Volume 11, Issue 1, January 2, 2019

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CDC Science Clips: Volume 11, Issue 1, January 2, 2019

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

The report consists of these components:

  1. 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. Social media is increasingly being used as an information source and tool for individuals and organizations to share resources and engage in conversations about health topics. Because the public tends to learn about health topics and genetics from online social media sources, it is imperative to understand the amount, type, and quality of information being shared. We performed a retrospective analysis of tweets related to hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) between January 1, 2017 and December 31, 2017. A total of 63,770 tweets were included in our dataset. The majority were retweets (59.9%) and users came from 744 different cities. Most tweets were considered “informational” (51.4%) and were designed to provide resources to the public. Online communities (25%), organizations (20%), and providers or researchers (15%) were among the most common contributors. Our results demonstrated that conversations were primarily focused on information and resource sharing, along with individuals discussing their personal stories and testimonials about their experiences with these HBOC and LS. Future studies could consider ways to harness Twitter to help tailor and deliver health communication campaigns and education interventions to improve the public’s understanding of these complex topics.

      2. Cancer in Canada: Stage at diagnosisexternal icon
        Bryan S, Masoud H, Weir HK, Woods R, Lockwood G, Smith L, Brierley J, Gospodarowicz M, Badets N.
        Health Rep. 2018 Dec 19;29(12):21-25.

        This article presents national data (excluding Quebec) on cancer incidence by stage at diagnosis for lung, colorectal, female breast and prostate cancers. Data from the Canadian Cancer Registry are combined for the diagnosis years 2011 to 2015. Half of all new lung cancers were diagnosed at stage IV, and of the two types of lung cancer, small cell was more often diagnosed at this stage than non-small cell. About half of colorectal cancers were diagnosed at stages III and IV, and stage-specific incidence rates were generally higher for males than females. More than 80% of female breast and almost three-quarters of prostate cancers were diagnosed at stages I and II. Later-stage diagnosis was more common in older age groups for both cancers.

      3. Diabetic ketoacidosis at diagnosis of type 1 diabetes and glycemic control over time: The SEARCH for Diabetes in Youth Studyexternal icon
        Duca LM, Reboussin BA, Pihoker C, Imperatore G, Saydah S, Mayer-Davis E, Rewers A, Dabelea D.
        Pediatr Diabetes. 2018 Dec 17.

        BACKGROUND: The diagnosis of type 1 diabetes (T1D) in youth is often associated with diabetic ketoacidosis (DKA). We aimed to evaluate if the presence of DKA at diagnosis of T1D is associated with less favorable hemoglobin A1c (HbA1c) trajectories over time. METHODS: The SEARCH for Diabetes in Youth study of 1396 youth aged <20 years with newly diagnosed T1D were followed for up to 13 [median 8 (IQR 6-9)] years post-diagnosis. Of these, 397 (28%) had DKA (bicarbonate level<15 mmol/l and/or pH<7.25 (venous) or <7.30 (arterial or capillary) or mention of DKA in medical records) at diabetes onset. Longitudinal HbA1c levels were measured at each follow-up visit (average number of HbA1c measures 3.4). A linear piecewise mixed effects model was used to analyze the effect of DKA status at diagnosis of T1D on long-term glycemic control, adjusting for age at diagnosis, diabetes duration at baseline, sex, race/ethnicity, household income, health insurance status, time-varying insulin regimen and glucose self-monitoring, study site, and baseline fasting C-peptide level. RESULTS: At baseline, HbA1c levels were significantly higher in youth with T1D diagnosed in DKA versus those who were not (9.9%+/-1.5% vs. 8.5%+/-1.4%, respectively). After the first year with diabetes, there was a significant difference in the rate of change in HbA1c levels by DKA status: HbA1c was 0.16% higher each year in youth with DKA compared to those without (interaction p-value<.0001), after adjusting for aforementioned covariates. CONCLUSION/INTERPRETATION: DKA at T1D diagnosis is associated with worsening glycemic control over time, independent of demographic, socioeconomic and treatment-related factors and baseline fasting C-peptide. This article is protected by copyright. All rights reserved.

      4. How the Comprehensive Cancer Control National Partnership shapes the public health workforceexternal icon
        Farrell MM, Gibson KM, Marler A, Given L, Van Kirk Villalobos A, Maynard CD, Bright FS, Kirklin GT, Green TC, Ruhe M, Thorsness J, Weiss S.
        Cancer Causes Control. 2018 Dec 6.

        This paper explores how, through its extensive network of partners, the Comprehensive Cancer Control National Partnership (National Partnership) has provided a robust array of trainings, learning institutes, webinars, workshops, mentorship programs, and direct technical assistance to comprehensive cancer control programs and coalitions over the past 20 years. Mapping these activities to specific cancer control competencies revealed that the efforts of the National Partnership adequately address the core competencies necessary for an effective workforce and have the potential to increase practitioner capacity to adopt and implement evidence-based cancer control programs. Ensuring the continued availability and uptake of these tools, trainings and partnerships could potentially address gaps and barriers in the public health workforce related to evidence-based practice.

      5. Population-based assessment of HPV genotype-specific cervical cancer survival: CDC Cancer Registry Sentinel Surveillance Systemexternal icon
        Hallowell BD, Saraiya M, Thompson TD, Unger ER, Lynch CF, Tucker T, Copeland G, Hernandez BY, Peters ES, Wilkinson E, Goodman MT.
        JNCI Cancer Spectrum. 2018 01 Jul;2(3).

        Background: Human papillomavirus (HPV) genotype influences the development of invasive cervical cancer (ICC); however, there is uncertainty regarding the association of HPV genotype with survival among ICC patients. Method(s): Follow-up data were collected from 693 previously selected and HPV-typed ICC cases that were part of the Centers for Disease Control and Prevention Cancer Registry Surveillance System. Cases were diagnosed between 1994 and 2005. The Kaplan-Meier method was used to estimate five-year all-cause survival. A multivariable Cox proportional hazards model was used to estimate the effect of HPV genotype on survival after adjusting for demographic, tumor, and treatment characteristics. Result(s): Five-year all-cause survival rates varied by HPV status (HPV 16: 66.9%, HPV 18: 65.7%, HPV 31/33/45/52/58: 70.8%, other oncogenic HPV genotypes: 79.0%, nononcogenic HPV: 69.3%, HPV-negative: 54.0%). Following multivariable adjustment, no statistically significant survival differences were found for ICC patients with HPV 16-positive tumors compared with women with tumors positive for HPV 18, other oncogenic HPV types, or HPV-negative tumors. Women with detectable HPV 31/33/33/ 45/52/58 had a statistically significant 40% reduced hazard of death at five years (95% confidence interval [CI] = 0.38 to 0.95), and women who tested positive for nononcogenic HPV genotypes had a statistically significant 57% reduced hazard of death at five years (95% CI = 0.19 to 0.96) compared with women with HPV 16 tumors. Few statistically significant differences in HPV positivity, tumor characteristics, treatment, or survival were found by race/ethnicity. Conclusion(s): HPV genotype statistically significantly influenced five-year survival rates among women with ICC; however, screening and HPV vaccination remain the most important factors to improve patient prognosis and prevent future cases.

      6. Comprehensive cancer control in the U.S.: summarizing twenty years of progress and looking aheadexternal icon
        Hayes NS, Hohman K, Vinson C, Pratt-Chapman M.
        Cancer Causes Control. 2018 Dec 19.

        In order to celebrate the accomplishments of the Centers for Disease Control and Prevention’s (CDC) National Comprehensive Cancer Control Program (NCCCP), the Comprehensive Cancer Control National Partners (CCCNP) developed this Special Issue on Cancer Causes and Control. This, the third Special Issue on Comprehensive Cancer Control (CCC), is a reflection of 20 years of building successful partnerships to prevent and control cancer; planning and implementing strategic cancer control; collaborating to address national cancer prevention and control priorities; evaluating efforts; sharing successes; and, in later years, serving as a model for global cancer control planning and implementation. The CDC currently supports cancer control planning and implementation in all 50 states, the District of Columbia, eight tribes or tribal organizations, and seven Pacific Island Jurisdictions and U.S. territories through the NCCCP. CCC is an approach that brings together multi-sector partners to address the cancer burden in a community collectively by leveraging existing resources and identifying and addressing cancer related issues and needs. The Comprehensive Cancer Control National Partnership (CCCNP), a partnership of national organizations, has been committed to supporting comprehensive cancer control efforts since 1999. We summarize the efforts described in this Special Issue. We also describe opportunities and critical elements to continue the momentum for comprehensive cancer control well into the future.

      7. Uterine cancer incidence and mortality – United States, 1999-2016external icon
        Henley SJ, Miller JW, Dowling NF, Benard VB, Richardson LC.
        MMWR Morb Mortal Wkly Rep. 2018 Dec 7;67(48):1333-1338.

        Uterine cancer is one of the few cancers with increasing incidence and mortality in the United States, reflecting, in part, increases in the prevalence of overweight and obesity since the 1980s (1). It is the fourth most common cancer diagnosed and the seventh most common cause of cancer death among U.S. women (1). To assess recent trends in uterine cancer incidence and mortality by race and ethnicity, CDC analyzed incidence data from CDC’s National Program of Cancer Registries (NPCR) and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program and mortality data from the National Vital Statistics System (2). Most recent data available are through 2015 for incidence and through 2016 for mortality. Uterine cancer incidence rates increased 0.7% per year during 1999-2015, and death rates increased 1.1% per year during 1999-2016, with smaller increases observed among non-Hispanic white (white) women than among women in other racial/ethnic groups. In 2015, a total of 53,911 new uterine cancer cases, corresponding to 27 cases per 100,000 women, were reported in the United States, and 10,733 uterine cancer deaths (five deaths per 100,000 women) were reported in 2016. Uterine cancer incidence was higher among non-Hispanic black (black) and white women (27 cases per 100,000) than among other racial/ethnic groups (19-23 per 100,000). Uterine cancer deaths among black women (nine per 100,000) were higher than those among other racial/ethnic groups (four to five per 100,000). Public health efforts to help women achieve and maintain a healthy weight and obtain sufficient physical activity can reduce the risk for developing cancer of the endometrium (the lining of the uterus), the most common uterine cancer. Abnormal vaginal bleeding, including bleeding between periods or after sex or any unexpected bleeding after menopause, is an important symptom of uterine cancer (3). Through programs such as CDC’s Inside Knowledge* campaign, promoting awareness among women and health care providers of the need for timely evaluation of abnormal vaginal bleeding can increase the chance that uterine cancer is detected early and treated appropriately.

      8. National burden of heart failure events in the United States, 2006 to 2014external icon
        Jackson SL, Tong X, King RJ, Loustalot F, Hong Y, Ritchey MD.
        Circ Heart Fail. 2018 Dec;11(12):e004873.

        BACKGROUND: Heart failure (HF)-a serious and costly condition-is increasingly prevalent. We estimated the US burden including emergency department (ED) visits, inpatient hospitalizations and associated costs, and mortality. METHODS AND RESULTS: We analyzed 2006 to 2014 data from the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample, the Healthcare Cost and Utilization Project National (nationwide) Inpatient Sample, and the National Vital Statistics System. International Classification of Disease codes identified HF and comorbidities. Burden was estimated separately for ED visits, hospitalizations, and mortality. In addition, criteria were applied to identify total unique acute events. Rates of primary HF (primary diagnosis or underlying cause of death) and comorbid HF (comorbid diagnosis or contributing cause of death) were calculated, age standardized to the 2010 US population. In 2014, there were an estimated 1 068 412 ED visits, 978 135 hospitalizations, and 83 705 deaths with primary HF. There were 4 071 546 ED visits, 3 370 856 hospitalizations, and 230 963 deaths with comorbid HF. Between 2006 and 2014, the total unique acute event rate for primary HF declined from 536 to 449 per 100 000 (relative percent change of -16%; P for trend, <0.001) but increased for comorbid HF from 1467 to 1689 per 100 000 (relative percentage change, 15%; P for trend, <0.001). HF-related mortality decreased significantly from 2006 to 2009 but did not change meaningfully after 2009. For hospitalizations with primary HF, the estimated mean cost was $11 552 in 2014, totaling an estimated $11 billion. CONCLUSIONS: Given substantial healthcare and mortality burden of HF, rising healthcare costs, and the aging US population, continued improvements in HF prevention, management, and surveillance are important.

      9. Estimating state-level health burden of diabetes: Diabetes-attributable fractions for diabetes complicationsexternal icon
        Khavjou OA, Saydah SH, Zhang P, Poehler DC, Neuwahl SJ, Leib AR, Hoerger TJ, Wang J.
        Am J Prev Med. 2018 Dec 13.

        INTRODUCTION: Limited information is available on the health burden of diabetes at the state level. This study estimated state-specific attributable fractions and the number of cases attributable to diabetes for diabetes-related complications. METHODS: For each state, diabetes-attributable fractions for nine diabetes complications were estimated: three self-reported complications from the 2013 Behavioral Risk Factor Surveillance System, hospitalizations with three complications from 2011 to 2014 State Inpatient Databases, and three complications from 2013 Medicare data. Attributable fractions were calculated using RR and diabetes prevalence and the total number of cases using attributable fractions and total number of complications. Adjusted RR of each complication for people with and without diabetes by age and sex was estimated using a generalized linear model. Analyses were conducted in 2015-2016. RESULTS: Median state-level diabetes-attributable fractions for self-reported complications were 0.14 (range, 0.10-0.19) for mobility limitations; 0.13 (range, 0.04-0.21) for limitations in instrumental activities of daily living; and 0.12 (range, 0.06-0.20) for severe visual impairment or blindness. Median state-level diabetes-attributable fractions for diabetes-associated hospitalizations were 0.19 (range, 0.08-0.24) for congestive heart failure; 0.08 (range, 0.02-0.16) for myocardial infarction; and 0.62 (range, 0.46-0.73) for lower extremity amputations. Median state-level diabetes-attributable fractions for complications among Medicare beneficiaries were 0.17 (range, 0.14-0.23) for coronary heart disease; 0.28 (range, 0.24-0.33) for chronic kidney disease; and 0.22 (range, 0.08-0.32) for peripheral vascular disease. CONCLUSIONS: Diabetes carries a significant health burden, and results vary across states. Efforts to prevent or delay diabetes or to improve diabetes management could reduce the health burden because of diabetes.

      10. Sustained virological response does not improve long-term glycemic control in patients with type 2 diabetes and chronic hepatitis Cexternal icon
        Li J, Gordon SC, Rupp LB, Zhang T, Trudeau S, Holmberg SD, Moorman AC, Spradling PR, Teshale EH, Boscarino JA, Schmidt MA, Daida YG, Lu M.
        Liver Int. 2018 Dec 20.

        BACKGROUND: Sustained virological response (SVR) to treatment for chronic hepatitis C (HCV) may improve short-term glucose control among patients with type 2 diabetes (T2D), but the long-term impact remains largely unknown. We used data from the Chronic Hepatitis Cohort Study to investigate the impact of SVR on long-term trends in HbA1c in patients with T2D. METHODS: “Index date” was defined as the date of treatment initiation (treated patients) or HCV diagnosis (untreated patients). To address treatment selection bias, we used a propensity score approach. We used a piecewise, linear-spline, mixed-effects model to evaluate changes in HbA1c over a five-year period. RESULTS: Our sample included 384 HCV patients with T2D (192 untreated, 192 treated, with SVR or treatment failure [TF]). After adjusting for BMI, HbA1c was stable among untreated and TF patients. In SVR patients, Hb1Ac trajectories evolved in three phases: 1) index through 6 months post-index, average HbA1c decreased significantly from 7.7-5.4% per 90 days (p<0.001); 2) 6-30 months post-index, HbA1c rebounded at a rate of 1.5% every 90 days (p=0.003); and 3) from 30 months onward, HbA1c stabilized at an average level of 7.9 (p-value =0.34). Results from an analysis restricted to patients receiving direct-acting antivirals were consistent with the main findings. CONCLUSION: Successful HCV treatment among patients with T2D significantly reduces HbA1 shortly after treatment, but these decreases are not sustained long-term. Less than three years after SVR, HbA1c rebounds to levels similar to untreated/TF patients, and higher than recommended for type 2 diabetic maintenance. This article is protected by copyright. All rights reserved.

      11. Association between plasma trans-fatty acid concentrations and diabetes in a nationally representative sample of US adultsexternal icon
        Liu B, Sun Y, Snetselaar LG, Sun Q, Yang Q, Zhang Z, Liu L, Hu FB, Bao W.
        J Diabetes. 2018 Aug;10(8):653-664.

        BACKGROUND: A diet high in trans-fatty acids (TFA) induces insulin resistance in rodent models and primates. However, previous epidemiological studies on the association between TFAs, based primarily on self-reported intake from the diet, and diabetes in humans have yielded conflicting results. Herein we examined the associations of objectively measured plasma TFA concentrations with diabetes in a large population-based study among US adults. METHODS: We included 3801 participants aged >/=20 years from the National Health and Nutrition Examination Survey 1999-2000 and 2009-10. Four major TFAs, namely palmitelaidic acid (C16:1 n-7t), elaidic acid (C18:1 n-9t), vaccenic acid (C18:1 n-7t), and linolelaidic acid (C18:2 n-6t, 9t), were measured in fasting plasma using gas chromatography-mass spectrometry. Diabetes was defined by self-reported physician diagnosis, plasma fasting glucose >/=126 mg/dL, or HbA1c >/=6.5%. RESULTS: After adjustment for other major risk factors, the odds ratios (95% confidence intervals) of diabetes comparing the highest with lowest quintile of plasma TFAs was 2.19 (1.27-3.79) for total TFAs (Ptrend = 0.01), 2.34 (1.48-3.72) for elaidic acid (Ptrend = 0.0004), 1.33 (0.82-2.15) for linolelaidic acid (Ptrend = 0.18), 1.58 (0.97-2.58) for palmitelaidic acid (Ptrend = 0.02), and 1.64 (0.95-2.84) for vaccenic acid (Ptrend = 0.08). In addition, total TFAs, elaidic acid, palmitelaidic acid, and vaccenic acid were significantly associated with fasting glucose, fasting insulin, the insulin resistance index, and HbA1c. CONCLUSIONS: In a nationally representative population, plasma TFAs, in particular elaidic acid, were positively associated with diabetes and biomarkers of glucose metabolism.

      12. INTRODUCTION: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are risk factors for hepatocellular carcinoma, a type of primary liver cancer, and are most prevalent in people born 1945-1965. Relatively little information is available for liver cancer prevention, compared to other cancers. In this review, we provide a summary of current promising public health practices for liver cancer prevention from the literature, as well as liver cancer-related initiatives in the National Comprehensive Cancer Control Program (NCCCP). METHODS: Two types of source materials were analyzed for this review: published literature (2005-present), and current cancer plans from the NCCCP (2005-2022). A search strategy was developed to include a review of several scientific databases. Of the 73 articles identified as potentially eligible, 20 articles were eligible for inclusion in the review. Eligible articles were abstracted using a data abstraction tool. Three independent keyword searches on 65 NCCCP plans were conducted. Keyword searches within each of the plans to identify activities related to liver cancer were conducted. Relevant information was abstracted from the plans and saved in a data table. RESULTS: Of the 20 eligible articles, 15 articles provided information on interventions related to liver cancer and hepatitis B or hepatitis C prevention. All 15 of the intervention articles were related to hepatitis; 13 were hepatitis B-focused, two were hepatitis C-focused, and 14 focused on Asian/Pacific Islander American populations. The independent keyword search of NCCCP plans produced 46 results for liver, 27 results for hepatitis, and 52 results for alcohol. Two plans included activities related to liver cancer. Twenty-four plans included activities related to hepatitis. DISCUSSION: A majority of the intervention articles published focused on HBV infection in Asian/Pacific Islander American populations, and a small percentage of NCCCP plans included liver-related content. The findings from this review will inform the development of an Action Plan on liver cancer prevention for the NCCCP, which will assist programs with the adoption and uptake of promising practices for the prevention of liver cancer.

      13. Arthritis prevalence: which case definition should be used for surveillance? Comment on the article by Jafarzadeh and Felsonexternal icon
        Murphy LB, Sacks JJ, Helmick CG, Brady TJ, Barbour KE, Hootman JM, Boring MA, Moss S, Guglielmo D, Theis KA.
        Arthritis Rheumatol. 2018 Sep 24.

        [No abstract]

      14. Purpose: To estimate prevalence and severity of diabetic retinopathy (DR) among U.S. adults with diabetes and with or without chronic kidney disease (CKD), and assess associated risk of mortality. Design(s): Cross-sectional study with national survey data. Method(s): The cohort included adults >=40 years old with diabetes in the National Health and Nutrition Examination Surveys (NHANES) 2005-2008. Vital status was determined through December 31, 2011. We defined diabetes as hemoglobin A1c >=6.5% or self-report and CKD by urinary albumin/creatinine >=30 mg/g or glomerular filtration rate <60 mL/min/1.73 m<sup>2</sup>. The main outcomes were DR and mortality. Result(s): Prevalence of DR was 27.8% (95% CI 24.3-31.7), 36.2% (95%CI 30.1-42.7), and 23.4% (95% CI 19.2-28.1), overall, with and without CKD. Prevalence of vision-threatening DR was 4.2% (95% CI 3.2-5.5), 8.2% (95% CI 5.4-12.2), and 2.0% (95% CI 1.2-3.5), respectively. In a multivariable adjusted model, DR was positively but nonsignificantly associated with CKD (OR = 1.1, 95% CI 0.7-1.7), was 40% higher per 1% increase in hemoglobin A1c (OR = 1.4, 95% CI 1.1-1.6), was 30% higher per 5 years additional diabetes duration (OR = 1.3, 95% CI 1.1-1.5), was 30% higher per 10 mm Hg increase in systolic blood pressure (OR = 1.3, 95% CI 1.1-1.5), and was 6-fold higher with insulin treatment (OR = 6.2, 95% CI 2.6-14.8). Compared with diabetic participants with neither DR nor CKD, those with DR and CKD had a 3.6-fold (95% CI 1.5-9.1) increased adjusted risk for all-cause mortality. Conclusion(s): Over one third of persons with diabetes and CKD had DR. The risk of death was higher with than without CKD and DR. Many of the studied risk factors associated with DR are modifiable.

      15. The National Comprehensive Cancer Control Program has experienced exponential growth over the past 20 years due to the coordination and collaboration of many stakeholders to sustain multisector coalitions, develop and execute data-driven plans, and successfully implement evidenced-based interventions across the United States. These stakeholders have worked tirelessly to address the burden of cancer by employing strategies that promote healthy behaviors to reduce cancer risk, facilitate screening, and address the needs of cancer survivors. The interaction between the comprehensive cancer control program and the coalitions to engage in this work has been coined the 3Ps: the partnership, the CCC plan, and CCC program interventions. This article describes the efforts to evaluate the growth of the comprehensive cancer control movement, especially as it pertains to coalition contribution, plan priority development and implementation, and intervention implementation. It describes successes and lessons learned from an evaluation whose findings can be used to bolster and sustain comprehensive cancer control programs and coalitions across the U.S.

      16. BACKGROUND: Colonoscopy is the most widely used colorectal cancer (CRC) screening test in the United States. Through the detection and removal of potentially precancerous polyps, it can prevent CRC. However, CRC screening remains low among adults who are recommended for screening. The New Hampshire Colorectal Cancer Screening Program implemented a patient navigation (PN) intervention to increase colonoscopy screening among low-income patients in health centers in New Hampshire. In the current study, the authors examined the cost-effectiveness of this intervention. METHODS: A decision tree model was constructed using Markov state transitions to calculate the costs and effectiveness associated with PN. Costs were calculated for the implementation of PN in a statewide public health program and in endoscopy centers. The main study outcome was colonoscopy screening completion. The main decision variable was the incremental cost-effectiveness ratio associated with the PN intervention compared with usual care. RESULTS: The average cost per screening with PN was $1089 (95% confidence interval, $1075-$1103) compared with $894 with usual care (95% confidence interval, $886-$908). Among patients who were navigated, approximately 96.2% completed colonoscopy screening compared with 69.3% of those receiving usual care (odds ratio, 11.2; P <. 001). The incremental cost-effectiveness ratio indicated that 1 additional screening completion cost approximately $725 in a public health program and $548 in an endoscopy center with PN compared with usual care, both of which are less than the average Medicare reimbursement of $737 for a colonoscopy procedure. CONCLUSIONS: PN was found to be cost-effective in increasing colonoscopy screening among low-income adults in the New Hampshire Colorectal Cancer Screening Program, even at the threshold of current Medicare reimbursement rates for colonoscopy. The results of the current study support the implementation of PN in statewide public health programs and endoscopy centers.

      17. BACKGROUND: Prostate cancer carries emasculating symptoms and treatment effects. These symptoms and treatment effects impact a man’s sexual function; a central-theme to masculinity. This study seeks to assess the impact of sexual function on perceptions of masculinity. METHODS: A voluntary-sample of men self-selected into the registry. Data were based on a series of questions related to Health-Related Quality of Life and functional status. RESULTS: Based on the analysis, 50.2% of men did not feel less masculine, 33.2% of men were still interested in sex, 40.2% of men still engaged in sex “a little bit,” and 34.8% of men still found sex “quite a bit” enjoyable. Additionally, 31.1% of identified issues with erectile dysfunction and 45.5% of men showed no discomfort with being sexually active. CONCLUSION: Sexual function has an impact on perceptions of masculinity but additional underlying issues outside of sexual function may contribute to perceptions of masculinity.

      18. Purpose: Health disparities persist across the cancer care continuum. Patient navigator (PN) and community health worker (CHW) interventions are designed to increase health equity. National Comprehensive Cancer Control Program (NCCCP) awardees develop and implement plans to coordinate cancer prevention and control activities, including supporting PN and CHW interventions. This content analysis examined NCCCP action plans to assess the extent to which jurisdictions report engaging in PN and/or CHW activities. Methods: We abstracted PN and CHW content from NCCCP action plans and coded content according to specific areas of PN and/or CHW intervention (e.g., screening, survivorship, and cancer type), used descriptive statistics to characterize overall results, and calculated chi-squares to determine whether programs engaged PNs and CHWs differently. Results: Eighty-two percent (n=53) of 65 NCCCP action plans had content related to PN and/or CHW activities, with more PN language (83%) than CHW (58%). These action plans described engaging PNs and CHWs in activities across the cancer continuum, but particularly for screening (60%) and survivorship (55%). Eighty-one percent of these plans described activities related to workforce development, such as training and standardizing roles and competencies. Programs engaged CHWs more often than PNs for outreach and in community settings. Conclusion: The majority of NCCCP awardees reported engaging in PN and/or CHW activities. Understanding how NCCCP awardees engage PNs and CHWs, including awardees’ needs for workforce development in this area, can help Centers for Disease Control and Prevention provide more focused technical assistance as programs increase engagement of PNs and CHWs to improve health equity.

      19. Comprehensive cancer control: promoting survivor health and wellnessexternal icon
        Rohan EA, Miller N, Bonner F, Fultz-Butts K, Pratt-Chapman ML, Alfano CM, Santiago KC, Bergman K, Tai E.
        Cancer Causes Control. 2018 Dec 1.

        PURPOSE: As of 2016, an estimated 15.5 million cancer survivors were living in the United States and the number of cancer survivors is expected to increase to 20.3 million by 2026. Numerous clinical studies have shown that comorbidities, such as obesity and diabetes, and unhealthy lifestyle choices, such as physical inactivity and heavy smoking, negatively influence overall quality of life and long-term survival of cancer survivors. Accordingly, survivorship programs seek to focus on overall wellness, including symptom management, monitoring for late effects of treatment, monitoring for recurrence, helping patients adapt healthy behaviors, and quality of life. This paper provides a broad overview of public health efforts to address the needs of cancer survivors. METHODS: To describe a range of examples of survivorship initiatives in comprehensive cancer control, we analyzed documents from comprehensive cancer control programs and coalitions and solicited detailed examples from several national partners. RESULTS: Comprehensive cancer control programs, coalitions, and partners are undertaking myriad initiatives to address cancer survivorship and building upon evidence-based interventions to promote healthy behaviors for cancer survivors across the country. CONCLUSION: A coordinated public health approach to caring for the growing population of cancer survivors can help address the long-term physical, psychosocial, and economic effects of cancer treatment on cancer survivors and their families.

      20. BACKGROUND: Out-of-school time (OST) programs are an important setting for supporting student health and academic achievement. This study describes the prevalence and characteristics of school-based OST programs, which can inform efforts to promote healthy behaviors in this setting. METHODS: A nationally representative sample of public elementary schools (N = 640) completed surveys in 2013-2014. Administrators reported on OST programs and policies at their school. Multivariable logistic regression models estimated the prevalence of school-based OST programs, adjusting for school characteristics. Among schools with OST programs (N = 475), chi-square tests identified school characteristics associated with having an OST policy about physical activity or nutrition. RESULTS: Three fourths of elementary schools (75.6%) had a full- or partial-year school-based OST program, with 30.8% having both. Full- and partial-year programs were significantly less prevalent in rural and township areas versus urban settings. Only 27.5% of schools with OST programs reported having physical activity and/or nutrition policies. CONCLUSIONS: Most US elementary schools have an on-site OST program, but disparities in access exist, and most lack policies or awareness of existing policies regarding physical activity and nutrition. To maximize OST programs’ potential benefits, strategies are needed to increase access to programs and physical activity and/or nutrition policy adoption.

      21. A phase 2 trial of regorafenib as a single agent in patients with chemotherapy-refractory, advanced, and metastatic biliary tract adenocarcinomaexternal icon
        Sun W, Patel A, Normolle D, Patel K, Ohr J, Lee JJ, Bahary N, Chu E, Streeter N, Drummond S.
        Cancer. 2018 Dec 18.

        BACKGROUND: Biliary tract cancers are rare, aggressive neoplasms. Most patients present with advanced/unresectable or metastatic disease at diagnosis, and no second-line regimen has demonstrated clinical benefit. This was a phase 2 study evaluating the efficacy and safety of regorafenib in patients who had advanced/unresectable or metastatic disease after receiving standard therapy. METHODS: In this single arm-study, patients with advanced/unresectable or metastatic biliary tract cancer who failed at least 1 line of systemic chemotherapy received regorafenib once daily on a schedule of 21-days on/7-days off in a 28-day cycle. Patients initially received a standard 160 mg dose. After toxicity assessments in the first 3 patients, the dose was reduced to 120 mg for subsequent patients, as preplanned. The primary endpoint was progression-free survival (PFS). Secondary objectives included overall survival (OS), the objective response rate, and the disease control rate. RESULTS: Forty-three patients received at least 1 dose of regorafenib, and 34 patients who received at least 1 cycle of treatment were evaluable for tumor response. The median PFS was 15.6 weeks (90% confidence interval, 12.9-24.7 weeks), and the median OS was 31.8 weeks (90% confidence interval, 13.3-74.3 weeks), with survival rates 40% at 12 months and 32% at 18 months. A partial response was achieved in 5 patients (11%), and 19 had stable disease (44%), for a disease control rate of 56%. The toxicity profile was as expected, with grade 3 and 4 adverse events reported in 40% of patients. The most common toxicities were hypophosphatemia (40%), hyperbilirubinemia (26%), hypertension (23%), and hand-foot skin reaction (7%). CONCLUSIONS: The current results suggest promising efficacy of regorafenib in patients with chemotherapy-refractory, advanced/metastatic biliary tract cancer, warranting further studies to confirm its clinical efficacy. There is a clear unmet need for effective therapies in patients who have advanced and metastatic biliary tract cancer.

      22. Identifying optimal approaches to scale up colorectal cancer screening: an overview of the Centers for Disease Control and Prevention (CDC)’s learning laboratoryexternal icon
        Tangka FK, Subramanian S, Hoover S, Lara C, Eastman C, Glaze B, Conn ME, DeGroff A, Wong FL, Richardson LC.
        Cancer Causes Control. 2018 Dec 14.

        Use of recommended screening tests can reduce new colorectal cancers (CRC) and deaths, but screening uptake is suboptimal in the United States (U.S.). The Centers for Disease Control and Prevention (CDC) funded a second round of the Colorectal Cancer Control Program (CRCCP) in 2015 to increase screening rates among individuals aged 50-75 years. The 30 state, university, and tribal awardees supported by the CRCCP implement a range of multicomponent interventions targeting health systems that have low CRC screening uptake, including low-income and minority populations. CDC invited a select subset of 16 CRCCP awardees to form a learning laboratory with the goal of performing targeted evaluations to identify optimal approaches to scale-up interventions to increase uptake of CRC screening among vulnerable populations. This commentary provides an overview of the CRCCP learning laboratory, presents findings from the implementation of multicomponent interventions at four FQHCs participating in the learning laboratory, and summarizes key lessons learned on intervention implementation approaches. Lessons learned can support future program implementation to ensure scalability and sustainability of the interventions as well as guide future implementation science and evaluation studies conducted by the CRCCP learning laboratory.

      23. A decade of improvement in door-to-needle time among acute ischemic stroke patients, 2008 to 2017external icon
        Tong X, Wiltz JL, George MG, Odom EC, Coleman King SM, Chang T, Yin X, Merritt RK.
        Circ Cardiovasc Qual Outcomes. 2018 Dec;11(12):e004981.

        BACKGROUND: The clinical benefit of intravenous (IV) alteplase in acute ischemic stroke is time dependent. We assessed the overall temporal changes in door-to-needle (DTN) time and examine the factors associated with DTN time </=60 and </=45 minutes. METHODS AND RESULTS: A total of 496 336 acute ischemic stroke admissions were identified in the Paul Coverdell National Acute Stroke Program from 2008 to 2017. We used generalized estimating equations models to examine the factors associated with DTN time </=60 and </=45 minutes, and calculated adjusted odds ratios and 95% CI. Between 2008 and 2017, the percentage of acute ischemic stroke patients who received IV alteplase including those transferred, increased from 6.4% to 15.3%. After excluding those who received IV alteplase at an outside hospital, a total of 39 737 (8%) acute ischemic stroke patients received IV alteplase within 4.5 hours of the time the patient last known to be well. Significant increases were seen in DTN time </=60 minutes (26.4% in 2008 to 66.2% in 2017, P<0.001), as well as DTN time </=45 minutes (10.7% in 2008 to 40.5% in 2017, P<0.001). Patients aged 55 to 84 years were more likely to receive IV alteplase within 60 minutes, while those aged 55 to 74 years were more likely to receive IV alteplase within 45 minutes, as compared with those aged 18 to 54 years. Arrival by emergency medical service, and patients with severe stroke were more likely to receive IV alteplase within 60 and 45 minutes. Conversely, women, black patients as compared with white, and patients with a medical history of diseases associated with stroke were less likely to receive DTN time </=60 or 45 minutes. CONCLUSIONS: Rapid improvements in DTN time were observed in the Paul Coverdell National Acute Stroke Program; however, opportunities to reduce disparities remain.

    • Communicable Diseases

      1. Case Report: Cervicovaginal co-colonization with Entamoeba gingivalis and Entamoeba polecki in association with an intrauterine deviceexternal icon
        Bradbury RS, Roy S, Ali IK, Morrison JR, Waldner D, Hebbeln K, Aldous W, Jepson R, Delavan HR, Ndubuisi M, Bishop HS.
        Am J Trop Med Hyg. 2018 Dec 10.

        Amoebic trophozoites were identified in the cervicovaginal smear of a U.S. patient without travel history at the time of intrauterine device (IUD) removal. Subsequent morphologic analysis and DNA sequencing identified a mixed cervicovaginal colonization of the female genital tract with both Entamoeba gingivalis and Entamoeba polecki in association with Actinomyces species bacteria. This highlights to the potential for colonization of the genital tract with E. gingivalis, particularly in association with IUD placement, and represents the first report of E. polecki in this context.

      2. Viral suppression among persons in HIV care in the United States during 2009-2013: sampling bias in Medical Monitoring Project surveillance estimatesexternal icon
        Bradley H, Althoff KN, Buchacz K, Brooks JT, Gill MJ, Horberg MA, Kitahata MM, Marconi V, Mayer KH, Mayor A, Moore R, Mugavero M, Napravnik S, Paz-Bailey G, Prejean J, Rebeiro PF, Rentsch CT, Shouse RL, Silverberg MJ, Sullivan PS, Thorne JE, Yehia B, Rosenberg ES.
        Ann Epidemiol. 2018 Nov 22.

        PURPOSE: To assess sampling bias in national viral suppression (VS) estimates derived from the Medical Monitoring Project (MMP) resulting from use of an abbreviated (four-month) annual sampling period. We aimed to improve VS estimates using cohort data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) and a novel cohort-adjustment method. METHODS: Using full calendar years of NA-ACCORD data, we assessed timing of HIV care attendance (inside vs. exclusively outside MMP’s four-month sampling period), VS status at last test (<200 vs. >/=200 copies/mL), and associated demographics. These external estimates were used to standardize MMP to NA-ACCORD data with multivariable regression models of care attendance and VS, yielding adjusted 2009-2013 VS estimates with 95% confidence intervals. RESULTS: Weighted percentages of VS among persons in HIV care were 67% in 2009 and 77% in 2013. These estimates are slightly lower than previously published MMP estimates (72% and 80% in 2009 and 2013, respectively). The number of persons receiving HIV care was previously underestimated by 20%, because patients receiving care exclusively outside the MMP sampling period did not contribute toward the weighted population estimate. CONCLUSIONS: Careful examination of national surveillance estimates using data triangulation and novel methodologies can improve the robustness of VS estimates.

      3. State minimum wage laws and newly diagnosed cases of HIV among heterosexual black residents of US metropolitan areasexternal icon
        Cloud DH, Beane S, Adimora A, Friedman SR, Jefferson K, Hall HI, Hatzenbuehler M, Johnson AS, Stall R, Tempalski B, Wingood GM, Wise A, Komro K, Cooper HL.
        SSM – Population Health. 2019 April;7 (100327).

        This ecologic cohort study explores the relationship between state minimum wage laws and rates of HIV diagnoses among heterosexual black residents of U.S metropolitan areas over an 8-year span. Specifically, we applied hierarchical linear modeling to investigate whether state-level variations in minimum wage laws, adjusted for cost-of-living and inflation, were associated with rates of new HIV diagnoses among heterosexual black residents of metropolitan statistical areas (MSAs; n=73), between 2008 and 2015. Findings suggest that an inverse relationship exists between baseline state minimum wages and initial rates of newly diagnosed HIV cases among heterosexual black individuals, after adjusting for potential confounders. MSAs with a minimum wage that was $1 higher at baseline had a 27.12% lower rate of newly diagnosed HIV cases. Exploratory analyses suggest that income inequality may mediate this relationship. If subsequent research establishes a causal relationship between minimum wage and this outcome, efforts to increase minimum wages should be incorporated into HIV prevention strategies for this vulnerable population.

      4. Household transmission of seasonal influenza from HIV-infected and -uninfected individuals in South Africa, 2013-2014external icon
        Cohen C, Tshangela A, Valley-Omar Z, Iyengar P, von Mollendorf C, Walaza S, Hellferscee O, Venter M, Martinson N, Mahlase G, McMorrow M, Cowling BJ, Treurnicht FK, Cohen AL, Tempia S.
        J Infect Dis. 2018 Dec 12.

        Background: Differential transmission from HIV-infected compared to HIV-uninfected individuals may impact influenza burden. We estimated the household secondary infection risk (SIR) and serial interval (SI) for influenza transmission from HIV-infected and HIV-uninfected index cases and identified associated factors. Methods: Index cases were the first symptomatic person in a household with influenza-like illness, testing influenza positive on real-time reverse transcription polymerase chain reaction (rRT-PCR). Nasopharyngeal swabs collected from household contacts every four days were tested by rRT-PCR. Factors associated with SIR were evaluated using logistic regression. Results: We enrolled 28 HIV-infected and 57 HIV-uninfected index cases. On multivariable analysis, HIV-infected index cases were less likely to transmit influenza to household contacts (odds ratio (OR) 0.2 95% CI 0.1-0.6)(SIR 16%, 18/113 vs 27%, 59/220). Factors associated with increased SIR included index age group 1-4 years (OR 3.6, 95% CI 1.2-11.3) and 25-44 years (OR 8.0, 95% CI 1.8-36.7) and contact age group 1-4 years (OR 3.5, 95%CI 1.2-10.3) compared to 5-14 years and sleeping with index case (OR 2.7, 95%CI 1.3-5.5). HIV-infection of index case was not associated with SI. Conclusions: HIV-infection was not associated with SI. Increased infectiousness of HIV-infected individuals is likely not an important driver of community influenza transmission.

      5. Antiretroviral drug concentrations in breastmilk, maternal HIV viral load, and HIV transmission to the infant: results from the BAN studyexternal icon
        Davis NL, Corbett A, Kaullen J, Nelson JA, Chasela CS, Sichali D, Hudgens MG, Miller WC, Jamieson DJ, Kourtis AP.
        J Acquir Immune Defic Syndr. 2018 Dec 12.

        BACKGROUND: Concentration of antiretroviral (ARV) drug found in plasma, and amounts of drug excreted into breastmilk, may affect HIV viral load and potentially perinatal HIV transmission. METHODS: In this cohort study with two-phase sampling, we included mothers randomized to postpartum maternal ARVs or daily infant nevirapine during 28 weeks of breastfeeding in the Breastfeeding, Antiretrovirals and Nutrition (BAN) study. Among these, we included all mothers who transmitted HIV to their infants between 2-28 weeks and 15% of mothers who did not (n=27 and 227, respectively). Spearman correlation coefficients (r2) were used to assess correlation between maternal plasma and breastmilk ARV concentration. Associations between the median effective drug concentration (EC50) and detectable maternal viral load (plasma: >40 copies/ml, breastmilk: >56 copies/ml) were assessed using mixed effects models. Cox models were used to estimate the association between maternal or infant plasma drug concentration and breastmilk HIV transmission from 2-28 weeks. RESULTS: All ARV compounds exhibited substantial correlations between maternal plasma and breastmilk concentrations (r2: 0.85-0.98, p-value <0.0001). Having plasma drug concentration above the EC50 was associated with lower odds of having detectable HIV RNA (maternal plasma OR 0.64, 95%CI 0.45-0.91; breastmilk OR 0.22, 95% CI 0.14-0.35) and a reduced rate of breastmilk HIV transmission (HR 0.40, 95% CI 0.18-0.93). Having breastmilk drug concentration above the EC50 was also associated with lower odds of having detectable maternal HIV RNA (plasma OR 0.62, 95%CI 0.45-0.85; breastmilk OR 0.42, 95% CI 0.29-0.59). CONCLUSION: Ensuring adequate drug concentration is important for viral suppression and preventing breastmilk HIV transmission.

      6. Where are the positives? HIV testing in sub-Saharan Africa in the era of test and treatexternal icon
        De Cock KM, Barker JL, Baggaley R, El Sadr WM.
        Aids. 2019 Feb 1;33(2):349-352.

        [No abstract]

      7. PURPOSE OF REVIEW: Influenza causes a range of illnesses in children, from uncomplicated self-limited illness to severe disease and death. This review provides an update on the severity and burden of influenza in US children over recent seasons. RECENT FINDINGS: The 2017-2018 influenza season was widespread and severe across all ages, including children. Disease severity is influenced by influenza virologic characteristics and host factors, as well as public health interventions such as influenza vaccination and antiviral treatment. In recent influenza A (H3N2)-predominant seasons (2016-2017 and 2017-2018), influenza vaccination effectiveness was higher in younger children compared with older children and adolescents, although the reasons for this are unclear. Interestingly, even in seasons when influenza A (H3N2) viruses predominate, influenza A (H1N1)pdm09 and B viruses can play a large role in severe pediatric disease. Although children less than 5 years of age and those with underlying medical conditions are at increased risk for severe disease, influenza-associated hospitalizations and deaths occur every season in healthy children. SUMMARY: Influenza causes a substantial burden of outpatient visits, hospitalizations, and deaths among children. Ongoing research is important to better characterize factors that contribute to influenza severity, and to identify strategies to improve the impact of influenza vaccination and treatment.

      8. Trends in geographic rates of HIV diagnoses among black females in the United States, 2010-2015external icon
        Elmore K, Bradley EL, Lima AC, Khalil GM, Obi-Tabot E, Gant Z, Dean HD, McCree DH.
        J Womens Health (Larchmt). 2018 Dec 8.

        BACKGROUND: HIV diagnoses among females in the United States declined 22% from 2010 to 2015, including a 27% decline in diagnoses among black females. Despite this progress, disparities persist. Black females accounted for 60% of new HIV diagnoses among females in 2015. Geographic disparities also exist. This article describes geographic differences in HIV diagnoses among black females in the United States, from 2010 to 2015. MATERIALS AND METHODS: We examined HIV surveillance data from 2010 to 2015 to determine in which geographic areas decreases or increases in HIV diagnoses occurred. We used data from the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention’s (NCHHSTP) AtlasPlus to calculate percent changes in HIV diagnosis rates by geographic region for black females >/=13 years of age. RESULTS: The number of new HIV diagnoses declined 27% among black females from 2010 to 2015. The highest rates of HIV diagnosis per 100,000 population of black females, from 2010 to 2015, were in the Northeast and the South. In 2015, five of the eight states reporting the highest rates of HIV diagnosis (i.e., the highest quartile) were in the South. CONCLUSIONS: HIV diagnosis rates decreased nationally among black females, but the decreases were not uniform within regions or across the United States. Some states experienced increases, and black females in the South and Northeast remain disproportionately affected. Additional research is needed to ascertain factors associated with the increases to continue progress toward reducing HIV-related disparities among females in the United States.

      9. Trends and gaps in national blood transfusion services – 14 sub-Saharan African countries, 2014-2016external icon
        Kanagasabai U, Chevalier MS, Drammeh B, Mili FD, Qualls ML, Bock N, Benech I, Nelson LJ, Alemnji G, Watts DH, Kimani D, Selenic D.
        MMWR Morb Mortal Wkly Rep. 2018 Dec 21;67(50):1392-1396.

        Ensuring availability of safe blood products through recruitment of voluntary, nonremunerated, blood donors (VNRDs) and prevention of transfusion-transmissible infections (TTIs), including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis, is important for public health (1,2). During 2004-2016, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) provided approximately $468 million in financial support and technical assistance* to 14 sub-Saharan African countries(dagger) with high HIV prevalence to strengthen national blood transfusion services (NBTSs)( section sign) and improve blood safety and availability. CDC analyzed these countries’ 2014-2016 blood safety surveillance data to update previous reports (1,2) and summarize achievements and programmatic gaps as some NBTSs begin to transition funding and technical support from PEPFAR to local ministries of health (MOHs) (2,3). Despite a 60% increase in blood supply since 2004 and steady declines in HIV prevalence (to <1% among blood donors in seven of the 14 countries), HIV prevalence among blood donors still remains higher than that recommended by the World Health Organization (WHO) (4). PEPFAR support has contributed to significant reductions in HIV prevalence among blood donors in the majority of PEPFAR-supported countries, and linking donors who screen HIV-positive to confirmatory testing and indicated treatment, as well as further reducing TTIs, remains a public health priority (5).

      10. Data triangulation to estimate age-specific coverage of voluntary medical male circumcision for HIV prevention in four Kenyan countiesexternal icon
        Kripke K, Opuni M, Odoyo-June E, Onyango M, Young P, Serrem K, Ojiambo V, Schnure M, Stegman P, Njeuhmeli E.
        PLoS One. 2018 ;13(12):e0209385.

        BACKGROUND: Kenya is 1 of 14 priority countries in Africa scaling up voluntary medical male circumcision (VMMC) for HIV prevention following the recommendations of the World Health Organization and the Joint United Nations Programme on HIV/AIDS. To inform VMMC target setting, we modeled the impact of circumcising specific client age groups across several Kenyan geographic areas. METHODS: The Decision Makers’ Program Planning Tool, Version 2 (DMPPT 2) was applied in Kisumu, Siaya, Homa Bay, and Migori counties. Initial modeling done in mid-2016 showed coverage estimates above 100% in age groups and geographic areas where demand for VMMC continued to be high. On the basis of information obtained from country policy makers and VMMC program implementers, we adjusted circumcision coverage for duplicate reporting, county-level population estimates, migration across county boundaries for VMMC services, and replacement of traditional circumcision with circumcisions in the VMMC program. To address residual inflated coverage following these adjustments we applied county-specific correction factors computed by triangulating model results with coverage estimates from population surveys. RESULTS: A program record review identified duplicate reporting in Homa Bay, Kisumu, and Siaya. Using county population estimates from the Kenya National Bureau of Statistics, we found that adjusting for migration and correcting for replacement of traditional circumcision with VMMC led to lower estimates of 2016 male circumcision coverage especially for Kisumu, Migori, and Siaya. Even after addressing these issues, overestimation of 2016 male circumcision coverage persisted, especially in Homa Bay. We estimated male circumcision coverage in 2016 by applying correction factors. Modeled estimates for 2016 circumcision coverage for the 10- to 14-year age group ranged from 50% in Homa Bay to approximately 90% in Kisumu. Results for the 15- to 19-year age group suggest almost complete coverage in Kisumu, Migori, and Siaya. Coverage for the 20- to 24-year age group ranged from about 80% in Siaya to about 90% in Homa Bay, coverage for those aged 25-29 years ranged from about 60% in Siaya to 80% in Migori, and coverage in those aged 30-34 years ranged from about 50% in Siaya to about 70% in Migori. CONCLUSIONS: Our analysis points to solutions for some of the data issues encountered in Kenya. Kenya is the first country in which these data issues have been encountered because baseline circumcision rates were high. We anticipate that some of the modeling methods we developed for Kenya will be applicable in other countries.

      11. Background: Although measles was declared eliminated from the United States in 2000, measles cases and outbreaks continue to occur, resulting from importations of the disease from countries where it remains endemic. Methods: We describe the epidemiology of international importations of measles virus into the United States during the post-elimination era. Results: From 2001 to 2016, 553 imported measles cases were reported to the Centers for Disease Control and Prevention. A median of 28 importations occurred each year (range: 1880). The median age of imported case-patients was 18 years (range: three months75 years); 87% were unvaccinated or had an unknown vaccination status. U.S. residents (as opposed to foreign visitors) accounted for 62% of imported measles cases. Overall, 62% of all imported case-patients reported travel to countries in the Western Pacific and European Regions of the World Health Organization during their exposure periods. The number of measles importations from specific countries was related to the incidence of measles in and the volume of travel to and from the source country. Conclusions: ur findings emphasize the importance of measles vaccination of U.S. residents aged >/=6 months before international travel according to Advisory Committee on Immunization Practices recommendations and supporting global measles elimination efforts.

      12. Clinical and epidemiologic profiles for identifying norovirus in acute gastroenteritis outbreak investigationsexternal icon
        Lively JY, Johnson SD, Wikswo M, Gu W, Leon J, Hall AJ.
        Open Forum Infect Dis. 2018 Apr;5(4):ofy049.

        Background: Noroviruses are the leading cause of acute gastroenteritis (AGE) outbreaks in the United States. However, outbreaks attributed to norovirus often lack confirmation by diagnostic testing. Clinical and epidemiologic profiles, such as the Kaplan criteria (vomiting in >50% cases, mean incubation period of 24-48 hours, mean duration of illness for 12-60 hours, and negative bacterial stool culture), have been used to distinguish norovirus outbreaks from those caused by bacteria. Methods: Kaplan criteria were evaluated among 10 023 outbreaks reported to the National Outbreak Reporting System (NORS) during 2009-2012. An alternate profile for distinguishing norovirus outbreaks from outbreaks caused by nonviral etiologies was identified using classification and regression tree (CART) modeling. Performance of the Kaplan criteria and alternate profile were compared among laboratory-confirmed outbreaks. Results: The Kaplan criteria were 63.9% sensitive and 100% specific in discriminating norovirus from nonviral outbreaks, but only 3.3% of norovirus and 1.2% of nonviral outbreaks reported all criteria. Clinical and epidemiologic characteristics identified with CART modeling (ratio of proportion of cases with fever to the proportion of cases with vomiting <1, proportion of cases with bloody stool <0.1, proportion of cases with vomiting >/=0.26) were 85.7% sensitive and 92.4% specific for distinguishing norovirus from nonviral outbreaks and were applicable to more than 8 times as many outbreaks compared with the Kaplan criteria. Conclusions: Compared with the Kaplan criteria, the CART-derived profile had higher sensitivity and broader application in reported AGE outbreaks. Thus, this alternate profile may provide a more useful tool for identifying norovirus during outbreak investigations.

      13. Molecular epidemiology of noroviruses in children under 5 years of age with acute gastroenteritis in Yaounde, Cameroonexternal icon
        Mugyia AE, Ndze VN, Akoachere JT, Browne H, Boula A, Ndombo PK, Cannon JL, Vinje J, Ndip LM.
        J Med Virol. 2018 Dec 20.

        Norovirus is a common cause of acute gastroenteritis (AGE) among children in developing countries. Limited data on the prevalence and genetic variability of norovirus are available in Cameroon, where early childhood mortality due to AGE is common. We tested 902 fecal specimens from children younger than 5 years of age hospitalized with AGE between January 2010 and December 2013. Overall, 76 (8.4%) samples tested positive for norovirus, of which 83% (63/76) were among children < 12 months old. Most of the noroviruses detected were in children infected between July and December of each year. All norovirus-positive specimens were genotyped, with 80% (61/76) being GII.4 (three variants detected). Genotypes GI.2, GI.6, GII.1, GII.2, GII.3, GII.6, GII.16, GII.17, and GII.21 genotypes were also detected. Interestingly, GII.4 Sydney and GII.17 Kawasaki viruses were found as early as 2010, years before their emergence globally. This study suggests norovirus is a significant cause of moderate to severe gastroenteritis among young children in Cameroon. Results are important to highlight appropriate prevention and control strategies for reducing the burden of norovirus disease. This article is protected by copyright. All rights reserved.

      14. Wild poliovirus (WPV) is nearing eradication, and only three countries have never interrupted WPV transmission (Pakistan, Afghanistan, and Nigeria). WPV2 was last detected in 1999, and it was declared eradicated in 2015. WPV3 has not been detected since 2012. Since 2016, WPV1 has been detected in only two countries (Afghanistan and Pakistan), with only 22 cases reported in 2017 and 12 cases reported in 2018 (as of July 10). Because of WPV2 eradication and the risk of emergence of type 2 vaccine-derived polioviruses from continued use of trivalent oral polio vaccine (OPV), trivalent OPV was replaced by bivalent OPV (types 1 and 3) in a globally coordinated effort in 2016. WPV2 eradication and trivalent OPV cessation also mean that breach of containment in a facility working with type 2 poliovirus is now a major risk to reseed type 2 circulation in the community. As a result, the World Health Organization has developed a “Global Action Plan to minimize poliovirus facility-associated risk after type-specific eradication of wild polioviruses and sequential cessation of oral polio vaccine use.” Because poliovirus has long been used as a standard for qualification of intravenous immunoglobulin, disinfectant products, and sanitation methods, poliovirus containment has implications far beyond poliovirus laboratories.

      15. Electronic medical record data structure prevents easy population-level monitoring of hepatitis C virus (HCV) treatment uptake and cure. Using an HCV registry from a public hospital system in Atlanta, Georgia, we developed multiple algorithms using serial HCV RNA test results as proxy measures for direct acting antiviral (DAA) treatment initiation and sustained virologic response (SVR). We calculated sensitivity and positive predictive values by comparing the algorithms to the DAA initiation and SVR results from the registry. From December 2013 – August 2016, 1,807 persons actively infected with HCV were identified in the registry. Of those, 698 initiated DAA treatment based on medical record abstraction; of 442 patients with treatment start and/or end dates, 314 had documented SVR. Treatment algorithm 2 (detectable HCV RNA result followed by 2 sequential HCV RNA tests results) and treatment algorithm 5 (detectable HCV RNA result followed by 2 sequential HCV RNA tests results > 6 weeks apart) had the highest sensitivity (87% and 85% respectively) and positive predictive value (80% and 82% respectively) combinations. Four SVR algorithms relied on fulfilling treatment algorithm definitions and having an undetectable HCV RNA test result >/= 12 weeks after the last HCV RNA result; sensitivity for all was 79% and positive predictive value was 92-93%. Algorithms using serial quantitative HCV RNA results can serve as proxy measures for evaluating population-level DAA treatment and SVR outcomes.

      16. The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africaexternal icon
        Park SE, Pham DT, Boinett C, Wong VK, Pak GD, Panzner U, Espinoza LM, von Kalckreuth V, Im J, Schutt-Gerowitt H, Crump JA, Breiman RF, et al .
        Nat Commun. 2018 Nov 30;9(1):5094.

        There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S. Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S. Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S. Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa.

      17. Respiratory syncytial virus hospitalization during pregnancy in 4 high-income countries, 2010-2016external icon
        Regan AK, Klein NP, Langley G, Drews SJ, Buchan S, Ball S, Kwong JC, Naleway A, Thompson M, Wyant BE, Levy A, Chung H, Feldman B, Katz MA.
        Clin Infect Dis. 2018 Nov 28;67(12):1915-1918.

        Few studies have addressed respiratory syncytial virus (RSV) infection during pregnancy. Among 846 pregnant women hospitalized with respiratory illness and tested for RSV, 21 (2%) were RSV positive, of whom 8 (38%) were diagnosed with pneumonia. Despite study limitations, these data can help inform decisions about RSV prevention strategies.

      18. Low admission plasma gelsolin concentrations identify community-acquired pneumonia patients at high risk for severe outcomesexternal icon
        Self WH, Wunderink RG, DiNubile MJ, Stossel TP, Levinson SL, Williams DJ, Anderson EJ, Bramley AM, Jain S, Edwards KM, Grijalva CG.
        Clin Infect Dis. 2018 Dec 17.

        Background: Plasma gelsolin (pGSN) is an abundant circulating protein that neutralizes actin exposed by damaged cells, modulates inflammatory responses, and enhances alveolar macrophage antimicrobial activity. We investigated whether adults with low pGSN at hospital admission for community-acquired pneumonia (CAP) were at high risk for severe outcomes. Methods: Admission pGSN concentrations were measured by enzyme-linked immunosorbent assay in 455 adults hospitalized with CAP. Patients were grouped into four hierarchical, mutually-exclusive categories based on maximum clinical severity experienced during their hospitalization: (1) general floor care without intensive care (ICU) unit admission, invasive respiratory or vasopressor support (IRVS), or death; (2) ICU care without IRVS or death; (3) IRVS without death; or (4) death. Admission pGSN concentrations were compared across these discrete outcome categories. Additionally, outcomes among patients in the lowest quartile of pGSN concentration were compared with those in the upper three quartiles. Results: Overall, median (interquartile range) pGSN concentration was 38.1 (32.1, 45.7) mug/mL. Patients with more severe outcomes had lower pGSN concentrations (p=0.0001); median values were: 40.3 mug/ml for floor patients; 36.7 mug/ml for ICU patients; 36.5 mug/ml for patients receiving IRVS; and 25.7 mug/ml for patients who died. Compared with patients with higher pGSN concentrations, patients in the lowest quartile (pGSN </=32.1 mug/ml) more often required IRVS (21.2% vs 11.7%, p=0.0114) and died (8.8% vs 0.9%, p<0.0001). Conclusions: Among adults hospitalized with CAP, lower pGSN concentrations were associated with more severe clinical outcomes. Future studies are planned to investigate possible therapeutic benefits of recombinant human pGSN in this population.

      19. Serological and PCR-based markers of ocular Chlamydia trachomatis transmission in northern Ghana after elimination of trachoma as a public health problemexternal icon
        Senyonjo LG, Debrah O, Martin DL, Asante-Poku A, Migchelsen SJ, Gwyn S, deSouza DK, Solomon AW, Agyemang D, Biritwum-Kwadwo N, Marfo B, Bakajika D, Mensah EO, Aboe A, Koroma J, Addy J, Bailey R.
        PLoS Negl Trop Dis. 2018 Dec 14;12(12):e0007027.

        BACKGROUND: Validation of elimination of trachoma as a public health problem is based on clinical indicators, using the WHO simplified grading system. Chlamydia trachomatis (Ct) infection and anti-Ct antibody responses (anti-Pgp3) have both been evaluated as alternative indicators in settings with varying levels of trachoma. There is a need to evaluate the feasibility of using tests for Ct infection and anti-Pgp3 antibodies at scale in a trachoma-endemic country and to establish the added value of the data generated for understanding transmission dynamics in the peri-elimination setting. METHODOLOGY/PRINCIPAL FINDINGS: Dried blood spots for serological testing and ocular swabs for Ct infection testing (taken from children aged 1-9 years) were integrated into the pre-validation trachoma surveys conducted in the Northern and Upper West regions of Ghana in 2015 and 2016. Ct infection was detected using the GeneXpert PCR platform and the presence of anti-Pgp3 antibodies was detected using both the ELISA assay and multiplex bead array (MBA). The overall mean cluster-summarised TF prevalence (the clinical indicator) was 0.8% (95% CI: 0.6-1.0) and Ct infection prevalence was 0.04% (95%CI: 0.00-0.12). Anti-Pgp3 seroprevalence using the ELISA was 5.5% (95% CI: 4.8-6.3) compared to 4.3% (95%CI: 3.7-4.9) using the MBA. There was strong evidence from both assays that seropositivity increased with age (p<0.001), although the seroconversion rate was estimated to be very low (between 1.2 to 1.3 yearly events per 100 children). CONCLUSIONS/SIGNIFICANCE: Infection and serological data provide useful information to aid in understanding Ct transmission dynamics. Elimination of trachoma as a public health problem does not equate to the absence of ocular Ct infection nor cessation in acquisition of anti-Ct antibodies.

      20. A strategy for PrEP clinicians to manage ambiguous HIV test results during follow-up visitsexternal icon
        Smith DK, Switzer WM, Peters P, Delaney KP, Granade TC, Masciotra S, Shouse L, Brooks JT.
        Open Forum Infect Dis. 2018 Aug;5(8):ofy180.

        Prompt determination of HIV infection status is critical during follow-up visits for patients taking pre-exposure prophylaxis (PrEP) medication. Those who are uninfected can then continue safely taking PrEP, and those few who have acquired HIV infection can initiate an effective treatment regimen. However, a few recent cases have been reported of ambiguous HIV test results using common testing algorithms in PrEP patients. We review published reports of such cases and testing options that can be used to clarify true HIV status in these situations. In addition, we review the benefits and risks of 3 antiretroviral management options in these patients: (1) continue PrEP while conducting additional HIV tests, (2) initiate antiretroviral therapy for presumptive HIV infection while conducting confirmatory tests, or (3) discontinue PrEP to reassess HIV status after a brief antiretroviral-free interval. A clinical consultation resource is also provided.

      21. OBJECTIVE: To describe recent syphilis trends among pregnant women and to evaluate the prevalence of reported high-risk behaviors in this population. METHODS: We analyzed U.S. national case report data for 2012-2016 to assess trends among pregnant women with all stages of syphilis. Risk behavior data collected through case interviews during routine local health department investigation of syphilis cases were used to evaluate the number of pregnant women with syphilis reporting these behaviors. RESULTS: During 2012-2016, the number of syphilis cases among pregnant women increased 61%, from 1,561 to 2,508, and this increase was observed across all races and ethnicities, all women aged 15-45 years, and all U.S. regions. Of 15 queried risk factors, including high-risk sexual behaviors and drug use, 49% of pregnant women with syphilis did not report any in the past year. The most commonly reported risk behaviors were a history of a sexually transmitted disease (43%) and more than one sex partner in the past year (30%). CONCLUSION: Syphilis cases among pregnant women increased from 2012 to 2016, and in half, no traditional behavioral risk factors were reported. Efforts to reduce syphilis among pregnant women should involve increasing health care provider awareness of the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists’ recommendations, which include screening all pregnant women for syphilis at the first prenatal visit and rescreening high-risk women during the third trimester and at delivery. Health care providers should also consider local syphilis prevalence in addition to individual reported risk factors when deciding whether to repeat screening.

      22. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenzaexternal icon
        Uyeki TM, Bernstein HH, Bradley JS, Englund JA, File TM, Fry AM, Gravenstein S, Hayden FG, Harper SA, Hirshon JM, Ison MG, Johnston BL, Knight SL, McGeer A, Riley LE, Wolfe CR, Alexander PE, Pavia AT.
        Clin Infect Dis. 2018 Dec 19.

        These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic. This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza. It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza. The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients.

      23. Maintenance and reappearance of extremely divergent intra-host HIV-1 variantsexternal icon
        Wertheim JO, Oster AM, Murrell B, Saduvala N, Heneine W, Switzer WM, Johnson JA.
        Virus Evol. 2018 Jul;4(2):vey030.

        Understanding genetic variation in human immunodeficiency virus (HIV) is clinically and immunologically important for patient treatment and vaccine development. We investigated the longitudinal intra-host genetic variation of HIV in over 3,000 individuals in the US National HIV Surveillance System with at least four reported HIV-1 polymerase (pol) sequences. In this population, we identified 149 putative instances of superinfection (i.e. an individual sequentially infected with genetically divergent, polyphyletic viruses). Unexpectedly, we discovered a group of 240 individuals with consecutively sampled viral strains that were >0.015 substitutions/site divergent, despite remaining monophyletic in the phylogeny. Viruses in some of these individuals had a maximum genetic divergence approaching that found between two random, unrelated HIV-1 subtype-B pol sequences within the US population. Individuals with these highly divergent viruses tended to be diagnosed nearly a decade earlier in the epidemic than people with superinfection or virus with less intra-host genetic variation, and they had distinct transmission risk factor profiles. To better understand this genetic variation in cases with extremely divergent, monophyletic viruses, we performed molecular clock phylogenetic analysis. Our findings suggest that, like Hepatitis C virus, extremely divergent HIV lineages can be maintained within an individual and reemerge over a period of years.

    • Community Health Services

      1. Predictors of receipt of school services in a national sample of youth with ADHDexternal icon
        DuPaul GJ, Chronis-Tuscano A, Danielson ML, Visser SN.
        J Atten Disord. 2018 Dec 10.

        OBJECTIVE: The objective of the study is to describe the extent to which students with ADHD received school-based intervention services and identify demographic, diagnostic, and impairment-related variables that are associated with service receipt in a large, nationally drawn sample. METHOD: Parent-reported data were obtained for 2,495 children with ADHD aged 4 to 17 years from the National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome (NS-DATA). RESULTS: The majority (69.3%) of students with ADHD currently receive one or more school services. Educational support (62.3%) was nearly twice as prevalent as classroom behavior management (32.0%). More than 3 times as many students with ADHD had an individualized education program (IEP; 42.9%) as a Section 504 plan (13.6%). CONCLUSION: At least one in five students with ADHD do not receive school services despite experiencing significant academic and social impairment, a gap that is particularly evident for adolescents and youth from non-English-speaking and/or lower income families.

    • Disaster Control and Emergency Services

      1. Nerve agent incidents and public health preparednessexternal icon
        Chang A, Thomas J, Johnson R, Gorman SE, Schier J, Yip L.
        Ann Intern Med. 2018 Dec 18.

        [No abstract]

      2. Bioaerosol sampling for respiratory viruses in Singapore’s mass rapid transit networkexternal icon
        Coleman KK, Nguyen TT, Yadana S, Hansen-Estruch C, Lindsley WG, Gray GC.
        Sci Rep. 2018 Nov 30;8(1):17476.

        As a leading global city with a high population density, Singapore is at risk for the introduction of novel biological threats. This risk has been recently reinforced by human epidemics in Singapore of SARS coronavirus, 2009 pandemic H1N1 influenza A virus, and enterovirus 71. Other major threats to Singapore include MERS-coronavirus and various avian and swine influenza viruses. The ability to quickly identify and robustly track such threats to initiate an early emergency response remains a significant challenge. In an effort to enhance respiratory virus surveillance in Singapore, our team conducted a pilot study employing a noninvasive bioaerosol sampling method to detect respiratory viruses in Singapore’s Mass Rapid Transit (MRT) network. Over a period of 52 weeks, 89 aerosol samples were collected during peak MRT ridership hours. Nine (10%) tested positive for adenovirus, four (4.5%) tested positive for respiratory syncytial virus type A, and one (1%) tested positive for influenza A virus using real-time RT-PCR/PCR. To our knowledge, this is the first time molecular evidence for any infectious respiratory agent has been collected from Singapore’s MRT. Our pilot study data support the possibility of employing bioaerosol samplers in crowded public spaces to noninvasively monitor for respiratory viruses circulating in communities.

      3. Infants, children, and adolescents can be exposed unexpectedly to ionizing radiation from nuclear power plant events, improvised nuclear or radiologic dispersal device explosions, or inappropriate disposal of radiotherapy equipment. Children are likely to experience higher external and internal radiation exposure levels than adults because of their smaller body and organ size and other physiologic characteristics as well as their tendency to pick up contaminated items and consume contaminated milk or foodstuffs. This technical report accompanies the revision of the 2003 American Academy of Pediatrics policy statement on pediatric radiation emergencies by summarizing newer scientific data from studies of the Chernobyl and the Fukushima Daiichi nuclear power plant events, use of improvised radiologic dispersal devices, exposures from inappropriate disposal of radiotherapy equipment, and potential health effects from residential proximity to nuclear plants. Also included are recommendations from epidemiological studies and biokinetic models to address mitigation efforts. The report includes major emphases on acute radiation syndrome, acute and long-term psychological effects, cancer risks, and other late tissue reactions after low-to-high levels of radiation exposure. Results, along with public health and clinical implications, are described from studies of the Japanese atomic bomb survivors, nuclear plant accidents (eg, Three Mile Island, Chernobyl, and Fukushima), improper disposal of radiotherapy equipment in Goiania, Brazil, and residence in proximity to nuclear plants. Measures to reduce radiation exposure in the immediate aftermath of a radiologic or nuclear disaster are described, including the diagnosis and management of external and internal contamination, use of potassium iodide, and actions in relation to breastfeeding.

    • Disease Reservoirs and Vectors

      1. Clustering of necropsy-confirmed porcine cysticercosis surrounding Taenia solium tapeworm carriers in Peruexternal icon
        Lescano AG, Pray IW, Gonzalez AE, Gilman RH, Tsang VC, Gamboa R, Guezala MC, Aybar V, Rodriguez S, Moulton LH, Leontsini E, Gonzalvez G, O’Neal SE, Garcia HH.
        Am J Trop Med Hyg. 2018 Dec 17.

        The pork tapeworm, Taenia solium, is among the leading causes of preventable epilepsy in the world and is common in rural areas of developing countries where sanitation is limited and pigs have access to human feces. Prior studies in rural villages of Peru have observed clusters of T. solium cysticercosis among pigs that live near human tapeworm carriers. Such spatial analyses, however, have been limited by incomplete participation and substandard diagnostic tests. In this study, we evaluated the association between necropsy-confirmed cysticercosis in pigs and their distance to T. solium tapeworm carriers in six villages in northern Peru. A total of six (1.4%) tapeworm carriers were detected using enzyme-linked immunosorbent assay-coproantigen assay, and seven of 10 (70%) pigs belonging to the tapeworm carriers were found with viable cyst infection on necropsy. This was significantly greater than the prevalence of viable cyst infection among pigs living < 500 m (11%) and > 500 m (0.5%) from a tapeworm carrier (P < 0.001 for distance trend). Similar statistically significant prevalence gradients were observed after adjustment for possible confounders and for other pig-level outcomes including infection with > 10 viable cysts, degenerated cyst infection, and serological outcomes. This investigation confirms that porcine cysticercosis clusters strongly around tapeworm carriers in endemic rural regions of northern Peru and supports interventions that target these hot spots.

    • Drug Safety

      1. Africa Centres for Disease Control and Prevention’s framework for antimicrobial resistance control in Africaexternal icon
        Varma JK, Oppong-Otoo J, Ondoa P, Perovic O, Park BJ, Laxminarayan R, Peeling RW, Schultsz C, Li H, Ihekweazu C, Sall AA, Jaw B, Nkengasong JN.
        Afr J Lab Med. 2018 ;7(2):830.

        [No abstract]

    • Environmental Health

      1. [No abstract]

      2. Prepubertal and pubertal endocrine-disrupting chemical exposure and breast density among Chilean adolescentsexternal icon
        Binder AM, Corvalan C, Pereira A, Calafat AM, Ye X, Shepherd J, Michels KB.
        Cancer Epidemiol Biomarkers Prev. 2018 Dec;27(12):1491-1499.

        BACKGROUND: During puberty, mammary tissue undergoes rapid development, which provides a window of heightened susceptibility of breast composition to the influence of endogenous and exogenous hormones. Exposure to endocrine-disrupting chemicals (EDC) may affect breast development and composition and the risk of developing breast cancer in adulthood. METHODS: We evaluated the associations between breast density and urinary concentrations of phenols and phthalates collected at Tanner 1 (B1) and Tanner 4 (B4) in 200 Chilean girls. Total breast volume (BV), fibroglandular volume (FGV), and percent dense breast (%FGV) were evaluated at B4 using dual X-ray absorptiometry. Generalized estimating equations were used to analyze the association between concentrations of EDC biomarkers across puberty and breast density. RESULTS: The geometric mean %FGV was 7% higher among girls in the highest relative to the lowest tertile of monocarboxyisooctyl phthalate [1.07; 95% confidence interval (CI), 1.01-1.14]. Monoethyl phthalate concentrations at B4 were positively associated with FGV (highest vs. lowest tertile: 1.22; 95% CI, 1.06-1.40). Bisphenol A displayed a U-shaped association with FGV; girls in the middle tertile had at least 10% lower FGV than girls in the lowest or highest tertiles. Monocarboxyisononyl phthalate showed a nonlinear association with BV. No other statistically significant associations were observed. CONCLUSIONS: Our results suggest that the developing breast tissue is susceptible to select EDCs during childhood and adolescence. IMPACT: This study may spur further investigations into environmental influences on breast development during puberty and how shifts in pubertal breast density track through the life course to modify breast cancer risk.

      3. Lead exposure during childhood and subsequent anthropometry through adolescence in girlsexternal icon
        Deierlein AL, Teitelbaum SL, Windham GC, Pinney SM, Galvez MP, Caldwell KL, Jarrett JM, Gajek R, Kushi LH, Biro F, Wolff MS.
        Environ Int. 2018 Nov 28.

        INTRODUCTION: Cross-sectional studies suggest that postnatal blood lead (PbB) concentrations are negatively associated with child growth. Few studies prospectively examined this association in populations with lower PbB concentrations. We investigated longitudinal associations of childhood PbB concentrations and subsequent anthropometric measurements in a multi-ethnic cohort of girls. METHODS: Data were from The Breast Cancer and the Environment Research Program at three sites in the United States (U.S.): New York City, Cincinnati, and San Francisco Bay Area. Girls were enrolled at ages 6-8years in 2004-2007. Girls with PbB concentrations collected at </=10years old (mean 7.8years, standard deviation (SD) 0.82) and anthropometry collected at >/=3 follow-up visits were included (n=683). The median PbB concentration was 0.99mug/d (10th percentile=0.59mug/dL and 90th percentile=2.00mug/dL) and the geometric mean was 1.03mug/dL (95% Confidence Interval (CI): 0.99, 1.06). For analyses, PbB concentrations were dichotomized as <1mug/dL (n=342) and >/=1mug/dL (n=341). Anthropometric measurements of height, body mass index (BMI), waist circumference (WC), and percent body fat (%BF) were collected at enrollment and follow-up visits through 2015. Linear mixed effects regression estimated how PbB concentrations related to changes in girls’ measurements from ages 7-14years. RESULTS: At 7years, mean difference in height was -2.0cm (95% CI: -3.0, -1.0) for girls with >/=1mug/dL versus <1mug/dL PbB concentrations; differences persisted, but were attenuated, with age to -1.5cm (95% CI: -2.5, -0.4) at 14years. Mean differences for BMI, WC, and BF% at 7years between girls with >/=1mug/dL versus <1mug/dL PbB concentrations were -0.7kg/m(2) (95% CI: -1.2, -0.2), -2.2cm (95% CI: -3.8, -0.6), and -1.8% (95% CI: -3.2, -0.4), respectively. Overall, these differences generally persisted with advancing age and at 14years, differences were -0.8kg/m(2) (95% CI: -1.5, -0.02), -2.9cm (95% CI: -4.8, -0.9), and -1.7% (95% CI: -3.1, -0.4) for BMI, WC, and BF%, respectively. CONCLUSIONS: These findings suggest that higher concentrations of PbB during childhood, even though relatively low by screening standards, may be inversely associated with anthropometric measurements in girls.

      4. Water quality, availability, and acute gastroenteritis on the Navajo Nation – a pilot case-control studyexternal icon
        Grytdal SP, Weatherholtz R, Esposito DH, Campbell J, Reid R, Gregoricus N, Schneeberger C, Lusk TS, Xiao L, Garrett N, Bopp C, Hammitt LL, Vinje J, Hill VR, O’Brien KL, Hall AJ.
        J Water Health. 2018 Dec;16(6):1018-1028.

        The Navajo Nation includes approximately 250,000 American Indians living in a remote high desert environment with limited access to public water systems. We conducted a pilot case-control study to assess associations between acute gastroenteritis (AGE) and water availability, use patterns, and quality. Case patients with AGE and non-AGE controls who presented for care to two Indian Health Service hospitals were recruited. Data on demographics and water use practices were collected using a standard questionnaire. Household drinking water was tested for presence of pathogens, coliforms, and residual chlorine. Sixty-one subjects (32 cases and 29 controls) participated in the study. Cases and controls were not significantly different with respect to water sources, quality, or patterns of use. Twenty-one percent (n = 12) of study participants resided in dwellings not connected to a community water system. Eleven percent (n = 7) of subjects reported drinking hauled water from unregulated sources. Coliform bacteria were present in 44% (n = 27) of household water samples, and 68% (n = 40) of samples contained residual chlorine concentrations of <0.2 mg/L. This study highlights issues with water availability, quality, and use patterns within the Navajo Nation, including sub-optimal access to community water systems, and use of water hauled from unregulated sources.

      5. Correlation and temporal variability of urinary biomarkers of chemicals among couples: Implications for reproductive epidemiological studiesexternal icon
        Nassan FL, Williams PL, Gaskins AJ, Braun JM, Ford JB, Calafat AM, Hauser R.
        Environ Int. 2018 Dec 5;123:181-188.

        BACKGROUND: Exposure to some environmental chemicals is ubiquitous and linked to a variety of adverse outcomes, including children’s health. While few studies have assessed the contribution of both male and female exposures to children’s health, understanding the patterns of couple’s exposure is needed to understand their joint effects. OBJECTIVE: We assessed the correlation patterns between male and female partners’ concentrations of 37 environmental chemical biomarkers. We also assessed the temporal reliability of the biomarkers within couples. METHODS: We calculated Spearman pairwise correlations between specific gravity adjusted urinary biomarker concentrations and hair mercury concentrations among 380 couples enrolled in the Environment and Reproductive Health (EARTH) study at the Massachusetts General Hospital Fertility Center (2004-2017). We calculated intra-class correlation coefficients (ICCs) for couple’s biomarkers to assess the temporal variability of these exposures within a couple using multiple paired-samples from couples. RESULTS: All biomarkers were positively correlated within couples (range: 0.05 for tert-butylphenyl phenyl phosphate to 0.66 for triclosan). In general, the biomarkers with the highest within couple correlation were those of chemicals for which diet (e.g., di(2-ethylhexyl) phthalate), personal care products use (e.g., triclosan, benzophenone-3), and the indoor environment (e.g., 2,5-dichlorophenol) are considered primary exposure sources. Most other biomarkers were moderately correlated (0.3-<0.6). Similar patterns of temporal reliability were observed across biomarkers. CONCLUSIONS: Urinary concentrations of several biomarkers were mostly moderately correlated within couples, suggesting similar exposure sources. Future epidemiological studies should collect samples from both partners to be able to accurately determine the contribution of maternal and paternal exposures to offspring health.

      6. BACKGROUND: Di-2-ethylhexyl terephthalate (DEHTP) is used as a replacement plasticizer for other phthalates, including di-2-ethylhexyl phthalate (DEHP). Use of consumer products containing DEHTP may result in human exposure to DEHTP. OBJECTIVE: To assess exposure to DEHTP in a nationally representative sample of the U.S. general population 3years and older from the 2015-2016 National Health and Nutrition Examination Survey (NHANES). METHOD: We quantified two DEHTP metabolites, mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP) and mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) in 2970 urine samples by using online solid-phase extraction coupled with isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. We used linear regression to examine associations between MEHHTP and MECTPP and several parameters including age, sex, race/ethnicity, and household income. We also compared the MEHHTP and MECPTP results to those of their corresponding DEHP metabolite analogs, namely mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) and mono-2-ethyl-5-carboxypentyl phthalate (MECPP). RESULTS: The weighted detection frequencies were 96% (MEHHTP) and 99.9% (MECPTP); urinary concentrations of the two metabolites correlated significantly (Pearson correlation coefficient=0.89, p<0.0001). MECPTP concentrations were higher than MEHHTP in all age, sex, race/ethnicity groups examined. Furthermore, MECPTP adjusted geometric mean (GM) concentrations were significantly higher in samples collected in the evening than in the morning or afternoon. Females had significantly higher adjusted GM concentrations of MEHHTP and MECPTP than males. We observed no significant associations between the adjusted GM concentrations of the metabolites and race/ethnicity. Both metabolite adjusted GM concentrations increased significantly with household income, and decreased significantly with age. Only household income was significantly associated with the concentrations of MECPP, but not of MEHHP, the two DEHP metabolites. The adjusted GM of the [MEHHTP]:[MECPTP] molar concentrations ratio increased with age, and was significantly higher in samples collected in the morning than in those collected in the afternoon or evening. CONCLUSIONS: Exposure to DEHTP is widespread in the U.S. general population 3years and older. These data represent the first U.S. population-based representative background exposure to DEHTP.

      7. Exposure to polybrominated diphenyl ethers (PBDEs) during childhood and adiposity measures at age 8yearsexternal icon
        Vuong AM, Braun JM, Wang Z, Yolton K, Xie C, Sjodin A, Webster GM, Lanphear BP, Chen A.
        Environ Int. 2018 Dec 4;123:148-155.

        BACKGROUND: Animal studies suggest polybrominated diphenyl ethers (PBDEs) may be obesogens. However, epidemiologic studies investigating childhood exposure to PBDEs and adiposity are limited, with several reporting an inverse association. OBJECTIVES: To investigate associations between repeated childhood PBDE concentrations and adiposity measures at age 8years. METHODS: We examined 206 children from the Health Outcomes and Measures of the Environment Study, a birth cohort in Cincinnati, OH (2003-2006). Serum PBDEs were measured at ages 1, 2, 3, 5, and 8years. We used multiple imputation to estimate missing PBDE concentrations. At 8years, we measured weight, height, waist circumference, and body fat percentage. We used multiple informant models to estimate age-specific associations between PBDEs and adiposity measures. RESULTS: We observed significant inverse associations between BDE-153 with all adiposity measures that became increasingly stronger with later childhood measurements. A 10-fold increase in BDE-153 at ages 1 and 8years was associated with 2% (95% CI -3.9, -0.1) and 7% (95% CI -9.1, -4.7) lower body fat, respectively. No statistically significant associations were found with BDE-28, -47, -99, or -100. Child sex modified some associations; inverse associations between BDE-153 and body fat were stronger among boys, while positive and null associations were noted among girls. CONCLUSIONS: Childhood BDE-153 concentrations were inversely associated with adiposity measures and these associations became stronger as BDE-153 measurements were more proximal to adiposity measures. Inverse associations could be attributed to reverse causality arising from greater storage of PBDEs in adipose tissue of children with higher adiposity.

      8. Urinary concentrations of monohydroxylated polycyclic aromatic hydrocarbons in adults from the U.S. Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014)external icon
        Wang Y, Wong LY, Meng L, Pittman EN, Trinidad DA, Hubbard KL, Etheredge A, Del Valle-Pinero AY, Zamoiski R, van Bemmel DM, Borek N, Patel V, Kimmel HL, Conway KP, Lawrence C, Edwards KC, Hyland A, Goniewicz ML, Hatsukami D, Hecht SS, Calafat AM.
        Environ Int. 2018 Dec 6;123:201-208.

        BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants formed from incomplete combustion of organic matter; some PAHs are carcinogens. Smoking, diet, and other activities contribute to exposure to PAHs. Exposure data to PAHs among combustible tobacco product users (e.g. cigarette smokers) exist; however, among non-combustible tobacco products users (e.g., e-cigarette users), such data are rather limited. OBJECTIVES: We sought to evaluate exposure to PAHs among participants in Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study based on the type of tobacco product (combustible vs non-combustible), and frequency and intensity of product use. METHODS: We quantified seven PAH urinary biomarkers in 11,519 PATH Study participants. From self-reported information, we categorized 8327 participants based on their use of tobacco products as never-tobacco user (never user, n=1700), exclusive current established combustible products user (combustible products user, n=5767), and exclusive current established non-combustible products user (non-combustible products user, n=860). We further classified tobacco users as exclusive cigarette user (cigarette user, n=3964), exclusive smokeless product user (SLT user, n=509), and exclusive e-cigarette user (e-cigarette user, n=280). Last, we categorized frequency of product use (everyday vs some days) and time since use (last hour, within 3days, over 3days). We calculated geometric mean (GM) concentrations, and evaluated associations between tobacco product user categories and PAH biomarkers concentrations. RESULTS: Combustible products users had significantly higher GMs of all biomarkers than non-combustible products users and never users; non-combustible products users had significantly higher GMs than never users for four of seven biomarkers. For all biomarkers examined, cigarette users had the highest GMs compared to other tobacco-product users. Interestingly, GMs of 2-hydroxyfluorene, 3-hydroxyfluorene and summation operator2,3-hydroxyphenanthrene were significantly higher in SLT users than in e-cigarette users; 3-hydroxyfluorene and 1-hydroxypyrene were also significantly higher in e-cigarette and SLT users than in never users. Everyday cigarette and SLT users had significantly higher GMs for most biomarkers than some days’ users; cigarette and SLT users who used the product in the last hour had significantly higher GMs of most biomarkers than other occasional cigarette or SLT users respectively. By contrast, everyday e-cigarette users’ GMs of most biomarkers did not differ significantly from those in some days’ e-cigarette users; we did not observe clear trends by time of last use among e-cigarette users. CONCLUSIONS: Users of tobacco products had higher PAH urinary biomarker concentrations compared to never users, and concentrations differed by type and frequency of tobacco product use.

    • Genetics and Genomics

      1. The contribution of parent-to-offspring transmission of telomeres to the heritability of telomere length in humansexternal icon
        Delgado DA, Zhang C, Gleason K, Demanelis K, Chen LS, Gao J, Roy S, Shinkle J, Sabarinathan M, Argos M, Tong L, Ahmed A, Islam T, Rakibuz-Zaman M, Sarwar G, Shahriar H, Rahman M, Yunus M, Doherty JA, Jasmine F, Kibriya MG, Ahsan H, Pierce BL.
        Hum Genet. 2018 Dec 10.

        Leukocyte telomere length (LTL) is a heritable trait with two potential sources of heritability (h(2)): inherited variation in non-telomeric regions (e.g., SNPs that influence telomere maintenance) and variability in the lengths of telomeres in gametes that produce offspring zygotes (i.e., “direct” inheritance). Prior studies of LTL h(2) have not attempted to disentangle these two sources. Here, we use a novel approach for detecting the direct inheritance of telomeres by studying the association between identity-by-descent (IBD) sharing at chromosome ends and phenotypic similarity in LTL. We measured genome-wide SNPs and LTL for a sample of 5069 Bangladeshi adults with substantial relatedness. For each of the 6318 relative pairs identified, we used SNPs near the telomeres to estimate the number of chromosome ends shared IBD, a proxy for the number of telomeres shared IBD (Tshared). We then estimated the association between Tshared and the squared pairwise difference in LTL ((DeltaLTL)(2)) within various classes of relatives (siblings, avuncular, cousins, and distant), adjusting for overall genetic relatedness (varphi). The association between Tshared and (DeltaLTL)(2) was inverse among all relative pair types. In a meta-analysis including all relative pairs (varphi > 0.05), the association between Tshared and (DeltaLTL)(2) (P = 0.01) was stronger than the association between varphi and (DeltaLTL)(2) (P = 0.43). Our results provide strong evidence that telomere length (TL) in parental germ cells impacts TL in offspring cells and contributes to LTL h(2) despite telomere “reprogramming” during embryonic development. Applying our method to larger studies will enable robust estimation of LTL h(2) attributable to direct transmission of telomeres.

      2. Draft genome sequences of nine Vibrio sp. isolates from across the United States closely related to Vibrio choleraeexternal icon
        Islam MT, Liang K, Im MS, Winkjer J, Busby S, Tarr CL, Boucher Y.
        Microbiol Resour Announc. 2018 Nov;7(21).

        We are reporting whole-genome sequences of nine Vibrio sp. isolates closely related to the waterborne human pathogen Vibrio cholerae. These isolates were recovered from sources, including human samples, from different regions of the United States. Genome analysis suggests that this group of isolates represents a highly divergent basal V. cholerae lineage or a closely related novel species.

      3. Whole genome sequencing to characterize capsule locus and predict serogroup of invasive meningococcal isolatesexternal icon
        Marjuki H, Topaz N, Rodriguez-Rivera LD, Ramos E, Potts CC, Chen A, Retchless AC, Doho GH, Wang X.
        J Clin Microbiol. 2018 Dec 19.

        Invasive meningococcal disease is mainly caused by Neisseria meningitidis (Nm) serogroups A, B, C, X, W and Y. Serogroup is typically determined by slide agglutination serogrouping (SASG) and real-time PCR (rt-PCR). We describe a whole-genome sequencing (WGS)-based method to characterize the capsule polysaccharide synthesis (cps) locus, classify Nm serogroups, and identify mechanisms for nongroupability using 453 isolates from a global strain collection. We identified novel genomic organizations within functional cps loci, consisting of insertion-sequence (IS) elements in unique positions that did not disrupt the coding sequence. Genetic mutations (partial gene deletion, missing genes, IS insertion, internal stop, and phase variable off) that led to nongroupability were identified. WGS and SASG were in 91-100% agreement for all serogroups, while WGS and rt-PCR showed 99-100% agreement. Among isolates determined nongroupable by WGS (31 of 453), all three methods agreed 100% for those without a capsule polymerase gene. However, 61% (WGS vs. SASG) and 36% (WGS vs. rt-PCR) agreements were observed for isolates particularly with phase variations or internal stops in cps loci, which warrant further characterization by additional tests. Our WGS-based serogrouping method provides comprehensive characterization of the Nm capsule, which is critical for meningococcal surveillance and outbreak investigations.

      4. Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging speciesexternal icon
        Munoz JF, Gade L, Chow NA, Loparev VN, Juieng P, Berkow EL, Farrer RA, Litvintseva AP, Cuomo CA.
        Nat Commun. 2018 Dec 17;9(1):5346.

        Candida auris is an emergent multidrug-resistant fungal pathogen causing increasing reports of outbreaks. While distantly related to C. albicans and C. glabrata, C. auris is closely related to rarely observed and often multidrug-resistant species from the C. haemulonii clade. Here, we analyze near complete genome assemblies for the four C. auris clades and three related species, and map intra- and inter-species rearrangements across the seven chromosomes. Using RNA-Seq-guided gene predictions, we find that most mating and meiosis genes are conserved and that clades contain either the MTLa or MTLalpha mating loci. Comparing the genomes of these emerging species to those of other Candida species identifies genes linked to drug resistance and virulence, including expanded families of transporters and lipases, as well as mutations and copy number variants in ERG11. Gene expression analysis identifies transporters and metabolic regulators specific to C. auris and those conserved with related species which may contribute to differences in drug response in this emerging fungal clade.

    • Health Behavior and Risk
      1. Objective: There is growing interest in mindful parenting and how this form of intentional, compassionate interactions with youth are associated with developmental outcomes. We investigated how mindful parenting changes over time, either naturally or in response to interventions, and how that change is associated with other proximal developmental changes. Method: We used data from a longitudinal, randomized-controlled study design (N 5 432 families) to investigate the associations between changes in mindful parenting and 3 outcomes: positive parenting, parent-youth relationship quality, and youth aggression. Differences across 3 intervention conditions and between mothers and fathers were tested. Results: Across conditions, changes in mindful parenting were strongly associated with changes in all 3 outcomes for both fathers and mothers. Changes in mindful parenting showed considerable variability within and across conditions. For fathers, differences in mindful parenting change were driven primarily by changes in the core mindful parenting dimension of emotional awareness. Mothers showed comparable changes in mindful parenting across conditions. Conclusions: Findings illustrate how changes in mindful parenting are associated with proximal changes that could lead to reduced youth behavior problems (e.g., aggression or substance use) and provide additional evidence for the contribution that mindfulness activities can make to standard parent training.

    • Healthcare Associated Infections

      1. Outbreak of epidemic keratoconjunctivitis caused by human adenovirus type D53 in an eye care clinic – Los Angeles County, 2017external icon
        OYong K, Killerby M, Pan CY, Huynh T, Green NM, Wadford DA, Terashita D.
        MMWR Morb Mortal Wkly Rep. 2018 Dec 7;67(48):1347-1349.

        On June 22, 2017, the Los Angeles County Department of Public Health (LAC DPH) was notified of seven patients who were seen at an eye care clinic on June 8, 2017, and later developed symptoms of epidemic keratoconjunctivitis (EKC). EKC is a contagious, severe form of viral conjunctivitis that can cause pain and blurred vision for up to 4 weeks (1). LAC DPH conducted an investigation, which identified 17 patients with EKC, including 15 who had visited the optometry clinic and two who were household contacts of clinic patients. Observations in the clinic found deficiencies in disinfection of tonometers (an instrument connected to a slit lamp and used to test for glaucoma by measuring intraocular pressure) and multiuse eye drop administration. Staff member education and revision of disinfection practices interrupted further transmission. Patient specimens tested positive for human adenovirus (HAdV) type D53 (HAdV-53). As the first documented EKC outbreak associated with HAdV-D53 in the United States, this outbreak highlights the need for rigorous implementation of recommended infection prevention practices in eye care settings.

      2. Notes from the field: Infections after receipt of bacterially contaminated umbilical cord blood-derived stem cell products for other than hematopoietic or immunologic reconstitution – United States, 2018external icon
        Perkins KM, Spoto S, Rankin DA, Dotson NQ, Malarkey M, Mendoza M, McNeill L, Gable P, Powell KM.
        MMWR Morb Mortal Wkly Rep. 2018 Dec 21;67(50):1397-1399.

        [No abstract]

    • Immunity and Immunization

      1. A population-based descriptive atlas of invasive pneumococcal strains recovered within the U.S. during 2015-2016external icon
        Beall B, Chochua S, Gertz RE, Li Y, Li Z, McGee L, Metcalf BJ, Ricaldi J, Tran T, Walker H, Pilishvili T.
        Front Microbiol. 2018 ;9:2670.

        Invasive pneumococcal disease (IPD) has greatly decreased since implementation in the U.S. of the 7 valent conjugate vaccine (PCV7) in 2000 and 13 valent conjugate vaccine (PCV13) in 2010. We used whole genome sequencing (WGS) to predict phenotypic traits (serotypes, antimicrobial phenotypes, and pilus determinants) and determine multilocus genotypes from 5334 isolates (~90% of cases) recovered during 2015-2016 through Active Bacterial Core surveillance. We identified 44 serotypes; 26 accounted for 98% of the isolates. PCV13 serotypes (inclusive of serotype 6C) accounted for 1503 (28.2%) isolates, with serotype 3 most common (657/5334, 12.3%), while serotypes 1 and 5 were undetected. Of 305 isolates from children <5 yrs, 60 (19.7%) were of PCV13 serotypes 19A, 19F, 3, 6B, and 23F (58/60 were 19A, 19F, or 3). We quantitated MLST-based lineages first detected during the post-PCV era (since 2002) that potentially arose through serotype-switching. The 7 predominant emergent post-PCV strain complexes included 23B/CC338, 15BC/CC3280, 19A/CC244, 4/CC439, 15A/CC156, 35B/CC156, and 15BC/CC156. These strains accounted for 332 isolates (6.2% of total) and were more frequently observed in children <5 yrs (17.7%; 54/305). Fifty-seven categories of recently emerged (in the post PCV7 period) putative serotype-switch variants were identified, accounting for 402 isolates. Many of these putative switch variants represented newly emerged resistant strains. Penicillin-nonsusceptibility (MICs > 0.12 mug/ml) was found among 22.4% (1193/5334) isolates, with higher penicillin MICs (2-8 mug/ml) found in 8.0% (425/5334) of isolates that were primarily (372/425, 87.5%) serotypes 35B and 19A. Most (792/1193, 66.4%) penicillin-nonsusceptible isolates were macrolide-resistant, 410 (34.4%) of which were erm gene positive and clindamycin-resistant. The proportion of macrolide-resistant isolates increased with increasing penicillin MICs; even isolates with reduced penicillin susceptibility (MIC = 0.06 mug/ml) were much more likely to be macrolide-resistant than basally penicillin-susceptible isolates (MIC < 0.03 mug/ml). The contribution of recombination to strain diversification was assessed through quantitating 35B/CC558-specific bioinformatic pipeline features among non-CC558 CCs and determining the sizes of gene replacements. Although IPD has decreased greatly and stabilized in the post-PCV13 era, the species continually generates recombinants that adapt to selective pressures exerted by vaccines and antimicrobials. These data serve as a baseline for monitoring future changes within each invasive serotype.

      2. Provider perspectives on demand creation for maternal vaccines in Kenyaexternal icon
        Bergenfeld I, Nganga SW, Andrews CA, Fenimore VL, Otieno NA, Wilson AD, Chaves SS, Verani JR, Widdowson MA, Wairimu WN, Wandera SN, Atito RO, Adero MO, Frew PM, Omer SB, Malik FA.
        Gates Open Res. 2018 Jul 19;2:34.

        Background . Expansion of maternal immunization, which offers some of the most effective protection against morbidity and mortality in pregnant women and neonates, requires broad acceptance by healthcare providers and their patients. We aimed to describe issues surrounding acceptance and demand creation for maternal vaccines in Kenya from a provider perspective. Methods . Nurses and clinical officers were recruited for semi-structured interviews covering resources for vaccine delivery, patient education, knowledge and attitudes surrounding maternal vaccines, and opportunities for demand creation for new vaccines. Interviews were conducted in English and Swahili, transcribed verbatim from audio recordings, and analyzed using codes developed from interview guide questions and emergent themes. Results . Providers expressed favorable attitudes about currently available maternal immunizations and introduction of additional vaccines, viewing themselves as primarily responsible for vaccine promotion and patient education. The importance of educational resources for both patients and providers to maintain high levels of maternal immunization coverage was a common theme. Most identified barriers to vaccine acceptance and delivery were cultural and systematic in nature. Suggestions for improvement included improved patient and provider education, including material resources, and community engagement through religious and cultural leaders. Conclusions . The distribution of standardized, evidence-based print materials for patient education may reduce provider overwork and facilitate in-clinic efforts to inform women about maternal vaccines. Continuing education for providers should address communication surrounding current vaccines and those under consideration for introduction into routine schedules. Engagement of religious and community leaders, as well as male decision-makers in the household, will enhance future acceptance of maternal vaccines.

      3. Global funders consortium for universal influenza vaccine developmentexternal icon
        Bresee JS, McKinlay MA, Abramson J, Klugman KP, Wairagkar N.
        Vaccine. 2018 Nov 29.

        [No abstract]

      4. Prevention of influenza hospitalization among adults in the US, 2015-16: Results from the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN)external icon
        Ferdinands JM, Gaglani M, Martin ET, Middleton D, Monto AS, Murthy K, Silveira FP, Talbot HK, Zimmerman R, Alyanak E, Strickland C, Spencer S, Fry AM.
        J Infect Dis. 2018 Dec 14.

        Background: Evidence establishing effectiveness of influenza vaccination for prevention of severe illness is limited. The US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) is a multi-year test-negative case-control study initiated in 2015-16 to estimate effectiveness of vaccine in preventing influenza hospitalization among adults. Methods: Adults aged >/=18 years admitted to eight US hospitals with acute respiratory illness and testing positive for influenza by PCR were cases; those testing negative were controls. VE was estimated with logistic regression adjusting for age, comorbidities and other confounding factors and stratified by frailty, two-year vaccination history, and clinical presentation. Results: We analyzed data from 236 cases and 1231 controls; mean age was 58 years. Over 90% of patients had >/=1 comorbidity elevating risk of influenza complications. Fifty percent of cases and 70% of controls were vaccinated. Vaccination was 51% (95%CI 29, 65) and 53% (95%CI 11, 76) effective in preventing hospitalization due to influenza A(H1N1)pdm09 and influenza B virus infection, respectively. Vaccine was protective for all age groups. Conclusions: During the 2015-16 US influenza A(H1N1)pdm09-predominant season, we found that vaccination halved the risk of influenza-association hospitalization among adults, most of whom were at increased risk of serious influenza complications due to comorbidity or age.

      5. Influenza vaccine effectivenessexternal icon
        Ferdinands JM, Patel MM, Foppa IM, Fry AM.
        Clin Infect Dis. 2018 Dec 18.

        [No abstract]

      6. [No abstract]

      7. Cost of a human papillomavirus vaccination project, Zimbabweexternal icon
        Hidle A, Gwati G, Abimbola T, Pallas SW, Hyde T, Petu A, McFarland D, Manangazira P.
        Bull World Health Organ. 2018 Dec 1;96(12):834-842.

        Objective: To determine the cost of Zimbabwe’s human papillomavirus (HPV) vaccination demonstration project. Methods: The government of Zimbabwe conducted the project from 2014-2015, delivering two doses of HPV vaccine to 10-year-old girls in two districts. School delivery was the primary vaccination strategy, with health facilities and outreach as secondary strategies. A retrospective cost analysis was conducted from the provider perspective. Financial costs (government expenditure) and economic costs (financial plus the value of existing or donated resources including vaccines) were calculated by activity, per dose and per fully immunized girl. Results: The project delivered 11 599 vaccine doses, resulting in 5724 fully immunized girls (5540 at schools, 168 at health facilities and 16 at outreach points). The financial cost for service delivery per fully immunized girl was United States dollars (US$) 5.34 in schools, US$ 34.90 at health facilities and US$ 288.63 at outreach; the economic costs were US$ 17.39, US$ 41.25 and US$ 635.84, respectively. The mean financial cost per dose was US$ 19.76 and per fully immunized girl was US$ 40.03 (economic costs were US$ 45.00 and US$ 91.19, respectively). The largest number of doses delivered (5788) occurred during the second vaccination round (the second group’s first dose concurrently delivered with the first group’s second dose), resulting in the lowest financial and economic service delivery costs per dose: US$ 1.97 and US$ 6.79, respectively. Conclusion: The mean service delivery cost was lower in schools (primary strategy) and when more girls were vaccinated in each round, demonstrating scale efficiency.

      8. Cost-effectiveness of adult vaccinations: A systematic reviewexternal icon
        Leidner AJ, Murthy N, Chesson HW, Biggerstaff M, Stoecker C, Harris AM, Acosta A, Dooling K, Bridges CB.
        Vaccine. 2018 Dec 4.

        BACKGROUND: Coverage levels for many recommended adult vaccinations are low. The cost-effectiveness research literature on adult vaccinations has not been synthesized in recent years, which may contribute to low awareness of the value of adult vaccinations and to their under-utilization. We assessed research literature since 1980 to summarize economic evidence for adult vaccinations included on the adult immunization schedule. METHODS: We searched PubMed, EMBASE, EconLit, and Cochrane Library from 1980 to 2016 and identified economic evaluation or cost-effectiveness analysis for vaccinations targeting persons aged >/=18years in the U.S. or Canada. After excluding records based on title and abstract reviews, the remaining publications had a full-text review from two independent reviewers, who extracted economic values that compared vaccination to “no vaccination” scenarios. RESULTS: The systematic searches yielded 1688 publications. After removing duplicates, off-topic publications, and publications without a “no vaccination” comparison, 78 publications were included in the final analysis (influenza=25, pneumococcal=18, human papillomavirus=9, herpes zoster=7, tetanus-diphtheria-pertussis=9, hepatitis B=9, and multiple vaccines=1). Among outcomes assessing age-based vaccinations, the percent indicating cost-savings was 56% for influenza, 31% for pneumococcal, and 23% for tetanus-diphtheria-pertussis vaccinations. Among age-based vaccination outcomes reporting $/QALY, the percent of outcomes indicating a cost per QALY of </=$100,000 was 100% for influenza, 100% for pneumococcal, 69% for human papillomavirus, 71% for herpes zoster, and 50% for tetanus-diphtheria-pertussis vaccinations. CONCLUSIONS: The majority of published studies report favorable cost-effectiveness profiles for adult vaccinations, which supports efforts to improve the implementation of adult vaccination recommendations.

      9. Hospital, maternal and birth factors associated with hepatitis B vaccination at birth: West Virginia, 2015external icon
        Massey J, Nair A, Dietz S, Snaman D, Bixler D.
        Pediatr Infect Dis J. 2018 Jul;37(7):691-696.

        BACKGROUND: Hepatitis B virus is a bloodborne pathogen typically transmitted through sexual contact, injection drug use or perinatally. A hepatitis B vaccine (HepB) is available; the first dose is recommended at birth. We sought to identify hospital policy, maternal characteristics and birth factors associated with HepB receipt at birth in West Virginia. METHODS: We conducted a retrospective cohort study of West Virginia live births in 2015 using vital records matched to immunization registry records to determine frequency of HepB birth dose receipt (<3 days postdelivery). We surveyed all West Virginia birthing facilities in 2015 (N = 26) about perinatal hepatitis B virus prevention policies. We examined associations of hospital policy, maternal characteristics and birth factors with HepB receipt at birth by using a mixed-effects regression model to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs). RESULTS: Of 17,458 births, 14,006 (80.2%) infants received a HepB birth dose. Hospital use of preprinted newborn routine admission vaccination orders was associated with HepB birth dose receipt (aPR: 10.60; 95% CI: 2.12-52.72). Not using illicit drugs during pregnancy, maternal age <35 years and weekday births were associated with HepB birth dose receipt (aPR: 1.81; 95% CI: 1.54-2.13; aPR: 1.34, 95% CI: 1.17-1.54 and aPR: 1.15; 95% CI: 1.03-1.28, respectively). CONCLUSIONS: Hospitals using preprinted admission orders had higher frequencies of HepB birth dose receipt. Additional study is needed to identify HepB birth dose receipt barriers among infants with maternal illicit drug use, maternal age >/=35 years or deliveries during a weekend.

      10. Introduction: A number of enhanced influenza vaccines have been developed for use in older adults, including the high-dose, MF59-adjuvanted, and intradermal vaccines. Methods: We conducted a systematic review examining the improvements in antibody responses measured by the hemagglutination inhibition (HAI) assay associated with these enhanced vaccines, compared to each other, and compared to standard-dose vaccine using random effects models. Results: Thirty-nine trials were included. Compared to adults aged 60 years receiving standard-dose vaccines, those receiving enhanced vaccines had significantly higher post-vaccination titers (for all vaccine strains) and higher proportions with elevated titers >/=40 (for most vaccine strains). High-dose vaccine elicited 82% higher post-vaccination titer to A(H3N2) compared to standard-dose vaccine; this was significantly higher than 52% estimated for MF59-adjuvanted versus standard-dose vaccines (p=0.04), which was higher than 32% estimated for intradermal versus standard-dose vaccines (p<0.01). Conclusions: Overall, by summarizing current evidence, we found enhanced vaccines had greater antibody responses than standard-dose vaccine. Indications of differences among enhanced vaccines highlight that further research is needed in order to compare new vaccine options; this is especially needed during seasons with mismatched circulating strains and for immune outcomes other than HAI titers as well as vaccine efficacy.

      11. Obstetrician-gynecologists’ strategies to address vaccine refusal among pregnant womenexternal icon
        O’Leary ST, Riley LE, Lindley MC, Allison MA, Albert AP, Fisher A, Jiles AJ, Crane LA, Hurley LP, Beaty B, Brtnikova M, Kempe A.
        Obstet Gynecol. 2018 Dec 4.

        OBJECTIVE: To describe 1) obstetrician-gynecologists’ (ob-gyns’) perceptions of the frequency of vaccine refusal among pregnant patients and perceived reasons for refusal and 2) ob-gyns’ strategies used when encountering vaccine refusal and perceived effectiveness of those strategies. METHODS: We conducted an email and mail survey among a nationally representative network of ob-gyns from March 2016 to June 2016. RESULTS: The response rate was 69% (331/477). Health care providers perceived that pregnant women more commonly refused influenza vaccine than tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine: 62% of respondents reported 10% or greater of pregnant women they care for in a typical month refused influenza vaccine compared with 32% reporting this for Tdap vaccine. The most commonly reported reasons for vaccine refusal were patients’ belief that influenza vaccine makes them sick (48%), belief they are unlikely to get a vaccine-preventable disease (38%), general worries about vaccines (32%), desire to maintain a natural pregnancy (31%), and concern that their child could develop autism as a result of maternal vaccination (25%). The most commonly reported strategies ob-gyns used to address refusal were stating that it is safe to receive vaccines in pregnancy (96%), explaining that not getting the vaccine puts the fetus or newborn at risk (90%), or that not getting the vaccine puts the pregnant woman’s health at risk (84%). The strategy perceived as most effective was stating that not getting vaccinated puts the fetus or newborn at risk. CONCLUSION: Ob-gyns perceive vaccine refusal among pregnant women as common and refusal of influenza vaccine as more common than refusal of Tdap vaccine. Emphasizing the risk of disease to the fetus or newborn may be an effective strategy to increase vaccine uptake.

      12. INTRODUCTION: In 1998, the first licensed rotavirus vaccine was associated with intussusception, an unexpected adverse event, following reports of this condition to an adverse event reporting system. This rotavirus vaccine was withdrawn from the market and newer rotavirus vaccines have been extensively evaluated for an association with intussusception. Areas Covered: We review the different study designs that have been used both pre- and post-licensure to evaluate the association of rotavirus vaccines with intussusception and discuss the pros and cons of each design. Each of these study designs has their own strengths and weaknesses and the choice of the design often depends on the objective and the timing of the study and the resources available. For post-licensure monitoring of rotavirus vaccines, the self-controlled case-series design has become the most commonly used design to monitor this association. Expert Opinion: Use of this common study design has enabled comparison of findings across diverse settings. As new rotavirus vaccines enter the market, use of the self-controlled case-series design will enable examination of this association in a timely manner.

      13. Influenza virus N-linked glycosylation and innate immunityexternal icon
        York IA, Stevens J, Alymova IV.
        Biosci Rep. 2018 Dec 14.

        Influenza viruses cause seasonal epidemics and sporadic pandemics in humans. The virus’s ability to change its antigenic nature through mutation and recombination, and the difficulty in developing highly effective universal vaccines against it, make it a serious global public health challenge. Influenza virus’s surface glycoproteins, hemagglutinin and neuraminidase, are all modified by the host cell’s N-linked glycosylation pathways. Host innate immune responses are the first line of defense against infection, and glycosylation of these major antigens plays an important role in the generation of host innate responses toward the virus. Here, we review the principal findings in the analytical techniques used to study influenza N-linked glycosylation, the evolutionary dynamics of N-linked glycosylation in seasonal vs. pandemic and zoonotic strains, its role in host innate immune responses, and the prospects for lectin-based therapies. As the efficiency of innate immune responses is a critical determinant of disease severity and adaptive immunity, the study of influenza glycobiology is of clinical as well as research interest.

    • Informatics

      1. Detecting moderate or complex congenital heart defects in adults from an electronic health records systemexternal icon
        Diallo AO, Krishnaswamy A, Shapira SK, Oster ME, George MG, Adams JC, Walker ER, Weiss P, Ali MK, Book W.
        J Am Med Inform Assoc. 2018 Dec 1;25(12):1634-1642.

        Background: The prevalence of moderate or complex (moderate-complex) congenital heart defects (CHDs) among adults is increasing due to improved survival, but many patients experience lapses in specialty care or their CHDs are undocumented in the medical system. There is, to date, no efficient approach to identify this population. Objective: To develop and assess the performance of a risk score to identify adults aged 20-60 years with undocumented specific moderate-complex CHDs from electronic health records (EHR). Methods: We used a case-control study (596 adults with specific moderate-complex CHDs and 2384 controls). We extracted age, race/ethnicity, electrocardiogram (EKG), and blood tests from routine outpatient visits (1/2009 through 12/2012). We used multivariable logistic regression models and a split-sample (4: 1 ratio) approach to develop and internally validate the risk score, respectively. We generated receiver operating characteristic (ROC) c-statistics and Brier scores to assess the ability of models to predict the presence of specific moderate-complex CHDs. Results: Out of six models, the non-blood biomarker model that included age, sex, and EKG parameters offered a high ROC c-statistic of 0.96 [95% confidence interval: 0.95, 0.97] and low Brier score (0.05) relative to the other models. The adult moderate-complex congenital heart defect risk score demonstrated good accuracy with 96.4% sensitivity and 80.0% specificity at a threshold score of 10. Conclusions: A simple risk score based on age, sex, and EKG parameters offers early proof of concept and may help accurately identify adults with specific moderate-complex CHDs from routine EHR systems who may benefit from specialty care.

    • Injury and Violence

      1. Willingness to change medications linked to increased fall risk: A comparison between age groupsexternal icon
        Haddad YK, Karani MV, Bergen G, Marcum ZA.
        J Am Geriatr Soc. 2018 Dec 13.

        OBJECTIVE: To describe and compare two age groups’ knowledge of medications linked to falls and willingness to change these medications to reduce their fall risk. METHOD: We analyzed data from community-dwelling adults age 55 and older (n = 1812): 855 adults aged 55 to 64 years and 957 older adults (65 and older) who participated in the 2016 summer wave of the ConsumerStyles survey, an annual Web-based survey. The data are weighted to match the US Current Population Survey proportions on nine US Census Bureau demographic characteristics. MEASUREMENTS: Survey respondents were asked about medication use, knowledge of side effects, their willingness to change their medications to reduce fall risk, communication in the previous year about fall risk with their healthcare provider, and their comfort in discussing fall risk with their healthcare provider. All data were weighted to match the 2016 population estimates. Descriptive statistics and chi(2) (p </= .05) were used to identify differences between the two age groups. RESULTS: About one-fifth of all respondents reported using at least one class of medication that increases fall risk. Older adults were less likely to report using medications for mood or sadness, less likely to report knowing the side effects of pain medications, and more willing to change their sleep medications compared with their younger counterparts. Among all respondents using these medication classes, less than one-third knew the potential fall-related side effects. However, most of them expressed willingness to change their medication if advised by their healthcare provider. CONCLUSION: Most older adults were unaware of potential fall risks associated with medications prescribed to address pain, difficulty sleeping, mood or sadness, and anxiety- or nervousness-related health issues. However, most were willing to change their medication if recommended by a healthcare provider.

      2. Effective, accessible prevention programs are needed for adults at heightened risk for intimate partner violence (IPV). This parallel group randomized controlled trial examines whether such couples receiving the American version of Couple CARE for Parents of Newborns (CCP; Halford et al. 2009) following the birth of a child, compared with controls, report fewer first occurrences of clinically significant IPV, less frequent physical and psychological IPV, and improved relationship functioning. Further, we test whether intervention effects are moderated by level of risk for IPV. Couples at elevated risk for IPV (N = 368) recruited from maternity units were randomized to CCP (n = 188) or a 24-month waitlist (n = 180) and completed measures of IPV and relationship functioning at baseline, post-program (when child was 8 months old), and two follow-ups (at 15 and 24 months). Intervention effects were tested using intent to treat (ITT) as well as complier average causal effect (CACE; Jo and Muthen 2001) structural equation models. CCP did not significantly prevent clinically significant IPV nor were there significant main effects of CCP on clinically significant IPV, frequency of IPV, or most relationship outcomes in the CACE or ITT analyses. Risk moderated the effect of CCP on male-to-female physical IPV at post-program, with couples with a planned pregnancy declining, but those with unplanned pregnancies increasing. This study adds to previous findings that prevention programs for at-risk couples are not often effective and may even be iatrogenic for some couples.

      3. INTRODUCTION: Each year from 1999 through 2015, residential fires caused between 2,000 and 3,000 deaths in the U.S., totaling approximately 45,000 deaths during this period. A disproportionate number of such deaths are attributable to smoking in the home. This study examines national trends in residential fire death rates, overall and smoking-related, and their relationship to adult cigarette smoking prevalence, over this same period. METHODS: Summary data characterizing annual U.S. residential fire deaths and annual prevalence of adult cigarette smoking for the years 1999-2015, drawn from the National Vital Statistics System, the National Fire Protection Association, and the National Health Interview Survey were used to relate trends in overall and smoking-related rates of residential fire death to changes in adult cigarette smoking prevalence. RESULTS: Statistically significant downward trends were identified for both the rate of residential fire death (an average annual decrease of 2.2% – 2.6%) and the rate of residential fire death attributed to smoking (an average annual decrease of 3.5%). The decreasing rate of residential fire death was strongly correlated with a gradually declining year-to-year prevalence of adult cigarette smoking (r=0.83), as was the decreasing rate of residential fire death attributed to smoking (r=0.80). CONCLUSIONS AND PRACTICAL APPLICATIONS: Decreasing U.S. residential fire death rates, both overall and smoking-related, coincided with a declining prevalence of adult cigarette smoking during 1999-2015. These findings further support tobacco control efforts and fire prevention strategies that include promotion of smoke-free homes. While the general health benefits of refraining from smoking are widely accepted, injury prevention represents a potential benefit that is less recognized.

      4. [No abstract]

      5. Suicide timing in 18 states of the United States from 2003-2014external icon
        Tian N, Zack M, Fowler KA, Hesdorffer DC.
        Arch Suicide Res. 2018 May 23:1-21.

        OBJECTIVES: We investigated suicide timing over different time periods by age, sex and race/ethnicity. METHODS: 122,107 suicide deaths were identified from the population-based U.S. National Violent Death Reporting System in 18 U.S. States from 2003 through 2014. RESULTS: Suicides significantly increased (p < 0.05) from March to peak in September before falling, the first week of the month, and early in the week. Suicides also significantly increased (p < 0.05) in the morning, mainly peaking during the afternoon, although suicides in adolescents peaked in the evening and in those 65 years and older peaked in the morning. CONCLUSIONS: Comprehensive prevention efforts should focus on those at overall increased suicide risk and at peaks of high suicide frequency, especially among those vulnerable subgroups.

      6. Rates of neglect in a national sample: Child and family characteristics and psychological impactexternal icon
        Vanderminden J, Hamby S, David-Ferdon C, Kacha-Ochana A, Merrick M, Simon TR, Finkelhor D, Turner H.
        Child Abuse Negl. 2018 Dec 10;88:256-265.

        BACKGROUND: Childhood neglect is an understudied form of childhood maltreatment despite being the most commonly reported to authorities. OBJECTIVE: This study provides national estimates of neglect subtypes, demographic variations in exposure to neglect subtypes, and examines the psychological impact. PARTICIPANTS AND SETTING: Pooled data from two representative U.S. samples from the National Surveys of Children’s Exposure to Violence (NatSCEV) survey conducted in 2011 and 2014, representing the experiences of children and youth aged 1 month to 17 years (N = 8503). METHODS: Telephone surveys were used to obtain sociodemographic characteristics, six measures of past year and lifetime exposure to neglect, and assessments of trauma symptoms, suicidal ideation, alcohol use, and illicit drug use. RESULTS: More than 1 in 17 U.S. children (6.07%) experienced some form of neglect in the past year, and more than 1 in 7 (15.14%) experienced neglect at some point in their lives. Supervisory neglect, due to parental incapacitation or parental absence, was most common. Families with two biological parents had lower rates (4.29% in the past year) than other household configurations (range from 7.95% to 14.10%; p < .05). All types of neglect were associated with increased trauma symptoms and suicidal ideation (for 10-17 year olds), and several were associated with increased risk of underage alcohol and illicit drug use. CONCLUSION: More attention needs to be paid to the impact of supervisory neglect. These results underscore the importance of prevention strategies that provide the supports necessary to build safe, stable, and nurturing relationships and environments that help children thrive.

    • Laboratory Sciences

      1. A high throughput neutralization test based on GFP expression by recombinant rabies virusexternal icon
        Burgado J, Greenberg L, Niezgoda M, Kumar A, Olson V, Wu X, Satheshkumar PS.
        PLoS Negl Trop Dis. 2018 Dec 14;12(12):e0007011.

        The effectiveness of rabies vaccination in both humans and animals is determined by the presence of virus neutralizing antibodies (VNAs). The Rapid Fluorescent Focus Inhibition Test (RFFIT) is the method traditionally used for detection and quantification of VNAs. It is a functional in vitro test for assessing the ability of antibodies in serum to bind and prevent infection of cultured cells with rabies virus (RABV). The RFFIT is a labor intensive, low throughput and semi-quantitative assay performed by trained laboratorians. It requires staining of RABV-infected cells by rabies specific fluorescent antibodies and manual quantification of fluorescent fields for titer determination. Although the quantification of fluorescent fields observed in each sample is recorded, the corresponding images are not stored or captured to be used for future analysis. To circumvent several of these disadvantages, we have developed an alternative, automated high throughput neutralization test (HTNT) for determination of rabies VNAs based on green fluorescent protein (GFP) expression by a recombinant RABV and compared with the RFFIT. The HTNT assay utilizes the recombinant RABV ERA variant expressing GFP with a nuclear localization signal (NLS) for efficient quantification. The HTNT is a quantitative method where the number of RABV-infected cells are determined and the images are stored for future analysis. Both RFFIT and HTNT results correlated 100% for a panel of human and animal positive and negative rabies serum samples. Although, the VNA titer values are generally agreeable, HTNT titers tend to be lower than that of RFFIT, probably due to the differences in quantification methods. Our data demonstrates the potential for HTNT assays in determination of rabies VNA titers.

      2. Impact of external quality assurance on the quality of Xpert MTB/RIF testing in Viet Namexternal icon
        Gumma V, DeGruy K, Bennett D, Kim Thanh N, Albert H, Bond KB, Gutreuter S, Alexander H, Lan Thi Phong N, Rush TH, Viet Nhung N, Hung NV.
        J Clin Microbiol. 2018 Dec 19.

        Following the World Health Organization’s (WHO) endorsement of the Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) assay in 2010, Viet Nam’s National TB Control Programme (NTP) began implementing GeneXpert instruments in NTP laboratories. In 2013, Viet Nam’s National Tuberculosis (TB) Programme implemented an Xpert MTB/RIF External Quality Assurance (EQA) programme in collaboration with the United States Centers for Disease Control and Prevention (CDC) and the Foundation for Innovative New Diagnostics (FIND). Proficiency testing (PT) panels comprising five dried tube specimens (DTS) were sent to participating sites approximately twice per annum from October 2013 to July 2016. The number of enrolled laboratories increased from 22 to 39 during the study period. Testing accuracy was assessed by comparing reported and expected results, percentage scores were assigned, and feedback reports were provided to sites. On-site evaluation (OSE) was conducted for under-performing laboratories. Results from the first five rounds demonstrate the positive impact of PT and targeted OSE visits on testing quality. On average, for every additional round of feedback, the odds of achieving PT scores of >/=80% increased 2.04-fold (95% CI 1.39-3.00). Future work will include scale up of PT to all sites and maintaining performance of participating laboratories, while developing local panel production capacity.

      3. Rapid detection of new B/Victoria-lineage haemagglutinin variants of influenza B viruses by pyrosequencingexternal icon
        Lau H, Deng YM, Xu X, Sessions W, Barr IG.
        Diagn Microbiol Infect Dis. 2018 Nov 13.

        During 2016/2017, several antigenically and genetically distinct variant viruses of the influenza B/Victoria/2/87-lineage (B/Vic) viruses, which have either deletions or mutations in the haemagglutinin (HA) emerged and co-circulated with other influenza B viruses from both the B/Vic and B/Yamagata/16/88-lineages (B/Yam). In this study we developed a pyrosequencing assay that can detect and differentiate multiple influenza B virus variants currently in circulation. The assay targets a region of HA sequence that is unique for each of the B/Yam, B/Vic and B/Vic variant viruses. Our results demonstrated that it is a rapid, robust, high-throughput assay, highly sensitive and specific in differentiating among the B/Yam, B/Vic and B/Vic variant viruses, giving it an advantage over an existing rRT-PCR method. It works well for influenza virus isolates as well as original clinical respiratory specimens, and can therefore be used to provide important information for surveillance by closely monitoring the spread of these B/Vic variants.

      4. Streptococcus mitis expressing pneumococcal serotype 1 capsuleexternal icon
        Lessa FC, Milucky J, Rouphael NG, Bennett NM, Talbot HK, Harrison LH, Farley MM, Walston J, Pimenta F, Gertz RE, Rajam G, Carvalho MD, Beall B, Whitney CG.
        Sci Rep. 2018 Dec 19;8(1):17959.

        Streptococcus pneumoniae’s polysaccharide capsule is an important virulence factor; vaccine-induced immunity to specific capsular polysaccharide effectively prevents disease. Serotype 1 S. pneumoniae is rarely found in healthy persons, but is highly invasive and a common cause of meningitis outbreaks and invasive disease outside of the United States. Here we show that genes for polysaccharide capsule similar to those expressed by pneumococci were commonly detected by polymerase chain reaction among upper respiratory tract samples from older US adults not carrying pneumococci. Serotype 1-specific genes were predominantly detected. In five oropharyngeal samples tested, serotype 1 gene belonging to S. mitis expressed capsules immunologically indistinct from pneumococcal capsules. Whole genome sequencing revealed three distinct S. mitis clones, each representing a cps1 operon highly similar to the pneumococcal cps1 reference operon. These findings raise important questions about the contribution of commensal streptococci to natural immunity against pneumococci, a leading cause of mortality worldwide.

      5. BACKGROUND: For Yersinia pestis, Burkholderia pseudomallei, and Burkholderia mallei, conventional broth microdilution (BMD) is considered the gold standard for antimicrobial susceptibility testing (AST) and, depending on the species, requires an incubation period of 16-20 h, or 24-48 h according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. After a diagnosis of plague, melioidosis or glanders during an outbreak or after an exposure event, the timely distribution of appropriate antibiotics for treatment or post-exposure prophylaxis of affected populations could reduce mortality rates. RESULTS: Herein, we developed and evaluated a rapid, automated susceptibility test for these Gram-negative bacterial pathogens based on time-lapse imaging of cells incubating in BMD microtitre drug panels using an optical screening instrument (oCelloScope). In real-time, the instrument screened each inoculated well containing broth with various concentrations of antibiotics published by CLSI for primary testing: ciprofloxacin (CIP), doxycycline (DOX) and gentamicin (GEN) for Y. pestis; imipenem (IPM), ceftazidime (CAZ) and DOX for B. mallei; and IPM, DOX, CAZ, amoxicillin-clavulanic acid (AMC) and trimethoprim-sulfamethoxazole (SXT) for B. pseudomallei. Based on automated growth kinetic data, the time required to accurately determine susceptibility decreased by >/=70% for Y. pestis and >/= 50% for B. mallei and B. pseudomallei compared to the times required for conventional BMD testing. Susceptibility to GEN, IPM and DOX could be determined in as early as three to six hours. In the presence of CAZ, susceptibility based on instrument-derived growth values could not be determined for the majority of B. pseudomallei and B. mallei strains tested. Time-lapse video imaging of these cultures revealed that the formation of filaments in the presence of this cephalosporin at inhibitory concentrations was detected as growth. Other beta-lactam-induced cell morphology changes, such as the formation of spheroplasts and rapid cell lysis, were also observed and appear to be strain- and antibiotic concentration-dependent. CONCLUSIONS: A rapid, functional AST was developed and real-time video footage captured beta-lactam-induced morphologies of wild-type B. mallei and B. pseudomallei strains in broth. Optical screening reduced the time to results required for AST of three Gram-negative biothreat pathogens using clinically relevant, first-line antibiotics compared to conventional BMD.

      6. In vitro activity of EDTA and TOL-463 against Neisseria gonorrhoeaeexternal icon
        Nash EE, Henning TC, Pham CD, Pettus K, Sharpe S, Kersh EN.
        Diagn Microbiol Infect Dis. 2018 Nov 10.

        Neisseria gonorrhoeae quickly develops drug resistance. Time-kill curves revealed that EDTA and TOL-463 inhibit growth similar to penicillin, ciprofloxacin, and azithromycin. Furthermore, synergistic and additive antimicrobial interactions occurred when EDTA and TOL-463 were combined with penicillin or azithromycin, respectively, suggesting that further investigations into these unconventional antimicrobials may be advantageous.

      7. Prolonged occupational exposure to hand-held vibrating tools leads to pain and reductions in tactile sensitivity, grip strength and manual dexterity. The goal of the current study was to use a rat-tail vibration model to determine how vibration frequency influences factors related to nerve injury and dysfunction. Rats were exposed to restraint, or restraint plus tail vibration at 62.5 Hz or 250 Hz. Nerve function was assessed using the current perception threshold (CPT) test. Exposure to vibration at 62.5 and 250 Hz, resulted in a reduction in the CPT at 2000 and 250 Hz electrical stimulation (i.e. increased Abeta and Adelta, nerve fiber sensitivity). Vibration exposure at 250 Hz also resulted in an increased sensitivity of C-fibers to electrical stimulation and thermal nociception. These changes in nerve fiber sensitivity were associated with increased expression of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha in ventral tail nerves, and increases in circulating concentrations of IL-1 beta in rats exposed to 250 Hz vibration. There was an increase in glutathione, but no changes in other measures of oxidative activity in the peripheral nerve. However, measures of oxidative stress were increased in the dorsal root ganglia (DRG). These changes in pro-inflammatory factors and markers of oxidative stress in the peripheral nerve and DRG were associated with inflammation, and reductions in myelin basic protein and post-synaptic density protein (PSD)-95 gene expression, suggesting that vibration induced changes in sensory function may be the result of changes at the exposed nerve, the DRG and/or the spinal cord.

      8. Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serumexternal icon
        Patton JB, Bennuru S, Eberhard ML, Hess JA, Torigian A, Lustigman S, Nutman TB, Abraham D.
        PLoS Negl Trop Dis. 2018 Dec 12;12(12):e0006977.

        BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, thymus and CD34+ stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice. CONCLUSIONS/SIGNIFICANCE: The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus.

      9. Identifying preanalytic and postanalytic laboratory quality gaps using a data warehouse and structured multidisciplinary processexternal icon
        Raebel MA, Quintana LM, Schroeder EB, Shetterly SM, Pieper LE, Epner PL, Bechtel LK, Smith DH, Sterrett AT, Chorny JA, Lubin IM.
        Arch Pathol Lab Med. 2018 Dec 10.

        CONTEXT.-: The laboratory total testing process includes preanalytic, analytic, and postanalytic phases, but most laboratory quality improvement efforts address the analytic phase. Expanding quality improvement to preanalytic and postanalytic phases via use of medical data warehouses, repositories that include clinical, utilization, and administrative data, can improve patient care by ensuring appropriate test utilization. Cross-department, multidisciplinary collaboration to address gaps and improve patient and system outcomes is beneficial. OBJECTIVE.-: To demonstrate medical data warehouse utility for characterizing laboratory-associated quality gaps amenable to preanalytic or postanalytic interventions. DESIGN.-: A multidisciplinary team identified quality gaps. Medical data warehouse data were queried to characterize gaps. Organizational leaders were interviewed about quality improvement priorities. A decision aid with elements including national guidelines, local and national importance, and measurable outcomes was completed for each gap. RESULTS.-: Gaps identified included (1) test ordering; (2) diagnosis, detection, and documentation, and (3) high-risk medication monitoring. After examination of medical data warehouse data including enrollment, diagnoses, laboratory, pharmacy, and procedures for baseline performance, high-risk medication monitoring was selected, specifically alanine aminotransferase, aspartate aminotransferase, complete blood count, and creatinine testing among patients receiving disease-modifying antirheumatic drugs. The test utilization gap was in monitoring timeliness (eg, >60% of patients had a monitoring gap exceeding the guideline recommended frequency). Other contributors to selecting this gap were organizational enthusiasm, regulatory labeling, and feasibility of a significant laboratory role in addressing the gap. CONCLUSIONS.-: A multidisciplinary process facilitated identification and selection of a laboratory medicine quality gap. Medical data warehouse data were instrumental in characterizing gaps.

      10. Novel mass spectrometry based detection and identification of variants of rabies virus nucleoprotein in infected brain tissuesexternal icon
        Reed M, Stuchlik O, Carson WC, Orciari L, Yager PA, Olson V, Li Y, Wu X, Pohl J, Satheshkumar PS.
        PLoS Negl Trop Dis. 2018 Dec 14;12(12):e0006984.

        Human rabies is an encephalitic disease transmitted by animals infected with lyssaviruses. The most common lyssavirus that causes human infection is rabies virus (RABV), the prototypic member of the genus. The incubation period of RABV in humans varies from few weeks to several months in some instances. During this prodromal period, neither antibodies nor virus is detected. Antibodies, antigen and nucleic acids are detectable only after the onset of encephalitic symptoms, at which point the outcome of the disease is nearly 100% fatal. Hence, the primary intervention for human RABV exposure and subsequent post-exposure prophylaxis relies on testing animals suspected of having rabies. The most widely used diagnostic tests in animals focus on antigen detection, RABV-encoded nucleoprotein (N protein) in brain tissues. N protein accumulates in the cytoplasm of infected cells as large and granular inclusions, which are visualized in infected brain tissues by immuno-microscopy using anti-N protein antibodies. In this study, we explored a mass spectrometry (MS) based method for N protein detection without the need for any specific antibody reagents or microscopy. The MS-based method described here is unbiased, label-free, requires no amplification and determines any previously sequenced N protein available in the database. The results demonstrate the ability of MS/MS based method for N protein detection and amino acid sequence determination in animal diagnostic samples to obtain RABV variant information. This study demonstrates a potential for future developments of rabies diagnostic tests based on MS platforms.

      11. Chronic stress exposure and daily stress appraisals relate to biological aging marker p16(INK4a)external icon
        Rentscher KE, Carroll JE, Repetti RL, Cole SW, Reynolds BM, Robles TF.
        Psychoneuroendocrinology. 2018 Dec 7;102:139-148.

        Previous research has linked exposure to adverse social conditions with DNA damage and accelerated telomere shortening, raising the possibility that chronic stress may impact biological aging pathways, ultimately increasing risk for age-related diseases. Less clear, however, is whether these stress-related effects extend to additional hallmarks of biological aging, including cellular senescence, a stable state of cell cycle arrest. The present study aimed to investigate associations between psychosocial stress and two markers of cellular aging-leukocyte telomere length (LTL) and cellular senescence signal p16(INK4a). Seventy-three adults (Mage = 43.0, SD = 7.2; 55% female) with children between 8-13 years of age completed interview-based and questionnaire measures of their exposures to and experiences of stress, as well as daily reports of stress appraisals over an 8-week diary period. Blood samples were used to assess markers of cellular aging: LTL and gene expression of senescent cell signal p16(INK4a) (CDKN2A). Random effects models covarying for age, sex, ethnicity/race, and BMI revealed that participants with greater chronic stress exposure over the previous 6 months (b = 0.011, p = .04), perceived stress (b = 0.020, p < .001), and accumulated daily stress appraisals over the 8-week period (b = 0.013, p = .02) showed increased p16(INK4a). No significant associations with LTL were found. These findings extend previous work on the impact of stress on biological aging by linking chronic stress exposure and daily stressful experiences to an accumulation of senescent cells. Findings also support the hypothesis that chronic stress is associated with accelerated aging by inducing cellular senescence, a common correlate of age-related diseases.

      12. Sputum smear microscopy in the Xpert((R)) MTB/RIF eraexternal icon
        Van Deun A, Tahseen S, Affolabi D, Hossain MA, Joloba ML, Angra PK, Ridderhof JC, de Jong BC, Rieder HL.
        Int J Tuberc Lung Dis. 2018 Dec 19.

        A balanced perspective is advocated for the assessment and application of the most recent and the oldest diagnostic methods for pulmonary tuberculosis (TB)&mdash;the molecular Xpert(&reg;) MTB/RIF assay and microscopy for acid-fast bacilli. We discuss their respective merits and shortcomings and identify threats that may hamper their use in TB control. Neither test on its own provides all the information needed for diagnosis and treatment monitoring. Considering all aspects important for both individual patient care and disease control, neither seems &lsquo;better&apos; than the other. The required advancement of microscopy had already been hampered before the introduction of the GeneXpert technology by unsuccessful and probably misguided attempts to decentralise culture-based diagnosis and drug susceptibility testing. It seems evident that systematic replacement of microscopy by Xpert is not a viable option for the foreseeable future. Instead, the two methods should complement each other to arrive at a comprehensive, accessible and continuous service for a maximum number of patients. This will intrinsically prioritise targeting the most potent transmitters with the worst prognosis, simultaneously offering optimised prospects for efficient TB control. New microscopy and Xpert applications are expected to ultimately make control programmes independent of culture-based methods in diagnosis, treatment monitoring and outcome assessment.

      13. The fungal Cyp51 specific inhibitor VT-1598 demonstrates in vitro and in vivo activity against Candida aurisexternal icon
        Wiederhold NP, Lockhart SR, Najvar LK, Berkow EL, Jaramillo R, Olivo M, Garvey EP, Yates CM, Schotzinger RJ, Catano G, Patterson TF.
        Antimicrob Agents Chemother. 2018 Dec 10.

        Candida auris is an emerging pathogen associated with significant mortality and often multi-drug resistance. VT-1598, a tetrazole-based fungal CYP51-specific inhibitor, was evaluated in vitro and in vivo against C. auris Susceptibility testing was performed against 100 clinical isolates of C. auris by broth microdilution. Neutropenic mice were infected intravenously with C. auris, and treatment began 24 hours post-inoculation with vehicle control, oral VT-1598 (5, 15, and 50 mg/kg once daily), oral fluconazole (20 mg/kg once daily), or intraperitoneal caspofungin (10 mg/kg once daily), which continued for 7 days. Fungal burden was assessed in the kidneys and brains on day 8 in the fungal burden arm, and on the days the mice succumbed to infection or on day 21 in the survival arm. VT-1598 plasma trough concentrations were also assessed on day 8. VT-1598 demonstrated in vitro activity against C. auris, with a mode MIC of 0.25 mug/mL and MICs ranging from 0.03 to 8 mug/mL. Treatment with VT-1598 resulted in significant and dose-dependent improvements in survival (median survival 15 and >21 days for VT-1598 15 and 50 mg/kg, respectively) and reductions in kidney and brain fungal burden (1.88 to 3.61 log10 CFU/g reduction) compared to control (5 days). The reductions in fungal burden correlated with plasma trough concentrations. Treatment with caspofungin, but not fluconazole, also resulted in significant improvements in survival and reductions in fungal burden compared to control. These results suggest that VT-1598 may be a future option for the treatment of invasive infections caused by C. auris.

    • Maternal and Child Health

      1. Health care, family, and community factors associated with mental, behavioral, and developmental disorders and poverty among children aged 2-8 years – United States, 2016external icon
        Cree RA, Bitsko RH, Robinson LR, Holbrook JR, Danielson ML, Smith C, Kaminski JW, Kenney MK, Peacock G.
        MMWR Morb Mortal Wkly Rep. 2018 Dec 21;67(50):1377-1383.

        Childhood mental, behavioral, and developmental disorders (MBDDs) are associated with adverse outcomes that can persist into adulthood (1,2). Pediatric clinical settings are important for identifying and treating MBDDs (3). Early identification and treatment of MBDDs can promote healthy development for all children (4), especially those living in poverty who are at increased risk for MBDDs (3,5) but might have reduced access to care (6). CDC analyzed data from the 2016 National Survey of Children’s Health (NSCH) on MBDDs, risk factors, and use of federal assistance programs (e.g., Supplemental Nutrition Assistance Program [SNAP]) to identify points to reach children in poverty. In line with previous research (3,6), compared with children in higher-income households, those in lower-income households more often had ever received a diagnosis of an MBDD (22.1% versus 13.9%), and less often had seen a health care provider in the previous year (80.4% versus 93.8%). Among children living below 200% of the federal poverty level (FPL) who did not see a health care provider in the previous year, seven of 10 were in families receiving at least one public assistance benefit. Public assistance programs might offer collaboration opportunities to provide families living in poverty with information, co-located screening programs or services, or connection to care.

      2. OBJECTIVE: To identify children with ADHD enrolled in New York State (NYS) Medicaid and characterize ADHD-associated costs by treatment category. METHOD: In 2013, 1.4 million children aged 2 to 17 years were enrolled in NYS Medicaid. Medicaid claims and encounters were used to identify children with ADHD, classify them by type of treatment received, and estimate associated costs. RESULTS: The ADHD cohort comprised 5.4% of all Medicaid-enrolled children, with 35.0% receiving medication only, 16.2% receiving psychological services only, 42.2% receiving both, and 6.6% receiving neither. The total costs for the ADHD cohort (US$729.3 million) accounted for 18.1% of the total costs for children enrolled in NYS Medicaid. CONCLUSION: This study underscores the importance of achieving a better understanding of children with ADHD enrolled in NYS Medicaid. A framework to categorize children with ADHD based on their treatment categories may help to target interventions to improve the quality of care and reduce costs.

      3. Previous studies have focused on the comparison of specific laws among multiple countries and regions; for example, laws related to facilitating treatments with orphan drugs or laws seeking to address the multiple needs of patients with rare diseases. The purpose of this scoping review is to examine and compare published reports on national plans, polices and legislation related to all rare diseases in different countries. We also examine strategies or programs that countries may have for these diseases. Articles were obtained from journals and books published between January 1, 2000, through December 15, 2017. Reports from the grey literature (documents issued by government and private organizations) were included if they were available on the internet. The databases used were Google and Google Scholar, PubMed, and the websites of Orphanet and the National Organization for Rare Disorders (NORD). We obtained information on 23 countries. Among these countries, the way in which rare diseases were defined varied from having similar definitions to no definition. Multinational programs supported by common or similar laws are likely to have a greater impact on rare diseases than single country programs.

    • Mining

      1. Analysis of gateroad stability at two longwall mines based on field monitoring results and numerical model analysisexternal icon
        Esterhuizen GS, Gearhart DF, Klemetti T, Dougherty H, van Dyke M.
        Int J Min Sci Technol. 2018 .

        Coal mine longwall gateroads are subject to changing loading conditions induced by the advancing longwall face. The ground response and support requirements are closely related to the magnitude and orientation of the stress changes, as well as the local geology. This paper presents the monitoring results of gateroad response and support performance at two longwall mines at a 180-m and 600-m depth of cover. At the first mine, a three-entry gateroad layout was used. The second mine used a four-entry, yield-abutment-yield gateroad pillar system. Local ground deformation and support response were monitored at both sites. The monitoring period started during the development stage and continued during first panel retreat and up to second panel retreat. The two data sets were used to compare the response of the entries in two very different geotechnical settings and different gateroad layouts. The monitoring results were used to validate numerical models that simulate the loading conditions and entry response for these widely differing conditions. The validated models were used to compare the load path and ground response at the two mines. This paper demonstrates the potential for numerical models to assist mine engineers in optimizing longwall layouts and gateroad support systems.

      2. [No abstract]

      3. [No abstract]

    • Nutritional Sciences

      1. Four years after implementation of a national micronutrient powder program in Kyrgyzstan, prevalence of iron deficiency and iron deficiency anemia is lower, but prevalence of vitamin A deficiency is higherexternal icon
        Lundeen EA, Lind JN, Clarke KE, Aburto NJ, Imanalieva C, Mamyrbaeva T, Ismailova A, Timmer A, Whitehead RD, Praslova L, Samohleb G, Minbaev M, Addo OY, Serdula MK.
        Eur J Clin Nutr. 2018 Dec 6.

        BACKGROUND/OBJECTIVES: In 2009, the Ministry of Health of Kyrgyzstan launched a national Infant and Young Child Nutrition (IYCN) program which included point-of-use fortification of foods with micronutrient powders (MNP) containing iron, vitamin A, and other micronutrients. Caretakers of children aged 6-23 months were given 30 sachets of MNP every 2 months. Micronutrient surveys were conducted in 2009 and 2013. The objective of the study was to compare the prevalence of anemia and deficiencies of iron and vitamin A among children aged 6-29 months prior to the MNP program (2009) with those after full implementation (2013). SUBJECTS/METHODS: Cross-sectional national surveys were conducted in 2009 (n = 666) and 2013 (n = 2150). Capillary blood samples were collected to measure hemoglobin, iron (ferritin and soluble transferrin receptor [sTfR]) and vitamin A (retinol binding protein [RBP]) status, and inflammation status (C-reactive protein [CRP] and alpha-1-acid glycoprotein [AGP]). Ferritin, sTfR, and RBP were adjusted for inflammation; hemoglobin was adjusted for altitude. RESULTS: The prevalence of anemia was non-significantly lower in 2013 compared to 2009 (32.7% vs. 39.0%, p = 0.076). Prevalence of inflammation-adjusted iron deficiency (54.8% vs. 74.2%, p<0.001) and iron deficiency anemia (IDA, 25.5% vs. 35.1%, p = 0.003) were lower and the prevalence of inflammation-adjusted vitamin A deficiency was higher (4.3% vs. 2.0%, p = 0.013) in 2013 compared to 2009. CONCLUSIONS: Four years after the initiation of a national Infant and Young Child Nutrition program including the introduction of point-of-use fortification with MNP, the prevalence of iron deficiency and IDA is lower, but the prevalence of vitamin A deficiency is higher.

    • Occupational Safety and Health

      1. Field evaluation of sequential hand wipes for flame retardant exposure in an electronics recycling facilityexternal icon
        Beaucham CC, Ceballos D, Mueller C, Page E, La Guardia MJ.
        Chemosphere. 2018 Dec 5;219:472-481.

        Flame retardants have been associated with endocrine disorders, thyroid disruption, reproductive toxicity, and immunological interference. Through dismantling and recycling electronics and electric products, flame retardants can be released into the air and settle on work surfaces which may lead to dermal exposure. Hand wipe sampling is commonly used to evaluate dermal exposure. This study assesses the removal efficiency of wipes on the hands of recycling employees, and to compare the efficacy of two common surface wipe sampling materials. We used three sequential hand wipes and quantified the percentage of flame retardants that was removed by each hand wipe in the sequence. Two common wipe materials (gauze and twill) were used to compare the ability to remove flame retardants. The wipes were collected from 12 employees at a U.S. electronics recycling facility immediately at the end of their shift, prior to washing their hands. Results show that although the first wipe removed the highest median percent of the sum of the three wipes for most flame retardants, there was a wide range of the percentages of total individual flame retardants removed by both gauze (4%-98%) or twill hand wipe (1%-89%). Approximately half of the flame retardants a high percentage (>50%) removed by the second and third wipes. This suggests that a single wipe is not sufficient to characterize the extent of dermal contamination. The average of the total amount of flame retardants removed by twill wipes was greater than the average using gauze, but the difference was not statistically significant.

      2. Objective This study evaluated the effectiveness of a no-cost-to-workers, slip-resistant footwear (SRF) program in preventing workers’ compensation injury claims caused by slipping on wet or greasy floors. Methods The study population was a dynamic cohort of food service workers from 226 school districts’ kindergarten through 12th grade food service operations. A two-arm cluster randomized controlled study design was implemented, with school districts randomized to the intervention group receiving SRF. Data were analyzed according to the intent-to-treat principle. Logistic regression was used to analyze dichotomous response data (injured based on workers’ compensation injury claims data, or not injured, for each month worked). Changes in slipping injury rates from baseline to post-intervention follow-up periods were compared between treatment groups. Results The probability of a slipping injury was reduced significantly in the intervention group, from a baseline measure of 3.54 slipping injuries per 10 000 worker-months to 1.18 slipping injuries per 10 000 worker-months in the follow-up period [adjusted odds ratio (OR adj) 0.33, 95% confidence interval (CI) 0.17-0.63]. In the control group, slipping injuries were 2.01 per 10 000 worker-months in the baseline, and 2.30 per 10 000 worker-months in the follow-up. The interaction between treatment group and time period (baseline or follow-up) indicated that the decline seen in the intervention group was significantly different than the increase seen in the control group (OR adj0.29, 95% CI 0.11-0.74, adjusted for age >55 years). Conclusions This study provides evidence for the effectiveness of a no-cost-to-workers SRF program in reducing slipping-related workers’ compensation injury claims in food service workers.

      3. NIOSH’s Respiratory Health Division: 50 years of science and serviceexternal icon
        Cummings KJ, Johns DO, Mazurek JM, Hearl FJ, Weissman DN.
        Arch Environ Occup Health. 2018 Dec 2:1-15.

        The year 2017 marked the 50th anniversary of NIOSH’s Respiratory Health Division (RHD). RHD began in 1967 as the Appalachian Laboratory for Occupational Respiratory Diseases (ALFORD), with a focus on coal workers’ pneumoconiosis. ALFORD became part of NIOSH in 1971 and added activities to address work-related respiratory disease more generally. Health hazard evaluations played an important role in understanding novel respiratory hazards such as nylon flock, diacetyl, and indium-tin oxide. Epidemiologic and laboratory studies addressed many respiratory hazards, including coal mine dust, silica, asbestos, cotton dust, beryllium, diesel exhaust, and dampness and mold. Surveillance activities tracked the burden of diseases and enhanced the quality of spirometry and chest radiography used to screen workers. RHD’s efforts to improve scientific understanding, inform strategies for prevention, and disseminate knowledge remain important now and for the future.

      4. Introduction: The NIOSH Fire Fighter Fatality Investigation and Prevention Program (FFFIPP) conducts independent investigations of selected fire fighter line-of-duty deaths (LODD) and offers recommendations to prevent similar deaths. The purpose of the current study was to provide information on more recent FFFIPP recommendations and to determine if recommendations have changed over time. Methods: Fatality investigations completed from 2006 to 2014 were selected for this study with recommendations being assigned into twelve major categories when possible. The most frequently occurring recommendations were then rank ordered overall and then by medical and traumatic fire fighter LODD. Results: There were 1,067 total recommendations made in the published fire fighter investigative reports for both medical and trauma-related fire fighter fatalities for the period 2006?2014. Of these, 784 (73%) could be placed within one of the 12 categories noted previously. The top 10 recommendation categories overall were: 1. Medical screening, 2. Fitness and wellness program, 3. Training, 4. Medical clearance, 5. Standard Operating Procedures/Standard Operating Guidelines (SOPs/SOGs), 6. Incident command, 7. Strategy and tactics, 8. Communications, 9. Personal protective equipment and 10. Staffing. Conclusions: The leading recommendations from the NIOSH FFFIPP medical investigations between 2006 and 2014 did not change “ompared to those made between 1998 and 2005, with the exception of the addition of “medical clearance for duty”. There were changes for the traumatic injury leading recommendations for 2006?2014, with the major change being ?training” which was the leading FFFIPP recommendation for traumatic injuries for this time period. Practical applications: The intent of the FFFIPP is to influence fire departments and fire fighters to critically assess and evaluate situations/circumstances similar to those identified by NIOSH investigations and implement the recommendations offered to prevent additional fire fighter fatalities.

      5. INTRODUCTION: This study estimated the prevalence of spirometry-defined airflow obstruction by industry and occupation and chronic obstructive pulmonary disease (COPD) among ever-employed U.S. adults. METHODS: Data came from the National Health and Nutrition Examination Survey (NHANES) 2007-2008 to 2011-2012, a nationally representative study of the non-institutionalized civilian U.S. POPULATION: Data on respondent’s current and/or longest held job were used to create prevalence estimates and adjusted prevalence odds ratios (PORs) for airflow obstruction and COPD. RESULTS: Among ever-employed U.S. adults, airflow obstruction prevalence was 12.40% and COPD was 3.47%. High airflow obstruction prevalence and significant PORs were reported in mining; manufacturing; construction; and services to buildings industries as well as extraction; bookbinders, prepress, and printing; installers and repairers; and construction occupations. CONCLUSION: Prevalence of airflow obstruction varies by industry and occupation. Industries and occupations with increased risk were identified using the most current NHANES data including detailed occupations and spirometry.

      6. CE: Original research: Antineoplastic drug administration by pregnant and nonpregnant nurses: An exploration of the use of protective gloves and gownsexternal icon
        Lawson CC, Johnson CY, Nassan FL, Connor TH, Boiano JM, Rocheleau CM, Chavarro JE, Rich-Edwards JW.
        Am J Nurs. 2018 Dec 12.

        Findings from this cross-sectional study indicate a need for expanded training in safe handling practices. ABSTRACT: Background: Many antineoplastic (chemotherapeutic) drugs are known or probable human carcinogens, and many have been shown to be reproductive toxicants in cancer patients. Evidence from occupational exposure studies suggests that health care workers who have long-term, low-level occupational exposure to antineoplastic drugs have an increased risk of adverse reproductive outcomes. It’s recommended that, at minimum, nurses who handle or administer such drugs should wear double gloves and a nonabsorbent gown to protect themselves. But it’s unclear to what extent nurses do. PURPOSE: This study assessed glove and gown use by female pregnant and nonpregnant nurses who administer antineoplastic drugs in the United States and Canada. METHODS: We used data collected from more than 40,000 nurses participating in the Nurses’ Health Study 3. The use of gloves and gowns and administration of antineoplastic drugs within the past month (among nonpregnant nurses) or within the first 20 weeks of pregnancy (among pregnant nurses) were self-reported via questionnaire. RESULTS: Administration of antineoplastic drugs at any time during their career was reported by 36% of nonpregnant nurses, including 27% who reported administering these drugs within the past month. Seven percent of pregnant nurses reported administering antineoplastic drugs during the first 20 weeks of pregnancy. Twelve percent of nonpregnant nurses and 9% of pregnant nurses indicated that they never wore gloves when administering antineoplastic drugs, and 42% of nonpregnant nurses and 38% of pregnant nurses reported never using a gown. The percentage of nonpregnant nurses who reported not wearing gloves varied by type of administration: 32% of those who administered antineoplastic drugs only as crushed pills never wore gloves, compared with 5% of those who administered such drugs only via infusion. CONCLUSIONS: Despite longstanding recommendations for the safe handling of antineoplastic and other hazardous drugs, many nurses-including those who are pregnant-reported not wearing protective gloves and gowns, which are considered the minimum protective equipment when administering such drugs. These findings underscore the need for further education and training to ensure that both employers and nurses understand the risks involved and know which precautionary measures will minimize such exposures.

      7. Evaluation of exposure assessment tools under REACH: Part II-Higher Tier Toolsexternal icon
        Lee EG, Lamb J, Savic N, Basinas I, Gasic B, Jung C, Kashon ML, Kim J, Tischer M, van Tongeren M, Vernez D, Harper M.
        Ann Work Expo Health. 2018 Dec 9.

        Stoffenmanager(R)v4.5 and Advanced REACH Tool (ART) v1.5, two higher tier exposure assessment tools for use under REACH, were evaluated by determining accuracy and robustness. A total of 282 exposure measurements from 51 exposure situations (ESs) were collected and categorized by exposure category. In this study, only the results of liquids with vapor pressure (VP) > 10 Pa category having a sufficient number of exposure measurements (n = 251 with 42 ESs) were utilized. In addition, the results were presented by handling/activity description and input parameters for the same exposure category. It should be noted that the performance results of Stoffenmanager and ART in this study cannot be directly compared for some ESs because ART allows a combination of up to four subtasks (and nonexposed periods) to be included, whereas the database for Stoffenmanager, separately developed under the permission of the legal owner of Stoffenmanager, permits the use of only one task to predict exposure estimates. Thus, it would be most appropriate to compare full-shift measurements against ART predictions (full shift including nonexposed periods) and task-based measurements against task-based Stoffenmanager predictions. For liquids with VP > 10 Pa category, Stoffenmanager(R)v4.5 appeared to be reasonably accurate and robust when predicting exposures [percentage of measurements exceeding the tool’s 90th percentile estimate (%M > T) was 15%]. Areas that could potentially be improved include ESs involving the task of handling of liquids on large surfaces or large work pieces, allocation of high and medium VP inputs, and absence of local exhaust ventilation input. Although the ART’s median predictions appeared to be reasonably accurate for liquids with VP > 10 Pa, the %M > T for the 90th percentile estimates was 41%, indicating that variance in exposure levels is underestimated by ART. The %M > T using the estimates of the upper value of 90% confidence interval (CI) of the 90th percentile estimate (UCI90) was considerably reduced to 18% for liquids with VP > 10 Pa. On the basis of this observation, users might be to consider using the upper limit value of 90% CI of the 90th percentile estimate for predicting reasonable worst case situations. Nevertheless, for some activities and input parameters, ART still shows areas to be improved. Hence, it is suggested that ART developers review the assumptions in relation to exposure variability within the tool, toward improving the tool performance in estimating percentile exposure levels. In addition, for both tools, only some handling/activity descriptions and input parameters were considered. Thus, further validation studies are still necessary.

      8. Evaluation of exposure assessment tools under REACH: Part I-Tier 1 Toolsexternal icon
        Lee EG, Lamb J, Savic N, Basinas I, Gasic B, Jung C, Kashon ML, Kim J, Tischer M, van Tongeren M, Vernez D, Harper M.
        Ann Work Expo Health. 2018 Dec 9.

        Tier 1 occupational exposure assessment tools recommended for use under the Registration, Evaluation, Authorization, and restriction of CHemicals (REACH) were evaluated using newly collected measurement data. Evaluated tools included the ECETOC TRAv2 and TRAv3, MEASEv1.02.01, and EMKG-EXPO-TOOL. Fifty-three exposure situations (ESs) based on tasks/chemicals were developed from National Institute for Occupational Safety and Health field surveys. During the field surveys, high quality contextual information required for evaluating the tools was also collected. For each ES, applicable tools were then used to generate exposure estimates using a consensus approach. Among 53 ESs, only those related to an exposure category of liquids with vapor pressure (VP) > 10 Pa had sufficient numbers of exposure measurements (42 ESs with n = 251 for TRAv2 and TRAv3 and 40 ESs with n = 243 for EMKG-EXPO-TOOL) to be considered in detail. The results for other exposure categories (aqueous solutions, liquids with VP </= 10 Pa, metal processing, powders, and solid objects) had insufficient measurement to allow detailed analyses (results listed in the Supplementary File). Overall, EMKG-EXPO-TOOL generated more conservative results than TRAv2 and TRAv3 for liquids with high VP. This finding is at least partly due to the fact that the EMKG-EXPO-TOOL only considers pure substances and not mixtures of chemical agents. For 34 out of 40 ESs available for chemicals with VP > 10 Pa, the liquid was a mixture rather than a pure substance. TRAv3 was less conservative than TRAv2, probably due to additional refinement of some input parameters. The percentages of exposure measurement results exceeding the corresponding tool estimates for liquids with VP > 10 Pa by process category and by input parameters were always higher for TRAv3 compared to those for TRAv2. Although the conclusions of this study are limited to liquids with VP > 10 Pa and few process categories, this study utilized the most transparent contextual information compared to previous studies, reducing uncertainty from assumptions for unknown input parameters. A further validation is recommended by collecting sufficient exposure data covering other exposure categories and all process categories under REACH.

      9. Insights into emissions and exposures from use of industrial-scale additive manufacturing machinesexternal icon
        Stefaniak AB, Johnson AR, du Preez S, Hammond DR, Wells JR, Ham JE, LeBouf RF, Martin SB, Duling MG, Bowers LN, Knepp AK, de Beer DJ, du Plessis JL.
        Saf Health Work. 2018 2018/11/09/.

        Background Emerging reports suggest the potential for adverse health effects from exposure to emissions from some additive manufacturing (AM) processes. There is a paucity of real-world data on emissions from AM machines in industrial workplaces and personal exposures among AM operators. Methods Airborne particle and organic chemical emissions and personal exposures were characterized using real-time and time-integrated sampling techniques in four manufacturing facilities using industrial-scale material extrusion and material jetting AM processes. Results Using a condensation nuclei counter, number-based particle emission rates (ERs) (number/min) from material extrusion AM machines ranged from 4.1?x 1010 (Ultem?filament) to 2.2?x 1011 [acrylonitrile butadiene styrene and polycarbonate filaments). For these same machines, total volatile organic compound ERs (microg/min) ranged from 1.9?x?104 (acrylonitrile butadiene styrene and polycarbonate) to 9.4?x 104 (Ultem). For the material jetting machines, the number-based particle ER was higher when the lid was open (2.3?x 1010 number/min) than when the lid was closed (1.5-5.5?x 109 number/min); total volatile organic compound ERs were similar regardless of the lid position. Low levels of acetone, benzene, toluene, and m,p-xylene were common to both AM processes. Carbonyl compounds were detected; however, none were specifically attributed to the AM processes. Personal exposures to metals (aluminum and iron) and eight volatile organic compounds were all below National Institute for Occupational Safety and Health (NIOSH)-recommended exposure levels. Conclusion Industrial-scale AM machines using thermoplastics and resins released particles and organic vapors into workplace air. More research is needed to understand factors influencing real-world industrial-scale AM process emissions and exposures.

    • Occupational Safety and Health – Mining

      1. [No abstract]

      2. [No abstract]

      3. Using performance management strategies to improve mine emergency training and preparednessexternal icon
        Ryan ME, Diamond J, Brnich MJ, Hoebbel C.
        Coal Age. 2018 ;123(9):37-39.

        [No abstract]

      4. Patterns of heat strain among a sample of U.S. underground minersexternal icon
        Yeoman K, DuBose W, Bauerle T, Victoroff T, Finley S, Poplin G.
        J Occup Environ Med. 2018 Dec 7.

        OBJECTIVE: This study characterizes physiological measures of heat exposure among U.S. underground miners. METHODS: Core body temperature measured by using ingestible sensors during subjects’ normal work shifts was categorized into four temperature zones: <37.5 degrees C, 37.5 degrees C to <38 degrees C, 38 degrees C to <38.5 degrees C, and >/=38.5 degrees C. RESULTS: On average, subjects changed temperature zones 13.8 times per shift. Temperatures increased above the recommended limit of 38 degrees C nearly 5 times per shift for an average of 26 minutes each episode. CONCLUSIONS: Unlike previous heat stress research that reported only maximum and mean temperature measurements, this analysis demonstrates a dynamic pattern of physiologic heat strain, with core body temperatures changing frequently and exceeding the 38 degrees C limit multiple times per shift. Further research is needed on the impact of multiple short-term, intermittent heat exposures on miners.

    • Parasitic Diseases
      1. BACKGROUND: Mobile health (mHealth), which uses technology such as mobile phones to improve patient health and health care delivery, is increasingly being tested as an intervention to promote health worker (HW) performance. This study assessed the effect of short messaging services (SMS) reminders in a study setting. Following a trial of text-message reminders to HWs to improve case management of malaria and other childhood diseases in southern Malawi that showed little effect, qualitative data was collected to explore the reasons why the intervention was ineffective and describe lessons learned. METHODS: Qualitative data collection was undertaken to lend insight into quantitative results from a trial in which 105 health facilities were randomized to three arms: (1) twice-daily text-message reminders to HWs, including clinicians and drug dispensers, on case management of malaria; (2) twice-daily text-message reminders to HWs on case management of malaria, pneumonia and diarrhoea; and, (3) a control arm. In-depth interviews were conducted with 50 HWs in the intervention arms across seven districts. HWs were asked about acceptability and feasibility of the text-messaging intervention and its perceived impact on recommended case management. The interviews were recorded, transcribed and translated into English for a thematic and framework analysis. Nvivo 11 software was used for data management and analysis. RESULTS: A total of 50 HWs were interviewed at 22 facilities. HWs expressed high acceptance of text-message reminders and appreciated messages as job aids and practical reference material for their day-to-day work. However, HWs said that health systems barriers, including very high outpatient workload, commodity stock-outs, and lack of supportive supervision and financial incentives demotivated them, limited their ability to act on messages and therefore adherence to case management guidelines. Drug dispensers were more likely than clinicians to report usage of text-message reminders. Despite these challenges, nearly all HWs expressed a desire for a longer duration of the SMS intervention. CONCLUSIONS: Text-message reminders to HWs can provide a platform to improve understanding of treatment guidelines and case management decision-making skills, but might not improve actual adherence to guidelines. More interaction, for example through targeted supervision or two-way technology communication, might be an essential intervention component to help address structural barriers and facilitate improved clinical practice.

      2. Evaluating the quality of routinely reported data on malaria commodity stocks in Guinea, 2014-2016external icon
        Sun Y, Guilavogui T, Camara A, Dioubate M, Toure BD, Bahati C, Fargier MP, Butts J, Condo P, Sarr A, Plucinski MM.
        Malar J. 2018 Dec 7;17(1):461.

        BACKGROUND: Ensuring malaria commodity availability at health facilities is a cornerstone of malaria control. Since 2013, the Guinea National Malaria Control Programme has been routinely collecting data on stock levels of key malaria commodities through a monthly routine malaria information system (RMIS). In parallel, biannual end-user verification (EUV) surveys have also assessed malaria commodity availability at a subset of health facilities, potentially representing a duplication of efforts. METHODS: Data on 12 malaria commodity stock levels verified during four EUV surveys conducted between 2014 and 2016 was compared to data for the corresponding months submitted by the same health facilities through the RMIS. The sensitivity and specificity of the RMIS in detecting stock-outs was calculated, as was the percent difference between average stock levels reported through the two systems. RESULTS: Of the 171 health facilities visited during the four EUV surveys, 129 (75%) had data available in the RMIS. Of 351 commodity stock-outs observed during the EUV in the sampled reporting health facilities, 256 (73%) were also signaled through the corresponding RMIS reports. When the presence of malaria commodity stocks was confirmed during the EUV surveys, the RMIS also reported available stock 87% (677/775) of the time. For all commodities, the median percent difference in average stock levels between the EUV and RMIS was 4% (interquartile range – 7 to 27%). CONCLUSION: The concordance between stock levels reported through the RMIS and those verified during the EUV visits provides certain evidence that RMIS data can inform quantification and procurement decisions. However, lower than acceptable rates of reporting and incomplete detection of stock-outs from facilities that do report suggest that further systems strengthening is needed to improve RMIS reporting completeness and data quality.

      3. Community-based participatory research in travel medicine to identify barriers to preventing malaria in VFR travelersexternal icon
        Walz EJ, Wanduragala D, Adedimeji AA, Volkman HR, Gaines J, Angelo KM, Boumi AE, Coyle C, Dunlop SJ, Stauffer WM.
        J Travel Med. 2018 Dec 11.

        [No abstract]

    • Public Health Leadership and Management
      1. This qualitative review of 57 published case reports aimed to analyze primary care and public health integration efforts in 45 states to summarize collaboration aims, participants, and systemic, organizational, and interactional success determinants. Chronic disease management, maternal and child health, and wellness and health promotion were the most commonly reported aims of collaboration between primary care and public health entities in the United States. Typical participants were government public health structures, health delivery systems, communities, academia, state professional medical associations, and employers and businesses. Systemic, organizational, and interactional determinants included adequate funding, multiple stakeholder engagement, leadership, data and information sharing, capitalization on collaborator resources, community engagement, steering committees, effective communication, regular meetings, shared mission, vision, and goals, previous positive relationships, collaborations, and partnerships. The present study contributes to the body of knowledge of when, where, and under what contextual circumstances collaboration and integration have been perceived as effective. Future research could extrapolate which determinants are more essential than others and focus on how systemic, organizational, and interactional factors are interrelated. To advance the practice of successful integration between primary care and public health entities, longitudinal research is needed to examine the degree of integration and sustainability.

    • Reproductive Health

      1. Father-son communication about consistent and correct condom useexternal icon
        Guilamo-Ramos V, Thimm-Kaiser M, Benzekri A, Rodriguez C, Fuller TR, Warner L, Koumans EH.
        Pediatrics. 2018 Dec 17.

        OBJECTIVES: With this study, we explore communication about consistent and correct condom use among African American and Latino male adolescents ages 15 to 19 and their fathers. METHODS: Twenty-five father-son dyads completed semistructured interviews designed to elicit specific preferences for teaching and learning about consistent and correct condom use and strategies for addressing common condom use errors and problems. For analysis, we used in vivo coding and vertical and horizontal analysis techniques. RESULTS: Fathers and sons agreed that communication about condom use is feasible and acceptable. However, fathers tended to convey vague messages regarding protecting oneself from the negative consequences of sexual activity. Furthermore, both fathers and sons reported barriers hindering conversations. Secondly, the style and frequency of condom use conversations can help overcome barriers and support father-son relationship management. Talking frequently in 1-on-1 settings and using strategies to reduce discomfort made communication easier. Lastly, fathers and sons reported distinct preferences for teaching and learning about condom use. Sons wanted fathers to give specific guidance on the use and management of condoms. Fathers expressed interest in opportunities for improving their own condom knowledge and skills. Fathers identified gaps in their own condom use knowledge as a limitation to effective instruction of their sons. CONCLUSIONS: A father-focused communication intervention about condom use is feasible and acceptable. Enhancing the intergenerational benefits of father-son communication by addressing specific father-son preferences and learning needs for condom use instruction, as well as communication barriers, represents a novel mechanism for reducing male sexual reproductive health disparities.

      2. Effect of population-based antenatal screening and treatment of genitourinary tract infections on birth outcomes in Sylhet, Bangladesh (MIST): a cluster-randomised clinical trialexternal icon
        Lee AC, Mullany LC, Quaiyum M, Mitra DK, Labrique A, Christian P, Ahmed P, Uddin J, Rafiqullah I, DasGupta S, Rahman M, Koumans EH, Ahmed S, Saha SK, Baqui AH.
        Lancet Glob Health. 2019 Jan;7(1):e148-e159.

        BACKGROUND: One-third of preterm births are attributed to pregnancy infections. We implemented a community-based intervention to screen and treat maternal genitourinary tract infections, with the aim of reducing the incidence of preterm birth. METHODS: We did an unblinded cluster-randomised controlled trial in two subdistricts of Sylhet, Bangladesh. Clusters were defined as the contiguous area served by a single community health worker, and each cluster comprised several contiguous villages, contained roughly 4000 people, and had about 120 births per year. Eligible participants within clusters were all ever-married women and girls of reproductive age (ie, aged 15-49 years) who became pregnant during the study period. Clusters were randomly assigned (1:1) to the intervention or control groups via a restricted randomisation procedure. In both groups, community health workers made home visits to identify pregnant women and girls and provide antenatal and postnatal care. Between 13 and 19 weeks’ gestation, participants in the intervention group received home-based screening for abnormal vaginal flora and urinary tract infections. A random 10% of the control group also received the intervention to examine the similarity of infection prevalence between groups. If present, abnormal vaginal flora (ie, Nugent score >/=4 was treated with oral clindamycin (300 mg twice daily for 5 days) and urinary tract infections with cefixime (400 mg once daily for 3 days) or oral nitrofurantoin (100 mg twice daily for 7 days). Both infections were retreated if persistent. The primary outcome was the incidence of preterm livebirths before 37 weeks’ gestation among all livebirths. This trial is registered with ClinicalTrials.gov, number NCT01572532. The trial is closed to new participants, with follow-up completed. FINDINGS: Between Jan 2, 2012, and July 28, 2015, 9712 pregnancies were enrolled (4840 in the intervention group, 4391 in the control group, and 481 in the control subsample). 3818 livebirths in the intervention group and 3557 livebirths in the control group were included in the primary analysis. In the intervention group, the prevalence of abnormal vaginal flora was 16.3% (95% CI 15.1-17.6) and that of urinary tract infection was 8.6% (7.7-9.5). The effective coverage of successful treatment in the intervention group was 58% in participants with abnormal vaginal flora (ie, abnormal vaginal flora resolved in 361 [58%] of the 622 participants who initially tested positive), and 71% in those with urinary tract infections (ie, resolution in 224 [71%] of the 317 participants who initially tested positive). Overall, the incidence of preterm livebirths before 37 weeks’ gestation did not differ significantly between the intervention and control groups (21.8% vs 20.6%; relative risk 1.07 [95% CI 0.91-1.24]). INTERPRETATION: A population-based antenatal screening and treatment programme for genitourinary tract infections did not reduce the incidence of preterm birth in Bangladesh. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development and Saving Lives at Birth Grand Challenges.

      3. Affordable Care Act-dependent insurance coverage and access to care among young adult women with a recent live birthexternal icon
        Li R, Bauman B, D’Angelo DV, Harrison LL, Warner L, Barfield W, Cox S.
        Med Care. 2018 Dec 18.

        BACKGROUND: The Affordable Care Act (ACA)-dependent coverage Provision (the Provision), implemented in 2010, extended family insurance coverage to adult children until age 26. OBJECTIVES: To examine the impact of the ACA Provision on insurance coverage and care among women with a recent live birth. RESEARCH DESIGN, SUBJECTS, AND OUTCOME MEASURES: We conducted a difference-in-difference analysis to assess the effect of the Provision using data from the Pregnancy Risk Assessment Monitoring System among 22,599 women aged 19-25 (treatment group) and 22,361 women aged 27-31 years (control group). Outcomes include insurance coverage in the month before and during pregnancy, and at delivery, and receipt of timely prenatal care, a postpartum check-up, and postpartum contraceptive use. RESULTS: Compared with the control group, the Provision was associated with a 4.7-percentage point decrease in being uninsured and a 5.9-percentage point increase in private insurance coverage in the month before pregnancy, and a 5.4-percentage point increase in private insurance coverage and a 5.9-percentage point decrease in Medicaid coverage during pregnancy, with similar changes in insurance coverage at delivery. Findings demonstrated a 3.6-percentage point increase in receipt of timely prenatal care, and no change in receipt of a postpartum check-up or postpartum contraceptive use. CONCLUSIONS: Among women with a recent live birth, the Provision was associated with a decreased likelihood of being uninsured and increased private insurance coverage in the month before pregnancy, a shift from Medicaid to private insurance coverage during pregnancy and at delivery, and an increased likelihood of receiving timely prenatal care.

      4. Effect of menstruation on girls and their schooling, and facilitators of menstrual hygiene management in schools: surveys in government schools in three states in India, 2015external icon
        Sivakami M, Maria van Eijk A, Thakur H, Kakade N, Patil C, Shinde S, Surani N, Bauman A, Zulaika G, Kabir Y, Dobhal A, Singh P, Tahiliani B, Mason L, Alexander KT, Thakkar MB, Laserson KF, Phillips-Howard PA.
        J Glob Health. 2019 Jun;9(1):010408.

        Background: Lack of menstrual knowledge, poor access to sanitary products and a non-facilitating school environment can make it difficult for girls to attend school. In India, interventions have been developed to reduce the burden of menstruation for school girls by government and non-governmental organizations (NGOs). We sought to identify challenges related to menstruation, and facilitators of menstrual management in schools in three states in India. Methods: Surveys were conducted among menstruating school girls in class 8-10 (above 12 years of age) of 43 government schools selected through stratified random sampling in three Indian states (Maharashtra, Chhattisgarh, Tamil Nadu) in 2015. For comparison, ten model schools supported by NGOs or UNICEF with a focussed menstrual hygiene education program were selected purposely in the same states to represent the better-case scenario. We examined awareness about menarche, items used for menstruation, and facilitators on girls’ experience of menstruation in regular schools and compared with model schools. Factors associated with school absence during menstruation were explored using multivariate analysis. Findings: More girls (mean age 14.1 years) were informed about menstruation before menarche in model schools (56%, n = 492) than in regular schools (36%, n = 2072, P < 0.001). Girls reported menstruation affected school attendance (6% vs 11% in model vs regular schools respectively, P = 0.003) and concentration (40% vs 45%, P = 0.1) and was associated with pain (31% vs 38%, P = 0.004) and fear of stain or smell (11% vs 16%, P = 0.002). About 45% of girls reported using disposable pads in both model and regular schools, but only 55% and 29% of pad-users reported good disposal facilities, respectively (P < 0.001). In multivariate analysis, reported absenteeism during menstruation was significantly lower in Tamil Nadu (adjusted prevalence ratio (APR) 95% confidence interval (CI) = 0.24, 0.14-0.40) and Maharashtra (APR 0.56, CI = 0.40-0.77) compared to Chhattisgarh, and halved in model compared to regular schools (APR 0.50, CI = 0.34-0.73). Pain medication in school (APR 0.71, CI = 0.51-0.97) and use of disposable pads (APR 0.57, CI = 0.42-0.77) were associated with lower absenteeism and inadequate sanitary facilities with higher absenteeism during menstruation. Conclusions: Menstrual hygiene education, accessible sanitary products, pain relief, and adequate sanitary facilities at school would improve the schooling-experience of adolescent girls in India.

      5. [No abstract]

    • Statistics as Topic
      1. A logistic regression with random effects model is commonly applied to analyze clustered binary data, and every cluster is assumed to have a different proportion of success. However, it could be of interest to obtain the proportion of success over clusters (i.e. the marginal proportion of success). Furthermore, the degree of correlation among data of the same cluster (intraclass correlation) is also a relevant concept to assess, but when using logistic regression with random effects it is not possible to get an analytical expression of the estimators for marginal proportion and intraclass correlation. In our paper, we assess and compare approaches using different kinds of approximations: based on the logistic-normal mixed effects model (LN), linear mixed model (LMM), and generalized estimating equations (GEE). The comparisons are completed by using two real data examples and a simulation study. The results show the performance of the approaches strongly depends on the magnitude of the marginal proportion, the intraclass correlation, and the sample size. In general, the reliability of the approaches get worsen with low marginal proportion and large intraclass correlation. LMM and GEE approaches arises as reliable approaches when the sample size is large.

      2. An alternative approach to relapse analysis: using Monte Carlo methods and proportional rates of responseexternal icon
        Friedel JE, Galizio A, Berry MS, Sweeney MM, Odum AL.
        J Exp Anal Behav. 2018 Dec 17.

        Relapse is the recovery of a previously suppressed response. Animal models have been useful in examining the mechanisms underlying relapse (e.g., reinstatement, renewal, reacquisition, resurgence). However, there are several challenges to analyzing relapse data using traditional approaches. For example, null hypothesis significance testing is commonly used to determine whether relapse has occurred. However, this method requires several a priori assumptions about the data, as well as a large sample size for between-subjects comparisons or repeated testing for within-subjects comparisons. Monte Carlo methods may represent an improved analytic technique, because these methods require no prior assumptions, permit smaller sample sizes, and can be tailored to account for all of the data from an experiment instead of some limited set. In the present study, we conducted reanalyses of three studies of relapse (Berry, Sweeney, & Odum, ; Galizio et al., ; Odum & Shahan, ) using Monte Carlo techniques to determine if relapse occurred and if there were differences in rate of response based on relevant independent variables (such as group membership or schedule of reinforcement). These reanalyses supported the previous findings. Finally, we provide general recommendations for using Monte Carlo methods in studies of relapse.

    • Substance Use and Abuse

      1. The progress of tobacco control research in sub-Saharan Africa in the past 50 years: A systematic review of the design and methods of the studiesexternal icon
        Mamudu HM, Subedi P, Alamin AE, Veeranki SP, Owusu D, Poole A, Mbulo L, Ogwell Ouma AE, Oke A.
        Int J Environ Res Public Health. 2018 Dec 4;15(12).

        Over one billion of the world’s population are smokers, with increasing tobacco use in low- and middle-income countries. However, information about the methodology of studies on tobacco control is limited. We conducted a literature search to examine and evaluate the methodological designs of published tobacco research in Sub-Saharan Africa (SSA) over the past 50 years. The first phase was completed in 2015 using PubMed, Embase, CINAHL, and Cochrane Central Register of Controlled Trials. An additional search was completed in February 2017 using PubMed. Only tobacco/smoking research in SSA countries with human subjects and published in English was selected. Out of 1796 articles, 447 met the inclusion criteria and were from 26 countries, 11 of which had one study each. Over half of the publications were from South Africa and Nigeria. The earliest publication was in 1968 and the highest number of publications was in 2014 (n = 46). The majority of publications used quantitative methods (91.28%) and were cross-sectional (80.98%). The commonest data collection methods were self-administered questionnaires (38.53%), interviews (32.57%), and observation (20.41%). Around half of the studies were among adults and in urban settings. We conclud that SSA remains a “research desert” and needs more investment in tobacco control research and training.

      2. [No abstract]

      3. Exposure to secondhand smoke among nonsmokers – United States, 1988-2014external icon
        Tsai J, Homa DM, Gentzke AS, Mahoney M, Sharapova SR, Sosnoff CS, Caron KT, Wang L, Melstrom PC, Trivers KF.
        MMWR Morb Mortal Wkly Rep. 2018 Dec 7;67(48):1342-1346.

        Exposure to secondhand smoke from burning tobacco products can cause sudden infant death syndrome, respiratory infections, ear infections, and asthma attacks in infants and children, and coronary heart disease, stroke, and lung cancer in adult nonsmokers (1). There is no risk-free level of secondhand smoke exposure (2). CDC analyzed questionnaire and laboratory data from the National Health and Nutrition Examination Survey (NHANES) to assess patterns of secondhand smoke exposure among U.S. nonsmokers. The prevalence of secondhand smoke exposure among U.S. nonsmokers declined substantially during 1988-2014, from 87.5% to 25.2%. However, no change in exposure occurred between 2011-2012 and 2013-2014, and an estimated one in four nonsmokers, or approximately 58 million persons, were still exposed to secondhand smoke during 2013-2014. Moreover, marked disparities persisted across population groups. Exposure prevalence was highest among nonsmokers aged 3-11 years (37.9%), non-Hispanic blacks (50.3%), and those who were living in poverty (47.9%), in rental housing (38.6%), or with someone who smoked inside the home (73.0%), or among persons who had less than a high school education (30.7%). Comprehensive smoke-free laws and policies for workplaces and public places and smoke-free rules for homes and vehicles can further reduce secondhand smoke exposure among all nonsmokers.

    • Veterinary Medicine

      1. Morphometric and genetic variation in 8 breeds of Ethiopian camels (Camelus dromedarius)external icon
        Legesse YW, Dunn CD, Mauldin MR, Ordonez-Garza N, Rowden GR, Gebre YM, Kurtu MY, Mohammed Ali S, Whibesilassie WD, Ballou M, Tefera M, Perry G, Bradley RD.
        J Anim Sci. 2018 Dec 3;96(12):4925-4934.

        Dromedary camels (Camelus dromedarius) are a domesticated and closely guarded economic staple of indigenous people located throughout Ethiopian territorial states. Seventeen morphometric variables were examined to determine intraspecific variation among 8 pastoralist-designated breeds of camels. Additionally, DNA sequences from mitochondrial cytochrome-b gene and genotyping of 6 nuclear microsatellite loci were examined to assess genetic diversity and phylogenetic relationship of Ethiopian camels. Examination of 525 individuals revealed significant morphometric differentiation in Afar as compared with the remaining 7 breeds. Analysis of cytochrome-b sequences failed to recover monophyletic groups associated with pastoralist-recognized breeds. Analysis of 6 microsatellite loci from 104 individuals depicted no resolution of distinct genetic lineages in accordance to geographical or designated breeds. Overall, separation of 2 ecotypes based on the morphometric data was supported; however, genetic analysis of cytochrome-b and microsatellite data failed to support any unique genetic lineage or statistically significant population structure.

    • Zoonotic and Vectorborne Diseases

      1. Sounding the alarm: Defining thresholds to trigger a public health response to monkeypoxexternal icon
        Guagliardo SA, Reynolds MG, Kabamba J, Nguete B, Shongo Lushima R, Wemakoy OE, McCollum AM.
        PLoS Negl Trop Dis. 2018 Dec 20;12(12):e0007034.

        Endemic to the Democratic Republic of the Congo (DRC), monkeypox is a zoonotic disease that causes smallpox-like illness in humans. Observed fluctuations in reported cases over time raises questions about when it is appropriate to mount a public health response, and what specific actions should be taken. We evaluated three different thresholds to differentiate between baseline and heightened disease incidence, and propose a novel, tiered algorithm for public health action. Monkeypox surveillance data from Tshuapa Province, 2011-2013, were used to calculate three different statistical thresholds: Cullen, c-sum, and a World Health Organization (WHO) method based on monthly incidence. When the observed cases exceeded the threshold for a given month, that month was considered to be ‘aberrant’. For each approach, the number of aberrant months detected was summed by year-each method produced vastly different results. The Cullen approach generated a number of aberrant signals over the period of consideration (9/36 months). The c-sum method was the most sensitive (30/36 months), followed by the WHO method (12/24 months). We conclude that triggering public health action based on signals detected by a single method may be inefficient and overly simplistic for monkeypox. We propose instead a response algorithm that integrates an objective threshold (WHO method) with contextual information about epidemiological and spatiotemporal links between suspected cases to determine whether a response should be operating under i) routine surveillance ii) alert status, or iii) outbreak status. This framework could be modified and adopted by national and zone level health workers in monkeypox-endemic countries. Lastly, we discuss considerations for selecting thresholds for monkeypox outbreaks across gradients of endemicity and public health resources.

      2. Rabies in a dog imported from Egypt – Connecticut, 2017external icon
        Hercules Y, Bryant NJ, Wallace RM, Nelson R, Palumbo G, Williams JN, Ocana JM, Shapiro S, Leavitt H, Slavinsk S, Newman A, Crum DA, Joseph BE, Orciari LA, Li Y, Yager P, Condori RE, Stauffer KE, Brown C.
        MMWR Morb Mortal Wkly Rep. 2018 Dec 21;67(50):1388-1391.

        In 2007, the United States successfully eliminated canine rabies virus variant. Globally, however, dogs remain the principal source of human rabies infections. Since 2007, three cases of canine rabies virus variant were reported in dogs imported into the United States, one each from India (2007), Iraq (2008), and Egypt (2015) (1-3). On December 20, 2017, a dog imported into the United States from Egypt was identified with rabies, representing the second case from Egypt in 3 years. An Egyptian-based animal rescue organization delivered four dogs from Cairo, Egypt, to a flight parent (a person solicited through social media, often not affiliated with the rescue organization, and usually compensated with an airline ticket), who transported the dogs to the United States. The flight parent arrived at John F. Kennedy International Airport (JFK) in New York City and, via transporters (persons who shuttle dogs from one state to another), transferred the dogs to foster families; the dogs ultimately were adopted in three states. The Connecticut Department of Public Health Laboratory (CDPHL) confirmed the presence of a canine rabies virus variant in one of the dogs, a male aged 6 months that was adopted by a Connecticut family. An investigation revealed the possibility of falsified rabies vaccination documentation presented on entry at JFK, allowing the unvaccinated dog entry to the United States. This report highlights the continuing risk posed by the importation of dogs inadequately vaccinated against rabies from high-risk countries and the difficulties in verifying any imported dog’s health status and rabies vaccination history.

      3. Notes from the field: An outbreak of Salmonella agbeni infections linked to turtle exposure – United States, 2017external icon
        Koski L, Stevenson L, Huffman J, Robbins A, Latash J, Omoregie E, Kline K, Nichols M.
        MMWR Morb Mortal Wkly Rep. 2018 Dec 7;67(48):1350.

        [No abstract]

      4. Human tularaemia associated with exposure to domestic dogs-United States, 2006-2016external icon
        Kwit NA, Schwartz A, Kugeler KJ, Mead PS, Nelson CA.
        Zoonoses Public Health. 2018 Dec 16.

        Dogs have been implicated in the zoonotic transmission of numerous pathogens. Whereas cats are known to transmit Francisella tularensis to humans via bite and other routes, the role of dogs in facilitating infection is much less understood. We reviewed tularaemia case investigation records collected through national surveillance during 2006-2016 to summarize those with dog involvement, characterize the nature of dog-related exposure and describe associated clinical characteristics. Among 1,814 human tularaemia cases, 735 (41%) supplemental case investigation records were available for review; and of those, 24 (3.3%) were classified as dog-related. Median age of patients was 51 years (range: 1-82); 54% were female. Two thirds (67%) of cases presented with ulceroglandular/glandular tularaemia; pneumonic (13%) and oropharyngeal (13%) illness occurred less frequently. Dog-related exposures were classified as follows: direct contact via bite, scratch or face snuggling/licking (n = 12; 50%); direct contact with dead animals retrieved by domestic dogs (n = 8; 33%); and contact with infected ticks acquired from domestic dogs (n = 4; 17%). Prevention of dog-related tularaemia necessitates enhanced tularaemia awareness and tick avoidance among pet owners, veterinarians, health care providers and the general public.

      5. Enhanced arboviral surveillance to increase detection of Jamestown Canyon Virus Infections, Wisconsin, 2011-2016external icon
        Matkovic E, Hoang Johnson DK, Staples JE, Mora-Pinzon MC, Elbadawi LI, Osborn RA, Warshauer DM, Wegner MV, Davis JP.
        Am J Trop Med Hyg. 2018 Dec 10.

        Jamestown Canyon virus (JCV), a mosquito-borne Orthobunyavirus (within the California serogroup), can cause severe neuroinvasive disease. According to national data during 2000-2013, 42% of the 31 documented JCV disease cases in the United States were detected in residents from Wisconsin. The Wisconsin Division of Public Health enhanced JCV surveillance by implementing routine use of JCV-specific immunoglobulin M (IgM) antibody testing followed by confirmatory JCV-specific plaque reduction neutralization testing on all patients with suspected cases of arboviral infection who had tests positive for arboviral immunoglobin at commercial laboratories. During 2011-2016, of the 287 Wisconsin specimens tested on the Arbovirus IgM Antibody Panel, 30 JCV cases were identified (26 confirmed and four probable). Twenty-seven (90%) JCV cases were detected after 2013. Among all cases, 17 (56%) were male and the median age was 54 years (range: 10-84 years). Fifteen patients had neuroinvasive disease, including meningitis (n = 9) and meningoencephalitis (n = 6). Although historically considered rare, the relatively high rate (0.12 cases/100,000 population) of diagnosis of JCV infections among Wisconsin residents during 2013-2016 compared with that in previous years suggests occurrence is widespread throughout Wisconsin and historically may have been under-recognized. This study aims to raise awareness of JCV infection for differential diagnosis among the arboviral diseases. Improved and timely diagnosis of arboviral disease is important in that it will provide more information regarding emerging infections and promote preventive measures to avoid mosquito-borne exposure and infection among residents of and visitors to affected areas.

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CDC Science Clips Production Staff

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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
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