Volume 12, Issue, 5 February 18, 2020

CDC Science Clips: Volume 12, Issue 5, February 18, 2020

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

  1. CDC Public Health Grand Rounds
    • Communicable Diseases - Measles
      1. National Update on Measles Cases and Outbreaks - United States, January 1-October 1, 2019
        Patel M, Lee AD, Clemmons NS, Redd SB, Poser S, Blog D, Zucker JR, Leung J, Link-Gelles R, Pham H, Arciuolo RJ, Rausch-Phung E, Bankamp B, Rota PA, Weinbaum CM, Gastanaduy PA.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 11;68(40):893-896.

      2. Spread of measles in Europe and implications for US travelersexternal icon
        Angelo KM, Gastanaduy PA, Walker AT, Patel M , Reef S, Lee CV, Nemhauser J.
        Pediatrics. 2019 ;144(1):e20190414.
        From January 2018 to June 2018, World Health Organization (WHO) European Region countries reported >41 000 measles cases, including 37 deaths, a record high since the 1990s. Low vaccination coverage in previous years is the biggest contributing factor to the increase in cases. The Ukraine reported the majority of cases, but France, Georgia, Greece, Italy, the Russian Federation, and Serbia also reported high case counts. Europe is the most common travel destination worldwide and is widely perceived as being without substantial infectious disease risks. For this reason, travelers may not consider the relevance of a pretravel health consultation, including vaccination, in their predeparture plans. Measles is highly contagious, and the record number of measles cases in the WHO European Region not only puts unvaccinated and inadequately vaccinated travelers at risk but also increases the risk for nontraveling US residents who come into close contact with returned travelers who are ill. The US Centers for Disease Control and Prevention encourage US travelers to be aware of measles virus transmission in Europe and receive all recommended vaccinations, including for measles, before traveling abroad. Health care providers must maintain a high degree of suspicion for measles among travelers returning from Europe or people with close contact with international travelers who present with a febrile rash illness. The current WHO European Region outbreak should serve to remind health care providers to stay current with the epidemiology of highly transmissible diseases, such as measles, through media, WHO, and Centers for Disease Control and Prevention reports and encourage measles vaccination for international travelers.

      3. Public health responses during measles outbreaks in elimination settings: Strategies and challengesexternal icon
        Gastanaduy P, Banerjee E, DeBolt C, Bravo-Alcántara P, Samad S, Pastor D, Rota P, Patel M, Crowcroft N, Durrheim D.
        Hum Vaccin Immunother. 2018 ;14(9):2222-2238.
        In late September 2016, the Americas became the first region in the world to have eliminated endemic transmission of measles virus. Several other countries have also verified measles elimination, and countries in all six World Health Organization regions have adopted measles elimination goals. The public health strategies used to respond to measles outbreaks in elimination settings are thus becoming relevant to more countries. This review highlights the strategies used to limit measles spread in elimination settings: (1) assembly of an outbreak control committee; (2) isolation of measles cases while infectious; (3) exclusion and quarantining of individuals without evidence of immunity; (4) vaccination of susceptible individuals; (5) use of immunoglobulin to prevent measles in exposed susceptible high-risk persons; (6) and maintaining laboratory proficiency for confirmation of measles. Deciding on the extent of containment efforts should be based on the expected benefit of reactive interventions, balanced against the logistical challenges in implementing them.

      4. Factors associated with measles transmission in the United States during the postelimination eraexternal icon
        Gastanaduy P, Funk S, Lopman B, Rota P, Gambhir M, Grenfell B, Paul P.
        JAMA pediatrics. 2019 ;174(1):56-62.
        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.

      5. Vaccination Coverage by Age 24 Months Among Children Born in 2015 and 2016 - National Immunization Survey-Child, United States, 2016-2018external icon
        Hill H, Singleton J, Yankey D, Elam-Evans L, Pingali SC, Kang Y.
        MMWR. Morbidity and mortality weekly report. 2019 ;68(41):913-918.
        The Advisory Committee on Immunization Practices (ACIP) recommends that children be vaccinated against 14 potentially serious illnesses during the first 24 months of life (1). CDC used data from the National Immunization Survey-Child (NIS-Child) to assess vaccination coverage with the recommended number of doses of each vaccine at the national, state, territorial, and selected local levels* among children born in 2015 and 2016. Coverage by age 24 months was at least 90% nationally for ≥3 doses of poliovirus vaccine, ≥1 dose of measles, mumps, and rubella vaccine (MMR), ≥3 doses of hepatitis B vaccine (HepB), and ≥1 dose of varicella vaccine, although MMR coverage was <90% in 20 states. Children were least likely to be up to date by age 24 months with ≥2 doses of influenza vaccine (56.6%). Only 1.3% of children born in 2015 and 2016 had received no vaccinations by the second birthday. Coverage was lower for uninsured children and for children insured by Medicaid than for those with private health insurance. Vaccination coverage can be increased by improving access to vaccine providers and eliminating missed opportunities to vaccinate children during health care visits. Increased use of local vaccination coverage data is needed to identify communities at higher risk for outbreaks of measles and other vaccine-preventable diseases.

      6. The Clinical Impact and Cost-effectiveness of Measles-Mumps-Rubella Vaccination to Prevent Measles Importations Among International Travelers From the United Statesexternal icon
        Hyle E, Fields N, Fiebelkorn A, Walker A, Gastanaduy P, Rao S, Ryan E, LaRocque R, Walensky R.
        Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2019 ;69(2):306-315.
        BACKGROUND: Measles importations and the subsequent spread from US travelers returning from abroad are responsible for most measles cases in the United States. Increasing measles-mumps-rubella (MMR) vaccination among departing US travelers could reduce the clinical impact and costs of measles in the United States. METHODS: We designed a decision tree to evaluate MMR vaccination at a pretravel health encounter (PHE), compared with no encounter. We derived input parameters from Global TravEpiNet data and literature. We quantified Riskexposure to measles while traveling and the average number of US-acquired cases and contacts due to a measles importation. In sensitivity analyses, we examined the impact of destination-specific Riskexposure, including hot spots with active measles outbreaks; the percentage of previously-unvaccinated travelers; and the percentage of travelers returning to US communities with heterogeneous MMR coverage. RESULTS: The no-encounter strategy projected 22 imported and 66 US-acquired measles cases, costing $14.8M per 10M travelers. The PHE strategy projected 15 imported and 35 US-acquired cases at $190.3M per 10M travelers. PHE was not cost effective for all international travelers (incremental cost-effectiveness ratio [ICER] $4.6M/measles case averted), but offered better value (ICER <$100 000/measles case averted) or was even cost saving for travelers to hot spots, especially if travelers were previously unvaccinated or returning to US communities with heterogeneous MMR coverage. CONCLUSIONS: PHEs that improve MMR vaccination among US international travelers could reduce measles cases, but are costly. The best value is for travelers with a high likelihood of measles exposure, especially if the travelers are previously unvaccinated or will return to US communities with heterogeneous MMR coverage.

      7. International Importations of Measles Virus into the United States During the Postelimination Era, 2001-2016external icon
        Lee A, Clemmons N, Patel M, Gastanaduy P.
        The Journal of infectious diseases. 2019 ;219(10):1616-1623.
        BACKGROUND: Although measles was declared eliminated from the United States in 2000, measles cases and outbreaks continue to occur, resulting from importations of the disease from countries where it remains endemic. METHODS: We describe the epidemiology of international importations of measles virus into the United States during the postelimination era. RESULTS: From 2001 to 2016, 553 imported measles cases were reported to the Centers for Disease Control and Prevention. A median of 28 importations occurred each year (range: 18-80). The median age of imported case-patients was 18 years (range: 3 months-75 years); 87% were unvaccinated or had an unknown vaccination status. US residents (as opposed to foreign visitors) accounted for 62% of imported measles cases. Overall, 62% of all imported case-patients reported travel to countries in the Western Pacific and European Regions of the World Health Organization during their exposure periods. The number of measles importations from specific countries was related to the incidence of measles in and the volume of travel to and from the source country. CONCLUSIONS: Our findings emphasize the importance of measles vaccination of US residents aged ≥6 months before international travel according to the Advisory Committee on Immunization Practices recommendations and supporting global measles elimination efforts.

  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. Policy Points Although preventable chronic conditions such as type 2 diabetes carry a significant cost and health burden, few lifestyle interventions have been scaled at a national policy level. The translation of the National Diabetes Prevention Program lifestyle intervention from research to a Medicare-covered service can serve as a model for national adoption of other interventions that have the potential to improve population health. The successful translation of the National Diabetes Prevention Program has depended on the collaboration of government agencies, academic researchers, community-based healthcare providers, payers, and other parties. CONTEXT: Many evidence-based health interventions never achieve national implementation. This article analyzes factors that supported the translation and national implementation of a lifestyle change intervention to prevent or delay type 2 diabetes in individuals with prediabetes. METHODS: We used the Knowledge to Action framework, which was developed to map how science is translated into effective health programs, to examine how the evidence-based intervention from the 2002 Diabetes Prevention Program trial was translated into the Centers for Disease Control and Prevention's large-scale National Diabetes Prevention Program, eventually resulting in payment for the lifestyle intervention as a Medicare-covered service. FINDINGS: Key findings of our analysis include the importance of a collaboration among researchers, policymakers, and payers to encourage early adopters; development of evidence-based, national standards to support widespread adoption of the intervention; and use of public input from community organizations to scale the intervention to a national level. CONCLUSIONS: This analysis offers timely lessons for other high-value, scalable interventions attempting to move beyond the evidence-gathering phase and into translation and institutionalization.

      2. Prevalence of overweight and obesity in US-bound refugees: 2009-2017external icon
        Davis D, Phares CR, Salas J, Scherrer J.
        J Immigr Minor Health. 2020 Jan 23.
        Refugees are an often understudied population and vulnerable to poor health outcomes. No large-scale analyses have evaluated the prevalence of overweight and obesity in US-bound refugees. Using data obtained from the Centers for Disease Control (CDC) Electronic Disease Notification system, we quantified the prevalence of overweight and obesity in adult US-bound refugees by nationality from 2009 through 2017. This repeated cross-sectional analysis used CDC data to quantify and examine body mass index (BMI) trends in US-bound adult refugees during 2009-2017. Utilizing data from an overseas medical exam required for all US-bound refugees, we determined BMI for 334,746 refugees >/= 18 years old who arrived in the United States during January 1, 2009-December 31, 2017. We calculated and compared the prevalence of overweight and obesity as well as changes in demographic characteristics (age, sex, and nationality) by year. Adjusted prevalence and prevalence ratios (APR) for yearly trends were assessed using a modified Poisson regression model with robust error variances. After adjusting for age, sex, and nationality, we observed a significant linear trend in the prevalence of overweight/obesity with an average annual relative percent increase of 3% for refugees entering the United States from 2009 through 2017 (APR = 1.031; 95% CI 1.029-1.033). The adjusted prevalence of overweight/obesity increased from 35.7% in 2009 to 44.7% in 2017. The prevalence of overweight and obesity in US-bound refugees increased steadily over the analysis period. Investigation into pre-migration and post-resettlement interventions is warranted.

      3. The pathogenesis of nodding syndromeexternal icon
        Johnson TP, Sejvar J, Nutman TB, Nath A.
        Annu Rev Pathol. 2020 Jan 24;15:395-417.
        Nodding syndrome is a rare, enigmatic form of pediatric epilepsy that has occurred in an epidemic fashion beginning in the early 2000s in geographically distinct regions of Africa. Despite extensive investigation, the etiology of nodding syndrome remains unclear, although much progress has been made in understanding the pathogenesis of the disease, as well as in treatment and prevention. Nodding syndrome is recognized as a defined disease entity, but it is likely one manifestation along a continuum of Onchocerca volvulus-associated neurological complications. This review examines the epidemiology of nodding syndrome and its association with environmental factors. It provides a critical analysis of the data that support or contradict the leading hypotheses of the etiologies underlying the pathogenesis of the syndrome. It also highlights the important progress made in treating and preventing this devastating neurological disease and prioritizes important areas for future research.

      4. An expanded agenda for the primary prevention of breast cancer: Charting a course for the futureexternal icon
        White MC, Kavanaugh-Lynch M, Davis-Patterson S, Buermeyer N.
        Int J Environ Res Public Health. 2020 Jan 22;17(3).
        Advances in breast cancer science, early detection, and treatment have resulted in improvements in breast cancer survival but not in breast cancer incidence. After skin cancer, breast cancer is the most common cancer diagnosis in the United States. Each year, nearly a quarter million U.S. women receive a breast cancer diagnosis, and the number continues to rise each year with the growth in the population of older women. Although much remains to be understood about breast cancer origins and prevention, action can be taken on the existing scientific knowledge to address the systemic factors that drive breast cancer risk at the population level. The California Breast Cancer Research Program funded a team at Breast Cancer Prevention Partners (BCPP) to convene leaders in advocacy, policy, and research related to breast cancer prevention from across the state of California. The objective was the development of a strategic plan to direct collective efforts toward specific and measurable objectives to reduce the incidence of breast cancer. The structured, innovative approach used by BCPP to integrate scientific evidence with community perspectives provides a model for other states to consider, to potentially change the future trajectory of breast cancer incidence in the United States.

    • Communicable Diseases
      1. Leprosy post-exposure prophylaxis with single-dose rifampicin: Toolkit for implementationexternal icon
        Barth-Jaeggi T, Cavaliero A, Aerts A, Anand S, Arif M, Ay SS, Aye TM, Banstola NL, Baskota R, Blaney D, Bonenberger M, Van Brakel W, Cross H, Das VK, Budiawan T, Fernando N, Gani Z, Greter H, Ignotti E, Kamara D, Kasang C, Komm B, Kumar A, Lay S, Mieras L, Mirza F, Mutayoba B, Njako B, Pakasi T, Richardus JH, Saunderson P, Smith CS, Staheli R, Suriyarachchi N, Shwe T, Tiwari A, Wijesinghe MS, Van Berkel J, Plaetse BV, Virmond M, Steinmann P.
        Leprosy Review. 2019 December;90(4):356-363.
        Objective: Leprosy post-exposure prophylaxis with single-dose rifampicin (SDRPEP) has proven effective and feasible, and is recommended by WHO since 2018. This SDR-PEP toolkit was developed through the experience of the leprosy postexposure prophylaxis (LPEP) programme. It has been designed to facilitate and standardise the implementation of contact tracing and SDR-PEP administration in regions and countries that start the intervention. Result(s): Four tools were developed, incorporating the current evidence for SDRPEP and the methods and learnings from the LPEP project in eight countries. (1) the SDR-PEP policy/advocacy PowerPoint slide deck which will help to inform policy makers about the evidence, practicalities and resources needed for SDR-PEP, (2) the SDR-PEP field implementation training PowerPoint slide deck to be used to train front line staff to implement contact tracing and PEP with SDR, (3) the SDR-PEP generic field guide which can be used as a basis to create a location specific field protocol for contact tracing and SDR-PEP serving as a reference for frontline field staff. Finally, (4) the SDR-PEP toolkit guide, summarising the different components of the toolkit and providing instructions on its optimal use. Conclusion(s): In response to interest expressed by countries to implement contact tracing and leprosy PEP with SDR in the light of the WHO recommendation of SDRPEP, this evidence-based, concrete yet flexible toolkit has been designed to serve national leprosy programme managers and support them with the practical means to translate policy into practice. The toolkit is freely accessible on the Infolep homepages and updated as required:

      2. Hepatitis C virus prevalence in 50 U.S. states and D.C. by sex, birth cohort, and race: 2013-2016external icon
        Bradley H, Hall EW, Rosenthal EM, Sullivan PS, Ryerson AB, Rosenberg ES.
        Hepatology Communications. 2020 .
        Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity and mortality, and more than 2 million adults in the United States are estimated to be currently infected. Reducing HCV burden will require an understanding of demographic disparities and targeted efforts to reduce prevalence in populations with disproportionate disease rates. We modeled state-level estimates of hepatitis C prevalence among U.S. adults by sex, birth cohort, and race during 2013-2016. National Health and Nutrition Examination Survey data were used in combination with state-level HCV-related and narcotic overdose-related mortality data from the National Vital Statistics System and estimates from external literature review on populations not sampled in the National Health and Nutrition Examination Survey. Nationally, estimated hepatitis C prevalence was 1.3% among males and 0.6% among females (prevalence ratio [PR] = 2.3). Among persons born during 1945 to 1969, prevalence was 1.6% compared with 0.5% among persons born after 1969 (PR = 3.2). Among persons born during 1945 to 1969, prevalence ranged from 0.7% in North Dakota to 3.6% in Oklahoma and 6.8% in the District of Columbia. Among persons born after 1969, prevalence was more than twice as high in Kentucky, New Mexico, Oklahoma, and West Virginia compared with the national average. Hepatitis C prevalence was 1.8% among non-Hispanic black persons and 0.8% among persons of other races (PR = 2.2), and the magnitude of this disparity varied widely across jurisdictions (PR range: 1.3-7.8). Overall, 23% of prevalent HCV infections occurred among non-Hispanic black persons, whereas 12% of the population was represented by this racial group. These estimates provide information on prevalent HCV infections that jurisdictions can use for understanding and monitoring local disease patterns and racial disparities in burden of disease.

      3. Improving HIV medical care engagement by attending to status disclosure and social supportexternal icon
        Carnes NA, Carey JW, Gelaude DJ, Denson DJ, Bessler PA.
        AIDS Care. 2020 Jan 28:1-7.
        Expeditious linkage and consistent engagement in medical care is important for people with HIV's (PWH) health. One theory on fostering linkage and engagement involves HIV status disclosure to mobilize social support. To assess disclosure and social support's association with linkage and engagement, we conducted a qualitative study sampling black and Latino men who have sex with men (MSM of color) in the U.S. Participants' narratives presented mixed results. For instance, several participants who reported delaying, inconsistent access, or detachment from care also reported disclosing for support purposes, yet sporadic engagement suggests that their disclosure or any subsequent social support have not assisted. The findings contribute to the literature that questions disclosure and social support's influence on care engagement, especially when decontextualized from circumstances and intentions. Our findings suggest the mechanics of disclosure and social support require planned implementation if intending to affect outcomes, especially among MSM of color. From the findings, we explore steps that may bolster interventions seeking to anchor medical care engagement.

      4. High-dose rifapentine with or without moxifloxacin for shortening treatment of pulmonary tuberculosis: Study protocol for TBTC study 31/ACTG A5349 phase 3 clinical trialexternal icon
        Dorman SE, Nahid P, Kurbatova EV, Goldberg SV, Bozeman L, Burman WJ, Chang KC, Chen M, Cotton M, Dooley KE, Engle M, Feng PJ, Fletcher CV, Ha P, Heilig CM, Johnson JL, Lessem E, Metchock B, Miro JM, Nhung NV, Pettit AC, Phillips PP, Podany AT, Purfield AE, Robergeau K, Samaneka W, Scott NA, Sizemore E, Vernon A, Weiner M, Swindells S, Chaisson RE.
        Contemp Clin Trials. 2020 Jan 22:105938.
        INTRODUCTION: Phase 2 clinical trials of tuberculosis treatment have shown that once-daily regimens in which rifampin is replaced by high dose rifapentine have potent antimicrobial activity that may be sufficient to shorten overall treatment duration. Herein we describe the design of an ongoing phase 3 clinical trial testing the hypothesis that once-daily regimens containing high dose rifapentine in combination with other anti-tuberculosis drugs administered for four months can achieve cure rates not worse than the conventional six-month treatment regimen. METHODS/DESIGN: S31/A5349 is a multicenter randomized controlled phase 3 non-inferiority trial that compares two four-month regimens with the standard six-month regimen for treating drug-susceptible pulmonary tuberculosis in HIV-negative and HIV-positive patients. Both of the four-month regimens contain high-dose rifapentine instead of rifampin, with ethambutol replaced by moxifloxacin in one regimen. All drugs are administered seven days per week, and under direct observation at least five days per week. The primary outcome is tuberculosis disease-free survival at twelve months after study treatment assignment. A total of 2500 participants will be randomized; this gives 90% power to show non-inferiority with a 6.6% margin of non-inferiority. DISCUSSION: This phase 3 trial formally tests the hypothesis that augmentation of rifamycin exposures can shorten tuberculosis treatment to four months. Trial design and standardized implementation optimize the likelihood of obtaining valid results. Results of this trial may have important implications for clinical management of tuberculosis at both individual and programmatic levels. TRIAL REGISTRATION: NCT02410772. Registered 8 April 2015,

      5. Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meetingexternal icon
        Driscoll AJ, Arshad SH, Bont L, Brunwasser SM, Cherian T, Englund JA, Fell DB, Hammitt LL, Hartert TV, Innis BL, Karron RA, Langley GE, Mulholland EK, Munywoki PK, Nair H, Ortiz JR, Savitz DA, Scheltema NM, Simoes EA, Smith PG, Were F, Zar HJ, Feikin DR.
        Vaccine. 2020 Jan 20.
        Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12-13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies.

      6. Identifying persons with human immunodeficiency virus (HIV) infection who are unaware of their status and linking them to care are critical steps in achieving viral suppression and reducing the risk for transmitting HIV (1). In 2017, 43% of new diagnoses of HIV infection were among persons who self-identify as blacks or African Americans (blacks) (2), who represent 13% of the U.S. population (3). Fewer blacks, compared with whites, were linked to HIV medical care within 90 days of diagnosis, retained in care, or virally suppressed (4). Ending the HIV Epidemic (EHE) is an initiative intended to reduce new HIV infections by 90% from 2020 to 2030 (5). EHE's Phase 1 is focused on 50 jurisdictions* that accounted for >50% of new diagnoses during 2016-2017 and seven states(dagger) with disproportionate HIV prevalence in rural areas (5). The purpose of this analysis was to examine HIV testing outcomes among blacks in high prevalence EHE jurisdictions, using CDC's 2017 National HIV Prevention Program Monitoring and Evaluation data. Blacks accounted for 43.2% of CDC-funded tests and 49.1% of new diagnoses of HIV infection. Seventy-nine percent of blacks with newly diagnosed HIV infection were linked to HIV medical care within 90 days (below the 2010 National HIV/AIDS Strategy goal of 85%), 71.4% interviewed for partner services, and 81.8% referred to prevention services. To achieve the goals of EHE, HIV prevention programs should focus on locally tailored evidence-based( section sign) testing strategies to enhance and overcome barriers for linkage to and retention in care and reduce onward HIV transmission and HIV-related disparities.

      7. Incident gonorrhoea and chlamydia among a prospective cohort of men who have sex with men in Kisumu, Kenyaexternal icon
        Otieno F, Ng'ety G, Okall D, Aketch C, Obondi E, Graham SM, Nyunya BO, Djomand G, Bailey RC, Mehta SD.
        Sex Transm Infect. 2020 Jan 23.
        OBJECTIVE: STIs disproportionately affect men who have sex with men (MSM) in sub-Saharan Africa. We identified factors associated with incident Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections among MSM in the Anza Mapema cohort study in Kisumu, Kenya. METHODS: We enrolled 711 MSM who underwent HIV testing and counselling, medical history and examination, and collection of demographic and behavioural information. They also provided urine and rectal swab specimens for CT and NG testing by qualitative PCR at baseline and at months 6 and 12. Separate multivariable Cox regression models identified factors associated with first incident urethral or rectal infection. RESULTS: Among the 619 men aged 18-54 years included in this analysis, there were 83 first incident urethral CT/NG infections (14.4 cases per 100 person-years (PY)) and 40 first incident rectal infections (6.84 cases per 100 PY), and an overall incidence of 18.0 cases per 100 PY (95% CI 14.8 to 21.8). Most urethral (84%) and rectal (81%) infections were asymptomatic. In the adjusted model, the risk of first incident urethral CT/NG decreased by 4% for each 1-year increase in age and was 41% lower for men who reported their partner used condom at last sexual encounter. Men who were HIV-positive had a 68% less risk of urogenital CT/NG compared with those who were negative. Men who reported being usually receptive or versatile as compared with usually insertive had an 81% increased risk of incident urogenital CT/NG. CONCLUSION: Our study demonstrated a high incidence of urethral CT/NG infection, with somewhat lower incidence of rectal CT/NG infection, despite repeated testing and treatment, highlighting the need for preventive interventions to decrease the burden of CT/NG among Kenyan MSM. Most infections were asymptomatic, and routine aetiological screening for STIs is recommended.

      8. Temporal changes in HIV transmission patterns among young men who have sex with men, United States, 2009-2016external icon
        Panneer N, France AM, Whiteside YO, Zhang T, Wertheim JO, Oster AM.
        J Acquir Immune Defic Syndr. 2020 Jan 17.
        BACKGROUND: In the United States (U.S.), young (aged 13-24 years) men who have sex with men (MSM) bear a disproportionate burden of HIV. Transmission among MSM has been found to be disassortative by age. METHODS: We analyzed HIV-1 pol sequences reported to the U.S. National HIV Surveillance System from MSM with HIV diagnosed during 2009-2016. Using an HIV genetic transmission network, we identified persons with closely related viruses (i.e., genetic distance </=1.5%) and used multivariable logistic regression to examine changes from 2009-2012 to 2013-2016 in proportions of MSM linked to young MSM who were > 5 years older or of the same race/ethnicity. RESULTS: Among 9,510 young MSM linked to another MSM with a closely related virus, 37% linked to an older MSM and 62% linked to a MSM of the same race/ethnicity. Comparing 2013-2016 with 2009-2012, we found increases in linkage of older MSM to young MSM, with the most substantial increases seen in Hispanic/Latinos aged 13-19 (adjusted prevalence ratio [APR]=1.31, 95% confidence interval [CI]=1.11-1.56) and blacks aged 13-19 (APR=1.23, CI=1.06-1.41) and 20-24 (APR=1.14, CI=1.02-1.28). In contrast, change in linkage patterns among racial/ethnic groups was unremarkable. CONCLUSIONS: We found evidence of increased age mixing among MSM with respect to HIV transmission over time, which coincides temporally with changes in partner-seeking behavior such as increased use of mobile applications. These findings indicate the importance of social factors on HIV sexual and transmission networks and suggest that prevention efforts need to effectively reach MSM of all ages.

      9. Willingness to take multidrug-resistant tuberculosis (MDR-TB) preventive therapy among adult and adolescent household contacts of MDR-TB index cases: An international multisite cross-sectional studyexternal icon
        Suryavanshi N, Murrill M, Gupta A, Hughes M, Hesseling A, Kim S, Naini L, Jones L, Smith B, Gupte N, Dawson R, Mave V, Meshram S, Mendoza-Ticona A, Sanchez J, Kumarasamy N, Comins K, Conradie F, Shenje J, Nerette Fontain S, Garcia-Prats A, Asmelash A, Nedsuwan S, Mohapi L, Lalloo U, Cristina Garcia Ferreira A, Okeyo E, Swindells S, Churchyard G, Shah NS.
        Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020 ;70(3):436-445.
        BACKGROUND: Household contacts (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB) are at high risk of infection and subsequent disease. There is limited evidence on the willingness of MDR-TB HHCs to take MDR-TB preventive therapy (MDR TPT) to decrease their risk of TB disease. METHODS: In this cross-sectional study of HHCs of MDR-TB and rifampicin-resistant tuberculosis (RR-TB) index cases from 16 clinical research sites in 8 countries, enrollees were interviewed to assess willingness to take a hypothetical, newly developed MDR TPT if offered. To identify factors associated with willingness to take MDR TPT, a marginal logistic model was fitted using generalized estimating equations to account for household-level clustering. RESULTS: From 278 MDR-TB/RR-TB index case households, 743 HHCs were enrolled; the median age of HHCs was 33 (interquartile range, 22-49) years, and 62% were women. HHC willingness to take hypothetical MDR TPT was high (79%) and remained high even with the potential for mild side effects (70%). Increased willingness was significantly associated with current employment or schooling (adjusted odds ratio [aOR], 1.83 [95% confidence interval {CI}, 1.07-3.13]), appropriate TB-related knowledge (aOR, 2.22 [95% CI, 1.23-3.99]), confidence in taking MDR TPT (aOR, 7.16 [95% CI, 3.33-15.42]), and being comfortable telling others about taking MDR TPT (aOR, 2.29 [95% CI, 1.29-4.06]). CONCLUSIONS: The high percentage of HHCs of MDR-TB/RR-TB index cases willing to take hypothetical MDR TPT provides important evidence for the potential uptake of effective MDR TPT when implemented. Identified HHC-level variables associated with willingness may inform education and counseling efforts to increase HHC confidence in and uptake of MDR TPT.

    • Disaster Control and Emergency Services
      1. A spatial and temporal investigation of medical surge in Dallas-Fort Worth during Hurricane Harvey, Texas 2017external icon
        Stephens W, Wilt GE, Lehnert EA, Molinari NM, LeBlanc TT.
        Disaster Med Public Health Prep. 2020 Jan 30:1-8.
        OBJECTIVE: When 2017 Hurricane Harvey struck the coastline of Texas on August 25, 2017, it resulted in 88 fatalities and more than US $125 billion in damage to infrastructure. The floods associated with the storm created a toxic mix of chemicals, sewage and other biohazards, and over 6 million cubic meters of garbage in Houston alone. The level of biohazard exposure and injuries from trauma among persons residing in affected areas was widespread and likely contributed to increases in emergency department (ED) visits in Houston and cities receiving hurricane evacuees. We investigated medical surge resulting from these evacuations in Dallas-Fort Worth (DFW) metroplex EDs. METHODS: We used data sourced from the North Texas Syndromic Surveillance Region 2/3 in ESSENCE to investigate ED visit surge following the storm in DFW hospitals because this area received evacuees from the 60 counties with disaster declarations due to the storm. We used the interrupted time series (ITS) analysis to estimate the magnitude and duration of the ED surge. ITS was applied to all ED visits in DFW and visits made by patients residing in any of the 60 counties with disaster declarations due to the storm. The DFW metropolitan statistical area included 55 hospitals. Time series analyses examined data from March 1, 2017-January 6, 2018 with focus on the storm impact period, August 14-September 15, 2017. Data from before, during, and after the storm were visualized spatially and temporally to characterize magnitude, duration, and spatial variation of medical surge attributable to Hurricane Harvey. RESULTS: During the study period overall, ED visits in the DFW area rose immediately by about 11% (95% CI: 9%, 13%), amounting to ~16 500 excess total visits before returning to the baseline on September 21, 2017. Visits by patients identified as residing in disaster declaration counties to DFW hospitals rose immediately by 127% (95% CI: 125%, 129%), amounting to 654 excess visits by September 29, 2017, when visits returned to the baseline. A spatial analysis revealed that evacuated patients were strongly clustered (Moran's I = 0.35, P < 0.0001) among 5 of the counties with disaster declarations in the 11-day window during the storm surge. CONCLUSIONS: The observed increase in ED visits in DFW due to Hurricane Harvey and ensuing evacuation was significant. Anticipating medical surge following large-scale hurricanes is critical for community preparedness planning. Coordinated planning across stakeholders is necessary to safeguard the population and for a skillful response to medical surge needs. Plans that address hurricane response, in particular, should have contingencies for support beyond the expected disaster areas.

    • Disease Reservoirs and Vectors
      1. Isolation of Angola-like Marburg virus from Egyptian rousette bats from West Africaexternal icon
        Amman BR, Bird BH, Bakarr IA, Bangura J, Schuh AJ, Johnny J, Sealy TK, Conteh I, Koroma AH, Foday I, Amara E, Bangura AA, Gbakima AA, Tremeau-Bravard A, Belaganahalli M, Dhanota J, Chow A, Ontiveros V, Gibson A, Turay J, Patel K, Graziano J, Bangura C, Kamanda ES, Osborne A, Saidu E, Musa J, Bangura D, Williams SM, Wadsworth R, Turay M, Edwin L, Mereweather-Thompson V, Kargbo D, Bairoh FV, Kanu M, Robert W, Lungai V, Guetiya Wadoum RE, Coomber M, Kanu O, Jambai A, Kamara SM, Taboy CH, Singh T, Mazet JA, Nichol ST, Goldstein T, Towner JS, Lebbie A.
        Nat Commun. 2020 Jan 24;11(1):510.
        Marburg virus (MARV) causes sporadic outbreaks of severe Marburg virus disease (MVD). Most MVD outbreaks originated in East Africa and field studies in East Africa, South Africa, Zambia, and Gabon identified the Egyptian rousette bat (ERB; Rousettus aegyptiacus) as a natural reservoir. However, the largest recorded MVD outbreak with the highest case-fatality ratio happened in 2005 in Angola, where direct spillover from bats was not shown. Here, collaborative studies by the Centers for Disease Control and Prevention, Njala University, University of California, Davis USAID-PREDICT, and the University of Makeni identify MARV circulating in ERBs in Sierra Leone. PCR, antibody and virus isolation data from 1755 bats of 42 species shows active MARV infection in approximately 2.5% of ERBs. Phylogenetic analysis identifies MARVs that are similar to the Angola strain. These results provide evidence of MARV circulation in West Africa and demonstrate the value of pathogen surveillance to identify previously undetected threats.

      2. Swine influenza A viruses and the tangled relationship with humansexternal icon
        Anderson TK, Chang J, Arendsee ZW, Venkatesh D, Souza CK, Kimble JB, Lewis NS, Davis CT, Vincent AL.
        Cold Spring Harb Perspect Med. 2020 Jan 27.
        Influenza A viruses (IAVs) are the causative agents of one of the most important viral respiratory diseases in pigs and humans. Human and swine IAV are prone to interspecies transmission, leading to regular incursions from human to pig and vice versa. This bidirectional transmission of IAV has heavily influenced the evolutionary history of IAV in both species. Transmission of distinct human seasonal lineages to pigs, followed by sustained within-host transmission and rapid adaptation and evolution, represent a considerable challenge for pig health and production. Consequently, although only subtypes of H1N1, H1N2, and H3N2 are endemic in swine around the world, extensive diversity can be found in the hemagglutinin (HA) and neuraminidase (NA) genes, as well as the remaining six genes. We review the complicated global epidemiology of IAV in swine and the inextricably entangled implications for public health and influenza pandemic planning.

    • Environmental Health
      1. Anhydrous ammonia chemical release - Lake County, Illinois, April 2019external icon
        Rispens JR, Jones SA, Clemmons NS, Ahmed S, Harduar-Morano L, Johnson MD, Edge C, Vyas A, Bourgikos E, Orr MF.
        MMWR. Morbidity and mortality weekly report. 2020 Jan 31;69(4):109-113.
        On April 25, 2019, a farm tractor towing two 2-ton ammonia tanks on a county road in Lake County, Illinois, experienced a mechanical failure that resulted in the release of anhydrous ammonia, a colorless, pungent, irritating gas that can cause severe respiratory and ocular damage (1). Approximately 80% of anhydrous ammonia produced in the United States is used as a fertilizer in agriculture (1). Eighty-three persons, including first responders, motorists, and neighborhood residents, were evaluated at area hospitals because of exposure to the gas. Two weeks after the release, the Agency for Toxic Substances and Disease Registry (ATSDR) and CDC's National Center for Environmental Health (NCEH) collaborated with the Lake County Health Department and the Illinois Department of Public Health on an investigation using ATSDR's Assessment of Chemical Exposures program to describe the release, review the emergency response, and determine health effects associated with the exposure. First responders, community residents, and hospital personnel reported communication challenges related to the nature of the gas release and effective protective measures. Among the 83 persons evaluated at six area hospitals for effects of the chemical release, 14 (17%) were hospitalized, including eight (10%) who were admitted to the intensive care unit (ICU), seven (8%) of whom required endotracheal intubation and mechanical ventilation; no deaths occurred. In addition, ICU health care providers experienced symptoms of secondary exposure. The National Institute for Occupational Safety and Health's Emergency Responder Health Monitoring and Surveillance Program has specific recommendations and tools to protect responders during all phases of a response (2). Hospitals also need to review institutional policies and procedures for chemical mass casualty events, including decontamination (3). Prompt and correct identification of hazardous material (hazmat) events, and clear communication among responding entities, including on-scene and hospital responders, is important to ensure effective response after a chemical release.

      2. Associations between select blood VOCs and hematological measures in NHANES 2005-2010external icon
        Vaughan Watson C, Naik S, Lewin M, Ragin-Wilson A, Irvin-Barnwell E.
        J Expo Sci Environ Epidemiol. 2020 Jan 27.
        Exposure to VOCs is linked to health effects ranging from asthma to cancer and to negative impacts on the hematopoietic system. We examined the association between select blood VOC concentrations and hematological measures in a representative sample of the U.S. population from NHANES cycles spanning the years 2005 to 2010. We used Cox regression to assess the association between complete blood count with five-part differential (CBC) parameters and seven select blood VOCs, while addressing low detection rates among VOCs. Tobacco smoke exposure was classified using serum cotinine levels. The not-smoke-exposed group had lower VOC levels for most analytes compared with the smoke-exposed. Correlations between benzene, toluene, ethylbenzene, and xylenes (BTEX) were moderate to strong. Statistical associations were found between benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS) and hematocrit, hemoglobin, and white blood cell count among the smoke-exposed. Among the not-smoke-exposed, there was an association between BTEX and platelet count. We considered benzene most likely to be associated with higher levels of CBC concentrations. Our findings suggest VOC levels currently found in the general U.S. population are associated with changes in hematological measures, and smoking could be a contributor.

    • Health Disparities
      1. Disparities in cessation behaviors between Hispanic and non-Hispanic white adult cigarette smokers in the United States, 2000-2015external icon
        Babb S, Malarcher A, Asman K, Johns M, Caraballo R, VanFrank B, Garrett B.
        Prev Chronic Dis. 2020 Jan 30;17:E10.
        INTRODUCTION: Hispanic adults make up a growing share of US adult smokers, and smoking is a major preventable cause of disease and death among Hispanic adults. No previous study has compared trends in smoking cessation behaviors among Hispanic adults and non-Hispanic white adults over time. We examined trends in cessation behaviors among Hispanic and non-Hispanic white adult cigarette smokers during 2000-2015. METHODS: Using self-reported data from the National Health Interview Survey, we compared trends in quit attempts, receipt of advice to quit from a health professional, and use of cessation treatment (counseling and/or medication) among Hispanic and non-Hispanic white adult smokers. We also assessed these behaviors among 4 Hispanic subgroups. We conducted analyses in 2018-2019. RESULTS: Past-year quit attempts increased during 2000-2015 among both non-Hispanic white and Hispanic smokers, with no significant differences between these groups. Receiving advice to quit increased significantly among non-Hispanic white adults but did not increase significantly among Hispanic adults. Cessation treatment use increased among both non-Hispanic white and Hispanic adults. Throughout 2000-2015, the prevalence of receiving advice to quit and using cessation treatments was lower among Hispanic adults than non-Hispanic white adults. In 2015, a higher proportion of Hispanic than non-Hispanic white smokers visited a health care provider without receiving advice to quit. CONCLUSION: Hispanic adult smokers are less likely to receive advice to quit and to use proven cessation treatments than non-Hispanic white smokers, and this pattern persisted over time. Culturally competent educational initiatives directed at both providers and Hispanic communities could help eliminate this marked and persistent disparity.

    • Health Economics
      1. Cost comparison between 2 responses to hepatitis A virus incidents in restaurant food handlers - New York City, 2015 and 2017external icon
        Baum SE, Reddy V, Vora NM, Balter S, Daskalakis D, Barbot O, Misener M, Rakeman J, Rojas J, Starr D, Waechter H, Zucker J, Lee D.
        J Public Health Manag Pract. 2020 Mar/Apr;26(2):176-179.
        CONTEXT: While the New York City Department of Health and Mental Hygiene (DOHMH) can use agency-wide emergency activation to respond to a hepatitis A virus-infected food handler, there is a need to identify alternative responses that conserve scarce resources. OBJECTIVE: To compare the costs incurred by DOHMH of responding to a hepatitis A case in restaurant food handlers using an agency-wide emergency activation (2015) versus the cost of collaborating with a private network of urgent care clinics (2017). DESIGN: We partially evaluate the costs incurred by DOHMH of responding to a hepatitis A case in a restaurant food handler using agency-wide emergency activation (2015) with the cost of collaborating with a private network of urgent care clinics (2017) estimated for a scenario in which DOHMH incurred the retail cost of services rendered. RESULTS: Costs incurred by DOHMH for emergency activation were $65 831 ($238 per restaurant employee evaluated) of which DOHMH personnel services accounted for 85% ($55 854). Costs of collaboration would have totaled $50 914 ($253 per restaurant employee evaluated) of which personnel services accounted for 6% ($3146). CONCLUSIONS: Accounting for incident size, collaborating with the clinic network was more expensive than agency-wide emergency activation, though required fewer DOHMH personnel services.

    • Immunity and Immunization
      1. For lifetime protection against diphtheria and tetanus, the World Health Organization (WHO) recommends six doses of diphtheria and tetanus containing vaccines. Td (reduced diphtheria toxoid, >/=2-5 IU) vaccines are currently licensed for ages 7 years and older, but use of Td vaccine for ages 4 years and older would have advantages for immunization programs in many low- and middle-income countries. For this reason, WHO convened an expert consultation to review the currently available evidence for the use of Td vaccine from 4 to 7 years of age which concluded: (1) no relevant biological difference in immune response in the relevant age group compared with children over 7 years of age; (2) adequate seroprotection in several studies with Td vaccine in the 4-7 age group and many studies using combination vaccines; (3) durable and protective response of at least 9-11 years duration in several longitudinal and modelling studies, (4) less reactogenicity compared with use of full-dose diphtheria vaccine, potentially improving the vaccination experience; and (5) adequate control of diphtheria in several countries using Td-containing combination vaccines in 4-7 year old children. On this basis, the experts concluded that from a programmatic perspective, Td vaccine given in ages 4-7 years, as a second booster dose in a six-dose series, would provide adequate protection against diphtheria and tetanus and recommended steps to include this change in age extension listed in the package insert.

      2. INTRODUCTION: Japanese encephalitis (JE) is a rare but potentially severe disease among travelers. JE vaccine in the United States costs $500-$600 for a 2-dose series and is safe and effective but rare serious adverse events can occur. Our survey investigated likelihood of vaccine receipt for travel. METHODS: An electronically-administered survey was conducted among U.S. adults. Participants were presented a hypothetical scenario on travel to a JE-endemic country and JE vaccine characteristics and responded on likelihood of vaccination. RESULTS: Overall, 6384 (59%) of 10,904 persons completed the questions. Population estimates indicated 32% would be likely and 42% were unlikely to be vaccinated, and 26% were unsure. Among those likely to get vaccinated, important factors were disease risk and severity, and vaccine safety. Among those unlikely, cost, disease risk, and possibility of serious side effects ranked highest. CONCLUSIONS: There is population heterogeneity in perception of JE disease risk and value of vaccination.

      3. Survey of influenza vaccine knowledge, attitudes, and beliefs among pregnant women in the 2016-17 seasonexternal icon
        King JP, Hanson KE, Donahue JG, Glanz JM, Klein NP, Naleway AL, DeStefano F, Weintraub E, Belongia EA.
        Vaccine. 2020 Jan 25.
        OBJECTIVES: Influenza vaccination coverage among pregnant women in the United States is suboptimal. We surveyed women who were pregnant during the 2016-17 influenza season to assess knowledge and attitudes regarding influenza vaccination. METHODS: We identified and sampled pregnant women to include approximately equal numbers of vaccinated and unvaccinated women from strata defined by vaccination status and trimester from four integrated health systems in the Vaccine Safety Datalink (VSD). Potential participants were contacted via mail and telephone to complete a standardized survey. Characteristics and responses of women vaccinated and unvaccinated during pregnancy were compared. RESULTS: The survey was completed by 510 (48%) of 1062 contacted women; 500 were included in the analysis. Vaccine receipt while pregnant was associated with primigravida status (p = 0.02), college degree (p = 0.01), employment in health care (p < 0.01), and history of routine annual influenza vaccination (p < 0.01). Among 330 vaccinated women, the primary reasons for vaccination included protection of self and baby from influenza (n = 233, 71%), and medical professional recommendation (n = 46, 14%). Multiple reasons were given for nonvaccination, but concern about 'negative effects' was cited most often (n = 44, 29%). Vaccinated women were significantly more likely to believe that influenza vaccines are safe and effective, and to recognize the potential for harm from influenza infection. Nearly all women reported receiving at least one influenza vaccination recommendation from a healthcare provider. CONCLUSIONS: Vaccinated pregnant women were more likely to receive routine annual influenza vaccine compared to those not vaccinated. Recommendations by obstetric providers should be supplemented with efforts to encourage women of childbearing age to receive annual vaccination.

      4. The science of vaccine safety: Summary of meeting at Wellcome Trustexternal icon
        Plotkin SA, Offit PA, DeStefano F, Larson HJ, Arora NK, Zuber PL, Fombonne E, Sejvar J, Lambert PH, Hviid A, Halsey N, Garcon N, Peden K, Pollard AJ, Markowitz LE, Glanz J.
        Vaccine. 2020 Jan 24.
        Vaccines are everywhere hugely successful but are also under attack. The reason for the latter is the perception by some people that vaccines are unsafe. However that may be, vaccine safety, life any other scientific subject, must be constantly studied. It was from this point of view that a meeting was organized at the Wellcome Trust in London in May 2019 to assess some aspects of vaccine safety as subjects for scientific study. The objective of the meeting was to assess what is known beyond reasonable doubt and conversely what areas need additional studies. Although the meeting could not cover all aspects of vaccine safety science, many of the most important issues were addressed by a group of about 30 experts to determine what is already known and what additional studies are merited to assess the safety of the vaccines currently in use. The meeting began with reviews of the current situation in different parts of the world, followed by reviews of specific controversial areas, including the incidence of certain conditions after vaccination and the safety of certain vaccine components. Lastly, information about the human papillomavirus vaccine was considered because its safety has been particularly challenged by vaccine opponents. The following is a summary of the meeting findings. In addition to this summary, the meeting organizers will explore opportunities to perform studies that would enlarge knowledge of vaccine safety.

      5. Maternal vaccination in Argentina: Tetanus, diphtheria, and acellular pertussis vaccine effectiveness during pregnancy in preventing pertussis in infants <2 months of ageexternal icon
        Romanin V, Acosta AM, Juarez MD, Briere E, Sanchez SM, Cordoba BL, Sevilla ME, Lucion MF, Urrutia A, Sagradini S, Skoff TH, Vizzotti C.
        Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020 ;70(3):380-387.
        BACKGROUND: In 2011, Argentina experienced its highest pertussis incidence and mortality rates of the last decade; 60% of deaths were among infants aged <2 months. In response, a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine was recommended for all pregnant women at ≥20 weeks of gestation. Although recent studies suggest that maternal Tdap vaccination is effective at preventing infant disease, no data have come from low- or middle-income countries, nor from ones using whole-cell pertussis vaccines for primary immunization. METHODS: We conducted a matched case-control evaluation to assess the effectiveness of maternal Tdap vaccination in preventing pertussis among infants aged <2 months in Argentina. Pertussis case patients identified from September 2012 to March 2016 at 6 hospital sites and confirmed by polymerase chain reaction testing were included. Five randomly selected controls were matched to each case patient by hospital site and mother's health district. We used multivariable conditional logistic regression to calculate odds ratios (ORs). Vaccine effectiveness (VE) was estimated as (1 - OR) × 100%. RESULTS: Seventy-one case patients and 300 controls were included in the analysis. Forty-nine percent of case patients and 78% of controls had mothers who were vaccinated during pregnancy. Overall Tdap VE was estimated at 80.7% (95% confidence interval, 52.1%-92.2%). We found similar VE whether Tdap was administered during the second or third trimester. CONCLUSIONS: Tdap vaccination during pregnancy is effective in preventing pertussis in infants aged <2 months in Argentina, with similar effectiveness whether administered during the second or third trimester of pregnancy.

    • Injury and Violence
      1. An examination of 4 questions assessing self-reported concussions among high school students participating in team sportsexternal icon
        DePadilla L, Miller GF, Jones SE.
        J Public Health Manag Pract. 2020 Mar/Apr;26(2):E23-e27.
        OBJECTIVE: Current prevalence estimates of youth sports-related concussions are inconsistent because of variation in methodology and potentially unreported concussions. METHODS: In 2013, Connecticut, Ohio, and Utah each added different questions that assessed self-reported concussions to the Youth Risk Behavior Survey. Two questions referenced recognition of a concussion by the student, 1 referenced identification by a doctor, and 1 referenced suspicion by a coach. Chi-square analyses were used to identify whether there was an association between demographic characteristics and the concussion questions among high school students who played on at least 1 sports team. RESULTS: The percentage of students who reported concussions ranged from 17.6% to 20.1%. CONCLUSIONS: These estimates are higher than rates of concussions diagnosed in emergency departments or reported by athletic trainers but were similar across the 4 questions. The field would benefit from a better understanding of the impact of question wording and format on estimates of concussion prevalence.

      2. Characteristics of ride share services for older adults in the United Statesexternal icon
        Freund K, Bayne A, Beck L, Siegfried A, Warren J, Nadel T, Natarajan A.
        J Safety Res. 2020 ;72:9-19.
        Introduction: Safe and accessible transportation options are important for older adults health, safety, mobility, and independence. Ride share services may promote older adult health and well-being. This is the first study that describes ride share services available to older adults (65+ years) in the United States, including factors that may affect use of services. Methods: We analyzed secondary data from two research and administrative databases provided by ITNAmerica, a national non-profit transportation service for older adults: ITNRides, which tracks information on older adults who used ITN in 29 locations across the United States from 1996 to 2019, and Rides in Sight, the largest national data source on ride share services for older adults. We conducted a literature review, and telephone interviews with nine key informants representing ride share services, referral services, and other organizations. We offer a conceptual framework describing factors that may affect older adults use of ride share services. Results: This study identified 917 non-profit ride share services and eleven for-profit ride share services available for older adults in the United States as of August 2018. Services varied by corporate structure, location, use of technology, and business model. The majority of non-profit services served primarily older adults, while the for-profit services served primarily younger adults. Riders from one multi-site non-profit service had a median age of 82. Use of ride share services is affected by individual needs and preferences; social conditions; and business and policy factors. Conclusion: Ride share services may offer a promising alternative to driving for older adults and may help to address negative health consequences associated with driving cessation. Practical applications: These findings may help policy makers, practitioners, and other stakeholders understand older adults needs related to use of ride share services in order to offer solutions that prioritize public health and safety.

      3. Reducing the number of children entering foster care: Effects of state earned income tax creditsexternal icon
        Rostad WL, Ports KA, Tang S, Klevens J.
        Child Maltreat. 2020 Jan 24:1077559519900922.
        Foster care caseloads, an indicator of child maltreatment, are increasing. Children living in poverty are significantly more likely to be reported to the child welfare system and are overrepresented in foster care. Thus, it is critical to identify prevention strategies that can stem the flow of foster care entries, particularly among populations at higher risk. We used variations in the adoption and refund status of state-level Earned Income Tax Credit (EITC), a socioeconomic policy intended to reduce poverty, to examine their effect on foster care entry rates. Fixed-effects models, accounting for year- and state-fixed effects, demonstrated that a refundable EITC was associated with an 11% decrease in foster care entries compared to states without a state-level EITC after controlling for child poverty rate, racial/ethnic composition, education, and unemployment. Policies that strengthen economic supports for families may prevent child maltreatment and reduce foster care entries and associated costs.

      4. The contemporary public health model for injury and violence prevention is a four-step process, which has been difficult to fully actualize in real-world contexts. This difficulty results from challenges in bridging science to practice and developing and applying population-level approaches. Prevention programmes and policies are embedded within and impacted by a range of system-level factors, which must be considered and actively managed when addressing complex public health challenges involving multiple sectors and stakeholders. To address these concerns, a systemic approach to population-level injury and violence prevention is being developed and explored by the Division of Analysis, Research, and Practice Integration in the National Center for Injury Prevention and Control at the Centers for Disease Control and Prevention. This article makes the case for and provides a high-level overview of this systemic approach, its various components, and how it is being applied in one governmental unit. Published 2020. This article is a U.S. Government work and is in the public domain in the USA

      5. Syndromic surveillance of suicidal ideation and self-directed violence - United States, January 2017-December 2018external icon
        Zwald ML, Holland KM, Annor FB, Kite-Powell A, Sumner SA, Bowen DA, Vivolo-Kantor AM, Stone DM, Crosby AE.
        MMWR. Morbidity and mortality weekly report. 2020 Jan 31;69(4):103-108.
        Suicide is a growing public health problem in the United States, claiming approximately 47,000 lives in 2017 (1). However, deaths from suicide represent only a small part of a larger problem because each year millions of persons experience suicidal ideation and engage in suicidal and nonsuicidal self-directed violence, both risk factors for suicide (2). Emergency departments (EDs) are an important setting for monitoring these events in near real time (3-5). From 2001 to 2016, ED visit rates for nonfatal self-harm increased 42% among persons aged >/=10 years (1). Using data from CDC's National Syndromic Surveillance Program (NSSP), ED visits for suicidal ideation, self-directed violence, or both among persons aged >/=10 years during January 2017-December 2018 were examined by sex, age group, and U.S. region. During the 24-month period, the rate of ED visits for suicidal ideation, self-directed violence, or both increased 25.5% overall, with an average increase of 1.2% per month. Suicide prevention requires comprehensive and multisectoral approaches to addressing risk at personal, relationship, community, and societal levels. ED syndromic surveillance data can provide timely trend information and can support more targeted and prompt public health investigation and response. CDC's Preventing Suicide: A Technical Package of Policy, Programs, and Practices includes tailored suicide prevention strategies for health care settings (6).

    • Laboratory Sciences
      1. Inhalation of printer-emitted particles impairs cardiac conduction, hemodynamics, and autonomic regulation and induces arrhythmia and electrical remodeling in ratsexternal icon
        Carll AP, Salatini R, Pirela SV, Wang Y, Xie Z, Lorkiewicz P, Naeem N, Qian Y, Castranova V, Godleski JJ, Demokritou P.
        Part Fibre Toxicol. 2020 Jan 29;17(1):7.
        BACKGROUND: Using engineered nanomaterial-based toners, laser printers generate aerosols with alarming levels of nanoparticles that bear high bioactivity and potential health risks. Yet, the cardiac impacts of printer-emitted particles (PEPs) are unknown. Inhalation of particulate matter (PM) promotes cardiovascular morbidity and mortality, and ultra-fine particulates (< 0.1 mum aerodynamic diameter) may bear toxicity unique from larger particles. Toxicological studies suggest that PM impairs left ventricular (LV) performance; however, such investigations have heretofore required animal restraint, anesthesia, or ex vivo preparations that can confound physiologic endpoints and/or prohibit LV mechanical assessments during exposure. To assess the acute and chronic effects of PEPs on cardiac physiology, male Sprague Dawley rats were exposed to PEPs (21 days, 5 h/day) while monitoring LV pressure (LVP) and electrocardiogram (ECG) via conscious telemetry, analyzing LVP and heart rate variability (HRV) in four-day increments from exposure days 1 to 21, as well as ECG and baroreflex sensitivity. At 2, 35, and 70 days after PEPs exposure ceased, rats received stress tests. RESULTS: On day 21 of exposure, PEPs significantly (P < 0.05 vs. Air) increased LV end systolic pressure (LVESP, + 18 mmHg) and rate-pressure-product (+ 19%), and decreased HRV indicating sympathetic dominance (root means squared of successive differences [RMSSD], - 21%). Overall, PEPs decreased LV ejection time (- 9%), relaxation time (- 3%), tau (- 5%), RMSSD (- 21%), and P-wave duration (- 9%). PEPs increased QTc interval (+ 5%) and low:high frequency HRV (+ 24%; all P < 0.05 vs. Air), while tending to decrease baroreflex sensitivity and contractility index (- 15% and - 3%, P < 0.10 vs. Air). Relative to Air, at both 2 and 35 days after PEPs, ventricular arrhythmias increased, and at 70 days post-exposure LVESP increased. PEPs impaired ventricular repolarization at 2 and 35 days post-exposure, but only during stress tests. At 72 days post-exposure, PEPs increased urinary dopamine 5-fold and protein expression of ventricular repolarizing channels, Kv1.5, Kv4.2, and Kv7.1, by 50%. CONCLUSIONS: Our findings suggest exposure to PEPs increases cardiovascular risk by augmenting sympathetic influence, impairing ventricular performance and repolarization, and inducing hypertension and arrhythmia. PEPs may present significant health risks through adverse cardiovascular effects, especially in occupational settings, among susceptible individuals, and with long-term exposure.

      2. Performance evaluation of four point-of-care HIV tests using unprocessed specimensexternal icon
        Chavez PR, Bradley HM, Wesolowski LG, Violette LR, Katz DA, Niemann LA, McMahan VM, McDougal S, Cornelius-Hudson AM, Ethridge SF, Stekler JD, Delaney KP.
        J Clin Virol. 2020 Jan 16;124:104282.
        BACKGROUND: The performance of recently approved point-of-care (POC) HIV tests should be assessed using unprocessed specimens. OBJECTIVE: To evaluate the sensitivity and specificity of four POC HIV tests using whole blood (WB) and two using oral fluid (OF) among persons recruited from health clinics in Seattle, Washington, during September 2015-September 2017. STUDY DESIGN: Participants were tested with the POC tests, additional plasma and serum were collected for laboratory testing, and participant- reported use of antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP) was recorded. Participants testing negative on all tests could reenroll every 90 days. Specimens from persons previously diagnosed with HIV infection as well as from those who were newly diagnosed during the study were included in the sensitivity estimate. Sensitivity and specificity were calculated based on HIV status determined by laboratory testing. RESULTS: Of 1,256 visits, 179 were from persons with HIV infection; 120 of these were taking ART. Among 1,077 visits from participants not diagnosed with HIV, PrEP use was reported at 155 (14.4%) visits. Sensitivity was similar among POC WB tests (95.53%-97.21%; p>0.05). Among participants on ART, sensitivity was lower for the same test performed on OF compared to WB (p<0.003). Specificity was high for all tests (99.44%- 100.00%); we did not detect specificity differences with PrEP use. CONCLUSIONS: These POC tests displayed relatively high sensitivity and specificity using unprocessed specimens, suggesting their effectiveness in identifying HIV infections whenever laboratory-based testing is not feasible. Nonetheless, clients with recent risk should retest to rule out the possibility of a false-negative result.

      3. Molecular epidemiology of norovirus outbreaks in Argentina, 2013-2018external icon
        Degiuseppe JI, Barclay L, Gomes KA, Costantini V, Vinje J, Stupka JA.
        J Med Virol. 2020 Jan 25.
        Noroviruses are a leading cause of endemic and epidemic acute gastroenteritis in all age groups. However, in Latin America there are limited and updated data regarding circulating genotypes. The aim of this study was to assess the prevalence and genetic diversity of norovirus outbreaks in Argentina from 2013-2018. Stool samples from 29 AGE outbreaks were available for viral testing. Norovirus was detected in samples from 18 (62.1%) outbreaks (2 GI and 16 GII). Both GI outbreaks were typed as GI.6[P11] whereas 10 different GII genotypes were detected, in which GII.4 viruses were the most frequently detected (29.4%, associated with GII.P31 and GII.P16) followed by GII.1[P33] and GII.6[P7] (17.6% each). Like GII.4 viruses, GII.2 viruses were also detected in association with different polymerases (GII.P2 and GII.P16). Our findings underscore the importance of dual RdRp-VP1 typing since recombinant strains with new polymerase sequences emerge frequently suggesting a possible role in improved fitness of these viruses. This study represents the most recent multi-year assessment of the molecular epidemiology of norovirus strains associated with AGE outbreaks in Argentina. Molecular surveillance of norovirus has to be considered to monitor possible changes in dominant genotypes which may assist to inform the formulation of future vaccines. This article is protected by copyright. All rights reserved.

      4. Difficult-to-detect Staphylococcus aureus: mecA-positive isolates associated with oxacillin and cefoxitin false-susceptible resultsexternal icon
        Gargis AS, Yoo BB, Lonsway DR, Anderson K, Campbell D, Ewing T, Lawsin A, Machado MJ, Yamamoto N, Halpin AL, Lutgring JD, Karlsson M, Rasheed JK, Elkins CA.
        J Clin Microbiol. 2020 Jan 29.
        In August of 2018, the United States Food and Drug Administration (FDA) announced a Class I recall associated with a methicillin-resistant Staphylococcus aureus (MRSA) Safety Alert.

      5. Predicting dissolution and transformation of inhaled nanoparticles in the lung using abiotic flow cells: The case of barium sulfateexternal icon
        Keller JG, Graham UM, Koltermann-Jully J, Gelein R, Ma-Hock L, Landsiedel R, Wiemann M, Oberdorster G, Elder A, Wohlleben W.
        Sci Rep. 2020 ;10(1):458-458.
        Barium sulfate (BaSO(4)) was considered to be poorly-soluble and of low toxicity, but BaSO(4) NM-220 showed a surprisingly short retention after intratracheal instillation in rat lungs, and incorporation of Ba within the bones. Here we show that static abiotic dissolution cannot rationalize this result, whereas two dynamic abiotic dissolution systems (one flow-through and one flow-by) indicated 50% dissolution after 5 to 6 days at non-saturating conditions regardless of flow orientation, which is close to the in vivo half-time of 9.6 days. Non-equilibrium conditions were thus essential to simulate in vivo biodissolution. Instead of shrinking from 32 nm to 23 nm (to match the mass loss to ions), TEM scans of particles retrieved from flow-cells showed an increase to 40 nm. Such transformation suggested either material transport through interfacial contact or Ostwald ripening at super-saturating conditions and was also observed in vivo inside macrophages by high-resolution TEM following 12 months inhalation exposure. The abiotic flow cells thus adequately predicted the overall pulmonary biopersistence of the particles that was mediated by non-equilibrium dissolution and recrystallization. The present methodology for dissolution and transformation fills a high priority gap in nanomaterial hazard assessment and is proposed for the implementation of grouping and read-across by dissolution rates.

      6. Comparative analysis of lung and blood transcriptomes in mice exposed to multi-walled carbon nanotubesexternal icon
        Khaliullin TO, Yanamala N, Newman MS, Kisin ER, Fatkhutdinova LM, Shvedova AA.
        Toxicol Appl Pharmacol. 2020 Jan 21:114898.
        Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) causes inflammation, fibroproliferation, immunotoxicity, and systemic responses in rodents. However, the search for representative biomarkers of exposure is an ongoing endeavor. Whole blood gene expression profiling is a promising new approach for the identification of novel disease biomarkers. We asked if the whole blood transcriptome reflects pathology-specific changes in lung gene expression caused by MWCNT. To answer this question, we performed mRNA sequencing analysis of the whole blood and lung in mice administered MWCNT or vehicle solution via pharyngeal aspiration and sacrificed 56days later. The pattern of lung mRNA expression as determined using Ingenuity Pathway Analysis (IPA) was indicative of continued inflammation, immune cell trafficking, phagocytosis, and adaptive immune responses. Simultaneously, innate immunity-related transcripts (Plunc, Bpifb1, Reg3g) and cancer-related pathways were downregulated. IPA analysis of the differentially expressed genes in the whole blood suggested increased hematopoiesis, predicted activation of cancer/tumor development pathways, and atopy. There were several common upregulated genes between whole blood and lungs, important for adaptive immune responses: Cxcr1, Cd72, Sharpin, and Slc11a1. Trim24, important for TH2 cell effector function, was downregulated in both datasets. Hla-dqa1 mRNA was upregulated in the lungs and downregulated in the blood, as was Lilrb4, which controls the reactivity of immune response. "Cancer" disease category had opposing activation status in the two datasets, while the only commonality was "hypersensitivity". Transcriptome changes occurring in the lungs did not produce a completely replicable pattern in whole blood; however, specific systemic responses may be shared between transcriptomic profiles.

      7. Identification and pilot evaluation of salivary peptides from Anopheles albimanus as biomarkers for bite exposure and malaria infection in Colombiaexternal icon
        Londono-Renteria B, Drame PM, Montiel J, Vasquez AM, Tobon-Castano A, Taylor M, Vizcaino L, Lenhart AA.
        Int J Mol Sci. 2020 Jan 21;21(3).
        Insect saliva induces significant antibody responses associated with the intensity of exposure to bites and the risk of disease in humans. Several salivary biomarkers have been characterized to determine exposure intensity to Old World Anopheles mosquito species. However, new tools are needed to quantify the intensity of human exposure to Anopheles bites and understand the risk of malaria in low-transmission areas in the Americas. To address this need, we conducted proteomic and bioinformatic analyses of immunogenic candidate proteins present in the saliva of uninfected Anopheles albimanus from two separate colonies-one originating from Central America (STECLA strain) and one originating from South America (Cartagena strain). A ~65 kDa band was identified by IgG antibodies in serum samples from healthy volunteers living in a malaria endemic area in Colombia, and a total of five peptides were designed from the sequences of two immunogenic candidate proteins that were shared by both strains. ELISA-based testing of human IgG antibody levels against the peptides revealed that the transferrin-derived peptides, TRANS-P1, TRANS-P2 and a salivary peroxidase peptide (PEROX-P3) were able to distinguish between malaria-infected and uninfected groups. Interestingly, IgG antibody levels against PEROX-P3 were significantly lower in people that have never experienced malaria, suggesting that it may be a good marker for mosquito bite exposure in naive populations such as travelers and deployed military personnel. In addition, the strength of the differences in the IgG levels against the peptides varied according to location, suggesting that the peptides may able to detect differences in intensities of bite exposure according to the mosquito population density. Thus, the An. albimanus salivary peptides TRANS-P1, TRANS-P2, and PEROX-P3 are promising biomarkers that could be exploited in a quantitative immunoassay for determination of human-vector contact and calculation of disease risk.

      8. Could HIV-1 RNA be an option as the second step in the HIV diagnostic algorithm?external icon
        Masciotra S, Luo W, Rossetti R, Smith T, Ethridge S, Delaney KP, Wesolowski LG, Owen SM.
        Sex Transm Dis. 2020 Jan 21.
        BACKGROUND: There is benefit to early HIV-1 diagnosis and treatment, but there is no FDA-approved quantitative assay with a diagnostic claim. We compared the performance of the Hologic Aptima HIV-1 Quant (APT-Quant) and Aptima HIV-1 Qual (APT-Qual) assays for diagnostic use and the performance of a diagnostic algorithm consisting of Bio-Rad BioPlex 2200 HIV Ag-Ab assay (BPC) followed by APT-Quant (two-test) compare to BPC followed by Geenius HIV-1/2 supplemental assay (Geenius) with reflex to APT-Qual (three-test). METHODS: 524 plasma, which included 419 longitudinal specimens from HIV-1 seroconverters (78 were after initiating antiretroviral therapy (ART)) and 105 from ART-naive persons with established HIV-1 infections, were used to evaluate APT-Quant performance for diagnostic use. Specimens from 200 HIV-negative persons were used to measure specificity. For the algorithm comparison, BPC-reactive specimens were evaluated with the two-test or three-test algorithm. McNemar's test was used to compare performance. RESULTS: APT-Quant detected more samples early in infection compared with APT-Qual. APT-Quant specificity was 99.8%. Before ART initiation, the algorithms performed similarly among samples from different stages of infection. After ART initiation, the three-test algorithm performed significantly better (p=0.0233). CONCLUSIONS: APT-Quant has excellent performance for diagnostic use. The two-test algorithm works well in ART-naive samples, but its performance decreases after the IgG response is elicited and with ART-induced suppressed viremia. Providing confirmation and VL with one test result could be advantageous for patient care. However, additional factors and challenges associated with the implementation of this two-test algorithm such as cost, specimen type and collection need further evaluation.

      9. Neck musculoskeletal model generation through anthropometric scalingexternal icon
        Roos PE, Vasavada A, Zheng L, Zhou X.
        PLoS One. 2020 ;15(1):e0219954.
        A new methodology was developed to quickly generate whole body models with detailed neck musculoskeletal architecture that are properly scaled in terms of anthropometry and muscle strength. This method was implemented in an anthropometric model generation software that allows users to interactively generate any new male or female musculoskeletal models with adjustment of anthropometric parameters (such as height, weight, neck circumference, and neck length) without the need of subject-specific motion capture or medical images. 50th percentile male and female models were developed based on the 2012 US Army Anthropometric Survey (ANSUR II) database and optimized with a novel bilevel optimization method to have strengths comparable to experimentally measured values in the literature. Other percentile models (ranging from the 1st to 99th percentile) were generated based on anthropometric scaling of the 50th percentile models and compared. The resultant models are reasonably accurate in terms of both musculoskeletal geometry and neck strength, demonstrating the effectiveness of the developed methodology for interactive neck model generation with anthropometric scaling.

      10. Recommendations for the nomenclature of enteroviruses and rhinovirusesexternal icon
        Simmonds P, Gorbalenya AE, Harvala H, Hovi T, Knowles NJ, Lindberg AM, Oberste MS, Palmenberg AC, Reuter G, Skern T, Tapparel C, Wolthers KC, Woo PC, Zell R.
        Arch Virol. 2020 Jan 25.
        Enteroviruses (EVs) and rhinoviruses (RVs) are significant pathogens of humans and are the subject of intensive clinical and epidemiological research and public health measures, notably in the eradication of poliovirus and in the investigation and control of emerging pathogenic EV types worldwide. EVs and RVs are highly diverse in their antigenic properties, tissue tropism, disease associations and evolutionary relationships, but the latter often conflict with previously developed biologically defined terms, such as "coxsackieviruses", "polioviruses" and "echoviruses", which were used before their genetic interrelationships were understood. This has created widespread formatting problems and inconsistencies in the nomenclature for EV and RV types and species in the literature and public databases. As members of the International Committee for Taxonomy of Viruses (ICTV) Picornaviridae Study Group, we describe the correct use of taxon names for these viruses and have produced a series of recommendations for the nomenclature of EV and RV types and their abbreviations. We believe their adoption will promote greater clarity and consistency in the terminology used in the scientific and medical literature. The recommendations will additionally provide a useful reference guide for journals, other publications and public databases seeking to use standardised terms for the growing multitude of enteroviruses and rhinoviruses described worldwide.

      11. An isothermal, multiplex amplification assay for detection and genotyping of human papillomaviruses in formalin-fixed, paraffin-embedded tissuesexternal icon
        Tang YW, Lozano L, Chen X, Querec TD, Katabi N, Moreno-Docon A, Wang H, Fix D, De Brot L, McMillen TA, Yoon JY, Torroba A, Wang Y, Unger ER, Park KJ.
        J Mol Diagn. 2020 Jan 21.
        Rapid and accurate identification of human papillomavirus (HPV) is important for both clinical management and population screening. We performed analytic validation of Atila AmpFire Multiplex HPV assays on formalin-fixed, paraffin-embedded (FFPE) cervix/vulva and oropharynx diagnostic tissue samples. The AmpFire assay incorporates a novel isothermal multiplex amplification coupled with real-time fluorescent detection to detect and genotype 15 high-risk (HR) HPV genotypes. Limits of detection determined by plasmids cloned with HPV genotype-specific sequences were 2 copies/reaction for HPV16, HPV18, and some HR HPV genotypes, and 20 copies/reaction for the remaining HR HPV genotypes. The performance of the AmpFire assays in clinical samples was evaluated using 214 FFPE specimens. The AmpFire assay failed in one clinical specimen for an invalid rate of 0.5%. The AmpFire assay detected HPV in clinical samples with positive percent agreements of 100.0% for HPV16, 100.0% for HPV18, and 94.7% for non-16/18 HR-HPV, and 100% negative percent agreements for HPV16, HPV18, and non-16/18 HR-HPV. Qualitative detection agreement was obtained in the reproducibility study. In summary, the Atila AmpFire HPV assay demonstrated excellent analytic sensitivity and specificity for detection and genotyping of 15 HR HPV genotypes. Assay parameters of simple specimen processing, small sample size requirement, rapid turnaround time, and being near instrument-free render it well suited for HPV detection and genotyping in FFPE specimens.

      12. Quality control of multiplex antibody detection in samples from large-scale surveys: the example of malaria in Haitiexternal icon
        van den Hoogen LL, Presume J, Romilus I, Mondelus G, Elisme T, Sepulveda N, Stresman G, Druetz T, Ashton RA, Joseph V, Eisele TP, Hamre KE, Chang MA, Lemoine JF, Tetteh KK, Boncy J, Existe A, Drakeley C, Rogier E.
        Sci Rep. 2020 Jan 24;10(1):1135.
        Measuring antimalarial antibodies can estimate transmission in a population. To compare outputs, standardized laboratory testing is required. Here we describe the in-country establishment and quality control (QC) of a multiplex bead assay (MBA) for three sero-surveys in Haiti. Total IgG data against 21 antigens were collected for 32,758 participants. Titration curves of hyperimmune sera were included on assay plates, assay signals underwent 5-parameter regression, and inspection of the median and interquartile range (IQR) for the y-inflection point was used to determine assay precision. The medians and IQRs were similar for Surveys 1 and 2 for most antigens, while the IQRs increased for some antigens in Survey 3. Levey-Jennings charts for selected antigens provided a pass/fail criterion for each assay plate and, of 387 assay plates, 13 (3.4%) were repeated. Individual samples failed if IgG binding to the generic glutathione-S-transferase protein was observed, with 659 (2.0%) samples failing. An additional 455 (1.4%) observations failed due to low bead numbers (<20/analyte). The final dataset included 609,438 anti-malaria IgG data points from 32,099 participants; 96.6% of all potential data points if no QC failures had occurred. The MBA can be deployed with high-throughput data collection and low inter-plate variability while ensuring data quality.

      13. Invasiveness of the Yersinia pestis ail protein contributes to host dissemination in pneumonic and oral plagueexternal icon
        Zhang Y, Ying X, He Y, Jiang L, Zhang S, Bartra SS, Plano GV, Klena JD, Skurnik M, Chen H, Cai H, Chen T.
        Microb Pathog. 2020 Jan 24:103993.
        Yersinia pestis, a Gram-negative bacterium, is the etiologic agent of plague. A hallmark of Y. pestis infection is the organism's ability to rapidly disseminate through an animal host. Y. pestis expresses the outer membrane protein, Ail (Attachment invasion locus), which is associated with host invasion and serum resistance. However, whether Ail plays a role in host dissemination remains unclear. In this study, C57BL/6J mice were challenged with a defined Y. pestis strain, KimD27, or an isogenic ail-deleted mutant derived from KimD27 via metacarpal paw pad inoculation, nasal drops, orogastric infection, or tail vein injection to mimic bubonic, pneumonic, oral, or septicemic plague, respectively. Our results showed that ail-deleted Y. pestis KimD27 lost the ability to invade host cells, leading to failed host dissemination in the pneumonic and oral plague models but not in the bubonic or septicemic plague models, which do not require invasiveness. Therefore, this study demonstrated that whether Ail plays a role in Y. pestis pathogenesis depends on the infection route.

      14. For more than 20 years, researchers have used laboratory mice lacking type I or both type I and II interferon (IFN) responses to study high-containment viruses that cause hemorrhagic fevers (HF) in humans. With the exception of Rift Valley fever virus, agents that cause viral HF in humans, such as Ebola and Lassa virus, do not cause disease in mature immunocompetent mice. In contrast, IFN-deficient mice typically develop severe or fatal disease when inoculated with these agents. The sensitivity of IFN-deficient mice to disease has led to their widespread use in biocontainment laboratories to assess the efficacy of novel vaccines against HF viruses, often without considering whether adaptive immune responses in IFN-deficient mice accurately mirror those in immunocompetent humans. Failure to recognize these questions may lead to inappropriate expectations of the predictive value of mouse experiments. In two invited articles, we investigate these questions. The present article reviews the use of IFN-deficient mice for assessing novel vaccines against HF viruses, including Ebola, Lassa, Crimean-Congo hemorrhagic fever and Rift Valley fever viruses. A companion paper examines the general question of how the lack of IFN signaling may affect adaptive immune responses and the outcome of vaccine studies in mice.

    • Maternal and Child Health
      1. Rationale and design of CH STRONG: Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinGexternal icon
        Farr SL, Klewer SE, Nembhard WN, Alter C, Downing KF, Andrews JG, Collins RT, Glidewell J, Benavides A, Goudie A, Riehle-Colarusso T, Overman L, Riser AP, Oster ME.
        Am Heart J. 2020 Jan 9;221:106-113.
        Studies of outcomes among adults with congenital heart defects (CHDs) have focused on those receiving cardiac care, limiting generalizability. The Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG (CH STRONG) will assess comorbidities, health care utilization, quality of life, and social and educational outcomes from a US population-based sample of young adults living with CHD. METHODS: Individuals with CHD born between 1980 and 1997 were identified using active, population-based birth defects surveillance systems from 3 US locations (Arkansas [AR]; Arizona [AZ]; and Atlanta, Georgia [GA]) linked to death records. Individuals with current contact information responded to mailed survey materials during 2016 to 2019. Respondents and nonrespondents were compared using chi(2) tests. RESULTS: Sites obtained contact information for 74.6% of the 9,312 eligible individuals alive at recruitment. Of those, 1,656 returned surveys, either online (18.1%) or via paper (81.9%), for a response rate of 23.9% (AR: 18.3%; AZ: 30.7%; Atlanta, GA: 28.0%; P value < .01). For 20.0% of respondents, a proxy completed the survey, with 63.9% reporting that the individual with CHD was mentally unable. Among respondents and nonrespondents, respectively, sex (female: 54.0% and 47.3%), maternal race/ethnicity (non-Hispanic white: 74.3% and 63.0%), CHD severity (severe: 33.8% and 27.9%), and noncardiac congenital anomalies (34.8% and 38.9%) differed significantly (P value < .01); birth year (1991-1997: 56.0% and 57.5%) and presence of Down syndrome (9.2% and 8.9%) did not differ. CONCLUSIONS: CH STRONG will provide the first multisite, population-based findings on long-term outcomes among the growing population of US adults with CHD.

      2. Wandering among preschool children with and without autism spectrum disorderexternal icon
        Wiggins LD, DiGuiseppi C, Schieve L, Moody E, Soke G, Giarelli E, Levy S.
        J Dev Behav Pediatr. 2020 Jan 22.
        OBJECTIVES: (1) Report the occurrence of wandering, or leaving a supervised space, among children with confirmed autism spectrum disorder (ASD), other developmental delay (DD) with a previous but unconfirmed ASD diagnosis (DDprevASD), DD without a previous ASD diagnosis, and a population comparison group (POP) at an age when wandering is no longer expected and (2) explore whether ASD status is associated with wandering independent of behavioral, developmental, and maternal factors. METHOD: Parents and children aged 4 to 5 years enrolled in the Study to Explore Early Development Phase-1+2. All children were screened for ASD symptoms upon enrollment. Those with ASD symptoms and/or a previous ASD diagnosis received the Mullen Scales of Early Learning (MSEL) to determine their developmental level and 2 ASD diagnostic tests to determine their ASD status. All other children were evaluated with the MSEL alone. Mothers completed the Child Behavior Checklist/1(1/2)-5, which includes an item on whether the child wanders away (categorized as at least sometimes true vs not true) and items assessing behavior problems. RESULTS: Children with ASD (N = 1195) were significantly more likely to wander than children classified as DDprevASD (N = 230), DD (N = 1199), or POP (N = 1272) (60.4%, 41.3%, 22.3%, and 12.4%, respectively, p < 0.01). ASD status, very low developmental level, and affective, anxiety, attention, and oppositional problems were each independently associated with wandering behavior. CONCLUSION: Wandering is significantly more common among children with ASD and those with behavioral and developmental problems compared with other children. These findings can be used to increase the awareness of wandering among children with atypical development.

    • Mining
      1. The purpose of this study is to explore how the geochemical and petrographic components of coal may impact its physical properties and how these correlate with a history of reportable dynamic failure in coal mines. Dynamic failure events, also termed bumps, bounces, or bursts, are the explosive failures of rock in a mining environment. These events occur suddenly and often with no warning, resulting in worker injury up to and including fatality in greater than 60% of reportable cases through the Mine Safety and Health Administration (MSHA). A database of variables was compiled using publicly available datasets, which includes compositional geographic, strength, and Hardgrove grindability index (HGI) data. Results indicated that bumping coals were less mature, lower in carbon, higher in oxygen, softer, and less well cleated than coals that did not bump. High liptinite content was found to correlate with higher average uniaxial compressive strength (UCS) values. However, no clear and direct correlation between UCS and dynamic failure status was observed. The findings of this study established that differences existed between coals that had versus had not experienced reportable dynamic failure accidents. These differences were inherent to the coal itself and were independent of mining-induced risk factors. Results further illuminated how compositional attribute of coal influenced physical properties and began to clarify potential links between geochemistry and dynamic failure status. Only through the better understanding of risk can more effective mitigating strategies be enacted.

    • Occupational Safety and Health
      1. Recent increases in deaths in the United States from synthetic opioids such as fentanyl and fentanyl analogues (fentanyls) have raised concerns about possible occupational exposures to these potent agents. Medicolegal death investigators and autopsy suite staff might perform job tasks involving exposure to fentanyls. The potential for exposure to fentanyls among medicolegal death investigators and autopsy technicians at a state medical examiner's office was evaluated through review of caseload characteristics, injury and illness logs, and procedures and policies and discussions with management and employee representatives. The evaluation showed that this medical examiner's office had low potential for work-related exposure to fentanyls; its standard operating procedures and personal protective equipment requirements should reduce the potential for occupational exposure. Medicolegal death investigation agencies can develop and implement guidance to control exposures and provide workforce education and training to reduce the potential for work-related exposure to fentanyls.

      2. Eliminating take-home exposures: Recognizing the role of occupational health and safety in broader community healthexternal icon
        Kalweit A, Herrick RF, Flynn MA, Spengler JD, Berko JK, Levy JI, Ceballos DM.
        Ann Work Expo Health. 2020 Jan 29.
        Toxic contaminants inadvertently brought from the workplace to the home, known as take-home or paraoccupational exposures, have often been framed as a problem that arises due to unsanitary worker behavior. This review article conceptualizes take-home exposures as a public health hazard by (i) investigating the history of take-home contaminants and how they have been studied, (ii) arguing that an ecosocial view of the problem is essential for effective prevention, (iii) summarizing key structural vulnerabilities that lead populations to be at risk, and (iv) discussing future research and prevention effort needs. This article reframes take-home exposures as one of many chronic pathways that contributes to persistent health disparities among workers, their families, and communities. Including the role of work in community health will increase the comprehensiveness of prevention efforts for contaminants such as lead and pesticides that contribute to environmental disparities.

      3. Medicare claims paid by the Federal Black Lung Benefits Program: US Medicare beneficiaries, 1999 to 2016external icon
        Kurth L, Casey M, Schleiff P, Halldin C, Mazurek J, Blackley D.
        J Occup Environ Med. 2019 ;61(12):e510-e515.
        OBJECTIVE: To establish the burden of totally disabling respiratory impairment among coal miners, we identified the healthcare utilization and cost for Medicare claims where the Federal Black Lung Program (FBLP) was the primary payer. METHODS: We extracted FBLP claims from 1999 to 2016 institutional Medicare data along with beneficiary, comorbidity, and claim cost information. Healthcare utilization was evaluated and compared to the 2016 Medicare population. RESULTS: The FBLP was the primary payer on 75,690 claims from 19,700 beneficiaries and paid an increasing percentage of the total paid to providers annually. Claims decreased from 1999 to 2016 but cost per claim increased. Beneficiaries were hospitalized and visited the ER for respiratory and cardiovascular conditions. CONCLUSIONS: Medicare beneficiaries with FBLP primary payer claims have higher healthcare utilization and comorbidities compared with Medicare enrollees, indicative of increased financial and healthcare burden.

    • Occupational Safety and Health - Mining
      1. Geotechnical mapping, rock mass characterization, and inspections of underground excavations are critical to ensuring that excavation geometry and ground support design are appropriate for stable conditions. A lack of access, poor timing, or hazardous conditions are all factors that can prohibit engineering personnel from collecting high-quality data in the field. Advances in unmanned aerial vehicles (UAV) and portable sensor technology now allow engineering personnel to remotely capture data from underground workings that can be used for developing designs, generating inputs for analyses, and making more informed decisions. Ground falls are a source of many accidents in the underground environment, and they are the focus of many geotechnical investigations and analyses. In this study, the authors investigated how portable UAV-mounted thermal and multispectral imagers could be used to detect and quantify adverse geological discontinuities in hard rock masses that are structurally controlled. Multiple thermal, multispectral, RGB (red, green, and blue), and LiDAR (light detection and ranging) data sets were captured from 5 flights in sub-level open stopes at the Barrick Golden Sunlight Mine in the state of Montana in the western United States of America. Using off-the-shelf software, the thermal, RGB, and multispectral images were processed to create individual three-dimensional point clouds and meshes, which were georeferenced using the LiDAR data. Discontinuities identified in the three-dimensional point clouds and meshes were mapped using tools found in the freeware CloudCompare. One of the thermal models identified wedges that had developed in the crown pillar of an open stope, and 4 of the multispectral models contained enough detail for mapping individual discontinuities. The results of this investigation indicate that these portable imagers are viable tools that can be used to aid engineering personnel in identifying and mapping adverse geological discontinuities and unique rock mass composition. The techniques for capturing, processing, and interpreting thermal and multispectral imagery captured in underground excavations are described in this paper and can be used as the basis for future investigations at individual underground sites.

    • Public Health Leadership and Management
      1. OBJECTIVES: To characterize agreement between senior governmental public health staff and their subordinates concerning drivers for staff turnover, and skill importance and ability. DESIGN: Data were combined from 2 national surveys conducted in 2017; one was a nationally representative, individual-level survey of public health workers, and one was an individual-level survey of their leadership. SETTING: State health agencies. PARTICIPANTS: Respondents who held scientific, nonsupervisory positions at state health agency central offices (n = 3606) were matched with leadership (n = 193) who provided programmatic area oversight. MAIN OUTCOME MEASURES: Drivers of turnover and training needs are the primary outcomes examined in this article. RESULTS: Leaders and their staff agreed on the main 2 drivers of turnover (low salary and lack of opportunities for advancement), but discordance was observed for other major drivers of turnover. Substantial discordance was observed between leaders and their staff in terms of perceived staff proficiency with selected skills. CONCLUSIONS: This multilevel assessment of workplace perceptions offers evidence around training needs and drivers of turnover in state health agencies. Although staff and leaders agree on some major drivers of turnover, other potential reasons for leaving cited by staff, and the difference in perceptions of skills, can help target job satisfaction, training, and retention efforts in state health agencies.

    • Substance Use and Abuse
      1. Biomarkers of exposure among adult smokeless tobacco users in the population assessment of Tobacco and Health Study (Wave 1, 2013-14)external icon
        Cheng YC, Reyes-Guzman CM, Christensen CH, Rostron BL, Edwards KC, Wang L, Feng J, Jarrett JM, Ward CD, Xia B, Kimmel HL, Conway K, Leggett C, Taylor K, Lawrence C, Niaura R, Travers MJ, Hyland A, Hecht SS, Hatsukami DK, Goniewicz ML, Borek N, Blount BC, van Bemmel DM.
        Cancer Epidemiol Biomarkers Prev. 2020 Jan 27.
        BACKGROUND: Monitoring population-level toxicant exposures from smokeless tobacco (SLT) use is important for assessing population health risks due to product use. In this study, we assessed tobacco biomarkers of exposure (BOEs) among SLT users from the Wave 1 (2013-14) of the Population Assessment of Tobacco and Health (PATH) Study. METHODS: Urinary biospecimens were collected from adults aged 18 and older. Biomarkers of nicotine, tobacco-specific nitrosamines (TSNAs), polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), metals, and inorganic arsenic were analyzed and reported among exclusive current established SLT users in comparison to exclusive current established cigarette smokers, dual SLT and cigarette users, and never tobacco users. RESULTS: In general, SLT users (n=448) have significantly higher concentrations of biomarkers of exposure to nicotine, TSNAs and PAHs compared to never tobacco users; significant dose-response relationships between frequency of SLT use and biomarker concentrations were also reported among exclusive SLT daily users. Exclusive SLT daily users have higher geometric mean concentrations of total nicotine equivalent-2 (TNE2) and TSNAs than exclusive cigarette daily smokers. In contrast, geometric mean concentrations of PAHs and VOCs were substantially lower among exclusive SLT daily users than exclusive cigarette daily smokers. CONCLUSIONS: Our study produced a comprehensive assessment of SLT product use and 52 biomarkers of tobacco exposure. Compared to cigarette smokers, SLT users experience greater concentrations of some tobacco toxicants, including nicotine and TSNAs. IMPACT: Our data add information on the risk assessment of exposure to SLT-related toxicants. High levels of harmful constituents in SLT remain a health concern.

      2. PhenX: Host: Biobehavioral measures for tobacco regulatory researchexternal icon
        Giovino GA, Swan GE, Blount B, O'Malley S, Brown DC, Hendershot TP.
        Tob Control. 2020 Jan;29(Suppl 1):s13-s19.
        A working group (WG) of experts from diverse fields related to nicotine and tobacco addiction was constituted to identify constructs and measures for the PhenX (Phenotypes and eXposures) Tobacco Regulatory Research (TRR) Host: Biobehavioral Collection with potential relevance to users of both conventional and newer tobacco products. This paper describes the methods and results the WG used to identify, select, approve and place measures in the PhenX TRR Collection. The WG recognised 13 constructs of importance to guide their categorisation of measures already in the PhenX Toolkit ('complementary measures') and to identify novel or improved measures of special relevance to tobacco regulatory science. In addition to the 22 complementary measures of relevance to tobacco use already in the PhenX Toolkit, the WG identified and recommended nine additional Host: Biobehavioral measures characterising the use, exposure and health outcomes of tobacco products for application to TRR. Of these, five were self-administered or interviewer-administered measures: amount, type and frequency of recent tobacco use; flavor preference in e-cigarette users (adult and youth); pregnancy status and tobacco use; pregnancy status-mother and baby health and withdrawal from tobacco use. The remaining four measures were laboratory-based: cotinine in serum, expired carbon monoxide, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in urine and cue reactivity. Although a number of validated tools are now available in the Host: Biobehavioral Collection, several gaps were identified, including a need to develop and test the identified measures in adolescent samples and to develop or identify measures of nicotine dependence, tolerance and withdrawal associated with newer non-combusted tobacco products.

      3. Adverse childhood experiences increase risk for prescription opioid misuseexternal icon
        Merrick MT, Ford DC, Haegerich TM, Simon T.
        J Prim Prev. 2020 Jan 28.
        The United States is in the midst of an opioid overdose epidemic, with a significant portion of the burden associated with prescription opioids. In response, the CDC released a Guideline for Prescribing Opioids for Chronic Pain, which promotes access to treatment for opioid use disorder. Decades of research have linked childhood adversity to negative health and risk behavior outcomes, including substance misuse. Our present study builds upon this work to examine the relationship between adverse childhood experiences (ACEs) and prescription opioid misuse. We compiled data from the Behavioral Risk Factor Surveillance System implemented by Montana and Florida in 2010 and 2011, respectively. Logistic regressions (run in 2017) tested the associations between ACEs and subsequent prescription pain medicine/opioid misuse outcomes in adulthood. ACEs were prevalent, with 62.7% of respondents in Montana and 50% in Florida reporting at least one ACE. The presence of ACEs was positively associated with prescription opioid misuse across both samples. Respondents reporting three or more ACEs had increased odds of taking opioids more than prescribed, without a prescription, and for the feeling they cause. Our results support a strong link between ACEs and prescription opioid misuse. Opportunities to prevent opioid misuse start with assuring safe, stable, nurturing relationships and environments in childhood and across the lifespan to prevent ACEs from occurring, and intervening appropriately when they do occur. Substance use prevention programs for adolescents, appropriate pain management and opioid prescribing protocols, and treatments for opioid use disorder can address ACEs by enhancing treatment safety and effectiveness and can reduce the intergenerational continuity of early adversity.

      4. PhenX: Agent measures for tobacco regulatory researchexternal icon
        O'Connor R, Watson CH, Swan GE, Nettles DS, Geisler RC, Hendershot TP.
        Tob Control. 2020 Jan;29(Suppl 1):s20-s26.
        The current paper describes the PhenX (Phenotypes and eXposures) Toolkit Tobacco Regulatory Research Agent specialty area and the Agent Working Group's (WG's) 6-month consensus process to identify high-priority, scientifically supported measures for cross-study comparison and analysis. Eleven measures were selected for inclusion in the Toolkit. Eight of these are interviewer-administered or self-administered protocols: history of switching to lower tar and nicotine cigarettes, passive exposures to tobacco products, tobacco brand and variety (covering cigars, cigarettes and smokeless tobacco separately), tobacco product adulteration (vent-blocking or filter-blocking) and tobacco warning label exposure and recall. The remaining three protocols are either laboratory-based or visual inspection-based: measurement of nicotine content in smoked or smokeless tobacco products and the physical properties of these two classes of products. Supplemental protocols include a biomarker of exposure and smoking topography. The WG identified the lack of standard measurement protocols to assess subjective ratings of tobacco product flavours and their appeal to consumers as a major gap. As the characteristics of tobacco products that influence perception and use are tobacco regulatory research priorities, the reliable assessment of flavours remains an area requiring further development.

      5. Opioid prescribing behaviors - Prescription Behavior Surveillance System, 11 states, 2010-2016external icon
        Strickler GK, Kreiner PW, Halpin JF, Doyle E, Paulozzi LJ.
        MMWR Surveill Summ. 2020 Jan 31;69(1):1-14.
        PROBLEM/CONDITION: In 2017, a total of 70,237 persons in the United States died from a drug overdose, and 67.8% of these deaths involved an opioid. Historically, the opioid overdose epidemic in the United States has been closely associated with a parallel increase in opioid prescribing and with widespread misuse of these medications. National and state policy makers have introduced multiple measures to attempt to assess and control the opioid overdose epidemic since 2010, including improvements in surveillance systems. PERIOD COVERED: 2010-2016 DESCRIPTION OF SYSTEM: The Prescription Behavior Surveillance System (PBSS) was created in 2011. Its goal was to track rates of prescribing of controlled substances and possible misuse of such drugs using data from selected state prescription drug monitoring programs (PDMP). PBSS data measure prescribing behaviors for prescription opioids using multiple measures calculated from PDMP data including 1) opioid prescribing, 2) average daily opioid dosage, 3) proportion of patients with daily opioid dosages >/=90 morphine milligram equivalents, 4) overlapping opioid prescriptions, 5) overlapping opioid and benzodiazepine prescriptions, and 6) multiple-provider episodes. For this analysis, PBSS data were available for 2010-2016 from 11 states representing approximately 38.0% of the U.S. POPULATION: Average quarterly percent changes (AQPC) in the rates of opioid prescribing and possible opioid misuse measures were calculated for each state. RESULTS AND INTERPRETATION: Opioid prescribing rates declined in all 11 states during 2010-2016 (range: 14.9% to 33.0%). Daily dosage declined least (AQPC: -0.4%) in Idaho and Maine, and most (AQPC: -1.6%) in Florida. The percentage of patients with high daily dosage had AQPCs ranging from -0.4% in Idaho to -2.3% in Louisiana. Multiple-provider episode rates declined by at least 62% in the seven states with available data. Variations in trends across the 11 states might reflect differences in state policies and possible differential effects of similar policies. PUBLIC HEALTH ACTIONS: Use of PDMP data from individual states enables a more detailed examination of trends in opioid prescribing behaviors and indicators of possible misuse than is feasible with national commercially available prescription data. Comparison of opioid prescribing trends among states can be used to monitor the temporal association of national or state policy interventions and might help public health policymakers recognize changes in the use or possible misuse of controlled prescription drugs over time and allow for prompt intervention through amended or new opioid-related policies.

    • Veterinary Medicine
      1. Francisella tularensis infection in dogs: 88 cases (2014-2016)external icon
        Kwit NA, Middaugh NA, VinHatton ES, Melman SD, Onischuk L, Aragon AS, Nelson CA, Mead PS, Ettestad PJ.
        J Am Vet Med Assoc. 2020 ;256(2):220-225.
        OBJECTIVE: To characterize the epidemiology, clinical signs, and treatment of dogs with Francisella tularensis infection in New Mexico. ANIMALS: 87 dogs in which 88 cases of tularemia (1 dog had 2 distinct cases) were confirmed by the New Mexico Department of Health Scientific Laboratory Division from 2014 through 2016 and for which medical records were available. PROCEDURES: Dogs were confirmed to have tularemia if they had a 4-fold or greater increase in anti-F tularensis antibody titer between acute and convalescent serum samples or F tularensis had been isolated from a clinical or necropsy specimen. Epidemiological, clinical, and treatment information were collected from the dogs' medical records and summarized. RESULTS: All 88 cases of tularemia were confirmed by paired serologic titers; the first (acute) serologic test result was negative for 84 (95%) cases. The most common reported exposure to F tularensis was wild rodent or rabbit contact (53/88 [60%]). Dogs had a median number of 3 clinical signs at initial evaluation; lethargy (81/88 [92%]), pyrexia (80/88 [91%]), anorexia (67/88 [76%]), and lymphadenopathy (18/88 [20%]) were most common. For 32 (36%) cases, the dog was hospitalized; all hospitalized dogs survived. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with F tularensis infection often had nonspecific clinical signs and developed moderate to severe illness, sometimes requiring hospitalization. Veterinarians examining dogs from tularemia-enzootic areas should be aware of the epidemiology and clinical signs of tularemia, inquire about potential exposures, and discuss prevention methods with owners, including reducing exposure to reservoir hosts and promptly seeking care for ill animals.

    • Zoonotic and Vectorborne Diseases
      1. The detection of anti-dengue virus IgM in urine in participants enrolled in an acute febrile illness study in Puerto Ricoexternal icon
        Caraballo E, Poole-Smith BK, Tomashek KM, Torres-Velasquez B, Alvarado LI, Lorenzi OD, Ramos C, Carrion J, Hunsperger E.
        PLoS Negl Trop Dis. 2020 Jan;14(1):e0007971.
        BACKGROUND: Dengue is an important arboviral disease with about 100 million dengue cases per year, of which, ~5% result in severe disease. Clinical differentiation of dengue from other acute febrile illnesses (AFI) is difficult, and diagnostic blood tests are costly. We evaluated the utility of anti-DENV IgM in urine to identify dengue cases among AFI patients enrolled in a clinical study. METHODS: Between May 2012-March 2013, 1538 study participants with fever for </=7 days were enrolled, a medical history was obtained, and serum and urine specimens were collected. Serum was tested for DENV RNA and anti-DENV IgM. Urine was tested for anti-DENV IgM, and its sensitivity and specificity to detect sera laboratory-positive dengue cases were calculated. We evaluated if urine anti-DENV IgM positivity early (</=5 days post-illness onset [DPO]) and late (6-14 DPO) in the clinical course was associated with dengue severity. RESULTS: Urine anti-DENV IgM sensitivity and specificity were 47.4% and 98.5%, respectively, when compared with serum anti-DENV IgM ELISA results, and 29.7% and 91.1% when compared with serum rRT-PCR results. There was no correlation between urine anti-DENV IgM positivity and patient sex or pre-existing chronic disease. Early in the clinical course, a significantly higher proportion of those who developed dengue with warning signs had anti-DENV IgM in their urine when compared to those without warning signs (20.4% vs. 4.3%). There was no difference in the proportion with urine anti-DENV IgM positivity between severity groups late in the clinical course. CONCLUSION: While detection of urine anti-DENV IgM lacked adequate diagnostic sensitivity, it is a highly specific marker for laboratory-positive dengue, and its presence early in the clinical course may distinguish those with more severe disease. Further assessment of urine anti-DENV IgM by DPO is warranted to determine its utility as an early diagnostic (and possibly prognostic) marker for dengue.

      2. Typhus group rickettsioses (TGRs) are vector-borne diseases that include murine typhus (Rickettsia typhi) and epidemic typhus (R. prowazekii). Twentieth-century public health interventions led to dramatic decreases in incidence; little is known about the contemporary TGR prevalence because neither disease is nationally notifiable. We summarized administrative claims data in a commercially insured population to examine trends in TGR medical encounters. We analysed data from 2003 to 2016 IBM(R) MarketScan(R) Commercial Databases to identify persons with inpatient or outpatient visits with an International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification TGR-specific code. We summarized epidemiologic characteristics associated with incident diagnosis. We identified 1,799 patients diagnosed with a TGR. Patients resided in 46 states, and most were female (n = 1,019/1,799; 56.6%); the median age was 42 years (range: 0-64 years). Epidemic typhus (n = 931/1,799; 51.8%) was the most common TGRs, followed by murine typhus (n = 722/1,799; 40.1%). The majority of TGR patients were diagnosed in an outpatient setting (n = 1,725/1,799; 95.9%); among hospitalized patients, the majority received a murine typhus diagnosis (n = 67/74; 90.5%). TGRs are rarely diagnosed diseases. More patients were diagnosed with epidemic than murine typhus, even though R. prowazekii transmission requires body louse or flying squirrel exposure. Patients from all geographic regions were diagnosed with murine and epidemic typhus, despite historically recognized ranges for these diseases. The epidemiologic misalignment of insurance claims data versus historic TGRs data highlights the challenges of finding appropriate alternative data sources to serve as a proxy when national surveillance data do not exist.

      3. Do monkeypox exposures vary by ethnicity? Comparison of Aka and Bantu suspected monkeypox casesexternal icon
        Guagliardo SA, Doshi RH, Reynolds MG, Dzabatou-Babeaux A, Ndakala N, Moses C, McCollum AM, Petersen BW.
        Am J Trop Med Hyg. 2020 ;102(1):202-205.
        In 2017, a monkeypox outbreak occurred in Likouala Department, Republic of the Congo. Many of the affected individuals were of Aka ethnicity, hunter-gatherers indigenous to Central Africa who have worse health outcomes in comparison with other forest-dwelling peoples. To test the hypothesis that Aka people have different risk factors for monkeypox, we analyzed questionnaire data for 39 suspected cases, comparing Aka and Bantu groups. Aka people were more likely to touch animal urine/feces, find dead animals in/around the home, eat an animal that was found dead, or to have been scratched or bitten by an animal (P < 0.05, all variables). They were also more likely to visit the forest ≥ once/week, sleep outside, or sleep on the ground (P < 0.001, all variables), providing opportunities for contact with monkeypox reservoirs during the night. The Aka and possibly other vulnerable groups may warrant special attention during educational and health promotion programs.

      4. Quantifying the risk of rabies in biting dogs in Haitiexternal icon
        Ma X, Blanton JD, Millien MF, Medley AM, Etheart MD, Fenelon N, Wallace RM.
        Sci Rep. 2020 Jan 23;10(1):1062.
        Rabies is a fatal viral disease typically transmitted through the bite of rabid animal. Domestic dogs cause over 99% of human rabies deaths. Over half of the world's population lives in a country where the canine rabies virus variant is endemic and dog bites are common. An estimated 29 million people worldwide receive post-bite vaccination after being exposed to animals suspected of rabies. Accurate and timely risk assessment of rabies in biting dogs is critical to ensure that rabies PEP is administered to all persons with a suspected rabies exposure, while avoiding PEP administration in situations where rabies can be definitively ruled out. In this study, a logistic regression model was developed to quantify the risk of rabies in biting dogs, using data from Haiti's animal rabies surveillance program. Significant risk factors identified in the model were used to quantify the probability of rabies in biting dogs. The risk of rabies in a biting dog as assessed through Haiti's rabies surveillance program was highly elevated when the dog displayed hypersalivation (OR = 34.6, 95% CI 11.3-106.5) or paralysis (OR = 19.0, 95% CI 4.8-74.8) and when the dog was dead at the time of the assessment (OR = 20.7, 95% CI 6.7-63.7). Lack of prior rabies vaccination, biting 2 or more people, and if the dog was a puppy also increased the probability that a biting dog would have rabies. The model showed high sensitivity (100%) and specificity (97%) when examined using validation data. This model enables us to project the risk of rabies in biting dogs in Haiti shortly after the bite event and make provisional PEP recommendations prior to laboratory testing or dog quarantine results. Application of this model may improve adherence to PEP for bite victims who can be educated on the quantitative risk of the exposure event. This model can also be used to reduce unnecessary PEP costs when the risk of rabies is determined as sufficiently low and the animal is available for observation.

      5. Public Veterinary Medicine: Public Health: Rabies surveillance in the United States during 2018external icon
        Ma X, Monroe BP, Cleaton JM, Orciari LA, Gigante CM, Kirby JD, Chipman RB, Fehlner-Gardiner C, Gutierrez Cedillo V, Petersen BW, Olson V, Wallace RM.
        J Am Vet Med Assoc. 2020 ;256(2):195-208.
        OBJECTIVE: To describe rabies and rabies-related events occurring during 2018 in the United States. ANIMALS: All animals submitted for laboratory diagnosis of rabies in the United States during 2018. PROCEDURES: State and territorial public health departments provided data on animals submitted for rabies testing in 2018. Data were analyzed temporally and geographically to assess trends in domestic animal and wildlife rabies cases. RESULTS: During 2018, 54 jurisdictions reported 4,951 rabid animals to the CDC, representing an 11.2% increase from the 4,454 rabid animals reported in 2017. Texas (n = 695 [14.0%]), Virginia (382 [7.7%]), Pennsylvania (356 [7.2%]), North Carolina (332 [6.7%]), Colorado (328 [6.6%]), and New York (320 [6.5%]) together accounted for almost half of all rabid animals reported in 2018. Of the total reported rabies cases, 4,589 (92.7%) involved wildlife, with bats (n = 1,635 [33.0%]), raccoons (1,499 [30.3%]), skunks (1,004 [20.3%]), and foxes (357 [7.2%]) being the major species. Rabid cats (n = 241 [4.9%]) and dogs (63 [1.3%]) accounted for > 80% of rabid domestic animals reported in 2018. There was a 4.6% increase in the number of samples submitted for testing in 2018, compared with the number submitted in 2017. Three human rabies deaths were reported in 2018, compared with 2 in 2017. CONCLUSIONS AND CLINICAL RELEVANCE: The overall number of animal rabies cases increased from 2017 to 2018. Laboratory diagnosis of rabies in animals is critical to ensure that human rabies postexposure prophylaxis is administered judiciously.

      6. Evaluation of species identification and rabies virus characterization among bat rabies cases in the United Statesexternal icon
        Pieracci EG, Brown JA, Bergman DL, Gilbert A, Wallace RM, Blanton JD, Velasco-Villa A, Morgan CN, Lindquist S, Chipman RB.
        J Am Vet Med Assoc. 2020 ;256(1):77-84.
        OBJECTIVE: To evaluate species identification and rabies virus (RABV) characterization among samples from bats submitted for rabies testing in the United States and assess whether a standardized approach to specimen selection for RABV characterization could enhance detection of a sentinel event in virus dissemination among bats. SAMPLE: United States public health rabies surveillance system data collected in January 2010 through December 2015. PROCEDURES: The number of rabies-tested bats for which species was reported and the number of RABV-positive samples for which virus characterization would likely provide information regarding introduction of novel RABV variants and translocation and host-shift events were calculated. These specimens were designated as specimens of epizootiological importance (SEIs). Additionally, the estimated test load that public health laboratories could expect if all SEIs underwent RABV characterization was determined. RESULTS: Species was reported for 74,928 of 160,017 (47%) bats submitted for rabies testing. Identified SEIs were grouped in 3 subcategories, namely nonindigenous bats; bats in southern border states, Florida, Puerto Rico, and the US Virgin Islands; and bats of species that are not commonly found to be inflected with RABV. Annually, 692 (95% CI, 600 to 784) SEIs were identified, of which only 295 (95% CI, 148 to 442) underwent virus characterization. Virus characterization of all SEIs would be expected to increase public health laboratories' overall test load by 397 (95% CI, 287 to 506) samples each year. CONCLUSIONS AND CLINICAL RELEVANCE: Species identification and RABV characterization may aid detection of a sentinel event in bat RABV dissemination. With additional resources, RABV characterization of all SEIs as a standardized approach to testing could contribute to knowledge of circulating bat RABV variants.

      7. Evaluation of rabies virus characterization to enhance early detection of important rabies epizootic events in the United Statesexternal icon
        Pieracci EG, Chipman RB, Morgan CN, Brown CM, Kirby JD, Blanton JD, Velasco-Villa A, Martin AD, Nelson KM, Singh A, LeMasters E, Weiner Z, Wallace RM.
        J Am Vet Med Assoc. 2020 ;256(1):66-76.
        OBJECTIVE: To evaluate rabies virus (RABV) characterization data obtained from animal specimens submitted to the US public health rabies surveillance system and propose a standardized approach to sample selection for RABV characterization that could enhance early detection of important rabies epizootic events in the United States. SAMPLE: United States public health rabies surveillance system data collected from January 1, 2010, through December 31, 2015. PROCEDURES: Data were reviewed to identify RABV-positive specimens for which virus characterization would likely provide information regarding any of 4 overarching events (discovery of novel variants, translocation of RABV variants, host-shift events, and any unusual rabies-related event) that could substantially alter animal rabies epizootiology in the United States. These specimens were designated as specimens of epizootiological importance (SEIs). Estimates of the additional number of specimens that public health laboratories could expect to process each year if all SEIs underwent RABV characterization were calculated. RESULTS: During the 6-year period, the mean annual number of SEIs was 855 (95% CI, 739 to 971); the mean number of SEIs that underwent virus characterization was 270 (95% CI, 187 to 353). Virus characterization of all SEIs would be expected to increase the public health laboratories' test load by approximately 585 (95% CI, 543 to 625) specimens/y. CONCLUSIONS AND CLINICAL RELEVANCE: Prioritization of RABV characterization of SEIs may improve early detection of rabies events associated with RABV host shifts, variant translocations, and importation. Characterization of SEIs may help refine wildlife rabies management practices. Each public health laboratory should evaluate testing of SEIs to ensure diagnostic laboratory capacity is not overstretched.

      8. Zoonotic disease exposure risk and rabies vaccination among wildlife professionalsexternal icon
        Tarrant S, Grewal J, Yaglom H, Lawaczeck E, Venkat H.
        Ecohealth. 2020 Jan 28.
        More than 70% of zoonotic diseases are wildlife associated putting wildlife professionals at increased risk of occupational exposure. In 2008 and 2018, the Arizona Department of Health Services surveyed Arizona wildlife professionals from multiple agencies to assess the risk of disease exposure, rabies pre-exposure prophylaxis (PrEP) history, personal protective equipment (PPE) use, and zoonoses knowledge. In 2008, a 12-question survey was distributed at a state wildlife professional meeting using an anonymous email link. In 2018, a 20-question survey was distributed using an anonymous email link to wildlife agency employees. We received 164 and 81 complete responses in the 2008 and 2018 surveys, respectively. Bites from rabies reservoir or spillover species were higher in 2008 (42%) than in 2018 (16%). More respondents received PrEP in 2018 (53%) than in 2008 (45%). Among 43 respondents who performed necropsies or collected animal samples within the past 5 years (2014-2018), only 60% always wore latex or nitrile gloves, and 79% never wore a facemask. Respondents indicated lower awareness of certain zoonoses, including brucellosis (72%) and leptospirosis (60%). Results on zoonoses awareness and reasons for non-use of PPE highlighted targets for education to improve practices, including facilitation of PPE training to prevent future disease transmission.

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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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