Data for pregnancies and live births among active duty military women, 2003-2014, from the Department of Defense Birth and Infant Health Research program were linked with pharmacy data to determine antimalarial exposure. Multivariable Cox and logistic regression models were used to assess the relationship of antimalarial exposure with fetal and infant outcomes, respectively. RESULTS: Among 198,164 pregnancies, 50 were exposed to AP, 156 to MQ, and 131 to CQ. Overall, 17.6% of unexposed pregnancies and 28.0%, 16.0%, and 6.1% of pregnancies exposed to AP, MQ, and CQ, respectively, ended in fetal loss (spontaneous abortion or stillbirth) (adjusted hazard ratios [aHR]=1.46, 95% confidence interval [CI] 0.87-2.46; aHR=1.06, 95% CI 0.72-1.57, and aHR=0.47, 95% CI 0.24-0.94, respectively). CONCLUSIONS: The small number of AP exposed pregnancies highlights the difficulty in assessing safety. While definitive conclusions are not possible, these data suggest further research of AP exposure in pregnancy and fetal loss is warranted. TWITTER LINE: More research on fetal loss following atovaquone-proguanil exposure in pregnancy is warranted.

      3. Guidance for using tafenoquine for prevention and antirelapse therapy for malaria – United States, 2019external icon
        Haston JC, Hwang J, Tan KR.
        MMWR Morb Mortal Wkly Rep. 2019 Nov 22;68(46):1062-1068.
        An estimated 219 million cases of malaria occurred worldwide in 2017, causing approximately 435,000 deaths (1). Malaria is caused by intraerythrocytic protozoa of the genus Plasmodium transmitted to humans through the bite of an infective Anopheles mosquito. Five Plasmodium species that regularly cause illness in humans are P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi (2). The parasite first develops in the liver before infecting red blood cells. Travelers to areas with endemic malaria can prevent malaria by taking chemoprophylaxis. However, most antimalarials do not kill the liver stages of the parasite, including hypnozoites that cause relapses of disease caused by P. vivax or P. ovale. Therefore, patients with these relapsing species must be treated with two medications: one for the acute infection, and another to treat the hypnozoites (antirelapse therapy). Until recently, primaquine was the only drug available worldwide to kill hypnozoites. Tafenoquine, a long-acting 8-aminoquinoline drug related to primaquine, was approved by the Food and Drug Administration (FDA) on July 20, 2018, for antirelapse therapy (Krintafel) and August 8, 2018, for chemoprophylaxis (Arakoda) (3,4). This report reviews evidence for the efficacy and safety of tafenoquine and provides CDC guidance for clinicians who prescribe chemoprophylaxis for travelers to areas with endemic malaria and treat malaria.

      4. A case of primary amebic meningoencephalitis caused by Naegleria fowleri in Bangladeshexternal icon
        Sazzad HM, Luby SP, Sejvar J, Rahman M, Gurley ES, Hill V, Murphy JL, Roy S, Cope JR, Ali IK.
        Parasitol Res. 2019 Nov 16.
        We present the first recognized case of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri in a 15-year-old male from Bangladesh. He performed daily nasal rinsing with untreated ground water and bathed in untreated ground water or river water, which likely exposed him to N. fowleri.

    • Reproductive Health
      1. Perinatal outcomes among young donor oocyte recipientsexternal icon
        Schwartz KM, Boulet SL, Kawwass JF, Kissin DM.
        Hum Reprod. 2019 Nov 21.
        STUDY QUESTION: Is the use of donor oocytes in women <35 years of age associated with an increased risk of adverse perinatal outcomes compared to use of autologous oocytes? SUMMARY ANSWER: Among fresh assisted reproductive technology (ART) cycles performed in women under age 35, donor oocyte use is associated with a higher risk of preterm birth, low birth weight and stillbirth (when zero embryos were cryopreserved) as compared to autologous oocytes. WHAT IS KNOWN ALREADY: Previous studies demonstrated elevated risk of poor perinatal outcomes with donor versus autologous oocytes during ART, primarily among older women. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study using data reported to Centers for Disease Control and Prevention’s National ART Surveillance System (NASS) during the period from 2010 to 2015 in order to best reflect advances in clinical practice. Approximately 98% of all US ART cycles are reported to NASS, and discrepancy rates were <6% for all fields evaluated in 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included all non-banking fresh and frozen ART cycles performed between 2010 and 2015 in women under age 35 using autologous or donor eggs. Cycles using cryopreserved eggs, donated embryos or a gestational carrier were excluded. Among fresh embryo transfer cycles, we calculated predicted marginal proportions to estimate the unadjusted and adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for the association between donor versus autologous oocyte use and stillbirth, spontaneous abortion, preterm delivery and low birth weight among singleton pregnancies or births. Stillbirth models were stratified by number of embryos cryopreserved. All models were adjusted for patient and treatment characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 71 720 singleton pregnancies occurring during 2010-2015, singletons resulting from donor oocytes were more likely to be preterm (15.6% versus 11.0%; aRRs 1.39: CI 1.20-1.61) and have low birth weight (11.8% versus 8.8%; aRRs 1.34; CI 1.16-1.55) than those resulting from autologous oocytes. With zero embryos cryopreserved, donor versus autologous oocyte use was associated with increased risk for stillbirth (2.1% versus 0.6%; aRRs 3.73; CI 1.96-7.11); no association with stillbirth was found when >/=1 embryo was cryopreserved (0.54% versus 0.56%; aRR 1.15; CI 0.59-2.25). LIMITATIONS, REASONS FOR CAUTION: The data come from a national surveillance system and is thus limited by the accuracy of the data entered by individual providers and clinics. There may be unmeasured differences between women using donor eggs versus their own eggs that could be contributing to the reported associations. Given the large sample size, statistically significant findings may not reflect clinically important variations. WIDER IMPLICATIONS OF THE FINDINGS: Risks of preterm birth, low birth weight and stillbirth among singleton pregnancies using donor oocytes were increased compared to those using autologous oocytes. Further study regarding the pathophysiology of the potentially increased risks among donor oocyte recipient pregnancy is warranted. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

      2. Whereas progress has been made on increasing access to comprehensive healthcare for individuals with intellectual and developmental disabilities (I/DD), disparities continue in health outcomes, including those related to the reproductive health of adolescent and adult women with I/DD. This review summarizes reproductive care considerations for adolescent and adult women with I/DD and current practices regarding the delivery of contraceptive services to these women. Forty-seven (47) articles based on research conducted in the US between 1999 and 2019 were selected for inclusion in the review. Primary themes discussed include (1) common reproductive health concerns for adolescent and adult women with I/DD, other than pregnancy prevention; (2) contraceptive methods and disability-related concerns; (3) informed consent and reproductive decision-making; and (4) provider knowledge and education. The management of menses and hormonal dysregulation were identified as concerns that providers encounter among patients with I/DD and their families. Disability-related concerns with regard to use of contraception in general and considerations regarding certain methods in particular include challenges with prescription adherence, physical effects of hormonal therapies, drug interactions for individuals with additional health conditions, and legal and ethical concerns involved with decision-making and consent. The results of this review also suggest that focused efforts in partnership with health care providers may be needed to address barriers that adolescent and adult women with I/DD face when trying to obtain quality reproductive health services and contraceptive guidance.

    • Substance Use and Abuse
      1. A review of network simulation models of hepatitis C virus and HIV among people who inject drugsexternal icon
        Bellerose M, Zhu L, Hagan LM, Thompson WW, Randall LM, Malyuta Y, Salomon JA, Linas BP.
        Int J Drug Policy. 2019 Nov 15:102580.
        Network modelling is a valuable tool for simulating hepatitis C virus (HCV) and HIV transmission among people who inject drugs (PWID) and assessing the potential impact of treatment and harm-reduction interventions. In this paper, we review literature on network simulation models, highlighting key structural considerations and questions that network models are well suited to address. We describe five approaches (Erdos-Renyi, Stochastic Block, Watts-Strogatz, Barabasi-Albert, and Exponential Random Graph Model) used to model partnership formation with emphasis on the strengths of each approach in simulating different features of real-world PWID networks. We also review two important structural considerations when designing or interpreting results from a network simulation study: (1) dynamic vs. static network and (2) injection only vs. both injection and sexual networks. Dynamic network simulations allow partnerships to evolve and disintegrate over time, capturing corresponding shifts in individual and population-level risk behaviour; however, their high level of complexity and reliance on difficult-to-observe data has driven others to develop static network models. Incorporating both sexual and injection partnerships increases model complexity and data demands, but more accurately represents HIV transmission between PWID and their sexual partners who may not also use drugs. Network models add the greatest value when used to investigate how leveraging network structure can maximize the effectiveness of health interventions and optimize investments. For example, network models have shown that features of a given network and epidemic influence whether the greatest community benefit would be achieved by allocating hepatitis C or HIV treatment randomly, versus to those with the most partners. They have also demonstrated the potential for syringe services and “buddy sharing” programs to reduce disease transmission.

      2. Characteristics of hospitalized and nonhospitalized patients in a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury – United States, November 2019external icon
        Chatham-Stephens K, Roguski K, Jang Y, Cho P, Jatlaoui TC, Kabbani S, Glidden E, Ussery EN, Trivers KF, Evans ME, King BA, Rose DA, Jones CM, Baldwin G, Delaney LJ, Briss P, Ritchey MD.
        MMWR Morb Mortal Wkly Rep. 2019 Nov 22;68(46):1076-1080.
        CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders are investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). As of November 13, 2019, 49 states, the District of Columbia, and two U.S. territories (Puerto Rico and U.S. Virgin Islands) have reported 2,172 EVALI cases to CDC, including 42 (1.9%) EVALI-associated deaths. To inform EVALI surveillance, including during the 2019-20 influenza season, case report information supplied by states for hospitalized and nonhospitalized patients with EVALI were analyzed using data collected as of November 5, 2019. Among 2,016 EVALI patients with available data on hospitalization status, 1,906 (95%) were hospitalized, and 110 (5%) were not hospitalized. Demographic characteristics of hospitalized and nonhospitalized patients were similar; most were male (68% of hospitalized versus 65% of nonhospitalized patients), and most were aged <35 years (78% of hospitalized versus 74% of nonhospitalized patients). These patients also reported similar use of tetrahydrocannabinol (THC)-containing products (83% of hospitalized versus 84% of nonhospitalized patients). Given the similarity between hospitalized and nonhospitalized EVALI patients, the potential for large numbers of respiratory infections during the emerging 2019-20 influenza season, and the potential difficulty in distinguishing EVALI from respiratory infections, CDC will no longer collect national data on nonhospitalized EVALI patients. Further collection of data on nonhospitalized patients will be at the discretion of individual state, local, and territorial health departments. Candidates for outpatient management of EVALI should have normal oxygen saturation (>/=95% while breathing room air), no respiratory distress, no comorbidities that might compromise pulmonary reserve, reliable access to care, strong social support systems, and should be able to ensure follow-up within 24-48 hours of initial evaluation and to seek medical care promptly if respiratory symptoms worsen. Health care providers should emphasize the importance of annual influenza vaccination for all persons aged >/=6 months, including persons who use e-cigarette, or vaping, products (2,3).

      3. Youth access to tobacco products in the United States, 2016-2018external icon
        Liu ST, Snyder K, Tynan MA, Wang TW.
        Tob Regul Sci. 2019 Nov;5(6):491-501.
        Objectives: In 2018, approximately 4.9 million US middle and high school students reported past 30-day use of any tobacco product. This study describes how and where youth obtained tobacco products and whether refusal of sale occurred during 2016-2018. Methods: Data from 3 annual waves (2016-2018) of the National Youth Tobacco Survey, a school-based survey of US youth in grades 6-12, were analyzed among current (past 30-day) tobacco product users aged 9 to 17 years. Results: During 2016-2018, youth tobacco product users most commonly obtained tobacco products from social sources. Although the percentage of users who reported buying tobacco products significantly decreased from 2016 to 2018 (2016: 15.6%; 2018: 11.4%), no significant differences in the prevalence of being refused sale were observed (2016: 24.7%; 2018: 25.5%). Conclusions: Whereas the number of youth users who report buying tobacco products has declined, sales of tobacco products to youth remain a public health concern, as only one in 4 youth who attempted to buy were refused sale in 2018. Monitoring youth tobacco product purchases, retailer compliance check inspections, and retailer penalties for sales to minors remain important for reducing youth access at retail sources.

      4. [No abstract]

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

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