Volume 11, Issue 13 March 26, 2019

CDC Science Clips: Volume 11, Issue 13, March 26, 2019

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

This week Science Clips is pleased to feature articles from the Global Health: Science and Practice supplement: Saving Mothers, Giving Life: A Systems Approach to Reducing Maternal and Perinatal Deaths in Uganda and ZambiaExternal.

The Saving Mothers, Giving Life Initiative (SMGL) is a public-private partnership in Uganda and Zambia to rapidly reduce the number of deaths that are due to complications of pregnancy and childbirth by promoting evidence-based, effective interventions during labor, delivery and immediately after birth.  This initiative seeks to augment existing national maternal, neonatal, and child health programs by strengthening the district health system platforms (infrastructure, human resources, commodities, quality of care, accountability for and use of results in program management), improving access, and generating increased demand for health services.

As one of the SMGL partners, CDC’s Division of Reproductive Health (DRH) provided technical assistance on designing, planning, and implementing multiple monitoring and evaluation (M&E) approaches, as well as analyzing and interpreting the M&E data.

  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.
    • Reproductive Health – Saving Mothers, Giving Life
      1. Saving Mothers, Giving Life: It takes a system to save a motherExternal
        Conlon CM, Serbanescu F, Marum L, Healey J, LaBrecque J, Hobson R, Levitt M, Kekitiinwa A, Picho B, Soud F, Spigel L, Steffen M, Velasco J, Cohen R, Weiss W.
        Glob Health Sci Pract. 2019 Mar 11;7(Suppl 1):S6-s26.
        BACKGROUND: Ending preventable maternal and newborn deaths remains a global health imperative under United Nations Sustainable Development Goal targets 3.1 and 3.2. Saving Mothers, Giving Life (SMGL) was designed in 2011 within the Global Health Initiative as a public-private partnership between the U.S. government, Merck for Mothers, Every Mother Counts, the American College of Obstetricians and Gynecologists, the government of Norway, and Project C.U.R.E. SMGL’s initial aim was to dramatically reduce maternal mortality in low-resource, high-burden sub-Saharan African countries. SMGL used a district health systems strengthening approach combining both supply- and demand-side interventions to address the 3 key delays to accessing effective maternity care in a timely manner: delays in seeking, reaching, and receiving quality obstetric services. IMPLEMENTATION: The SMGL approach was piloted from June 2012 to December 2013 in 8 rural districts (4 each) in Uganda and Zambia with high levels of maternal deaths. Over the next 4 years, SMGL expanded to a total of 13 districts in Uganda and 18 in Zambia. SMGL built on existing host government and private maternal and child health platforms, and was aligned with and guided by Ugandan and Zambian maternal and newborn health policies and programs. A 35% reduction in the maternal mortality ratio (MMR) was achieved in SMGL-designated facilities in both countries during the first 12 months of implementation. RESULTS: Maternal health outcomes achieved after 5 years of implementation in the SMGL-designated pilot districts were substantial: a 44% reduction in both facility and districtwide MMR in Uganda, and a 38% decrease in facility and a 41% decline in districtwide MMR in Zambia. Facility deliveries increased by 47% (from 46% to 67%) in Uganda and by 44% (from 62% to 90%) in Zambia. Cesarean delivery rates also increased: by 71% in Uganda (from 5.3% to 9.0%) and by 79% in Zambia (from 2.7% to 4.8%). The average annual rate of reduction for maternal deaths in the SMGL-supported districts exceeded that found countrywide: 11.5% versus 3.5% in Uganda and 10.5% versus 2.8% in Zambia. The changes in stillbirth rates were significant (-13% in Uganda and -36% in Zambia) but those for pre-discharge neonatal mortality rates were not significant in either Uganda or Zambia. CONCLUSION: A district health systems strengthening approach to addressing the 3 delays to accessing timely, appropriate, high-quality care for pregnant women can save women’s lives from preventable causes and reduce stillbirths. The approach appears not to significantly impact pre-discharge neonatal mortality.

      2. The costs and cost-effectiveness of a district-strengthening strategy to mitigate the 3 delays to quality maternal health care: Results From Uganda and ZambiaExternal
        Johns B, Hangoma P, Atuyambe L, Faye S, Tumwine M, Zulu C, Levitt M, Tembo T, Healey J, Li R, Mugasha C, Serbanescu F, Conlon CM.
        Glob Health Sci Pract. 2019 Mar 11;7(Suppl 1):S104-s122.
        The primary objective of this study was to estimate the costs and the incremental cost-effectiveness of maternal and newborn care associated with the Saving Mothers, Giving Life (SMGL) initiative-a comprehensive district-strengthening approach addressing the 3 delays associated with maternal mortality-in Uganda and Zambia. To assess effectiveness, we used a before-after design comparing facility outcome data from 2012 (before) and 2016 (after). To estimate costs, we used unit costs collected from comparison districts in 2016 coupled with data on health services utilization from 2012 in SMGL-supported districts to estimate the costs before the start of SMGL. We collected data from health facilities, ministerial health offices, and implementing partners for the year 2016 in 2 SMGL-supported districts in each country and in 3 comparison non-SMGL districts (2 in Zambia, 1 in Uganda). Incremental costs for maternal and newborn health care per SMGL-supported district in 2016 was estimated to be US$845,000 in Uganda and $760,000 in Zambia. The incremental cost per delivery was estimated to be $38 in Uganda and $95 in Zambia. For the districts included in this study, SMGL maternal and newborn health activities were associated with approximately 164 deaths averted in Uganda and 121 deaths averted in Zambia in 2016 compared to 2012. In Uganda, the cost per death averted was $10,311, or $177 per life-year gained. In Zambia, the cost per death averted was $12,514, or $206 per life-year gained. The SMGL approach can be very cost-effective, with the cost per life-year gained as a percentage of the gross domestic product (GDP) being 25.6% and 16.4% in Uganda and Zambia, respectively. In terms of affordability, the SMGL approach could be paid for by increasing health spending from 7.3% to 7.5% of GDP in Uganda and from 5.4% to 5.8% in Zambia.

      3. Addressing the third delay in Saving Mothers, Giving Life Districts in Uganda and Zambia: Ensuring adequate and appropriate facility-based maternal and perinatal health careExternal
        Morof D, Serbanescu F, Goodwin MM, Hamer DH, Asiimwe AR, Hamomba L, Musumali M, Binzen S, Kekitiinwa A, Picho B, Kaharuza F, Namukanja PM, Murokora D, Kamara V, Dynes M, Blanton C, Nalutaaya A, Luwaga F, Schmitz MM, LaBrecque J, Conlon CM, McCarthy B, Kroelinger C, Clark T.
        Glob Health Sci Pract. 2019 Mar 11;7(Suppl 1):S85-s103.
        BACKGROUND: Saving Mothers, Giving Life (SMGL) is a 5-year initiative implemented in participating districts in Uganda and Zambia that aimed to reduce deaths related to pregnancy and childbirth by targeting the 3 delays to receiving appropriate care: seeking, reaching, and receiving. Approaches to addressing the third delay included adequate health facility infrastructure, specifically sufficient equipment and medications; trained providers to provide quality evidence-based care; support for referrals to higher-level care; and effective maternal and perinatal death surveillance and response. METHODS: SMGL used a mixed-methods approach to describe intervention strategies, outcomes, and health impacts. Programmatic and monitoring and evaluation data-health facility assessments, facility and community surveillance, and population-based mortality studies-were used to document the effectiveness of intervention components. RESULTS: During the SMGL initiative, the proportion of facilities providing emergency obstetric and newborn care (EmONC) increased from 10% to 25% in Uganda and from 6% to 12% in Zambia. Correspondingly, the delivery rate occurring in EmONC facilities increased from 28.2% to 41.0% in Uganda and from 26.0% to 29.1% in Zambia. Nearly all facilities had at least one trained provider on staff by the endline evaluation. Staffing increases allowed a higher proportion of health centers to provide care 24 hours a day/7 days a week by endline-from 74.6% to 82.9% in Uganda and from 64.8% to 95.5% in Zambia. During this period, referral communication improved from 93.3% to 99.0% in Uganda and from 44.6% to 100% in Zambia, and data systems to identify and analyze causes of maternal and perinatal deaths were established and strengthened. CONCLUSION: SMGL’s approach was associated with improvements in facility infrastructure, equipment, medication, access to skilled staff, and referral mechanisms and led to declines in facility maternal and perinatal mortality rates. Further work is needed to sustain these gains and to eliminate preventable maternal and perinatal deaths.

      4. Addressing the second delay in Saving Mothers, Giving Life Districts in Uganda and Zambia: Reaching appropriate maternal care in a timely mannerExternal
        Ngoma T, Asiimwe AR, Mukasa J, Binzen S, Serbanescu F, Henry EG, Hamer DH, Lori JR, Schmitz MM, Marum L, Picho B, Naggayi A, Musonda G, Conlon CM, Komakech P, Kamara V, Scott NA.
        Glob Health Sci Pract. 2019 Mar 11;7(Suppl 1):S68-s84.
        BACKGROUND: Between June 2011 and December 2016, the Saving Mothers, Giving Life (SMGL) initiative in Uganda and Zambia implemented a comprehensive approach targeting the persistent barriers that impact a woman’s decision to seek care (first delay), ability to reach care (second delay), and ability to receive adequate care (third delay). This article addresses how SMGL partners implemented strategies specifically targeting the second delay, including decreasing the distance to facilities capable of managing emergency obstetric and newborn complications, ensuring sufficient numbers of skilled birth attendants, and addressing transportation challenges. METHODS: Both quantitative and qualitative data collected by SMGL implementing partners for the purpose of monitoring and evaluation were used to document the intervention strategies and to describe the change in outputs and outcomes related to the second delay. Quantitative data sources included pregnancy outcome monitoring data in facilities, health facility assessments, and population-based surveys. Qualitative data were derived from population-level verbal autopsy narratives, programmatic reports and SMGL-related publications, and partner-specific evaluations that include focus group discussions and in-depth interviews. RESULTS: The proportion of deliveries in any health facility or hospital increased from 46% to 67% in Uganda and from 63% to 90% in Zambia between baseline and endline. Distance to health facilities was reduced by increasing the number of health facilities capable of providing basic emergency obstetric and newborn care services in both Uganda and Zambia-a 200% and 167% increase, respectively. Access to facilities improved through integrated transportation and communication services efforts. In Uganda there was a 6% increase in the number of health facilities with communication equipment and a 258% increase in facility deliveries supported by transportation vouchers. In Zambia, there was a 31% increase in health facilities with available transportation, and the renovation and construction of maternity waiting homes resulted in a 69% increase in the number of health facilities with associated maternity waiting homes. CONCLUSION: The collective SMGL strategies addressing the second delay resulted in increased access to delivery services as seen by the increase in the proportion of facility deliveries in SMGL districts, improved communication and transportation services, and an increase in the number of facilities with associated maternity waiting homes. Sustaining and improving on these efforts will need to be ongoing to continue to address the second delay in Uganda and Zambia.

      5. Community perspectives of a 3-delays model intervention: A qualitative evaluation of saving mothers, giving life in ZambiaExternal
        Ngoma-Hazemba A, Hamomba L, Silumbwe A, Munakampe MN, Soud F.
        Glob Health Sci Pract. 2019 Mar 11;7(Suppl 1):S139-s150.
        BACKGROUND: Saving Mothers, Giving Life (SMGL), a health systems strengthening approach based on the 3-delays model, aimed to reduce maternal and perinatal mortality in 6 districts in Zambia between 2012 and 2017. By 2016, the maternal mortality ratio in SMGL-supported districts declined by 41% compared to its level at the beginning of SMGL-from 480 to 284 deaths per 100,000 live births. The 10.5% annual reduction between the baseline and 2016 was about 4.5 times higher than the annual reduction rate for sub-Saharan Africa and about 2.6 times higher than the annual reduction estimated for Zambia as a whole. OBJECTIVES: While outcome measures demonstrate reductions in maternal and perinatal mortality, this qualitative endline evaluation assessed community perceptions of the SMGL intervention package, including (1) messaging about use of maternal health services, (2) access to maternal health services, and (3) quality improvement of maternal health services. METHODS: We used purposive sampling to conduct semistructured in-depth interviews with women who delivered at home (n=20), women who delivered in health facilities (n=20), community leaders (n=8), clinicians (n=15), and public health stakeholders (n=15). We also conducted 12 focus group discussions with a total of 93 men and women from the community and Safe Motherhood Action Group members. Data were coded and analyzed using NVivo version 10. RESULTS: Delay 1: Participants were receptive to SMGL’s messages related to early antenatal care, health facility-based deliveries, and involving male partners in pregnancy and childbirth. However, top-down pressure to increase health facility deliveries led to unintended consequences, such as community-imposed penalty fees for home deliveries. Delay 2: Community members perceived some improvements, such as refurbished maternity waiting homes and dedicated maternity ambulances, but many still had difficulty reaching the health facilities in time to deliver. Delay 3: SMGL’s clinician trainings were considered a strength, but the increased demand for health facility deliveries led to human resource challenges, which affected perceived quality of care. CONCLUSION AND LESSONS LEARNED: While SMGL’s health systems strengthening approach aimed to reduce challenges related to the 3 delays, participants still reported significant barriers accessing maternal and newborn health care. More research is needed to understand the necessary intervention package to affect system-wide change.

      6. Did saving mothers, giving life expand timely access to lifesaving care in Uganda? A spatial district-level analysis of travel time to emergency obstetric and newborn careExternal
        Schmitz MM, Serbanescu F, Kamara V, Kraft JM, Cunningham M, Opio G, Komakech P, Conlon CM, Goodwin MM.
        Glob Health Sci Pract. 2019 Mar 11;7(Suppl 1):S151-s167.
        INTRODUCTION: Interventions for the Saving Mothers, Giving Life (SMGL) initiative aimed to ensure all pregnant women in SMGL-supported districts have timely access to emergency obstetric and newborn care (EmONC). Spatial travel-time analyses provide a visualization of changes in timely access. METHODS: We compared travel-time estimates to EmONC health facilities in SMGL-supported districts in western Uganda in 2012, 2013, and 2016. To examine EmONC access, we analyzed a categorical variable of travel-time duration in 30-minute increments. Data sources included health facility assessments, geographic coordinates of EmONC facilities, geolocated population estimates of women of reproductive age (WRA), and other road network and geographic sources. RESULTS: The number of EmONC facilities almost tripled between 2012 and 2016, increasing geographic access to EmONC. Estimated travel time to EmONC facilities declined significantly during the 5-year period. The proportion of WRA able to access any EmONC and comprehensive EmONC (CEmONC) facility within 2 hours by motorcycle increased by 18% (from 61.3% to 72.1%, P < .01) and 37% (from 51.1% to 69.8%, P < .01), respectively from baseline to 2016. Similar increases occurred among WRA accessing EmONC and CEmONC respectively if 4-wheeled vehicles (14% and 31% increase, P < .01) could be used. Increases in timely access were also substantial for nonmotorized transportation such as walking and/or bicycling. CONCLUSIONS: Largely due to the SMGL-supported expansion of EmONC capability, timely access to EmONC significantly improved. Our analysis developed a geographic outline of facility accessibility using multiple types of transportation. Spatial travel-time analyses, along with other EmONC indicators, can be used by planners and policy makers to estimate need and target underserved populations to achieve further gains in EmONC accessibility. In addition to increasing the number and geographic distribution of EmONC facilities, complementary efforts to make motorized transportation available are necessary to achieve meaningful increases in EmONC access.

      7. Impact of the Saving Mothers, Giving Life approach on decreasing maternal and perinatal deaths in Uganda and ZambiaExternal
        Serbanescu F, Clark TA, Goodwin MM, Nelson LJ, Boyd MA, Kekitiinwa AR, Kaharuza F, Picho B, Morof D, Blanton C, Mumba M, Komakech P, Carlosama F, Schmitz MM, Conlon CM.
        Glob Health Sci Pract. 2019 Mar 11;7(Suppl 1):S27-s47.
        BACKGROUND: Maternal and perinatal mortality is a global development priority that continues to present major challenges in sub-Saharan Africa. Saving Mothers, Giving Life (SMGL) was a multipartner initiative implemented from 2012 to 2017 with the goal of improving maternal and perinatal health in high-mortality settings. The initiative accomplished this by reducing delays to timely and appropriate obstetric care through the introduction and support of community and facility evidence-based and district-wide health systems strengthening interventions. METHODS: SMGL-designated pilot districts in Uganda and Zambia documented baseline and endline maternal and perinatal health outcomes using multiple approaches. These included health facility assessments, pregnancy outcome monitoring, enhanced maternal mortality detection in facilities, and district population-based identification and investigation of maternal deaths in communities. RESULTS: Over the course of the 5-year SMGL initiative, population-based estimates documented a 44% reduction in the SMGL-supported district-wide maternal mortality ratio (MMR) in Uganda (from 452 to 255 maternal deaths per 100,000 live births) and a 41% reduction in Zambia (from 480 to 284 maternal deaths per 100,000 live births). The MMR in SMGL-supported health facilities declined by 44% in Uganda and by 38% in Zambia. The institutional delivery rate increased by 47% in Uganda (from 45.5% to 66.8% of district births) and by 44% in Zambia (from 62.6% to 90.2% of district births). The number of facilities providing emergency obstetric and newborn care (EmONC) rose from 10 to 26 in Uganda and from 7 to 13 in Zambia, and lower- and mid-level facilities increased the number of EmONC signal functions performed. Cesarean delivery rates increased by more than 70% in both countries, reaching 9% and 5% of all births in Uganda and Zambia districts, respectively. Maternal deaths in facilities due to obstetric hemorrhage declined by 42% in Uganda and 65% in Zambia. Overall, perinatal mortality rates declined, largely due to reductions in stillbirths in both countries; however, no statistically significant changes were found in predischarge neonatal death rates in predischarge either country. CONCLUSIONS: MMRs fell significantly in Uganda and Zambia following the introduction of the SMGL interventions, and SMGL’s comprehensive district systems-strengthening approach successfully improved coverage and quality of care for mothers and newborns. The lessons learned from the initiative can inform policy makers and program managers in other low- and middle-income settings where similar approaches could be used to rapidly reduce preventable maternal and newborn deaths.

      8. Addressing the first delay in Saving Mothers, Giving Life districts in Uganda and Zambia: Approaches and results for increasing demand for facility delivery servicesExternal
        Serbanescu F, Goodwin MM, Binzen S, Morof D, Asiimwe AR, Kelly L, Wakefield C, Picho B, Healey J, Nalutaaya A, Hamomba L, Kamara V, Opio G, Kaharuza F, Blanton C, Luwaga F, Steffen M, Conlon CM.
        Glob Health Sci Pract. 2019 Mar 11;7(Suppl 1):S48-s67.
        Saving Mothers, Giving Life (SMGL), a 5-year initiative implemented in selected districts in Uganda and Zambia, was designed to reduce deaths related to pregnancy and childbirth by targeting the 3 delays to receiving appropriate care at birth. While originally the “Three Delays” model was designed to focus on curative services that encompass emergency obstetric care, SMGL expanded its application to primary and secondary prevention of obstetric complications. Prevention of the “first delay” focused on addressing factors influencing the decision to seek delivery care at a health facility. Numerous factors can contribute to the first delay, including a lack of birth planning, unfamiliarity with pregnancy danger signs, poor perceptions of facility care, and financial or geographic barriers. SMGL addressed these barriers through community engagement on safe motherhood, public health outreach, community workers who identified pregnant women and encouraged facility delivery, and incentives to deliver in a health facility. SMGL used qualitative and quantitative methods to describe intervention strategies, intervention outcomes, and health impacts. Partner reports, health facility assessments (HFAs), facility and community surveillance, and population-based mortality studies were used to document activities and measure health outcomes in SMGL-supported districts. SMGL’s approach led to unprecedented community outreach on safe motherhood issues in SMGL districts. About 3,800 community health care workers in Uganda and 1,558 in Zambia were engaged. HFAs indicated that facility deliveries rose significantly in SMGL districts. In Uganda, the proportion of births that took place in facilities rose from 45.5% to 66.8% (47% increase); similarly, in Zambia SMGL districts, facility deliveries increased from 62.6% to 90.2% (44% increase). In both countries, the proportion of women delivering in facilities equipped to provide emergency obstetric and newborn care also increased (from 28.2% to 41.0% in Uganda and from 26.0% to 29.1% in Zambia). The districts documented declines in the number of maternal deaths due to not accessing facility care during pregnancy, delivery, and the postpartum period in both countries. This reduction played a significant role in the decline of the maternal mortality ratio in SMGL-supported districts in Uganda but not in Zambia. Further work is needed to sustain gains and to eliminate preventable maternal and perinatal deaths.

  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. Resurgence of diabetes-related nontraumatic lower-extremity amputation in the young and middle-aged adult U.S. populationExternal
        Geiss LS, Li Y, Hora I, Albright A, Rolka D, Gregg EW.
        Diabetes Care. 2019 Jan;42(1):50-54.
        OBJECTIVE: To determine whether declining trends in lower-extremity amputations have continued into the current decade. RESEARCH DESIGN AND METHODS: We calculated hospitalization rates for nontraumatic lower-extremity amputation (NLEA) for the years 2000-2015 using nationally representative, serial cross-sectional data from the Nationwide Inpatient Sample on NLEA procedures and from the National Health Interview Survey for estimates of the populations with and without diabetes. RESULTS: Age-adjusted NLEA rates per 1,000 adults with diabetes decreased 43% between 2000 (5.38 [95% CI 4.93-5.84]) and 2009 (3.07 [95% CI 2.79-3.34]) (P < 0.001) and then rebounded by 50% between 2009 and 2015 (4.62 [95% CI 4.25-5.00]) (P < 0.001). In contrast, age-adjusted NLEA rates per 1,000 adults without diabetes decreased 22%, from 0.23 per 1,000 (95% CI 0.22-0.25) in 2000 to 0.18 per 1,000 (95% CI 0.17-0.18) in 2015 (P < 0.001). The increase in diabetes-related NLEA rates between 2009 and 2015 was driven by a 62% increase in the rate of minor amputations (from 2.03 [95% CI 1.83-2.22] to 3.29 [95% CI 3.01-3.57], P < 0.001) and a smaller, but also statistically significant, 29% increase in major NLEAs (from 1.04 [95% CI 0.94-1.13] to 1.34 [95% CI 1.22-1.45]). The increases in rates of total, major, and minor amputations were most pronounced in young (age 18-44 years) and middle-aged (age 45-64 years) adults and more pronounced in men than women. CONCLUSIONS: After a two-decade decline in lower-extremity amputations, the U.S. may now be experiencing a reversal in the progress, particularly in young and middle-aged adults.

      2. Human papillomavirus DNA detection, p16 INK4a, and oral cavity cancer in a U.S. populationExternal
        Hernandez BY, Lynch CF, Chan OT, Goodman MT, Unger ER, Steinau M, Thompson TD, Gillison M, Lyu C, Saraiya M.
        Oral Oncology. 2019 ;91:92-96.
        Objectives: The role of HPV in oral cavity cancers was investigated using two markers of viral exposure. Materials and methods: HPV DNA and p16 INK4a expression were evaluated in tumor tissue from a U.S. population-based sample of 122 invasive oral cavity cancer cases. Results: HPV DNA was detected in 38 of 122 (31%) oral cavity tumors. Seven genotypes were detected including HPV 16, which was found in 22% of tumors. p16 INK4a was expressed in 30% of tumors and was poorly correlated with HPV DNA detection (Kappa <0.1). Joint positivity for HPV 16 and/or 18 and p16 INK4a was observed in only 7% of cases. When comparing cases diagnosed in 1993-1999 and in 2000-2004, positivity for HPV DNA 16/18 increased from 19% to 39% (p = 0.02) and joint HPV 16/18 – p16 INK4a positivity increased from 0% to 12% (p = 0.01). For gingival tumors, HPV 16 and/or 18 positivity was 67% compared to 11-38% for other sites (p = 0.02); joint HPV 16/18 – p16 INK4a positivity was 33% compared to 0-8% for other sites (p = 0.01). The association of HPV with gingival tumors and more recent diagnosis period remained after adjustment for age and stage (p< 0.05). Neither HPV DNA nor p16 INK4a were associated with overall survival. Conclusions: Based on both HPV DNA and p16 INK4a , HPV is etiologically linked to a limited subset of oral cavity cancers. However, the role of HPV in oral cavity cancer may vary widely by subsite and may have increased over time, similar to trends observed for oropharyngeal cancer.

      3. Erectile dysfunction is highly prevalent in men with newly diagnosed inflammatory bowel diseaseExternal
        Shmidt E, Suarez-Farinas M, Mallette M, Moniz H, Bright R, Shah SA, Merrick M, Shapiro J, Xu F, Saha S, Sands BE.
        Inflamm Bowel Dis. 2019 Mar 11.
        BACKGROUND AND AIMS: Cross-sectional studies on sexual function in men with inflammatory bowel disease (IBD) yield mixed results. Using a prospective incidence cohort, we aimed to describe sexual function at baseline and over time and to identify factors associated with impaired sexual function in men with IBD. METHODS: Men 18 years and older enrolled between April 2008 and January 2013 in the Ocean State Crohn’s and Colitis Area Registry (OSCCAR) with a minimum of 2 years of follow-up were eligible for study. Male sexual function was assessed using the International Index of Erectile Function (IIEF), a self-administered questionnaire that assesses 5 dimensions of sexual function over the most recent 4 weeks. To assess changes in the IIEF per various demographic and clinical factors, linear mixed effects models were used. RESULTS: Sixty-nine of 82 eligible men (84%) completed the questionnaire (41 Crohn’s disease, 28 ulcerative colitis). The mean age (SD) of the cohort at diagnosis was 43.4 (19.2) years. At baseline, 39% of men had global sexual dysfunction, and 94% had erectile dysfunction. Independent factors associated with erectile dysfunction are older age and lower physical and mental component summary scores on the Short Form Health Survey (SF-36). CONCLUSION: In an incident cohort of IBD patients, most men had erectile dysfunction. Physicians should be aware of the high prevalence of erectile dysfunction and its associated risk factors among men with newly diagnosed IBD to direct multidisciplinary treatment planning.

    • Communicable Diseases
      1. Investigating an outbreak of measles in Kamwenge District, Uganda, July 2015External
        Ario AR, Nsubuga F, Bulage L, Zhu BP.
        Pan Afr Med J. 2018 ;30(Suppl 1):9.
        Globalization has opened many fronts for disease outbreaks because of the quick movement of people and porous borders around the world. The emergence of zoonotic diseases and other communicable diseases highlights the need for implementation of the Global Health Security Agenda packages if countries are to achieve compliance with International Health Regulations (IHR 2005). Health workforce development is one of the critical components that must be addressed with utmost urgency if gaps in early disease detection and response are to be addressed. In this regard, this case study is based on a measles outbreak investigation in Uganda simulating a real-life outbreak investigation by field epidemiologists and seeks to demonstrate the principles of applied epidemiology outlining the critical steps in outbreak investigations and generation of evidence for decision making. It aims to shore up the health workforce capacity by providing practical training for field epidemiology students and professionals that builds their skills in outbreak investigation. This case study can be completed in less than three hours.

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

      3. Cost-effectiveness of hepatitis B virus infection screening and treatment or vaccination in 6 high-risk populations in the United StatesExternal
        Chahal HS, Peters MG, Harris AM, McCabe D, Volberding P, Kahn JG.
        Open Forum Infect Dis. 2019 ;6(1).
        Background. Two million individuals with chronic hepatitis B (CHB) in the United States are at risk for premature death due to liver cancer and cirrhosis. CHB can be prevented by vaccination and controlled with treatment. Methods. We created a lifetime Markov model to estimate the cost-effectiveness of strategies to prevent or treat CHB in 6 highrisk populations: foreign-born Asian/Pacific Islanders (API), Africa-born blacks (AbB), incarcerated, refugees, persons who inject drugs (PWID), and men who have sex with men (MSM). We studied 3 strategies: (a) screen for HBV infection and treat infected (“treatment only”), (b) screen for HBV susceptibility and vaccinate susceptible (“vaccination only”), and (c) screen for both and follow-up appropriately (“inclusive”). Outcomes were expressed in incremental cost-effectiveness ratios (ICERs), clinical outcomes, and new infections. Results. Vaccination-only and treatment-only strategies had ICERs of $6000-$21 000 per quality-adjusted life-year (QALY) gained, respectively. The inclusive strategy added minimal cost with substantial clinical benefit, with the following costs per QALY gained vs no intervention: incarcerated $3203, PWID $8514, MSM $10 954, AbB $17 089, refugees $17 432, and API $18 009. Clinical complications dropped in the short/intermediate (1%-25%) and long (0.4%-16%) term. Findings were sensitive to age, discount rate, health state utility in immune or susceptible stages, progression rate to cirrhosis or inactive disease, and tenofovir cost. The probability of an inclusive program costing <$50 000 per QALY gained varied between 61% and 97% by population. Conclusions. An inclusive strategy to screen and treat or vaccinate is cost-effective in reducing the burden of hepatitis B virus among all 6 high-risk, high-prevalence populations.

      4. Notes from the Field: HIV diagnoses among persons who inject drugs – northeastern Massachusetts, 2015-2018External
        Cranston K, Alpren C, John B, Dawson E, Roosevelt K, Burrage A, Bryant J, Switzer WM, Breen C, Peters PJ, Stiles T, Murray A, Fukuda HD, Adih W, Goldman L, Panneer N, Callis B, Campbell EM, Randall L, France AM, Klevens RM, Lyss S, Onofrey S, Agnew-Brune C, Goulart M, Jia H, Tumpney M, McClung P, Dasgupta S, Bixler D, Hampton K, Jaeger JL, Buchacz K, DeMaria A.
        MMWR Morb Mortal Wkly Rep. 2019 Mar 15;68(10):253-254.

        [No abstract]

      5. BACKGROUND: Calculating national rates of HIV diagnosis, incidence, and prevalence can quantify disease burden, and is important for planning and evaluating programs. We calculated HIV rates among MSM, persons who inject drugs (PWID), and heterosexuals in 2010 and 2015. METHODS: We used proportion estimates of the US population classified as MSM, PWID, and heterosexuals along with census data to calculate the population sizes which were used as the denominators for calculating HIV rates. The numerators (HIV diagnosis, incidence, and prevalence) were based on data submitted to the National HIV Surveillance System through June 2017. RESULTS: The estimated HIV diagnosis and incidence rates in 2015 were 574.7 and 583.6 per 100 000 MSM; 34.3 and 32.7 per 100 000 PWID; and 4.1 and 3.8 per 100 000 heterosexuals. The estimated HIV prevalence in 2015 was 12 372.9 per 100 000 MSM; 1937.2 per 100 000 PWID; and 126.7 per 100 000 heterosexuals. The HIV diagnosis rates decreased from 2010 to 2015 in all three transmission categories. Black individuals had the highest HIV diagnosis rates at both time points. The HIV incidence rates decreased among white MSM, MSM aged 13-24 years, PWID overall, and male and female heterosexual individuals; however, it increased among MSM aged 25-34 years. CONCLUSIONS: The estimated HIV diagnosis and HIV infection rates decreased for several transmission categories, and also race/ethnicity and age subgroups. MSM continue to be disproportionately affected. Disparities remain and have widened for some groups. Efforts are needed to strengthen prevention, care, and supportive services for all persons with HIV infection.

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

      7. Effect of acute respiratory illness on short-term frailty status of older adults in Nakhon Phanom, Thailand-June 2015 to June 2016: A prospective matched cohort studyExternal
        Hughes MM, Praphasiri P, Dawood FS, Sornwong K, Ditsungnoen D, Mott JA, Prasert K.
        Influenza Other Respir Viruses. 2019 Mar 7.
        BACKGROUND: Frailty is associated with increased risk of mortality and decline in functional status among older adults. Older adults are at increased risk of severe disease from acute respiratory illness (ARIs), but ARI effects on frailty status among older adults are not well understood. We evaluated how ARIs affect short-term frailty status among community-dwelling adults aged >/=65 years in Nakhon Phanom, Thailand. METHODS: During May 2015 to May 2017, older adults were contacted weekly to identify ARIs as part of a community-based longitudinal cohort study. Each participant’s frailty status was assessed at baseline and every 6 months using the Vulnerable Elders Survey-13 (VES-13). We selected cohort participants with an ARI and compared them with a sample of participants without an ARI matched on age, sex, influenza vaccination status, and most recent VES-13 score. For these matched cohort members, an additional VES-13 was recorded at 3-4 weeks after the ARI episode date. RESULTS: Of 3220 cohort study participants, 114 participants with an ARI and 111 comparison participants without an ARI were selected for the matched cohort; three comparison participants were matched to two ARI cases. We found no statistically significant difference between ARI and non-ARI participants in modified VES-13 score 3-4 weeks post-episode (cases = 0.90, controls = 0.63, P = 0.07). Only two ARI episodes required hospitalization. CONCLUSIONS: Primarily mild ARIs did not affect short-term frailty status among community-dwelling older adults in Thailand. As few cases of severe ARI were detected, the contribution of severe ARI to changes in frailty requires further investigation.

      8. Improvements in the HIV care continuum needed to meaningfully reduce HIV incidence among men who have sex with men in Baltimore, US: a modelling study for HPTN 078External
        Mitchell KM, Hoots B, Dimitrov D, German D, Flynn C, Farley JE, Gelman M, Hughes JP, Donnell D, Adeyeye A, Remien RH, Beyrer C, Paz-Bailey G, Boily MC.
        J Int AIDS Soc. 2019 Mar;22(3):e25246.
        INTRODUCTION: HIV prevalence is high among men who have sex with men (MSM) in Baltimore, Maryland, United States, and the levels of viral suppression among HIV-positive MSM are relatively low. The HIV Prevention Trials Network 078 trial seeks to increase the levels of viral suppression among US MSM by increasing the rates of diagnosis and linkage to care and treatment. We estimated the increases in viral suppression needed to reach different HIV incidence reduction targets, and the impact of meeting diagnosis and treatment targets. METHODS: We used a mathematical model of HIV transmission among MSM from Baltimore, US, parameterised with behavioural data and fitted to HIV prevalence and care continuum data for Baltimore wherever possible, to project increases in viral suppression needed to reduce the HIV incidence rate among Baltimore MSM by 10, 20, 30 or 50% after 2, 5 and 10 years. We also projected HIV incidence reductions achieved if US national targets – 90% of people living with HIV (PLHIV) know their HIV serostatus, 90% of those diagnosed are retained in HIV medical care and 80% of those diagnosed are virally suppressed – or UNAIDS 90-90-90 targets (90% of PLHIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), 90% of those receiving ART are virally suppressed) are each met by 2020. RESULTS: To reduce the HIV incidence rate by 20% and 50% after five years (compared with the base-case at the same time point), the proportion of all HIV-positive MSM who are virally suppressed must increase above 2015 levels by a median 13 percentage points (95% uncertainty interval 9 to 16 percentage points) from median 49% to 60%, and 27 percentage points (22 to 35) from 49% to 75% respectively. Meeting all three US or 90-90-90 UNAIDS targets results in a 48% (31% to 63%) and 51% (38% to 65%) HIV incidence rate reduction in 2020 respectively. CONCLUSIONS: Substantial improvements in levels of viral suppression will be needed to achieve significant incidence reductions among MSM in Baltimore, and to meet 2020 US and UNAIDS targets. Future modelling studies should additionally consider the impact of pre-exposure prophylaxis for MSM.

      9. OBJECTIVES: To investigate treatment outcomes and associated characteristics of persons experiencing homelessness who received 12-weekly doses of directly observed isoniazid and rifapentine (3HP/DOT) treatment for latent TB infection (LTBI). METHODS: Among homeless persons treated with 3HP/DOT during July 2011 -June 2015 in 11 U.S. TB programs, we conducted descriptive analyses of observational data, and identified associations between sociodemographic factors and treatment outcomes. Qualitative interviews were conducted to understand programmatic experiences. RESULTS: Of 393 persons experiencing homelessness (median age: 50 years; range: 13-74 years), 301 (76.6%) completed treatment, 55 (14.0%) were lost to follow-up, 18 (4.6%) stopped because of an adverse event (AE), and 19 (4.8%) stopped after relocations or refusing treatment. Eighty-one (20.6%) had at least one AE. Persons aged >/=65 were more likely to discontinue treatment than persons aged 31-44 years. Programs reported difficulty in following up with persons experiencing homelessness because of relocations, mistrust, and alcohol or drug use. CONCLUSIONS: This study demonstrates the feasibility of administering the 3HP/DOT LTBI regimen to persons experiencing homelessness, a high-risk population.

      10. A generalizable method for estimating duration of HIV infections using clinical testing history and HIV test resultsExternal
        Pilcher CD, Porco TC, Facente SN, Grebe E, Delaney KP, Masciotra S, Kassanjee R, Busch MP, Murphy G, Owen SM, Welte A.
        Aids. 2019 Mar 11.
        OBJECTIVE: To determine the precision of new and established methods for estimating duration of HIV infection. DESIGN: A retrospective analysis of HIV testing results from serial samples in commercially-available panels, taking advantage of extensive testing previously conducted on 53 seroconverters. METHODS: We initially investigated four methods for estimating infection timing: 1) “Fiebig stages” based on test results from a single specimen; 2) an updated “4 gen” method similar to Fiebig stages but using antigen/antibody tests in place of the p24 antigen test; 3) modeling of “viral ramp-up” dynamics using quantitative HIV-1 viral load data from antibody-negative specimens; and 4) using detailed clinical testing history to define a plausible interval and best estimate of infection time. We then investigated a “two-step method” using data from both methods 3 and 4, allowing for test results to have come from specimens collected on different days. RESULTS: Fiebig and “4 gen” staging method estimates of time since detectable viremia had similar and modest correlation with observed data. Correlation of estimates from both new methods (3 and 4), and from a combination of these two (“2-step method”) was markedly improved and variability significantly reduced when compared with Fiebig estimates on the same specimens. CONCLUSIONS: The new “two-step” method more accurately estimates timing of infection and is intended to be generalizable to more situations in clinical medicine, research, and surveillance than previous methods. An online tool is now available that enables researchers/clinicians to input data related to method 4, and generate estimated dates of detectable infection.

      11. A case of inguinal lymphogranuloma venereum imitating malignancy on CT imagingExternal
        Promer K, Pillay A, Chi KH, Vahdat N, Katz SS, Chen CY, Fierer J.
        Radiol Case Rep. 2019 ;14(5):581-583.
        Lymphogranuloma venereum is a sexually transmitted infection caused by serovars L1, L2, and L3 of Chlamydia trachomatis. We here report a case of Lymphogranuloma venereum, confirmed by PCR testing, which mimicked malignancy on CT imaging.

      12. Using discrete choice experiments to inform the design of complex interventionsExternal
        Terris-Prestholt F, Neke N, Grund JM, Plotkin M, Kuringe E, Osaki H, Ong JJ, Tucker JD, Mshana G, Mahler H, Weiss HA, Wambura M.
        Trials. 2019 Mar 4;20(1):157.
        BACKGROUND: Complex health interventions must incorporate user preferences to maximize their potential effectiveness. Discrete choice experiments (DCEs) quantify the strength of user preferences and identify preference heterogeneity across users. We present the process of using a DCE to supplement conventional qualitative formative research in the design of a demand creation intervention for voluntary medical male circumcision (VMMC) to prevent HIV in Tanzania. METHODS: The VMMC intervention was designed within a 3-month formative phase. In-depth interviews (n = 30) and participatory group discussions (n = 20) sought to identify broad setting-specific barriers to and facilitators of VMMC among adult men. Qualitative results informed the DCE development, identifying the role of female partners, service providers’ attitudes and social stigma. A DCE among 325 men in Njombe and Tabora, Tanzania, subsequently measured preferences for modifiable VMMC service characteristics. The final VMMC demand creation intervention design drew jointly on the qualitative and DCE findings. RESULTS: While the qualitative research informed the community mobilization intervention, the DCE guided the specific VMMC service configuration. The significant positive utilities (u) for availability of partner counselling (u = 0.43, p < 0.01) and age-separated waiting areas (u = 0.21, p < 0.05) led to the provision of community information booths for partners and provision of age-separated waiting areas. The strong disutility of female healthcare providers (u = – 0.24, p < 0.01) led to re-training all providers on client-friendliness. CONCLUSION: This is, to our knowledge, the first study documenting how user preferences from DCEs can directly inform the design of a complex intervention. The use of DCEs as formative research may help increase user uptake and adherence to complex interventions.

      13. Estimating the population size of female sex workers in Namibia using a respondent-driven sampling adjustment to the reverse tracking method: A novel approachExternal
        Wesson PD, Adhikary R, Jonas A, Gerndt K, Mirzazadeh A, Katuta F, Maher A, Banda K, Mutenda N, McFarland W, Lowrance D, Prybylski D, Patel S.
        JMIR Public Health Surveill. 2019 Mar 14;5(1):e11737.
        BACKGROUND: Key populations, including female sex workers (FSWs), are at a disproportionately high risk for HIV infection. Estimates of the size of these populations serve as denominator data to inform HIV prevention and treatment programming and are necessary for the equitable allocation of limited public health resources. OBJECTIVE: This study aimed to present the respondent-driven sampling (RDS) adjusted reverse tracking method (RTM; RadR), a novel population size estimation approach that combines venue mapping data with RDS data to estimate the population size, adjusted for double counting and nonattendance biases. METHODS: We used data from a 2014 RDS survey of FSWs in Windhoek and Katima Mulilo, Namibia, to demonstrate the RadR method. Information from venue mapping and enumeration from the survey formative assessment phase were combined with survey-based venue-inquiry questions to estimate population size, adjusting for double counting, and FSWs who do not attend venues. RadR estimates were compared with the official population size estimates, published by the Namibian Ministry of Health and Social Services (MoHSS), and with the unadjusted RTM. RESULTS: Using the RadR method, we estimated 1552 (95% simulation interval, SI, 1101-2387) FSWs in Windhoek and 453 (95% SI: 336-656) FSWs in Katima Mulilo. These estimates were slightly more conservative than the MoHSS estimates-Windhoek: 3000 (1800-3400); Katima Mulilo: 800 (380-2000)-though not statistically different. We also found 75 additional venues in Windhoek and 59 additional venues in Katima Mulilo identified by RDS participants’ responses that were not detected during the initial mapping exercise. CONCLUSIONS: The RadR estimates were comparable with official estimates from the MoHSS. The RadR method is easily integrated into RDS studies, producing plausible population size estimates, and can also validate and update key population maps for outreach and venue-based sampling.

    • Environmental Health
      1. Legionnaires’ disease at a hotel in Missouri, 2015: The importance of environmental health expertise in understanding water systemsExternal
        Ahmed SS, Hunter CM, Mercante JW, Garrison LE, Turabelidze G, Kunz J, Cooley LA.
        J Environ Health. 2019 ;81(7):8-13.
        During a Legionnaires’ disease outbreak at a Missouri hotel in 2015, the Centers for Disease Control and Prevention assisted state and local health departments to identify possible sources and transmission factors and to recommend improvements to water management. We performed an environmental assessment to understand the hotel’s water systems and identify areas of risk for Legionella amplifi cation and transmission. We obtained samples from the pool, spa, and potable water systems for Legionella culture. In the potable water system, we noted temperatures ideal for Legionella amplifi cation and areas of water stagnation. Additionally, we found inadequate documentation of pool and spa disinfection and maintenance. Of 40 water samples, Legionella pneumophila serogroup 1 that matched the sequence type of one available clinical isolate was recovered from five sink and shower fixtures. A comprehensive environmental assessment proved crucial to identifying maintenance issues in the hotel’s water systems and underscored the need for a water management program to reduce Legionnaires’ disease risk.

      2. Confluent impact of housing and geology on indoor radon concentrations in Atlanta, Georgia, United StatesExternal
        Dai D, Neal FB, Diem J, Deocampo DM, Stauber C, Dignam T.
        Sci Total Environ. 2019 Feb 20;668:500-511.
        Radon is a naturally released radioactive carcinogenic gas. To estimate radon exposure, studies have examined various risk factors, but limited information exists pertaining to the confluent impact of housing characteristics and geology. This study evaluated the efficacy of housing and geological characteristics to predict radon risk in DeKalb County, Georgia, USA. Four major types of data were used: (1) three databases of indoor radon concentrations (n=6757); (2) geologic maps of rock types and fault zones; (3) a database of 402 in situ measurements of gamma emissions, and (4) two databases of housing characteristics. The Getis-Ord method was used to delineate hot spots of radon concentrations. Empirical Bayesian Kriging was used to predict gamma radiation at each radon test site. Chi-square tests, bivariate correlation coefficients, and logistic regression were used to examine the impact of geological and housing factors on radon. The results showed that indoor radon levels were more likely to exceed the action level-4 pCi/L (148Bq/m(3)) designated by the U.S. Environmental Protection Agency-in fault zones, were significantly positively correlated to gamma readings, but significantly negatively related to the presence of a crawlspace foundation and its combination with a slab. The findings suggest that fault mapping and in situ gamma ray measurements, coupled with analysis of foundation types and delineation of hot spots, may be used to prioritize areas for radon screening.

      3. Urinary concentrations of phthalate biomarkers and weight change among postmenopausal women: a prospective cohort studyExternal
        Diaz Santana MV, Hankinson SE, Bigelow C, Sturgeon SR, Zoeller RT, Tinker L, Manson JA, Calafat AM, Meliker JR, Reeves KW.
        Environ Health. 2019 Mar 12;18(1):20.
        BACKGROUND: Some phthalates are endocrine disrupting chemicals used as plasticizers in consumer products, and have been associated with obesity in cross-sectional studies, yet prospective evaluations of weight change are lacking. Our objective was to evaluate associations between phthalate biomarker concentrations and weight and weight change among postmenopausal women. METHODS: We performed cross-sectional (N = 997) and longitudinal analyses (N = 660) among postmenopausal Women’s Health Initiative participants. We measured 13 phthalate metabolites and creatinine in spot urine samples provided at baseline. Participants’ weight and height measured at in-person clinic visits at baseline, year 3, and year 6 were used to calculate body mass index (BMI). We fit multivariable multinomial logistic regression models to explore cross-sectional associations between each phthalate biomarker and baseline BMI category. We evaluated longitudinal associations between each biomarker and weight change using mixed effects linear regression models. RESULTS: In cross-sectional analyses, urinary concentrations of some biomarkers were positively associated with obesity prevalence (e.g. sum of di (2-ethylhexyl) phthalate metabolites [SigmaDEHP] 4th vs 1st quartile OR = 3.29, 95% CI 1.80-6.03 [p trend< 0.001] vs normal). In longitudinal analyses, positive trends with weight gain between baseline and year 3 were observed for mono-(2-ethyl-5-oxohexyl) phthalate, monoethyl phthalate (MEP), mono-hydroxybutyl phthalate, and mono-hydroxyisobutyl phthalate (e.g. + 2.32 kg [95% CI 0.93-3.72] for 4th vs 1st quartile of MEP; p trend < 0.001). No statistically significant associations were observed between biomarkers and weight gain over 6 years. CONCLUSIONS: Certain phthalates may contribute to short-term weight gain among postmenopausal women.

      4. Personal ultraviolet radiation exposure in a cohort of Chinese mother and child pairs: the Chinese families and children studyExternal
        Kimlin MG, Fang L, Feng Y, Wang L, Hao L, Fan J, Wang N, Meng F, Yang R, Cong S, Liang X, Wang B, Linet M, Potischman N, Kitahara C, Chao A, Wang Y, Sun J, Brodie A.
        BMC Public Health. 2019 Mar 8;19(1):281.
        BACKGROUND: Few studies in China have examined personal ultraviolet radiation (UVR) exposure using polysulfone dosimetry. METHODS: In this study, 93 mother and adolescent child pairs (N = 186) from two locations in China, one rural (higher latitude) and one urban (lower latitude), completed 3 days of personal UVR dosimetry and a sun/clothing diary, as part of a larger pilot study. RESULTS: The average daily ambient UVR in each location as measured by dosimetry was 20.24 Minimal Erythemal Doses (MED) in the rural location and 20.53 MED in the urban location. Rural mothers had more average daily time outdoors than urban mothers (5.5 h, compared with 1.5 h, in urban mothers) and a much higher daily average personal UVR exposure (4.50 MED, compared with 0.78 MED in urban mothers). Amongst adolescents, rural males had the highest average daily personal UVR exposure, followed by rural females, urban females and urban males (average 2.16, 1.05, 0.81, and 0.48 MED, respectively). CONCLUSIONS: Although based on small numbers, our findings show the importance of geographic location, age, work/school responsibilities, and sex of the adolescents in determining personal UVR exposure in China. These results suggest that latitude of residence may not be a good proxy for personal UVR exposure in all circumstances.

    • Food Safety
      1. Notes from the Field: Botulism outbreak associated with home-canned peas – New York City, 2018External
        Bergeron G, Latash J, Da Costa-Carter CA, Egan C, Stavinsky F, Kileci JA, Winstead A, Zhao B, Perry MJ, Chatham-Stephens K, Sarpel D, Hughes S, Conlon MA, Edmunds S, Mohanraj M, Rakeman JL, Centurioni DA, Luquez C, Chiefari AK, Harper S.
        MMWR Morb Mortal Wkly Rep. 2019 Mar 15;68(10):251-252.

        [No abstract]

    • Genetics and Genomics
      1. Whole-genome sequencing for characterization of capsule locus and prediction of serogroup of invasive meningococcal isolatesExternal
        Marjuki H, Topaz N, Rodriguez-Rivera LD, Ramos E, Potts CC, Chen A, Retchless AC, Doho GH, Wang X.
        J Clin Microbiol. 2019 Mar;57(3).
        Invasive meningococcal disease is mainly caused by Neisseria meningitidis serogroups A, B, C, X, W, and Y. The serogroup is typically determined by slide agglutination serogrouping (SASG) and real-time PCR (RT-PCR). We describe a whole-genome sequencing (WGS)-based method to characterize the capsule polysaccharide synthesis (cps) locus, classify N. meningitidis serogroups, and identify mechanisms for nongroupability using 453 isolates from a global strain collection. We identified novel genomic organizations within functional cps loci, consisting of insertion sequence (IS) elements in unique positions that did not disrupt the coding sequence. Genetic mutations (partial gene deletion, missing genes, IS insertion, internal stop, and phase-variable off) that led to nongroupability were identified. The results of WGS and SASG were in 91% to 100% agreement for all serogroups, while the results of WGS and RT-PCR showed 99% to 100% agreement. Among isolates determined to be nongroupable by WGS (31 of 453), the results of all three methods agreed 100% for those without a capsule polymerase gene. However, 61% (WGS versus SASG) and 36% (WGS versus RT-PCR) agreements were observed for the isolates, particularly those with phase variations or internal stops in cps loci, which warrant further characterization by additional tests. Our WGS-based serogrouping method provides comprehensive characterization of the N. meningitidis capsule, which is critical for meningococcal surveillance and outbreak investigations.

    • Global Health
      1. Definitions matter: migrants, immigrants, asylum seekers and refugeesExternal
        Douglas P, Cetron M, Spiegel P.
        J Travel Med. 2019 Feb 1;26(2).

        [No abstract]

    • Health Communication and Education
      1. PURPOSE: Many young people are not aware of their rights to confidential sexual and reproductive health (SRH) care. Given that online health information seeking is common among adolescents, we examined how health education Web content about SRH for young people addresses confidentiality. METHODS: In Spring 2017, we conducted Google keyword searches (e.g., “teens” and “sex education”) to identify health promotion Web sites operated by public health/medical organizations in the United States and providing original content about SRH for adolescents/young adults. Thirty-two Web sites met inclusion criteria. We uploaded Web site PDFs to qualitative analysis software to identify confidentiality-related content and conduct thematic analysis of the 29 Web sites with confidentiality content. RESULTS: Sexually transmitted infection testing and contraception were the SRH services most commonly described as confidential. Clear and comprehensive definitions of confidentiality were lacking; Web sites typically described confidentiality in relation to legal rights to receive care without parental consent or notification. Few mentioned the importance of time alone with a medical provider. Only half of the Web sites described potential inadvertent breaches of confidentiality associated with billing and even fewer described other restrictions to confidentiality practices (e.g., mandatory reporting laws). Although many Web sites recommended that adolescents verify confidentiality, guidance for doing so was not routinely provided. Information about confidentiality often encouraged adolescents to communicate with parents. CONCLUSIONS: There is a need to provide comprehensive information, assurances, and resources about confidentiality practices while also addressing limitations to confidentiality in a way that does not create an undue burden on adolescents or reinforce and exacerbate confidentiality concerns.

    • Health Disparities
      1. State inequality, socioeconomic position and subjective cognitive decline in the United StatesExternal
        Peterson RL, Carvajal SC, McGuire LC, Fain MJ, Bell ML.
        SSM – Population Health. 2019 ;7.
        Background: Social gradients in health have been observed for many health conditions and are suggested to operate through the effects of status anxiety. However, the gradient between education and Alzheimer’s disease is presumed to operate through cognitive stimulation. We examined the possible role of status anxiety through testing for state-level income inequality and social gradients in markers of socioeconomic position (SEP) for Alzheimer’s disease risk. Methods: Using data from the cross-sectional 2015 and 2016 Behavioral Risk Factor Surveillance System (BRFSS) and the U.S. Census Bureau’s American Community Survey, we tested for the association between U.S. state-level income inequality and individual SEP on subjective cognitive decline (SCD) – a marker of dementia risk – using a generalized estimating equation and clustering by state. Results: State income inequality was not significantly associated with SCD in our multivariable model (OR 1.2; 95% CI: 0.9, 1.6; p=0.49). We observed a clear linear relationship between household income and SCD where those with an annual household income of 50k to 75k had 1.4 (95% CI: 1.3, 1.6) times the odds and those with household incomes of less than $10,000 had 4.7 (95% CI: 3.8, 5.7) times the odds of SCD compared to those with household income of more than $75,000. We also found that college graduates (ref.) and those who completed high school (OR: 1.1; 95% CI 1.04, 1.2) fared better than those with some college (OR: 1.3, 95% CI 1.2, 1.4) or less than a high school degree (OR: 1.5; 95% CI: 1.4, 1.7). Conclusions: Income inequality does not play a dominant role in SCD, though a social gradient in individual income for SCD suggests the relationship may operate in part via status anxiety.

    • Healthcare Associated Infections
      1. Hepatitis B and C virus infections transmitted through organ transplantation investigated by CDC, United States, 2014-2017External
        Bixler D, Annambholta P, Abara WE, Collier MG, Jones J, Mixson-Hayden T, Basavaraju SV, Ramachandran S, Kamili S, Moorman A.
        Am J Transplant. 2019 Mar 12.
        We evaluated clinical outcomes among organ recipients with donor-derived hepatitis B virus (HBV) or hepatitis C virus (HCV) infections investigated by CDC from 2014-2017 in the United States. We characterized new HBV infections in organ recipients if donors tested negative for total anti-HBc, HBsAg and HBV DNA, and new recipient HCV infections if donors tested negative for anti-HCV and HCV RNA. Donor risk behaviors were abstracted from next-of-kin interviews and medical records. During 2014-2017, seven new recipient HBV infections associated with seven donors were identified; six (86%) recipients survived. At last follow-up, all survivors had functioning grafts and five (83%) had started antiviral therapy. Twenty new recipient HCV infections associated with nine donors were identified; 19 (95%) recipients survived. At last follow-up, 18 (95%) survivors had functioning grafts and 14 (74%) had started antiviral treatment. Combining donor next-of kin interviews and medical records, 11/16 (69%) donors had evidence of injection drug use and all met Public Health Service increased risk donor (IRD) criteria. IRD designation led to early diagnosis of recipient infection, and prompt implementation of therapy, likely reducing the risk of graft failure, liver disease and death. This article is protected by copyright. All rights reserved.

      2. Chlorhexidine versus routine bathing to prevent multidrug-resistant organisms and all-cause bloodstream infections in general medical and surgical units (ABATE Infection trial): a cluster-randomised trialExternal
        Huang SS, Septimus E, Kleinman K, Moody J, Hickok J, Heim L, Gombosev A, Avery TR, Haffenreffer K, Shimelman L, Hayden MK, Weinstein RA, Spencer-Smith C, Kaganov RE, Murphy MV, Forehand T, Lankiewicz J, Coady MH, Portillo L, Sarup-Patel J, Jernigan JA, Perlin JB, Platt R.
        Lancet. 2019 Mar 4.
        BACKGROUND: Universal skin and nasal decolonisation reduces multidrug-resistant pathogens and bloodstream infections in intensive care units. The effect of universal decolonisation on pathogens and infections in non-critical-care units is unknown. The aim of the ABATE Infection trial was to evaluate the use of chlorhexidine bathing in non-critical-care units, with an intervention similar to one that was found to reduce multidrug-resistant organisms and bacteraemia in intensive care units. METHODS: The ABATE Infection (active bathing to eliminate infection) trial was a cluster-randomised trial of 53 hospitals comparing routine bathing to decolonisation with universal chlorhexidine and targeted nasal mupirocin in non-critical-care units. The trial was done in hospitals affiliated with HCA Healthcare and consisted of a 12-month baseline period from March 1, 2013, to Feb 28, 2014, a 2-month phase-in period from April 1, 2014, to May 31, 2014, and a 21-month intervention period from June 1, 2014, to Feb 29, 2016. Hospitals were randomised and their participating non-critical-care units assigned to either routine care or daily chlorhexidine bathing for all patients plus mupirocin for known methicillin-resistant Staphylococcus aureus (MRSA) carriers. The primary outcome was MRSA or vancomycin-resistant enterococcus clinical cultures attributed to participating units, measured in the unadjusted, intention-to-treat population as the HR for the intervention period versus the baseline period in the decolonisation group versus the HR in the routine care group. Proportional hazards models assessed differences in outcome reductions across groups, accounting for clustering within hospitals. This trial is registered with, number NCT02063867. FINDINGS: There were 189 081 patients in the baseline period and 339 902 patients (156 889 patients in the routine care group and 183 013 patients in the decolonisation group) in the intervention period across 194 non-critical-care units in 53 hospitals. For the primary outcome of unit-attributable MRSA-positive or VRE-positive clinical cultures (figure 2), the HR for the intervention period versus the baseline period was 0.79 (0.73-0.87) in the decolonisation group versus 0.87 (95% CI 0.79-0.95) in the routine care group. No difference was seen in the relative HRs (p=0.17). There were 25 (<1%) adverse events, all involving chlorhexidine, among 183 013 patients in units assigned to chlorhexidine, and none were reported for mupirocin. INTERPRETATION: Decolonisation with universal chlorhexidine bathing and targeted mupirocin for MRSA carriers did not significantly reduce multidrug-resistant organisms in non-critical-care patients. FUNDING: National Institutes of Health.

      3. The expansion of National Healthcare Safety Network enrollment and reporting in nursing homes: Lessons learned from a national qualitative studyExternal
        Stone PW, Chastain AM, Dorritie R, Tark A, Dick AW, Bell JM, Stone ND, Quigley DD, Sorbero ME.
        Am J Infect Control. 2019 Mar 5.
        BACKGROUND: This study explored nursing home (NH) personnel perceptions of the National Healthcare Safety Network (NHSN). METHODS: NHs were purposively sampled based on NHSN enrollment and reporting status, and other facility characteristics. We recruited NH personnel knowledgeable about the facility’s decision-making processes and infection prevention program. Interviews were conducted over-the-phone and audio-recorded; transcripts were analyzed using conventional content analysis. RESULTS: We enrolled 14 NHs across the United States and interviewed 42 personnel. Six themes emerged: Benefits of NHSN, External Support and Motivation, Need for a Champion, Barriers, Risk Adjustment, and Data Integrity. We did not find substantive differences in perceptions of NHSN value related to participants’ professional roles or enrollment category. Some participants from newly enrolled NHs felt well supported through the NHSN enrollment process, while participants from earlier enrolled NHs perceived the process to be burdensome. Among participants from non-enrolled NHs, as well as some from enrolled NHs, there was a lack of knowledge of NHSN. CONCLUSIONS: This qualitative study helps fill a gap in our understanding of barriers and facilitators to NHSN enrollment and reporting in NHs. Improved understanding of factors influencing decision-making processes to enroll in and maintain reporting to NHSN is an important first step towards strengthening infection surveillance in NHs.

    • Immune System Disorders
      1. Novel cutaneous mediators of chemical allergyExternal
        Shane HL, Long CM, Anderson SE.
        J Immunotoxicol. 2019 Mar 1:1-15.
        Chemical allergy can manifest into allergic contact dermatitis and asthma and the importance of skin sensitization in both of these diseases is increasingly being recognized. Given the unique characteristics of chemical allergy, coupled with the distinct immunological microenvironment of the skin research is still unraveling the mechanisms through which sensitization and elicitation occur. This review first describes the features of chemical sensitization and the known steps that must occur to develop a chemical allergy. Next, the unique immunological properties of the skin – which may influence chemical sensitization – are highlighted. Additionally, mediators involved with the development of allergy are reviewed, starting with early ones – including the properties of haptens, skin integrity, the microbiome, the inflammasome, and toll-like receptors (TLR). Novel cellular mediators of chemical sensitization are highlighted, including innate lymphoid cells, mast cells, T-helper (TH) cell subsets, and skin intrinsic populations including gammadelta T-cells and resident memory T-cells. Finally, this review discusses two epigenetic mechanisms that can influence chemical sensitization, microRNAs and DNA methylation. Overall, this review highlights recent research investigating novel mediators of chemical allergy that are present in the skin. It also emphasizes the need to further explore these mediators to gain a better understanding of what makes a chemical an allergen, and how best to prevent the development of chemical-induced allergic diseases.

    • Immunity and Immunization
      1. Successes and challenges for preventing measles, mumps and rubella by vaccinationExternal
        Bankamp B, Hickman C, Icenogle JP, Rota PA.
        Curr Opin Virol. 2019 Mar 7;34:110-116.
        The measles, mumps and rubella (MMR) vaccine has an outstanding safety record and is highly efficacious. High coverage with MMR has led to the elimination of endemic measles, rubella, and congenital rubella syndrome in the US. The biggest challenges to global measles and rubella control and elimination are insufficient vaccination coverage globally and increasing hesitancy. Despite high two dose coverage rates, mumps has made a resurgence in the US and other countries. Mumps outbreaks have occurred primarily in close contact, high-density settings and most cases had received a second dose 10 or more years previously. Waning humoral immunity and antigenic variation of circulating wild-type mumps strains may play a role in the mumps resurgence.

      2. Rapid disappearance of poliovirus type 2 immunity in young children following withdrawal of oral poliovirus type 2 containing vaccine in VietnamExternal
        Huyen DT, Mach O, Trung NT, Thai PQ, Thang HV, Weldon WC, Oberste MS, Jeyaseelan V, Sutter RW, Anh DD.
        J Infect Dis. 2019 Mar 14.
        BACKGROUND: Due to global shortage of inactivated poliovirus vaccine and global withdrawal of poliovirus type-2 (PV2) containing oral vaccine in May 2016, Vietnam has not used any PV2-containing vaccine between May 2016-October 2018. We assessed population immunity gap to PV2. METHODS: A cross-sectional survey in children 1-18 months of age was carried out in January 2018: one blood sample was obtained and analysed for the presence of poliovirus neutralizing antibodies. In children with detectable anti-PV2 antibodies, a second blood sample was obtained and analysed four months later to distinguish between passive (maternally-derived) and active (induced by secondary transmission or vaccination) immunity. RESULTS: Analysable sera were obtained from 1,106/1,110 enrolled children. Seroprevalence of PV2 antibodies was 87/368 (23.6%) among 1-7-month-old; 27/471 (5.7%) in the 8-15-month-old; and 19/267 (7.1%) in the 16-18-month-old. Seroprevalence declined with age in the 1-7 month-old group, and in children 8-18 months it remained without significant change by age. Four months later, 11/87 (14%), 9/27 (32%), and 12/19 (37%) remained seropositive in the 1-7, 8-15, and 16-18-month groups, respectively. INTERPRETATION: We found declining immunity to PV2, suggesting that Vietnam is at risk for an outbreak of type 2 vaccine-derived poliovirus in case of importation or new emergence.

      3. Cost-effectiveness of birth-dose hepatitis B vaccination among refugee populations in the African region: a series of case studiesExternal
        Reardon JM, O’Connor SM, Njau JD, Lam EK, Staton CA, Cookson ST.
        Confl Health. 2019 ;13:5.
        Background: Hepatitis B affects 257 million people worldwide. Mother-to-child hepatitis B virus (HBV) transmission is a preventable cause of substantial morbidity and mortality and poses greatest risk for developing chronic HBV infection. The World Health Organization recommends that all countries institute universal hepatitis B birth dose (HepB BD) vaccination during the first 24 h of life, followed by timely completion of routine immunization. The objective of this analysis was to assess the cost-effectiveness of adding HepB BD vaccination among sub-Saharan African refugee populations where the host country’s national immunization policy includes HepB BD. Methods: We performed a cost-effectiveness analysis of three hepatitis B vaccination strategy scenarios for camp-based refugee populations in the African Region (AFR): routine immunization (RI), RI plus universal HepB BD, and RI plus HepB BD only for newborns of hepatitis B surface antigen-positive mothers identified through rapid diagnostic testing (RDT). We focused analyses on refugee populations living in countries that include HepB BD in national immunization schedules: Djibouti, Algeria and Mauritania. We used a decision tree model to estimate costs of vaccination and testing, and costs of life-years lost due to complications of chronic hepatitis B. Results: Compared with RI alone, addition of HepB BD among displaced Somali refugees in Djibouti camps would save 9807 life-years/year, with an incremental cost-effectiveness ratio (ICER) of 0.15 USD (US dollars) per life-year saved. The RI plus HepB BD strategy among Western Saharan refugees in Algerian camps and Malian refugees in Mauritania camps would save 27,108 life-years/year with an ICER of 0.11 USD and 18,417 life-years/year with an ICER of 0.16 USD, respectively. The RI plus RDT-directed HepB BD was less cost-effective than RI plus delivery of universal HepB BD vaccination or RI alone. Conclusions: Based on our model, addition of HepB BD vaccination is very cost-effective among three sub-Saharan refugee populations, using relative life-years saved. This analysis shows the potential benefit of implementing HepB BD vaccination among other camp-based refugee populations as more AFR countries introduce national HepB BD policies.

      4. Phylogenetic relationships and regional spread of meningococcal strains in the meningitis belt, 2011-2016External
        Topaz N, Caugant DA, Taha MK, Brynildsrud OB, Debech N, Hong E, Deghmane AE, Ouedraogo R, Ousmane S, Gamougame K, Njanpop-Lafourcade BM, Diarra S, Fox LM, Wang X.
        EBioMedicine. 2019 Mar 4.
        BACKGROUND: Historically, the major cause of meningococcal epidemics in the meningitis belt of sub-Saharan Africa has been Neisseria meningitidis serogroup A (NmA), but the incidence has been substantially reduced since the introduction of a serogroup A conjugate vaccine starting in 2010. We performed whole-genome sequencing on isolates collected post-2010 to assess their phylogenetic relationships and inter-country transmission. METHODS: A total of 716 invasive meningococcal isolates collected between 2011 and 2016 from 11 meningitis belt countries were whole-genome sequenced for molecular characterization by the three WHO Collaborating Centers for Meningitis. FINDINGS: We identified three previously-reported clonal complexes (CC): CC11 (n=434), CC181 (n=62) and CC5 (n=90) primarily associated with NmW, NmX, and NmA, respectively, and an emerging CC10217 (n=126) associated with NmC. CC11 expanded throughout the meningitis belt independent of the 2000 Hajj outbreak strain, with isolates from Central African countries forming a distinct sub-lineage within this expansion. Two major sub-lineages were identified for CC181 isolates, one mainly expanding in West African countries and the other found in Chad. CC10217 isolates from the large outbreaks in Nigeria and Niger were more closely related than those from the few cases in Mali and Burkina Faso. INTERPRETATIONS: Whole-genome based phylogenies revealed geographically distinct strain circulation as well as inter-country transmission events. Our results stress the importance of continued meningococcal molecular surveillance in the region, as well as the development of an affordable vaccine targeting these strains. FUND: Meningitis Research Foundation; CDC’s Office of Advanced Molecular Detection; GAVI, the Vaccine Alliance.

      5. Trends in Tdap vaccination among privately insured pregnant women in the United States, 2009-2016External
        Zhou F, Xu J, Black CL, Ding H, Cho BH, Lu PJ, Lindley MC.
        Vaccine. 2019 Feb 27.
        BACKGROUND: Infants younger than 6months are at increased risk of complications and mortality from pertussis infection. In October 2012, the Advisory Committee on Immunization Practices revised its recommendation to include a Tdap dose during each pregnancy, ideally between 27 and 36weeks gestation. OBJECTIVE: Assess trends in Tdap vaccination coverage among privately insured pregnant women from 2009 to 2016 including timing of Tdap vaccination (before, during, or after pregnancy), trimester of vaccination for women vaccinated during pregnancy, and missed vaccination opportunities for unvaccinated women. Identify factors associated with vaccination during the optimal period of 27-36weeks gestation. STUDY DESIGN: Retrospective analysis of privately insured women 15-49years who delivered live births during 2009-2016 conducted using 2009-2016 MarketScan data. Tdap vaccination coverage and the timing of Tdap vaccine administration were assessed for women continuously enrolled from 6months before pregnancy to 1month after delivery. Multivariable logistic regression was performed to identify factors independently associated with receipt of Tdap vaccine at 27-36weeks gestation. RESULTS: Tdap vaccination coverage during pregnancy increased from 0.4% in 2009 to 6.2% in 2012 and to 53.2% in 2016. The proportion of vaccinated women receiving Tdap at 27-36weeks gestation increased from <10% in 2009 to nearly 90% in 2016, with most vaccination occurring at 27-32weeks gestation. Women of older age, residing in a metropolitan statistical area, residing outside the South, and having a capitated health insurance plan were more likely to receive Tdap at 27-36weeks gestation than their counterparts. Among women not vaccinated during pregnancy, 77.7% had a pregnancy-related medical claim between 27 and 36weeks gestation. CONCLUSION: Tdap vaccination coverage during pregnancy increased significantly from 2009 to 2016, with the greatest increase occurring after the revised Advisory Committee on Immunization Practices recommendation. Most women who did not receive Tdap vaccine had a missed vaccination opportunity during pregnancy, indicating potential for much higher vaccination coverage and consequent infant protection against pertussis.

    • Informatics
      1. Iterative development of a tailored mHealth intervention for adolescent and young adult survivors of childhood cancerExternal
        Schwartz LA, Psihogios AM, Henry-Moss D, Daniel LC, Ver Hoeve ES, Velazquez-Martin B, Butler E, Hobbie WL, Buchanan Lunsford N, Sabatino SA, Barakat LP, Ginsberg JP, Fleisher L, Deatrick JA, Jacobs LA, O’Hagan B, Anderson L, Fredericks E, Amaral S, Dowshen N, Houston K, Vachani C, Hampshire MK, Metz J, Hill-Kayser CE, Szalda D.
        Clin Pract Pediatr Psychol. 2019 Mar;7(1):31-43.
        Objective: Methods for developing mobile health (mHealth) interventions are not well described. To guide the development of future mHealth interventions, we describe the application of the agile science framework to iteratively develop an mHealth intervention for adolescent and young adult (AYA) survivors of childhood cancer. Method: We created the AYA STEPS mobile app (AYA Self-management via Texting, Education, and Plans for Survivorship) by modifying and integrating 2 existing programs: an online survivorship care plan (SCP) generator and a text messaging self-management intervention for AYA off treatment. The iterative development process involved 3 stages of agile science: (1) formative work, (2) obtaining feedback about the first AYA STEPS prototype, and (3) pilot testing and finalization of a prototype. We determined preferences of AYA stakeholders as well as discovered and addressed technology problems prior to beginning a subsequent randomized controlled trial. Results: AYA survivors reported that the app and the embedded tailored messages related to their health and SCP were easy to use and generally satisfying and beneficial. Usage data supported that AYA were engaged in the app. Technology glitches were discovered in the pilot and addressed. Conclusion: The iterative development of AYA STEPS was essential for creating a consistent and acceptable end user experience. This study serves as one example of how behavioral scientists may apply agile science to their own mHealth research.

    • Injury and Violence
      1. Emergency department visits for sports- and recreation-related traumatic brain injuries among children – United States, 2010-2016External
        Sarmiento K, Thomas KE, Daugherty J, Waltzman D, Haarbauer-Krupa JK, Peterson AB, Haileyesus T, Breiding MJ.
        MMWR Morb Mortal Wkly Rep. 2019 Mar 15;68(10):237-242.
        Traumatic brain injuries (TBIs), including concussions, are at the forefront of public concern about athletic injuries sustained by children. Caused by an impact to the head or body, a TBI can lead to emotional, physiologic, and cognitive sequelae in children (1). Physiologic factors (such as a child’s developing nervous system and thinner cranial bones) might place children at increased risk for TBI (2,3). A previous study demonstrated that 70% of emergency department (ED) visits for sports- and recreation-related TBIs (SRR-TBIs) were among children (4). Because surveillance data can help develop prevention efforts, CDC analyzed data from the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP)* by examining SRR-TBI ED visits during 2010-2016. An average of 283,000 children aged <18 years sought care in EDs each year for SRR-TBIs, with overall rates leveling off in recent years. The highest rates were among males and children aged 10-14 and 15-17 years. TBIs sustained in contact sports accounted for approximately 45% of all SRR-TBI ED visits. Activities associated with the highest number of ED visits were football, bicycling, basketball, playground activities, and soccer. Limiting player-to-player contact and rule changes that reduce risk for collisions are critical to preventing TBI in contact and limited-contact sports. If a TBI does occur, effective diagnosis and management can promote positive health outcomes among children.

    • Laboratory Sciences
      1. Pulmonary exposure to inhaled particulates elicits complex inflammatory and fibrotic responses that may progress to chronic fibrosis. The fibrogenic potentials of respirable particulates are influenced by their physicochemical properties and their interactions with major pathways to drive fibrotic development in the lung. Macrophages were exposed to six carbon nanotubes (CNTs) of varying dimensions, crystalline silica, or carbon black (CB), with lipopolysaccharide (LPS) and transforming growth factor (TGF)-beta1 as positive controls. Macrophage-conditioned media was collected and applied to cultures of human pulmonary fibroblast line WI38-VA13 to induce myofibroblast transformation. Multi-walled and single-walled CNTs (MWCNTs and SWCNTs, respectively) and silica, but not CB, stimulated robust myofibroblast transformation through macrophage-conditioned media. On an equal weight basis, MWCNTs induced higher induction than SWCNTs. High induction was observed for MWCNTs with a long and slender or a short and rigid shape, and silica, at levels comparable to those by LPS and TGF-beta1. Fibrogenic particulates induced high levels of IL-1beta mRNA expression and protein secretion that are required for macrophage-guided myofibroblast transformation. Induction of IL-1beta is dependent on the activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome and ROS (reactive oxygen species) production in macrophages, as inhibition of NLRP3 by MCC950 and reduction of ROS production by N-acetylcysteine blocked NLRP3 activation, IL-1beta induction, and fibroblast activation and differentiation. Therefore, fibrogenic CNTs and silica, but not CB, elicit robust macrophage-guided myofibroblast transformation, which depends on the induction of IL-1beta through the NLRP3 inflammasome pathway and the increased production of ROS in macrophages.

      2. Differential responses to stress of two Mycoplasma hyopneumoniae strainsExternal
        Paes JA, Leal Zimmer FM, Moura H, Barr JR, Ferreira HB.
        J Proteomics. 2019 Mar 9.
        Mycoplasma hyopneumoniae is a respiratory pathogen, causing porcine enzootic pneumonia. To survive in the porcine respiratory tract, M. hyopneumoniae must cope with both oxidative and heat stress imposed by the host. To get insights into M. hyopneumoniae stress responses and pathogenicity mechanisms, the protein profiles of two M. hyopneumoniae strains, pathogenic 7448 strain and non-pathogenic strain J, were surveyed under oxidative (OS) or heat (HS) stress. M. hyopneumoniae strains were submitted to OS (0.5% hydrogen peroxide) or HS (temperature shifts to 42 degrees C) conditions and protein profiling was carried out by LC-MS/MS and label-free quantitative analyses. Data are available via ProteomeXchange with identifier PXD012742. Qualitative and quantitative differences involving 40-60M. hyopneumoniae proteins were observed for both strains when comparing bacteria exposed to OS or HS to non-treated controls. However, no differences in abundance were found in proteins classically related to stress responses, as peroxidases and chaperones, suggesting that these proteins would be constitutively present in both strains in the tested conditions. Interestingly, under stress conditions, more virulence-related proteins were detected in M. hyopneumoniae 7448 differentially represented proteins than in M. hyopneumoniae J, suggesting that stress may trigger a differential response of the corresponding genes, shared by both strains.

      3. The fungal Cyp51-specific inhibitor VT-1598 demonstrates in vitro and in vivo activity against Candida aurisExternal
        Wiederhold NP, Lockhart SR, Najvar LK, Berkow EL, Jaramillo R, Olivo M, Garvey EP, Yates CM, Schotzinger RJ, Catano G, Patterson TF.
        Antimicrob Agents Chemother. 2019 Mar;63(3).
        Candida auris is an emerging pathogen associated with significant mortality and often multidrug resistance. VT-1598, a tetrazole-based fungal CYP51-specific inhibitor, was evaluated in vitro and in vivo against C. auris Susceptibility testing was performed against 100 clinical isolates of C. auris by broth microdilution. Neutropenic mice were infected intravenously with C. auris, and treatment began 24 h postinoculation with a vehicle control, oral VT-1598 (5, 15, and 50 mg/kg of body weight once daily), oral fluconazole (20 mg/kg once daily), or intraperitoneal caspofungin (10 mg/kg once daily), which continued for 7 days. Fungal burden was assessed in the kidneys and brains on day 8 in the fungal burden arm and on the days the mice succumbed to infection or on day 21 in the survival arm. VT-1598 plasma trough concentrations were also assessed on day 8. VT-1598 demonstrated in vitro activity against C. auris, with a mode MIC of 0.25 mug/ml and MICs ranging from 0.03 to 8 mug/ml. Treatment with VT-1598 resulted in significant and dose-dependent improvements in survival (median survival, 15 and >21 days for VT-1598 at 15 and 50 mg/kg, respectively) and reductions in kidney and brain fungal burden (reductions of 1.88 to 3.61 log10 CFU/g) compared to the control (5 days). The reductions in fungal burden correlated with plasma trough concentrations. Treatment with caspofungin, but not fluconazole, also resulted in significant improvements in survival and reductions in fungal burden compared to those with the control. These results suggest that VT-1598 may be a future option for the treatment of invasive infections caused by C. auris.

    • Maternal and Child Health
      1. Studies report inconsistent findings on the relationship between ASD and breastfeeding. We explored associations between ASD and breastfeeding initiation (yes/no) and duration (months categorized in tertiles) in the Study to Explore Early Development, a community-based case-control study in six sites in the Unites States. We adjusted for various child and mother demographic and pregnancy factors. Breastfeeding initiation was reported in 85.7% of mothers of children with ASD and 90.6% of mothers of controls. After adjustment, we found no significant difference in breastfeeding initiation (adjusted odds-ratio [aOR]: 0.88 and 95% confidence interval (CI) 0.60-1.28). However, mothers of children with ASD were less likely to report duration of breastfeeding in the high (>/=12 months) versus low tertile (<6 months) (aOR and 95% CI: 0.61 [0.45-0.84]) or the middle (6-<12 months) versus low tertile (0.72: 0.54-0.98). The association of ASD and breastfeeding duration was slightly attenuated when the presence of the broader autism phenotype (BAP) in the mother was accounted for, but still remained for the highest tertile. This association does not appear to be totally explained by maternal BAP. We were unable to distinguish whether the difference in duration was due to difficulties breastfeeding children who later develop ASD, other factors not adjusted in our study, or greater ASD risk resulting from shorter breastfeeding duration. Longitudinal studies that compare reasons why mothers stop breastfeeding between ASD and controls and establish a temporal relation between ASD and breastfeeding are needed. Future studies should also evaluate interactions between ASD risk genes and breastfeeding. Autism Res 2019. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this study, we compared breastfeeding practices between mothers of children with and without autism spectrum disorder (ASD). We found that the percentage of mothers who started breastfeeding was similar between the two groups, but mothers of children with ASD breastfed for a shorter amount of time compared to mothers of children without ASD. Future studies are needed to evaluate the reasons why the duration of breastfeeding was shorter for mothers of children with ASD compared to those without ASD.

      2. DSM-5 criteria for autism spectrum disorder maximizes diagnostic sensitivity and specificity in preschool childrenExternal
        Wiggins LD, Rice CE, Barger B, Soke GN, Lee LC, Moody E, Edmondson-Pretzel R, Levy SE.
        Soc Psychiatry Psychiatr Epidemiol. 2019 Mar 8.
        PURPOSE: The criteria for autism spectrum disorder (ASD) were revised in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). The objective of this study was to compare the sensitivity and specificity of DSM-IV-Text Revision (DSM-IV-TR) and DSM-5 definitions of ASD in a community-based sample of preschool children. METHODS: Children between 2 and 5 years of age were enrolled in the Study to Explore Early Development-Phase 2 (SEED2) and received a comprehensive developmental evaluation. The clinician(s) who evaluated the child completed two diagnostic checklists that indicated the presence and severity of DSM-IV-TR and DSM-5 criteria. Definitions for DSM-5 ASD, DSM-IV-TR autistic disorder, and DSM-IV-TR Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) were created from the diagnostic checklists. RESULTS: 773 children met SEED2 criteria for ASD and 288 met criteria for another developmental disorder (DD). Agreement between DSM-5 and DSM-IV-TR definitions of ASD were good for autistic disorder (0.78) and moderate for PDD-NOS (0.57 and 0.59). Children who met DSM-IV-TR autistic disorder but not DSM-5 ASD (n = 71) were more likely to have mild ASD symptoms, or symptoms accounted for by another disorder. Children who met PDD-NOS but not DSM-5 ASD (n = 66), or vice versa (n = 120) were less likely to have intellectual disability and more likely to be female. Sensitivity and specificity were best balanced with DSM-5 ASD criteria (0.95 and 0.78, respectively). CONCLUSIONS: The DSM-5 definition of ASD maximizes diagnostic sensitivity and specificity in the SEED2 sample. These findings support the DSM-5 conceptualization of ASD in preschool children.

      3. Geographic disparities in treatment for children with autism spectrum disorderExternal
        Zablotsky B, Maenner MJ, Blumberg SJ.
        Acad Pediatr. 2019 Mar 8.
        OBJECTIVE: Geographic differences may provide insight into what factors influence the likelihood that a child is diagnosed with ASD in the US, yet there have been few nationally representative surveys that have explored this topic. The current study expands the limited literature by analyzing regional differences in ASD prevalence, service utilization, and the presence of unmet needs within a nationally representative sample of children. METHODS: Data were drawn from the 2014-2016 National Health Interview Survey (NHIS), a nationally representative household survey of the noninstitutionalized US population. Children 3-17 were included in the analytic sample. Prevalence estimates accounted for the complex survey design of the NHIS, and differences between geographic regions were compared using logistic/linear regressions with and without adjustment for child/family characteristics. RESULTS: The prevalence of ASD was highest in the Northeast (3.0%), followed by the Midwest (2.4%), South (2.4%), and West (2.3%). A significant difference was found between the Northeast and West (p<.05). However, after accounting for child and family characteristics, this difference was no longer significant. Children with ASD in the Northeast were the most likely to have seen a specialist in the past year. Approximately 1 in 8 children with ASD experienced at least one unmet need, but there were no differences found by geographic region. CONCLUSIONS: Although differences in prevalence were not significant after adjustment, service utilization differences remained. It appears children with ASD in the Northeast utilize the greatest number of specialty services when compared to children with ASD from other parts of the country.

    • Nutritional Sciences
      1. Integrating small-quantity lipid-based nutrient supplements (SQ-LNS) into infant and young child feeding (IYCF) programmes can increase consumption of essential nutrients among children in vulnerable populations; however, few studies have assessed the impact of integrated IYCF-SQ-LNS programmes on IYCF practices. A 2-year, enhanced IYCF intervention targeting pregnant women and infants (0-12 months) was implemented in a health zone in the Democratic Republic of Congo (DRC). The enhanced IYCF intervention included community- and facility-based counselling for mothers on handwashing, SQ-LNS, and IYCF practices, plus monthly SQ-LNS distributions for children 6-12 months; a control zone received the national IYCF programme (facility-based IYCF counselling with no SQ-LNS distributions). Cross-sectional preintervention and postintervention surveys (n = 650 and 638 in intervention and control areas at baseline; n = 654 and 653 in each area at endline, respectively) were conducted in mothers of children 6-18 months representative of both zones. Difference in differences (DiD) analyses used mixed linear regression models. There were significantly greater increases in the proportion of mothers in the intervention (vs. control) zone who reported: initiating breastfeeding within 1 hr of birth (Adj. DiD [95% CI]: +56.4% [49.3, 63.4], P < 0.001), waiting until 6 months to introduce water (+66.9% [60.6, 73.2], P < 0.001) and complementary foods (+56.4% [49.3, 63.4], P < 0.001), feeding the minimum meal frequency the previous day (+9.2% [2.7, 15.7], P = 0.005); feeding the child in a separate bowl (+9.7% [2.2, 17.2], P = 0.01); awareness of anaemia (+16.9% [10.4, 23.3], P < 0.001); owning soap (+14.9% [8.3, 21.5], P < 0.001); and washing hands after defecating and before cooking and feeding the child the previous day (+10.5% [5.8, 15.2], +12.5% [9.3, 15.6] and +15.0% [11.2, 18.8], respectively, P < 0.001 for all). The enhanced IYCF intervention in the DRC was associated with an improvement in several important IYCF practices but was not associated with a change in dietary diversity (minimum dietary diversity and minimum acceptable diet remained below 10% in both zones without significant differences between zones). The provision of fortified complementary foods, such as SQ-LNS, may be an important source of micronutrients and macronutrients for young children in areas with high rates of poverty and limited access to diverse foods. Future research should verify the potential of integrated IYCF-SQ-LNS to improve IYCF practices, and ultimately children’s nutritional status.

    • Occupational Safety and Health
      1. The composition of emissions from sawing Corian(R), a solid surface composite materialExternal
        Kang S, Liang H, Qian Y, Qi C.
        Ann Work Expo Health. 2019 Feb 10.
        We conducted detailed analyses of the composition of emissions from sawing Corian(R), a solid surface composite material, in a laboratory testing system. The analyses included the aluminum content of size-selective dust samples, semivolatile organic compounds (SVOCs) in respirable dust samples, and volatile organic compounds (VOCs). The normalized respirable dust generation rate found using a Micro-Orifice Uniform Deposit Impactor was 5.9 milligrams per gram (mg g-1) suggesting that 0.59% of the mass removed from sawing Corian(R) becomes respirable dust. The alumina trihydrate content of the dust was consistently above 85% in most parts of the respirable size range, verifying an earlier finding that it is the dominant composition of the airborne particles of all sizes, including ultrafine particles. VOC analyses revealed that methyl methacrylate (MMA) was the most abundant compound, with a generation rate of 6.9 mg g-1 (0.69% of the mass removed from sawing Corian(R) became MMA vapor). The SVOC analysis only found a small amount of MMA (0.55%) in the bulk dust.

      2. New Jersey Home Health Care Aides Survey ResultsExternal
        Ridenour ML, Hendricks S, Hartley D, Blando JD.
        Home Health Care Manag Pract. 2019 .
        The objective of the study was to report on what violence-based training home health care aides received, their participation in health promotion classes, and home health care aides? experience with workplace violence. In 2013, a mail survey was completed by 513 home health care aides in the state of New Jersey. Ninety-four percent of the respondents were female. Respondents whose agency was part of a hospital were more likely to receive violence-based safety training than respondents whose agency was not part of a hospital (p =.0313). When the perpetrator of violence was a patient or family member, the respondents experienced verbal abuse the most (26%), then physical assault (16%) and exposure to bodily fluids (13%). Home health care aides whose agency was part of a hospital were more likely to receive violence-based safety training. Training is an important component of a workplace violence prevention program.

      3. BACKGROUND: More than 13 million employees are working in the public education sector which includes more than just teachers in the United States. This industry sector also employs custodians, maintenance, and administration. To date, there is very limited information about the type and frequency of injuries for these employees. OBJECTIVE: To identify injury trends related to frequency and severity for different occupational injuries in a large urban school district. METHODS: Between 2014-2015, school district employees reported a total of 598 occupational injuries. Initial analysis of the data provided the frequency of injuries overall and for individual occupational categories. The Severity Index provides a score for job category and injury type based on severity and frequency. RESULTS: Overall, the Slip, Trip and Fall category had the highest frequency, followed by Combative Situations, and Over-exertion. Teacher and Para-professional workers experienced the greatest number of injuries with violence being the most frequent cause. Based on the Severity Index, Over-exertion was identified as the primary exposure concern for Custodians, while Slip, Trip and Fall category had the greatest impact on Building Engineers. CONCLUSIONS: With the diversity of negative outcomes, the administration will need targeted interventions for the various professions represented in the school systems. The injury severity profile indicates non-teachers should be a high priority for interventions with over-exertion and slips, trips and falls leading the risk.

    • Occupational Safety and Health – Mining
      1. Advancing the application of safety and health (S&H) technologies is likely to remain a value in the mining industry. However, any information that technologies generate must be translated from the organization to the workforce in a targeted way to result in sustainable change. Using a case study approach with continuous personal dust monitors (CPDMs), this paper argues for an organizational focus on technology integration. Although CPDMs provide mineworkers with near real-time feedback about their respirable coal dust exposure, they do not ensure that workers or the organization will continuously use the information to learn about and reduce exposure sources. This study used self-determination theory (SDT) to help three mines manage and communicate about information learned from the CPDM technology. Specifically, 35 mineworkers participated in two mixed-method data collection efforts to discuss why they do or do not use CPDMs to engage in dust-reducing practices. Subsequently, the data was analyzed to better understand how organizations can improve the integration of technology through their management systems. Results indicate that using the CPDM to reduce sources of dust exposure is consistent with mineworkers? self-values to protect their health and not necessarily because of compliance to a manager or mine.

    • Parasitic Diseases
      1. Case report: Ocular toxocariasis: A report of three cases from the Mississippi DeltaExternal
        Inagaki K, Kirmse B, Bradbury RS, Moorthy RS, Arguello I, McGuffey CD, Tieu B, Hobbs CV.
        Am J Trop Med Hyg. 2019 Mar 11.
        Ocular toxocariasis can be vision threatening, and is commonly reported from tropical or subtropical regions. Knowledge of clinical manifestations from the United States, particularly in underserved areas such as the American South, is lacking. We report three cases of ocular toxocariasis in individuals from the Mississippi Delta, a rural community with prevalent poverty. Visual acuity was severely affected in two of the three cases. Increased awareness of ocular toxocariasis, which may have under-recognized frequency, will contribute to prompt diagnosis and treatment, which will ultimately improve patient health in the region.

    • Physical Activity
      1. Association of leisure-time physical activity across the adult life course with all-cause and cause-specific mortalityExternal
        Saint-Maurice PF, Coughlan D, Kelly SP, Keadle SK, Cook MB, Carlson SA, Fulton JE, Matthews CE.
        JAMA Netw Open. 2019 Mar 1;2(3):e190355.
        Importance: Although the benefits of leisure-time physical activity (LTPA) in middle age are established, the health effects of long-term participation and changes in LTPA between adolescence and middle age have not been documented. Objective: To determine whether an association exists between LTPA life course patterns and mortality. Design, Setting, and Participants: This prospective cohort study used data from the National Institutes of Health-AARP (formerly American Association of Retired Persons) Diet and Health Study established in 1995 to 1996. Data analysis was conducted from March 2017 through February 2018. Data were analyzed for 315059 adult AARP members living in 6 states, namely, California, Florida, Louisiana, New Jersey, North Carolina, or Pennsylvania, or 2 metropolitan areas, Atlanta, Georgia, or Detroit, Michigan. Exposures: Self-reported LTPA (hours per week) at the baseline interview for ages grouped as 15 to 18, 19 to 29, 35 to 39, and 40 to 61 years. Main Outcomes and Measures: All-cause, cardiovascular disease (CVD)-related, and cancer-related mortality records available through December 31, 2011. Results: Of 315059 participants, 183451 (58.2%) were men, and the participants were 50 to 71 years of age at enrollment. Ten LTPA trajectories (categorized as maintaining, increasing, and decreasing LTPA across time) were identified, and 71377 deaths due to all causes, 22219 deaths due to CVD, and 16388 deaths due to cancer occurred. Compared with participants who were consistently inactive throughout adulthood, participants who maintained the highest amount of LTPA in each age period were at lower risks for all-cause, CVD-related, and cancer-related mortality. For example, compared with participants who were consistently inactive, maintaining higher amounts of LTPA was associated with lower all-cause (hazard ratio [HR], 0.64; 95% CI, 0.60-0.68), CVD-related (HR, 0.58; 95% CI, 0.53-0.64), and cancer-related (HR, 0.86; 95% CI, 0.77-0.97) mortality. Adults who were less active throughout most of the adult life course but increased LTPA in later adulthood (40-61 years of age) also had lower risk for all-cause (HR, 0.65; 95% CI, 0.62-0.68), CVD-related (HR, 0.57; 95% CI, 0.53-0.61), and cancer-related (HR, 0.84; 95% CI, 0.77-0.92) mortality. Conclusions and Relevance: Maintaining higher LTPA levels and increasing LTPA in later adulthood were associated with comparable low risk of mortality, suggesting that midlife is not too late to start physical activity. Inactive adults may be encouraged to be more active, whereas young adults who are already active may strive to maintain their activity level as they get older.

      2. African American men are disproportionately affected by, not only HIV/AIDS, but also chronic non-communicable diseases. Despite the known benefits of physical activity for reducing chronic non-communicable diseases, scant research has identified factors that may influence physical activity in this population. A growing literature centers on the syndemic theory, the notion that multiple adverse conditions interact synergistically, contributing to excess morbidity. This secondary data analysis examined two primary questions: whether syndemic conditions prospectively predicted physical activity, and whether, consistent with the syndemic theory, syndemic conditions interacted to predict physical activity. Participants were 595 African American men who have sex with men (MSM), a population underrepresented in health research, enrolled in a health-promotion intervention trial from 2008-2011. We used generalized-estimating-equations models to test the associations of syndemic conditions and resilience factors measured pre-intervention to self-reported physical activity 6 and 12 months post-intervention. As hypothesized, reporting more syndemic conditions pre-intervention predicted reporting less physical activity 6 and 12 months post-intervention, adjusting for the intervention. However, contrary to the syndemic theory, we did not find evidence for the interaction effects of syndemic conditions in predicting physical activity. Receiving high school education and having greater social network diversity predicted more physical activity whereas older age predicted less physical activity. To our knowledge, this is the first study to examine the syndemic theory in relation to physical activity. Although reporting a greater number of syndemic conditions was related to reduced physical activity, there was no evidence for synergy among syndemic conditions.

    • Reproductive Health
      1. Putting the ‘M’ back in maternal-fetal medicine: A five-year report card on a collaborative effort to address maternal morbidity and mortality in the U.SExternal
        D’Alton ME, Friedman AM, Bernstein PS, Brown HL, Callaghan WM, Clark SL, Grobman WA, Kilpatrick SJ, O’Keeffe DF, Montgomery DM, Srinivas SK, Wendel GD, Wenstrom KD, Foley MR.
        Am J Obstet Gynecol. 2019 Mar 5.
        The Centers for Disease Control and Prevention have demonstrated continuous increased risk for maternal mortality and severe morbidity with racial disparities among non-Hispanic black women an important contributing factor. More than 50,000 women experienced severe maternal morbidity in 2014 with a mortality rate of 18.0 per 100,000, higher than many other developed countries. In 2012 the first “Putting the ‘M’ back in Maternal Fetal Medicine” session was held at the Society for Maternal Fetal Medicine’s (SMFM) Annual Meeting. With the realization that rising risk for severe maternal morbidity and mortality required action, the “M in MFM” meeting identified urgent needs to: (i) enhance education and training in maternal care for maternal-fetal medicine (MFM) fellows; (ii) improve the medical care and management of pregnant women across the country; and (iii) address critical research gaps in maternal medicine. Since that first meeting a broad collaborative effort has made a number of major steps forward including the proliferation of maternal mortality review committees, advances in research, increasing educational focus on maternal critical care, and development of comprehensive clinical strategies to reduce maternal risk. Five years later, the 2017 “M in MFM” meeting served as a “report card” looking back at progress made but also looking forward to what needs to be done over the next five years given that too many mothers still experience preventable harm and adverse outcomes.

      2. “Every Newborn-BIRTH” protocol: observational study validating indicators for coverage and quality of maternal and newborn health care in Bangladesh, Nepal and TanzaniaExternal
        Day LT, Ruysen H, Gordeev VS, Gore-Langton GR, Boggs D, Cousens S, Moxon SG, Blencowe H, Baschieri A, Rahman AE, Tahsina T, Zaman SB, Hossain T, Rahman QS, Ameen S, El Arifeen S, Kc A, Shrestha SK, Kc NP, Singh D, Jha AK, Jha B, Rana N, Basnet O, Joshi E, Paudel A, Shrestha PR, Jha D, Bastola RC, Ghimire JJ, Paudel R, Salim N, Shamb D, Manji K, Shabani J, Shirima K, Mkopi N, Mrisho M, Manzi F, Jaribu J, Kija E, Assenga E, Kisenge R, Pembe A, Hanson C, Mbaruku G, Masanja H, Amouzou A, Azim T, Jackson D, Kabuteni TJ, Mathai M, Monet JP, Moran A, Ram P, Rawlins B, Saebo JI, Serbanescu F, Vaz L, Zaka N, Lawn JE.
        J Glob Health. 2019 Jun;9(1):010902.
        Background: To achieve Sustainable Development Goals and Universal Health Coverage, programmatic data are essential. The Every Newborn Action Plan, agreed by all United Nations member states and >80 development partners, includes an ambitious Measurement Improvement Roadmap. Quality of care at birth is prioritised by both Every Newborn and Ending Preventable Maternal Mortality strategies, hence metrics need to advance from health service contact alone, to content of care. As facility births increase, monitoring using routine facility data in DHIS2 has potential, yet validation research has mainly focussed on maternal recall surveys. The Every Newborn – Birth Indicators Research Tracking in Hospitals (EN-BIRTH) study aims to validate selected newborn and maternal indicators for routine tracking of coverage and quality of facility-based care for use at district, national and global levels. Methods: EN-BIRTH is an observational study including >20 000 facility births in three countries (Tanzania, Bangladesh and Nepal) to validate selected indicators. Direct clinical observation will be compared with facility register data and a pre-discharge maternal recall survey for indicators including: uterotonic administration, immediate newborn care, neonatal resuscitation and Kangaroo mother care. Indicators including neonatal infection management and antenatal corticosteroid administration, which cannot be easily observed, will be validated using inpatient records. Trained clinical observers in Labour/Delivery ward, Operation theatre, and Kangaroo mother care ward/areas will collect data using a tablet-based customised data capturing application. Sensitivity will be calculated for numerators of all indicators and specificity for those numerators with adequate information. Other objectives include comparison of denominator options (ie, true target population or surrogates) and quality of care analyses, especially regarding intervention timing. Barriers and enablers to routine recording and data usage will be assessed by data flow assessments, quantitative and qualitative analyses. Conclusions: To our knowledge, this is the first large, multi-country study validating facility-based routine data compared to direct observation for maternal and newborn care, designed to provide evidence to inform selection of a core list of indicators recommended for inclusion in national DHIS2. Availability and use of such data are fundamental to drive progress towards ending the annual 5.5 million preventable stillbirths, maternal and newborn deaths.

    • Substance Use and Abuse
      1. U.S. emergency department visits resulting from nonmedical use of pharmaceuticals, 2016External
        Geller AI, Dowell D, Lovegrove MC, McAninch JK, Goring SK, Rose KO, Weidle NJ, Budnitz DS.
        Am J Prev Med. 2019 Mar 4.
        INTRODUCTION: National data on morbidity from nonmedical use of pharmaceuticals are limited. This study used nationally representative, public health surveillance data to characterize U.S. emergency department visits for acute harms from nonmedical use of pharmaceuticals and to guide prevention efforts. METHODS: Data collected in 2016 from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were analyzed in 2018 to calculate national estimates of emergency department visits for harms from nonmedical use of pharmaceuticals. RESULTS: Based on 5,130 surveillance cases, there were an estimated 358,247 emergency department visits (95% CI=280,675, 435,819) in 2016 for harms from nonmedical use of pharmaceuticals and 41.1% resulted in hospitalization (95% CI=32.3%, 49.8%). One half (50.9%, 95% CI=46.6%, 55.3%) of estimated visits involved patients aged </=34 years; more than one half of estimated visits also involved non-pharmaceutical substances (52.9%, 95% CI=49.7%, 56.1%), including illicit drugs in 34.1% (95% CI=30.9%, 37.2%) and alcohol in 21.8% (95% CI=19.8%, 23.9%). Overall, benzodiazepines were implicated in 46.9% (95% CI=42.5%, 51.2%) of estimated emergency department visits for nonmedical use of pharmaceuticals but were the only substance implicated in just 6.5% (95% CI=5.1%, 7.9%). Prescription opioids were implicated in 36.2% (95% CI=30.8%, 41.7%) of estimated emergency department visits and were the only substance implicated in 11.3% (95% CI=8.6%, 14.0%). CONCLUSIONS: Although prescription opioids or benzodiazepines are frequently implicated in emergency department visits for nonmedical use, because other substances and additional pharmaceuticals are most often involved, prescribing clinicians should consider implementing specific screening to address polysubstance use and, when warranted, treatment interventions.

    • Zoonotic and Vectorborne Diseases
      1. Diagnostic methods used to classify confirmed and probable cases of spotted fever rickettsioses – United States, 2010-2015External
        Binder AM, Nichols Heitman K, Drexler NA.
        MMWR Morb Mortal Wkly Rep. 2019 Mar 15;68(10):243-246.
        Spotted fever rickettsioses (SFR), including Rocky Mountain spotted fever (RMSF), are nationally notifiable diseases in the United States caused by spotted fever group Rickettsia. The annual incidence of SFR increased from 1.7 cases per 1 million persons in 2000 to 13.2 in 2016 (1,2). Although this demonstrates a substantial increase in SFR cases, the actual magnitude of the increase is questionable because the current case definition allows for nonspecific laboratory criteria to support diagnosis (3). To analyze the quality of laboratory data used to support the diagnosis of SFR cases with illness onset during 2010-2015, CDC examined supplementary case report forms. Among 16,807 reported cases, only 167 (1.0%) met the confirmed case definition, and the remaining 16,640 (99.0%) met the probable case definition. The most common supportive laboratory evidence for probable cases was elevated immunoglobulin G (IgG) antibody titer by indirect immunofluorescence assay (IFA), which was reported for 14,784 (88.8%) probable cases. Antibodies to spotted fever group Rickettsia can persist for months or years following infection, making a single antibody titer unreliable for diagnosing incident disease without a convalescent specimen. Increased use of molecular assays and use of paired and appropriately timed IFA IgG testing practices could improve understanding of SFR epidemiology and increase the accuracy of disease incidence estimates.

      2. Metabolomic insights into human arboviral infections: Dengue, chikungunya, and Zika virusesExternal
        Byers NM, Fleshman AC, Perera R, Molins CR.
        Viruses. 2019 Mar 6;11(3).
        The global burden of arboviral diseases and the limited success in controlling them calls for innovative methods to understand arbovirus infections. Metabolomics has been applied to detect alterations in host physiology during infection. This approach relies on mass spectrometry or nuclear magnetic resonance spectroscopy to evaluate how perturbations in biological systems alter metabolic pathways, allowing for differentiation of closely related conditions. Because viruses heavily depend on host resources and pathways, they present unique challenges for characterizing metabolic changes. Here, we review the literature on metabolomics of arboviruses and focus on the interpretation of identified molecular features. Metabolomics has revealed biomarkers that differentiate disease states and outcomes, and has shown similarities in metabolic alterations caused by different viruses (e.g., lipid metabolism). Researchers investigating such metabolomic alterations aim to better understand host(-)virus dynamics, identify diagnostically useful molecular features, discern perturbed pathways for therapeutics, and guide further biochemical research. This review focuses on lessons derived from metabolomics studies on samples from arbovirus-infected humans.

      3. Comprehensive evaluation of differential serodiagnosis between Zika and dengue viral infectionsExternal
        Chao DY, Whitney MT, Davis BS, Medina FA, Munoz JL, Chang GJ.
        J Clin Microbiol. 2019 Mar;57(3).
        Diagnostic testing for Zika virus (ZIKV) or dengue virus (DENV) infection can be accomplished by a nucleic acid detection method; however, a negative result does not exclude infection due to the low virus titer during infection depending on the timing of sample collection. Therefore, a ZIKV- or DENV-specific serological assay is essential for the accurate diagnosis of patients and to mitigate potential severe health outcomes. A retrospective study design with dual approaches of collecting human serum samples for testing was developed. All serum samples were extensively evaluated by using both noninfectious wild-type (wt) virus-like particles (VLPs) and soluble nonstructural protein 1 (NS1) in the standard immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Both ZIKV-derived wt-VLP- and NS1-MAC-ELISAs were found to have similar sensitivities for detecting anti-premembrane/envelope and NS1 antibodies from ZIKV-infected patient sera, although lower cross-reactivity to DENV2/3-NS1 was observed. Furthermore, group cross-reactive (GR)-antibody-ablated homologous fusion peptide-mutated (FP)-VLPs consistently showed higher positive-to-negative values than homologous wt-VLPs. Therefore, we used DENV-2/3 and ZIKV FP-VLPs to develop a novel, serological algorithm for differentiating ZIKV from DENV infection. Overall, the sensitivity and specificity of the FP-VLP-MAC-ELISA and the NS1-MAC-ELISA were each higher than 80%, with no statistical significance. The accuracy can reach up to 95% with the combination of FP-VLP and NS1 assays. In comparison to current guidelines using neutralization tests to measure ZIKV antibody, this approach can facilitate laboratory screening for ZIKV infection, especially in regions where DENV infection is endemic and capacity for neutralization testing does not exist.

      4. Introduction of Ebola virus into a remote border district of Sierra Leone, 2014: use of field epidemiology and RNA sequencing to describe chains of transmissionExternal
        DeSilva MB, Styles T, Basler C, Moses FL, Husain F, Reichler M, Whitmer S, McAuley J, Belay E, Friedman M, Muoghalu IS, Swaray P, Stroher U, Redd JT.
        Epidemiol Infect. 2019 Jan;147:e88.
        In early October 2014, 7 months after the 2014-2015 Ebola epidemic in West Africa began, a cluster of reported deaths in Koinadugu, a remote district of Sierra Leone, was the first evidence of Ebola virus disease (Ebola) in the district. Prior to this event, geographic isolation was thought to have prevented the introduction of Ebola to this area. We describe our initial investigation of this cluster of deaths and subsequent public health actions after Ebola was confirmed, and present challenges to our investigation and methods of overcoming them. We present a transmission tree and results of whole genome sequencing of selected isolates to identify the source of infection in Koinadugu and demonstrate transmission between its villages. Koinadugu’s experience highlights the danger of assuming that remote location and geographic isolation can prevent the spread of Ebola, but also demonstrates how deployment of rapid field response teams can help limit spread once Ebola is detected.

      5. An epidemic of chikungunya in northwestern Bangladesh in 2011External
        Haque F, Rahman M, Banu NN, Sharif AR, Jubayer S, Shamsuzzaman A, Alamgir A, Erasmus JH, Guzman H, Forrester N, Luby SP, Gurley ES.
        PLoS One. 2019 ;14(3):e0212218.
        BACKGROUND: In November 2011, a government hospital physician in Shibganj sub-district of Bangladesh reported a cluster of patients with fever and joint pain or rash. A multi-disciplinary team investigated to characterize the outbreak; confirm the cause; and recommend control and prevention measures. METHODS: Shibganj’s residents with new onset of fever and joint pain or rash between 1 September and 15 December 2011 were defined as chikungunya fever (CHIKF) suspect cases. To estimate the attack rate, we identified 16 outpatient clinics in 16 selected wards across 16 unions in Shibganj and searched for suspect cases in the 80 households nearest to each outpatient clinic. One suspect case from the first 30 households in each ward was invited to visit the nearest outpatient clinic for clinical assessment and to provide a blood sample for laboratory testing and analyses. RESULTS: We identified 1,769 CHIKF suspect cases from among 5,902 residents surveyed (30%). Their median age was 28 (IQR:15-42) years. The average attack rate in the sub-district was 30% (95% CI: 27%-33%). The lowest attack rate was found in children <5 years (15%). Anti-CHIKV IgM antibodies were detected by ELISA in 78% (264) of the 338 case samples tested. In addition to fever, predominant symptoms of serologically-confirmed cases included joint pain (97%), weakness (54%), myalgia (47%), rash (42%), itching (37%) and malaise (31%). Among the sero-positive patients, 79% (209/264) sought healthcare from outpatient clinics. CHIKV was isolated from two cases and phylogenetic analyses of full genome sequences placed these viruses within the Indian Ocean Lineage (IOL). Molecular analysis identified mutations in E2 and E1 glycoproteins and contained the E1 A226V point mutation. CONCLUSION: The consistently high attack rate by age groups suggested recent introduction of chikungunya in this community. Mosquito control efforts should be enhanced to reduce the risk of continued transmission and to improve global health security.

      6. 2018 U.S. Virgin Islands Zika health brigade: Providing recommended pediatric health screenings for infants born to mothers with laboratory evidence of Zika virus exposure during pregnancyExternal
        Hillman B, Petersen DN, Galang RR, Godfred-Cato S, Mayers C, Thomas Y, Prosper A, Hawley J, Halbert M, Noe M, Reynolds M, Schoelles D, Brown-Shuler L, Fehrenbach N, Ellis EM.
        Birth Defects Res. 2019 Mar 11.

        [No abstract]

      7. Postnatally acquired Zika virus disease among children, United States, 2016-2017External
        Lindsey NP, Porse CC, Potts E, Hyun J, Sandhu K, Schiffman E, Cervantes KB, White JL, Mason K, Owens K, Holsinger C, Fischer M, Staples JE.
        Clin Infect Dis. 2019 Mar 11.
        BACKGROUND: The clinical findings among children with postnatally acquired Zika virus disease are not well characterized. We describe and compare clinical signs and symptoms for children aged <18 years. METHODS: Zika virus disease cases were included if they met the national surveillance case definition, had illness onset in 2016 or 2017, resided in a participating state, and were reported to CDC. Pediatric cases were aged <18 years; congenital and perinatal infections were excluded. Pediatric cases were matched to adult cases (1849 years). Clinical information was compared between younger and older pediatric cases and between children and adults. RESULTS: A total of 141 pediatric Zika virus disease cases were identified; none experienced neurologic disease. Overall, 28 (20%) were treated in an emergency department, 1 (<1%) was hospitalized; none died. Of the four primary clinical signs and symptoms associated with Zika virus disease, 133 (94%) children had rash, 104 (74%) fever, 67 (48%) arthralgia, and 51 (36%) conjunctivitis. Fever, arthralgia, and myalgia were more common in older children (1217 years) than younger children (111 years). Arthralgia, arthritis, edema, and myalgia were more common in adults compared to children. CONCLUSIONS: This report supports previous findings that Zika virus disease is generally mild in children. The most common symptoms are similar to other childhood infections, and clinical findings and outcomes are similar to those in adults. Healthcare providers should consider a diagnosis of Zika virus infection in children with fever, rash, arthralgia, or conjunctivitis, who reside in or have traveled to an area where Zika virus transmission is occurring.

      8. Tick talk: Keeping environmental health up with current trendsExternal
        Vanover C, Ruiz A.
        J Environ Health. 2019 ;81(7):36-38.

        [No abstract]

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

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