Volume 10, Issue 47, December 11, 2018

CDC Science Clips: Volume 10, Issue 47, December 11, 2018

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

As the nation’s health protection agency,  the U.S. Centers for Disease Control and Prevention (CDC) works with countries and partners around the world to build health security capabilities and keep America safe from public health threats. CDC’s Division of Global Health Protection (DGHP) leads the agency’s global health security efforts in disease surveillance, laboratory systems strengthening, workforce development, and outbreak investigation and emergency response. DGHP also develops the evidence base for interventions that can be used to enhance a country’s health security capacity. 

The recently released Health Security supplement entitled “Building the Evidence Base for Global Health Security,” shares lessons learned from efforts to build effective health systems in multiple countries spanning Africa, Asia, and Latin America. Articles provide examples of impactful interventions, lessons learned, and strategies for improving the efficiency of ongoing programs. The two opening commentaries highlight the importance of establishing a scientific framework for global health security that can be used by public health practitioners, donors, and governments to develop or improve interventions designed to strengthen global health security. The supplement also highlights how CDC is working with partners to address gaps and build country capacities to prevent, detect, and respond to global health threats.

More information about CDC’s global health security work is available here.

  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs). The names of CDC authors are indicated in bold text.
    • Global Health Security
      1. Strengthening global health security through Africa’s first absolute post-master’s fellowship program in field epidemiology in UgandaExternal
        Ario AR, Wanyenze RK, Opio A, Tusiime P, Kadobera D, Kwesiga B, Bulage L, Kihembo C, Kabwama SN, Matovu JK, Becknell S, Zhu BP.
        Health Secur. 2018 Fall;16(S1):S87-s97.

        Uganda is prone to epidemics of deadly infectious diseases and other public health emergencies. Though significant progress has been made in response to emergencies during the past 2 decades, system weaknesses still exist, including lack of a robust workforce with competencies to identify, investigate, and control disease outbreaks at the source. These deficiencies hamper global health security broadly. To address need for a highly competent workforce to combat infectious diseases, the Uganda Ministry of Health established the Public Health Fellowship Program (PHFP), the advanced-level Field Epidemiology Training Program (FETP), closely modeled after the CDC’s Epidemic Intelligence Service (EIS) program. The 2-year, full-time, non-degree granting program is the first absolute post-master’s FETP in Africa for mid-career public health professionals. Fellows gain competencies in 7 main domains, which are demonstrated by deliverables, while learning through service delivery 80% of the time in the ministry of health. During 2015-2017, PHFP enrolled 3 cohorts of 31 fellows. By January 2018, PHFP had graduated 2 cohorts (2015 and 2016) of 19 fellows. Fellows were placed in 17 priority areas of the ministry of health. They completed 153 projects (including 60 outbreak investigations, 12 refugee assessments, 40 surveillance projects, and 31 applied epidemiologic studies), of which 49 involved potential bioterrorism agents or epidemic-prone diseases. They made 132 conference presentations, prepared 40 manuscripts for peer-reviewed publication (17 published as of December 2017), and produced 3 case studies. Many of these projects have resulted in public health interventions that led to improvements in disease control and surveillance systems. The program has produced 19 issues of ministry of health bulletins. One year after graduation, graduates have been placed in key public health decision-making positions. Within 3 years, PHFP has strengthened global health security through improvement in public health emergency response; identification, investigation and control of outbreaks at their sources; and documentation and dissemination of findings to inform decision making by relevant stakeholders.

      2. Use of the staged development tool for assessing, planning, and measuring progress in the development of National Public Health InstitutesExternal
        Barzilay EJ, Vandi H, Binder S, Udo I, Ospina ML, Ihekweazu C, Bratton S.
        Health Secur. 2018 Fall;16(S1):S18-s24.

        The Staged Development Tool (SDT) was created to help national public health institutes (NPHIs) assess their current capacity and develop roadmaps for achieving a higher level of functioning. This article discusses the current use of the SDT by national public health institutes to establish baseline capacity and inform strategic planning and its proposed use in a 3-step sequence for measuring the impact of capacity-building interventions over time. The article also includes descriptions of how national public health institutes have been using the SDT to assess their baseline capacity in management issues and core public health functions. The first use of the SDT by a national public health institute provides essential baseline information on their capacities and levels of functioning and plans for addressing gaps. By repeating the SDT after time for the plans to be implemented, the SDT can be used to evaluate changes in capacity and the effectiveness of the interventions made. Because the SDT is built to be complementary to existing assessments and public health strengthening tools and guidelines, implementing the SDT provides concrete, complementary information that can help countries achieve global health security goals and address current and future threats to public health.

      3. Factors influencing community event-based surveillance: Lessons learned from pilot implementation in VietnamExternal
        Clara A, Dao AT, Do TT, Tran PD, Tran QD, Ngu ND, Ngo TH, Phan HC, Nguyen TT, Bernadotte-Schmidt C, Nguyen HT, Alroy KA, Balajee SA, Mounts AW.
        Health Secur. 2018 Fall;16(S1):S66-s75.

        Community event-based surveillance aims to enhance the early detection of emerging public health threats and thus build health security. The Ministry of Health of Vietnam launched a community event-based surveillance pilot program in 6 provinces to improve the early warning functions of the existing surveillance system. An evaluation of the pilot program took place in 2017 and 2018. Data from this evaluation were analyzed to determine which factors were associated with increased detection and reporting. Results show that a number of small, local events were detected and reported through community event-based surveillance, supporting the notion that it would also facilitate the rapid detection and reporting of potentially larger events or outbreaks. The study showed the value of supportive supervision and monitoring to sustain community health worker reporting and the importance of conducting evaluations for community event-based surveillance programs to identify barriers to effective implementation.

      4. Building simulation exercise capacity in Latin America to manage public health emergenciesExternal
        Hanson K, Hernandez L, Banaski JA.
        Health Secur. 2018 Fall;16(S1):S98-s102.

        Simulation exercises, whether discussion- or operations-based, are an essential component of public health emergency preparedness and response-so much so that the ability to conduct exercises is included as a key indicator for measurement of emergency response operations in the Joint External Evaluation and as a requirement of the International Health Regulations. Exercises allow ministry of health partners to actually practice and demonstrate their learned capacities and show progress toward those global health security goals. In recent years, the general technique in the global health security arena has been for external partners to design, facilitate, and evaluate public health emergency exercises for ministry of health partners. However, in 2017, the Centers for Disease Control and Prevention (CDC) Global Response Preparedness Team (GRPT) piloted regional training for ministry of health representatives from 4 countries in Latin America to build their internal capacity to design, facilitate, and evaluate simulation exercises using the US Homeland Security Exercise Evaluation Program (HSEEP). Using this program as the source material, the team modified the content for application to an international audience, facilitated it as a 4-day workshop, and designed an evaluation protocol to measure participants’ satisfaction with the course as well as their ability to apply concepts learned in their day-to-day jobs. Representatives of 3 of the 4 ministries of health that attended the workshop designed exercises to implement in their home countries, with 2 having completed the facilitation and evaluation of their exercises at the time of this publication.

      5. Establishment of a sentinel laboratory-based antimicrobial resistance surveillance network in EthiopiaExternal
        Hazim C, Abubeker Ibrahim R, Westercamp M, Belete GA, Amare Kibret B, Kanter T, Yimer G, Adem TS, Stevenson KB, Urrego M, Kale KN, Omondi MW, VanderEnde D, Park BJ, Parsons MM, Gallagher KM.
        Health Secur. 2018 Fall;16(S1):S30-s36.

        In 2014, as part of the Global Health Security Agenda, Ethiopia was provided the technical and financial resources needed to prioritize antimicrobial resistance (AMR) in the national public health sphere. Under the direction of a multi-stakeholder working group, AMR surveillance was launched in July 2017 at 4 sentinel sites across the country. The AMR surveillance initiative in Ethiopia represents one of the first systematic efforts to prospectively collect, analyze, and report national-level microbiology results from a network of hospitals and public health laboratories in the country. Baseline readiness assessments were conducted to identify potential challenges to implementation to be addressed through capacity-building efforts. As part of these efforts, the working group leveraged existing resources, initiated laboratory capacity building through mentorship, and established infrastructure and systems for quality assurance, data management, and improved coordination. As a result, AMR surveillance data are being reported and analyzed for use; data from more than 1,700 patients were collected between July 2017 and March 2018. The critical challenges and effective solutions identified through surveillance planning and implementation have provided lessons to help guide successful AMR surveillance in other settings. Ultimately, the surveillance infrastructure, laboratory expertise, and communication frameworks built specifically for AMR surveillance in Ethiopia can be extended for use with other infectious diseases and potential public health emergencies. Thus, building AMR surveillance in Ethiopia has illustrated how laying the foundation for a specific public health initiative can develop capacity for core public health functions with potential benefit.

      6. Global health security implementation: Expanding the evidence baseExternal
        Kennedy ED, Morgan J, Knight NW.
        Health Secur. 2018 Fall;16(S1):S1-s4.

        [No abstract]

      7. A cross-cutting approach to surveillance and laboratory capacity as a platform to improve health security in UgandaExternal
        Lamorde M, Mpimbaza A, Walwema R, Kamya M, Kapisi J, Kajumbula H, Sserwanga A, Namuganga JF, Kusemererwa A, Tasimwa H, Makumbi I, Kayiwa J, Lutwama J, Behumbiize P, Tagoola A, Nanteza JF, Aniku G, Workneh M, Manabe Y, Borchert JN, Brown V, Appiah GD, Mintz ED, Homsy J, Odongo GS, Ransom RL, Freeman MM, Stoddard RA, Galloway R, Mikoleit M, Kato C, Rosenberg R, Mossel EC, Mead PS, Kugeler KJ.
        Health Secur. 2018 Fall;16(S1):S76-s86.

        Global health security depends on effective surveillance for infectious diseases. In Uganda, resources are inadequate to support collection and reporting of data necessary for an effective and responsive surveillance system. We used a cross-cutting approach to improve surveillance and laboratory capacity in Uganda by leveraging an existing pediatric inpatient malaria sentinel surveillance system to collect data on expanded causes of illness, facilitate development of real-time surveillance, and provide data on antimicrobial resistance. Capacity for blood culture collection was established, along with options for serologic testing for select zoonotic conditions, including arboviral infection, brucellosis, and leptospirosis. Detailed demographic, clinical, and laboratory data for all admissions were captured through a web-based system accessible at participating hospitals, laboratories, and the Uganda Public Health Emergency Operations Center. Between July 2016 and December 2017, the expanded system was activated in pediatric wards of 6 regional government hospitals. During that time, patient data were collected from 30,500 pediatric admissions, half of whom were febrile but lacked evidence of malaria. More than 5,000 blood cultures were performed; 4% yielded bacterial pathogens, and another 4% yielded likely contaminants. Several WHO antimicrobial resistance priority pathogens were identified, some with multidrug-resistant phenotypes, including Acinetobacter spp., Citrobacter spp., Escherichia coli, Staphylococcus aureus, and typhoidal and nontyphoidal Salmonella spp. Leptospirosis and arboviral infections (alphaviruses and flaviviruses) were documented. The lessons learned and early results from the development of this multisectoral surveillance system provide the knowledge, infrastructure, and workforce capacity to serve as a foundation to enhance the capacity to detect, report, and rapidly respond to wide-ranging public health concerns in Uganda.

      8. Institutionalizing One Health: From assessment to actionExternal
        Machalaba CC, Salerno RH, Barton Behravesh C, Benigno S, Berthe FC, Chungong S, Duale S, Echalar R, Karesh WB, Ormel HJ, Pelican K, Rahman M, Rasmuson M, Scribner S, Stratton J, Suryantoro L, Wannous C.
        Health Secur. 2018 Fall;16(S1):S37-s43.

        A One Health approach is critical to strengthening health security at country, regional, and global levels. However, operationally its uptake remains limited. Recent momentum in assessing capacity to effectively prevent, detect, and respond to disease threats has resulted in identification of gaps that require dedicated action. This article highlights relevant tools, standards, and guidance to assist countries and institutions in meeting the collective vision articulated at the 2018 Prince Mahidol Award Conference on “Making the World Safe from the Threats of Emerging Infectious Diseases.” Taking stock of assessment findings, resources, priorities, and implementation initiatives across human and animal health, environment and disaster risk reduction sectors can help expand participation in global health security, target risk drivers, and form synergies for collective action and shared gains for both emerging and endemic disease challenges. In addition to health security gains, a multisectoral, One Health approach can drive benefits for wider health sector and global development goals.

      9. Law and the JEE: Lessons for IHR implementationExternal
        Menon AN, Rosenfeld E, Brush CA.
        Health Secur. 2018 Fall;16(S1):S11-s17.

        In an increasingly globalized world, countries face infectious disease threats and public health emergencies that transcend borders, making health security of paramount importance. Legal frameworks, at both the international and national levels, can empower governments to strengthen public health and preparedness systems to better detect and respond to infectious disease threats and public health emergencies. The development of the International Health Regulations (IHR) (2005) and the Global Health Security Agenda (GHSA), and the resulting Joint External Evaluation (JEE), are examples of coordinated global efforts to build capacity to prevent, detect, and respond to the international spread of disease. This article uses 3 case studies to describe a role for law in IHR implementation. It highlights the Centers for Disease Control and Prevention’s (CDC’s) Global Health Security Public Health Law Project and describes how legal mapping data and the resources developed are being used by countries to strengthen health systems and support IHR implementation.

      10. Building global health security capacity: The role for implementation scienceExternal
        Morgan J, Kennedy ED, Pesik N, Angulo FJ, Craig AS, Knight NW, Bunnell RE.
        Health Secur. 2018 Fall;16(S1):S5-s7.

        [No abstract]

      11. Development of a costed national action plan for health security in Pakistan: Lessons learnedExternal
        Safi M, Ijaz K, Samhouri D, Malik M, Sabih F, Kandel N, Salman M, Suryantoro L, Liban A, Jafari H, Hafeez A.
        Health Secur. 2018 Fall;16(S1):S25-s29.

        In order to assess progress toward achieving compliance with the International Health Regulations (2005), member states may voluntarily request a Joint External Evaluation (JEE). Pakistan was the first country in the WHO Eastern Mediterranean Region to volunteer for and complete a JEE to establish the baseline of the country’s public health capacity across multiple sectors covering 19 technical areas. It subsequently developed a post-JEE costed National Action Plan for Health Security (NAPHS). The process for developing the costed NAPHS was based on objectives and activities related to the 3 to 5 priority actions for each of the 19 JEE technical areas. Four key lessons were learned during the process of developing the NAPHS. First, multisectoral coordination at both federal and provincial levels is important in a devolved health system, where provinces are autonomous from a public health sector standpoint. Second, the development of a costed NAPHS requires engagement and investment of the country’s own resources for sustainability as well as donor coordination among national and international donors and partners. Engagement from the ministries of Finance, Planning and Development, and Foreign Affairs and from WHO was also important. Third, development of predefined goals, targets, and indicators aligned with the JEE as part of the NAPHS process proved to be critical, as they can be used to monitor progress toward implementation of the NAPHS and provide data for repeat JEEs. Lastly, several challenges were identified related to the NAPHS process and costing tool, which need to be addressed by WHO and partners to help countries develop their plans.

      12. Building laboratory-based arbovirus sentinel surveillance capacity during an ongoing dengue outbreak, Burkina Faso, 2017External
        Sanou AS, Dirlikov E, Sondo KA, Kagone TS, Yameogo I, Sow HE, Adjami AG, Traore SM, Dicko A, Tinto B, Diendere EA, Ouedraogo-Konate S, Kiemtore T, Kangoye DT, Sangare L, Dama ET, Fuller JA, Major CG, Tosado-Acevedo R, Sharp TM, Kone RG, Bicaba BW.
        Health Secur. 2018 Fall;16(S1):S103-s110.

        In West Africa, identification of nonmalarial acute febrile illness (AFI) etiologic pathogens is challenging, given limited epidemiologic surveillance and laboratory testing, including for AFI caused by arboviruses. Consequently, public health action to prevent, detect, and respond to outbreaks is constrained, as experienced during dengue outbreaks in several African countries. We describe the successful implementation of laboratory-based arbovirus sentinel surveillance during a dengue outbreak in Burkina Faso during fall 2017. We describe implementation, surveillance methods, and associated costs of enhanced surveillance during an outbreak response as an effort to build capacity to better understand the burden of disease caused by arboviruses in Burkina Faso. The system improved on existing routine surveillance through an improved case report form, systematic testing of specimens, and linking patient information with laboratory results through a data management system. Lessons learned will improve arbovirus surveillance in Burkina Faso and will contribute to enhancing global health security in the region. Elements critical to the success of this intervention include responding to a specific and urgent request by the government of Burkina Faso and building on existing systems and infrastructure already supported by CDC’s global health security program.

      13. Strengthening healthcare facilities through Water, Sanitation, and Hygiene (WASH) Improvements: A Pilot Evaluation of “WASH FIT” in TogoExternal
        Weber N, Martinsen AL, Sani A, Assigbley EK, Azzouz C, Hayter A, Ayite K, Baba AA, Davi KM, Gelting R.
        Health Secur. 2018 Fall;16(S1):S54-s65.

        Water, sanitation, and hygiene (WASH) services in healthcare facilities are essential to ensure quality health care and to facilitate infection, prevention, and control practices. They are critical to responding to outbreaks and preventing healthcare-associated infections and, therefore, critical to global health security. Many healthcare facilities in low- and middle-income settings have limited WASH services. One tool to address this issue is the World Health Organization (WHO) and United Nations Children’s Fund (UNICEF) Water and Sanitation for Health Facility Improvement Tool, or “WASH FIT.” WASH FIT is a continuous improvement tool based on key WHO environmental health and infection, prevention, and control standards. While using WASH FIT, internal teams regularly perform self-assessments at their facilities, using up to 65 WASH indicators to develop and implement an improvement plan. The Ministry of Health and Social Protection (MSPS) in Togo, with support from WHO and the US Centers for Disease Control and Prevention (CDC), piloted this tool in 3 healthcare facilities. The pilot included facility assessments at 3 time points and in-depth interviews and document review 7 months after initiating WASH FIT. Facilities made improvements without significant external financial or material support. On average, pilot facilities improved from 18% of total indicators meeting standards at baseline to 44% after 7 months. Examples included improved drinking water supply, medical waste segregation, and increased soap at handwashing stations. Participants reported improvements in staff and patient satisfaction, hand hygiene, and occupational safety. Findings suggest that WASH FIT, coupled with training and supervision, may help facilities improve WASH services and practices, thus contributing to global health security. Based on these findings, the Togolese MSPS plans to scale up nationwide.

  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. Identifying high-risk individuals for chronic kidney disease: Results of the CHERISH Community Demonstration ProjectExternal
        Burrows NR, Vassalotti JA, Saydah SH, Stewart R, Gannon M, Chen SC, Li S, Pederson S, Collins AJ, Williams DE.
        Am J Nephrol. 2018 Nov 23;48(6):447-455.

        BACKGROUND: Most people with chronic kidney disease (CKD) are not aware of their condition. OBJECTIVES: To assess screening criteria in identifying a population with or at high risk for CKD and to determine their level of control of CKD risk factors. METHOD: CKD Health Evaluation Risk Information Sharing (CHERISH), a demonstration project of the Centers for Disease Control and Prevention, hosted screenings at 2 community locations in each of 4 states. People with diabetes, hypertension, or aged >/=50 years were eligible to participate. In addition to CKD, screening included testing and measures of hemoglobin A1C, blood pressure, and lipids. -Results: In this targeted population, among 894 people screened, CKD prevalence was 34%. Of participants with diabetes, 61% had A1C < 7%; of those with hypertension, 23% had blood pressure < 130/80 mm Hg; and of those with high cholesterol, 22% had low-density lipoprotein < 100 mg/dL. CONCLUSIONS: Using targeted selection criteria and simple clinical measures, CHERISH successfully identified a population with a high CKD prevalence and with poor control of CKD risk factors. CHERISH may prove helpful to state and local programs in implementing CKD detection programs in their communities.

      2. Achieving excellence in the practice of chronic disease epidemiologyExternal
        Calanan RM, Sandoval-Rosario M, Price JD, Samanic CM, Lu H, Barbour KE.
        Prev Chronic Dis. 2018 Nov 29;15:E146.

        [No abstract]

      3. Trends in liver cancer mortality in the United States: Dual burden among foreign- and US-born personsExternal
        Endeshaw M, Hallowell BD, Razzaghi H, Senkomago V, McKenna MT, Saraiya M.
        Cancer. 2018 Nov 27.

        BACKGROUND: Since the mid-1980s, the burden of liver cancer in the United States has doubled, with 31,411 new cases and 24,698 deaths occurring in 2014. Foreign-born individuals may be more likely to die of liver cancer than individuals in the general US-born population because of higher rates of hepatitis B infection, a low socioeconomic position, and language barriers that limit the receipt of early cancer detection and effective treatment. METHODS: To determine whether liver cancer mortality rates were higher among foreign-born individuals versus US-born individuals in the United States, population-based cancer mortality data were obtained from the National Center for Health Statistics of the Centers for Disease Control and Prevention. Annual population estimates were obtained from the US Census Bureau’s American Community Survey. Age-adjusted mortality rates and rate ratios (RRs) for liver cancer stratified by birth place were calculated, and the average annual percent change (AAPC) was used to evaluate trends. RESULTS: A total of 198,557 deaths from liver and intrahepatic bile duct cancer were recorded during 2005-2014, and 16% occurred among foreign-born individuals. Overall, foreign-born individuals had a 24% higher risk of liver cancer mortality than US-born individuals (RR, 1.24; 95% confidence interval [CI], 1.22-1.25). Foreign-born individuals did not have any significant changes in liver cancer mortality rates overall, but among US-born individuals, liver cancer mortality rates significantly increased (AAPC, 2.7; 95% CI, 2.1-3.3). CONCLUSIONS: Efforts that address the major risk factors for liver cancer are needed to help to alleviate the health disparities observed among foreign-born individuals and reverse the increasing trend observed in the US-born population.

      4. Long-term survivorship care after cancer treatment – summary of a 2017 National Cancer Policy Forum WorkshopExternal
        Kline RM, Arora NK, Bradley CJ, Brauer ER, Graves DL, Lunsford NB, McCabe MS, Nasso SF, Nekhlyudov L, Rowland JH, Schear RM, Ganz PA.
        J Natl Cancer Inst. 2018 Nov 29.

        The National Cancer Policy Forum of the National Academies of Sciences, Engineering and Medicine sponsored a workshop on July 24 and 25, 2017 on Long-Term Survivorship after Cancer Treatment. The workshop brought together diverse stakeholders (patients, advocates, academicians, clinicians, research funders, and policymakers) to review progress and ongoing challenges since the Institute of Medicine (IOM)’s seminal report on the subject of adult cancer survivors published in 2006. This commentary profiles the content of the meeting sessions and concludes with recommendations that stem from the workshop discussions. Although there has been progress over the past decade, many of the recommendations from the 2006 report have not been fully implemented. Obstacles related to the routine delivery of standardized physical and psychosocial care services to cancer survivors are substantial, with important gaps in care for patients and caregivers. Innovative care models for cancer survivors have emerged, and changes in accreditation requirements such as the Commission on Cancer’s (CoC) requirement for survivorship care planning have put cancer survivorship on the radar. The Center for Medicare & Medicaid Innovation’s Oncology Care Model (OCM), which requires psychosocial services and the creation of survivorship care plans for its beneficiary participants, has placed increased emphasis on this service. The OCM, in conjunction with the CoC requirement, is encouraging electronic health record vendors to incorporate survivorship care planning functionality into updated versions of their products. As new models of care emerge, coordination and communication among survivors and their clinicians will be required to implement patient- and community-centered strategies.

      5. Lung cancer screening inconsistent with U.S. Preventive Services Task Force recommendationsExternal
        Richards TB, Doria-Rose VP, Soman A, Klabunde CN, Caraballo RS, Gray SC, Houston KA, White MC.
        Am J Prev Med. 2018 Nov 12.

        INTRODUCTION: Prior studies suggest overuse of nonrecommended lung cancer screening tests in U.S. community practice and underuse of recommended tests. METHODS: Data from the 2010 and 2015 National Health Interview Surveys was analyzed from 2016 to 2018. Prevalence, populations, and number of chest computed tomography (CT) and chest x-ray tests were estimated for people who did and did not meet U.S. Preventive Services Task Force (USPSTF) criteria for lung cancer screening, among people aged >/=40 years without lung cancer. RESULTS: In 2015, among those who met USPSTF criteria, 4.4% (95% CI=3.0%, 6.6%), or 360,000 (95% CI=240,000, 535,000) people reported lung cancer screening with a chest CT; and 8.5% (95% CI=6.5%, 11.1%), or 689,000 (95% CI=526,000, 898,000) people reported a chest x ray. Among those who did not meet USPSTF criteria, 2.3% (95% CI=2.0%, 2.6%), or 3,259,000 (95% CI=2,850,000, 3,724,000) people reported a chest x ray; and 1.3% (95% CI=1.1%, 1.5%), or 1,806,000 (95% CI=1,495,000, 2,173,000) people reported a chest CT. The estimated population meeting USPSTF criteria for lung cancer screening in 2015 was 8,098,000 (95% CI=7,533,000, 8,702,000), which was smaller than the 9,620,000 people (95% CI=8,960,000, 10,325,000) in 2010. CONCLUSIONS: The number of adults inappropriately screened for lung cancer greatly exceeds the number screened according to USPSTF recommendations, the prevalence of appropriate lung cancer screening is low, and the population meeting USPSTF criteria is shrinking. To realize the potential benefits of screening, better processes to appropriately triage eligible individuals to screening, plus screening with a USPSTF-recommended test, would be beneficial.

      6. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapyExternal
        Witt DM, Nieuwlaat R, Clark NP, Ansell J, Holbrook A, Skov J, Shehab N, Mock J, Myers T, Dentali F, Crowther MA, Agarwal A, Bhatt M, Khatib R, Riva JJ, Zhang Y, Guyatt G.
        Blood Adv. 2018 Nov 27;2(22):3257-3291.

        BACKGROUND: Clinicians confront numerous practical issues in optimizing the use of anticoagulants to treat venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians and other health care professionals in their decisions about the use of anticoagulants in the management of VTE. These guidelines assume the choice of anticoagulant has already been made. METHODS: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 25 recommendations and 2 good practice statements to optimize management of patients receiving anticoagulants. CONCLUSIONS: Strong recommendations included using patient self-management of international normalized ratio (INR) with home point-of-care INR monitoring for vitamin K antagonist therapy and against using periprocedural low-molecular-weight heparin (LMWH) bridging therapy. Conditional recommendations included basing treatment dosing of LMWH on actual body weight, not using anti-factor Xa monitoring to guide LMWH dosing, using specialized anticoagulation management services, and resuming anticoagulation after episodes of life-threatening bleeding.

      7. High birth weight, early UV exposure, and melanoma risk in children, adolescents and young adultsExternal
        Wojcik KY, Escobedo LA, Wysong A, Heck JE, Ritz B, Hamilton AS, Milam J, Cockburn MG.
        Epidemiology. 2018 Nov 29.

        BACKGROUND: Melanoma, the deadliest form of skin cancer, is the second most common cancer diagnosed before age 30. Little is known about potentially modifiable or intervenable risk factors specific to developing melanoma at a young age. The objective was to determine if high birth weight or higher early life ultraviolet (UV) radiation exposure would be associated with increased risk of melanoma in young patients. METHODS: Population-based, case-control study of 1,396 cases of melanoma diagnosed before age 30 in 1988-2013 and 27,920 controls, obtained by linking cancer registry data to birth records in California. RESULTS: High birth weight (>4000g) was associated with 19% higher risk of melanoma (OR:1.19; 95% CI: 1.02, 1.39), while low birth weight (<2500g) was associated with 41% lower risk (OR:0.59; 95% CI: 0.43, 0.82), compared to normal birth weight (2500-4000g); dose-response per 1000g increase was also evident (OR:1.24; 95% CI:1.13, 1.36). All quartiles of birthplace UV greater than the lowest quartile were associated with increased melanoma risk. The strongest relationship between birthplace UV and melanoma was for 15-19 years of age at diagnosis. CONCLUSIONS: High birth weight and high early-life UV exposure may be important independent risk factors for melanoma diagnosis before age 30. The implication is that adopting skin-protective behaviors as early as infancy could be important for primary prevention of melanoma in younger people. However, research that accounts for early-life behavioral patterns of skin protection during infancy is needed to advance our understanding of how birth weight and early-life UV may influence development of early onset melanoma.

    • Communicable Diseases
      1. Eliminating neglected tropical diseases in urban areas: A review of challenges, strategies and research directions for successful mass drug administrationExternal
        Adams AM, Vuckovic M, Birch E, Brant TA, Bialek S, Yoon D, Koroma J, Direny A, Shott J, Lemoine JF, Dembele M, Baker MC.
        Trop Med Infect Dis. 2018 Nov 21;3(4).

        Since 1950, the global urban population grew from 746 million to almost 4 billion and is expected to reach 6.4 billion by mid-century. Almost 90% of this increase will take place in Asia and Africa and disproportionately in urban slums. In this context, concerns about the amplification of several neglected tropical diseases (NTDs) are warranted and efforts towards achieving effective mass drug administration (MDA) coverage become even more important. This narrative review considers the published literature on MDA implementation for specific NTDs and in-country experiences under the ENVISION and END in Africa projects to surface features of urban settings that challenge delivery strategies known to work in rural areas. Discussed under the thematics of governance, population heterogeneity, mobility and community trust in MDA, these features include weak public health infrastructure and programs, challenges related to engaging diverse and dynamic populations and the limited accessibility of certain urban settings such as slums. Although the core components of MDA programs for NTDs in urban settings are similar to those in rural areas, their delivery may need adjustment. Effective coverage of MDA in diverse urban populations can be supported by tailored approaches informed by mapping studies, research that identifies context-specific methods to increase MDA coverage and rigorous monitoring and evaluation.

      2. BACKGROUND: Transgender women (transwomen) in the United States have been shown to have high HIV risk with Black and Hispanic transwomen being particularly vulnerable. Growing research on transgender men (transmen) also shows increased HIV risk and burden, although not as much is known for this transgender population. OBJECTIVES: This systematic review estimates the prevalence of self-reported and laboratory-confirmed HIV infection, reported sexual and injection behaviors, and contextual factors associated with HIV risk of transgender persons living in the United States. SEARCH METHODS: We searched the HIV Prevention Research Synthesis database and MEDLINE, EMBASE, PsycINFO, CINAHL, and Sociological Abstracts databases from January 2006 to March 2017 and January 2006 to May 2017, respectively. Additional hand searches were conducted in December 2017 to obtain studies not found in the literature searches. SELECTION CRITERIA: Eligible reports were published US-based studies that included transgender persons and reported HIV status. DATA COLLECTION AND ANALYSIS: Data were double-coded and quality assessed. We used random-effects models employing the DerSimonian-Laird method to calculate overall prevalence of HIV infection, risk behaviors, and contextual factors for transwomen, transmen, and race/ethnicity subgroups. MAIN RESULTS: We reviewed 88 studies, the majority of which were cross-sectional surveys. Overall laboratory-confirmed estimated prevalence of HIV infection was 9.2% (95% confidence interval [CI] = 6.0%, 13.7%; kappa = 24). Among transwomen and transmen, HIV infection prevalence estimates were 14.1% (95% CI = 8.7%, 22.2%; kappa = 13) and 3.2% (95% CI = 1.4%, 7.1%; kappa = 8), respectively. Self-reported HIV infection was 16.1% (95% CI = 12.0%, 21.2%; kappa = 44), 21.0% (95% CI = 15.9%, 27.2%; kappa = 30), and 1.2% (95% CI = 0.4%, 3.1%; kappa = 7) for overall, transwomen, and transmen, respectively. HIV infection estimates were highest among Blacks (44.2%; 95% CI = 23.2%, 67.5%; kappa = 4). Overall, participation in sex work was 31.0% (95% CI = 23.9%, 39.0%; kappa = 39). Transwomen (37.9%; 95% CI = 29.0%, 47.7%; kappa = 29) reported higher participation in sex work than transmen (13.1%; 95% CI = 6.6%, 24.3%; kappa = 10; P = .001). Most outcomes indicated high heterogeneity in the overall and subgroup analyses. CONCLUSIONS: The availability of more data allowed us to calculate estimates separately for transwomen and transmen. HIV prevalence estimates for US transwomen were lower than previous estimates, but estimates for HIV prevalence and participation in sex work were higher when compared with transmen. Evidence gaps remain for transmen and the syndemic relationship of HIV, risky behaviors, and contextual factors specific to the transgender experience. Public Health Implications. This study highlights gender disparities for HIV and risky sexual behavior, as well as evidence gaps that exist for transmen. Tailored programs and services for the transgender population need to be developed to encourage use of and access to HIV prevention services. (Am J Public Health. Published online ahead of print November 29, 2018: e1-e8. doi:10.2105/AJPH.2018.304727).

      3. Since 2012, U.S. clinical guidelines for antiretroviral therapy (ART) initiation have recommended universal ART prescription barring patient contraindications. Although ART prescription has significantly increased among U.S. HIV patients in recent years, the reasons for this increase, and why some patients are still not taking ART, are not well characterized. To fill these gaps, we analyzed data from the Medical Monitoring Project (MMP), to assess the proportion of persons who reported provider-advised ART deferral during 2009-2014, and used bivariate linear regression to estimate linear trends in provider-advised ART deferral over time by patient characteristics and clinical setting. During this period, the proportion of patients reporting provider-advised ART deferral decreased from 67% to 40%. Significant decreases were observed in all patient subgroups and clinical settings. Patients recently reporting non-provider-advised reasons for ART deferral were significantly less likely to be virally suppressed and more likely to have inconsistent care, be depressed, binge drink, and use illicit drugs. This work suggests that U.S. providers are recommending ART deferral for fewer patients, consistent with increasing adoption of 2012 universal prescribing guidelines. Addressing patients’ financial, mental health, and substance use barriers may be needed to achieve universal ART prescription in the United States.

      4. Diarrhoea, enteric pathogen detection and nutritional indicators among controls in the Global Enteric Multicenter Study, Kenya site: an opportunity to understand reference populations in case-control studies of diarrhoeaExternal
        Berendes DM, O’Reilly CE, Kim S, Omore R, Ochieng JB, Ayers T, Fagerli K, Farag TH, Nasrin D, Panchalingam S, Nataro JP, Kotloff KL, Levine MM, Oundo J, Laserson K, Breiman RF, Mintz ED.
        Epidemiol Infect. 2018 Nov 15:1-9.

        Given the challenges in accurately identifying unexposed controls in case-control studies of diarrhoea, we examined diarrhoea incidence, subclinical enteric infections and growth stunting within a reference population in the Global Enteric Multicenter Study, Kenya site. Within ‘control’ children (0-59 months old without diarrhoea in the 7 days before enrolment, n = 2384), we examined surveys at enrolment and 60-day follow-up, stool at enrolment and a 14-day post-enrolment memory aid for diarrhoea incidence. At enrolment, 19% of controls had 1 enteric pathogen associated with moderate-to-severe diarrhoea (‘MSD pathogens’) in stool; following enrolment, many reported diarrhoea (27% in 7 days, 39% in 14 days). Controls with and without reported diarrhoea had similar carriage of MSD pathogens at enrolment; however, controls reporting diarrhoea were more likely to report visiting a health facility for diarrhoea (27% vs. 7%) or fever (23% vs. 16%) at follow-up than controls without diarrhoea. Odds of stunting differed by both MSD and ‘any’ (including non-MSD pathogens) enteric pathogen carriage, but not diarrhoea, suggesting control classification may warrant modification when assessing long-term outcomes. High diarrhoea incidence following enrolment and prevalent carriage of enteric pathogens have implications for sequelae associated with subclinical enteric infections and for design and interpretation of case-control studies examining diarrhoea.

      5. Notes from the field: Multiple modes of transmission during a Thanksgiving day norovirus outbreak – Tennessee, 2017External
        Brennan J, Cavallo SJ, Garman K, Lewis K, Irving DJ, Moore C, Thomas L, Hill J, Villegas R, Norman JF, Dunn JR, Schaffner W, Jones TF.
        MMWR Morb Mortal Wkly Rep. 2018 Nov 23;67(46):1300-1301.

        [No abstract]

      6. The changing role of disease intervention specialists in modern public health programsExternal
        Cope AB, Mobley VL, Samoff E, O’Connor K, Peterman TA.
        Public Health Rep. 2018 Nov 30:33354918813549.

        [No abstract]

      7. University efforts to address confidentiality issues for STI servicesExternal
        Cuffe KM, Habel MA, Coor AE, Beltran O, Leichliter JS.
        J Am Coll Health. 2018 Nov 28:1-10.

        OBJECTIVE: This study assessed university policies for addressing confidentiality issues for students seeking STI services. PARTICIPANTS: Universities with sponsored health insurance plans (SHIP) and/or wellness centers were selected from a university health services survey in 2017. METHODS: STI service coverage and polices for addressing confidentiality issues related to explanation of benefit (EOB) forms were stratified by institution type (4-year versus 2-year) and minority serving institution (MSI) status. Rao-Scott chi-square tests were used to assess for differences in STI service coverage and polices. RESULTS: More non-MSIs (61.6%) had SHIPs compared to MSIs (40.0%, p < .001). Only 40.8% of health centers had a policy for addressing EOB-related confidently issues. Of those, the most reported policy was that students could pay out-of-pocket to avoid generating an EOB (36.2%). CONCLUSIONS: Reducing confidentiality barriers are important for STI prevention in students. Universities may consider establishing policies for addressing EOB-related confidentiality concerns.

      8. Progress toward regional measles elimination – worldwide, 2000-2017External
        Dabbagh A, Laws RL, Steulet C, Dumolard L, Mulders MN, Kretsinger K, Alexander JP, Rota PA, Goodson JL.
        MMWR Morb Mortal Wkly Rep. 2018 Nov 30;67(47):1323-1329.

        In 2010, the World Health Assembly set three milestones for measles prevention to be achieved by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) among children aged 1 year to >/=90% at the national level and to >/=80% in every district; 2) reduce global annual measles incidence to less than five cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (1). In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP),(dagger) with the objective of eliminating measles( section sign) in four of the six World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by 2020. This report describes progress toward global measles control milestones and regional measles elimination goals during 2000-2017 and updates a previous report (2). During 2000-2017, estimated MCV1 coverage increased globally from 72% to 85%; annual reported measles incidence decreased 83%, from 145 to 25 cases per million population; and annual estimated measles deaths decreased 80%, from 545,174 to 109,638. During this period, measles vaccination prevented an estimated 21.1 million deaths. However, measles elimination milestones have not been met, and three regions are experiencing a large measles resurgence. To make further progress, case-based surveillance needs to be strengthened, and coverage with MCV1 and the second dose of measles-containing vaccine (MCV2) needs to increase; in addition, it will be important to maintain political commitment and ensure substantial, sustained investments to achieve global and regional measles elimination goals.

      9. Eliminating perinatal HIV in the United States: mission possible?External
        Gnanashanmugam D, Rakhmanina N, Crawford K, Nesheim S, Ruel T, Birkhead GS, Chakraborty R, Lawrence R, Jean-Philippe P, Jayashankar L, Hoover A, Statton A, D’Souza P, Fitzgibbon J, Hazra R, Warren B, Smith S, Abrams EJ.
        Aids. 2018 Nov 19.

        In 2015, only 53 infants born in the United States acquired HIV, the lowest recorded number of perinatal HIV infections. Recognizing this significant achievement, we must acknowledge that the United States has not yet reached the goal of eliminating perinatal HIV transmission. This manuscript describes different approaches to perinatal HIV preventive services among five states and the District of Columbia as case studies. Continuous focus on improving identification, surveillance and prevention of HIV infection in pregnant women and their infants is necessary to reach the goal of eliminating perinatal HIV transmission in the United States.

      10. Geospatial cluster analyses of pneumonia-associated hospitalisations among adults in New York City, 2010-2014External
        Kache PA, Julien T, Corrado RE, Vora NM, Daskalakis DC, Varma JK, Lucero DE.
        Epidemiol Infect. 2018 Nov 19:1-10.

        Pneumonia is a leading cause of death in New York City (NYC). We identified spatial clusters of pneumonia-associated hospitalisation for persons residing in NYC, aged 18 years during 2010-2014. We detected pneumonia-associated hospitalisations using an all-payer inpatient dataset. Using geostatistical semivariogram modelling, local Moran’s I cluster analyses and chi2 tests, we characterised differences between ‘hot spots’ and ‘cold spots’ for pneumonia-associated hospitalisations. During 2010-2014, there were 141 730 pneumonia-associated hospitalisations across 188 NYC neighbourhoods, of which 43.5% (N = 61 712) were sub-classified as severe. Hot spots of pneumonia-associated hospitalisation spanned 26 neighbourhoods in the Bronx, Manhattan and Staten Island, whereas cold spots were found in lower Manhattan and northeastern Queens. We identified hot spots of severe pneumonia-associated hospitalisation in the northern Bronx and the northern tip of Staten Island. For severe pneumonia-associated hospitalisations, hot-spot patients were of lower mean age and a greater proportion identified as non-Hispanic Black compared with cold spot patients; additionally, hot-spot patients had a longer hospital stay and a greater proportion experienced in-hospital death compared with cold-spot patients. Pneumonia prevention efforts within NYC should consider examining the reasons for higher rates in hot-spot neighbourhoods, and focus interventions towards the Bronx, northern Manhattan and Staten Island.

      11. Impact of providing preexposure prophylaxis for human immunodeficiency virus at clinics for sexually transmitted infections in Baltimore City: An agent-based modelExternal
        Kasaie P, Berry SA, Shah MS, Rosenberg ES, Hoover KW, Gift TL, Chesson H, Pennington J, German D, Flynn CP, Beyrer C, Dowdy DW.
        Sex Transm Dis. 2018 Dec;45(12):791-797.

        BACKGROUND: Preexposure prophylaxis (PrEP) greatly reduces the risk of human immunodeficiency virus (HIV) acquisition, but its optimal delivery strategy remains uncertain. Clinics for sexually transmitted infections (STIs) can provide an efficient venue for PrEP delivery. METHODS: To quantify the added value of STI clinic-based PrEP delivery, we used an agent-based simulation of HIV transmission among men who have sex with men (MSM). We simulated the impact of PrEP delivery through STI clinics compared with PrEP delivery in other community-based settings. Our primary outcome was the projected 20-year reduction in HIV incidence among MSM. RESULTS: Assuming PrEP uptake and adherence of 60% each, evaluating STI clinic attendees and delivering PrEP to eligible MSM reduced HIV incidence by 16% [95% uncertainty range, 14%-18%] over 20 years, an impact that was 1.8 (1.7-2.0) times as great as that achieved by evaluating an equal number of MSM recruited from the community. Comparing strategies where an equal number of MSM received PrEP in each strategy (ie, evaluating more individuals for PrEP in the community-based strategy, because MSM attending STI clinics are more likely to be PrEP eligible), the reduction in HIV incidence under the STI clinic-based strategy was 1.3 (1.3-1.4) times as great as that of community-based delivery. CONCLUSIONS: Delivering PrEP to MSM who attend STI clinics can improve efficiency and effectiveness. If high levels of adherence can be achieved in this population, STI clinics may be an important venue for PrEP implementation.

      12. Progress towards polio eradication, worldwide, January 2016-March 2018Cdc-pdfExternal
        Khan F, Datta SD, Quddus A, Vertefeuille JF, Burns CC, Jorba J, Wassilak SG.
        Weekly Epidemiological Record. 2018 ;93(19):241-248.

        This report describes global progress towards polio eradication between January 2016 and March 2018 and updates previous reports. In 2017, 22 cases of polio due to WPV1 were reported, a 41% decrease from the 37 cases reported in 2016. As of 24 April 2018, 8 WPV1 cases had been reported (7 in Afghanistan and 1 in Pakistan), as compared with 5 cases during the same period in 2017. In Pakistan, continuing WPV1 transmission was confirmed in many areas in 2018 in samples isolated from wastewater. In Nigeria, ongoing endemic WPV1 transmission was confirmed in 2016;3 although WPV was not detected in 2017 and has not been detected in 2018 to date, limited access for vaccination and surveillance in insurgent-held areas in northeast Nigeria might result in continued undetected transmission of poliovirus. Substantial progress towards polio eradication has continued in recent years; however, WPV transmission can be interrupted only by overcoming the remaining challenges in reaching and vaccinating every missed child. Until poliovirus eradication is achieved, all countries must remain vigilant by maintaining high population immunity and sensitive poliovirus surveillance.

      13. Background: Differences in human papillomavirus (HPV) seroprevalence by sex have been observed, likely due to differences in the anatomic site of HPV exposure. Seroconversion may be more likely after exposure at non-keratinized (mucosal) compared to keratinized epithelium. We compared seroprevalence among self-identified gay/bisexual men who have sex with men (MSM) and females, two groups more likely exposed at mucosal epithelium, and men who only have sex with women (MSW), a group likely exposed primarily at keratinized epithelium, using data from the National Health and Nutrition Examination Survey from 2003-2010. Methods: HPV 6/11/16/18 serum antibody was detected using a multiplexed, competitive luminex immunoassay. Weighted seroprevalence was estimated among unvaccinated, sexually experienced 18-59 year-old MSM, MSW, and females, overall and by demographic and sexual behavior characteristics. Seroprevalences were compared using prevalence ratios adjusted for sexual behavior (aPRs). Results: Overall, seroprevalence in MSM, MSW, and females was 42.6%, 13.2%, and 37.1%, respectively. Seroprevalence in MSM was comparable to females (aPR: 0.85, 95% CI: 0.68-1.08) and higher than MSW (aPR: 2.72, 95% CI: 2.19-3.38). MSW had a significantly lower seroprevalence than females (aPR: 0.31, 95% CI: 0.28-0.34). Similar associations were seen in all sociodemographic subgroups. Seroprevalence increased with number of lifetime sex partners in all groups. Conclusions: In this population-based survey, HPV seroprevalence among groups likely exposed at mucosal epithelium (MSM, females) was comparable; seroprevalence in both groups was higher than in MSW. Future research could explore whether differences in seropositivity following infection results in differential protection from future infection.

      14. Trends of anogenital warts among sexually transmitted disease clinic patients – Sexually Transmitted Disease Surveillance Network, United States, 2010-2016External
        Mann LM, Llata E, Flagg EW, Hong J, Asbel L, Carlos-Henderson J, Kerani RP, Kohn R, Pathela P, Schumacher C, Torrone EA.
        J Infect Dis. 2018 Nov 29.

        Background: Approximately 90% of genital warts are caused by human papillomavirus (HPV) types 6 and 11. In the US, HPV vaccination has been recommended for females </=26 years; and since 2011, males </=21 years and gay, bisexual, and other men who have sex with men (MSM) </=26 years. Methods: Data were obtained from 27 clinics participating in the STD Surveillance Network (SSuN). Trends in the annual prevalence of anogenital warts (AGW) from 2010-2016 were described by sex and sex of sex partners. Results: From 2010-2016, significant declines in the prevalence of AGW were observed in women aged <40 years; men who have sex with women only (MSW) <40 years; and among all age categories of MSM. An inflection in trend was noted for MSW aged 20-24 and 25-29 years and MSM aged 20-24 years in 2012. Conclusions: The observed declines in AGW suggest that HPV morbidity is declining among populations attending STD clinics, including MSW, MSM, and women. Declines in younger age groups are consistent with what would be expected following the implementation of HPV vaccination. However, declines were also observed in older age groups, and are not likely to be the result of vaccination.

      15. Diagnosis of human immunodeficiency virus infectionExternal
        Parekh BS, Ou CY, Fonjungo PN, Kalou MB, Rottinghaus E, Puren A, Alexander H, Hurlston Cox M, Nkengasong JN.
        Clin Microbiol Rev. 2019 Jan;32(1).

        HIV diagnostics have played a central role in the remarkable progress in identifying, staging, initiating, and monitoring infected individuals on life-saving antiretroviral therapy. They are also useful in surveillance and outbreak responses, allowing for assessment of disease burden and identification of vulnerable populations and transmission “hot spots,” thus enabling planning, appropriate interventions, and allocation of appropriate funding. HIV diagnostics are critical in achieving epidemic control and require a hybrid of conventional laboratory-based diagnostic tests and new technologies, including point-of-care (POC) testing, to expand coverage, increase access, and positively impact patient management. In this review, we provide (i) a historical perspective on the evolution of HIV diagnostics (serologic and molecular) and their interplay with WHO normative guidelines, (ii) a description of the role of conventional and POC testing within the tiered laboratory diagnostic network, (iii) information on the evaluations and selection of appropriate diagnostics, (iv) a description of the quality management systems needed to ensure reliability of testing, and (v) strategies to increase access while reducing the time to return results to patients. Maintaining the central role of HIV diagnostics in programs requires periodic monitoring and optimization with quality assurance in order to inform adjustments or alignment to achieve epidemic control.

      16. Minimally invasive saliva testing to monitor norovirus infection in community settingsExternal
        Pisanic N, Ballard SB, Colquechagua FD, Francois R, Exum N, Yori PP, Schwab KJ, Granger DA, Detrick B, Olortegui MP, Mayta H, Sanchez GJ, Gilman RH, Heaney CD, Vinje J, Kosek MN.
        J Infect Dis. 2018 Dec 5.

        Background: Norovirus is a leading cause of acute gastroenteritis worldwide. Routine norovirus diagnosis requires stool collection. The goal of this study was to develop and validate a noninvasive method to diagnose norovirus to complement stool diagnostics and to facilitate studies on transmission. Methods: A multiplex immunoassay to measure salivary immunoglobulin G (IgG) responses to 5 common norovirus genotypes (GI.1, GII.2, GII.4, GII.6, and GII.17) was developed. The assay was validated using acute and convalescent saliva samples collected from Peruvian children <5 years of age with polymerase chain reaction (PCR)-diagnosed norovirus infections (n = 175) and controls (n = 32). The assay sensitivity and specificity were calculated to determine infection status based on fold rise of salivary norovirus genotype-specific IgG using norovirus genotype from stool as reference. Results: The salivary assay detected recent norovirus infections and correctly assigned the infecting genotype. Sensitivity was 71% and specificity was 96% across the evaluated genotypes compared to PCR-diagnosed norovirus infection. Conclusions: This saliva-based assay will be a useful tool to monitor norovirus transmission in high-risk settings such as daycare centers or hospitals. Cross-reactivity is limited between the tested genotypes, which represent the most commonly circulating genotypes.

      17. Recent and occult hepatitis B virus infections among blood donors in the United StatesExternal
        Ramachandran S, Groves JA, Xia GL, Saa P, Notari EP, Drobeniuc J, Poe A, Khudyakov N, Schillie SF, Murphy TV, Kamili S, Teo CG, Dodd RY, Khudyakov YE, Stramer SL.
        Transfusion. 2018 Nov 30.

        BACKGROUND: Characteristics of US blood donors with recent (RBI) or occult (OBI) hepatitis B virus (HBV) infection are not well defined. METHODS: Donors with RBI and OBI were identified by nucleic acid and serologic testing among 34.4 million donations during 2009-2015. Consenting donors were interviewed and their HBV S-gene sequenced. RESULTS: The overall rate of HBV-infected donors was 7.95 per 100,000; of these, 0.35 per 100,000 and 1.70 per 100,000 were RBI and OBI, respectively. RBI (n = 120) and OBI (n = 583) donors constituted 26% of all HBV-infected (n = 2735) donors. Detection of HBV DNA in 92% of OBI donors required individual donation nucleic acid testing. Donors with OBI compared to RBI were older (mean age, 48 vs 39 years; p < 0.0001) with lower median viral loads (9 vs. 529 IU/mL; p < 0.0001). A higher proportion of OBI than RBI donors were born or resided in an endemic country (39% vs. 5%; p = 0.0078). Seventy-seven percent of all RBI and OBI donors had multiple sex partners, an HBV-risk factor. Of 40 RBI and 10 OBI donors whose S gene was sequenced, 33 (83%) and 6 (60%), respectively, carried HBV subgenotype A2; 18 (55%) and 2 (33%), respectively, shared an identical sequence. Infection with 1 or more putative HBV-immune-escape mutants was identified in 5 (50%) of OBI but no RBI donors. CONCLUSION: RBI and OBI continue to be identified at low rates, confirming the importance of comprehensive HBV DNA screening of US blood donations. HBV-infected donors require referral for care and evaluation and contact tracing; their HBV strains may provide important information on emergent genotypes.

      18. Bacterial meningitis: more can be doneCdc-pdfExternal
        Sejvar JJ.
        Lancet Neurol. 2018 ;17(12):1028-1030.

        [No abstract]

      19. BACKGROUND: Increased gonorrhea detection highlights the need for additional prevention efforts. Gonorrhea may only be acquired when there is contact between infected and uninfected anatomical sites. With three sites of infection this leads to seven plausible routes of MSM transmission: urethra-to-rectum, rectum-to-urethra, urethra-to-oropharynx, rectum-to-oropharynx, oropharynx-to-urethra, oropharynx-to-rectum, and oropharynx-to-oropharynx. We characterize the uncertainty and potential importance of transmission from each anatomical site using a deterministic compartmental mathematical model. METHODS: We developed a model of site-specific gonococcal infection, where individuals are infected at zero, one, two, or all three sites. Sexual behavior and infection duration parameters were fixed similar to a recent model analysis of Australian MSM. Markov Chain Monte Carlo methods were used to sample the posterior distribution of transmission probabilities that were consistent with site-specific prevalence in American MSM populations under specific scenarios. Scenarios were defined by whether transmission routes may or may not transmit by constraining specific transmission probabilities to zero rather than fitting them. RESULTS: Transmission contributions from each site have greater uncertainty when more routes may transmit; in the most extreme case, when all routes may transmit, the oropharynx can contribute 0-100% of all transmissions. In contrast, when only anal or oral sex may transmit, transmission from the oropharynx can account for only 0-25% of transmission. Intervention effectiveness against transmission from each site also has greater uncertainty when more routes may transmit. CONCLUSION: Even under ideal conditions (i.e., when site-specific gonococcal prevalence, relative rates of specific sex acts, and duration of infection at each anatomical site are known and do not vary), the relative importance of different anatomical sites for gonococcal infection transmission cannot be inferred with precision. Additional data informing per act transmissibility are needed to understand site-specific gonococcal infection transmission. This understanding is essential for predicting population-specific intervention effectiveness.

      20. Risk factors for acquiring scrub typhus among children in Deoria and Gorakhpur Districts, Uttar Pradesh, India, 2017External
        Thangaraj JW, Vasanthapuram R, Machado L, Arunkumar G, Sodha SV, Zaman K, Bhatnagar T, Hameed SK, Kumar A, Abdulmajeed J, Velayudhan A, Deoshatwar A, Desai AS, Kumar KH, Gupta N, Laserson K, Murhekar M.
        Emerg Infect Dis. 2018 Dec;24(12):2364-2367.

        Scrub typhus is associated with outbreaks of acute encephalitis syndrome in Uttar Pradesh, India. A case-control study indicated that children residing, playing, or visiting fields; living with firewood stored indoors; handling cattle fodder; and practicing open defecation were at increased risk for scrub typhus. Communication messages should focus on changing these behaviors.

      21. National estimates and risk factors associated with early mother-to-child transmission of HIV after implementation of option B+: a cross-sectional analysisExternal
        Tippett Barr BA, van Lettow M, van Oosterhout JJ, Landes M, Shiraishi RW, Amene E, Schouten E, Wadonda-Kabondo N, Gupta S, Auld AF, Kalua T, Jahn A.
        Lancet HIV. 2018 Nov 19.

        BACKGROUND: Routine data from Malawi’s prevention of mother-to-child transmission (MTCT) option B+ programme suggest high uptake of antiretroviral therapy (ART) among pregnant women. Malawi’s Ministry of Health led the National Evaluation of Malawi’s PMTCT Program to obtain nationally representative data on maternal ART coverage and prevention of MTCT effectiveness. Here, we present the early transmission data for infants aged 4-12 weeks. METHODS: We used a multistage cluster design to recruit a nationally representative sample of HIV-exposed infants and their mothers in Malawi. Between October 16, 2014, and May 17, 2016, we screened for HIV in all mothers attending an under-5 vaccination or outpatient sick-child clinic with infants aged 4-26 weeks at 54 health facilities selected across ten districts and four regional sampling zones. Infants with mothers identified as HIV-infected were enrolled in the cohort. We calculated weighted MTCT rates for only the subset of infants aged 4-12 weeks at screening, thereby capturing MTCT from early pregnancy, to delivery, and early breastfeeding. We collected data on maternal and infant demographics and self-reported use of HIV services, ART, and antenatal clinics. We tested HIV-exposed infants for the virus and assessed associations of certain variables with infant HIV status. FINDINGS: We confirmed HIV exposure in 3542 (10.4%) of 33 980 mother (guardian)-infant pairs with infants aged 4-26 weeks. Of those, 2530 (2514 mothers and 16 guardians) had infants aged 4-12 weeks at the time of screening (2498 singlets and 32 twins). We excluded 25 infants from the analysis because no information was available about their HIV status. 91.3% (95% CI 85.6-96.9) of mothers were on ART during pregnancy. The MTCT rate was 3.7% (2.3-6.0) overall and ranged from 1.4% (0.4-4.4) in women who initiated ART before pregnancy to 19.9% (13.4-28.6) in women not on ART. In multivariable logistic regression analysis, the odds of early MTCT were higher in mothers starting ART post partum (adjusted odds ratio 16.7, 95% CI 1.6-171.5; p=0.022) and in those not on ART with an unknown HIV status during pregnancy (19.1, 8.5-43.0; p<0.0001) than in mothers on ART before pregnancy. Among HIV-exposed infants, 98.0% (95% CI 96.9-99.1) were reported by the mother to have received infant nevirapine prophylaxis, and only 45.6% (34.8-56.4) were already enrolled in an exposed infant HIV care clinic at the time of study screening. INTERPRETATION: These data suggest that Malawi’s decentralisation of ART services has resulted in higher ART coverage and lower early MTCT. However, the uptake of services for HIV-exposed infants remains suboptimal. FUNDING: President’s Emergency Plan for AIDS Relief.

      22. Prevention of mother-to-child transmission of HIV: a cross-sectional study in MalawiExternal
        van Lettow M, Landes M, van Oosterhout JJ, Schouten E, Phiri H, Nkhoma E, Kalua T, Gupta S, Wadonda N, Jahn A, Tippett-Barr B.
        Bull World Health Organ. 2018 Apr 1;96(4):256-265.

        Objective: To estimate the use and outcomes of the Malawian programme for the prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Methods: In a cross-sectional analysis of 33 744 mother-infant pairs, we estimated the weighted proportions of mothers who had received antenatal HIV testing and/or maternal antiretroviral therapy and infants who had received nevirapine prophylaxis and/or HIV testing. We calculated the ratios of MTCT at 4-26 weeks postpartum for subgroups that had missed none or at least one of these four steps. Findings: The estimated uptake of antenatal testing was 97.8%; while maternal antiretroviral therapy was 96.3%; infant prophylaxis was 92.3%; and infant HIV testing was 53.2%. Estimated ratios of MTCT were 4.7% overall and 7.7% for the pairs that had missed maternal antiretroviral therapy, 10.7% for missing both maternal antiretroviral therapy and infant prophylaxis and 11.4% for missing maternal antiretroviral therapy, infant prophylaxis and infant testing. Women younger than 19 years were more likely to have missed HIV testing (adjusted odds ratio, aOR: 4.9; 95% confidence interval, CI: 2.3-10.6) and infant prophylaxis (aOR: 6.9; 95% CI: 1.2-38.9) than older women. Women who had never started maternal antiretroviral therapy were more likely to have missed infant prophylaxis (aOR: 15.4; 95% CI: 7.2-32.9) and infant testing (aOR: 13.7; 95% CI: 4.2-83.3) than women who had. Conclusion: Most women used the Malawian programme for the prevention of MTCT. The risk of MTCT increased if any of the main steps in the programme were missed.

      23. Viral loads in congenital cytomegalovirus infection from a highly immune populationExternal
        Xu A, Wang S, Zhang W, Wang X, Wang T, Liu X, Wang H, Ma W, Amin M, Dollard S, Wang C.
        J Pediatric Infect Dis Soc. 2018 Aug 17;7(3):e160-e162.

        Among newborns with congenital cytomegalovirus (CMV) infection from China, there was no difference in CMV viral load in saliva specimens dried and stored at room temperature compared with those kept wet and stored cold, even after longer storage time for the former than the later (74 vs 58 days, P = .02).

    • Disaster Control and Emergency Services
      1. Preparedness Emergency Response Research Centers (PERRCs): Addressing public health preparedness knowledge gaps using a public health systems perspectiveExternal
        Savoia E, Guicciardi S, Bernard DP, Harriman N, Leinhos M, Testa M.
        Am J Public Health. 2018 Nov;108(S5):S363-s365.

        [No abstract]

      2. The Centers for Disease Control and Prevention’s Division of Select Agents and Toxins (DSAT) regulates the possession, use, and transfer of select agents and toxins throughout the United States as part of the Federal Select Agent Program. The Department of Health and Human Services (HHS) select agent regulations also include criteria for the exclusion of select agents and toxins from the requirements of the regulations (42 CFR section sign 73.3 and 73.4). An entity may request the exclusion of an attenuated strain of a select agent or a select toxin modified to be less potent or toxic. The Intragovernmental Select Agents and Toxins Technical Advisory Committee (ISATTAC) reviews the exclusion request by conducting a risk assessment to determine whether the attenuated strain or modified toxin has the potential to pose a severe risk to public health and safety. In this study, DSAT analyzed the number and types of exclusion requests reviewed by the ISATTAC from January 2003 through December 2017. As of December 2017, DSAT has excluded 50 strains of biological agents and 10 modified toxins from the select agent regulations. The select agent regulations provision for the exclusion of attenuated select agents or modified toxins that no longer have the potential to pose a severe threat to public health and safety is an important mechanism for reducing the regulatory burden on entities that do not need to work with the fully virulent or toxic forms of the agent or toxin. This provision may have the added benefit of encouraging entities to consider working with variants of select agents or toxins that are of less risk than the fully virulent or toxic forms in their research studies and as a positive control.

    • Disease Reservoirs and Vectors
      1. Human exposure to novel Bartonella species from contact with fruit batsExternal
        Bai Y, Osinubi MO, Osikowicz L, McKee C, Vora NM, Rizzo MR, Recuenco S, Davis L, Niezgoda M, Ehimiyein AM, Kia GS, Oyemakinde A, Adeniyi OS, Gbadegesin YH, Saliman OA, Ogunniyi A, Ogunkoya AB, Kosoy MY.
        Emerg Infect Dis. 2018 Dec;24(12):2317-2323.

        Twice a year in southwestern Nigeria, during a traditional bat festival, community participants enter designated caves to capture bats, which are then consumed for food or traded. We investigated the presence of Bartonella species in Egyptian fruit bats (Rousettus aegyptiacus) and bat flies (Eucampsipoda africana) from these caves and assessed whether Bartonella infections had occurred in persons from the surrounding communities. Our results indicate that these bats and flies harbor Bartonella strains, which multilocus sequence typing indicated probably represent a novel Bartonella species, proposed as Bartonella rousetti. In serum from 8 of 204 persons, we detected antibodies to B. rousetti without cross-reactivity to other Bartonella species. This work suggests that bat-associated Bartonella strains might be capable of infecting humans.

      2. Multistate Infestation with the exotic disease-vector tick Haemaphysalis longicornis – United States, August 2017-September 2018External
        Beard CB, Occi J, Bonilla DL, Egizi AM, Fonseca DM, Mertins JW, Backenson BP, Bajwa WI, Barbarin AM, Bertone MA, Brown J, Connally NP, Connell ND, Eisen RJ, Falco RC, James AM, Krell RK, Lahmers K, Lewis N, Little SE, Neault M, Perez de Leon AA, Randall AR, Ruder MG, Saleh MN, Schappach BL, Schroeder BA, Seraphin LL, Wehtje M, Wormser GP, Yabsley MJ, Halperin W.
        MMWR Morb Mortal Wkly Rep. 2018 Nov 30;67(47):1310-1313.

        Haemaphysalis longicornis is a tick indigenous to eastern Asia and an important vector of human and animal disease agents, resulting in such outcomes as human hemorrhagic fever and reduction of production in dairy cattle by 25%. H. longicornis was discovered on a sheep in New Jersey in August 2017 (1). This was the first detection in the United States outside of quarantine. In the spring of 2018, the tick was again detected at the index site, and later, in other counties in New Jersey, in seven other states in the eastern United States, and in Arkansas. The hosts included six species of domestic animals, six species of wildlife, and humans. To forestall adverse consequences in humans, pets, livestock, and wildlife, several critical actions are indicated, including expanded surveillance to determine the evolving distribution of H. longicornis, detection of pathogens that H. longicornis currently harbors, determination of the capacity of H. longicornis to serve as a vector for a range of potential pathogens, and evaluation of effective agents and methods for the control of H. longicornis.

      3. Novel Wolbachia strains in Anopheles malaria vectors from Sub-Saharan AfricaExternal
        Jeffries CL, Lawrence GG, Golovko G, Kristan M, Orsborne J, Spence K, Hurn E, Bandibabone J, Tantely LM, Raharimalala FN, Keita K, Camara D, Barry Y, Wat’senga F, Manzambi EZ, Afrane YA, Mohammed AR, Abeku TA, Hedge S, Khanipov K, Pimenova M, Fofanov Y, Boyer S, Irish SR, Hughes GL, Walker T.
        Wellcome Open Res. 2018 ;3:113.

        Background: Wolbachia, a common insect endosymbiotic bacterium that can influence pathogen transmission and manipulate host reproduction, has historically been considered absent from the Anopheles (An.) genera, but has recently been found in An. gambiae s.l. populations. As there are numerous Anopheles species that have the capacity to transmit malaria, we analysed a range of species to determine Wolbachia prevalence rates, characterise novel Wolbachia strains and determine any correlation between the presence of Plasmodium, Wolbachia and the competing endosymbiotic bacterium Asaia. Methods: Anopheles adult mosquitoes were collected from five malaria-endemic countries: Guinea, Democratic Republic of the Congo (DRC), Ghana, Uganda and Madagascar, between 2013 and 2017. Molecular analysis of samples was undertaken using quantitative PCR, Sanger sequencing, Wolbachia multilocus sequence typing (MLST) and high-throughput amplicon sequencing of the bacterial 16S rRNA gene. Results: Novel Wolbachia strains were discovered in five species: An. coluzzii, An. gambiae s.s., An. arabiensis, An. moucheti and An. species ‘A’, increasing the number of Anopheles species known to be naturally infected. Variable prevalence rates in different locations were observed and novel strains were phylogenetically diverse, clustering with Wolbachia supergroup B strains. We also provide evidence for resident strain variants within An. species ‘A’. Wolbachia is the dominant member of the microbiome in An. moucheti and An. species ‘A’, but present at lower densities in An. coluzzii. Interestingly, no evidence of Wolbachia/Asaia co-infections was seen and Asaia infection densities were also shown to be variable and location dependent. Conclusions: The important discovery of novel Wolbachia strains in Anopheles provides greater insight into the prevalence of resident Wolbachia strains in diverse malaria vectors. Novel Wolbachia strains (particularly high-density strains) are ideal candidate strains for transinfection to create stable infections in other Anopheles mosquito species, which could be used for population replacement or suppression control strategies.

      4. The Amblyomma maculatum Koch, 1844 (Acari: Ixodidae) group of ticks: phenotypic plasticity or incipient speciation?External
        Lado P, Nava S, Mendoza-Uribe L, Caceres AG, Delgado-de la Mora J, Licona-Enriquez JD, Delgado-de la Mora D, Labruna MB, Durden LA, Allerdice ME, Paddock CD, Szabo MP, Venzal JM, Guglielmone AA, Beati L.
        Parasit Vectors. 2018 Nov 29;11(1):610.

        BACKGROUND: The goal of this study was to reassess the taxonomic status of A. maculatum, A. triste and A. tigrinum by phylogenetic analysis of five molecular markers [four mitochondrial: 12S rDNA, 16S rDNA, the control region (DL) and cytochrome c oxidase 1 (cox1), and one nuclear: ribosomal intergenic transcribed spacer 2 (ITS2)]. In addition, the phenotypic diversity of adult ticks identified as A. maculatum and A. triste from geographically distinct populations was thoroughly re-examined. RESULTS: Microscopic examination identified four putative morphotypes distinguishable by disjunct geographical ranges, but very scant fixed characters. Analysis of the separated mitochondrial datasets mostly resulted in conflicting tree topologies. Nuclear gene sequences were almost identical throughout the geographical ranges of the two species, suggesting a very recent, almost explosive radiation of the terminal operational taxonomic units. Analysis of concatenated molecular datasets was more informative and indicated that, although genetically very close to the A. maculatum – A. triste lineage, A. tigrinum was a monophyletic separate entity. Within the A. maculatum – A. triste cluster, three main clades were supported. The two morphotypes, corresponding to the western North American and eastern North American populations, consistently grouped in a single monophyletic clade with many shared mitochondrial sequences among ticks of the two areas. Ticks from the two remaining morphotypes, south-eastern South America and Peruvian, corresponded to two distinct clades. CONCLUSIONS: Given the paucity of morphological characters, the minimal genetic distance separating morphotypes, and more importantly the fact that two morphotypes are genetically indistinguishable, our data suggest that A. maculatum and A. triste should be synonymized and that morphological differences merely reflect very recent local adaptation to distinct environments in taxa that might be undergoing the first steps of speciation but have yet to complete lineage sorting. Nonetheless, future investigations using more sensitive nuclear markers and/or crossbreeding experiments might reveal the occurrence of very rapid speciation events in this group of taxa. Tentative node dating revealed that the A. tigrinum and A. maculatum – A. triste clades split about 2 Mya, while the A. maculatum – A.triste cluster radiated no earlier than 700,000 years ago.

    • Drug Safety
      1. The increased use of opioids to treat chronic pain in the past 20 years has led to a drastic increase in opioid prescribing in the United States. The Centers for Disease Control and Prevention’s (CDC’s) Guideline for Prescribing Opioids for Chronic Pain recommends the use of nonopioid therapy as the preferred treatment for chronic pain. This study analyzes the prevalence of nonopioid prescribing among commercially insured patients with chronic pain. Data from the 2014 IBM (R) MarketScan (R) databases representing claims for commercially insured patients were used. International Classification of Diseases, Ninth Revision, codes were used to identify patients with chronic pain. Nonopioid prescriptions included nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics/antipyretics (e.g., acetaminophen), anticonvulsants, and antidepressant medications. The prevalence of nonopioid and opioid prescriptions was calculated by age, sex, insurance plan type, presence of a depressive or seizure disorder, and region. In 2014, among patients with chronic pain, 16% filled only an opioid, 17% filled only a nonopioid prescription, and 28% filled both a nonopioid and an opioid. NSAIDs and antidepressants were the most commonly prescribed nonopioids among patients with chronic pain. Having prescriptions for only nonopioids was more common among patients aged 50-64 years and among female patients. This study provides a baseline snapshot of nonopioid prescriptions before the release of the CDC Guideline and can be used to examine the impact of the CDC Guideline and other evidence-based guidelines on nonopioid use among commercially insured patients with chronic pain.

      2. Impact of a prescriber-driven antibiotic time-out on antibiotic use in hospitalized patientsExternal
        Thom KA, Tamma PD, Harris AD, Dzintars K, Morgan DJ, Li S, Pineles L, Srinivasan A, Avdic E, Cosgrove SE.
        Clin Infect Dis. 2018 Dec 4.

        A multicenter quasi-experimental study of a provider-driven antibiotic “time-out” in 3470 antibiotic courses showed no difference in antibiotic use before and after implementation, but did show a decrease in inappropriate therapy (45% vs 31%, P < .05). Single time-outs without input from antibiotic stewardship teams are insufficient to optimize prescribing.

    • Environmental Health
      1. Neonicotinoid insecticides are widely used replacements for organophosphate and carbamate insecticides, but the extent of human exposure is largely unknown. On the other hand, based on urinary concentrations of DEET metabolites, human exposure to N,N-diethyl-m-toluamide (DEET) appears to be widespread. We developed a fast online solid-phase extraction high-performance liquid chromatography-isotope dilution tandem mass spectrometry (HPLC-MS/MS) method to measure in 200 muL of human urine the concentrations of six neonicotinoid biomarkers (acetamiprid, N-desmethyl-acetamiprid, clothianidin, imidacloprid, 5-hydroxy-imidacloprid, thiacloprid), and two DEET biomarkers (3-diethyl-carbamoyl benzoic acid, 3-ethyl-carbamoyl benzoic acid). Limits of detection ranged from 0.01 to 0.1 mug/L, depending on the biomarker. Accuracy ranged from 91 to 116% and precision ranged from 3.7 to 10 %RSD. The presented method can be used to increase our understanding of exposure to neonicotinoid insecticides and DEET, and to evaluate the potential health effects from such exposures.

      2. Association of phthalates, parabens and phenols found in personal care products with pubertal timing in girls and boysExternal
        Harley KG, Berger KP, Kogut K, Parra K, Lustig RH, Greenspan LC, Calafat AM, Ye X, Eskenazi B.
        Hum Reprod. 2018 Dec 4.

        STUDY QUESTION: Are in-utero or peripubertal exposures to phthalates, parabens and other phenols found in personal care products associated with timing of pubertal onset in boys and girls? SUMMARY ANSWER: We found some associations of altered pubertal timing in girls, but little evidence in boys. WHAT IS KNOWN ALREADY: Certain chemicals in personal care and consumer products, including low molecular weight phthalates, parabens and phenols, or their precursors, are associated with altered pubertal timing in animal studies. STUDY DESIGN, SIZE, DURATION: Data were from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study which followed 338 children in the Salinas Valley, California, from before birth to adolescence. PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnant women were enrolled in 1999-2000. Mothers were mostly Latina, living below the federal poverty threshold and without a high school diploma. We measured concentrations of three phthalate metabolites (monoethyl phthalate [MEP], mono-n-butyl phthalate and mono-isobutyl phthalate), methyl and propyl paraben and four other phenols (triclosan, benzophenone-3 and 2,4- and 2,5-dichlorophenol) in urine collected from mothers during pregnancy and from children at age 9. Pubertal timing was assessed among 179 girls and 159 boys every 9 months between ages 9 and 13 using clinical Tanner staging. Accelerated failure time models were used to obtain mean shifts of pubertal timing associated with concentrations of prenatal and peripubertal biomarkers. MAIN RESULTS AND THE ROLE OF CHANCE: In girls, we observed earlier onset of pubic hair development with prenatal urinary MEP concentrations and earlier menarche with prenatal triclosan and 2,4-dichlorophenol concentrations. Regarding peripubertal biomarkers, we observed: earlier breast development, pubic hair development and menarche with methyl paraben; earlier menarche with propyl paraben; and later pubic hair development with 2,5-dichlorophenol. In boys, we observed no associations with prenatal urinary biomarker concentrations and only one association with peripubertal concentrations: earlier genital development with propyl paraben. LIMITATIONS, REASONS FOR CAUTION: These chemicals are quickly metabolized and one to two urinary measurements per developmental point may not accurately reflect usual exposure. Associations of peripubertal measurements with parabens may reflect reverse causality: children going through puberty early may be more likely to use personal care products. The study population was limited to Latino children of low socioeconomic status living in a farmworker community and may not be widely generalizable. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to a growing literature that suggests that exposure to certain endocrine disrupting chemicals may impact timing of puberty in children. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Institute of Environmental Health Sciences and the US Environmental Protection Agency. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

      3. Childhood polybrominated diphenyl ether (PBDE) serum concentration and reading ability at ages 5 and 8 years: The HOME StudyExternal
        Liang H, Vuong AM, Xie C, Webster GM, Sjodin A, Yuan W, Miao M, Braun JM, Dietrich KN, Yolton K, Lanphear BP, Chen A.
        Environ Int. 2018 .

        Background: Polybrominated diphenyl ethers (PBDEs) exist extensively in the environment and human beings. PBDE concentrations are higher in children than adults. A previous study found that prenatal PBDE exposure was associated with decreased reading skills in children; however, evidence is limited on the potential impact of childhood exposure to PBDEs. The study examined the association between childhood PBDE exposures and reading ability in children at ages 5 and 8 years. Methods: The study included 230 children from an ongoing prospective pregnancy and birth cohort study, the Health Outcomes and Measures of Environment (HOME) Study, conducted in Cincinnati, Ohio. Children’s serum concentrations of eleven PBDE congeners were measured at 1, 2, 3, 5, and 8 years. The Woodcock-Johnson Tests of Achievement – III and the Wide Range Achievement Test – 4 were administered to assess children’s reading skills at ages 5 and 8 years, respectively. We used multiple informant models to examine the associations between repeated measures of PBDEs and reading scores at ages 5 and 8 years. We also estimated the betas and 95% CIs of the association of PBDE measure at each age by including interaction terms between PBDE concentrations and child age in the models. Results: All childhood BDE-153 concentrations were inversely associated with reading scores at 5 and 8 years, but associations were not statistically significant after covariate adjustment. For example, a 10-fold increase in BDE-153 concentrations at ages 3 and 5 years was associated with a -5.0 (95% confidence interval (CI): -11.0, 1.0) and -5.5 (95% CI: -12.5, 1.4) point change in Basic Reading score at age 5 years, respectively. Similarly, the estimates for Brief Reading score at age 5 years were -4.5 (95% CI: -10.5, 1.5) and -5.2 (95% CI: -12.2, 1.7) point changes, respectively. Serum concentration of BDE-47, -99, -100, and Sum4PBDEs (sum of BDE-47, 99, 100, and 153) at every age were inversely associated with reading scores at ages 5 and 8 years in unadjusted analyses. While the adjusted estimates were much attenuated and became non-significant, the direction of most of the associations was not altered. Conclusion: Our study has shown a suggestive but non-significant trend of inverse associations between childhood PBDE serum concentrations, particularly BDE-153, and children’s reading skills. Future studies with a larger sample size are needed to examine these associations.

      4. Variability of urinary concentrations of phthalate metabolites during pregnancy in first morning voids and pooled samplesExternal
        Shin HM, Bennett DH, Barkoski J, Ye X, Calafat AM, Tancredi D, Hertz-Picciotto I.
        Environ Int. 2018 Nov 23.

        BACKGROUND: Because phthalates are quickly metabolized and excreted in urine, and human exposures tend to be episodic, phthalate metabolite concentrations measured in a maternal spot urine sample are only indicative of recent exposure. OBJECTIVE: To examine temporal variability of pregnant women’s phthalate exposure using multiple first morning voids (FMV) and pooled samples. METHODS: We quantified 14 metabolites of eight phthalates in 577 urine samples collected from 188 pregnancies in the MARBLES (Markers of Autism Risk in Babies – Learning Early Signs) study. We calculated intraclass correlation coefficients (ICCs) using two samples of the same urine type (i.e., two FMVs or two pools) collected across the 2nd and 3rd trimesters. We also calculated ICCs and FMV/pool concentration ratios using two samples (i.e., two FMVs or one FMV and one pool) collected within the same trimester. RESULTS: Overall, ICCs were higher in pooled samples (0.24-0.87) than in FMVs (0.08-0.69). Regardless of the sample type, ICCs tended to be higher for metabolites for which exposure sources are personal care products or indoor residential materials than those for which diet is an important exposure source. ICCs tended to increase and FMV/pool ratios tended to decrease with an increasing number of composite samples in the pools. CONCLUSIONS: Our study helped determine the number of samples needed to capture moderate to high reproducibility of individual’s average exposure to phthalates and the average exposure can be differently characterized depending on the number of samples in the pools.

    • Genetics and Genomics
      1. Complete genome sequence of streptacidiphilus sp. strain 15-057A, obtained from bronchial lavage fluidExternal
        Arthur RA, Gulvik CA, Humrighouse BW, Lasker BA, Batra D, Rowe LA, Igual JM, Nouioui I, Klenk HP, McQuiston JR.
        Microbiol Resour Announc. 2018 ;7(19).

        Streptacidiphilus sp. strain 15-057A was isolated from a bronchial lavage sample and represents the only member of the genus not isolated from acidic soils. A single circular chromosome of 7.01 Mb was obtained by combining Illumina and PacBio sequencing data. Bioinformatic analysis detected 63 putative secondary biosynthetic gene clusters and recognized 43 transposons.

    • Health Disparities
      1. Health disparities among American Indians/Alaska Natives – Arizona, 2017External
        Adakai M, Sandoval-Rosario M, Xu F, Aseret-Manygoats T, Allison M, Greenlund KJ, Barbour KE.
        MMWR Morb Mortal Wkly Rep. 2018 Nov 30;67(47):1314-1318.

        Compared with other racial/ethnic groups, American Indians/Alaska Natives (AI/AN) have a lower life expectancy, lower quality of life, and are disproportionately affected by many chronic conditions (1,2). Arizona has the third largest population of AI/AN in the United States (approximately 266,000 in 2017), and is home to 22 federally recognized American Indian tribal nations.* The small AI/AN sample size in previous Behavioral Risk Factor Surveillance System (BRFSS) surveys has presented analytic challenges in making statistical inferences about this population. To identify health disparities among AI/AN living in Arizona, the Arizona Department of Health Services (ADHS) and CDC analyzed data from the 2017 BRFSS survey, for which AI/AN were oversampled. Compared with whites, AI/AN had significantly higher prevalences of sugar-sweetened beverage consumption (33.0% versus 26.8%), being overweight or having obesity (76.7% versus 63.2%), diabetes (21.4% versus 8.0%), high blood pressure (32.9% versus 27.6%), report of fair or poor health status (28.7% versus 16.3%), and leisure-time physical inactivity during the past month (31.1% versus 23.0%). AI/AN also reported a lower prevalence of having a personal doctor or health care provider (63.1%) than did whites (72.8%). This report highlights the need to enhance surveillance measures at the local, state, and national levels and can inform interventions centered on confronting social inequities, developing culturally competent prevention strategies, and facilitating access to care to improve population health and work toward health equity.

      2. Advancing health disparities research in population healthExternal
        Jack L.
        Prev Chronic Dis. 2018 Nov 29;15:E147.

        [No abstract]

      3. Advancing health equity through the National Comprehensive Cancer Control ProgramExternal
        Momin B, Wanliss E, Davis L, Townsend JS, Lopez K, Steele B.
        Cancer Causes Control. 2018 Dec 4.

        Achieving health equity requires addressing social determinants of health. Promoting health equity as it relates to cancer control is one of six priorities of the National Comprehensive Cancer Control Program (NCCCP). This article describes recent activities implemented by three NCCCP awardees (North-west Portland Area Indian Health Board, Kansas, Michigan) and the CDC-funded National Behavior Health Network (NBHN), whose aim is to reduce health disparities among those with mental health and/or substance disorders. North-west Portland administered tribal surveys to help better understand tribal cancer-related risk factors, health behaviors, provide baseline data to support their cancer plan, and obtain resources for targeted interventions. Kansas established a health equity workgroup with a vision of addressing health equity through implementation and uptake of activities among all Kansans. Michigan provided trainings in health equity and social justice and developed health equity learning labs. As a result of the successful implementation of the NBHN’s Community of Practice, individuals currently living with mental illness and/or substance disorders have had increased access to tobacco cessation and other cancer support services. These efforts and key opportunities for public health practitioners and their partners to increase engagement in cancer health equity are summarized in this article.

    • Immunity and Immunization
      1. Background: In a 2012 phase II clinical trial (NCT01625689), 300 Bangladeshi children aged 24 to 59 months with no prior influenza vaccine exposure were randomized to receive a single dose of intra-nasally administered trivalent Russian-backbone live attenuated influenza vaccine (LAIV) or placebo. Protocol-defined analyses, presented in the companion manuscript, demonstrate decreased viral detection and immunogenicity for A/H1N1pdm09 relative to the A/H3N2 and B strains. This post-hoc analysis of the trial data aims to investigate the LAIV strain differences by testing the hypothesis that pre-existing immunity may influence viral recovery and immune responses after LAIV receipt. Methods: We used logistic regressions to evaluate the relations between markers of pre-existing immunity (i.e., hemagglutination inhibition (HAI), microneutralization, and IgA and IgG antibodies) and LAIV viral recovery in the week post-vaccination. We then tested for potential effect modification by baseline HAI titers (i.e., <10 versus >/=10) and week 1 viral recovery on the LAIV-induced serum and mucosal immune responses measured between days 0 and 21 post-vaccination. Results: Higher levels of pre-existing immunity to influenza A/H3N2 and B were strongly associated with strain-specific prevention of viral shedding upon LAIV receipt. While evidence of LAIV immunogenicity was observed for all three strains, the magnitudes of immune responses were most pronounced in children with no evidence of pre-existing HAI and in those with detectable virus. Conclusion: The results provide evidence for a bidirectional association between viral replication and immunity and underscore the importance of accounting for pre-existing immunity when evaluating virologic and immunologic responses to LAIVs.

      2. Developing a seasonal influenza vaccine recommendation in Kenya: Process and challenges faced by the National Immunization Technical Advisory Group (NITAG)External
        Dawa J, Chaves SS, Ba Nguz A, Kalani R, Anyango E, Mutie D, Muthoka P, Tabu C, Maritim M, Amukoye E, Were F.
        Vaccine. 2018 .

        Background: In 2014 the Kenya National Immunization Technical Advisory Group (KENITAG) was asked by the Ministry of Health to provide an evidence-based recommendation on whether the seasonal influenza vaccine should be introduced into the national immunization program (NIP). Methods: We reviewed KENITAG manuals, reports and meeting minutes generated between June 2014 and June 2016 in order to describe the process KENITAG used in arriving at that recommendation and the challenges encountered. Results: KENITAG developed a recommendation framework to identify critical, important and non-critical data elements that would guide deliberations on the subject. Literature searches were conducted in several databases and the quality of scientific articles obtained was assessed using the Critical Appraisal Skills Programme tool. There were significant gaps in knowledge on the national burden of influenza disease among key risk groups, i.e., pregnant women, individuals with co-morbidities, the elderly and health care workers. Insufficient funding and limited work force hindered KENITAG activities. In 2016 KENITAG recommended introduction of the annual seasonal influenza vaccine among children 6 to 23 months of age. However, the recommendation was contingent on implementation of a pilot study to address gaps in local data on the socio-economic impact of influenza vaccination programs, strategies for vaccine delivery, and the impact of the vaccination program on the healthcare workforce and existing immunization program. KENITAG did not recommend the influenza vaccine for any other risk group due to lack of local burden of disease data. Conclusion: Local data are a critical element in NITAG deliberations, however, where local data and in particular burden of disease data are lacking, there is need to adopt scientifically acceptable methods of utilizing findings from other countries to inform local decisions in a manner that is valid and acceptable to decision makers.

      3. Epidemiologic challenges in norovirus vaccine developmentExternal
        Hallowell BD, Parashar UD, Hall AJ.
        Hum Vaccin Immunother. 2018 Nov 27.

        Norovirus is the leading cause of acute gastroenteritis (AGE) worldwide. In the United States norovirus is estimated to cause 19-21 million illnesses, 1.7-1.9 million outpatient visits, 56,000-71,000 hospitalizations, and 570-800 deaths annually. Through direct costs and loss of productivity, norovirus disease cost the US economy more than $5.5 billion annually. Due to the lack of available therapies to treat norovirus infections and their highly infectious nature, preventing norovirus illness through vaccination is an appealing strategy. Currently, several norovirus vaccines are in development, including five vaccines in preclinical trials, an oral monovalent vaccine (Vaxart, Inc.) that recently completed a phase IB clinical trial, and a bivalent intramuscular vaccine (Takeda Pharmaceutical Company Limited) in a phase IIB clinical trial. However, no norovirus vaccines are currently available on the market. In this commentary we aim to describe some of the barriers faced in norovirus vaccine development, particularly focusing on vaccine effectiveness and defining the target population.

      4. Varicella vaccination can have complex direct and indirect influences on the epidemiology of herpes zoster among children. We evaluated pediatric herpes zoster trends using administrative databases. Incidence declined in a step-wise pattern since the varicella vaccination program was introduced, suggesting that rates may eventually decline in the entire population.

      5. Historic herpes zoster incidence trends in US adults have been hard to interpret. Using administrative databases, we extended previous descriptions of these trends through 2016. We observed an age-specific transition, with ongoing increases among younger adults but deceleration in older adults. The patterns are not readily explained.

      6. Defining the interval for monitoring potential adverse events following immunization (AEFIs) after receipt of live viral vectored vaccinesExternal
        Kochhar S, Excler JL, Bok K, Gurwith M, McNeil MM, Seligman SJ, Khuri-Bulos N, Klug B, Laderoute M, Robertson JS, Singh V, Chen RT.
        Vaccine. 2018 Nov 26.

        Live viral vectors that express heterologous antigens of the target pathogen are being investigated in the development of novel vaccines against serious infectious agents like HIV and Ebola. As some live recombinant vectored vaccines may be replication-competent, a key challenge is defining the length of time for monitoring potential adverse events following immunization (AEFI) in clinical trials and epidemiologic studies. This time period must be chosen with care and based on considerations of pre-clinical and clinical trials data, biological plausibility and practical feasibility. The available options include: (1) adapting from the current relevant regulatory guidelines; (2) convening a panel of experts to review the evidence from a systematic literature search to narrow down a list of likely potential or known AEFI and establish the optimal risk window(s); and (3) conducting “near real-time” prospective monitoring for unknown clustering’s of AEFI in validated large linked vaccine safety databases using Rapid Cycle Analysis for pre-specified adverse events of special interest (AESI) and Treescan to identify previously unsuspected outcomes. The risk window established by any of these options could be used along with (4) establishing a registry of clinically validated pre-specified AESI to include in case-control studies. Depending on the infrastructure, human resources and databases available in different countries, the appropriate option or combination of options can be determined by regulatory agencies and investigators.

      7. Similar relative risks of seizures following measles containing vaccination in children born preterm compared to full-term without previous seizures or seizure-related disordersExternal
        McClure DL, Jacobsen SJ, Klein NP, Naleway AL, Kharbanda EO, Glanz JM, Jackson LA, Weintraub ES, McLean HQ.
        Vaccine. 2018 Nov 23.

        BACKGROUND: Febrile seizures are associated with the first dose of measles-containing vaccines and the risk increases with chronologic age during the second year of life. We used the Vaccine Safety Datalink (VSD) to determine if the relative increase in risk of seizures following receipt of measles-containing vaccine differs by gestational age at birth. METHODS: Children were eligible if they received their first dose of measles-containing vaccine at age 12 through 23months from January 2003 through September 2015. Children were excluded if they had a history of seizure or conditions strongly related to seizure prior to 12months of age. Seizures were identified by diagnostic codes in the inpatient or emergency department settings. Using risk-interval analysis, we estimated the incidence rate ratio (IRR) for seizures in the 7 through 10days (risk period) vs 15 through 42days (control period) following receipt of measles-containing vaccines in children born preterm (<37weeks gestation age) and those born full-term (>/=37weeks). RESULTS: There were 532,375 children (45,343 preterm and 487,032 full-term) who received their first dose of measles-containing vaccine at age 12 through 23months. The IRRs of febrile seizures 7 through 10days compared with 15 through 42days after receipt of measles-containing vaccine were 3.9 (95% CI: 2.5-6.0) in preterm children and 3.2 (2.7-3.7) in full-term children; the ratio of IRRs: was 1.2 (0.76-1.9), p=0.41. IRRs were also similar across gestational age groups, by vaccine type received (measles-mumps-rubella [MMR] or measles-mumps-rubella-varicella [MMRV]) and age at vaccination (12-15 or 16-23months). CONCLUSION: Vaccination with a measles-containing vaccine in the second year of life is associated with a similar relative risk of a first seizure in children born preterm as in those who were born full-term.

      8. Prioritization of risk groups for influenza vaccination in resource limited settings – A case study from South AfricaExternal
        McMorrow ML, Tempia S, Walaza S, Treurnicht FK, Ramkrishna W, Azziz-Baumgartner E, Madhi SA, Cohen C.
        Vaccine. 2018 Nov 21.

        BACKGROUND: Due to competing health priorities, low- and middle-income countries (LMIC) may need to prioritize between different influenza vaccine risk groups. Risk group prioritization may differ in LMIC based upon programmatic feasibility, country-specific prevalence of risk conditions and influenza-associated morbidity and mortality. METHODS: In South Africa, we collected local disease burden data (both published and unpublished) and published vaccine efficacy data in risk groups and healthy adults. We used these data to aid policy makers with risk group prioritization for influenza vaccination. We used the following formula to assess potential vaccine averted disease in each risk group: rate of influenza-associated hospitalization (or death) per 100,000 population * influenza vaccine efficacy (VE). We further estimated the cost per hospital day averted and the cost per year of life saved by influenza vaccination. RESULTS: Pregnant women, HIV-infected adults, and adults and children with tuberculosis disease had among the highest estimates of hospitalizations averted per 100,000 vaccinated and adults aged 65years and older had the highest estimated deaths averted per 100,000 vaccinated. However, when assessing both the cost per hospital day averted (range: USD148-1,344) and the cost per year of life saved (range: USD112-1,230); adults and children with TB disease, HIV-infected adults and pregnant women had the lowest cost per outcome averted. DISCUSSION: An assessment of the potential disease outcomes averted and associated costs may aid policymakers in risk group prioritization for influenza vaccination.

      9. We identified 16 Advisory Committee on Immunization Practices (ACIP) presentations from 2012 to 2016 that indicated ‘cost’ or ‘economic’ content. Characteristics were reviewed, abstracted, and tabulated to quantify and assess the transparency and consistency of economic evidence presented to ACIP. To assess transparency, we documented if each study identified author affiliation, conflicts of interest, study limitations, a clearly described model structure and other model attributes. To assess consistency, we identified the frequency of specific modeling choices, including the perspective, types of health outcomes considered, inclusion of specific types of costs, discount rate, and use of sensitivity analyses. Our results indicate that the content in these presentations appear to be transparent overall and consistent in several important areas, such as study perspective and health outcomes. However, we find the inclusion of particular types of direct costs, indirect costs, program costs, and sensitivity analyses are areas that could improve consistency.

      10. Serological response to influenza vaccination among adults hospitalized with community acquired pneumoniaExternal
        Pratt CQ, Zhu Y, Grijalva CG, Wunderink RG, Courtney DM, Waterer G, Levine MZ, Jefferson S, Self WH, Williams DJ, Finelli L, Bramley AM, Edwards KM, Jain S, Anderson EJ.
        Influenza Other Respir Viruses. 2018 Nov 28.

        Ninety-five adults enrolled in the Etiology of Pneumonia in the Community study with negative admission influenza polymerase chain reaction (PCR) tests received influenza vaccination during hospitalization. Acute and convalescent influenza serology were performed. After vaccination, seropositive (>/=1:40) hemagglutination antibody titers (HAI) were achieved in 55% to influenza A(H1N1)pdm09, 58% to influenza A(H3N2), 77% to influenza B (Victoria), and 74% to influenza B (Yamagata) viruses. Sixty-six (69%) patients seroconverted (>/=4-fold HAI rise) to >/=1 strain. Failure to seroconvert was associated with diabetes, bacterial detection, baseline seropositive titers for influenza B (Yamagata), and influenza vaccination in the previous season. This article is protected by copyright. All rights reserved.

    • Informatics
      1. Natural language generation for electronic health recordsExternal
        Lee SH.
        NPJ Digit Med. 2018 01 Dec;1 (1) (63).

        One broad goal of biomedical informatics is to generate fully-synthetic, faithfully representative electronic health records (EHRs) to facilitate data sharing between healthcare providers and researchers and promote methodological research. A variety of methods existing for generating synthetic EHRs, but they are not capable of generating unstructured text, like emergency department (ED) chief complaints, history of present illness, or progress notes. Here, we use the encoder-decoder model, a deep learning algorithm that features in many contemporary machine translation systems, to generate synthetic chief complaints from discrete variables in EHRs, like age group, gender, and discharge diagnosis. After being trained end-to-end on authentic records, the model can generate realistic chief complaint text that appears to preserve the epidemiological information encoded in the original record-sentence pairs. As a side effect of the model’s optimization goal, these synthetic chief complaints are also free of relatively uncommon abbreviation and misspellings, and they include none of the personally identifiable information (PII) that was in the training data, suggesting that this model may be used to support the de-identification of text in EHRs. When combined with algorithms like generative adversarial networks (GANs), our model could be used to generate fully-synthetic EHRs, allowing healthcare providers to share faithful representations of multimodal medical data without compromising patient privacy. This is an important advance that we hope will facilitate the development of machine-learning methods for clinical decision support, disease surveillance, and other data-hungry applications in biomedical informatics.

    • Injury and Violence
      1. Suicide among persons with dementia, Georgia, 2013 to 2016External
        Annor FB, Bayakly RA, Morrison RA, Bryan MJ, Gilbert LK, Ivey-Stephenson AZ, Holland KM, Simon TR.
        J Geriatr Psychiatry Neurol. 2018 Nov 26:891988718814363.

        INTRODUCTION:: Findings from studies examining the relationship between dementia and suicide have been inconsistent. This study examined the characteristics, precipitants, and risk factors for suicide among persons with dementia. METHODS:: Data from the Georgia Alzheimer’s Disease and Related Dementia registry were linked with 2013 to 2016 data from Georgia Vital Records and Georgia Violent Death Reporting System. Descriptive statistics were calculated and logistic regression was used to examine risk factors for suicide. RESULTS:: Ninety-one Georgia residents with dementia who died by suicide were identified. Among decedents with known circumstances, common precipitants included depressed mood (38.7%) and physical health problems (72.6%). Suicide rate among persons with dementia was 9.3 per 100 000 person-years overall and substantially higher among those diagnosed in the past 12 months (424.5/100 000 person-years). Being male, dementia diagnosis before age 65, and a recent diagnosis of dementia independently predicted suicide, but not depression or cardiovascular diseases. CONCLUSION:: Prevention strategies that identify at-risk individuals, provide support, and ensure continuity of care for persons diagnosed with dementia may help reduce suicide in this population.

      2. Epidemiology of sports concussion in the United StatesExternal
        Baldwin GT, Breiding MJ, Dawn Comstock R.
        Handb Clin Neurol. 2018 ;158:63-74.

        Sports and recreation-related (SRR) activities are common in the United States. Beyond the benefits to health, SRR activities can create new friendships, give people a sense of belonging, foster teamwork and other leadership skills, and develop sportsmanship and a respect for rules that govern play. Public awareness about the risk of concussion has grown as the long-term consequences of traumatic brain injury (TBI) have become better known, and likely explains the increasing concussion incidence rates. Currently, surveillance systems capture SRR concussions among high school and college athletes participating in sanctioned sports. National estimates of SRR TBI presenting to an emergency department also exist. Persons under the age of 19 sustain a majority of SRR concussions. Concussion risk is greatest for boys in contact/collision sports like football, ice hockey, and lacrosse, and is more likely to occur in competition versus practice settings. Girls have elevated concussion rates in gender-comparable sports. Despite better data, concussions are still underreported, undermanaged, and often not properly identified. This is especially true for concussions occurring outside organized sports, in nonsport recreational activities, and for concussions either not seen or evaluated in nonemergency department settings. A new surveillance system proposed by the Centers for Disease Control and Prevention aims to fill the gap.

      3. Introduction: The Centers for Disease Control and Prevention (CDC) Pediatric Mild Traumatic Brain Injury (mTBI) Guideline was created to help standardize diagnosis, prognosis, and management and treatment of pediatric mTBI. This paper describes the process CDC used to develop educational tools, and a dissemination and implementation strategy, in support of the CDC Pediatric mTBI Guideline. Methods: Two qualitative data collection projects with healthcare providers who care for pediatric patients were conducted. In-depth interviews were used in both projects. Project One examined healthcare providers’ guideline use and dissemination preferences. Project Two assessed perceptions of the CDC Pediatric mTBI Guideline educational tools. Results: Project One brought to light four key areas related to Guideline usage and dissemination preferences, specifically a need for: (1) partnership with professional medical societies; (2) integration into electronic health records, mobile apps, and websites; (3) development of continuing medical education (CME) opportunities; and (4) dissemination through healthcare system leadership. In Project Two, healthcare providers reported that the CDC Pediatric mTBI Guideline educational tools were well-organized, clear and easy to navigate, and informative. Healthcare providers also requested more information on the Guideline methodology. Discussion: Assessment of pediatric healthcare providers’ current use of clinical guidelines and preferences for educational tools yielded important insights that helped inform CDC’s dissemination and implementation strategy for the Pediatric mTBI Guideline. Practical applications: The findings from these data collection projects can also inform other guideline implementation and dissemination efforts among healthcare providers.

      4. INTRODUCTION: Alcohol- or drug-impaired driving can cause motor vehicle crashes, injuries, and death. Estimates of drug-impaired driving are difficult to obtain. This study explores self-reported prevalence of and factors associated with alcohol, marijuana, and prescription opioid use and impaired driving among adults aged 21 years and older in the United States. METHODS: Self-reported data from 3,383 adults in the 2015 Fall ConsumerStyles survey were analyzed. Respondents were asked about alcohol, marijuana, and prescription opioid use and driving while impaired in the last 30 days. Weighted prevalence estimates were calculated. Prevalence ratios and Poisson log-linear regressions were used to identify factors associated with substance use and impaired driving. RESULTS: Alcohol use was reported by 49.5% (n = 1,676) of respondents; of these, 4.9% (n = 82) reported alcohol-impaired driving. Marijuana use was reported by 5.5% (n = 187) of respondents; of these, 31.6% (n = 59) reported marijuana-impaired driving. Prescription opioid use was reported by 8.8% (n = 298) of respondents; of these, 3.4% (n = 10) reported prescription opioid-impaired driving. Polysubstance use of alcohol and marijuana (concurrent use) was reported by 2.7% (n = 93) of respondents. Among those, 10.8% (n = 10) reported driving impaired by both alcohol and marijuana. CONCLUSIONS: Impaired driving was self-reported among alcohol, marijuana, and prescription opioid users. This article demonstrates the need for more robust alcohol- and drug-related data collection, reporting, and analyses, as well as the emerging need for surveillance of marijuana and prescription opioid-impaired driving. States can consider using proven strategies to prevent impaired driving and evaluate promising practices.

      5. Sampling design and methodology of the Violence Against Children and Youth SurveysExternal
        Nguyen KH, Kress H, Villaveces A, Massetti GM.
        Inj Prev. 2018 Nov 24.

        INTRODUCTION: Globally 1 billion children are exposed to violence every year. The Violence Against Children Surveys (VACS) are nationally representative surveys of males and females ages 13-24 that are intended to measure the burden of sexual, physical and emotional violence experienced in childhood, adolescence and young adulthood. It is important to document the methodological approach and design of the VACS to better understand the national estimates that are produced in each country, which are used to drive violence prevention efforts. METHODS: This study describes the surveys’ target population, sampling design, statistical considerations, data collection process, priority violence indicators and data dissemination. RESULTS: Twenty-four national household surveys have been completed or are being planned in countries across Africa, Asia, the Caribbean, Central and South America, and Eastern Europe. The sample sizes range from 891 to 7912 among females (72%-98% response rate) and 803-2717 among males (66%-98% response rate). Two face-to-face interviews are conducted: a Household and an Individual Questionnaire. A standard set of core priority indicators are generated for each country that range from prevalence of different types of violence, contexts, risk and protective factors, and health consequences. Results are disseminated through various platforms to expand the reach and impact of the survey results. CONCLUSION: Data obtained through VACS can inform development and implementation of effective prevention strategies and improve health service provision for all who experience violence. VACS serves as a standardised tool to inform and drive prevention through high-quality, comprehensive data.

      6. OBJECTIVE: This study examined trends and correlates of reported post-traumatic stress disorder (PTSD) among young male Veteran suicide decedents, using data from the National Violent Death Reporting System from 2005-2014 on 1,362 male U.S. Veteran suicide decedents aged 18-34 years. METHODS: Prevalence of reported PTSD (i.e., diagnosis/symptoms) was determined by mental health diagnostic fields and narratives and examined by year. Demographic, incident, and precipitating circumstance characteristics correlated with reported PTSD were identified. RESULTS: One-hundred ninety-eight (15%) decedents had PTSD evidence. A 30-fold increase in reported PTSD prevalence occurred among decedents aged 25-34 years; however, no increase was observed among younger decedents. Reported PTSD was associated with past deployments (odds ratio (OR): 14.5, 95% confidence interval (95% CI): 9.0-23.4); depression (OR: 1.8, 95% CI: 1.2-2.6); and divorce (OR: 1.7, 95% CI: 1.0-2.7). Recent crisis (OR: 0.6, 95% CI: 0.3-0.9) was inversely associated with reported PTSD. CONCLUSIONS: Reported PTSD prevalence substantially increased among Veteran suicide decedents aged 25-34 years suggesting it is beginning to play a larger role in suicide for this group. Few correlated suicide risk factors were found, suggesting that if symptoms of PTSD are present, heightened vigilance by providers for suicide risk might be warranted, irrespective of evidence of other risk factors.

      7. A case report of impaired driving performance after a concussionExternal
        Raukar N, Palms D, Boyle M, Baird J.
        R I Med J (2013). 2018 Dec 3;101(10):56-57.

        [No abstract]

      8. CDC Guideline on Mild Traumatic Brain Injury in Children: Important practice takeaways for sports medicine providersExternal
        Sarmiento K, Waltzman D, Lumba-Brown A, Yeates KO, Putukian M, Herring S.
        Clin J Sport Med. 2018 Nov 22.

        OBJECTIVES: The Centers for Disease Control and Prevention (CDC) published an evidence-based guideline on the diagnosis and management of pediatric mild traumatic brain injury (mTBI) in 2018. This commentary provides key practice takeaways for sports medicine providers outlined in the Guideline recommendations. DATA SOURCES: The CDC Pediatric mTBI Guideline was developed through a rigorous scientific process using a modified Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. A systematic review of the scientific literature published over a 25-year period for all causes of pediatric mTBI formed the basis of the Guideline. MAIN RESULTS: The key practice takeaways for sports medicine providers focus on preseason evaluations, neuroimaging, symptom-based assessment, managing recovery, monitoring for persistent symptoms, and return to activity, including sport and school. CONCLUSIONS: Sports medicine providers play an integral part in the implementation of evidence-based practices that promote appropriate diagnosis and management of mTBI in children. This commentary highlights key practice takeaways that sports medicine providers can implement.

    • Laboratory Sciences
      1. Preclinical pharmacokinetic evaluation to facilitate repurposing of tyrosine kinase inhibitors nilotinib and imatinib as antiviral agentsExternal
        Ananthula HK, Parker S, Touchette E, Buller RM, Patel G, Kalman D, Salzer JS, Gallardo-Romero N, Olson V, Damon IK, Moir-Savitz T, Sallans L, Werner MH, Sherwin CM, Desai PB.
        BMC Pharmacol Toxicol. 2018 Dec 4;19(1):80.

        BACKGROUND: Several tyrosine kinase inhibitors (TKIs) developed as anti-cancer drugs, also have anti-viral activity due to their ability to disrupt productive replication and dissemination in infected cells. Consequently, such drugs are attractive candidates for “repurposing” as anti-viral agents. However, clinical evaluation of therapeutics against infectious agents associated with high mortality, but low or infrequent incidence, is often unfeasible. The United States Food and Drug Administration formulated the “Animal Rule” to facilitate use of validated animal models for conducting anti-viral efficacy studies. METHODS: To enable such efficacy studies of two clinically approved TKIs, nilotinib, and imatinib, we first conducted comprehensive pharmacokinetic (PK) studies in relevant rodent and non-rodent animal models. PK of these agents following intravenous and oral dosing were evaluated in C57BL/6 mice, prairie dogs, guinea pigs and Cynomolgus monkeys. Plasma samples were analyzed using an LC-MS/MS method. Secondarily, we evaluated the utility of allometry-based inter-species scaling derived from previously published data to predict the PK parameters, systemic clearance (CL) and the steady state volume of distribution (Vss) of these two drugs in prairie dogs, an animal model not tested thus far. RESULTS: Marked inter-species variability in PK parameters and resulting oral bioavailability was observed. In general, elimination half-lives of these agents in mice and guinea pigs were much shorter (1-3 h) relative to those in larger species such as prairie dogs and monkeys. The longer nilotinib elimination half-life in prairie dogs (i.v., 6.5 h and oral, 7.5 h), facilitated multiple dosing PK and safety assessment. The allometry-based predicted values of the Vss and CL were within 2.0 and 2.5-fold, respectively, of the observed values. CONCLUSIONS: Our results suggest that prairie dogs and monkeys may be suitable rodent and non-rodent species to perform further efficacy testing of these TKIs against orthopoxvirus infections. The use of rodent models such as C57BL/6 mice and guinea pigs for assessing pre-clinical anti-viral efficacy of these two TKIs may be limited due to short elimination and/or low oral bioavailability. Allometry-based correlations, derived from existing literature data, may provide initial estimates, which may serve as a useful guide for pre-clinical PK studies in untested animal models.

      2. Global emergence and population dynamics of divergent serotype 3 CC180 pneumococciExternal
        Azarian T, Mitchell PK, Georgieva M, Thompson CM, Ghouila A, Pollard AJ, von Gottberg A, du Plessis M, Antonio M, Kwambana-Adams BA, Clarke SC, Everett D, Cornick J, Sadowy E, Hryniewicz W, Skoczynska A, Moisi JC, McGee L, Beall B, Metcalf BJ, Breiman RF, Ho PL, Reid R, O’Brien KL, Gladstone RA, Bentley SD, Hanage WP.
        PLoS Pathog. 2018 Nov 26;14(11):e1007438.

        Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the USA, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3-31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identified a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939-1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last of which resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease, as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development.

      3. CTX-M-65 extended-spectrum beta-lactamase-producing Salmonella enterica serotype infantis, United StatesExternal
        Brown AC, Chen JC, Watkins LK, Campbell D, Folster JP, Tate H, Wasilenko J, Van Tubbergen C, Friedman CR.
        Emerg Infect Dis. 2018 Dec;24(12):2284-2291.

        Extended-spectrum beta-lactamases (ESBLs) confer resistance to clinically important third-generation cephalosporins, which are often used to treat invasive salmonellosis. In the United States, ESBLs are rarely found in Salmonella. However, in 2014, the US Food and Drug Administration found blaCTX-M-65 ESBL-producing Salmonella enterica serotype Infantis in retail chicken meat. The isolate had a rare pulsed-field gel electrophoresis pattern. To clarify the sources and potential effects on human health, we examined isolates with this pattern obtained from human surveillance and associated metadata. Using broth microdilution for antimicrobial susceptibility testing and whole-genome sequencing, we characterized the isolates. Of 34 isolates, 29 carried the blaCTX-M-65 gene with <9 additional resistance genes on 1 plasmid. Of 19 patients with travel information available, 12 (63%) reported recent travel to South America. Genetically, isolates from travelers, nontravelers, and retail chicken meat were similar. Expanded surveillance is needed to determine domestic sources and potentially prevent spread of this ESBL-containing plasmid.

      4. Development of a PCR algorithm to detect and characterize Neisseria meningitidis carriage isolates in the African meningitis beltExternal
        Diallo K, Coulibaly MD, Rebbetts LS, Harrison OB, Lucidarme J, Gamougam K, Tekletsion YK, Bugri A, Toure A, Issaka B, Dieng M, Trotter C, Collard JM, Sow SO, Wang X, Mayer LW, Borrow R, Greenwood BM, Maiden MC, Manigart O.
        PLoS One. 2018 ;13(12):e0206453.

        Improved methods for the detection and characterization of carried Neisseria meningitidis isolates are needed. We evaluated a multiplex PCR algorithm for the detection of a variety of carriage strains in the meningitis belt. To further improve the sensitivity and specificity of the existing PCR assays, primers for gel-based PCR assays (sodC, H, Z) and primers/probe for real-time quantitative PCR (qPCR) assays (porA, cnl, sodC, H, E, Z) were modified or created using Primer Express software. Optimized multiplex PCR assays were tested on 247 well-characterised carriage isolates from six countries of the African meningitis belt. The PCR algorithm developed enabled the detection of N. meningitidis species using gel-based and real-time multiplex PCR targeting porA, sodC, cnl and characterization of capsule genes through sequential multiplex PCR assays for genogroups (A, W, X, then B, C, Y and finally H, E and Z). Targeting both porA and sodC genes together allowed the detection of meningococci with a sensitivity of 96% and 89% and a specificity of 78% and 67%, for qPCR and gel-based PCR respectively. The sensitivity and specificity ranges for capsular genogrouping of N. meningitidis are 67% – 100% and 98%-100% respectively for gel-based PCR and 90%-100% and 99%-100% for qPCR. We developed a PCR algorithm that allows simple, rapid and systematic detection and characterisation of most major and minor N. meningitidis capsular groups, including uncommon capsular groups (H, E, Z).

      5. BACKGROUND: There is limited information regarding isothiazolinone content in residential wall paints in the United States. OBJECTIVE: The aim of this study was to evaluate the prevalence of 5 isothiazolinones-methylisothiazolinone (MI), methylchloroisothiazolinone, benzisothiazolinone (BIT), butyl BIT, and octylisothiazolinone-in US residential wall paints. METHODS: Forty-seven paints were obtained from retailers in Minneapolis/St Paul, Minnesota. Paint samples were assessed for the presence of the 5 isothiazolinones using high-performance liquid chromatographic-mass spectrometry. RESULTS: At least 1 isothiazolinone was detected in all 47 paints. However, no paint contained butyl BIT, and only 1 paint had octylisothiazolinone. The MI and BIT were found in 96% and 94% of the paints, respectively. Methylisothiazolinone ranged in concentration from 17 to 358 ppm, whereas BIT varied from 29 to 1111 ppm. Methylchloroisothiazolinone was found solely in oil-based paints. Isothiazolinones were declared in 15% of Safety Data Sheets but did not correlate with high-performance liquid chromatographic-mass spectrometry. One “preservative-free” paint had BIT at 71.5 ppm. Paint sheen was not statistically associated with BIT or MI concentrations. Unpigmented paints and paints with volatile organic compound claims had significantly lower concentrations of MI, but not BIT. CONCLUSIONS: All paints contained at least 1 isothiazolinone. Methylisothiazolinone and BIT were the most common. Safety Data Sheets are insufficient for ascertaining isothiazolinone content in US paints.

      6. Evaluation and control of respirable crystalline silica (RCS) exposures are critical components of an effective mine industrial hygiene program. To provide more timely exposure data in the field, an end-of-shift Fourier transform infrared (FT-IR) spectrometry method has been developed for evaluation of direct-on-filter RCS. The present study aimed to apply this FT-IR method using field samples collected in three Northwestern U.S. metal/nonmetal mines and compare the results to traditional laboratory X-ray diffraction analysis (XRD). Seventy-five dust samples were analyzed using both methods. Samples for each mine were split in half by random assignment, with half used to create a calibration factor for the FT-IR analysis and half used to apply the calibration. Nonparametric correlational and two-sample comparative tests were used to assess the strength of association and the level of agreement between the two methods. Strong, positive correlations were observed between FT-IR and XRD RCS concentrations, with Spearman rank correlation coefficients ranging between 0.84 and 0.97. The mean RCS concentrations determined through FT-IR analysis were lower than through XRD analysis, with mean differences ranging from -4 to -133 ug/m(3) and mean percent errors ranging from 12% to 28%. There was a statistically significant improvement in the level of agreement between log FT-IR and log XRD RCS concentrations following calibration at two of the three mines, with mean differences of -0.03 (p = 0.002) and -0.02 (p = 0.044) in the log scale. The reduction in mean difference following calibration at the other mine was not statistically significant (mean log scale difference = -0.05, p = 0.215), but the differences between FT-IR and XRD were not significantly different without calibration (mean log scale difference = -0.07, p = 0.534). The results indicate that mine-specific calibration factors can improve the level of agreement between RCS concentrations determined via a field-based, end-of-shift FT-IR method in metal/non-metal mines as compared to traditional XRD analysis.

      7. Field performance evaluation of dual rapid HIV and syphilis tests in three antenatal care clinics in ZambiaExternal
        Kasaro MP, Bosomprah S, Taylor MM, Sindano N, Phiri C, Tambatamba B, Malumo S, Freeman B, Chibwe B, Laverty M, Owiredu MN, Newman L, Sikazwe I.
        Int J STD AIDS. 2018 Nov 25:956462418800872.

        This cross-sectional study of 3212 pregnant women assessed the field performance, acceptability, and feasibility of two dual HIV/syphilis rapid diagnostic tests, the Chembio DPP HIV-syphilis Assay and the SD Bioline HIV/syphilis Duo in antenatal clinics. Sensitivity and specificity for HIV and syphilis were calculated compared to the rapid Determine HIV-1/2 with Uni-Gold to confirm positive results for HIV and the Treponema pallidum particle agglutination assay for syphilis. RPR titers >/=1:4 were used to define active syphilis detection. Acceptability and feasibility were assessed using self-reported questionnaires. For Chembio, the HIV sensitivity was 90.6% (95%CI = 87.4, 93.0) and specificity was 97.2% (95%CI = 96.2, 97.8); syphilis sensitivity was 68.6% (95%CI = 61.9, 74.6) and specificity was 98.5% (95%CI = 97.8, 98.9). For SD Bioline, HIV sensitivity was 89.4% (95%CI = 86.1, 92.0) and specificity was 96.3% (95%CI = 95.3, 97.1); syphilis sensitivity was 66.2% (95%CI = 59.4, 72.4) and specificity was 97.2% (95%CI = 96.4, 97.9). Using the reference for active syphilis, syphilis sensitivity was 84.7% (95%CI = 76.1, 90.6) for Chembio and 81.6% (95%CI = 72.7, 88.1) for SD Bioline. Both rapid diagnostic tests were assessed as highly acceptable and feasible. In a field setting, the performance of both rapid diagnostic tests was comparable to other published field evaluations and each was rated highly acceptable and feasible. These findings can be used to guide further research and proposed scale up in antenatal clinic settings.

      8. An immunocompromised mouse model to infect Ixodes scapularis ticks with the relapsing fever spirochete, Borrelia miyamotoiExternal
        Lynn GE, Breuner NE, Eisen L, Hojgaard A, Replogle AJ, Eisen RJ.
        Ticks Tick Borne Dis. 2018 .

        The hard tick-borne relapsing fever spirochete, Borrelia miyamotoi, has recently gained attention as a cause of human illness, but fundamental aspects of its enzootic maintenance are still poorly understood. Challenges to experimental studies with B. miyamotoi-infected vector ticks include low prevalence of infection in field-collected ticks and seemingly inefficient horizontal transmission from infected immunocompetent rodents to feeding ticks. To reliably produce large numbers of B. miyamotoi-infected ticks in support of experimental studies, we developed an animal model where immunocompromised Mus musculus SCID mice were used as a source of B. miyamotoi-infection for larval and nymphal Ixodes scapularis ticks. Following needle inoculation with 1 x 105 spirochetes, the SCID mice developed a high spirochetemia (greater than 1 x 107 copies of B. miyamotoi purB per mL of blood) that persisted for at least 30 d after inoculation. In comparison, immunocompetent M. musculus CD-1 mice developed transient infections, detectable for only 2-8 d within the first 16 d after needle inoculation, with a brief, lower peak spirochetemia (8.5 x 104 – 5.6 x 105 purB copies per mL of blood). All larval or nymphal ticks fed on infected SCID mice acquired B. miyamotoi, but frequent loss of infection during the molt led to the proportion infected ticks of the resulting nymphal or adult stages declining to 22-29%. The ticks that remained infected after the molt had well-disseminated infections which then persisted through successive life stages, including transmission to larval offspring.

      9. Mechanistic basis for decreased antimicrobial susceptibility in a clinical isolate of Neisseria gonorrhoeae possessing a mosaic-like mtr efflux pump locusExternal
        Rouquette-Loughlin CE, Reimche JL, Balthazar JT, Dhulipala V, Gernert KM, Kersh EN, Pham CD, Pettus K, Abrams AJ, Trees DL, St Cyr S, Shafer WM.
        MBio. 2018 Nov 27;9(6).

        Recent reports suggest that mosaic-like sequences within the mtr (multiple transferable resistance) efflux pump locus of Neisseria gonorrhoeae, likely originating from commensal Neisseria sp. by transformation, can increase the ability of gonococci to resist structurally diverse antimicrobials. Thus, acquisition of numerous nucleotide changes within the mtrR gene encoding the transcriptional repressor (MtrR) of the mtrCDE efflux pump-encoding operon or overlapping promoter region for both along with those that cause amino acid changes in the MtrD transporter protein were recently reported to decrease gonococcal susceptibility to numerous antimicrobials, including azithromycin (Azi) (C. B. Wadsworth, B. J. Arnold, M. R. A. Satar, and Y. H. Grad, mBio 9:e01419-18, 2018, https://doi.org/10.1128/mBio.01419-18). We performed detailed genetic and molecular studies to define the mechanistic basis for why such strains can exhibit decreased susceptibility to MtrCDE antimicrobial substrates, including Azi. We report that a strong cis-acting transcriptional impact of a single nucleotide change within the -35 hexamer of the mtrCDE promoter as well gain-of-function amino acid changes at the C-terminal region of MtrD can mechanistically account for the decreased antimicrobial susceptibility of gonococci with a mosaic-like mtr locus.IMPORTANCE Historically, after introduction of an antibiotic for treatment of gonorrhea, strains of N. gonorrhoeae emerge that display clinical resistance due to spontaneous mutation or acquisition of resistance genes. Genetic exchange between members of the Neisseria genus occurring by transformation can cause significant changes in gonococci that impact the structure of an antibiotic target or expression of genes involved in resistance. The results presented here provide a framework for understanding how mosaic-like DNA sequences from commensal Neisseria that recombine within the gonococcal mtr efflux pump locus function to decrease bacterial susceptibility to antimicrobials, including antibiotics used in therapy of gonorrhea.

      10. The DEVD motif of Crimean-Congo hemorrhagic fever virus nucleoprotein is essential for viral replication in tick cellsExternal
        Salata C, Monteil V, Karlberg H, Celestino M, Devignot S, Leijon M, Bell-Sakyi L, Bergeron E, Weber F, Mirazimi A.
        Emerg Microbes Infect. 2018 Nov 28;7(1):190.

        [No abstract]

      11. Direct detection of emergent fungal pathogen Candida auris in clinical skin swabs by SYBR green-based quantitative PCR assayExternal
        Sexton DJ, Kordalewska M, Bentz ML, Welsh RM, Perlin DS, Litvintseva AP.
        J Clin Microbiol. 2018 Dec;56(12).

        The recent emergence of the multidrug-resistant and pathogenic yeast Candida auris continues to cause public health concern worldwide. C. auris is alarming because it causes health care-associated outbreaks and can establish invasive infections with high mortality rates. Transmission between patients is facilitated by the ability of C. auris to persistently colonize multiple body sites, including the skin, and survive for weeks on surfaces in health care settings. Rapid identification of colonized patients is needed to implement timely infection control measures. Currently, CDC laboratories use an enrichment culture-based approach that can take up to 2 weeks to identify C. auris from composite swabs from the bilateral axillae and groin. A rapid SYBR green quantitative PCR (qPCR) assay that can identify C. auris in a single day was recently described. In this study, we developed the SYBR green qPCR assay further by incorporating a DNA extraction procedure for skin swabs and by including an internal amplification control based on the distinguishable melt curve of a lambda DNA amplicon. The assay was conducted using 103 clinical axilla/groin skin swab samples. Using the enrichment culture-based approach as a gold standard, we determined that the SYBR green C. auris qPCR has a sensitivity of 0.93 and specificity of 0.96. Overall, we found that the SYBR green C. auris qPCR assay can be successfully applied for rapid and accurate detection of C. auris in patient skin swabs, thereby increasing diagnostic options for this emerging pathogen.

      12. Reliable creatinine measurements are important to evaluate kidney function and for creatinine correction to reduce biological variability of other urinary analytes. A high-throughput, accurate liquid chromatography tandem mass spectrometry method for quantitation of human urinary creatinine has been developed and validated. Sample preparation was fully automated including cryovial decapping, sample ID scanning and two serial dilution steps. Quantitation was performed using a stable isotope-labeled internal standard. Multiplexed chromatographic separation of creatinine was achieved within a one-minute analysis and followed by tandem mass spectrometry in positive electrospray ionization mode. The precursor and product ions of creatinine and D3-creatinine were monitored in selected reaction monitoring mode. Method validation results showed reproducibility with within-run precision of 3.59, 3.49 and 2.84% and between-run precision of 4.01, 3.28 and 3.57% for low, medium and high quality control materials prepared from pooled donor urine, respectively. The method showed excellent accuracy with a bias of -1.94%, -0.78% and -1.07% for three levels of certified reference material. The calibration curve was linear throughout a 7.50-300 mg/dL (0.663-26.5 mmol/L) measurement range (R2 = 0.999), with the mean slope of 0.0115 (95%CI, 0.0108-0.0122) and intercept of 0.0027 (95%CI, 0.0003-0.0051). The limit of detection (LOD) of the method was 3.17 mg/dL (0.280 mmol/L). Analytical specificity was achieved by chromatographically separating creatinine from potentially interfering creatine within a one-minute run and monitoring the Quantitation Ion/Confirmation Ion (QI/CI) ratios in samples. A simple, accurate, high-throughput method was successfully developed for measuring creatinine in human urine samples.

    • Maternal and Child Health
      1. The prevalence of parent-reported autism spectrum disorder among US childrenExternal
        Kogan MD, Vladutiu CJ, Schieve LA, Ghandour RM, Blumberg SJ, Zablotsky B, Perrin JM, Shattuck P, Kuhlthau KA, Harwood RL, Lu MC.
        Pediatrics. 2018 Nov 26.

        OBJECTIVES: To estimate the national prevalence of parent-reported autism spectrum disorder (ASD) diagnosis among US children aged 3 to 17 years as well as their treatment and health care experiences using the 2016 National Survey of Children’s Health (NSCH). METHODS: The 2016 NSCH is a nationally representative survey of 50 212 children focused on the health and well-being of children aged 0 to 17 years. The NSCH collected parent-reported information on whether children ever received an ASD diagnosis by a care provider, current ASD status, health care use, access and challenges, and methods of treatment. We calculated weighted prevalence estimates of ASD, compared health care experiences of children with ASD to other children, and examined factors associated with increased likelihood of medication and behavioral treatment. RESULTS: Parents of an estimated 1.5 million US children aged 3 to 17 years (2.50%) reported that their child had ever received an ASD diagnosis and currently had the condition. Children with parent-reported ASD diagnosis were more likely to have greater health care needs and difficulties accessing health care than children with other emotional or behavioral disorders (attention-deficit/hyperactivity disorder, anxiety, behavioral or conduct problems, depression, developmental delay, Down syndrome, intellectual disability, learning disability, Tourette syndrome) and children without these conditions. Of children with current ASD, 27% were taking medication for ASD-related symptoms, whereas 64% received behavioral treatments in the last 12 months, with variations by sociodemographic characteristics and co-occurring conditions. CONCLUSIONS: The estimated prevalence of US children with a parent-reported ASD diagnosis is now 1 in 40, with rates of ASD-specific treatment usage varying by children’s sociodemographic and co-occurring conditions.

      2. Positive predictive value of administrative data for neonatal abstinence syndromeExternal
        Maalouf FI, Cooper WO, Stratton SM, Dudley JA, Ko J, Banerji A, Patrick SW.
        Pediatrics. 2018 Dec 4.

        OBJECTIVES: Neonatal abstinence syndrome (NAS) is a postnatal withdrawal syndrome experienced by some infants with opioid exposure. Hospital administrative data are commonly used for research and surveillance but have not been validated for NAS. Our objectives for this study were to validate the diagnostic codes for NAS and to develop an algorithm to optimize identification. METHODS: Tennessee Medicaid claims from 2009 to 2011 (primary sample) and 2016 (secondary sample; post-International Classification of Diseases, 10th Revision, Clinical Modification [ICD-10-CM]) were obtained. Cases of NAS were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification code (2009-2011) 779.5 and ICD-10-CM code (2016) P96.1. Medical record review cases were then conducted by 2 physicians using a standardized algorithm, and positive predictive value (PPV) was calculated. Algorithms were developed for optimizing the identification of NAS in administrative data. RESULTS: In our primary sample of 112 029 mother-infant dyads, 950 potential NAS cases were identified from Medicaid claims data and reviewed. Among reviewed records, 863 were confirmed as having NAS (including 628 [66.1%] cases identified as NAS requiring pharmacotherapy, 224 [23.5%] as NAS not requiring pharmacotherapy, and 11 [1.2%] as iatrogenic NAS), and 87 (9.2%) did not meet clinical criteria for NAS. The PPV of the International Classification of Diseases, Ninth Revision, Clinical Modification code for NAS in clinically confirmed NAS was 91% (95% confidence interval: 88.8%-92.5%). Similarly, the PPV for the ICD-10-CM code in the secondary sample was 98.2% (95% confidence interval: 95.4%-99.2%). Algorithms using elements from the Medicaid claims and from length of stay improved PPV. CONCLUSIONS: In a large population-based cohort of Medicaid participants, hospital administrative data had a high PPV in identifying cases of clinically diagnosed NAS.

      3. Infections in children with autism spectrum disorder: Study to Explore Early Development (SEED)External
        Sabourin KR, Reynolds A, Schendel D, Rosenberg S, Croen LA, Pinto-Martin JA, Schieve LA, Newschaffer C, Lee LC, DiGuiseppi C.
        Autism Res. 2018 Nov 26.

        Immune system abnormalities have been widely reported among children with autism spectrum disorder (ASD), which may increase the risk of childhood infections. The Study to Explore Early Development (SEED) is a multisite case-control study of children aged 30-69 months, born in 2003-2006. Cases are children previously diagnosed and newly identified with ASD enrolled from education and clinical settings. Children with a previously diagnosed non-ASD developmental condition were included in the developmental delay/disorder (DD) control group. The population (POP) control group included children randomly sampled from birth certificates. Clinical illness from infection during the first 28 days (“neonatal,” from medical records) and first three years of life (caregiver report) in cases was compared to DD and POP controls; and between cases with and without regression. Children with ASD had greater odds of neonatal (OR = 1.8; 95%CI: 1.1, 2.9) and early childhood infection (OR = 1.7; 95%CI: 1.5, 1.9) compared to POP children, and greater odds of neonatal infection (OR = 1.5; 95%CI: 1.1, 2.0) compared to DD children. Cases with regression had 1.6 times the odds (95%CI: 1.1, 2.3) of caregiver-reported infection during the first year of life compared to cases without regression, but neonatal infection risk and overall early childhood infection risk did not differ. Our results support the hypothesis that children with ASD are more likely to have infection early in life compared to the general population and to children with other developmental conditions. Future studies should examine the contributions of different causes, timing, frequency, and severity of infection to ASD risk. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We looked at infections during early childhood in relation to autism spectrum disorder (ASD). We found that children with ASD were more likely to have an infection in the first 28 days of life and before age three compared to children with typical development. Children with ASD were also more likely than children with other developmental delays or disorders to have an infection in the first 28 days of life.

      4. [No abstract]

      5. For the first time, the Autism and Developmental Disabilities Monitoring Network (ADDM) at the Centers for Disease Control and Prevention (CDC) reported prevalence estimates based on two different diagnostic schemes in the 2014 surveillance period. Results found substantial agreement between surveillance case status based on Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR) criteria and DSM-5 criteria ASD (kappa = 0.85). No study has replicated this agreement in another independent sample of surveillance records. The objectives of this study were to (1) replicate agreement between surveillance status based on DSM-IV-TR criteria and DSM-5 criteria for ASD, (2) quantify the number of children who met surveillance status based on only DSM-IV-TR criteria and only DSM-5 criteria for ASD, and (3) evaluate differences in characteristics of these latter two groups of children. The study sample was 8-year-old children who had health and education records reviewed for ASD surveillance in metropolitan Atlanta, GA in the 2012 surveillance year. Results found substantial agreement between child’s surveillance status using DSM-IV-TR criteria and DSM-5 criteria for ASD (kappa = 0.80). There were no differences in child race/ethnicity, child sex, or intellectual disability between surveillance status defined by DSM-IV-TR criteria and that defined by DSM-5 criteria. Children who met surveillance status based on DSM-IV-TR criteria, but not DSM-5 criteria, were more likely to have developmental concerns and evaluations in the first three years. Children who met surveillance status based on DSM-5 criteria, but not DSM-IV-TR criteria, were more likely to have been receiving autism-related services or previously diagnosed with ASD. These results suggest that surveillance status of ASD based on DSM-5 criteria is largely comparable to that based on DSM-IV-TR criteria, and identifies children with similar demographic and intellectual characteristics.

    • Nutritional Sciences
      1. Errors in estimating usual sodium intake by the Kawasaki formula alter its relationship with mortality: implications for public healthExternal
        He FJ, Campbell NR, Ma Y, MacGregor GA, Cogswell ME, Cook NR.
        Int J Epidemiol. 2018 Dec 1;47(6):1784-1795.

        Background: Several cohort studies with inaccurate estimates of sodium reported a J-shaped relationship with mortality. We compared various estimated sodium intakes with that measured by the gold-standard method of multiple non-consecutive 24-h urine collections and assessed their relationship with mortality. Methods: We analysed the Trials of Hypertension Prevention follow-up data. Sodium intake was assessed in four ways: (i) average measured (gold standard): mean of three to seven 24-h urinary sodium measurements during the trial periods; (ii) average estimated: mean of three to seven estimated 24-h urinary sodium excretions from sodium concentration of 24-h urine using the Kawasaki formula; (iii) first measured: 24-h urinary sodium measured at the beginning of each trial; (iv) first estimated: 24-h urinary sodium estimated from sodium concentration of the first 24-h urine using the Kawasaki formula. We included 2974 individuals aged 30-54 years with pre-hypertension, not assigned to sodium intervention. Results: During a median follow-up of 24 years, 272 deaths occurred. The average sodium intake measured by the gold-standard method was 3769 +/- 1282 mg/d. The average estimated sodium over-estimated the intake by 1297 mg/d (95% confidence interval: 1267-1326). The average estimated value was systematically biased with over-estimation at lower levels and under-estimation at higher levels. The average measured sodium showed a linear relationship with mortality. The average estimated sodium appeared to show a J-shaped relationship with mortality. The first measured and the first estimated sodium both flattened the relationship. Conclusions: Accurately measured sodium intake showed a linear relationship with mortality. Inaccurately estimated sodium changed the relationship and could explain much of the paradoxical J-shaped findings reported in some cohort studies.

    • Occupational Safety and Health
      1. [No abstract]

      2. Worker well-being in the United States: Finding variation across job categoriesCdc-pdfExternal
        Stiehl E, Jones-Jack NH, Baron S, Muramatsu N.
        Prev Med Rep. 2019 March;13:5-10.

        Job categories shape the contexts that contribute to worker well-being, including their health, connectivity, and engagement. Using data from the 2014 Gallup Daily tracking survey, this study documented the distribution of worker well-being across 11 broad job categories among a national sample of employed adults in the United States. Well-being was measured by Gallup-Sharecare Well-Being 5TM, a composite measure of five well-being dimensions (purpose, community, physical, financial, and social). Analysis of variance (ANOVA) was used to examine how well-being varied across job categories and the extent to which household income modified that relationship, controlling for demographic factors. Well-being varied significantly across job categories, even after adjusting for household income and demographic factors. Well-being was higher among business owners, professionals, managers, and farming/fishing workers and lower among clerical/office, service, manufacturing/production, and transportation workers. Purpose well-being (e.g., liking what you do and being motivated to achieve your goals) showed the greatest variability across job categories-there were small differences across income levels for business owners, professionals, managers, and farming/fishing workers, and statistically significant gaps between the high income group and the two lower income groups among clerical/office, service, manufacturing/production, and transportation workers. Physical well-being exhibited the smallest gaps across income groups within job categories. The findings suggest that job category is an important component of worker well-being that extends beyond the financial dimension to purpose well-being. Our results suggest well-being inequity across job categories, and highlight areas for future research, policy and practice, including targeted interventions to promote worker and workplace well-being.

    • Occupational Safety and Health – Mining
      1. Diesel exhaust, respirable dust, and ischemic heart disease: an application of the parametric g-formulaExternal
        Neophytou AM, Costello S, Picciotto S, Brown DM, Attfield MD, Blair A, Lubin JH, Stewart PA, Vermeulen R, Silverman DT, Eisen EA.
        Epidemiology. 2018 Nov 27.

        BACKGROUND: Although general population studies of air pollution suggest that particulate matter – diesel exhaust emissions in particular – is a potential risk factor for cardiovascular disease, direct evidence from occupational cohorts using quantitative metrics of exposure is limited. In this study, we assess counterfactual risk of ischemic heart disease (IHD) mortality under hypothetical scenarios limiting exposure levels of diesel exhaust and of respirable mine/ore dust in the Diesel Exhaust in Miners Study (DEMS) cohort. METHODS: We analyzed data on 10,779 male miners from 8 non-metal, non-coal mines – hired after diesel equipment was introduced in the respective facilities – and followed from 1948 to 1997, with 297 observed IHD deaths in this sample. We applied the parametric g-formula to assess risk under hypothetical scenarios with various limits for respirable elemental carbon (a surrogate for diesel exhaust), and respirable dust, separately and jointly. RESULTS: The risk ratio comparing the observed risk to cumulative IHD mortality risk at age 80 under a hypothetical scenario where exposures to elemental carbon and respirable dust are eliminated was 0.79 (95% confidence interval (CI): 0.64, 0.97). The corresponding risk difference was -3.0% (95% CI: -5.7, -0.3). CONCLUSION: Our findings, based on data from a cohort of non-metal miners, are consistent with the hypothesis that interventions to eliminate exposures to diesel exhaust and respirable dust would reduce IHD mortality risk.

    • Reproductive Health
      1. Fertility treatment use and breastfeeding outcomesExternal
        Barrera CM, Kawwass JF, Boulet SL, Nelson JM, Perrine CG.
        Am J Obstet Gynecol. 2018 Dec 1.

        BACKGROUND: About 15% of women aged 15-44 in the US experience infertility. Factors associated with infertility and fertility treatments may also be associated with lactation difficulties. Limited data exist examining the impact of infertility or mode of conception on breastfeeding outcomes. OBJECTIVE: The objectives of this study were to report breastfeeding outcomes (initiation and duration at 8 weeks) among women who conceived spontaneously compared to women who conceived using fertility treatments (assisted reproductive technology, intrauterine insemination, or fertility-enhancing drugs). STUDY DESIGN: Maternal-reported data from four states from the 2012-2015 Pregnancy Risk Assessment and Monitoring System (PRAMS) were used to explore use of fertility treatment and breastfeeding initiation and continuation at 8 weeks (n=15,615). Data were weighted to represent all women delivering live births within each state; SAS survey procedures were used to account for PRAMS complex survey design. Stepwise, multivariable logistic regression, adjusted for maternal demographics, parity, plurality, mode of delivery, preterm birth, and maternal pre-pregnancy health conditions, was used to quantify the associations between fertility treatment use and breastfeeding. RESULTS: Mode of conception was not associated with breastfeeding outcomes when comparing women who conceived spontaneously to women who conceived using any fertility treatment. The odds of breastfeeding at 8 weeks were lower among women who conceived using assisted reproductive technology, after adjusting for basic demographic covariates (aOR: 0.71; 95% CI: 0.52-0.97) and additionally adjusting for maternal health conditions (aOR: 0.68; 95% CI: 0.49-0.93), but this difference was no longer significant after adjusting for plurality and preterm birth (aOR: 0.74; 95% CI: 0.54-1.02). CONCLUSIONS: This study suggests that mothers who conceive using assisted reproductive technology may breastfeed for shorter durations than mothers who conceive spontaneously, partially mediated by an increased likelihood of multiples and infants born preterm. Studies are needed to elucidate these associations and to understand the intentions and barriers to breastfeeding among women who conceive with the help of assisted reproductive technology.

      2. Implementing adolescent sexual and reproductive health clinical best practice in the Bronx, New YorkExternal
        Travers M, O’Uhuru D, Mueller T, Bedell J.
        J Adolesc Health. 2018 Nov 30.

        PURPOSE: Inequitable access to quality adolescent sexual and reproductive health (ASRH) care may contribute to the high rate of teen pregnancy in the Bronx, New York. Bronx Teens Connection (BxTC), a community-wide intervention, sought to increase the number of ASRH best practices implemented and the number of females 12-19 years old receiving services by health centers in the Bronx. METHODS: To promote best practices, BxTC provided training and technical assistance to partnering health centers from 2011 to 2014. Health center staff completed a 26-item survey annually to document clinic practices and service utilization. Significance of changes was assessed with paired t tests. RESULTS: BxTC provided 285 hours of training and technical assistance to 12 partnering health centers. Eight health centers consistently completed the survey. Of the possible 31 ASRH best practices, the average number implemented increased from 23 in 2011 to 28 in 2014. Increases in unduplicated female adolescent patients were observed among Hispanics/Latinas (p=.026) and all females aged 15-17 (p=.035). Contraceptive coverage reported by six of the eight health centers increased among Hispanic/Latinas (32%-55%, p=.006), patients ages 15-17 (33%-53%, p=.005), and patients 18-19 (38%-56%, p=.036). The total number of hormonal implants provided to teens increased from two in 2011 to 173 in 2014. CONCLUSIONS: Other jurisdictions may consider prioritizing clinical linkages in order to improve ASRH outcomes by supporting best practices and expanding access to services in the most disinvested neighborhoods.

    • Substance Use and Abuse
      1. Introduction: People living with mental health conditions (MH+) are more likely to smoke cigarettes than people without mental health conditions (MH-) and to experience tobacco-related disparities. The Tips From Former Smokers(R) (Tips(R)) campaign is a proven population-level strategy for motivating smokers to quit. In 2016, Tips included ads featuring Rebecca, a former smoker with depression. We evaluated self-reported frequency of exposure to the Rebecca and other Tips ads in association with quit intentions and quit attempts among MH+ and MH- smokers. Methods: Intentions to quit and past 6-month quit attempts lasting at least 24 hours were reported from a two-wave longitudinal online survey conducted before and after the 2016 Tips campaign with a nationally representative sample of US adult cigarette smokers with (MH+, N = 777) and without (MH-, N = 1806) lifetime mental health conditions. Results: In 2016, among MH+ respondents, greater exposure to the Rebecca ads was significantly associated with increased odds of intending to quit in the next 30 days (adjusted odds ratio [AOR] = 1.40, p < .05) and with reporting a quit attempt in the past 6 months (AOR = 1.25, p < .05). Among MH- respondents, greater exposure to the other Tips ads was associated with increased odds of making a quit attempt (AOR = 1.19, p < .05). Conclusions: Exposure to the Rebecca ads was associated with a greater likelihood of intentions to quit and quit attempts among MH+ smokers; whereas, exposure to the other (non-mental-health-related) Tips ads was associated with a greater likelihood of quit attempts among MH- smokers. Implications: National media campaigns are an important population-level strategy for reaching specific population groups who are experiencing tobacco-related disparities. The findings support the inclusion of ads featuring people living with mental health conditions in national tobacco education media campaigns, such as Tips.

      2. INTRODUCTION: Tobacco use mostly begins in adolescence and young adulthood. Earlier age of initiation of cigarette smoking is associated with greater nicotine dependence and sustained tobacco use. However, data are limited on the age of initiation of non-cigarette tobacco products, and the association between using these products and nicotine dependence and progression to established use. METHODS: Combined 2014-2016 National Youth Tobacco Survey data, a nationally representative cross-sectional survey of US students in grades 6-12 yielded 19 580 respondents who reported ever using any of five tobacco products: electronic cigarettes, cigarettes, cigars, smokeless tobacco and hookah. Analyses assessed age of reported first use of each product among ever-users, overall and by sex and race/ethnicity. Current daily use, past 30-day use, feelings of craving tobacco and time to first tobacco use after waking were assessed by age of first use. RESULTS: Among ever-users, weighted median age for first use was 12.6 years for cigarettes, 13.8 years for cigars, 13.4 years for smokeless tobacco, 14.1 years for hookah and 14.1 years for e-cigarettes. First trying these tobacco products at age </=13 years was associated with greater current use of the respective product and nicotine dependence compared with initiating use at age >13 years. CONCLUSIONS: First tobacco use at age </=13 years is associated with current daily and past 30-day use of non-cigarette tobacco products, and with the development of nicotine dependence among youth ever-users. Proven tobacco prevention interventions that reach early adolescents are important to reduce overall youth tobacco use.

      3. U.S. adult attitudes about electronic vapor product use in indoor public placesExternal
        Wang TW, Marynak KM, Gentzke AS, King BA.
        Am J Prev Med. 2018 Nov 13.

        INTRODUCTION: The U.S. Surgeon General has concluded that aerosol from electronic vapor products, such as e-cigarettes, can contain harmful and potentially harmful constituents. This study assessed the prevalence and determinants of U.S. adult attitudes toward electronic vapor product use in indoor public places. METHODS: Data from 2017 Summer Styles, an Internet survey of U.S. adults aged >/=18 years (n=4,107) were analyzed in 2017. Respondents were asked, Do you favor or oppose allowing the use of electronic vapor products in indoor public places such as workplaces, restaurants, and bars? Responses were strongly favor, somewhat favor, somewhat oppose, and strongly oppose. Multivariate Poisson regression was used to determine sociodemographic correlates of opposition (somewhat or strongly). RESULTS: In 2017, a total of 82.4% of adults strongly or somewhat opposed the use of electronic vapor products in indoor public places, including 28.0% of current (past 30-day) electronic vapor product users and 52.7% of current cigarette smokers. After adjustment, opposition was significantly lower among current and former electronic vapor product users than never users, current cigarette smokers than never smokers, and people living with tobacco product users. Opposition was significantly higher among adults aged >/=45 years than those aged 18-24 years and among adults who had rules prohibiting electronic vapor product use in their vehicles or homes than those without such rules. CONCLUSIONS: Approximately eight in ten U.S. adults, including more than one quarter of electronic vapor product users, opposed electronic vapor product use in indoor public places. Prohibiting electronic vapor product use in indoor public areas can protect bystanders from the health risks of secondhand electronic vapor product aerosol exposure.

    • Zoonotic and Vectorborne Diseases
      1. Outbreak of dengue virus type 2 – American Samoa, November 2016-October 2018External
        Cotter CJ, Tufa AJ, Johnson S, Matai’a M, Sciulli R, Ryff KR, Hancock WT, Whelen C, Sharp TM, Anesi MS.
        MMWR Morb Mortal Wkly Rep. 2018 Nov 30;67(47):1319-1322.

        The U.S. territory of American Samoa has experienced recent outbreaks of illnesses caused by viruses transmitted by Aedes species mosquitoes, including dengue, chikungunya, and Zika virus. In November 2016, a traveler from the Solomon Islands tested positive for infection with dengue virus type 2 (DENV-2). Additional dengue cases were identified in the subsequent weeks through passive and active surveillance. Suspected dengue cases were tested locally with a dengue rapid diagnostic test (RDT) for DENV nonstructural protein 1 (NS1). Specimens from RDT-positive cases and patients meeting the dengue case definition were tested by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) at Hawaii State Laboratories. During November 2016-October 2018, a total of 3,240 patients were tested for evidence of DENV infection (118 by RDT-NS1 alone, 1,089 by real-time RT-PCR alone, and 2,033 by both methods), 1,081 (33.4%) of whom tested positive for dengue (19.5 per 1,000 population). All 941 real-time RT-PCR-positive specimens were positive for DENV-2. The monthly number of laboratory-confirmed cases peaked at 120 during December 2017. Among laboratory-confirmed dengue cases, 380 (35.2%) patients were hospitalized; one patient, who was transferred to American Samoa for care late in his illness, died. The public health response to this outbreak included disposal of solid waste to remove mosquito breeding sites, indoor residual spraying of pesticides in schools, reinforcement of dengue patient management education, and public education on mosquito avoidance and seeking medical care for symptoms of dengue.

      2. Influences of community interventions on Zika prevention behaviors of pregnant women, Puerto Rico, July 2016-June 2017External
        Earle-Richardson G, Prue C, Turay K, Thomas D.
        Emerg Infect Dis. 2018 Dec;24(12):2251-2261.

        We assessed how community education efforts influenced pregnant women’s Zika prevention behaviors during the 2016 Centers for Disease Control and Prevention-Puerto Rico Department of Health Zika virus response. Efforts included Zika virus training, distribution of Zika prevention kits, a mass media campaign, and free home mosquito spraying. We used telephone interview data from pregnant women participating in Puerto Rico’s Women, Infants, and Children Program to test associations between program participation and Zika prevention behaviors. Behavior percentages ranged from 4% (wearing long-sleeved shirt) to 90% (removing standing water). Appropriate mosquito repellent use (28%) and condom use (44%) were common. Receiving a Zika prevention kit was significantly associated with larvicide application (odds ratio [OR] 8.0) and bed net use (OR 3.1), suggesting the kit’s importance for lesser-known behaviors. Offer of free residential spraying was associated with spraying home for mosquitoes (OR 13.1), indicating that women supported home spraying when barriers were removed.

      3. Rabies post-exposure prophylaxis started during or after travel: A GeoSentinel analysisExternal
        Gautret P, Angelo KM, Asgeirsson H, Lalloo DG, Shaw M, Schwartz E, Libman M, Kain KC, Piyaphanee W, Murphy H, Leder K, Vincelette J, Jensenius M, Waggoner J, Leung D, Borwein S, Blumberg L, Schlagenhauf P, Barnett ED, Hamer DH.
        PLoS Negl Trop Dis. 2018 Nov;12(11):e0006951.

        BACKGROUND: Recent studies demonstrate that rabies post-exposure prophylaxis (RPEP) in international travelers is suboptimal, with only 5-20% of travelers receiving rabies immune globulin (RIG) in the country of exposure when indicated. We hypothesized that travelers may not be receiving RIG appropriately, and practices may vary between countries. We aim to describe the characteristics of travelers who received RIG and/or RPEP during travel. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multi-center review of international travelers exposed to potentially rabid animals, collecting information on RPEP administration. Travelers who started RPEP before (Group A) and at (Group B) presentation to a GeoSentinel clinic during September 2014-July 2017 were included. We included 920 travelers who started RPEP. About two-thirds of Group A travelers with an indication for rabies immunoglobulin (RIG) did not receive it. Travelers exposed in Indonesia were less likely to receive RIG in the country of exposure (relative risk: 0.30; 95% confidence interval: 0.12-0.73; P = 0.01). Travelers exposed in Thailand [Relative risk (RR) 1.38, 95% Confidence Interval (95% CI): 1.0-1.8; P = 0.02], Sri Lanka (RR 3.99, 95% CI: 3.99-11.9; P = 0.013), and the Philippines (RR 19.95, 95% CI: 2.5-157.2; P = 0.01), were more likely to receive RIG in the country of exposure. CONCLUSIONS/SIGNIFICANCE: This analysis highlights gaps in early delivery of RIG to travelers and identifies specific countries where travelers may be more or less likely to receive RIG. More detailed country-level information helps inform risk education of international travelers regarding appropriate rabies prevention.

      4. [No abstract]

      5. The reference standard for the confirmation of a recent rickettsial infection is by the observation of a four-fold or greater rise in antibody titres when testing paired acute and convalescent (two to four weeks after illness resolution) sera by serological assays (Figure 1). At the acute stage of illness, diagnosis is performed by molecular detection methods most effectively on DNA extracted from tissue biopsies (eschars, skin rash, and organs) or eschar swabs. Less invasive and more convenient samples such as blood and serum may also be used for detection; however, the low number of circulating bacteria raises the possibility of false negative results. Optimal sampling practices and enhanced sensitivity must therefore be considered in order to provide a more accurate laboratory diagnosis.

      6. Seasonal and interannual risks of dengue introduction from South-East Asia into China, 2005-2015External
        Lai S, Johansson MA, Yin W, Wardrop NA, van Panhuis WG, Wesolowski A, Kraemer MU, Bogoch , Kain D, Findlater A, Choisy M, Huang Z, Mu D, Li Y, He Y, Chen Q, Yang J, Khan K, Tatem AJ, Yu H.
        PLoS Negl Trop Dis. 2018 Nov;12(11):e0006743.

        Due to worldwide increased human mobility, air-transportation data and mathematical models have been widely used to measure risks of global dispersal of pathogens. However, the seasonal and interannual risks of pathogens importation and onward transmission from endemic countries have rarely been quantified and validated. We constructed a modelling framework, integrating air travel, epidemiological, demographical, entomological and meteorological data, to measure the seasonal probability of dengue introduction from endemic countries. This framework has been applied retrospectively to elucidate spatiotemporal patterns and increasing seasonal risk of dengue importation from South-East Asia into China via air travel in multiple populations, Chinese travelers and local residents, over a decade of 2005-15. We found that the volume of airline travelers from South-East Asia into China has quadrupled from 2005 to 2015 with Chinese travelers increased rapidly. Following the growth of air traffic, the probability of dengue importation from South-East Asia into China has increased dramatically from 2005 to 2015. This study also revealed seasonal asymmetries of transmission routes: Sri Lanka and Maldives have emerged as origins; neglected cities at central and coastal China have been increasingly vulnerable to dengue importation and onward transmission. Compared to the monthly occurrence of dengue reported in China, our model performed robustly for importation and onward transmission risk estimates. The approach and evidence could facilitate to understand and mitigate the changing seasonal threat of arbovirus from endemic regions.

      7. Sequential neuroimaging of the fetus and newborn with in utero Zika virus exposureExternal
        Mulkey SB, Bulas DI, Vezina G, Fourzali Y, Morales A, Arroyave-Wessel M, Swisher CB, Cristante C, Russo SM, Encinales L, Pacheco N, Kousa YA, Lanciotti RS, Cure C, DeBiasi RL, du Plessis AJ.
        JAMA Pediatr. 2018 Nov 26.

        Importance: The evolution of fetal brain injury by Zika virus (ZIKV) infection is not well described. Objectives: To perform longitudinal neuroimaging of fetuses and infants exposed to in utero maternal ZIKV infection using concomitant magnetic resonance imaging (MRI) and ultrasonography (US), as well as to determine the duration of viremia in pregnant women with ZIKV infection and whether the duration of viremia correlated with fetal and/or infant brain abnormalities. Design, Setting, and Participants: A cohort of 82 pregnant women with clinical criteria for probable ZIKV infection in Barranquilla, Colombia, and Washington, DC, were enrolled from June 15, 2016, through June 27, 2017, with Colombian women identified by community recruitment and physician referral and travel-related cases of American women recruited from a Congenital Zika Program. Interventions and Exposures: Women received 1 or more MRI and US examinations during the second and/or third trimesters. Postnatally, infants underwent brain MRI and cranial US. Blood samples were tested for ZIKV. Main Outcomes and Measures: The neuroimaging studies were evaluated for brain injury and cerebral biometry. Results: Of the 82 women, 80 were from Colombia and 2 were from the United States. In 3 of 82 cases (4%), fetal MRI demonstrated abnormalities consistent with congenital ZIKV infection. Two cases had heterotopias and malformations in cortical development and 1 case had a parietal encephalocele, Chiari II malformation, and microcephaly. In 1 case, US results remained normal despite fetal abnormalities detected on MRI. Prolonged maternal polymerase chain reaction positivity was present in 1 case. Of the remaining 79 cases with normal results of prenatal imaging, postnatal brain MRI was acquired in 53 infants and demonstrated mild abnormalities in 7 (13%). Fifty-seven infants underwent postnatal cranial US, which detected changes of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification in 21 infants (37%). Conclusions and Relevance: In a cohort of pregnant women with ZIKV infection, prenatal US examination appeared to detect all but 1 abnormal fetal case. Postnatal neuroimaging in infants who had normal prenatal imaging revealed new mild abnormalities. For most patients, prenatal and postnatal US may identify ZIKV-related brain injury.

      8. Stillbirths and neonatal deaths surveillance during the 2014-2015 Ebola virus disease outbreak in Sierra LeoneExternal
        Oduyebo T, Bennett SD, Nallo AS, Jamieson DJ, Ellington S, Souza K, Meaney-Delman D, Redd JT.
        Int J Gynaecol Obstet. 2018 Nov 22.

        OBJECTIVE: To determine rates of stillbirth and neonatal mortality in Sierra Leone during the 2014-2015 Ebola virus disease (EVD) outbreak. METHODS: A cross-sectional study was performed using information from the Sierra Leone National Ebola Laboratory database to identify stillbirths and neonatal deaths that had been tested for Ebola virus from July 2, 2014, to October 18, 2015. Outcomes included the annualized rate of stillbirths and neonatal deaths; the percentage of all tested deaths attributable to stillbirths and neonatal deaths; and the proportion of stillbirths and neonatal deaths attributable to Ebola virus. RESULTS: In total, 1726 stillbirths and 4708 neonatal deaths were tested for Ebola virus, representing 2.6% and 7.2% of the total deaths tested (n=65 585), respectively. Of these, 25 stillbirths and neonatal deaths tested positive, accounting for 0.3% of EVD cases. In 2015, the annualized total number of reported stillbirths was higher than expected (3079 vs 1634), whereas reported neonatal deaths were lower (6351 vs 7770). CONCLUSIONS: Stillbirth and neonatal death reporting and testing improved over time. Systematic recording of these indicators might be used alongside retrospective surveillance to respond to the adverse effects of EVD on maternal and child health and guide response efforts for subsequent outbreaks. This article is protected by copyright. All rights reserved.

      9. Reported cases of vector-borne diseases in the United States have more than tripled since 2004, characterized by steadily increasing incidence of tick-borne diseases and sporadic outbreaks of domestic and invasive mosquito-borne diseases. An effective public health response to these trends relies on public health surveillance and laboratory systems, proven prevention and mitigation measures, scalable capacity to implement these measures, sensitive and specific diagnostics, and effective therapeutics. However, significant obstacles hinder successful implementation of these public health strategies. The recent emergence of Haemaphysalis longicornis, the first invasive tick to emerge in the United States in approximately 80 years, serves as the most recent example of the need for a coordinated public health response. Addressing the dual needs for innovation and discovery and for building state and local capacities may overcome current challenges in vector-borne disease prevention and control, but will require coordination across a national network of collaborators operating under a national strategy. Such an effort should reduce the impact of emerging vectors and could reverse the increasing trend of vector-borne disease incidence and associated morbidity and mortality.

      10. Towards global health security: response to the May 2018 Nipah virus outbreak linked to Pteropus bats in Kerala, IndiaExternal
        Sadanadan R, Arunkumar G, Laserson KF, Heretik KH, Singh S, Mourya DT, Gangakhedkar RR, Gupta N, Sharma R, Dhuria M, Jain SK, Nichol S, Gupta P, Bhargava B.
        BMJ Glob Health. 2018 ;3(6):e001086.

        [No abstract]

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