Volume 10, Issue 10, March 20, 2018

CDC Science Clips: Volume 10, Issue 10, March 20, 2018

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

  1. CDC Public Health Grand Rounds
    • Immunity and Immunization – Global New Vaccine Introduction
      1. State of equity: childhood immunization in the World Health Organization African RegionExternal
        Casey RM, Hampton LM, Anya BM, Gacic-Dobo M, Diallo MS, Wallace AS.
        Pan Afr Med J. 2017 ;27(Suppl 3):5.

        Introduction: In 2010, the Global Vaccine Action Plan called on all countries to reach and sustain 90% national coverage and 80% coverage in all districts for the third dose of diphtheria-tetanus-pertussis vaccine (DTP3) by 2015 and for all vaccines in national immunization schedules by 2020. The aims of this study are to analyze recent trends in national vaccination coverage in the World Health Organization African Region andto assess how these trends differ by country income category. Methods: We compared national vaccination coverage estimates for DTP3 and the first dose of measles-containing vaccine (MCV) obtained from the World Health Organization (WHO)/United Nations Children’s Fund (UNICEF) joint estimates of national immunization coverage for all African Region countries. Using United Nations (UN) population estimates of surviving infants and country income category for the corresponding year, we calculated population-weighted average vaccination coverage by country income category (i.e., low, lower middle, and upper middle-income) for the years 2000, 2005, 2010 and 2015. Results: DTP3 coverage in the African Region increased from 52% in 2000 to 76% in 2015,and MCV1 coverage increased from 53% to 74% during the same period, but with considerable differences among countries. Thirty-six African Region countries were low income in 2000 with an average DTP3 coverage of 50% while 26 were low income in 2015 with an average coverage of 80%. Five countries were lower middle-income in 2000 with an average DTP3 coverage of 84% while 12 were lower middle-income in 2015 with an average coverage of 69%. Five countries were upper middle-income in 2000 with an average DTP3 coverage of 73% and eight were upper middle-income in 2015 with an average coverage of 76%. Conclusion: Disparities in vaccination coverage by country persist in the African Region, with countries that were lower middle-income having the lowest coverage on average in 2015. Monitoring and addressing these disparities is essential for meeting global immunization targets.

      2. Ranking 93 health interventions for low- and middle-income countries by cost-effectivenessExternal
        Horton S, Gelband H, Jamison D, Levin C, Nugent R, Watkins D.
        PLoS One. 2017 ;12(8):e0182951.

        BACKGROUND: Cost-effectiveness rankings of health interventions are useful inputs for national healthcare planning and budgeting. Previous comprehensive rankings for low- and middle- income countries were undertaken in 2005 and 2006, accompanying the development of strategies for the Millennium Development Goals. We update the rankings using studies published since 2000, as strategies are being considered for the Sustainable Development Goals. METHODS: Expert systematic searches of the literature were undertaken for a broad range of health interventions. Cost-effectiveness results using Disability Adjusted Life-Years (DALYs) as the health outcome were standardized to 2012 US dollars. RESULTS: 149 individual studies of 93 interventions qualified for inclusion. Interventions for Reproductive, Maternal, Newborn and Child Health accounted for 37% of interventions, and major infectious diseases (AIDS, TB, malaria and neglected tropical diseases) for 24%, consistent with the priorities of the Millennium Development Goals. More than half of the interventions considered cost less than $200 per DALY and hence can be considered for inclusion in Universal Health Care packages even in low-income countries. DISCUSSION: Important changes have occurred in rankings since 2006. Priorities have changed as a result of new technologies, new methods for changing behavior, and significant price changes for some vaccines and drugs. Achieving the Sustainable Development Goals will require LMICs to study a broader range of health interventions, particularly in adult health. Some interventions are no longer studied, in some cases because they have become usual care, in other cases because they are no longer relevant. Updating cost-effectiveness rankings on a regular basis is potentially a valuable exercise.

      3. The impact of new vaccine introduction on immunization and health systems: a review of the published literatureExternal
        Hyde TB, Dentz H, Wang SA, Burchett HE, Mounier-Jack S, Mantel CF.
        Vaccine. 2012 Oct 5;30(45):6347-58.

        We conducted a systematic review of the published literature to examine the impact of new vaccine introduction on countries’ immunization and broader health systems. Six publication databases were searched using 104 vaccine and health system-related search terms. The search yielded 15,795 unique articles dating from December 31, 1911 to September 29, 2010. Based on review of the title and abstract, 654 (4%) of these articles were found to be potentially relevant and were referred for full review. After full review, 130 articles were found to be relevant and included in the analysis. These articles represented vaccines introduced to protect against 10 different diseases (hepatitis A, hepatitis B, Haemophilus influenzae type b disease, human papilloma virus infection, influenza, Japanese encephalitis, meningococcal meningitis, Streptococcus pneumoniae disease, rotavirus diarrhea and typhoid), in various formulations and combinations. Most reviewed articles (97 [75%]) reported experiences in high-income countries. New vaccine introduction was most efficient when the vaccine was introduced into an existing delivery platform and when introduced in combination with a vaccine already in the routine childhood immunization schedule (i.e., as a combination vaccine). New vaccine introduction did not impact coverage of vaccines already included in the routine childhood immunization schedule. The need for increased cold chain capacity was frequently reported. New vaccines facilitated the introduction and widespread use of auto-disable syringes into the immunization and the broader health systems. The importance of training and education for health care workers and social mobilization was frequently noted. There was evidence in high-income countries that new vaccine introduction was associated with reduced health-care costs. Future evaluations of new vaccine introductions should include the systematic and objective assessment of the impacts on a country’s immunization system and broader health system, especially in lower-income countries.

      4. Acceptance of multiple injectable vaccines in a single immunization visit in The Gambia pre and post introduction of inactivated polio vaccineExternal
        Idoko OT, Hampton LM, Mboizi RB, Agbla SC, Wallace AS, Harris JB, Sowe D, Ehlman DC, Kampmann B, Ota MO, Hyde TB.
        Vaccine. 2016 Sep 22;34(41):5034-5039.

        BACKGROUND: As the World Health Organization (WHO) currently recommends that children be protected against 11 different pathogens, it is becoming increasingly necessary to administer multiple injectable vaccines during a single immunization visit. In this study we assess Gambian healthcare providers’ and infant caregivers’ attitudes and practices related to the administration of multiple injectable vaccines to a child at a single immunization visit before and after the 2015 introduction of inactivated polio vaccine (IPV). IPV introduction increased the number of injectable vaccines recommended for the 4-month immunization visit from two to three in The Gambia. METHODS: We conducted a cross-sectional questionnaire-based survey before and after the introduction of IPV at 4months of age in a representative sample of all health facilities providing immunizations in The Gambia. Healthcare providers who administer vaccines at the selected health facilities and caregivers who brought infants for their 4month immunization visit were surveyed. FINDINGS: Prior to IPV introduction, 9.9% of healthcare providers and 35.7% of infant caregivers expressed concern about a child receiving more than 2 injections in a single visit. Nevertheless, 98.8% and 90.9% of infants received all required vaccinations for the visit before and after IPV introduction, respectively. The only reason why vaccines were not received was vaccine stock-outs. Infant caregivers generally agreed that vaccinators could be trusted to provide accurate information regarding the number of vaccines that a child needed. CONCLUSION: Healthcare providers and infant caregivers in this resource limited setting accepted an increase in the number of injectable vaccines administered at a single visit even though some expressed concerns about the increase.

      5. Financial sustainability plans (FSPs) were developed by over 50 of the world’s poorest countries receiving funding support from the Global Alliance for Vaccines and Immunization (GAVI) to introduce new and underused vaccines, injection safety and immunization service support between 2000 and 2006. These plans were analysed with respect to the strategies selected to promote financial sustainability, allowing classification of FSP strategies in three areas: (1) mobilizing additional resources, (2) increasing the reliability of resources, and (3) improving program efficiency. Despite some country successes and the magnitude of planned financial sustainability strategies, huge funding gaps remain for these countries due to the initial underlying assumptions of the GAVI and financial sustainability plan model.

      6. Status of new vaccine introduction – worldwide, September 2016External
        Loharikar A, Dumolard L, Chu S, Hyde T, Goodman T, Mantel C.
        MMWR Morb Mortal Wkly Rep. 2016 Oct 21;65(41):1136-1140.

        Since the global Expanded Program on Immunization (EPI) was launched in 1974, vaccination against six diseases (tuberculosis, polio, diphtheria, tetanus, pertussis, and measles) has prevented millions of deaths and disabilities (1). Significant advances have been made in the development and introduction of vaccines, and licensed vaccines are now available to prevent 25 diseases (2,3). Historically, new vaccines only became available in low-income and middle-income countries decades after being introduced in high-income countries. However, with the support of global partners, including the World Health Organization (WHO) and the United Nations Children’s Fund, which assist with vaccine prequalification and procurement, as well as Gavi, the Vaccine Alliance (Gavi) (4), which provides funding and shapes vaccine markets through forecasting and assurances of demand in low-income countries in exchange for lower vaccine prices, vaccines are now introduced more rapidly. Based on data compiled in the WHO Immunization Vaccines and Biologicals Database* (5), this report describes the current status of introduction of Haemophilus influenzae type b (Hib), hepatitis B, pneumococcal conjugate, rotavirus, human papillomavirus, and rubella vaccines, and the second dose of measles vaccine. As of September 2016, a total of 191 (99%) of 194 WHO member countries had introduced Hib vaccine, 190 (98%) had introduced hepatitis B vaccine, 132 (68%) had introduced pneumococcal conjugate vaccine (PCV), and 86 (44%) had introduced rotavirus vaccine into infant vaccination schedules. Human papillomavirus vaccine (HPV) had been introduced in 67 (35%) countries, primarily targeted for routine use in adolescent girls. A second dose of measles-containing vaccine (MCV2) had been introduced in 161 (83%) countries, and rubella vaccine had been introduced in 149 (77%). These efforts support the commitment outlined in the Global Vaccine Action Plan (GVAP), 2011-2020 (2), endorsed by the World Health Assembly in 2012, to extend the full benefits of immunization to all persons.

      7. Creating sustainable financing and support for immunization programs in fifteen developing countriesExternal
        McQuestion M, Gnawali D, Kamara C, Kizza D, Mambu-Ma-Disu H, Mbwangue J, de Quadros C.
        Health Aff (Millwood). 2011 Jun;30(6):1134-40.

        Immunization programs are important tools for reducing child mortality, and they need to be in place for each new generation. However, most national immunization programs in developing countries are financially and organizationally weak, in part because they depend heavily on funding from foreign sources. Through its Sustainable Immunization Financing Program, launched in 2007, the Sabin Vaccine Institute is working with fifteen African and Asian countries to establish stable internal funding for their immunization programs. The Sabin program advocates strengthening immunization programs through budget reforms, decentralization, and legislation. Six of the fifteen countries have increased their national immunization budgets, and nine are preparing legislation to finance immunization sustainably. Lessons from this work with immunization programs may be applicable in other countries as well as to other health programs.

      8. Return on investment from childhood immunization in low- and middle-income countries, 2011-20External
        Ozawa S, Clark S, Portnoy A, Grewal S, Brenzel L, Walker DG.
        Health Aff (Millwood). 2016 Feb;35(2):199-207.

        An analysis of return on investment can help policy makers support, optimize, and advocate for the expansion of immunization programs in the world’s poorest countries. We assessed the return on investment associated with achieving projected coverage levels for vaccinations to prevent diseases related to ten antigens in ninety-four low- and middle-income countries during 2011-20, the Decade of Vaccines. We derived these estimates by using costs of vaccines, supply chains, and service delivery and their associated economic benefits. Based on the costs of illnesses averted, we estimated that projected immunizations will yield a net return about 16 times greater than costs over the decade (uncertainty range: 10-25). Using a full-income approach, which quantifies the value that people place on living longer and healthier lives, we found that net returns amounted to 44 times the costs (uncertainty range: 27-67). Across all antigens, net returns were greater than costs. But to realize the substantial positive return on investment from immunization programs, it is essential that governments and donors provide the requisite investments.

      9. Overcoming challenges to sustainable immunization financing: early experiences from GAVI graduating countriesExternal
        Saxenian H, Hecht R, Kaddar M, Schmitt S, Ryckman T, Cornejo S.
        Health Policy Plan. 2015 Mar;30(2):197-205.

        Over the 5-year period ending in 2018, 16 countries with a combined birth cohort of over 6 million infants requiring life-saving immunizations are scheduled to transition (graduate) from outside financial and technical support for a number of their essential vaccines. This support has been provided over the past decade by the GAVI Alliance. Will these 16 countries be able to continue to sustain these vaccination efforts? To address this issue, GAVI and its partners are supporting transition planning, entailing country assessments of readiness to graduate and intensive dialogue with national officials to ensure a smooth transition process. This approach was piloted in Bhutan, Republic of Congo, Georgia, Moldova and Mongolia in 2012. The pilot showed that graduating countries are highly heterogeneous in their capacity to assume responsibility for their immunization programmes. Although all possess certain strengths, each country displayed weaknesses in some of the following areas: budgeting for vaccine purchase, national procurement practices, performance of national regulatory agencies, and technical capacity for vaccine planning and advocacy. The 2012 pilot experience further demonstrated the value of transition planning processes and tools. As a result, GAVI has decided to continue with transition planning in 2013 and beyond. As the graduation process advances, GAVI and graduating countries should continue to contribute to global collective thinking about how developing countries can successfully end their dependence on donor aid and achieve self-sufficiency.

      10. Report on WHO meeting on immunization in older adults: Geneva, Switzerland, 22-23 March 2017External
        Teresa Aguado M, Barratt J, Beard JR, Blomberg BB, Chen WH, Hickling J, Hyde TB, Jit M, Jones R, Poland GA, Friede M, Ortiz JR.
        Vaccine. 2018 Feb 8;36(7):921-931.

        Many industrialized countries have implemented routine immunization policies for older adults, but similar strategies have not been widely implemented in low- and middle-income countries (LMICs). In March 2017, the World Health Organization (WHO) convened a meeting to identify policies and activities to promote access to vaccination of older adults, specifically in LMICs. Participants included academic and industry researchers, funders, civil society organizations, implementers of global health interventions, and stakeholders from developing countries with adult immunization needs. These experts reviewed vaccine performance in older adults, the anticipated impact of adult vaccination programs, and the challenges and opportunities of building or strengthening an adult and older adult immunization platforms. Key conclusions of the meeting were that there is a need for discussion of new opportunities for vaccination of all adults as well as for vaccination of older adults, as reflected in the recent shift by WHO to a life-course approach to immunization; that immunization in adults should be viewed in the context of a much broader model based on an individual’s abilities rather than chronological age; and that immunization beyond infancy is a global priority that can be successfully integrated with other interventions to promote healthy ageing. As WHO is looking ahead to a global Decade of Healthy Ageing starting in 2020, it will seek to define a roadmap for interdisciplinary collaborations to integrate immunization with improving access to preventive and other healthcare interventions for adults worldwide.

      11. In 2016, some progress was made towards the goals set out in the Global Vaccine Action Plan (GVAP). The year saw the fewest number of cases of wild poliovirus ever reported, and three more countries were certified as having achieved maternal and neonatal tetanus elimination. Nine additional countries have introduced new vaccines. Overall DTP3 vaccination coverage increased, but by only 1% to 86%. Progress therefore still remains too slow for most goals to be reached by the end of the Decade of Vaccines in 2020. Furthermore, multiple global, regional and national issues threaten further progress, and have the potential to reverse hard-won gains. Economic uncertainty, conflicts and natural disasters, displacement and migration, and infectious disease outbreaks all pose major challenges to immunization programmes. At the same time, there are concerning signs of complacency and inadequate political commitment to immunization – as well as a global lack of appreciation of its power to achieve wider health and development objectives. Additional risks include growing levels of vaccine hesitancy and the worrying rise in stockouts disrupting access to vaccines – related primarily to shortcomings in vaccine procurement and distribution but also to some extent to vaccine production. The continued marked underperformance of certain countries relative to others within their region – ‘outlier’ countries – remains of grave concern. The potential impact of the phase-out of funding for polio eradication is also of concern. It is vital that the polio transition remains sufficiently flexible that it does not jeopardize ongoing outbreak control efforts or critical surveillance activities and post-eradication certification processes. Furthermore, there is a significant risk that wider surveillance activities and routine immunization programmes, and hence global health security, could be compromised during the polio transition. The potentially simultaneous phasing out of polio and Gavi funding and technical support is of further concern.

      12. Global Vaccine Action Plan 2011-2020External
        World Health Organization .
        Geneva: World Health Organization. 2013 .

        The Global Vaccine Action Plan (GVAP) – endorsed by the 194 Member States of the World Health Assembly in May 2012 – is a framework to prevent millions of deaths by 2020 through more equitable access to existing vaccines for people in all communities.

      13. Principles and considerations for adding a vaccine to a national immunization programme: From decision to implementation and monitoringExternal
        World Health Organization .
        Geneva: World Health Organization Department of Immunization, Vaccines, and Biologicals. 2014 April.

        This essential resource document reviews the principles and issues to be considered when making decisions about planning and implementing the introduction of a vaccine into a national immunization programme. Importantly, the document highlights ways to use the opportunity provided by the vaccine introduction to strengthen immunization and health systems. The comprehensive guidance also describes the latest references and tools related to vaccine decision-making, economic analyses, cold chain, integrated disease control and health promotion, vaccine safety, communications, monitoring, and more, and provides key URL links to many of these resources.

      14. State of Inequality: Childhood Immunization. Interactive Visualization of Health DataExternal
        World Health Organization .
        Geneva: World Health Organization. 2016 .

        The report addresses two overarching questions: What inequalities in childhood immunization coverage exist in low- and middle-income countries? And how have childhood immunization inequalities changed over the last 10 years? In answering these questions, this report draws on data about five childhood immunization indicators, disaggregated by four dimensions of inequality, and covering 69 countries. The findings of this report indicate that there is less inequality now than 10 years ago. Global improvements have been realized with variable patterns of change across countries and by indicator and dimension of inequality. The current situation in many countries shows that further improvement is needed to lessen inequalities; in particular, inequalities related to household economic status and mother’s education were the most prominent. This report is accompanied by electronic interactive visuals, which facilitates thorough and customizable exploration of the data.

  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. Cardiovascular and renal burdens of prediabetes in the USA: analysis of data from serial cross-sectional surveys, 1988-2014External
        Ali MK, Bullard KM, Saydah S, Imperatore G, Gregg EW.
        Lancet Diabetes Endocrinol. 2018 Feb 27.

        BACKGROUND: There is controversy over the usefulness of prediabetes as a diagnostic label. Using data from US National Health and Nutrition Examination Surveys (NHANES) between 1988 and 2014, we examined the cardiovascular and renal burdens in adults with prediabetes over time and compared patterns with other glycaemic status groups. METHODS: We analysed cross-sectional survey data from non-pregnant adults aged 20 years and older from the NHANES survey periods 1988-94, 1999-2004, 2005-10, and 2011-14. We defined diagnosed diabetes as patients’ self-report that they had been previously diagnosed by a physician or health professional; among those with no self-reported diabetes, prediabetes was defined as a fasting plasma glucose (FPG) concentration of 100-125 mg/dL (5.6-6.9 mmol/L) or an HbA1c of 5.7-6.4% (39-47 mmol/mol); undiagnosed diabetes as an FPG of 126 mg/dL (7.0 mmol/L) or higher or an HbA1c of 6.5% (48 mmol/mol) or higher; and normal glycaemic status as an FPG of less than 100 mg/dL (5.6 mmol/L) and an HbA1c of less than 5.7% (39 mmol/mol). We repeated the analyses using varying definitions of prediabetes (FPG 110-125 mg/dL [6.1-6.9 mmol/L] or HbA1c 5.7-6.4% [39-47 mmol/mol], FPG 110-125 mg/dL [6.1-6.9 mmol/L] or HbA1c 6.0-6.4% [42-47 mmol/mol], and FPG 100-125 mg/dL [5.6-6.9 mmol/L] and HbA1c 5.7-6.4% [39-47 mmol/mol]). For each group over time, we estimated the prevalences of hypertension and dyslipidaemia; and among individuals with those conditions, we estimated the proportions who had been treated and who were achieving care goals. By glycaemic group, we estimated those who were current, former, and never smokers; mean 10-year risk of cardiovascular disease (using estimators from the Framingham Heart Study, the United Kingdom Prospective Diabetes Study (UKPDS), and the ACC/AHA ASCVD guidelines); albuminuria (median and albumin-to-creatinine ratio >/=30 mg/g), estimated glomerular filtration rate (eGFR; mean and <60 mL/min per 1.73m(2)); and prevalence of myocardial infarction and stroke. For all estimates, we calculated predicted changes between 1988-94 and 2011-14 using logistic regression models adjusted for age, sex, and race or ethnic group. FINDINGS: We obtained data for 27 971 eligible individuals. In 2011-14, in the population of adults with prediabetes, 36.6% (95% CI 32.8-40.5) had hypertension, 51.2% (47.0-55.3) had dyslipidaemia, 24.3% (21.7-27.3) smoked; 7.7% (6.8-8.8) had albuminuria; 4.6% (3.7-5.9) had reduced eGFR; and 10-year cardiovascular event risk ranged from 5% to 7%. From 1988-94 to 2011-14, adults with prediabetes showed significant increases in hypertension (+9.7 percentage points [95% CI 5.4-14.0]); no change in dyslipidaemia; decreases in smoking (-6.4 percentage points [-10.7 to -2.1]); increased use of treatment to lower blood pressure (54.2% [49.0-59.3] to 81.4% [76.7-85.3], +27.2 percentage points [20.5-33.8] p<0.0001) and to reduce lipids (6.6% to 40.2%, +33.6 percentage points [30.2-37.0], p<0.0001); and increased goal achievements for blood pressure (25.8% to 62.0%, +36.2 percentage points [30.7-41.8], p<0.0001) and lipids (1.0% to 32.8%, +31.8 percentage points [29.1-34.4, p<0.0001]). People with prediabetes also showed decreases in cardiovascular risk (ASCVD -1.9 percentage points [-2.5 to -1.3] to UKPDS -2.7 [-3.5 to -1.9], p<0.0001); but no change in prevalence of albuminuria, reduced eGFR, myocardial infarction, or stroke. Prevalence and patterns were consistent across all prediabetes definitions examined. Compared with adults with prediabetes, adults with diagnosed diabetes showed much larger improvements in cardiovascular and renal risk treatments, apart from smoking, which did not decline. INTERPRETATION: Over 25 years, cardiovascular and renal risks and disease have become highly prevalent in adults with prediabetes, irrespective of the definitions used. Identification of people with prediabetes might increase the opportunity for cardiovascular and renal risk reduction. FUNDING: None.

      2. Multilevel small-area estimation of colorectal cancer screening in the United StatesExternal
        Berkowitz Z, Zhang X, Richards TB, Nadel M, Peipins LA, Holt J.
        Cancer Epidemiol Biomarkers Prev. 2018 Mar;27(3):245-253.

        Background: The U.S. Preventive Services Task Force recommends routine screening for colorectal cancer for adults ages 50 to 75 years. We generated small-area estimates for being current with colorectal cancer screening to examine sociogeographic differences among states and counties. To our knowledge, nationwide county-level estimates for colorectal cancer screening are rarely presented.Methods: We used county data from the 2014 Behavioral Risk Factor Surveillance System (BRFSS; n = 251,360 adults), linked it to the American Community Survey poverty data, and fitted multilevel logistic regression models. We post-stratified the data with the U.S. Census population data to run Monte Carlo simulations. We generated county-level screening prevalence estimates nationally and by race/ethnicity, mapped the estimates, and aggregated them into state and national estimates. We evaluated internal consistency of our modeled state-specific estimates with BRFSS direct state estimates using Spearman correlation coefficients.Results: Correlation coefficients were >/=0.95, indicating high internal consistency. We observed substantial variations in current colorectal cancer screening estimates among the states and counties within states. State mean estimates ranged from 58.92% in Wyoming to 75.03% in Massachusetts. County mean estimates ranged from 40.11% in Alaska to 79.76% in Florida. Larger county variations were observed in various race/ethnicity groups.Conclusions: State estimates mask county variations. However, both state and county estimates indicate that the country is far behind the “80% by 2018” target.Impact: County-modeled estimates help identify variation in colorectal cancer screening prevalence in the United States and guide education and enhanced screening efforts in areas of need, including areas without BRFSS direct-estimates. Cancer Epidemiol Biomarkers Prev; 27(3); 245-53. (c)2018 AACR.

      3. Is seizure frequency variance a predictable quantity?External
        Goldenholz DM, Goldenholz SR, Moss R, French J, Lowenstein D, Kuzniecky R, Haut S, Cristofaro S, Detyniecki K, Hixson J, Karoly P, Cook M, Strashny A, Theodore WH.
        Ann Clin Transl Neurol. 2018 Feb;5(2):201-207.

        Background: There is currently no formal method for predicting the range expected in an individual’s seizure counts. Having access to such a prediction would be of benefit for developing more efficient clinical trials, but also for improving clinical care in the outpatient setting. Methods: Using three independently collected patient diary datasets, we explored the predictability of seizure frequency. Three independent seizure diary databases were explored: SeizureTracker (n = 3016), Human Epilepsy Project (n = 93), and NeuroVista (n = 15). First, the relationship between mean and standard deviation in seizure frequency was assessed. Using that relationship, a prediction for the range of possible seizure frequencies was compared with a traditional prediction scheme commonly used in clinical trials. A validation dataset was obtained from a separate data export of SeizureTracker to further verify the predictions. Results: A consistent mathematical relationship was observed across datasets. The logarithm of the average seizure count was linearly related to the logarithm of the standard deviation with a high correlation (R(2) > 0.83). The three datasets showed high predictive accuracy for this log-log relationship of 94%, compared with a predictive accuracy of 77% for a traditional prediction scheme. The independent validation set showed that the log-log predicted 94% of the correct ranges while the RR50 predicted 77%. Conclusion: Reliably predicting seizure frequency variability is straightforward based on knowledge of mean seizure frequency, across several datasets. With further study, this may help to increase the power of RCTs, and guide clinical practice.

      4. Thyroid hormones and menstrual cycle function in a longitudinal cohort of premenopausal womenExternal
        Jacobson MH, Howards PP, Darrow LA, Meadows JW, Kesner JS, Spencer JB, Terrell ML, Marcus M.
        Paediatr Perinat Epidemiol. 2018 Mar 8.

        BACKGROUND: Previous studies have reported that hyperthyroid and hypothyroid women experience menstrual irregularities more often compared with euthyroid women, but reasons for this are not well-understood and studies on thyroid hormones among euthyroid women are lacking. In a prospective cohort study of euthyroid women, this study characterised the relationship between thyroid hormone concentrations and prospectively collected menstrual function outcomes. METHODS: Between 2004-2014, 86 euthyroid premenopausal women not lactating or taking hormonal medications participated in a study measuring menstrual function. Serum thyroid hormones were measured before the menstrual function study began. Women then collected first morning urine voids and completed daily bleeding diaries every day for three cycles. Urinary oestrogen and progesterone metabolites (estrone 3-glucuronide (E1 3G) and pregnanediol 3-glucuronide (Pd3G)) and follicle-stimulating hormone were measured and adjusted for creatinine (Cr). RESULTS: Total thyroxine (T4 ) concentrations were positively associated with Pd3G and E1 3G. Women with higher (vs lower) T4 had greater luteal phase maximum Pd3G (Pd3G = 11.7 mug/mg Cr for women with high T4 vs Pd3G = 9.5 and 8.1 mug/mg Cr for women with medium and low T4 , respectively) and greater follicular phase maximum E1 3G (E1 3G = 41.7 ng/mg Cr for women with high T4 vs E1 3G = 34.3 and 33.7 ng/mg Cr for women with medium and low T4 , respectively). CONCLUSIONS: Circulating thyroid hormone concentrations were associated with subtle differences in menstrual cycle function outcomes, particularly sex steroid hormone levels in healthy women. Results contribute to the understanding of the relationship between thyroid function and the menstrual cycle, and may have implications for fertility and chronic disease.

      5. Young women’s perceptions regarding communication with healthcare providers about breast cancer, risk, and preventionExternal
        Lunsford NB, Sapsis KF, Smither B, Reynolds J, Wilburn B, Fairley T.
        J Womens Health (Larchmt). 2018 Feb;27(2):162-170.

        BACKGROUND: Women younger than 45 years old have lower rates of breast cancer, but higher risk of recurrence and mortality after a cancer diagnosis. African American women are at risk for early onset and increased mortality; Ashkenazi Jewish women are at risk for genetic mutations leading to breast and ovarian cancer. Although younger women are encouraged to talk to doctors about their family history, little is known about these discussions. MATERIALS AND METHODS: In 2015, 167 women aged 18-44 years participated in 20 focus groups segmented by geographic location, age, race/ethnicity, and family history of breast and ovarian cancer. Transcript data were analyzed using NVivo 10 software. RESULTS: Although the majority of women talked to their doctor about breast and ovarian cancer, these conversations were brief and unsatisfying due to a lack of detail. Topics included family history, breast cancer screening, and breast self-examination. Some women with and without family history reported that healthcare providers offered screening and early detection advice based on their inquiries. However, few women took action or changed lifestyle behaviors with the intent to reduce risk as a result of the conversations. CONCLUSIONS: Conversations with young women revealed missed opportunities to: enhance patient-provider communication and increase knowledge about breast cancer screening and surveillance for higher risk patients. Physicians, allied health professionals, and the public health community can better assist women in getting accurate and timely information about breast and ovarian cancer, understanding their family history to determine risk, and increasing healthy behaviors.

      6. BACKGROUND: With a cholesterol-lowering focus for diabetic adults and in the age of polypharmacy, it is important to understand how lipid profile levels differ among those with and without diabetes. OBJECTIVE: Investigate the means, differences, and trends in lipid profile measures [TC, total cholesterol; LDL-c, low-density lipoprotein; HDL-c, high-density lipoprotein; and TG, triglycerides] among US adults by diabetes status and cholesterol-lowering medication. METHODS: Population number and proportion of adults aged >/=21 years with diabetes and taking cholesterol-lowering medication were estimated using data on 10,384 participants from NHANES 2003-2012. Age-standardized means, trends, and differences in lipid profile measures were estimated by diabetes status and cholesterol medication use. For trends and differences, linear regression analysis were used adjusted for age, gender, and race/ethnicity. RESULTS: Among diabetic adults, 52% were taking cholesterol-lowering medication compared to the 14% taking cholesterol-lowering medication without diabetes. Although diabetic adults had significantly lower TC and LDL-c levels than non-diabetic adults [% difference (95% confidence interval): TC = -5.2% (-6.8 –3.5), LDL-c = -8.0% (-10.4 –5.5)], the percent difference was greater among adults taking cholesterol medication [TC = -8.0% (-10.3 –5.7); LDL-c = -13.7% (-17.1 –10.2)] than adults not taking cholesterol medication [TC = -3.5% (-5.2 –1.6); LDL-c = -4.3% (-7.1 –1.5)] (interaction p-value: TC = <0.001; LDL-c = <0.001). From 2003-2012, mean TC and HDL-c significantly decreased among diabetic adults taking cholesterol medication [% difference per survey cycle (p-value for linear trend): TC = -2.3% (0.003) and HDL-c = -2.3% (0.033)]. Mean TC, HDL-c, and LDL-c levels did not significantly change from 2003 to 2012 in non-diabetic adults taking cholesterol medication or for adults not taking cholesterol medications. CONCLUSIONS: Diabetic adults were more likely to have lower lipid levels, except for triglyceride levels, than non-diabetic adults with profound differences when considering cholesterol medication use, possibly due to the positive effects from clinical diabetes management.

      7. Hypertension among persons living with HIV in medical care in the United States – Medical Monitoring Project, 2013-2014External
        Olaiya O, Weiser J, Zhou W, Patel P, Bradley H.
        Open Forum Infect Dis. 2018 Mar;5(3):ofy028.

        Hypertension is a leading modifiable risk factor for cardiovascular disease (CVD), and persons living with HIV are at increased risk for both hypertension and CVD. Therefore, using data from a nationally representative sample of patients living with HIV, we assessed missed opportunities for the optimal management of hypertension.

      8. Integrating HIV and hypertension management in low-resource settings: Lessons from MalawiExternal
        Patel P, Speight C, Maida A, Loustalot F, Giles D, Phiri S, Gupta S, Raghunathan P.
        PLoS Med. 2018 Mar;15(3):e1002523.

        Pragna Patel and colleagues describe the implementation of a hypertension management model for HIV-infected people in Malawi.

      9. Prevalence of major behavioral risk factors for type 2 diabetesExternal
        Siegel KR, Bullard KM, Imperatore G, Ali MK, Albright A, Mercado CI, Li R, Gregg EW.
        Diabetes Care. 2018 Mar 2.

        OBJECTIVE: We examined the proportion of American adults without type 2 diabetes that engages in lifestyle behaviors known to reduce type 2 diabetes risk. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional analysis of 3,679 nonpregnant, nonlactating individuals aged >/=20 years without diabetes (self-reported diagnosis or glycated hemoglobin >/=6.5% [8 mmol/mol] or fasting plasma glucose >/=126 mg/dL) and who provided 2 days of reliable dietary data in the 2007-2012 National Health and Nutrition Examination Surveys (NHANES). We used the average of 2 days of dietary recall and self-reported leisure-time physical activity to assess whether participants met type 2 diabetes risk reduction goals (meeting four or more MyPlate recommendations [adequate consumption of fruits, vegetables, dairy, grains, meat, beans, and eggs]; not exceeding three maximum allowances for alcoholic beverages, added sugars, fat, and cholesterol; and meeting physical activity recommendations [>/=150 min/week]). RESULTS: Approximately 21%, 29%, and 13% of individuals met fruit, vegetable, and dairy goals, respectively. Half (51.6%) met the goal for total grains, compared with 18% for whole grains, and 54.2% met the meat/beans goal and 40.6% met the oils goal. About one-third (37.8%) met the physical activity goal, and 58.6% met the weight loss/maintenance goal. Overall, 3.1% (95% CI 2.4-4.0) of individuals met the majority of type 2 diabetes risk reduction goals. Younger age and lower educational attainment were associated with lower probability of meeting goals. CONCLUSIONS: A small proportion of U.S. adults engages in risk reduction behaviors. Research and interventions targeted at young and less-educated segments of the population may help close gaps in risk reduction behaviors.

    • Communicable Diseases
      1. Statistical method to detect tuberculosis outbreaks among endemic clusters in a low-incidence settingExternal
        Althomsons SP, Hill AN, Harrist AV, France AM, Powell KM, Posey JE, Cowan LS, Navin TR.
        Emerg Infect Dis. 2018 Mar;24(3):573-575.

        We previously reported use of genotype surveillance data to predict outbreaks among incident tuberculosis clusters. We propose a method to detect possible outbreaks among endemic tuberculosis clusters. We detected 15 possible outbreaks, of which 10 had epidemiologic data or whole-genome sequencing results. Eight outbreaks were corroborated.

      2. Rotavirus is the leading cause of hospitalizations for severe acute gastroenteritis among Afghan children <5years oldExternal
        Anwari P, Safi N, Payne DC, Jennings MC, Rasikh S, Waciqi AS, Parwiz SM.
        Vaccine. 2018 Mar 3.

        BACKGROUND: Rotavirus gastroenteritis is estimated to cause approximately five thousand deaths annually among Afghan children under 5years old. Because laboratory confirmation of rotavirus is not routinely performed in clinical settings, assessing the precise burden of disease attributable to severe rotavirus gastroenteritis typically requires active surveillance efforts. This study describes the current burden of pediatric hospitalizations attributable to rotavirus gastroenteritis among Afghan children using surveillance data collected from 2013 to 2015. METHODS: Rotavirus surveillance was conducted from January 2013 through December 2015 at two of the largest hospitals in the country, Indira Gandhi Children Hospital in Kabul and Herat Regional Hospital. Children between 1 and 60months of age who were admitted to these hospitals for diarrhea were consented and enrolled. Information on age, gender, and seasonality were collected. Stool specimens were collected and tested by enzyme immunoassay for the presence of rotavirus at the central public health laboratory in Afghanistan. RESULTS: Overall, 1,413 of 2,737 (52%) of hospitalized children under five years old with diarrhea were rotavirus cases. The overwhelming majority of rotavirus hospitalizations occurred in children younger than two years of age (93%) while 42% of all rotavirus hospitalizations occurred in children between 6 and 11months of age. Rotavirus transmission occurred year-round. CONCLUSIONS: Rotavirus is a major cause of severe acute gastroenteritis hospitalizations in young Afghan children, responsible for over half of diarrheal hospitalizations in this population. The Afghanistan Ministry of Public Health has prioritized reducing child mortality by 2020 and is actively working towards the introduction of rotavirus vaccination in Afghan children. These data will be instrumental in understanding the potential impact upon child health that may be achieved through the introduction of rotavirus vaccines in Afghanistan.

      3. Multistate epidemiology of histoplasmosis, United States, 2011-2014External
        Armstrong PA, Jackson BR, Haselow D, Fields V, Ireland M, Austin C, Signs K, Fialkowski V, Patel R, Ellis P, Iwen PC, Pedati C, Gibbons-Burgener S, Anderson J, Dobbs T, Davidson S, McIntyre M, Warren K, Midla J, Luong N, Benedict K.
        Emerg Infect Dis. 2018 Mar;24(3):425-431.

        Histoplasmosis is one of the most common mycoses endemic to the United States, but it was reportable in only 10 states during 2016, when a national case definition was approved. To better characterize the epidemiologic features of histoplasmosis, we analyzed deidentified surveillance data for 2011-2014 from the following 12 states: Alabama, Arkansas, Delaware, Illinois, Indiana, Kentucky, Michigan, Minnesota, Mississippi, Nebraska, Pennsylvania, and Wisconsin. We examined epidemiologic and laboratory features and calculated state-specific annual and county-specific mean annual incidence rates. A total of 3,409 cases were reported. Median patient age was 49 (interquartile range 33-61) years, 2,079 (61%) patients were male, 1,273 (57%) patients were hospitalized, and 76 (7%) patients died. Incidence rates varied markedly between and within states. The high hospitalization rate suggests that histoplasmosis surveillance underestimates the true number of cases. Improved surveillance standardization and surveillance by additional states would provide more comprehensive knowledge of histoplasmosis in the United States.

      4. Results from the second year of a collaborative effort to forecast influenza seasons in the United StatesExternal
        Biggerstaff M, Johansson M, Alper D, Brooks LC, Chakraborty P, Farrow DC, Hyun S, Kandula S, McGowan C, Ramakrishnan N, Rosenfeld R, Shaman J, Tibshirani R, Tibshirani RJ, Vespignani A, Yang W, Zhang Q, Reed C.
        Epidemics. 2018 Feb 24.

        Accurate forecasts could enable more informed public health decisions. Since 2013, CDC has worked with external researchers to improve influenza forecasts by coordinating seasonal challenges for the United States and the 10 Health and Human Service Regions. Forecasted targets for the 2014-15 challenge were the onset week, peak week, and peak intensity of the season and the weekly percent of outpatient visits due to influenza-like illness (ILI) 1-4 weeks in advance. We used a logarithmic scoring rule to score the weekly forecasts, averaged the scores over an evaluation period, and then exponentiated the resulting logarithmic score. Poor forecasts had a score near 0, and perfect forecasts a score of 1. Five teams submitted forecasts from seven different models. At the national level, the team scores for onset week ranged from <0.01 to 0.41, peak week ranged from 0.08 to 0.49, and peak intensity ranged from <0.01 to 0.17. The scores for predictions of ILI 1-4 weeks in advance ranged from 0.02-0.38 and was highest 1 week ahead. Forecast skill varied by HHS region. Forecasts can predict epidemic characteristics that inform public health actions. CDC, state and local health officials, and researchers are working together to improve forecasts.

      5. Challenges and solutions implementing an SMS text message-based survey CASI and adherence reminders in an international biomedical HIV PrEP study (MTN 017)External
        Brown W, Giguere R, Sheinfil A, Ibitoye M, Balan I, Ho T, Brown B, Quispe L, Sukwicha W, Lama JR, Carballo-Dieguez A, Cranston RD.
        J Biomed Inform. 2018 Feb 28.

        BACKGROUND: We implemented a text message-based Short Message Service computer-assisted self-interviewing (SMS-CASI) system to aid adherence and monitor behavior in MTN-017, a phase 2 safety and acceptability study of rectally-applied reduced-glycerin 1% tenofovir gel compared to oral emtricitabine/tenofovir disoproxil fumarate tablets. We sought to implement SMS-based daily reminders and product use reporting, in four countries and five languages, and centralize data management/automated-backup. METHODS: We assessed features of five SMS programs against study criteria. After identifying the optimal program, we systematically implemented it in South Africa, Thailand, Peru, and the United States. The system consisted of four windows-based computers, a GSM dongle and sim card to send SMS. The SMS-CASI was, designed for 160 character SMS. Reminders and reporting sessions were initiated by date/time triggered messages. System, questions, responses, and instructions were triggered by predetermined key words. RESULTS: There were 142,177 total messages: sent 86,349 (60.73%), received 55,573 (39.09%), failed 255 (0.18%). 6,153 (4.33%) of the message were errors generated from either our SMS-CASI system or by participants. Implementation challenges included: high message costs; poor data access; slow data cleaning and analysis; difficulty reporting information to sites; a need for better participant privacy and data security; and mitigating variability in system performance across sites. We mitigated message costs and poor data access by federating the SMS-CASI system, and used secure email protocols to centralize data backup. We developed programming syntaxes to facilitate daily data cleaning and analysis, and a calendar template for reporting SMS behavior. Lastly, we ambiguated text message language to increase privacy, and standardized hardware and software across sites, minimizing operational variability. CONCLUSION: We identified factors that aid international implementation and operation of SMS-CASI for real-time adherence monitoring. The challenges and solutions we present can aid other researchers to develop and manage an international multilingual SMS-based adherence reminder and CASI system.

      6. Epidemiology and molecular identification and characterization of Mycoplasma pneumoniae, South Africa, 2012-2015External
        Carrim M, Wolter N, Benitez AJ, Tempia S, du Plessis M, Walaza S, Moosa F, Diaz MH, Wolff BJ, Treurnicht FK, Hellferscee O, Dawood H, Variava E, Cohen C, Winchell JM, von Gottberg A.
        Emerg Infect Dis. 2018 Mar;24(3):506-513.

        During 2012-2015, we tested respiratory specimens from patients with severe respiratory illness (SRI), patients with influenza-like illness (ILI), and controls in South Africa by real-time PCR for Mycoplasma pneumoniae, followed by culture and molecular characterization of positive samples. M. pneumoniae prevalence was 1.6% among SRI patients, 0.7% among ILI patients, and 0.2% among controls (p<0.001). Age <5 years (adjusted odd ratio 7.1; 95% CI 1.7-28.7) and HIV infection (adjusted odds ratio 23.8; 95% CI 4.1-138.2) among M. pneumonia-positive persons were associated with severe disease. The detection rate attributable to illness was 93.9% (95% CI 74.4%-98.5%) in SRI patients and 80.7% (95% CI 16.7%-95.6%) in ILI patients. The hospitalization rate was 28 cases/100,000 population. We observed the macrolide-susceptible M. pneumoniae genotype in all cases and found P1 types 1, 2, and a type 2 variant with multilocus variable number tandem repeat types 3/6/6/2, 3/5/6/2, and 4/5/7/2.

      7. Viral etiologies of influenza-like illness and severe acute respiratory infections in ThailandExternal
        Chittaganpitch M, Waicharoen S, Yingyong T, Praphasiri P, Sangkitporn S, Olsen SJ, Lindblade KA.
        Influenza Other Respir Viruses. 2018 Mar 8.

        BACKGROUND: Information on the burden, characteristics and seasonality of non-influenza respiratory viruses is limited in tropical countries. OBJECTIVES: Describe the epidemiology of selected non-influenza respiratory viruses in Thailand between June 2010 and May 2014 using a sentinel surveillance platform established for influenza. METHODS: Patients with influenza-like illness (ILI; history of fever or documented temperature >38 degrees C, cough, not requiring hospitalization) or severe acute respiratory infection (SARI; history of fever or documented temperature >38 degrees C, cough, onset <10 days, requiring hospitalization) were enrolled from 10 sites. Throat swabs were tested for influenza viruses, respiratory syncytial virus (RSV), metapneumovirus (MPV), parainfluenza viruses (PIV) 1-3, and adenoviruses by polymerase chain reaction (PCR) or real-time reverse transcriptase PCR RESULTS: We screened 15,369 persons with acute respiratory infections and enrolled 8106 cases of ILI (5069 cases <15 years old) and 1754 cases of SARI (1404 cases <15 years old). Among ILI cases <15 years old, influenza viruses (1173, 23%), RSV (447, 9%) and adenoviruses (430, 8%) were the most frequently identified respiratory viruses tested, while for SARI cases <15 years old, RSV (196, 14%) influenza (157, 11%) and adenoviruses (90, 6%) were the most common.. The RSV season significantly overlapped the larger influenza season from July-November in Thailand. CONCLUSIONS: The global expansion of influenza sentinel surveillance provides an opportunity to gather information on the characteristics of cases positive for non-influenza respiratory viruses, particularly seasonality, although adjustments to case definitions may be required. This article is protected by copyright. All rights reserved.

      8. Evaluating oseltamivir prescriptions in Centers for Medicare and Medicaid Services medical claims records as an indicator of seasonal influenza in the United StatesExternal
        Dahlgren FS, Shay DK, Izurieta HS, Forshee RA, Wernecke M, Chillarige Y, Lu Y, Kelman JA, Reed C.
        Influenza Other Respir Viruses. 2018 Mar 5.

        BACKGROUND: Over 34 million residents of the United States aged 65 years old and older are also Medicare prescription drug beneficiaries. Medical claims records for this age group potentially provide a wealth of data for better understanding influenza epidemiology. OBJECTIVE: The purpose of this study was to evaluate data on oseltamivir dispensing extracted from medical claims records as an indicator of influenza activity in the United States for the 2010-11 through 2014-15 influenza seasons. METHODS: We used Centers for Medicare and Medicaid Services (CMS) medical claims data to evaluate the weekly number of therapeutic oseltamivir prescriptions dispensed following a rapid influenza diagnostic test among beneficiaries 65 years old and older as an indicator of influenza timing and intensity. We compared the temporal changes in this indicator to changes in the proportion of influenza-like illnesses among outpatient visits in the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet) by administrative regions defined by the U.S. Department of Health and Human Services. Using the moving epidemic method, we determined intensity thresholds and categorized the severity of seasons for both CMS and ILINet data. RESULTS: CMS oseltamivir data and ILINet data were strongly correlated by administrative region (median Spearman’s rho = 0.78, interquartile range = 0.73-0.80). CMS oseltamivir data and ILINet data substantially agreed (Cohen’s weighted kappa = 0.62) as to the seasonal severity across administrative regions. CONCLUSIONS: Our results support the use of oseltamivir dispensing in medical claims data as an indicator of US influenza activity. This article is protected by copyright. All rights reserved.

      9. CD4 cell count threshold for cryptococcal antigen screening of HIV-infected individuals: A systematic review and meta-analysisExternal
        Ford N, Shubber Z, Jarvis JN, Chiller T, Greene G, Migone C, Vitoria M, Doherty M, Meintjes G.
        Clin Infect Dis. 2018 Mar 4;66(suppl_2):S152-s159.

        Background: Current guidelines recommend screening all people living with human immunodeficiency virus (PLHIV) who have a CD4 count </=100 cells/microL for cryptococcal antigen (CrAg) to identify those patients who could benefit from preemptive fluconazole treatment prior to the onset of meningitis. We conducted a systematic review to assess the prevalence of CrAg positivity at different CD4 cell counts. Methods: We searched 4 databases and abstracts from 3 conferences up to 1 September 2017 for studies reporting prevalence of CrAg positivity according to CD4 cell count strata. Prevalence estimates were pooled using random effects models. Results: Sixty studies met our inclusion criteria. The pooled prevalence of cryptococcal antigenemia was 6.5% (95% confidence interval [CI], 5.7%-7.3%; 54 studies) among patients with CD4 count </=100 cells/microL and 2.0% (95% CI, 1.2%-2.7%; 21 studies) among patients with CD4 count 101-200 cells/microL. Twenty-one studies provided sufficient information to compare CrAg prevalence per strata; overall, 18.6% (95% CI, 15.4%-22.2%) of the CrAg-positive cases identified at </=200 cells/microL (n = 11823) were identified among individuals with a CD4 count 101-200 cells/microL. CrAg prevalence was higher among inpatients (9.8% [95% CI, 4.0%-15.5%]) compared with outpatients (6.3% [95% CI, 5.3%-7.4%]). Conclusions: The findings of this review support current recommendations to screen all PLHIV who have a CD4 count </=100 cells/microL for CrAg and suggest that screening may be considered at CD4 cell count </=200 cells/microL.

      10. Coccidioidomycosis outbreaks, United States and worldwide, 1940-2015External
        Freedman M, Jackson BR, McCotter O, Benedict K.
        Emerg Infect Dis. 2018 Mar;24(3):417-423.

        Coccidioidomycosis causes substantial illness and death in the United States each year. Although most cases are sporadic, outbreaks provide insight into the clinical and environmental features of coccidioidomycosis, high-risk activities, and the geographic range of Coccidioides fungi. We identified reports published in English of 47 coccidioidomycosis outbreaks worldwide that resulted in 1,464 cases during 1940-2015. Most (85%) outbreaks were associated with environmental exposures; the 2 largest outbreaks resulted from an earthquake and a large dust storm. More than one third of outbreaks occurred in areas where the fungus was not previously known to be endemic, and more than half of outbreaks involved occupational exposures. Coccidioidomycosis outbreaks can be difficult to detect and challenging to prevent given the unknown effectiveness of environmental control methods and personal protective equipment; therefore, increased awareness of coccidioidomycosis outbreaks is needed among public health professionals, healthcare providers, and the public.

      11. Tenofovir versus placebo to prevent perinatal transmission of hepatitis BExternal
        Jourdain G, Ngo-Giang-Huong N, Harrison L, Decker L, Khamduang W, Tierney C, Salvadori N, Cressey TR, Sirirungsi W, Achalapong J, Yuthavisuthi P, Kanjanavikai P, Na Ayudhaya OP, Siriwachirachai T, Prommas S, Sabsanong P, Limtrakul A, Varadisai S, Putiyanun C, Suriyachai P, Liampongsabuddhi P, Sangsawang S, Matanasarawut W, Buranabanjasatean S, Puernngooluerm P, Bowonwatanuwong C, Puthanakit T, Klinbuayaem V, Thongsawat S, Thanprasertsuk S, Siberry GK, Watts DH, Chakhtoura N, Murphy TV, Nelson NP, Chung RT, Pol S, Chotivanich N.
        N Engl J Med. 2018 Mar 8;378(10):911-923.

        BACKGROUND: Pregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants’ receiving hepatitis B immune globulin. METHODS: In this multicenter, double-blind clinical trial performed in Thailand, we randomly assigned hepatitis B e antigen (HBeAg)-positive pregnant women with an alanine aminotransferase level of 60 IU or less per liter to receive tenofovir disoproxil fumarate (TDF) or placebo from 28 weeks of gestation to 2 months post partum. Infants received hepatitis B immune globulin at birth and hepatitis B vaccine at birth and at 1, 2, 4, and 6 months. The primary end point was a hepatitis B surface antigen (HBsAg)-positive status in the infant, confirmed by the HBV DNA level at 6 months of age. We calculated that a sample of 328 women would provide the trial with 90% power to detect a difference of at least 9 percentage points in the transmission rate (expected rate, 3% in the TDF group vs. 12% in the placebo group). RESULTS: From January 2013 to August 2015, we enrolled 331 women; 168 women were randomly assigned to the TDF group and 163 to the placebo group. At enrollment, the median gestational age was 28.3 weeks, and the median HBV DNA level was 8.0 log10 IU per milliliter. Among 322 deliveries (97% of the participants), there were 319 singleton births, two twin pairs, and one stillborn infant. The median time from birth to administration of hepatitis B immune globulin was 1.3 hours, and the median time from birth to administration of hepatitis B vaccine was 1.2 hours. In the primary analysis, none of the 147 infants (0%; 95% confidence interval [CI], 0 to 2) in the TDF group were infected, as compared with 3 of 147 (2%; 95% CI, 0 to 6) in the placebo group (P=0.12). The rate of adverse events did not differ significantly between groups. The incidence of a maternal alanine aminotransferase level of more than 300 IU per liter after discontinuation of the trial regimen was 6% in the TDF group and 3% in the placebo group (P=0.29). CONCLUSIONS: In a setting in which the rate of mother-to-child HBV transmission was low with the administration of hepatitis B immune globulin and hepatitis B vaccine in infants born to HBeAg-positive mothers, the additional maternal use of TDF did not result in a significantly lower rate of transmission. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01745822 .).

      12. A tale of two countries: progress towards UNAIDS 90-90-90 targets in Botswana and AustraliaExternal
        Marukutira T, Stoove M, Lockman S, Mills LA, Gaolathe T, Lebelonyane R, Jarvis JN, Kelly SL, Wilson DP, Luchters S, Crowe SM, Hellard M.
        J Int AIDS Soc. 2018 Mar;21(3).

        UNAIDS 90-90-90 targets and Fast-Track commitments are presented as precursors to ending the AIDS epidemic by 2030, through effecting a 90% reduction in new HIV infections and AIDS-related deaths from 2010 levels (HIV epidemic control). Botswana, a low to middle-income country with the third-highest HIV prevalence, and Australia, a low-prevalence high-income country with an epidemic concentrated among men who have sex with men (MSM), have made significant strides towards achieving the UNAIDS 90-90-90 targets. These two countries provide lessons for different epidemic settings. This paper discusses the lessons that can be drawn from Botswana and Australia with respect to their success in HIV testing, treatment, viral suppression and other HIV prevention strategies for HIV epidemic control. Botswana and Australia are on target to achieving the 90-90-90 targets for HIV epidemic control, made possible by comprehensive HIV testing and treatment programmes in the two countries. As of 2015, 70% of all people assumed to be living with HIV had viral suppression in Botswana and Australia. However, HIV incidence remains above one per cent in the general population in Botswana and in MSM in Australia. The two countries have demonstrated that rapid HIV testing that is accessible and targeted at key and vulnerable populations is required in order to continue identifying new HIV infections. All citizens living with HIV in both countries are eligible for antiretroviral therapy (ART) and viral load monitoring through government-funded programmes. Notwithstanding their success in reducing HIV transmission to date, programmes in both countries must continue to be supported at current levels to maintain epidemic suppression. Scaled HIV testing, linkage to care, universal ART, monitoring patients on treatment over and above strengthened HIV prevention strategies (e.g. male circumcision and pre-exposure prophylaxis) will all continue to require funding. The progress that Botswana and Australia have made towards meeting the 90-90-90 targets is commendable. However, in order to reduce HIV incidence significantly towards 2030, there is a need for sustained HIV testing, linkage to care and high treatment coverage. Botswana and Australia provide useful lessons for developing countries with generalized epidemics and high-income countries with concentrated epidemics.

      13. Strengthening acute flaccid paralysis surveillance through the village polio volunteers program in SomaliaExternal
        Mbaeyi C, Mohamed A, Owino BO, Mengistu KF, Ehrhardt D, Elsayed EA.
        Clin Infect Dis. 2018 Mar 2.

        Background: Surveillance for cases of acute flaccid paralysis (AFP) is a key strategy adopted for the eradication of polio. Detection of poliovirus circulation is often predicated on the ability to identify AFP cases and test their stool specimens for poliovirus infection in a timely manner. The Village Polio Volunteers (VPV) program was established in 2013 in a bid to strengthen polio eradication activities in Somalia, including AFP surveillance, given the country’s vulnerability to polio outbreaks. Methods: To assess the impact of the VPV program on AFP surveillance, we determined case counts, case-reporting sources, and non-polio AFP rates in the years before and after program introduction, i.e., 2011-2016. We also compared the stool adequacy and timeliness of cases reported by VPVs to those reported by other sources. Results: In the years following program introduction, VPVs accounted for a high proportion of AFP cases reported in Somalia. AFP case counts rose from 148 cases in 2012, the year before program introduction, to 279 cases in 2015, during which VPVs accounted for 40% of reported cases. Further, the non-polio AFP rate improved from 2.8 cases in 2012 to 4.8 cases per 100,000 persons <15 years by 2015. Stool adequacy rates have been consistently high and AFP cases have been detected in a timelier manner since the program was introduced. Conclusions: Given the impact of the VPV program on improving AFP surveillance indicators in Somalia, similar community-based programs could play a crucial role in enhancing surveillance activities in countries with limited healthcare infrastructure.

      14. Echinocandin resistance among Candida isolates at an academic medical centre 2005-15: analysis of trends and outcomesExternal
        McCarty TP, Lockhart SR, Moser SA, Whiddon J, Zurko J, Pham CD, Pappas PG.
        J Antimicrob Chemother. 2018 Feb 28.

        Objectives: To identify the frequency of micafungin resistance among clinically significant isolates of Candida stored at our institution from 2005 to 2015. Chart review of patients with resistant isolates then informed the clinical setting and outcomes associated with these infections. Methods: Clinical Candida isolates had been stored at -80 degrees C in Brucella broth with 20% glycerol from 2005. Isolates were tested using broth microdilution to determine micafungin MICs. All Candida glabrata isolates and all isolates demonstrating decreased susceptibility to micafungin were screened for FKS mutations using a Luminex assay. Results: In total, 3876 Candida isolates were tested for micafungin resistance, including 832 C. glabrata isolates. Of those, 33 isolates from 31 patients were found to have either decreased susceptibility to micafungin and/or an FKS mutation. C. glabrata accounted for the majority of these isolates. While bloodstream infections were found to have a very high mortality rate, isolates from other sites were uncommonly associated with 30-day mortality. Overall resistance rates were very low. Conclusions: Echinocandin resistance in C. glabrata has been increasingly reported but rates at our institution remain very low. We hypothesize that a focus on antifungal stewardship may have led to these observations. Knowledge of local resistance patterns is key to appropriate empirical treatment strategies.

      15. Taking aim at choleraExternal
        Mintz E.
        Lancet. 2018 Mar 1.

        [No abstract]

      16. Use of verbal autopsy to determine underlying cause of death during treatment of multidrug-resistant tuberculosis, IndiaExternal
        Naik PR, Moonan PK, Nirgude AS, Shewade HD, Satyanarayana S, Raghuveer P, Parmar M, Ravichandra C, Singarajipura A.
        Emerg Infect Dis. 2018 Mar;24(3):478-484.

        Of patients with multidrug-resistant tuberculosis (MDR TB), <50% complete treatment. Most treatment failures for patients with MDR TB are due to death during TB treatment. We sought to determine the proportion of deaths during MDR TB treatment attributable to TB itself. We used a structured verbal autopsy tool to interview family members of patients who died during MDR TB treatment in India during January-December 2016. A committee triangulated information from verbal autopsy, death certificate, or other medical records available with the family members to ascertain the underlying cause of death. For 66% of patient deaths (47/71), TB was the underlying cause of death. We assigned TB as the underlying cause of death for an additional 6 patients who died of suicide and 2 of pulmonary embolism. Deaths during TB treatment signify program failure; accurately determining the cause of death is the first step to designing appropriate, timely interventions to prevent premature deaths.

      17. BACKGROUND: The Centers for Disease Control and Prevention 2015 Sexually Transmitted Disease Treatment Guidelines recommend that clinicians consider cephalosporin treatment failure in patients who deny interval sexual exposure and are nucleic acid amplification test (NAAT) positive for Neisseria gonorrhoeae (NG) at least 7 days after adequate treatment. We evaluate the real-world implications of the interval the Centers for Disease Control and Prevention recommends for a NAAT test-of-cure (TOC), by ascertaining the frequency of NG NAAT positivity at different anatomic sites among men who have sex with men (MSM) at TOC 7 to 30 days after treatment. METHODS: We analyzed data from the medical records of MSM with laboratory-confirmed NG who were presumptively treated for NG during the period from June 2013 to April 2016 and returned for a TOC visit within 30 days. Data examined included symptoms, site of NG specimen collection, treatment regimen, follow-up testing, and intervening sexual activity. RESULTS: There were 1027 NG-positive specimens obtained from 763 MSM patients at 889 presumptive treatment visits. Of these, 44% (337/763) MSM returned for 1 or more TOC visits, and 413 specimens were collected a median of 10 days after presumptive treatment. Three percent (14/413) of specimens collected were NG NAAT positive at TOC a median of 13 days after treatment: 5% (12/256) of urethral specimens, 1% (1/147) of anorectal specimens (P = 0.037, urethral vs. anorectal), and 10% (1/10) of oropharyngeal specimens (P = 0.40, urethral vs. oropharyngeal). CONCLUSIONS: A small percent of patients were NG NAAT positive at TOC. Compared with anorectal specimens, urethral specimens were more frequently still positive at TOC. A large proportion of MSM will return for a TOC visit as part of standard clinical care.

      18. Gaps along the HIV care continuum: findings among a population seeking sexual health care services in New York CityExternal
        Pathela P, Jamison K, Braunstein SL, Schillinger JA, Tymejczyk O, Nash D.
        J Acquir Immune Defic Syndr. 2018 Mar 2.

        BACKGROUND: Linkage/re-linkage to HIV care for virally unsuppressed persons with new sexually transmitted infections is critical for ending the HIV epidemic. We quantified HIV care continuum gaps, and viral suppression, among HIV-positive patients attending New York City (NYC) sexual health clinics (SHC). METHODS: 1,649 HIV-positive patients and a 10% sample of 11,954 patients with unknown HIV status on clinic visit date (DOV) were matched against the NYC HIV registry. Using registry diagnosis dates, we categorized matched HIV-positive patients as “new-positives” (newly diagnosed on DOV), “recent-positives (diagnosed </=90 days before DOV), “prevalent-positives” (diagnosed >90 days before DOV), and “unknown-positives” (previously diagnosed, but status unknown to clinic on DOV). We assessed HIV care continuum outcomes before and after DOV for new-positives, prevalent-positives, and unknown-positives using registry laboratory data. RESULTS: In addition to 1,626 known HIV-positive patients, 5% of the unknown sample (63/1,196) matched to the registry, signifying that about 630 additional HIV-positive patients attended SHCs. Of new-positives, 65% were linked to care after DOV. Of prevalent-positives, 66% were in care on DOV; 43% of the out-of-care were re-linked after DOV. Of unknown-positives, 40% were in care on DOV; 21% of the out-of-care re-linked after DOV. Viral suppression was achieved by: 88% of in-care unknown-positives, 76% in-care prevalent-positives, 50% new-positives, 42% out-of-care prevalent-positives, and 16% out-of-care unknown-positives. CONCLUSIONS: Many HIV-positive persons, including those with uncontrolled HIV infection, attend SHCs and potentially contribute to HIV spread. However, HIV status often is not known to staff, resulting in missed linkage/re-linkage to care opportunities. Better outcomes could be facilitated by real-time ascertainment of HIV status and HIV care status.

      19. The seasonality of nonpolio enteroviruses in the United States: Patterns and driversExternal
        Pons-Salort M, Oberste MS, Pallansch MA, Abedi GR, Takahashi S, Grenfell BT, Grassly NC.
        Proc Natl Acad Sci U S A. 2018 Mar 5.

        Nonpolio enteroviruses are diverse and common viruses that can circulate year-round but tend to peak in summer. Although most infections are asymptomatic, they can result in a wide range of neurological and other diseases. Many serotypes circulate every year, and different serotypes predominate in different years, but the drivers of their geographical and temporal dynamics are not understood. We use national enterovirus surveillance data collected by the US Centers for Disease Control and Prevention during 1983-2013, as well as demographic and climatic data for the same period, to study the patterns and drivers of the seasonality of these infections. We find that the seasonal pattern of enterovirus cases is spatially structured in the United States and similar to that observed for historical prevaccination poliomyelitis (1931-1954). We identify latitudinal gradients for the amplitude and the timing of the peak of cases, meaning that those are more regularly distributed all year-round in the south and have a more pronounced peak that arrives later toward the north. The peak is estimated to occur between July and September across the United States, and 1 month earlier than that for historical poliomyelitis. Using mixed-effects models, we find that climate, but not demography, is likely to drive the seasonal pattern of enterovirus cases and that the dew point temperature alone explains approximately 30% of the variation in the intensity of transmission. Our study contributes to a better understanding of the epidemiology of enteroviruses, demonstrates important similarities in their circulation dynamics with polioviruses, and identifies potential drivers of their seasonality.

      20. Assessing new diagnoses of HIV among American Indian/Alaska Natives Served by the Indian Health Service, 2005-2014External
        Reilley B, Haberling DL, Person M, Leston J, Iralu J, Haverkate R, Siddiqi AE.
        Public Health Rep. 2018 Jan 1:33354917753118.

        OBJECTIVES: The objectives of this study were to use Indian Health Service (IHS) data from electronic health records to analyze human immunodeficiency virus (HIV) diagnoses among American Indian/Alaska Natives (AI/ANs) and to identify current rates and trends that can support data-driven policy implementation and resource allocation for this population. METHODS: We analyzed provider visit data from IHS to capture all AI/AN patients who met a definition of a new HIV diagnosis from 2005 through 2014 by using International Classification of Diseases, Ninth Revision, Clinical Modification codes. We calculated rates and trends of new HIV diagnoses by age, sex, region, and year per 100 000 AI/ANs in the IHS user population. RESULTS: A total of 2273 AI/ANs met the definition of newly diagnosed with HIV from 2005 through 2014, an average annual rate of 15.1 per 100 000 AI/ANs. Most (356/391) IHS health facilities recorded at least 1 new HIV diagnosis. The rate of new HIV diagnoses among males (21.3 per 100 000 AI/ANs) was twice as high as that among females (9.5 per 100 000 AI/ANs; rate ratio = 2.2; 95% confidence interval, 2.1-2.4); by age, rates were highest among those aged 20-54 for males and females. By region, the Southwest region had the highest number (n = 1016) and rate (19.9 per 100 000 AI/ANs) of new HIV diagnoses. Overall annual rates of new HIV diagnoses were stable from 2010 through 2014, although diagnosis rates increased among males ( P < .001) and those aged 15-19 ( P < .001), 45-59 ( P < .001), and 50-54 ( P = .01). CONCLUSIONS: New HIV diagnoses, derived from provider visit data, among AI/ANs were stable from 2010 through 2014. AI/ANs aged 20-54, particularly men, may benefit from increased HIV prevention and screening efforts. Additional services may benefit patients in regions with higher rates of new diagnoses and in remote settings in which reported HIV numbers are low.

      21. Current epidemiology and trends in invasive Haemophilus influenzae disease – United States, 2009-2015External
        Soeters HM, Blain A, Pondo T, Doman B, Farley MM, Harrison LH, Lynfield R, Miller L, Petit S, Reingold A, Schaffner W, Thomas A, Zansky SM, Wang X, Briere EC.
        Clin Infect Dis. 2018 Mar 2.

        Background: Following Haemophilus influenzae serotype b (Hib) conjugate vaccine introduction in the 1980s, Hib disease in young children dramatically decreased and epidemiology of invasive H. influenzae changed. Methods: Active surveillance for invasive H. influenzae disease was conducted through Active Bacterial Core surveillance sites. Incidence rates were directly standardized to the age and race distribution of the US population. Results: During 2009-2015, the estimated mean annual incidence of invasive H. influenzae disease was 1.70 cases per 100,000 population. Incidence was highest among adults >/=65 years (6.30) and children aged <1 year (8.45); many cases in infants aged <1 year occurred during the first month of life in preterm or low-birth weight infants. Among children aged <5 years (incidence: 2.84), incidence was substantially higher in American Indian and Alaska Natives (AI/AN) (15.19) than in all other races (2.62). Overall, 14.5% of cases were fatal; case-fatality was highest among adults aged >/=65 years (20%). Nontypeable H. influenzae had the highest incidence (1.22) and case-fatality (16%), as compared to Hib (0.03; 4%) and non-b encapsulated serotypes (0.45; 11%). Compared with 2002-2008, the estimated incidence of invasive H. influenzae disease increased by 16%, driven by increases in disease caused by serotype a and nontypeable strains. Conclusions: Invasive H. influenzae disease has increased, particularly due to nontypeable strains and serotype a. A considerable burden of invasive H. influenzae disease affects the oldest and youngest age groups, particularly AI/AN children. These data can inform prevention strategies, including vaccine development.

      22. How good is your rule of thumb? Validating male-to-female case ratio as a proxy for men who have sex with men involvement in N. gonorrhoeae incidence at the county levelExternal
        Stenger M, Bauer H, Klingler E, Bell T, Donnelly J, Eaglin M, Jespersen M, Madera R, Mattson M, Torrone E.
        Sex Transm Dis. 2018 Mar;45(3):212-215.

        BACKGROUND: Lacking information on men who have sex with men (MSM) for most reported cases, sexually transmitted disease (STD) programs in the United States have used crude measures such as male-to-female case ratios (MFCR) as a rule of thumb to gauge MSM involvement at the local level, primarily with respect to syphilis cases in the past. Suitability of this measure for gonorrhea incidence has not previously been investigated. METHODS: A random sample of gonorrhea cases reported from January 2010 through June 2013 were interviewed in selected counties participating in the STD Surveillance Network to obtain gender of sex partners and history of transactional sex. Weighted estimates of proportion of cases among MSM and proportion reporting transactional sex were developed; correlation between MFCR and proportion MSM was assessed. RESULTS: Male-to-female case ratio ranged from 0.66 to 8.7, and the proportion of cases occurring among MSM varied from 2.5% to 62.3%. The MFCR was strongly correlated with proportion of cases among MSM after controlling for transactional sex (Pearson partial r = 0.754, P < 0.0001). CONCLUSIONS: Male-to-female case ratio for gonorrhea at the county level is a reliable proxy measure indicating MSM involvement in gonorrhea case incidence and should be used by STD programs to tailor their programmatic mix to include MSM-specific interventions.

      23. Family history of zoster and risk of developing herpes zosterExternal
        Tseng HF, Chi M, Hung P, Harpaz R, Schmid DS, LaRussa P, Sy LS, Luo Y, Holmquist K, Takhar H, Jacobsen SJ.
        Int J Infect Dis. 2018 Jan;66:99-106.

        BACKGROUND: Studies have investigated a possible association between family history of HZ and the occurrence of HZ. However, the results were inconclusive and susceptible to bias. We evaluated this association in an elderly population. METHODS: The matched case-control study conducted at Kaiser Permanente Southern California in 2012-2015 included 656 incident HZ patients >/=60 whose skin lesion tested positive for varicella zoster virus by polymerase chain reaction. Half of the HZ patients were vaccinated with zoster vaccine as achieved by stratified sampling. The controls were randomly selected and 1:1 matched to the cases on sex, age (+/-1year), and zoster vaccination (+/-3 months of the case’s vaccination date). Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: Having any blood relative with a history of HZ was associated with a slightly increased risk of HZ (adjusted OR=1.37, 95% CI 1.05-1.79). The adjusted OR associated with having one and two categories of first-degree blood relatives with a history of HZ was 1.30 (95% CI: 0.97-1.73) and 2.53 (95% CI: 1.17-5.44), respectively. CONCLUSIONS: Our results suggested a weak association between the development of HZ and a positive family history of HZ among the elderly population.

      24. Estimated rates of influenza-associated outpatient visits during 2001-2010 in 6 US integrated healthcare delivery organizationsExternal
        Zhou H, Thompson WW, Belongia EA, Fowlkes A, Baxter R, Jacobsen SJ, Jackson ML, Glanz JM, Naleway AL, Ford DC, Weintraub E, Shay DK.
        Influenza Other Respir Viruses. 2018 Jan;12(1):122-131.

        BACKGROUND: Population-based estimates of influenza-associated outpatient visits including both pandemic and interpandemic seasons are uncommon. Comparisons of such estimates with laboratory-confirmed rates of outpatient influenza are rare. OBJECTIVE: To estimate influenza-associated outpatient visits in 6 US integrated healthcare delivery organizations enrolling ~7.7 million persons. METHODS: Using negative binomial regression methods, we modeled rates of influenza-associated visits with ICD-9-CM-coded pneumonia or acute respiratory outpatient visits during 2001-10. These estimated counts were added to visits coded specifically for influenza to derive estimated rates. We compared these rates with those observed in 2 contemporaneous studies recording RT-PCR-confirmed influenza outpatient visits. RESULTS: Outpatient rates estimated with pneumonia visits were 39 (95% confidence interval [CI], 30-70) and 203 (95% CI, 180-240) per 10 000 person-years, respectively, for interpandemic and pandemic seasons. Corresponding rates estimated with respiratory visits were 185 (95% CI, 161-255) and 542 (95% CI, 441-823) per 10 000 person-years. During the pandemic, children aged 2-17 years had the largest increase in rates (when estimated with pneumonia visits, from 64 [95% CI, 50-121] to 381 [95% CI, 366-481]). Rates estimated with pneumonia visits were consistent with rates of RT-PCR-confirmed influenza visits during 4 of 5 seasons in 1 comparison study. In another, rates estimated with pneumonia visits during the pandemic for children and adults were consistent in timing, peak, and magnitude. CONCLUSIONS: Estimated rates of influenza-associated outpatient visits were higher in children than adults during pre-pandemic and pandemic seasons. Rates estimated with pneumonia visits plus influenza-coded visits were similar to rates from studies using RT-PCR-confirmed influenza.

    • Disaster Control and Emergency Services
      1. Use of influenza risk assessment tool for prepandemic preparednessExternal
        Burke SA, Trock SC.
        Emerg Infect Dis. 2018 Mar;24(3):471-477.

        In 2010, the Centers for Disease Control and Prevention began to develop an Influenza Risk Assessment Tool (IRAT) to methodically capture and assess information relating to influenza A viruses not currently circulating among humans. The IRAT uses a multiattribute, additive model to generate a summary risk score for each virus. Although the IRAT is not intended to predict the next pandemic influenza A virus, it has provided input into prepandemic preparedness decisions.

    • Disease Reservoirs and Vectors
      1. Neutralizing antibodies against flaviviruses, Babanki virus, and Rift Valley fever virus in Ugandan batsExternal
        Kading RC, Kityo RM, Mossel EC, Borland EM, Nakayiki T, Nalikka B, Nyakarahuka L, Ledermann JP, Panella NA, Gilbert AT, Crabtree MB, Peterhans JK, Towner JS, Amman BR, Sealy TK, Nichol ST, Powers AM, Lutwama JJ, Miller BR.
        Infect Ecol Epidemiol. 2018 ;8(1):1439215.

        Introduction: A number of arboviruses have previously been isolated from naturally-infected East African bats, however the role of bats in arbovirus maintenance is poorly understood. The aim of this study was to investigate the exposure history of Ugandan bats to a panel of arboviruses. Materials and methods: Insectivorous and fruit bats were captured from multiple locations throughout Uganda during 2009 and 2011-2013. All serum samples were tested for neutralizing antibodies against West Nile virus (WNV), yellow fever virus (YFV), dengue 2 virus (DENV-2), Zika virus (ZIKV), Babanki virus (BBKV), and Rift Valley fever virus (RVFV) by plaque reduction neutralization test (PRNT). Sera from up to 626 bats were screened for antibodies against each virus. Results and Discussion: Key findings include the presence of neutralizing antibodies against RVFV in 5/52 (9.6%) of little epauletted fruit bats (Epomophorus labiatus) captured from Kawuku and 3/54 (5.6%) Egyptian rousette bats from Kasokero cave. Antibodies reactive to flaviviruses were widespread across bat taxa and sampling locations. Conclusion: The data presented demonstrate the widespread exposure of bats in Uganda to arboviruses, and highlight particular virus-bat associations that warrant further investigation.

    • Environmental Health
      1. Early life Triclosan exposure and child adiposity at 8 years of age: a prospective cohort studyExternal
        Kalloo G, Calafat AM, Chen A, Yolton K, Lanphear BP, Braun JM.
        Environ Health. 2018 Mar 5;17(1):24.

        BACKGROUND: Triclosan is an antimicrobial agent that may affect the gut microbiome and endocrine system to influence adiposity. However, little data from prospective studies examining prenatal and childhood exposures exist. We investigated the relationship between multiple, prospective early life measure of triclosan exposure and child adiposity. METHODS: In a prospective cohort of 220 mother-child pairs from Cincinnati, OH (enrolled 2003-2006), we quantified triclosan in urine samples collected twice during pregnancy, annually from 1 to 5 years of age, and once at 8 years. We assessed child adiposity at age 8 years using body mass index (BMI), waist circumference, and bioelectric impedance. We estimated covariate-adjusted associations of child adiposity with a 10-fold increase in average prenatal, average early childhood (average of 1-5 years), and 8-year triclosan concentrations. RESULTS: Among all children, there was no association between triclosan and child adiposity. While urinary triclosan concentrations at all three time periods were weakly, imprecisely, and inversely associated with all three measures of adiposity among girls, these associations did not differ significantly from those in boys (sex x triclosan p-values> 0.35). Among girls, the strongest associations were generally observed for prenatal triclosan when we adjusted for all three triclosan concentrations and covariates in the same model; BMI z-score (beta: -0.13; 95% CI: -0.42, 0.15), waist circumference (beta: – 1.7 cm; 95% CI: -4.2, 0.7), and percent body fat (beta :-0.6; 95% CI: -2.7, 1.3). In contrast, the associations between triclosan concentrations and adiposity measures were inconsistent among boys. CONCLUSION: We did not observe evidence of an association of repeated urinary triclosan concentrations during pregnancy and childhood with measures of child adiposity at age 8 years in this cohort.

      2. We report longitudinal serum concentrations of select persistent organic pollutants (POPs) in children at ages 7 and 9 years and in their mothers prenatally and again when the children were 9 years old. The participating families were enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal birth cohort study of low-income Hispanic families residing in the Salinas Valley, California. We observed decreasing concentrations in the mothers with year of serum collection (2009 vs 2011) for six out of seven polybrominated diphenyl ether (PBDE) congeners and for 2,2′,4,4′,5-pentachlorobiphenyl (CB-99; p < 0.05). The 9-year-old children had similarly decreasing serum concentrations of all seven PBDE congeners, CB-99, and 2,2′,3,4,4′,5′- and 2,3,3′,4,4′,6-hexachlorobiphenyl (CB-138/158) with year of serum collection (2009 vs 2011; p < 0.05). In mixed effect models accounting for weight gain as the children aged from 7 to 9 years, we observed an annual decrease (-8.3% to -13.4%) in tri- to hexaBDE concentrations (p < 0.001), except for 2,2′,3,4,4′-tetrabromodiphenyl ether (BDE-85) and 2,2′,4,4′,5,5′-hexabromodiphenyl ether (BDE-153). The concentrations of these congeners were not associated with time of serum collection and instead showed an -0.9% to -2.6% decrease per kilogram of weight gain during the study period (p < 0.05). In the case of tetra- to heptachlorobiphenyls, we observed -0.5% to -0.7% decrease in serum concentration per kilogram of weight gain (p < 0.05) and -3.0% to -3.7% decrease in serum concentration per year of aging (p < 0.05), except for 2,3′,4,4′,5-pentachlorobiphenyl (CB-118) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153), which were not associated with time of serum draw. 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p’-DDE) decreased -2.4%/kg of weight gain between the two sampling points (p < 0.001). These findings suggest that as children grow, dilution in a larger body size plays an important role in explaining reductions in body burden in the case of traditional POPs such as PCBs and p,p’-DDE. By contrast, in the case of PBDEs, reductions are likely explained by reduction in exposure, as illustrated by decreased concentrations in more recent years, possibly amplified by presumed shorter biological half-life than other POPs.

    • Food Safety
      1. Food safety practices linked with proper refrigerator temperatures in retail delisExternal
        Brown LG, Hoover ER, Faw BV, Hedeen NK, Nicholas D, Wong MR, Shepherd C, Gallagher DL, Kause JR.
        Foodborne Pathog Dis. 2018 Mar 2.

        Listeria monocytogenes (L. monocytogenes) causes the third highest number of foodborne illness deaths annually. L. monocytogenes contamination of sliced deli meats at the retail level is a significant contributing factor to L. monocytogenes illness. The Centers for Disease Control and Prevention’s Environmental Health Specialists Network (EHS-Net) conducted a study to learn more about retail delis’ practices concerning L. monocytogenes growth and cross-contamination prevention. This article presents data from this study on the frequency with which retail deli refrigerator temperatures exceed 41 degrees F, the Food and Drug Administration (FDA)-recommended maximum temperature for ready-to-eat food requiring time and temperature control for safety (TCS) (such as retail deli meat). This provision was designed to control bacterial growth in TCS foods. This article also presents data on deli and staff characteristics related to the frequency with which retail delis refrigerator temperatures exceed 41 degrees F. Data from observations of 445 refrigerators in 245 delis showed that in 17.1% of delis, at least one refrigerator was >41 degrees F. We also found that refrigeration temperatures reported in this study were lower than those reported in a related 2007 study. Delis with more than one refrigerator, that lacked refrigerator temperature recording, and had a manager who had never been food safety certified had greater odds of having a refrigerator temperature >41 degrees F. The data from this study suggest that retail temperature control is improving over time. They also identify a food safety gap: some delis have refrigerator temperatures that exceed 41 degrees F. We also found that two food safety interventions were related to better refrigerated storage practices: kitchen manager certification and recording refrigerated storage temperatures. Regulatory food safety programs and the retail industry may wish to consider encouraging or requiring kitchen manager certification and recording refrigerated storage temperatures.

      2. Notes from the Field: Brucella abortus vaccine strain RB51 infection and exposures associated with raw milk consumption – Wise County, Texas, 2017External
        Cossaboom CM, Kharod GA, Salzer JS, Tiller RV, Campbell LP, Wu K, Negron ME, Ayala N, Evert N, Radowicz J, Shuford J, Stonecipher S.
        MMWR Morb Mortal Wkly Rep. 2018 Mar 9;67(9):286.

        [No abstract]

    • Genetics and Genomics
      1. Expansion of a urethritis-associated Neisseria meningitidis clade in the United States with concurrent acquisition of N. gonorrhoeae allelesExternal
        Retchless AC, Kretz CB, Chang HY, Bazan JA, Abrams AJ, Norris Turner A, Jenkins LT, Trees DL, Tzeng YL, Stephens DS, MacNeil JR, Wang X.
        BMC Genomics. 2018 Mar 2;19(1):176.

        BACKGROUND: Increased reports of Neisseria meningitidis urethritis in multiple U.S. cities during 2015 have been attributed to the emergence of a novel clade of nongroupable N. meningitidis within the ST-11 clonal complex, the “U.S. NmNG urethritis clade”. Genetic recombination with N. gonorrhoeae has been proposed to enable efficient sexual transmission by this clade. To understand the evolutionary origin and diversification of the U.S. NmNG urethritis clade, whole-genome phylogenetic analysis was performed to identify its members among the N. meningitidis strain collection from the Centers for Disease Control and Prevention, including 209 urogenital and rectal N. meningitidis isolates submitted by U.S. public health departments in eleven states starting in 2015. RESULTS: The earliest representatives of the U.S. NmNG urethritis clade were identified from cases of invasive disease that occurred in 2013. Among 209 urogenital and rectal isolates submitted from January 2015 to September 2016, the clade accounted for 189/198 male urogenital isolates, 3/4 female urogenital isolates, and 1/7 rectal isolates. In total, members of the clade were isolated in thirteen states between 2013 and 2016, which evolved from a common ancestor that likely existed during 2011. The ancestor contained N. gonorrhoeae-like alleles in three regions of its genome, two of which may facilitate nitrite-dependent anaerobic growth during colonization of urogenital sites. Additional gonococcal-like alleles were acquired as the clade diversified. Notably, one isolate contained a sequence associated with azithromycin resistance in N. gonorrhoeae, but no other gonococcal antimicrobial resistance determinants were detected. CONCLUSIONS: Interspecies genetic recombination contributed to the early evolution and subsequent diversification of the U.S. NmNG urethritis clade. Ongoing acquisition of N. gonorrhoeae alleles by the U.S. NmNG urethritis clade may facilitate the expansion of its ecological niche while also increasing the frequency with which it causes urethritis.

    • Health Economics
      1. Medical costs of fatal and nonfatal falls in older adultsExternal
        Florence CS, Bergen G, Atherly A, Burns E, Stevens J, Drake C.
        J Am Geriatr Soc. 2018 Mar 7.

        OBJECTIVES: To estimate medical expenditures attributable to older adult falls using a methodology that can be updated annually to track these expenditures over time. DESIGN: Population data from the National Vital Statistics System (NVSS) and cost estimates from the Web-based Injury Statistics Query and Reporting System (WISQARS) for fatal falls, quasi-experimental regression analysis of data from the Medicare Current Beneficiaries Survey (MCBS) for nonfatal falls. SETTING: U.S. population aged 65 and older during 2015. PARTICIPANTS: Fatal falls from the 2015 NVSS (N=28,486); respondents to the 2011 MCBS (N=3,460). MEASUREMENTS: Total spending attributable to older adult falls in the United States in 2015, in dollars. RESULTS: In 2015, the estimated medical costs attributable to fatal and nonfatal falls was approximately $50.0 billion. For nonfatal falls, Medicare paid approximately $28.9 billion, Medicaid $8.7 billion, and private and other payers $12.0 billion. Overall medical spending for fatal falls was estimated to be $754 million. CONCLUSION: Older adult falls result in substantial medical costs. Measuring medical costs attributable to falls will provide vital information about the magnitude of the problem and the potential financial effect of effective prevention strategies.

    • Healthcare Associated Infections
      1. Organ donor screening practices for Strongyloides stercoralis infection among US organ procurement organizationsExternal
        Abanyie FA, Valice E, Delli Carpini KW, Gray EB, McAuliffe I, Chin-Hong PV, Handali S, Montgomery SP, Huprikar S.
        Transpl Infect Dis. 2018 Mar 7.

        BACKGROUND: Targeted donor screening for strongyloidiasis performed at the time of organ procurement can prevent this life-threatening donor-derived infection. METHOD: The Association of Organ Procurement Organizations surveyed members to determine the number of U.S. organ procurement organizations (OPOs) performing donor screening for Strongyloides infection and their screening practices. RESULTS: All 58 OPOs responded to the survey. Only six (10%) currently screen donors for strongyloidiasis; most OPOs started 6-36 months before the survey, one started 6 years prior. All used risk-based criteria to determine which donors to screen, though the criteria varied among OPOs. A median of 56 donors have been screened at each OPO since initiating their screening programs, with a median of two infected donors (range: 0-13) identified. Overall, 53 organs have been transplanted from 22 infected donors, including hearts, lungs, kidneys, and livers. Of 52 OPOs not currently screening, 20 had considered screening and one plans to start screening in the near future. Of those considering risk-based screening, most had not decided on the criteria. Uncertainty about the benefits of and guidelines for screening, and misconceptions about the interpretation of test results were concerns shared by non-screening OPOs. CONCLUSION: Continued education and advocacy on the importance of targeted donor screening is needed. This article is protected by copyright. All rights reserved.

      2. Update: Dura mater graft-associated Creutzfeldt-Jakob disease – Japan, 1975-2017External
        Ae R, Hamaguchi T, Nakamura Y, Yamada M, Tsukamoto T, Mizusawa H, Belay ED, Schonberger LB.
        MMWR Morb Mortal Wkly Rep. 2018 Mar 9;67(9):274-278.

        Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder that, according to the most well accepted hypothesis (1), is caused by replicating, transmissible, abnormal forms of a host-encoded prion protein (prions). Most CJD cases occur spontaneously (sporadic CJD) or are inherited (genetic CJD). Iatrogenic CJD can occur after exposure to prion-contaminated instruments or products in medical/surgical settings. Cadaveric dura mater graft-associated CJD (dCJD) accounts for a common form of iatrogenic CJD. This report summarizes the epidemiologic features of 154 cases of dCJD identified in Japan during 1975-2017; these cases account for >60% of dCJD cases reported worldwide (1,2). The unusually high prevalence of dCJD in Japan was first reported in 1997 (3). In 2008, a single brand of graft (Lyodura [B. Braun Melsungen AG, Melsungen, Germany]), frequently used as a patch in neurosurgical procedures, was identified as the probable vehicle of transmission (4). No international recall of the implicated Lyodura occurred, the product had a relatively long shelf life, and the grafts were used frequently in Japanese patients with non-life-threatening conditions (4,5). Since 2008, additional cases have been ascertained, reflecting the identification of previously missed cases and the occurrence of new cases with longer latency periods (interval from exposure to symptom onset) for dCJD (up to 30 years), underscoring the importance of maintaining surveillance for dCJD.

      3. Cytomegalovirus infections in lung and hematopoietic cell transplant recipients in the Organ Transplant Infection Prevention and Detection (OTIP) Study: a multi-year, multi-center prospective cohort studyExternal
        Avery RK, Silveira FP, Benedict K, Cleveland AA, Kauffman CA, Schuster MG, Dubberke ER, Husain S, Paterson D, Chiller T, Pappas P.
        Transpl Infect Dis. 2018 Mar 7.

        BACKGROUND: Most studies of post-transplant CMV infection have focused on either solid organ or hematopoietic cell transplant (HCT) recipients. A large prospective cohort study involving both lung and HCT recipients provided an opportunity to compare the epidemiology and outcomes of CMV infections in these two groups. METHODS: Patients were followed for 30 months in a 6-center prospective cohort study. Data on demographics, CMV infections, tissue-invasive disease, recurrences, rejection, and immunosuppression were recorded. RESULTS: The overall incidence of CMV infection was 83/293 (28.3%) in the lung transplant group and 154/444 (34.7%) in the HCT group (p = 0.0706). Tissue-invasive CMV disease occurred in 8/83 (9.6%) of lung and 6/154 (3.9%) of HCT recipients with CMV infection, respectively (p=0.087). Median time to CMV infection was longer in the lung transplant group (236 vs. 40 days, p < 0.0001), likely reflecting the effects of prophylaxis vs. pre-emptive therapy. Total IgG levels of < 350 mg/dl in lung recipients and graft versus host disease (GvHD) in HCT recipients were associated with increased CMV risk. HCT recipients had a higher mean number of CMV episodes (p=0.008), although duration of viremia was not significantly different between the two groups. CMV infection was not associated with reduced overall survival in either group. CONCLUSIONS: Current CMV prevention strategies have resulted in a low incidence of tissue-invasive disease in both lung transplant and HCT, although CMV viremia is still relatively common. Differences between the lung and HCT groups in terms of time to CMV and recurrences of CMV viremia likely reflect differences in underlying host immunobiology and in CMV prevention strategies in the modern era. This article is protected by copyright. All rights reserved.

    • Immunity and Immunization
      1. Successful use of interventions in combination to improve human papillomavirus vaccination coverage rates among adolescents – Chicago, 2013 to 2015External
        Choi N, Curtis CR, Loharikar A, Fricchione M, Jones E, Balzer E, Liu Y, Levin M, Chavez-Torres M, Morita J, Caskey R.
        Acad Pediatr. 2018 Mar;18(2s):S93-s100.

        In 2013, National Immunization Survey-Teen data indicated that >40% of female adolescents had not initiated the human papillomavirus (HPV) vaccine series and >60% had not completed the series, documenting vaccination rates much lower than those for other vaccines recommended for adolescents. The Chicago Department of Public Health (CDPH) was 1 of 22 jurisdictions nationwide to receive a Prevention and Public Health Fund award through the Centers for Disease Control and Prevention to improve HPV vaccination rates among adolescents. The CDPH implemented 5 interventions targeting the public, clinicians and their staff, and diverse immunization and cancer prevention stakeholders. Compared with 2013 jurisdiction-specific HPV vaccination rates among all adolescents, Chicago’s HPV vaccination rates were increased significantly in 2014 and 2015. This article details the methods and results of Chicago’s successful interventions, the particular strengths as well as barriers encountered, and future steps necessary for sustaining improvement.

      2. Effect of a health care professional communication training intervention on adolescent human papillomavirus vaccination: A cluster randomized clinical trialExternal
        Dempsey AF, Pyrznawoski J, Lockhart S, Barnard J, Campagna EJ, Garrett K, Fisher A, Dickinson LM, O’Leary ST.
        JAMA Pediatr. 2018 Mar 5:e180016.

        Importance: The incidence of human papillomavirus (HPV)-related cancers is more than 35000 cases in the United States each year. Effective HPV vaccines have been available in the United States for several years but are underused among adolescents, the target population for vaccination. Interventions to increase uptake are needed. Objective: To evaluate the effect of a 5-component health care professional HPV vaccine communication intervention on adolescent HPV vaccination. Design, Setting, and Participants: A cluster randomized clinical trial using covariate-constrained randomization to assign study arms and an intent-to-treat protocol was conducted in 16 primary care practices in the Denver, Colorado, metropolitan area. Participants included 188 medical professionals and 43132 adolescents. Interventions: The 5 components of the intervention were an HPV fact sheet library to create customized information sheets relevant to each practice’s patient population, a tailored parent education website, a set of HPV-related disease images, an HPV vaccine decision aid, and 2(1/2) hours of communication training on using a presumptive vaccine recommendation, followed by motivational interviewing if parents were resistant to vaccination. Each practice participated in a series of 2 intervention development meetings over a 6-month period (August 1, 2014, to January 31, 2015) before the intervention. Main Outcomes and Measures: Differences between control and intervention changes over time (ie, difference in differences between the baseline and intervention period cohorts of patients) in HPV vaccine series initiation (>/=1 dose) and completion (>/=3 doses) among patients aged 11 to 17 years seen at the practices between February 1, 2015, and January 31, 2016. Vaccination data were obtained from the practices’ records and augmented with state immunization information system data. Results: Sixteen practices and 43132 patients (50.3% female; median age, 12.6 years [interquartile range, 10.8-14.7 years] at the beginning of the study period) participated in this trial. Adolescents in the intervention practices had significantly higher odds of HPV vaccine series initiation (adjusted odds ratio [aOR], 1.46; 95% CI, 1.31-1.62) and completion (aOR, 1.56; 95% CI, 1.27-1.92) than those in the control practices (a 9.5-absolute percentage point increase in HPV vaccine series initiation and a 4.4-absolute percentage point increase in HPV vaccine series completion in intervention practices). The intervention had a greater effect in pediatric practices compared with family medicine practices and in private practices compared with public ones. Health care professionals reported that communication training and the fact sheets were the most used and useful intervention components. Conclusions and Relevance: A health care professional communication intervention significantly improved HPV vaccine series initiation and completion among adolescent patients. Trial Registration: clinicaltrials.gov Identifier: NCT02456077.

      3. Protecting healthcare personnel in outpatient settings: The influence of mandatory versus nonmandatory influenza vaccination policies on workplace absenteeism during multiple respiratory virus seasonsExternal
        Frederick J, Brown AC, Cummings DA, Gaydos CA, Gibert CL, Gorse GJ, Los JG, Nyquist AC, Perl TM, Price CS, Radonovich LJ, Reich NG, Rodriguez-Barradas MC, Bessesen MT, Simberkoff MS.
        Infect Control Hosp Epidemiol. 2018 Mar 8:1-10.

        OBJECTIVE To determine the effect of mandatory and nonmandatory influenza vaccination policies on vaccination rates and symptomatic absenteeism among healthcare personnel (HCP). DESIGN Retrospective observational cohort study. SETTING This study took place at 3 university medical centers with mandatory influenza vaccination policies and 4 Veterans Affairs (VA) healthcare systems with nonmandatory influenza vaccination policies. PARTICIPANTS The study included 2,304 outpatient HCP at mandatory vaccination sites and 1,759 outpatient HCP at nonmandatory vaccination sites. METHODS To determine the incidence and duration of absenteeism in outpatient settings, HCP participating in the Respiratory Protection Effectiveness Clinical Trial at both mandatory and nonmandatory vaccination sites over 3 viral respiratory illness (VRI) seasons (2012-2015) reported their influenza vaccination status and symptomatic days absent from work weekly throughout a 12-week period during the peak VRI season each year. The adjusted effects of vaccination and other modulating factors on absenteeism rates were estimated using multivariable regression models. RESULTS The proportion of participants who received influenza vaccination was lower each year at nonmandatory than at mandatory vaccination sites (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.07-0.11). Among HCP who reported at least 1 sick day, vaccinated HCP had lower symptomatic days absent compared to unvaccinated HCP (OR for 2012-2013 and 2013-2014, 0.82; 95% CI, 0.72-0.93; OR for 2014-2015, 0.81; 95% CI, 0.69-0.95). CONCLUSIONS These data suggest that mandatory HCP influenza vaccination policies increase influenza vaccination rates and that HCP symptomatic absenteeism diminishes as rates of influenza vaccination increase. These findings should be considered in formulating HCP influenza vaccination policies. Infect Control Hosp Epidemiol 2018;1-10.

      4. Association between estimated cumulative vaccine antigen exposure through the first 23 months of life and non-vaccine-targeted infections from 24 through 47 months of ageExternal
        Glanz JM, Newcomer SR, Daley MF, DeStefano F, Groom HC, Jackson ML, Lewin BJ, McCarthy NL, McClure DL, Narwaney KJ, Nordin JD, Zerbo O.
        Jama. 2018 Mar 6;319(9):906-913.

        Importance: Some parents are concerned that multiple vaccines in early childhood could weaken their child’s immune system. Biological data suggest that increased vaccine antigen exposure could increase the risk for infections not targeted by vaccines. Objective: To examine estimated cumulative vaccine antigen exposure through the first 23 months of life in children with and without non-vaccine-targeted infections from 24 through 47 months of age. Design, Setting, and Participants: A nested case-control study was conducted in 6 US health care organizations participating in the Vaccine Safety Datalink. Cases were identified by International Classification of Diseases codes for infectious diseases in the emergency department and inpatient medical settings and then validated by medical record review. Cases of non-vaccine-targeted infection were matched to controls by age, sex, health care organization site, and chronic disease status. Participants were children ages 24 through 47 months, born between January 1, 2003, and September 31, 2013, followed up until December 31, 2015. Exposures: Cumulative vaccine antigen exposure, estimated by summing the number of antigens in each vaccine dose received from birth through age 23 months. Main Outcomes and Measures: Non-vaccine-targeted infections, including upper and lower respiratory infections and gastrointestinal infections, from 24 through 47 months of age, and the association between these infections and estimated cumulative vaccine exposure from birth through 23 months. Conditional logistic regression was used to estimate matched odds ratios representing the odds of non-vaccine-targeted infections for every 30-unit increase in estimated cumulative number of antigens received. Results: Among the 944 patients (193 cases and 751 controls), the mean (SD) age was 32.5 (6.3) months, 422 (45%) were female, and 61 (7%) had a complex chronic condition. Through the first 23 months, the estimated mean (SD) cumulative vaccine antigen exposure was 240.6 (48.3) for cases and 242.9 (51.1) for controls. The between-group difference for estimated cumulative antigen exposure was -2.3 (95% CI, -10.1 to 5.4; P = .55). Among children with vs without non-vaccine-targeted infections from 24 through 47 months of age, the matched odds ratio for estimated cumulative antigen exposure through age 23 months was not significant (matched odds ratio, 0.94; 95% CI, 0.84 to 1.07). Conclusions and Relevance: Among children from 24 through 47 months of age with emergency department and inpatient visits for infectious diseases not targeted by vaccines, compared with children without such visits, there was no significant difference in estimated cumulative vaccine antigen exposure through the first 23 months of life.

      5. Seroprevalence of anti-polio antibodies in children from polio high risk area of Afghanistan: A cross sectional survey 2017External
        Hussain I, Mach O, Hamid NA, Bhatti ZS, Moore DD, Oberste MS, Khan S, Khan H, Weldon WC, Sutter RW, Bhutta ZA, Soofi SB.
        Vaccine. 2018 Mar 3.

        BACKGROUND: Afghanistan is one of the remaining wild-poliovirus (WPV) endemic countries. We conducted a seroprevalence survey of anti-poliovirus antibodies in Kandahar Province. METHODS: Children in two age groups (6-11months and 36-48months) visiting Mirwais hospital in Kandahar for minor ailments unrelated to polio were enrolled. After obtaining informed consent, we collected venous blood and conducted neutralization assay to detect poliovirus neutralizing antibodies. RESULTS: A total of 420 children were enrolled and 409/420 (97%) were analysed. Seroprevalence to poliovirus type 1 (PV1) was 97% and 100% in the younger and older age groups respectively; it was 71% and 91% for PV2; 93% and 98% for PV3. Age group (RR=3.6, CI 95%=2.2-5.6) and place of residence outside of Kandahar city (RR=1.8, CI 95%=1.2-2.6) were found to be significant risk factors for seronegativity. CONCLUSIONS: The polio eradication program in Kandahar achieved high serological protection, especially against PV1 and PV3. Lower PV2 seroprevalence in the younger age group is a result of a withdrawal of live type 2 vaccine in 2016 and is expected. Ability to reach all children with poliovirus vaccines is a pre-requisite for achieving poliovirus eradication.

      6. Human papillomavirus vaccine coverage and prevalence of missed opportunities for vaccination in an integrated healthcare systemExternal
        Irving SA, Groom HC, Stokley S, McNeil MM, Gee J, Smith N, Naleway AL.
        Acad Pediatr. 2018 Mar;18(2s):S85-s92.

        BACKGROUND: Human papillomavirus (HPV) vaccination has been recommended in the United States for female and male adolescents since 2006 and 2011, respectively. Coverage rates are lower than those for other adolescent vaccines. The objective of this study was to evaluate an assessment and feedback intervention designed to increase HPV vaccination coverage and quantify missed opportunities for HPV vaccine initiation at preventive care visits. METHODS: We examined changes in HPV vaccination coverage and missed opportunities within the adolescent (11-17 years) population at 9 Oregon-based Kaiser Permanente Northwest outpatient clinics after an assessment and feedback intervention. Quarterly coverage rates were calculated for the adolescent populations at the clinics, according to age group (11-12 and 13-17 years), sex, and department (Pediatrics and Family Medicine). Comparison coverage assessments were calculated at 3 nonintervention (control) clinics. Missed opportunities for HPV vaccine initiation, defined as preventive care visits in which a patient eligible for HPV dose 1 remained unvaccinated, were examined according to sex and age group. RESULTS: An average of 29,021 adolescents were included in coverage assessments. Before the intervention, 1-dose and 3-dose quarterly coverage rates were increasing at intervention as well as at control clinics in both age groups. Postimplementation quarterly trends in 1-dose or 3-dose coverage did not differ significantly between intervention and control clinics for either age group. One-dose coverage rates among adolescents with Pediatrics providers were significantly higher than those with Family Medicine providers (56% vs 41% for 11- to 12-year-old and 82% vs 69% for 13- to 17-year-old girls; 55% vs 40% for 11- to 12-year-old and 78% vs 62% for 13- to 17-year-old boys). CONCLUSIONS: No significant differences in HPV vaccine coverage were identified at intervention clinics. However, coverage rates were increasing before the start of the intervention and might have been influenced by ongoing health system best practices. HPV vaccine coverage rates varied significantly according to department, which could allow for targeted improvement opportunities.

      7. Ten years of human papillomavirus vaccination in the United StatesExternal
        Markowitz LE, Gee J, Chesson H, Stokley S.
        Acad Pediatr. 2018 Mar;18(2s):S3-s10.

        Since human papillomavirus (HPV) vaccine was first introduced for females in the United States in 2006, vaccination policy has evolved as additional HPV vaccines were licensed and new data became available. The United States adopted a gender neutral routine HPV immunization policy in 2011, the first country to do so. Vaccination coverage is increasing, although it remains lower than for other vaccines recommended for adolescents. There are various reasons for low coverage, and efforts are ongoing to increase vaccine uptake. The safety profile of HPV vaccine has been well established from 10 years of postlicensure monitoring. Despite low coverage, the early effects of the HPV vaccination program have exceeded expectations.

      8. Advancing human papillomavirus vaccine delivery: 12 priority research gapsExternal
        Reiter PL, Gerend MA, Gilkey MB, Perkins RB, Saslow D, Stokley S, Tiro JA, Zimet GD, Brewer NT.
        Acad Pediatr. 2018 Mar;18(2s):S14-s16.

        [No abstract]

      9. The end of human papillomavirus vaccine exceptionalismExternal
        Schuchat A.
        Acad Pediatr. 2018 Mar;18(2s):S17-s18.

        [No abstract]

      10. Improving human papillomavirus vaccination in the united states: Executive summaryExternal
        Stokley S, Szilagyi PG.
        Acad Pediatr. 2018 Mar;18(2s):S1-s2.

        [No abstract]

    • Injury and Violence
      1. Risk factors for unsafe behaviors toward grenades among rural populations affected by explosive devices in ColombiaExternal
        Boyd AT, Becknell K, Russell S, Blanton C, Cookson ST, Bilukha OO, Anderson M.
        Confl Health. 2018 ;12:4.

        Background: Following decades of armed conflict, Colombia remains highly affected by explosive device (ED) contamination, especially in rural areas. Many victims are injured by EDs despite knowing their dangers. Determining risk factors for unsafe behaviors toward EDs, including grenades, is critical for preventing injuries. Methods: In 2012, CDC assisted Colombian partners in conducting a multi-stage knowledge, attitudes, and practices survey in rural ED-affected areas. Within each of 40 clusters, 28 households were selected, and participants aged 10 years or older were asked about behaviors toward EDs. Participants reported actual behaviors toward past EDs encountered and theoretical behaviors toward EDs not encountered. Behaviors were a priori classified as unsafe or safe. This analysis focuses on behaviors toward the most commonly encountered device, grenades. Results: Of 928 adult and 562 child participants, 488 (52.5%) adults and 249 (43.9%) children encountered ED, while 121 (13.7%) adults and 148 (26.9%) children received mine risk education (MRE). Among the 430 (46.7%) adults who encountered grenades, 113 (25.7%) reported unsafe behaviors; multivariable analysis showed that unsafe behavior was associated with working outdoors (adjusted odds ratio [aOR]: 1.7, 95% confidence interval [CI]: 1.1-2.7). Among the 429 (46.5%) adults who did not encounter ED, 61 (14.6%) described unsafe theoretical behaviors toward grenades; multivariable analysis showed that unsafe behavior was associated with older age (aOR: 1.02, 95% confidence limit [CL]: 1.00-1.05) and black or Afro-Colombian identity (aOR: 2.5, 95% CI 1.3-5.1). Among the 181 (32.0%) children who encountered grenades, 41 (23.8%) reported unsafe behaviors, while among the 311 (55.9%) children who did not encounter ED, 30 (10.2%) reported unsafe behavior. In both groups of children, multivariable analysis showed that unsafe behavior was associated with lower mean score on knowledge of ED, with aOR: 0.7, 95% CL: 0.6-0.9, and aOR: 0.8, 95% CL: 0.6-0.98, respectively. Conclusions: Participants reported frequent ED exposure but low receipt of MRE. Our findings should guide MRE improvement in ED-affected areas by strengthening the connection between ED knowledge and avoiding unsafe behavior, with a particular focus on people working outdoors. MRE should promote knowledge of ED risks but should also recognize socioeconomic factors that lead to engaging in unsafe behaviors.

      2. The Bully-Sexual Violence Pathway theory has indicated that bullying perpetration predicts sexual violence perpetration among males and females over time in middle school, and that homophobic name-calling perpetration moderates that association among males. In this study, the Bully-Sexual Violence Pathway theory was tested across early to late adolescence. Participants included 3549 students from four Midwestern middle schools and six high schools. Surveys were administered across six time points from Spring 2008 to Spring 2013. At baseline, the sample was 32.2% White, 46.2% African American, 5.4% Hispanic, and 10.2% other. The sample was 50.2% female. The findings reveal that late middle school homophobic name-calling perpetration increased the odds of perpetrating sexual violence in high school among early middle school bullying male and female perpetrators, while homophobic name-calling victimization decreased the odds of high school sexual violence perpetration among females. The prevention of bullying and homophobic name-calling in middle school may prevent later sexual violence perpetration.

      3. With the increasing popularity of mobile Internet devices, the exposure of adolescents to media has significantly increased. There is limited information about associations between the types and frequency of media use and experiences of violence victimization and suicide risk. The current study sought to examine the association of bullying and teen dating violence (TDV) victimization, suicide risk with different types of media use (i.e., television and computer/video game use), and number of total media use hours per school day. Data from the nationally representative 2015 Youth Risk Behavior Survey ( n = 15,624) were used to examine the association between media use and violence victimization and suicide risk. Logistic regression models generated prevalence ratios adjusted for demographic characteristics and substance use behaviors to identify significant associations between media use and victimization and suicide risk, stratified by gender. Media use was associated with TDV victimization for male students only, while media use was related to experiences of bullying and suicide risk for both male and female students. In addition, limited (2 or fewer hours) and excessive (5 or more hours) media use emerged as significant correlates of suicide risk and bullying victimization, with limited media use associated with decreased risk and excessive media use with increased risk. Comprehensive, cross-cutting efforts to prevent different forms of victimization should take into account media use and its potential association with adolescent victimization and suicide risk. The current study results suggest limiting adolescent media use, as part of comprehensive prevention programming, might relate to reductions in risk for victimization and suicide.

      4. Crime Prevention Through Environmental Design (CPTED) characteristics associated with violence and safety in middle schoolsExternal
        Vagi KJ, Stevens MR, Simon TR, Basile KC, Carter SP, Carter SL.
        J Sch Health. 2018 Apr;88(4):296-305.

        BACKGROUND: This study used a new Crime Prevention Through Environmental Design (CPTED) assessment tool to test the associations between physical attributes of schools and violence-related behaviors and perceptions of students. METHODS: Data were collected from 4717 students from 50 middle schools. Student perceptions of risk and safety, and violence were assessed. Evaluators used the CPTED School Assessment (CSA) to quantify how well the physical elements of each school correspond to ideal CPTED principles. Generalized linear mixed models were used to adjust for school- and student-level characteristics. RESULTS: Higher CSA scores were generally associated with higher perceptions of safety and lower levels of violence perpetration and perceived risk in unadjusted models. Higher CSA scores were also associated with lower odds of missing school because of safety concerns in most adjusted models, with significant adjusted odds ratios (AORs) ranging from 0.32 to 0.63. CSA scores for parking and bus loading areas also remained associated with higher perceived safety (AORs = 1.28 and 1.32, respectively) and lower perceived risk (AORs = 0.73 and 0.66, respectively) in adjusted models. CONCLUSIONS: The CSA is useful for assessing school environments that are associated with violence-related behaviors and perceptions. The CSA might help guide school environmental modifications to reduce violence.

    • Laboratory Sciences
      1. Importance of neutralizing monoclonal antibodies targeting multiple antigenic sites on MERS-CoV Spike to avoid neutralization escapeExternal
        Wang L, Shi W, Chappell JD, Joyce MG, Zhang Y, Kanekiyo M, Becker MM, van Doremalen N, Fischer R, Wang N, Corbett KS, Choe M, Mason RD, Van Galen JG, Zhou T, Saunders KO, Tatti KM, Haynes LM, Kwong PD, Modjarrad K, Kong WP, McLellan JS, Denison MR, Munster VJ, Mascola JR, Graham BS.
        J Virol. 2018 Mar 7.

        Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with approximately 35% mortality. The potential for a future pandemic originating from animal reservoirs or healthcare-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell-cloning strategy, we have identified and characterized multiple neutralizing mAbs specifically binding to the receptor binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques. RBD-specific mAbs tended to have greater neutralizing potency than non-RBD S1-specific mAbs. Six RBD-specific and five S1-specific mAbs could be sorted into four RBD and three non-RBD distinct binding patterns, based on competition assays, mapping neutralization escape variants, and structural analysis. We determined co-crystal structures for two mAbs targeting RBD from different angles and show they can only bind RBD in the “out” position. We then showed that selected RBD-specific, non-RBD S1, and S2-specific mAbs given prophylactically prevented MERS-CoV replication in lungs and protected mice from lethal challenge. Importantly, combining RBD- and non-RBD mAbs delayed the emergence of escape mutations in a cell-based virus-escape assay. These studies identify mAbs targeting different antigenic sites on S that will be useful for defining mechanisms of MERS-CoV neutralization, and for developing more effective interventions to prevent or treat MERS-CoV infections.IMPORTANCE: MERS-CoV causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutic options are currently available. Based on continuing exposure from established reservoirs in dromedary camels and bats, transmission of MERS-CoV into humans and future outbreaks are expected. Using structurally-defined probes for the MERS-CoV Spike (S) glycoprotein, the target for neutralizing antibodies, single B cells were sorted from a convalescent human and immunized non-human primates (NHPs). mAbs produced from paired immunoglobulin gene sequences were mapped to multiple epitopes within and outside the receptor-binding domain (RBD) and protected against lethal MERS infection in a murine model following passive immunization. Importantly, combining mAbs targeting distinct epitopes prevented viral neutralization escape from RBD-directed mAbs. These data suggest that antibody responses to multiple domains on CoV Spike may improve immunity and will guide future vaccine and therapeutic development efforts.

    • Maternal and Child Health
      1. Demographic and operational factors predicting study completion in a multisite case-control study of preschool childrenExternal
        Bradley CB, Browne EN, Alexander AA, Collins J, Dahm JL, DiGuiseppi CG, Levy SE, Moody EJ, Schieve LA, Windham GC, Young L, Daniels JL.
        Am J Epidemiol. 2018 Mar 1;187(3):592-603.

        Participant attrition can limit inferences drawn from study results and inflate research costs. We examined factors associated with completion of the Study to Explore Early Development (2007-2011), a multiple-component, case-control study of risk factors for autism spectrum disorder in preschoolers, conducted in California, Colorado, Georgia, Maryland, North Carolina, and Pennsylvania. Participants (n = 3,769) were asked to complete phone interviews, questionnaires, an in-person evaluation, and biologic sampling. We examined whether participant demographic and administrative factors predicted completion using mixed-effects logistic regression models. Completion of individual key study components was generally 70% or higher. However, 58% of families completed all per-protocol data elements (defined a priori as key study components). Per-protocol completion differed according to mother’s age, race, educational level, driving distance to clinic, number of contact attempts to enroll, and number of telephone numbers provided (all P < 0.05). Case status was not associated with completion, despite additional data collection for case-confirmation. Analysis of a subset that completed an early interview revealed no differences in completion by household factors of income, primary language spoken, number of adults, or number of children with chronic conditions. Differences in completion by race and education were notable and need to be carefully considered in developing future recruitment and completion strategies.

      2. Patient and provider determinants for receipt of three dimensions of respectful maternity care in Kigoma Region, Tanzania-April-July, 2016External
        Dynes MM, Twentyman E, Kelly L, Maro G, Msuya AA, Dominico S, Chaote P, Rusibamayila R, Serbanescu F.
        Reprod Health. 2018 Mar 5;15(1):41.

        BACKGROUND: Lack of respectful maternity care (RMC) is increasingly recognized as a human rights issue and a key deterrent to women seeking facility-based deliveries. Ensuring facility-based RMC is essential for improving maternal and neonatal health, especially in sub-Saharan African countries where mortality and non-skilled delivery care remain high. Few studies have attempted to quantitatively identify patient and delivery factors associated with RMC, and none has modeled the influence of provider characteristics on RMC. This study aims to help fill these gaps through collection and analysis of interviews linked between clients and providers, allowing for description of both patient and provider characteristics and their association with receipt of RMC. METHODS: We conducted cross-sectional surveys across 61 facilities in Kigoma Region, Tanzania, from April to July 2016. Measures of RMC were developed using 21-items in a Principal Components Analysis (PCA). We conducted multilevel, mixed effects generalized linear regression analyses on matched data from 249 providers and 935 post-delivery clients. The outcomes of interest included three dimensions of RMC-Friendliness/Comfort/Attention; Information/Consent; and Non-abuse/Kindness-developed from the first three components of PCA. Significance level was set at p < 0.05. RESULTS: Significant client-level determinants for perceived Friendliness/Comfort/Attention RMC included age (30-39 versus 15-19 years: Coefficient [Coef] 0.63; 40-49 versus 15-19 years: Coef 0.79) and self-reported complications (reported complications versus did not: Coef – 0.41). Significant provider-level determinants included perception of fair pay (Perceives fair pay versus unfair pay: Coef 0.46), cadre (Nurses/midwives versus Clinicians: Coef – 0.46), and number of deliveries in the last month (11-20 versus < 11 deliveries: Coef – 0.35). Significant client-level determinants for Information/Consent RMC included labor companionship (Companion versus none: Coef 0.37) and religiosity (Attends services at least weekly versus less often: Coef – 0.31). Significant provider-level determinants included perception of fair pay (Perceives fair pay versus unfair: Coef 0.37), weekly work hours (Coef 0.01), and age (30-39 versus 20-29 years: Coef – 0.34; 40-49 versus 20-29 years: Coef – 0.58). Significant provider-level determinants for Non-abuse/Kindness RMC included the predictors of age (age 50+ versus 20-29 years: Coef 0.34) and access to electronic mentoring (Access to two mentoring types versus none: Coef 0.37). CONCLUSIONS: These findings illustrate the value of including both client and provider information in the analysis of RMC. Strategies that address provider-level determinants of RMC (such as equitable pay, work environment, access to mentoring platforms) may improve RMC and subsequently address uptake of facility delivery.

    • Nutritional Sciences
      1. A longitudinal study of estrogen-responsive tissues and hormone concentrations in infants fed soy formulaExternal
        Adgent MA, Umbach DM, Zemel BS, Kelly A, Schall JI, Ford EG, James K, Darge K, Botelho JC, Vesper HW, Chandler DW, Nakamoto JM, Rogan WJ, Stallings VA.
        J Clin Endocrinol Metab. 2018 Mar 1.

        Purpose: Chemicals with hormone-like activity, such as estrogenic isoflavones, may perturb human development. Infants exclusively fed soy-based formula are highly exposed to isoflavones, but their physiologic responses remain uncharacterized. Here, we compare estrogen-responsive postnatal development in infants exclusively fed soy formula, cow-milk formula and breast milk. Methods: We enrolled 410 infants born in Philadelphia area hospitals, 2010-2013; 283 infants were exclusively fed soy formula (n=102), cow-milk formula (n=111), or breast milk (n=70) throughout the study (birth to 28 [boys] or 36 [girls] weeks). We repeatedly measured maturation index (MI) in vaginal and urethral epithelial cells using standard cytological methods, uterine volume and breast-bud diameter using ultrasound, serum estradiol and, in girls, follicle-stimulating hormone. We estimated MI, organ-growth and hormone trajectories by diet using mixed-effects regression splines. Results: Maternal demographics did not differ between cow-milk-fed and soy-fed infants but did differ between formula-fed and breastfed infants. Vaginal cell MI trended higher (p=0.01) and uterine volume decreased more slowly (p=0.01) in soy-fed girls compared to cow-milk-fed girls; however, their trajectories of breast-bud diameter and hormone concentrations did not differ. We observed no significant differences between boys fed cow-milk formula versus soy formula; estradiol was not detectable. Breastfed infants differed from soy-formula-fed infants in vaginal cell MI, uterine volume, girls’ estradiol and boys’ breast-bud diameter trajectories. Conclusions: Relative to cow-milk formula-fed girls, soy formula-fed girls demonstrated tissue and organ-level developmental trajectories consistent with response to exogenous estrogen exposure. Additional studies are needed to further evaluate the effects of soy on child development.

      2. Estimated 24-hour urinary sodium and potassium excretion in US adultsExternal
        Cogswell ME, Loria CM, Terry AL, Zhao L, Wang CY, Chen TC, Wright JD, Pfeiffer CM, Merritt R, Moy CS, Appel LJ.
        Jama. 2018 Mar 7.

        Importance: In 2010, the Institute of Medicine (now the National Academy of Medicine) recommended collecting 24-hour urine to estimate US sodium intake because previous studies indicated 90% of sodium consumed was excreted in urine. Objective: To estimate mean population sodium intake and describe urinary potassium excretion among US adults. Design, Setting, and Participants: In a nationally representative cross-sectional survey of the US noninstitutionalized population, 827 of 1103 (75%) randomly selected, nonpregnant participants aged 20 to 69 years in the examination component of the National Health and Nutrition Examination Survey (NHANES) collected at least one 24-hour urine specimen in 2014. The overall survey response rate for the 24-hour urine collection was approximately 50% (75% [24-hour urine component response rate] x 66% [examination component response rate]). Exposures: 24-hour collection of urine. Main Outcomes and Measures: Mean 24-hour urinary sodium and potassium excretion. Weighted national estimates of demographic and health characteristics and mean electrolyte excretion accounting for the complex survey design, selection probabilities, and nonresponse. Results: The study sample (n = 827) represented a population of whom 48.8% were men; 63.7% were non-Hispanic white, 15.8% Hispanic, 11.9% non-Hispanic black, and 5.6% non-Hispanic Asian; 43.5% had hypertension (according to 2017 hypertension guidelines); and 10.0% reported a diagnosis of diabetes. Overall mean 24-hour urinary sodium excretion was 3608 mg (95% CI, 3414-3803). The overall median was 3320 mg (interquartile range, 2308-4524). In secondary analyses by sex, mean sodium excretion was 4205 mg (95% CI, 3959-4452) in men (n = 421) and 3039 mg (95% CI, 2844-3234) in women (n = 406). By age group, mean sodium excretion was 3699 mg (95% CI, 3449-3949) in adults aged 20 to 44 years (n = 432) and 3507 mg (95% CI, 3266-3748) in adults aged 45 to 69 years (n = 395). Overall mean 24-hour urinary potassium excretion was 2155 mg (95% CI, 2030-2280); by sex, 2399 mg (95% CI, 2253-2545) in men and 1922 mg (95% CI, 1757-2086) in women; and by age, 1986 mg (95% CI, 1878-2094) in adults aged 20 to 44 years and 2343 mg (95% CI, 2151-2534) in adults aged 45 to 69 years. Conclusions and Relevance: In cross-sectional data from a 2014 sample of US adults, estimated mean sodium intake was 3608 mg per day. The findings provide a benchmark for future studies.

    • Occupational Safety and Health
      1. A descriptive study of musculoskeletal injuries in long-haul truck drivers: A NIOSH national surveyExternal
        Combs B, Heaton K, Raju D, Vance DE, Sieber WK.
        Workplace Health Saf. 2018 Mar 1:2165079917750935.

        Long-haul truck drivers are significantly affected by musculoskeletal injuries with incidence rates 3.5 times higher than the national average. Yet, little is known about injuries that affect long-haul trucks drivers. In 2010, interviewers collected data from 1,265 long-haul truck drivers at 32 truck stops across the United States. These surveys were analyzed to describe all self-reported musculoskeletal injuries. Injuries to the arm (26.3%) and back (21.1%) were the two areas most reported in the survey. Musculoskeletal injuries were most often caused by falls (38.9%) and contact with an object or equipment (33.7%) resulting most commonly in sprains/strains (60%). This large scale survey highlights the significance of musculoskeletal injuries in long-haul truck drivers and suggests the need to develop interventions to prevent injuries and improve recovery once injuries occur.

      2. Control banding tools for engineered nanoparticles: What the practitioner needs to knowExternal
        Dunn KH, Eastlake AC, Story M, Kuempel ED.
        Annals of Work Exposures and Health. 2018 :wxy002-wxy002.

        Control banding (CB) has been widely recommended for the selection of exposure controls for engineered nanomaterials (ENMs) in the absence of ENM-specific occupational exposure limits (OELs). Several ENM-specific CB strategies have been developed but have not been systematically evaluated. In this article, we identify the data inputs and compare the guidance provided by eight CB tools, evaluated on six ENMs, and assuming a constant handling/use scenario. The ENMs evaluated include nanoscale silica, titanium dioxide, silver, carbon nanotubes, graphene, and cellulose. Several of the tools recommended the highest level of exposure control for each of the ENMs in the evaluation, which was driven largely by the hazard banding. Dustiness was a factor in determining the exposure band in many tools, although most tools did not provide explicit guidance on how to classify the dustiness (high, medium, low), and published data are limited on this topic. The CB tools that recommended more diverse control options based on ENM hazard and dustiness data appear to be better equipped to utilize the available information, although further validation is needed by comparison to exposure measurements and OELs for a variety of ENMs. In all CB tools, local exhaust ventilation was recommended at a minimum to control exposures to ENMs in the workplace. Generally, the same or more stringent control levels were recommended by these tools compared with the OELs proposed for these ENMs, suggesting that these CB tools would generally provide prudent exposure control guidance, including when data are limited.

      3. Dental personnel treated for idiopathic pulmonary fibrosis at a tertiary care center – Virginia, 2000-2015External
        Nett RJ, Cummings KJ, Cannon B, Cox-Ganser J, Nathan SD.
        MMWR Morb Mortal Wkly Rep. 2018 Mar 9;67(9):270-273.

        In April 2016, a Virginia dentist who had recently received a diagnosis of idiopathic pulmonary fibrosis (IPF) and was undergoing treatment at a specialty clinic at a Virginia tertiary care center contacted CDC to report concerns that IPF had been diagnosed in multiple Virginia dentists who had sought treatment at the same specialty clinic. IPF is a chronic, progressive lung disease of unknown cause and associated with a poor prognosis (1). Although IPF has been associated with certain occupations (2), no published data exist regarding IPF in dentists. The medical records for all 894 patients treated for IPF at the Virginia tertiary care center during September 1996-June 2017 were reviewed for evidence that the patient had worked as a dentist, dental hygienist, or dental technician; among these patients, eight (0.9%) were identified as dentists and one (0.1%) as a dental technician, and each had sought treatment during 2000-2015. Seven of these nine patients had died. A questionnaire was administered to one of the living patients, who reported polishing dental appliances and preparing amalgams and impressions without respiratory protection. Substances used during these tasks contained silica, polyvinyl siloxane, alginate, and other compounds with known or potential respiratory toxicity. Although no clear etiologies for this cluster exist, occupational exposures possibly contributed. This cluster of IPF cases reinforces the need to understand further the unique occupational exposures of dental personnel and the association between these exposures and the risk for developing IPF so that appropriate strategies can be developed for the prevention of potentially harmful exposures.

      4. Effort-reward imbalance in police work: associations with the cortisol awakening responseExternal
        Violanti JM, Fekedulegn D, Gu JK, Allison P, Mnatsakanova A, Tinney-Zara C, Andrew ME.
        Int Arch Occup Environ Health. 2018 Mar 7.

        PURPOSE: We hypothesized that effort-reward imbalance (ERI) is associated with an atypical cortisol response. ERI has been associated with higher job stress. Stress triggers cortisol secretion via the hypothalamic-pituitary-adrenal (HPA) axis, and significant deviation from a typical cortisol pattern can indicate HPA axis dysfunction. METHODS: 176 police officers participated from the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) Study. ERI was the exposure variable. Outcome variables were saliva-based peak and mean cortisol values, total area under the curve ground (AUCG) and baseline (AUCI); linear regression line fitted to log-transformed cortisol. Regression analyses were used to examine linear trend between ERI and cortisol parameters. Repeated measures analysis examined whether the pattern of cortisol over time differed between low ERI (< median) and high ERI (>/= median). RESULTS: Mean age was 46 years (SD = 6.6). After adjustment for potential confounders, there was a significant inverse association between ERI and peak cortisol (beta = – 0.20, p = 0.009), average cortisol (beta = – 0.23, p = 0.003), and total area under the curve (beta = – 0.21, p = 0.009). ERI was not significantly associated with AUCI (beta = – 0.11, p = 0.214); slope of the regression line fitted to the cortisol profile (beta = – 0.009, p = 0.908). Repeated measures analyses showed that the cortisol pattern did not vary significantly between high and low ERI using the median as a cut point (interaction p value = 0.790). CONCLUSIONS: ERI was inversely associated with the magnitude of awakening cortisol over time, indicating HPA axis dysregulation and potential future health outcomes.

    • Parasitic Diseases
      1. Major threat to malaria control programs by Plasmodium falciparum lacking histidine-rich protein 2, EritreaExternal
        Berhane A, Anderson K, Mihreteab S, Gresty K, Rogier E, Mohamed S, Hagos F, Embaye G, Chinorumba A, Zehaie A, Dowd S, Waters NC, Gatton ML, Udhayakumar V, Cheng Q, Cunningham J.
        Emerg Infect Dis. 2018 Mar;24(3):462-470.

        False-negative results for Plasmodium falciparum histidine-rich protein (HRP) 2-based rapid diagnostic tests (RDTs) are increasing in Eritrea. We investigated HRP gene 2/3 (pfhrp2/pfhrp3) status in 50 infected patients at 2 hospitals. We showed that 80.8% (21/26) of patients at Ghindae Hospital and 41.7% (10/24) at Massawa Hospital were infected with pfhrp2-negative parasites and 92.3% (24/26) of patients at Ghindae Hospital and 70.8% (17/24) at Massawa Hospital were infected with pfhrp3-negative parasites. Parasite densities between pfhrp2-positive and pfhrp2-negative patients were comparable. All pfhrp2-negative samples had no detectable HRP2/3 antigen and showed negative results for HRP2-based RDTs. pfhrp2-negative parasites were genetically less diverse and formed 2 clusters with no close relationships to parasites from Peru. These parasites probably emerged independently by selection in Eritrea. High prevalence of pfhrp2-negative parasites caused a high rate of false-negative results for RDTs. Determining prevalence of pfhrp2-negative parasites is urgently needed in neighboring countries to assist case management policies.

      2. Knowledge and adherence to the National Guidelines for Malaria Diagnosis in Pregnancy among health-care providers and drug-outlet dispensers in rural western KenyaExternal
        Riley C, Dellicour S, Ouma P, Kioko U, Omar A, Kariuki S, Ng’ang’a Z, Desai M, Buff AM, Gutman JR.
        Am J Trop Med Hyg. 2018 Mar 5.

        Prompt diagnosis and effective treatment of acute malaria in pregnancy (MiP) is important for the mother and fetus; data on health-care provider adherence to diagnostic guidelines in pregnancy are limited. From September to November 2013, a cross-sectional survey was conducted in 51 health facilities and 39 drug outlets in Western Kenya. Provider knowledge of national diagnostic guidelines for uncomplicated MiP were assessed using standardized questionnaires. The use of parasitologic testing was assessed in health facilities via exit interviews with febrile women of childbearing age and in drug outlets via simulated-client scenarios, posing as pregnant women or their spouses. Overall, 93% of providers tested for malaria or accurately described signs and symptoms consistent with clinical malaria. Malaria was parasitologically confirmed in 77% of all patients presenting with febrile illness at health facilities and 5% of simulated clients at drug outlets. Parasitological testing was available in 80% of health facilities; 92% of patients evaluated at these facilities were tested. Only 23% of drug outlets had malaria rapid diagnostic tests (RDTs); at these outlets, RDTs were offered in 17% of client simulations. No differences were observed in testing rates by pregnancy trimester. The study highlights gaps among health providers in diagnostic knowledge and practice related to MiP, and the lack of malaria diagnostic capacity, particularly in drug outlets. The most important factor associated with malaria testing of pregnant women was the availability of diagnostics at the point of service. Interventions that increase the availability of malaria diagnostic services might improve malaria case management in pregnant women.

    • Reproductive Health
      1. Unintended pregnancy and interpregnancy interval by maternal age, National Survey of Family GrowthExternal
        Ahrens KA, Thoma M, Copen C, Frederiksen B, Decker E, Moskosky S.
        Contraception. 2018 Mar 1.

        BACKGROUND: The relationship between unintended pregnancy and interpregnancy interval (IPI) across maternal age is not clear. METHODS: Using data from the National Survey of Family Growth, we estimated the percentages of pregnancies that were unintended among IPI groups (<6, 6-11, 12-17, 18-23, 24+ months) by maternal age at last live birth (15-19, 20-24, 25-29, 30-44years). RESULTS: Approximately 40% of pregnancies were unintended and 36% followed an IPI<18months. Within each maternal age group, the percentage of pregnancies that were unintended decreased as IPI increased. CONCLUSION: Unintended pregnancies are associated with shorter IPI across the reproductive age spectrum.

    • Substance Use and Abuse
      1. Quantifying the epidemic of prescription opioid overdose deathsExternal
        Seth P, Rudd RA, Noonan RK, Haegerich TM.
        Am J Public Health. 2018 Apr;108(4):500-502.

        [No abstract]

      2. Vital Signs: Trends in emergency department visits for suspected opioid overdoses – United States, July 2016-September 2017External
        Vivolo-Kantor AM, Seth P, Gladden RM, Mattson CL, Baldwin GT, Kite-Powell A, Coletta MA.
        MMWR Morb Mortal Wkly Rep. 2018 Mar 9;67(9):279-285.

        INTRODUCTION: From 2015 to 2016, opioid overdose deaths increased 27.7%, indicating a worsening of the opioid overdose epidemic and highlighting the importance of rapid data collection, analysis, and dissemination. METHODS: Emergency department (ED) syndromic and hospital billing data on opioid-involved overdoses during July 2016-September 2017 were examined. Temporal trends in opioid overdoses from 52 jurisdictions in 45 states were analyzed at the regional level and by demographic characteristics. To assess trends based on urban development, data from 16 states were analyzed by state and urbanization level. RESULTS: From July 2016 through September 2017, a total of 142,557 ED visits (15.7 per 10,000 visits) from 52 jurisdictions in 45 states were suspected opioid-involved overdoses. This rate increased on average by 5.6% per quarter. Rates increased across demographic groups and all five U.S. regions, with largest increases in the Southwest, Midwest, and West (approximately 7%-11% per quarter). In 16 states, 119,198 ED visits (26.7 per 10,000 visits) were suspected opioid-involved overdoses. Ten states (Delaware, Illinois, Indiana, Maine, Missouri, Nevada, North Carolina, Ohio, Pennsylvania, and Wisconsin) experienced significant quarterly rate increases from third quarter 2016 to third quarter 2017, and in one state (Kentucky), rates decreased significantly. The highest rate increases occurred in large central metropolitan areas. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: With continued increases in opioid overdoses, availability of timely data are important to inform actions taken by EDs and public health practitioners. Increases in opioid overdoses varied by region and urbanization level, indicating a need for localized responses. Educating ED physicians and staff members about appropriate services for immediate care and treatment and implementing a post-overdose protocol that includes naloxone provision and linking persons into treatment could assist EDs with preventing overdose.

      3. Harm perceptions of intermittent tobacco product use among U.S. youth, 2016External
        Wang TW, Trivers KF, Marynak KL, O’Brien EK, Persoskie A, Liu ST, King BA.
        J Adolesc Health. 2018 Feb 28.

        PURPOSE: We aimed to describe U.S. youth harm perceptions of intermittent tobacco use. METHODS: Using data from the 2016 National Youth Tobacco Survey of U.S. students (grades 6-12; N = 20,675), we examined prevalence and correlates of all respondents’ perceived harm of using four different tobacco products on “some days but not every day.” Associations between current (past 30-day) use and harm perceptions were assessed using multivariable regression. RESULTS: Perceiving that intermittent use causes “no” or “little” harm was 9.7% for cigarettes, 12.0% for smokeless tobacco, 18.7% for hookah, and 37.5% for e-cigarettes. Compared with those who reported “a lot” of harm, youth with lower harm perceptions were more likely to report current use. CONCLUSIONS: One in ten youth perceived intermittent cigarette smoking as causing “little” or “no” harm; this perception was higher among current users. Efforts to educate youth about the risks of even intermittent tobacco product use could reduce misperceptions of harm.

    • Zoonotic and Vectorborne Diseases
      1. Rift Valley Fever: A survey of knowledge, attitudes, and practice of slaughterhouse workers and community members in Kabale District, UgandaExternal
        de St Maurice A, Nyakarahuka L, Purpura L, Ervin E, Tumusiime A, Balinandi S, Kyondo J, Mulei S, Tusiime P, Manning C, Rollin PE, Knust B, Shoemaker T.
        PLoS Negl Trop Dis. 2018 Mar 5;12(3):e0006175.

        BACKGROUND: Rift Valley Fever virus (RVF) is a zoonotic virus in the Phenuiviridae family. RVF outbreaks can cause significant morbidity and mortality in humans and animals. Following the diagnosis of two RVF cases in March 2016 in southern Kabale district, Uganda, we conducted a knowledge, attitudes and practice (KAP) survey to identify knowledge gaps and at-risk behaviors related to RVF. METHODOLOGY/PRINCIPAL FINDINGS: A multidisciplinary team interviewed 657 community members, including abattoir workers, in and around Kabale District, Uganda. Most participants (90%) had knowledge of RVF and most (77%) cited radio as their primary information source. Greater proportions of farmers (68%), herdsmen (79%) and butchers (88%) thought they were at risk of contracting RVF compared to persons in other occupations (60%, p<0.01). Participants most frequently identified bleeding as a symptom of RVF. Less than half of all participants reported fever, vomiting, and diarrhea as common RVF symptoms in either humans or animals. The level of knowledge about human RVF symptoms did not vary by occupation; however more farmers and butchers (36% and 51%, respectively) had knowledge of RVF symptoms in animals compared to those in other occupations (30%, p<0.01). The use of personal protective equipment (PPE) when handling animals varied by occupation, with 77% of butchers using some PPE and 12% of farmers using PPE. Although most butchers said that they used PPE, most used gumboots (73%) and aprons (60%) and less than 20% of butchers used gloves or eye protection when slaughtering. CONCLUSIONS: Overall, knowledge, attitudes and practice regarding RVF in Kabale District Uganda could be improved through educational efforts targeting specific populations.

      2. What pediatricians should know about Lassa virusExternal
        Greenky D, Knust B, Dziuban EJ.
        JAMA Pediatr. 2018 Mar 5.

        [No abstract]

      3. Update: Noncongenital Zika virus disease cases – 50 U.S. states and the District of Columbia, 2016External
        Hall V, Walker WL, Lindsey NP, Lehman JA, Kolsin J, Landry K, Rabe IB, Hills SL, Fischer M, Staples JE, Gould CV, Martin SW.
        MMWR Morb Mortal Wkly Rep. 2018 Mar 9;67(9):265-269.

        Zika virus is a flavivirus primarily transmitted to humans by Aedes aegypti mosquitoes (1). Zika virus infections also have been documented through intrauterine transmission resulting in congenital infection; intrapartum transmission from a viremic mother to her newborn; sexual transmission; blood transfusion; and laboratory exposure (1-3). Most Zika virus infections are asymptomatic or result in mild clinical illness, characterized by acute onset of fever, maculopapular rash, arthralgia, or nonpurulent conjunctivitis; Guillain-Barre syndrome, meningoencephalitis, and severe thrombocytopenia rarely have been associated with Zika virus infection (1). However, congenital Zika virus infection can result in fetal loss, microcephaly, and other birth defects (1,2). In 2016, a total of 5,168 noncongenital Zika virus disease cases were reported from U.S. states and the District of Columbia. Most cases (4,897, 95%) were in travelers returning from Zika virus-affected areas. A total of 224 (4%) cases were acquired through presumed local mosquitoborne transmission, and 47 (1%) were acquired by other routes. It is important that providers in the United States continue to test symptomatic patients who live in or recently traveled to areas with ongoing Zika virus transmission or had unprotected sex with someone who lives in or traveled to those areas. All pregnant women and their partners should take measures to prevent Zika virus infection during pregnancy. A list of affected areas and specific recommendations on how to prevent Zika virus infection during pregnancy are available at https://www.cdc.gov/pregnancy/zika/protect-yourself.html.

      4. Zika virus preparedness and response efforts through the collaboration between a health care delivery system and a local public health departmentExternal
        Madad S, Tate A, Rand M, Quinn C, Vora NM, Allen M, Cagliuso NV, Rakeman JL, Studer S, Masci J, Varma JK, Wilson R.
        Disaster Med Public Health Prep. 2018 Mar 7:1-3.

        The Zika virus was largely unknown to many health care systems before the outbreak of 2015. The unique public health threat posed by the Zika virus and the evolving understanding of its pathology required continuous communication between a health care delivery system and a local public health department. By leveraging an existing relationship, NYC Health+Hospitals worked closely with New York City Department of Health and Mental Hygiene to ensure that Zika-related processes and procedures within NYC Health+Hospitals facilities aligned with the most current Zika virus guidance. Support given by the public health department included prenatal clinical and laboratory support and the sharing of data on NYC Health+Hospitals Zika virus screening and testing rates, thus enabling this health care delivery system to make informed decisions and practices. The close coordination, collaboration, and communication between the health care delivery system and the local public health department examined in this article demonstrate the importance of working together to combat a complex public health emergency and how this relationship can serve as a guide for other jurisdictions to optimize collaboration between external partners during major outbreaks, emerging threats, and disasters that affect public health. (Disaster Med Public Health Preparedness. 2018;page 1 of 3).

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

Page last reviewed: January 31, 2019