Issue 39, October 3, 2017

CDC Science Clips: Volume 9, Issue 39, October 3, 2017

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

This week, Science Clips is pleased to collaborate with CDC Vital Signs by featuring scientific articles from the October Vital Signs ( The articles marked with an asterisk are general review articles which may be of particular interest to clinicians and public health professionals seeking background information in this area.

  1. CDC Vital Signs
    • Chronic Diseases and Conditions – Obesity and Cancer
      1. *Adult weight gain and adiposity-related cancers: a dose-response meta-analysis of prospective observational studiesExternal
        Keum N, Greenwood DC, Lee DH, Kim R, Aune D, Ju W, Hu FB, Giovannucci EL.
        J Natl Cancer Inst. 2015 Feb;107(2).

        BACKGROUND: Adiposity, measured by body mass index, is implicated in carcinogenesis. While adult weight gain has diverse advantages over body mass index in measuring adiposity, systematic reviews on adult weight gain in relation to adiposity-related cancers are lacking. METHODS: PubMed and Embase were searched through September 2014 for prospective observational studies investigating the relationship between adult weight gain and the risk of 10 adiposity-related cancers. Dose-response meta-analyses were performed using a random-effects model to estimate summary relative risk (RR) and 95% confidence interval (CI) for each cancer type. All statistical tests were two-sided. RESULTS: A total of 50 studies were included. For each 5 kg increase in adult weight gain, the summary relative risk was 1.11 (95% CI = 1.08 to 1.13) for postmenopausal breast cancer among no- or low-hormone replacement therapy (HRT) users, 1.39 (95% CI = 1.29 to 1.49) and 1.09 (95% CI = 1.02 to 1.16) for postmenopausal endometrial cancer among HRT nonusers and users, respectively, 1.13 (95% CI = 1.03 to 1.23) for postmenopausal ovarian cancer among no or low HRT users, 1.09 (95% CI = 1.04 to 1.13) for colon cancer in men. The relative risk of kidney cancer comparing highest and lowest level of adult weight gain was 1.42 (95% CI = 1.11 to 1.81). Adult weight gain was unrelated to cancers of the breast (premenopausal women, postmenopausal HRT users), prostate, colon (women), pancreas, and thyroid. An increase in risk associated with adult weight gain for breast cancer was statistically significantly greater among postmenopausal women (P(heterogeneity) = .001) and HRT nonusers (P(heterogeneity) = .001); that for endometrial cancer was alike among HRT nonusers (P(heterogeneity) = .04). CONCLUSIONS: Avoiding adult weight gain itself may confer protection against certain types of cancers, particularly among HRT nonusers.

      2. *Body fatness and cancer – viewpoint of the IARC Working GroupExternal
        Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K.
        N Engl J Med. 2016 Aug 25;375(8):794-8.

        [No abstract]

      3. Body mass index and risk of gastric cancer: a meta-analysis of a population with more than ten million from 24 prospective studiesExternal
        Chen Y, Liu L, Wang X, Wang J, Yan Z, Cheng J, Gong G, Li G.
        Cancer Epidemiol Biomarkers Prev. 2013 Aug;22(8):1395-408.

        BACKGROUND: To provide a quantitative assessment of the association between body mass index (BMI) and the risk of gastric cancer, we summarized the evidence from prospective studies. METHODS: Eligible studies published up to November 30, 2012, were retrieved via computer searches of MEDLINE and EMBASE as well as manual review of references. Summary relative risks (SRR) with their corresponding 95% confidence intervals (CI) were calculated using a random-effects model. RESULTS: A total of 24 prospective studies of BMI and gastric cancer risk with 41,791 cases were included in our analysis. Overall, both overweight (BMI, 25-30 kg/m(2)) and obesity (BMI, >/=30 kg/m(2)) were not associated with risk of total gastric cancer (overweight: SRR, 1.01; 95% CI, 0.96-1.07; obesity: SRR, 1.06; 95% CI, 0.99-1.12). Furthermore, we found increased BMI was positively associated with the risk of gastric cardia cancer (GCC; SRR = 1.21 for overweight and 1.82 for obesity), but not with gastric non-cardia cancer (GNCC; SRR = 0.93 for overweight and SRR = 1.00 for obesity). Similar results were observed in a linear dose-response analysis. CONCLUSION: On the basis of meta-analysis of prospective studies, we find high BMI is positively associated with the risk of GCCs but not with GNCCs. IMPACT: (i) On the basis of more definite and quantitative evidence than previously available, we found that increasing BMI was not a clear risk factor for total gastric cancer. (ii) Increased BMI was positively associated with risk of GCC but not with GNCCs.

      4. Excess body weight and the risk of primary liver cancer: an updated meta-analysis of prospective studiesExternal
        Chen Y, Wang X, Wang J, Yan Z, Luo J.
        Eur J Cancer. 2012 Sep;48(14):2137-45.

        AIMS: To provide a quantitative assessment of the association between excess body weight (EBW) and the risk of primary liver cancer (PLC), we performed an updated meta-analysis of prospective observational studies. METHODS: We searched PUBMED and EMBASE for studies of body mass index and the risk of PLC published through 15 th September 2011. Summary relative risks (SRRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. The meta-regression and stratified methods were used to examine heterogeneity across studies. RESULTS: A total of 26 prospective studies, including 25,337 PLC cases, were included in this analysis. Overall, excess body weight (EBW: body mass index (BMI) >/= 25 kg/m2) and obesity (BMI >/= 30 kg/m2) were associated with an increased risk of PLC, with significant heterogeneity (EBW: SRRs 1.48, 95% CIs 1.31-1.67, P(h)<0.001, I2=83.6%; Obesity: SRRs 1.83, 95% CIs 1.59-2.11, P(h)<0.001, I2=75.0%). Subgroup analyses revealed that the positive associations were independent of geographic locations, alcohol consumption, history of diabetes or infections with hepatitis B (HBV) and/or hepatitis C virus (HCV). Obese males had a higher risk of PLC than obese females did (P=0.027). A stronger risk of PLC with EBW was observed for patients with HCV (but not HBV) infection or cirrhosis compared with the general population. CONCLUSIONS: Findings from this meta-analysis strongly support that EBW or obesity is associated with an increased risk of PLC in both males and females.

      5. Adult weight change and risk of postmenopausal breast cancerExternal
        Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE.
        Jama. 2006 Jul 12;296(2):193-201.

        CONTEXT: Endogenous hormones are a primary cause of breast cancer. Adiposity affects circulating hormones, particularly in postmenopausal women, and may be a modifiable risk factor for breast cancer. OBJECTIVE: To assess the associations of adult weight change since age 18 years and since menopause with the risk of breast cancer among postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study within the Nurses’ Health Study. A total of 87,143 postmenopausal women, aged 30 to 55 years and free of cancer, were followed up for up to 26 years (1976-2002) to assess weight change since age 18 years. Weight change since menopause was assessed among 49,514 women who were followed up for up to 24 years. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer. RESULTS: Overall, 4393 cases of invasive breast cancer were documented. Compared with those who maintained weight, women who gained 25.0 kg or more since age 18 years were at an increased risk of breast cancer (relative risk [RR], 1.45; 95% confidence interval [CI], 1.27-1.66; P<.001 for trend), with a stronger association among women who have never taken postmenopausal hormones (RR,1.98; 95% CI, 1.55-2.53). Compared with weight maintenance, women who gained 10.0 kg or more since menopause were at an increased risk of breast cancer (RR, 1.18; 95% CI, 1.03-1.35; P = .002 for trend). Women who had never used postmenopausal hormones, lost 10.0 kg or more since menopause, and kept the weight off were at a lower risk than those who maintained weight (RR, 0.43; 95% CI, 0.21-0.86; P = .01 for weight loss trend). Overall, 15.0% (95% CI, 12.8%-17.4%) of breast cancer cases in this population may be attributable to weight gain of 2.0 kg or more since age 18 years and 4.4% (95% CI, 3.6%-5.5%) attributable to weight gain of 2.0 kg or more since menopause. Among those who did not use postmenopausal hormones, the population attributable risks are 24.2% (95% CI, 19.8%-29.1%) for a weight gain since age 18 years and 7.6% (95% CI, 5.9%-9.7%) for weight gain since menopause. CONCLUSIONS: These data suggest that weight gain during adult life, specifically since menopause, increases the risk of breast cancer among postmenopausal women, whereas weight loss after menopause is associated with a decreased risk of breast cancer. Thus, in addition to other known benefits of healthy weight, our results provide another reason for women approaching menopause to maintain or lose weight, as appropriate.

      6. Body mass index in relation to oesophageal and oesophagogastric junction adenocarcinomas: a pooled analysis from the International BEACON ConsortiumExternal
        Hoyo C, Cook MB, Kamangar F, Freedman ND, Whiteman DC, Bernstein L, Brown LM, et al .
        Int J Epidemiol. 2012 Dec;41(6):1706-18.

        BACKGROUND: Previous studies suggest an association between obesity and oesophageal (OA) and oesophagogastric junction adenocarcinomas (OGJA). However, these studies have been limited in their ability to assess whether the effects of obesity vary by gender or by the presence of gastro-oesophageal reflux (GERD) symptoms. METHODS: Individual participant data from 12 epidemiological studies (8 North American, 3 European and 1 Australian) comprising 1997 OA cases, 1900 OGJA cases and 11 159 control subjects were pooled. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between body mass index (BMI, kg/m(2)) and the risk of OA and OGJA. Random-effects meta-analysis was used to combine these ORs. We also investigated effect modification and synergistic interaction of BMI with GERD symptoms and gender. RESULTS: The association of OA and OGJA increased directly with increasing BMI (P for trend <0.001). Compared with individuals with a BMI <25, BMI >/=40 was associated with both OA (OR 4.76, 95% CI 2.96-7.66) and OGJA (OR 3.07, 95% CI 1.89-4.99). These associations were similar when stratified by gender and GERD symptoms. There was evidence for synergistic interaction between BMI and GERD symptoms in relation to OA/OGJA risk. CONCLUSIONS: These data indicate that BMI is directly associated with OA and OGJA risk in both men and women and in those with and without GERD symptoms. Disentangling the relationship between BMI and GERD will be important for understanding preventive efforts for OA and OGJA.

      7. Intentional weight loss and endometrial cancer riskExternal
        Luo J, Chlebowski RT, Hendryx M, Rohan T, Wactawski-Wende J, Thomson CA, Felix AS, et al .
        J Clin Oncol. 2017 Apr 10;35(11):1189-1193.

        Purpose Although obesity is an established endometrial cancer risk factor, information about the influence of weight loss on endometrial cancer risk in postmenopausal women is limited. Therefore, we evaluated associations among weight change by intentionality with endometrial cancer in the Women’s Health Initiative (WHI) observational study. Patients and Methods Postmenopausal women (N = 36,794) ages 50 to 79 years at WHI enrollment had their body weights measured and body mass indices calculated at baseline and at year 3. Weight change during that period was categorized as follows: stable (change within +/- 5%), loss (change >/= 5%), and gain (change >/= 5%). Weight loss intentionality was assessed via self-report at year 3; change was characterized as intentional or unintentional. During the subsequent 11.4 years (mean) of follow-up, 566 incident endometrial cancer occurrences were confirmed by medical record review. Multivariable Cox proportional hazards regression models were used to evaluate relationships (hazard ratios [HRs] and 95% CIs) between weight change and endometrial cancer incidence. Results In multivariable analyses, compared with women who had stable weight (+/- 5%), women with weight loss had a significantly lower endometrial cancer risk (HR, 0.71; 95% CI, 0.54 to 0.95). The association was strongest among obese women with intentional weight loss (HR, 0.44; 95% CI, 0.25 to 0.78). Weight gain (>/= 10 pounds) was associated with a higher endometrial cancer risk than was stable weight, especially among women who had never used hormones. Conclusion Intentional weight loss in postmenopausal women is associated with a lower endometrial cancer risk, especially among women with obesity. These findings should motivate programs for weight loss in obese postmenopausal women.

      8. Obesity and risk of colorectal cancer: a systematic review of prospective studiesExternal
        Ma Y, Yang Y, Wang F, Zhang P, Shi C, Zou Y, Qin H.
        PLoS One. 2013 ;8(1):e53916.

        BACKGROUND: Mounting evidence indicates that obesity may be associated with the risk of colorectal cancer (CRC). To conduct a systematic review of prospective studies assessing the association of obesity with the risk of CRC using meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Relevant studies were identified by a search of MEDLINE and EMBASE databases before January 2012, with no restrictions. We also reviewed reference lists from retrieved articles. We included prospective studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between general obesity [measured using body mass index (BMI)] or central obesity [measured using waist circumference (WC)] and the risk of colorectal, colon, or rectal cancer. Approximately 9, 000, 000 participants from several countries were included in this analysis. 41 studies on general obesity and 13 studies on central obesity were included in the meta-analysis. The pooled RRs of CRC for the obese vs. normal category of BMI were 1.334 (95% CI, 1.253-1.420), and the highest vs. lowest category of WC were 1.455 (95% CI, 1.327-1.596). There was heterogeneity among studies of BMI (P<0.001) but not among studies of WC (P=0.323). CONCLUSIONS: Both of general and central obesity were positively associated with the risk of CRC in this meta-analysis.

      9. Obesity, diet and physical inactivity are risk factors for some cancers. Grantees of the National Comprehensive Cancer Control Program (NCCCP) in US states, tribes, and territories develop plans to coordinate funding and activities for cancer prevention and control. Including information and goals related to nutrition and physical activity (NPA) is a key opportunity for primary cancer prevention, but it is currently unclear to what extent NCCCP plans address these issues. We reviewed 69 NCCCP plans and searched for terms related to NPA. Plans were coded as (1) knowledge of NPA and cancer link; (2) goals to improve NPA behaviors; and (3) strategies to increase healthy NPA activities, environments, or systems changes. NPA content was consistently included in all cancer plans examined across all years. Only 4 (6 %) outlined only the relationship between NPA and cancer without goals or strategies. Fifty-nine plans (89 %) contained goals or strategies related to NPA, with 53 (82 %) including both. However, numbers of goals, strategies, and detail provided varied widely. All programs recognized the importance of NPA in cancer prevention. Most plans included NPA goals and strategies. Increasing the presence of NPA strategies that can be modified or adapted appropriately locally could help with more widespread implementation and measurement of NPA interventions.

      10. Type I and II endometrial cancers: have they different risk factors?External
        Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB, Wolk A, Wentzensen N, Weiss NS, Webb PM, van den Brandt PA, van de Vijver K, Thompson PJ, Strom BL, Spurdle AB, Soslow RA, Shu XO, Schairer C, Sacerdote C, Rohan TE, Robien K, Risch HA, Ricceri F, Rebbeck TR, Rastogi R, Prescott J, Polidoro S, Park Y, Olson SH, Moysich KB, Miller AB, McCullough ML, Matsuno RK, Magliocco AM, Lurie G, Lu L, Lissowska J, Liang X, Lacey JV, Kolonel LN, Henderson BE, Hankinson SE, Hakansson N, Goodman MT, Gaudet MM, Garcia-Closas M, Friedenreich CM, Freudenheim JL, Doherty J, De Vivo I, Courneya KS, Cook LS, Chen C, Cerhan JR, Cai H, Brinton LA, Bernstein L, Anderson KE, Anton-Culver H, Schouten LJ, Horn-Ross PL.
        J Clin Oncol. 2013 Jul 10;31(20):2607-18.

        PURPOSE: Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. PATIENTS AND METHODS: Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors. RESULTS: Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m(2) increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (P heterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar. CONCLUSION: The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed.

      11. Obesity is accepted as one of the major risk factors for renal cell cancer (RCC). However, conflicting results persist for the pooled risks based on the results from case-control and cohort studies combined, and the exact shape of the dose-response relationship has not been clearly defined yet. To help elucidate the role of obesity, PubMed and Embase databases were searched for published cohort studies on associations between body mass index (BMI) and risk of RCC. Random-effects models and dose-response meta-analyses were used to pool study results. Subgroup analyses were conducted by the available characteristics of studies and participants. Cohort studies (21) with 15,144 cases and 9,080,052 participants were identified. Compared to normal weight, the pooled relative risks and the corresponding 95% confidence intervals of RCC were 1.28(1.24-1.33) for preobesity and 1.77(1.68-1.87) for obesity, respectively. A nonlinear dose-response relationship was also found for RCC risk with BMI (p = 0.000), and the risk increased by 4% for each 1 kg/m(2) increment in BMI. There was no significant between-study heterogeneity among studies (I(2) = 35.6% for preobesity and I(2) = 44.2% for obesity, respectively). Subgroup analysis showed a basically consistent result with the overall analysis. These results suggest that increased BMI are associated with increased risk of RCC both for men and women.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. OBJECTIVE: The object of this study was to explore the use of complementary health approaches among U.S. adults with a cancer diagnosis in the past 5 years and distinguish use for general wellness from use specifically for treatment. METHODS: Using data from the 2002, 2007, and 2012 National Health Interview Survey, the study included 1359 persons with a cancer diagnosis of selected cancers in the past 5 years. Participants were asked about their use of complementary health approaches for general reasons and cancer treatment in the past 12 months. Responses were aggregated into the use of any complementary approach as well as examined by mode of practice. RESULTS: Overall, 35.3% of persons with a cancer diagnosis used complementary health approaches in the past 12 months. These persons were more likely to have used a biologically based approach (22.8%) compared with other approaches. Persons with breast cancer were significantly more likely to use any complementary health approach (43.6%) compared with those with other recently diagnosed cancers. Few persons with a cancer history (2.3%) used complementary approaches specifically for cancer treatment. However, prevalence of use for treatment varied by cancer type (0.4%-6.8%). CONCLUSIONS: This study highlights differences in the use of various types of complementary health approaches for different reasons among persons with recent diagnoses of some of the most commonly diagnosed cancers in the United States.

      2. Trends in cervical cancer screening in Title X-funded health centers – United States, 2005-2015External
        Fowler CI, Saraiya M, Moskosky SB, Miller JW, Gable J, Mautone-Smith N.
        MMWR Morb Mortal Wkly Rep. 2017 Sep 22;66(37):981-985.

        Cervical cancer screening is critical to early detection and treatment of precancerous cells and cervical cancer. In 2015, 83% of U.S. women reported being screened per current recommendations, which is below the Healthy People 2020 target of 93% (1,2). Disparities in screening persist for women who are younger (aged 21-30 years), have lower income, are less educated, are uninsured, lack a source of health care, or who self-identify as Asian or American Indian/Alaska Native (2). Women who are never screened or rarely screened are more likely to develop cancer and receive a cancer diagnosis at later stages than women who are screened regularly (3). In 2013, cervical cancer was diagnosed in 11,955 women in the United States, and 4,217 died from the disease (4). Aggregated administrative data from the Title X Family Planning Program were used to calculate the percentage of female clients served in Title X-funded health centers who received a Papanicolaou (Pap) test during 2005-2015. Trends in the percentage of Title X clients screened for cervical cancer were examined in relation to changes in cervical cancer screening guidelines, particularly the 2009 American College of Obstetricians and Gynecologists (ACOG) update that raised the age for starting cervical cancer screening to 21 years (5) and the 2012 alignment of screening guidelines from ACOG, the U.S. Preventive Services Task Force (USPSTF) and the American Cancer Society (ACS) on the starting age (21 years), screening interval (3 or 5 years), and type of screening test (6-8). During 2005-2015, the percentage of female clients screened for cervical cancer dropped continually, with the largest declines occurring in 2010 and 2013, notably a year after major updates to the recommendations. Although aggregated data contribute to understanding of cervical cancer screening trends in Title X centers, studies using client-level and encounter-level data are needed to assess the appropriateness of cervical cancer screening in individual cases.

      3. Viral and parasitic pathogen burden and the association with stroke in a population-based cohortExternal
        Pearce BD, Bracher A, Jones JL, Kruszon-Moran D.
        Int J Stroke. 2017 Jan 01:1747493017729269.

        Background Higher cumulative burden of viral and bacterial pathogens may increase the risk of stroke, but the contribution of parasitic infections in relation to cumulative pathogen burden and risk of stroke has rarely been examined. Aim To estimate the association of multiple persistent viral and parasitic infections with stroke in a representative sample of adults in the United States. Methods Serological evidence of prior infection was categorized as positive for 0-1, 2, 3, or 4-5 infections based on immunoglobulin G seropositivity to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. in 13,904 respondents from the National Health and Nutrition Examination Survey III. Regression analysis was used to estimate the cross-sectional association between serological evidence of prior infection and history of stroke adjusting for demographic risk factors, and potential mediators of stroke. Results Age-adjusted models that included serological evidence of prior infection to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. showed that adults in the highest serological evidence of prior infection category (4-5 infections) had a higher prevalence of stroke (5.50%, 95% confidence interval 2.44-10.46%) than those in the lowest serological evidence of prior infection categories (1.49%, 95% confidence interval 1.01-2.11%), and a trend test suggested a graded association between serological evidence of prior infection and stroke ( p = 0.02). In multivariable logistic regression models, the positive association of serological evidence of prior infection with stroke prevalence remained significant after adjustment for other significant risk factors (odds ratio = 1.4, p = 0.01) but was only significant among those aged 20-59 (odds ratio = 2.0, p = 0.005) and not among those aged 60-69 ( p = 0.78) or 70 and older ( p = 0.43). Conclusion We found support for a connection between serological evidence of prior infection to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. and stroke among those aged 20-59. There may be a need to consider common parasitic infections in addition to viral and bacterial pathogens when calculating serological evidence of prior infection in relation to cerebrovascular disease.

      4. Geographic access to cancer care and mortality among adolescentsExternal
        Tai E, Hallisey E, Peipins LA, Flanagan B, Buchanan Lunsford N, Wilt G, Graham S.
        J Adolesc Young Adult Oncol. 2017 Sep 21.

        PURPOSE: Adolescents with cancer have had less improvement in survival than other populations in the United States. This may be due, in part, to adolescents not receiving treatment at Children’s Oncology Group (COG) institutions, which have been shown to increase survival for some cancers. The objective of this ecologic study was to examine geographic distance to COG institutions and adolescent cancer mortality. METHODS: We calculated cancer mortality among adolescents and sociodemographic and healthcare access factors in four geographic zones at selected distances surrounding COG facilities: Zone A (area within 10 miles of any COG institution), Zones B and C (concentric rings with distances from a COG institution of >10-25 miles and >25-50 miles, respectively), and Zone D (area outside of 50 miles). RESULTS: The adolescent cancer death rate was highest in Zone A at 3.21 deaths/100,000, followed by Zone B at 3.05 deaths/100,000, Zone C at 2.94 deaths/100,000, and Zone D at 2.88 deaths/100,000. The United States-wide death rate for whites without Hispanic ethnicity, blacks without Hispanic ethnicity, and persons with Hispanic ethnicity was 2.96 deaths/100,000, 3.10 deaths/100,000, and 3.26 deaths/100,000, respectively. Zone A had high levels of poverty (15%), no health insurance coverage (16%), and no vehicle access (16%). CONCLUSIONS: Geographic access to COG institutions, as measured by distance alone, played no evident role in death rate differences across zones. Among adolescents, socioeconomic factors, such as poverty and health insurance coverage, may have a greater impact on cancer mortality than geographic distance to COG institution.

    • Communicable Diseases
      1. Norovirus is the leading cause of acute gastroenteritis. In older adults, it is responsible for an estimated 3.7 million illnesses; 320,000 outpatient visits; 69,000 emergency department visits; 39,000 hospitalizations; and 960 deaths annually in the United States. Older adults are particularly at risk for severe outcomes, including prolonged symptoms and death. Long-term care facilities and hospitals are the most common settings for norovirus outbreaks in developed countries. Diagnostic platforms are expanding. Several norovirus vaccines in clinical trials have the potential to reap benefits. This review summarizes current knowledge on norovirus infection in older adults.

      2. Short communication: Heightened HIV antibody responses in postpartum women as exemplified by recent infection assays: Implications for incidence estimatesExternal
        Hargrove JW, van Schalkwyk C, Humphrey JH, Mutasa K, Ntozini R, Owen SM, Masciotra S, Parekh BS, Duong YT, Dobbs T, Kilmarx PH, Gonese E.
        AIDS Res Hum Retroviruses. 2017 Sep;33(9):902-904.

        Laboratory assays that identify recent HIV infections are important for assessing impacts of interventions aimed at reducing HIV incidence. Kinetics of HIV humoral responses can vary with inherent assay properties, and between HIV subtypes, populations, and physiological states. They are important in determining mean duration of recent infection (MDRI) for antibody-based assays for detecting recent HIV infections. We determined MDRIs for multi-subtype peptide representing subtypes B, E and D (BED)-capture enzyme immunoassay, limiting antigen (LAg), and Bio-Rad Avidity Incidence (BRAI) assays for 101 seroconverting postpartum women, recruited in Harare from 1997 to 2000 during the Zimbabwe Vitamin A for Mothers and Babies trial, comparing them against published MDRIs estimated from seroconverting cases in the general population. We also compared MDRIs for women who seroconverted either during the first 9 months, or at later stages, postpartum. At cutoffs (C) of 0.8 for BED, 1.5 for LAg, and 40% for BRAI, estimated MDRIs for postpartum mothers were 192, 104, and 144 days, 33%, 32%, and 52% lower than published estimates of 287, 152 and 298 days, respectively, for clade C samples from general populations. Point estimates of MDRI values were 7%-19% shorter for women who seroconverted in the first 9 months postpartum than for those seroconverting later. MDRI values for three HIV incidence biomarkers are longer in the general population than among postpartum women, particularly those who recently gave birth, consistent with heightened immunological activation soon after birth. Our results provide a caution that MDRI may vary significantly between subjects in different physiological states.

      3. HIV viral suppression, 37 states and the District of Columbia, 2014External
        Hess KL, Hall HI.
        J Community Health. 2017 Sep 18.

        Achieving viral suppression among HIV-positive persons is a critical component of HIV treatment and prevention, because it leads to improved health outcomes for the individual and reduced risk of HIV transmission. There is wide variation in viral suppression across jurisdictions, races/ethnicities, age groups, and transmission risk groups. This analysis uses HIV surveillance data to examine rates of viral suppression among people living with diagnosed HIV (PLWDH) in 38 jurisdictions with complete lab reporting. Among people who received a diagnosis in 2014, the percentage with viral suppression within 12 months of diagnosis and the average time to viral suppression was assessed. Overall, among PLWDH in 2014, 57.9% were virally suppressed, and, among people with HIV diagnosed in 2014, 68.2% were suppressed within 12 months of diagnosis with an average time to suppression of 6.9 months. All outcomes varied by jurisdiction, but most had similar patterns of disparities with a few exceptions. These data highlight the need for tailored interventions at the local level. In addition, jurisdictions with relatively low viral suppression among particular groups could adapt effective interventions from jurisdictions who have higher rates of suppression.

      4. Notes from the field: Increase in reported hepatitis A infections among men who have sex with men – New York City, January-August 2017External
        Latash J, Dorsinville M, Del Rosso P, Antwi M, Reddy V, Waechter H, Lawler J, Boss H, Kurpiel P, Backenson PB, Gonzalez C, Rowe S, Poissant T, Lin Y, Xia GL, Balter S.
        MMWR Morb Mortal Wkly Rep. 2017 Sep 22;66(37):999-1000.

        Since 2011, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) has typically been notified of three or fewer cases of hepatitis A virus (HAV) infection each year among men who have sex with men (MSM) who reported no travel to countries where HAV is endemic. This year, DOHMH noted an increase in HAV infections among MSM with onsets in January-March 2017, and notified other public health jurisdictions via Epi-X, CDC’s communication exchange network. As a result, 51 patients with HAV infection involving MSM were linked to the increase in NYC.

      5. Monitoring HIV drug resistance: Early warning indicators to assess performance of Thailand’s antiretroviral treatment programExternal
        Lertpiriyasuwat C, Teeraratkul A, Suchonwanich Y, Chatharojwong N, Phokasawad K, Yuktanon P, Pattarapayoon N, Bhakeecheep S, Bertagnolio S, Roels TH, Thanprasertsuk S.
        J Med Assoc Thai. 2017 September;100(9):944-952.

        Objective: To describe trends in Thailand’s antiretroviral treatment (ART) program performance assessed by HIV drug resistance early warning indicators (EWIs), as recommended by WHO, between 2009 and 2013. Material and Method: Seven EWIs were monitored, viral load (VL) testing coverage, VL suppression, retention in ART, lost to follow-up (LTFU), antiretrovirals (ARVs) dispensing practices, on-time pill pick-up, and pharmacy stock-outs. Data from ART adult patients in National Health Security Office Scheme were analyzed except for pharmacy stock-outs, which were reported from hospitals. Aggregated averages were calculated for each EWI. Chi-square for trend was applied to measure significant changes. Results: By September 2013, 174,284 adults were receiving ART at 929 hospitals. Over time, improvement in VL testing coverage (53.8% in 2009 to 79.8% in 2013) was observed. VL suppression and on-time pill pick up rates were well above 90%. Rates of retention in ART declined from 84.0 to 82.9%, whereas LTFU rates increased from 8.3 to 9.2% (p<0.001). Prescriptions with inappropriate ARVs decreased from 0.32 to 0.10% (p<0.001). Of reporting hospitals, 96.1%, 96.3%, and 96.2% observed no ARVs stock-out between 2011 and 2013. Conclusion: EWI is a useful tool to monitor ART program performance and to identify area where improvement is needed.

      6. Notes from the field: Travel-associated melioidosis and resulting laboratory exposures – United States, 2016External
        Mitchell PK, Campbell C, Montgomery MP, Paoline J, Wilbur C, Posivak-Khouly L, Garafalo K, Elrod M, Liu L, Weltman A.
        MMWR Morb Mortal Wkly Rep. 2017 Sep 22;66(37):1001-1002.

        In mid-July 2016, a Pennsylvania resident aged 15 years who had recently returned from Thailand was treated by a pediatrician for sore throat, fever, and bilateral thigh abscesses at the sites of mosquito bites (Figure). She had traveled to northeast Thailand with nine other teens as part of an 18-day service-oriented trip run by an Ohio-based youth tour company that arranges travel to Thailand for approximately 500 persons annually. This trip included construction and agricultural activities and recreational mud exposures. The patient subsequently developed right inguinal lymphadenopathy and worsening abscesses, which prompted specimen collection for culture on August 25. This specimen was sent to a commercial laboratory in New Jersey, which identified Burkholderia pseudomallei, the causative organism of melioidosis, on August 30. The patient did not experience pneumonia or bacteremia, and recovered fully after 2 weeks of intensive therapy with parenteral ceftazidime and a 6-month outpatient course of eradication therapy with doxycycline.

      7. Molecular characterization of Neisseria meningitidis isolates recovered from 11-19-year-old meningococcal carriers in Salvador, BrazilExternal
        Moura A, Kretz CB, Ferreira IE, Nunes A, de Moraes JC, Reis MG, McBride AJ, Wang X, Campos LC.
        PLoS One. 2017 ;12(9):e0185038.

        Characterization of meningococci isolated from the pharynx is essential towards understanding the dynamics of meningococcal carriage and disease. Meningococcal isolates, collected from adolescents resident in Salvador, Brazil during 2014, were characterized by multilocus sequence typing, genotyping or whole-genome sequencing. Most were nongroupable (61.0%), followed by genogroups B (11.9%) and Y (8.5%). We identified 34 different sequence types (STs), eight were new STs, distributed among 14 clonal complexes (cc), cc1136 represented 20.3% of the nongroupable isolates. The porA and fetA genotypes included P1.18,25-37 (11.9%), P1.18-1,3 (10.2%); F5-5 (23.7%), F4-66 (16.9%) and F1-7 (13.6%). The porB class 3 protein and the fHbp subfamily A (variants 2 and 3) genotypes were found in 93.0 and 71.0% of the isolates, respectively. NHBA was present in all isolates, and while most lacked NadA (94.9%), we detected the hyperinvasive lineages B:P1.19,15:F5-1:ST-639 (cc32); C:P1.22,14-6:F3-9:ST-3780 (cc103) and W:P1.5,2:F1-1:ST-11 (cc11). This is the first report on the genetic diversity and vaccine antigen prevalence among N. meningitidis carriage isolates in the Northeast of Brazil. This study highlights the need for ongoing characterization of meningococcal isolates following the introduction of vaccines and for determining public health intervention strategies.

      8. Changing hearts and minds: Results from a multi-country gender and sexual diversity trainingExternal
        Poteat T, Park C, Solares D, Williams JK, Wolf RC, Metheny N, Vazzano A, Dent J, Gibbs A, Nonyane BA, Toiv N.
        PLoS One. 2017 ;12(9):e0184484.

        Engaging key populations, including gender and sexual minorities, is essential to meeting global targets for reducing new HIV infections and improving the HIV continuum of care. Negative attitudes toward gender and sexual minorities serve as a barrier to political will and effective programming for HIV health services. The President’s Emergency Plan for AIDS Relief (PEPFAR), established in 2003, provided Gender and Sexual Diversity Trainings for 2,825 participants including PEPFAR staff and program implementers, U.S. government staff, and local stakeholders in 38 countries. The outcomes of these one-day trainings were evaluated among a subset of participants using a mixed methods pre- and post-training study design. Findings suggest that sustainable decreases in negative attitudes toward gender and sexual minorities are achievable with a one-day training.

      9. Latent tuberculous infection testing among HIV-infected persons in clinical care, United States, 2010-2012External
        Reaves EJ, Shah NS, France AM, Morris SB, Kammerer S, Skarbinski J, Bradley H.
        Int J Tuberc Lung Dis. 2017 Oct 01;21(10):1118-1126.

        SETTING: Current guidelines recommend latent tuberculous infection (LTBI) testing at the time of human immunodeficiency virus (HIV) diagnosis and annually thereafter for persons at high risk of LTBI. OBJECTIVES: To estimate LTBI testing prevalence and describe the characteristics of HIV-infected persons who would benefit from annual LTBI testing. DESIGN: We estimated the proportions of LTBI testing among a nationally representative sample of HIV-infected adults in care between 2010 and 2012, and compared the patient characteristics of those with a positive LTBI test result to those with a negative result using chi2 tests. RESULTS: Among 2772 patients, 68.8% had been tested for LTBI at least once since HIV diagnosis, and 39.4% had been tested during the previous 12 months. Among patients tested at least once, 6.9% tested positive, 80.7% tested negative, and 12.4% had an indeterminate or undocumented result. Patients with a positive test were significantly more likely to be foreign-born, have lower educational attainment, and a household income at or below the federal poverty level. CONCLUSIONS: More than 30% of HIV-infected patients had never been tested for LTBI. Providers should test all patients for LTBI at the time of HIV diagnosis. The patient characteristics associated with a positive LTBI test result may guide provider decisions about annual testing.

      10. Rapid, actionable diagnosis of urban epidemic leptospirosis using a pathogenic Leptospira lipL32-based real-time PCR assayExternal
        Riediger IN, Stoddard RA, Ribeiro GS, Nakatani SM, Moreira SD, Skraba I, Biondo AW, Reis MG, Hoffmaster AR, Vinetz JM, Ko AI, Wunder EA.
        PLoS Negl Trop Dis. 2017 Sep 15;11(9):e0005940.

        BACKGROUND: With a conservatively estimated 1 million cases of leptospirosis worldwide and a 5-10% fatality rate, the rapid diagnosis of leptospirosis leading to effective clinical and public health decision making is of high importance, and yet remains a challenge. METHODOLOGY: Based on parallel, population-based studies in two leptospirosis-endemic regions in Brazil, a real-time PCR assay which detects lipL32, a gene specifically present in pathogenic Leptospira, was assessed for the diagnostic effectiveness and accuracy. Patients identified by active hospital-based surveillance in Salvador and Curitiba during large urban leptospirosis epidemics were tested. Real-time PCR reactions were performed with DNA-extracted samples obtained from 127 confirmed and 23 unconfirmed cases suspected of leptospirosis, 122 patients with an acute febrile illness other than leptospirosis, and 60 healthy blood donors. PRINCIPAL FINDINGS: The PCR assay had a limit of detection of 280 Leptospira genomic equivalents/mL. Sensitivity for confirmed cases was 61% for whole blood and 29% for serum samples. Sensitivity was higher (86%) for samples collected within the first 6 days after onset of illness compared to those collected after 7 days (34%). The real-time PCR assay was able to detect leptospiral DNA in blood from 56% of serological non-confirmed cases. The overall specificity of the assay was 99%. CONCLUSIONS: These findings indicate that real-time PCR may be a reliable tool for early diagnosis of leptospirosis, which is decisive for clinical management of severe and life-threatening cases and for public health decision making.

      11. We examined factors that may be associated with whether Black men who have sex with men a) disclose their sexual orientation to healthcare providers, and b) discuss their sexual health with healthcare providers to inform interventions to improve HIV prevention efforts and reduce HIV incidence rates among Black men who have sex with men. During 2011-2012, we conducted semi-structured individual in-depth interviews with Black men who have sex with men in New York City. Interviews were audio recorded. We examined transcribed responses for main themes using a qualitative exploratory approach followed by computer-assisted thematic analyses. Twenty-nine men participated. The median age was 25.3 years; 41% (n = 12) earned an annual income of < US$10,000; 72% (n = 21) had a college degree; 86% (n = 25) reported being single; 69% (n = 20) self-identified as gay or homosexual. We identified three main themes affecting whether the men discussed their sexual orientation and sexual health with healthcare providers: 1) comfort discussing sexual health needs; 2) health literacy; and 3) trust. Identifying strategies for improved comfort, health literacy and trust between Black men who have sex with men and healthcare providers may be an important strategy for increasing sexual health patient-provider communications, increasing opportunities for HIV prevention including testing and reducing HIV-related health disparities.

      12. Human bocavirus capsid messenger RNA detection in children with pneumoniaExternal
        Schlaberg R, Ampofo K, Tardif KD, Stockmann C, Simmon KE, Hymas W, Flygare S, Kennedy B, Blaschke A, Eilbeck K, Yandell M, McCullers JA, Williams DJ, Edwards K, Arnold SR, Bramley A, Jain S, Pavia AT.
        J Infect Dis. 2017 Sep 15;216(6):688-696.

        Background: The role of human bocavirus (HBoV) in respiratory illness is uncertain. HBoV genomic DNA is frequently detected in both ill and healthy children. We hypothesized that spliced viral capsid messenger RNA (mRNA) produced during active replication might be a better marker for acute infection. Methods: As part of the Etiology of Pneumonia in the Community (EPIC) study, children aged <18 years who were hospitalized with community-acquired pneumonia (CAP) and children asymptomatic at the time of elective outpatient surgery (controls) were enrolled. Nasopharyngeal/oropharyngeal specimens were tested for HBoV mRNA and genomic DNA by quantitative polymerase chain reaction. Results: HBoV DNA was detected in 10.4% of 1295 patients with CAP and 7.5% of 721 controls (odds ratio [OR], 1.4 [95% confidence interval {CI}, 1.0-2.0]); HBoV mRNA was detected in 2.1% and 0.4%, respectively (OR, 5.1 [95% CI, 1.6-26]). When adjusted for age, enrollment month, and detection of other respiratory viruses, HBoV mRNA detection (adjusted OR, 7.6 [95% CI, 1.5-38.4]) but not DNA (adjusted OR, 1.2 [95% CI, .6-2.4]) was associated with CAP. Among children with no other pathogens detected, HBoV mRNA (OR, 9.6 [95% CI, 1.9-82]) was strongly associated with CAP. Conclusions: Detection of HBoV mRNA but not DNA was associated with CAP, supporting a pathogenic role for HBoV in CAP. HBoV mRNA could be a useful target for diagnostic testing.

      13. HIV care outcomes among men who have sex with men with diagnosed HIV infection – United States, 2015External
        Singh S, Mitsch A, Wu B.
        MMWR Morb Mortal Wkly Rep. 2017 Sep 22;66(37):969-974.

        Gay, bisexual, and other men who have sex with men (collectively referred to as MSM) represent approximately 2% of the U.S. population (1), yet in 2015, MSM accounted for 70% of all diagnoses of human immunodeficiency virus (HIV) infection, including 3% who also were persons who inject drugs (2). During 2008-2014, incidence of HIV infection decreased for groups in all transmission categories except MSM (3). Testing, linkage to and retention in care, and viral suppression are important in reducing HIV transmission. National HIV Surveillance System (NHSS)* data are used to monitor progress toward reaching national goals.dagger To better guide prevention measures, CDC analyzed data from NHSS for MSM aged >/=13 years (excluding MSM who inject drugs) to determine stage at diagnosis of HIV infection and care outcomes. Among the 19,170 MSM with HIV infection diagnosed in 2015 in 38 jurisdictions with complete laboratory reporting, 3,666 (19.1%) had infection classified as stage 3 (acquired immunodeficiency syndrome [AIDS]) at diagnosis and 74.7% and 84.0% were linked to care within 1 month and 3 months, respectively. Among MSM living with diagnosed HIV infection at year-end 2014, 74.1% received any HIV care, 57.7% were retained in continuous care, and 61.2% had achieved viral suppression. Younger MSM and black or African American (black) MSM had the least favorable HIV care outcomes. Strengthening interventions that increase care and viral suppression among MSM, particularly those aged <25 years and black MSM with public and private partners is important.

      14. HIV disproportionately affects the foreign-born population in the United States. This analysis describes the prevalence of ever-testing for HIV among foreign-born individuals residing in the United States. Data from a national health survey of the civilian, non-institutionalized population was used to describe prevalence of ever-testing for HIV among foreign-born individuals by birth place. Multivariate logistic-regression procedures were used to determine factors associated with ever-testing for HIV among foreign-born men and women. The prevalence of ever-testing for HIV among foreign-born individuals varied by region of birth ranging from 31 to 67%. Factors related to ever-testing for HIV varied by gender. Efforts need to continue in order to improve HIV testing rates among Asian foreign-born individuals, lower educated foreign-born and foreign-born gay/bisexual men. Health care providers can play an important role by counseling new arrivals regarding the importance of testing for HIV and practicing HIV risk reduction activities.

      15. Migrant health is a critical public health issue, and in many countries attention to this topic has focused on the link between migration and communicable diseases, including tuberculosis (TB). When creating public health policies to address the complex challenges posed by TB and migration, countries should focus these policies on evidence, ethics, and human rights. This paper traces a commonly used migration route from sub-Saharan Africa to Europe, identifying situations at each stage in which human rights and ethical values might be affected in relation to TB care. This illustration provides the basis for discussing TB and migration from the perspective of human rights, with a focus on the right to health. We then highlight three strands of discussion in the ethics and justice literature in an effort to develop more comprehensive ethics of migrant health. These strands include theories of global justice and global health ethics, the creation of ‘firewalls’ to separate enforcement of immigration law from protection of human rights, and the importance of non-stigmatization to health justice. The paper closes by reflecting briefly on how TB programs can better incorporate human rights and ethical principles and values into public health practice.

    • Drug Safety
      1. Opioid overdose outbreak – West Virginia, August 2016External
        Massey J, Kilkenny M, Batdorf S, Sanders SK, Ellison D, Halpin J, Gladden RM, Bixler D, Haddy L, Gupta R.
        MMWR Morb Mortal Wkly Rep. 2017 Sep 22;66(37):975-980.

        On August 15, 2016, the Mayor’s Office of Drug Control Policy in Huntington, West Virginia, notified the Cabell-Huntington Health Department (CHHD) of multiple calls regarding opioid overdose received by the emergency medical system (EMS) during 3 p.m.-8 p.m. that day. A public health investigation and response conducted by the West Virginia Bureau for Public Health (BPH) and CHHD identified 20 opioid overdose cases within a 53-hour period in Cabell County; all cases included emergency department (ED) encounters. EMS personnel, other first responders, and ED providers administered the opioid antidote naloxone to 16 (80%) patients, six of whom were administered multiple doses, suggesting exposure to a highly potent opioid. No patients received referral for recovery support services. In addition to the public health investigation, a public safety investigation was conducted; comprehensive opioid toxicology testing of clinical specimens identified the synthetic opioid fentanyl* and novel fentanyl analogs, including carfentanil,dagger which had been used by patients who overdosed in Huntington. Results of these two investigations highlight the importance of collaboration between public health and public safety agencies to provide in-depth surveillance data from opioid overdose outbreaks that involve high-potency fentanyl analogs. These data facilitated a public health response through increased awareness of powerful opioid substances requiring multiple naloxone doses for reversal, and improved patient linkage to recovery support services and a harm reduction program from the ED after opioid overdose.

      2. Assessment of the quality of anti-tuberculosis medicines in Almaty, Kazakhstan, 2014External
        Nabirova D, Schmid G, Yusupova R, Kantarbayeva M, Ismailov SI, Moffett D, Jahnke RW, Nuorti JP.
        Int J Tuberc Lung Dis. 2017 Oct 01;21(10):1161-1168.

        SETTING: In 2009, the World Health Organization (WHO) conducted a survey of the quality of four anti-tuberculosis drugs in the former Soviet Union countries. Kazakhstan had the highest proportion of substandard drugs. OBJECTIVE: To assess the quality of anti-tuberculosis drugs used in Kazakhstan in 2014. DESIGN: Fourteen anti-tuberculosis drugs from the Almaty Interdistrict TB Dispensary were randomly selected and screened for quality using Global Pharma Health Fund Minilab testing. First, the product and packaging were physically inspected to determine whether tablets/capsules were intact (i.e., whether they contained the full amount of the drug, and whether the packaging was genuine). Second, the tablets/capsules were dissolved in water to test whether they could be adequately absorbed by the body. Finally, semi-quantitive analyses were undertaken using thin-layer chromatography to verify the presence and concentration of the active pharmaceutical ingredient and to detect impurities. RESULTS: We discovered no counterfeit medicines. However, 163 (19%) of the 854 anti-tuberculosis drugs sampled failed at least one of the three tests. These samples were found among 24/50 (48%) batches of 14 anti-tuberculosis drugs. CONCLUSION: Our study identified a high proportion of poor-quality first- and second-line anti-tuberculosis drugs. Use of these medicines may lead to treatment failure and the development of drug resistance. Confirmatory testing should be performed to determine if they should be removed from the market.

    • Environmental Health
      1. Relationship between total and bioaccessible lead on children’s blood lead levels in urban residential Philadelphia soilsExternal
        Bradham KD, Nelson CM, Kelly J, Pomales A, Scruton K, Dignam T, Misenheimer JC, Li K, Obenour DR, Thomas DJ.
        Environ Sci Technol. 2017 Sep 05;51(17):10005-10011.

        Relationships between total soil or bioaccessible lead (Pb), measured using an in vitro bioaccessibility assay, and children’s blood lead levels (BLL) were investigated in an urban neighborhood in Philadelphia, PA, with a history of soil Pb contamination. Soil samples from 38 homes were analyzed to determine whether accounting for the bioaccessible Pb fraction improves statistical relationships with children’s BLLs. Total soil Pb concentration ranged from 58 to 2821 mg/kg; the bioaccessible Pb concentration ranged from 47 to 2567 mg/kg. Children’s BLLs ranged from 0.3 to 9.8 mug/dL. Hierarchical models were used to compare relationships between total or bioaccessible Pb in soil and children’s BLLs. Total soil Pb concentration as the predictor accounted for 23% of the variability in child BLL; bioaccessible soil Pb concentration as the predictor accounted for 26% of BLL variability. A bootstrapping analysis confirmed a significant increase in R2 for the model using bioaccessible soil Pb concentration as the predictor with 99.0% of bootstraps showing a positive increase. Estimated increases of 1.3 mug/dL and 1.5 mug/dL in BLL per 1000 mg/kg Pb in soil were observed for this study area using total and bioaccessible Pb concentrations, respectively. Children’s age did not contribute significantly to the prediction of BLLs.

      2. Comparison of questionnaire-based estimation of pesticide residue intake from fruits and vegetables with urinary concentrations of pesticide biomarkersExternal
        Chiu YH, Williams PL, Minguez-Alarcon L, Gillman M, Sun Q, Ospina M, Calafat AM, Hauser R, Chavarro JE.
        J Expo Sci Environ Epidemiol. 2017 Sep 20.

        We developed a pesticide residue burden score (PRBS) based on a food frequency questionnaire and surveillance data on food pesticide residues to characterize dietary exposure over the past year. In the present study, we evaluated the association of the PRBS with urinary concentrations of pesticide biomarkers. Fruit and vegetable (FV) intake was classified as having high (PRBS>/=4) or low (PRBS<4) pesticide residues for 90 men from the EARTH study. Two urine samples per man were analyzed for seven biomarkers of organophosphate and pyrethroid insecticides, and the herbicide 2,4-dichlorophenoxyacetic acid. We used generalized estimating equations to analyze the association of the PRBS with urinary concentrations of pesticide biomarkers. Urinary concentrations of pesticide biomarkers were positively related to high pesticide FV intake but inversely related to low pesticide FV intake. The molar sum of urinary concentrations of pesticide biomarkers was 21% (95% confidence interval (CI): 2%, 44%) higher for each one serving/day increase in high pesticide FV intake, and 10% (95% CI: 1%, 18%) lower for each one serving/day increase in low pesticide FV intake. Furthermore, intake of high pesticide FVs positively related to most individual urinary biomarkers. Our findings support the usefulness of the PRBS approach to characterize dietary exposure to select pesticides.Journal of Exposure Science and Environmental Epidemiology advance online publication, 20 September 2017; doi:10.1038/jes.2017.22.

      3. Phenol concentrations during childhood and subsequent measures of adiposity among young girlsExternal
        Deierlein AL, Wolff MS, Pajak A, Pinney SM, Windham GC, Galvez MP, Rybak M, Calafat AM, Kushi LH, Biro FM, Teitelbaum SL.
        Am J Epidemiol. 2017 Sep 01;186(5):581-592.

        Phenolic compounds represent a class of environmental chemicals with potentially endocrine-disrupting capabilities. We investigated longitudinal associations between childhood exposure to phenols, from both manmade and natural sources, and subsequent measures of adiposity among girls enrolled in the Breast Cancer and the Environment Research Program between 2004 and 2007. Baseline (ages 6-8 years) urinary concentrations were obtained for creatinine and phenol metabolites: enterolactone, genistein, daidzein, benzophenone-3, bisphenol A, the sum of parabens (methyl, ethyl, and propyl parabens), 2,5-dichlorophenol, and triclosan. Body mass index (weight (kg)/height (m)2), waist circumference, and percent body fat were measured at annual or semiannual examinations through 2015 (n = 1,017). Linear mixed-effects regression was used to estimate how baseline concentrations of phenols (tertile groups) were related to changes in girls’ adiposity measurements from ages 7 through 15 years. Enterolactone was inversely associated with body mass index, waist circumference, and percent body fat, while 2,5-dichlorophenol was positively associated with these measurements. A nonmonotonic association was observed for triclosan and girls’ adiposity; however, it was due to effect modification by baseline overweight status. Triclosan was positively associated with adiposity only among overweight girls. These results suggest that exposure to specific phenols during childhood may influence adiposity through adolescence.

      4. Prenatal exposure to nonpersistent endocrine disruptors and behavior in boys at 3 and 5 yearsExternal
        Philippat C, Nakiwala D, Calafat A, Botton J, De Agostini M, Heude B, Slama R.
        Environ Health Perspect. 2017 ;125:1-9.

        BACKGROUND: Sex-specific associations have been reported between phthalates, bisphenol A (BPA), and child behavior. No data on large study populations are available for other phenols with possible endocrine-disrupting properties. OBJECTIVES: We aimed to study associations between prenatal exposure to phthalates and several phenols on behavior among male infants. METHODS: We quantified 11 phthalate metabolites and nine phenols (four parabens, benzophenone-3, BPA, two dichlorophenols, triclosan) in spot urine samples collected during pregnancy among EDEN cohort mothers who delivered a boy. Mothers completed the Strength and Difficulties Questionnaire (SDQ) when their children were 3.1 (n=529) and 5.6 (n=464) y old. RESULTS: BPA was positively associated with the relationship problems subscale at 3 y [incidence rate ratio (IRR): 1.11; 95% confidence interval (CI): 1.03, 1.20] and the hyperactivity-inattention subscale scores at 5 y (IRR: 1.08; 95% CI: 1.01, 1.14). Mono-n-butyl phthalate (MnBP) was positively associated with internalizing behavior, relationship problem, and emotional symptom scores at 3 y. Monobenzyl phthalate (MBzP) was positively associated with internalizing behavior and relationship problems scores at 3 y. After dichotomizing SDQ scores, triclosan tended to be positively associated with emotional symptom subscales at both 3 and 5 y. CONCLUSIONS: The observed associations between BPA, MnBP, and behavior in boys are consistent with previous findings. Further health impact assessment studies based on dose-response functions corrected for exposure misclassification are required to quantify the public health burden possibly entailed by such associations.

      5. Early-life phthalate exposure and adiposity at 8 years of ageExternal
        Shoaff J, Papandonatos G, Calafat A, Xiaoyun Y, Aimin C, Lanphear B, Yolton K, Braun J.
        Environ Health Perspect. 2017 ;125:1-8.

        Background: Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. Objective: To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. Methods: In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Results: Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (? DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ?DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. Conclusion: In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ?DEHP concentrations depended on the timing of exposure.

      6. In utero exposure to select phenols and phthalates and respiratory health in five-year-old boys: A prospective studyExternal
        Vernet C, Pin I, Giorgis-Allemand L, Philippat C, Benmerad M, Quentin J, Calafat AM, Ye X, Annesi-Maesano I, Siroux V, Slama R.
        Environ Health Perspect. 2017 Sep 08;125(9):097006.

        BACKGROUND: Phenols and phthalates may have immunomodulatory and proinflammatory effects and thereby adversely affect respiratory health. OBJECTIVE: We estimated the associations between gestational exposure to select phthalates and phenols and respiratory health in boys. METHODS: Among 587 pregnant women from the EDEN (Etude des Determinants pre et post natals du developpement et de la sante de l’Enfant) cohort who delivered a boy, 9 phenols and 11 phthalates metabolites were quantified in spot pregnancy urine samples. Respiratory outcomes were followed up by questionnaires until age 5, when forced expiratory volume in 1 s (FEV1) was measured by spirometry. Adjusted associations of urinary metabolites log-transformed concentrations with respiratory outcomes and FEV1 in percent predicted (FEV1%) were estimated by survival and linear regression models, respectively. RESULTS: No phenol or phthalate metabolite exhibited clear deleterious associations simultaneously with several respiratory outcomes. Ethyl-paraben was associated with increased asthma rate [hazard rate (HR)=1.10; 95% confidence interval (CI): 1.00, 1.21] and tended to be negatively associated with FEV1% (beta=-0.59; 95% CI: -1.24, 0.05); bisphenol A tended to be associated with increased rates of asthma diagnosis (HR=1.23; 95% CI: 0.97, 1.55) and bronchiolitis/bronchitis (HR=1.13; 95% CI: 0.99, 1.30). Isolated trends for deleterious associations were also observed between 2,5-dichlorophenol and wheezing, and between monocarboxynonyl phthalate, a metabolite of di-isodecyl phthalate (DIDP), and wheezing. CONCLUSION: Ethyl-paraben, bisphenol A, 2,5-dichlorophenol, and DIDP tended to be associated with altered respiratory health, with ethyl-paraben and bisphenol A exhibiting some consistency across respiratory outcomes. The trends between bisphenol A pregnancy level and increased asthma and bronchiolitis/bronchitis rates in childhood were consistent with a previous cohort study.

      7. Prenatal and postnatal polybrominated diphenyl ether (PBDE) exposure and measures of inattention and impulsivity in childrenExternal
        Vuong AM, Yolton K, Poston KL, Xie C, Webster GM, Sjodin A, Braun JM, Dietrich KN, Lanphear BP, Chen A.
        Neurotoxicol Teratol. 2017 Sep 11.

        Exposure to polybrominated diphenyl ethers (PBDEs) during fetal development may be associated with deficits in attention and impulse control. However, studies examining postnatal PBDE exposures and inattention and impulsivity have been inconsistent. Using data from 214 children in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort with enrollment from 2003 to 2006 in the Greater Cincinnati Area, we investigated the relationship of both prenatal and postnatal PBDE exposures with attention and impulse control. Serum PBDEs were measured at 16+/-3weeks of gestation and during childhood at 1, 2, 3, 5, and 8years. We assessed children’s attention and impulse control using the Conners’ Continuous Performance Test-Second Edition (CPT-II) at 8years. We used multiple informant models to estimate associations of repeated PBDE measures with inattention and impulsivity. There was a pattern of associations between PBDEs and poorer performance on CPT-II measures of attention. For BDE-153, adverse associations extended to exposures at preschool and kindergarten ages; ten-fold increases in exposure were associated with higher omission errors (BDE-153 at 3years: beta=4.0 [95% CI: -2.4, 10.4]; at 5years: beta=4.6 [95% CI: -2.8, 12.0]; at 8years: beta=4.1 [95% CI: -3.4, 11.5]). Longer hit reaction times, indicated by the exponential part of the hit reaction curve, were also observed with 10-fold increases in BDE-153 during the prenatal period and throughout childhood (Prenatal: beta=15.0 milliseconds (ms) [95% CI: -15.8, 45.8]; 5years: beta=20.6ms [95% CI: -20.8, 61.9]; 8years: beta=28.6ms [95% CI: -12.1, 69.4]). Significant impairment in discriminability, as indicated by detectability (d’), between targets and non-targets was also noted with 5 and 8-year PBDE concentrations. Associations between PBDEs and inattention significantly differed by child sex, with males performing more poorly than females with regard to omission errors and measures of reaction times. Collectively, these results do not strongly support that PBDEs are associated with poorer impulse and attention control among 8year old children. However, there may be a possible relationship between prenatal and concurrent PBDEs and inattention, which requires additional research.

    • Epidemiology and Surveillance
      1. Overcoming challenges in school-wide survey administrationExternal
        Rasberry CN, Rose I, Kroupa E, Hebert A, Geller A, Morris E, Lesesne CA.
        Health Promot Pract. 2017 Sep 01:1524839917733476.

        School-based surveys provide a useful method for gathering data from youth. Existing literature offers many examples of data collection through school-based surveys, and a small subset of literature describes methodological approaches or general recommendations for health promotion professionals seeking to conduct school-based data collection. Much less is available on real-life logistical challenges (e.g., minimizing disruption in the school day) and corresponding solutions. In this article, we fill that literature gap by offering practical considerations for the administration of school-based surveys. The protocol and practical considerations outlined in the article are based on a survey conducted with 11,681 students from seven large, urban public high schools in the southeast United States. We outline our protocol for implementing a school-based survey that was conducted with all students school-wide, and we describe six types of key challenges faced in conducting the survey: consent procedures, scheduling, locating students within the schools, teacher failure to administer the survey, improper administration of the survey, and minimizing disruption. For each challenge, we offer our key lessons learned and associated recommendations for successfully implementing school-based surveys, and we provide relevant tools for practitioners planning to conduct their own surveys in schools.

    • Food Safety
      1. An updated scheme for categorizing foods implicated in foodborne disease outbreaks: A tri-agency collaborationExternal
        Richardson LC, Bazaco MC, Parker CC, Dewey-Mattia D, Golden N, Jones K, Klontz K, Travis C, Zablotsky Kufel J, Cole D.
        Foodborne Pathog Dis. 2017 Sep 19.

        BACKGROUND: Foodborne disease data collected during outbreak investigations are used to estimate the percentage of foodborne illnesses attributable to specific food categories. Current food categories do not reflect whether or how the food has been processed and exclude many multiple-ingredient foods. MATERIALS AND METHODS: Representatives from three federal agencies worked collaboratively in the Interagency Food Safety Analytics Collaboration (IFSAC) to develop a hierarchical scheme for categorizing foods implicated in outbreaks, which accounts for the type of processing and provides more specific food categories for regulatory purposes. IFSAC also developed standard assumptions for assigning foods to specific food categories, including some multiple-ingredient foods. The number and percentage of outbreaks assignable to each level of the hierarchy were summarized. RESULTS: The IFSAC scheme is a five-level hierarchy for categorizing implicated foods with increasingly specific subcategories at each level, resulting in a total of 234 food categories. Subcategories allow distinguishing features of implicated foods to be reported, such as pasteurized versus unpasteurized fluid milk, shell eggs versus liquid egg products, ready-to-eat versus raw meats, and five different varieties of fruit categories. Twenty-four aggregate food categories contained a sufficient number of outbreaks for source attribution analyses. Among 9791 outbreaks reported from 1998 to 2014 with an identified food vehicle, 4607 (47%) were assignable to food categories using this scheme. Among these, 4218 (92%) were assigned to one of the 24 aggregate food categories, and 840 (18%) were assigned to the most specific category possible. CONCLUSIONS: Updates to the food categorization scheme and new methods for assigning implicated foods to specific food categories can help increase the number of outbreaks attributed to a single food category. The increased specificity of food categories in this scheme may help improve source attribution analyses, eventually leading to improved foodborne illness source attribution estimates and enhanced food safety and regulatory efforts.

    • Genetics and Genomics
      1. Trends in utilization and costs of BRCA testing among women aged 18-64 years in the United States, 2003-2014External
        Chen Z, Kolor K, Grosse SD, Rodriguez JL, Lynch JA, Green RF, Dotson WD, Bowen MS, Khoury MJ.
        Genet Med. 2017 Sep 21.

        Purpose We examined 12-year trends in BRCA testing rates and costs in the context of clinical guidelines, national policies, and other factors. Methods We estimated trends in BRCA testing rates and costs from 2003 to 2014 for women aged 18-64 years using private claims data and publicly reported revenues from the primary BRCA testing provider. Results The percentage of women with zero out-of-pocket payments for BRCA testing increased during 2013-2014, after 7 years of general decline, coinciding with a clarification of Affordable Care Act coverage of BRCA genetic testing. Beginning in 2007, family history accounted for an increasing proportion of women with BRCA tests compared with personal history, coinciding with BRCA testing guidelines for primary care settings and direct-to-consumer advertising campaigns. During 2013-2014, BRCA testing rates based on claims grew at a faster rate than revenues, following 3 years of similar growth, consistent with increased marketplace competition. In 2013, BRCA testing rates based on claims increased 57%, compared with 11% average annual increases over the preceding 3 years, coinciding with celebrity publicity. Conclusion The observed trends in BRCA testing rates and costs are consistent with possible effects of several factors, including the Affordable Care Act, clinical guidelines and celebrity publicity. GENETICS in MEDICINE advance online publication, 21 September 2017; doi:10.1038/gim.2017.118.

      2. Population and whole genome sequence based characterization of invasive group A streptococci recovered in the United States during 2015External
        Chochua S, Metcalf BJ, Li Z, Rivers J, Mathis S, Jackson D, Gertz RE, Srinivasan V, Lynfield R, Van Beneden C, McGee L, Beall B.
        MBio. 2017 Sep 19;8(5).

        Group A streptococci (GAS) are genetically diverse. Determination of strain features can reveal associations with disease and resistance and assist in vaccine formulation. We employed whole-genome sequence (WGS)-based characterization of 1,454 invasive GAS isolates recovered in 2015 by Active Bacterial Core Surveillance and performed conventional antimicrobial susceptibility testing. Predictions were made for genotype, GAS carbohydrate, antimicrobial resistance, surface proteins (M family, fibronectin binding, T, R28), secreted virulence proteins (Sda1, Sic, exotoxins), hyaluronate capsule, and an upregulated nga operon (encodes NADase and streptolysin O) promoter (Pnga3). Sixty-four M protein gene (emm) types were identified among 69 clonal complexes (CCs), including one CC of Streptococcus dysgalactiae subsp. equisimilisemm types predicted the presence or absence of active sof determinants and were segregated into sof-positive or sof-negative genetic complexes. Only one “emm type switch” between strains was apparent. sof-negative strains showed a propensity to cause infections in the first quarter of the year, while sof+ strain infections were more likely in summer. Of 1,454 isolates, 808 (55.6%) were Pnga3 positive and 637 (78.9%) were accounted for by types emm1, emm89, and emm12 Theoretical coverage of a 30-valent M vaccine combined with an M-related protein (Mrp) vaccine encompassed 98% of the isolates. WGS data predicted that 15.3, 13.8, 12.7, and 0.6% of the isolates were nonsusceptible to tetracycline, erythromycin plus clindamycin, erythromycin, and fluoroquinolones, respectively, with only 19 discordant phenotypic results. Close phylogenetic clustering of emm59 isolates was consistent with recent regional emergence. This study revealed strain traits informative for GAS disease incidence tracking, outbreak detection, vaccine strategy, and antimicrobial therapy.IMPORTANCE The current population-based WGS data from GAS strains causing invasive disease in the United States provide insights important for prevention and control strategies. Strain distribution data support recently proposed multivalent M type-specific and conserved M-like protein vaccine formulations that could potentially protect against nearly all invasive U.S. strains. The three most prevalent clonal complexes share key polymorphisms in the nga operon encoding two secreted virulence factors (NADase and streptolysin O) that have been previously associated with high strain virulence and transmissibility. We find that Streptococcus pyogenes is phylogenetically subdivided into loosely defined multilocus sequence type-based clusters consisting of solely sof-negative or sof-positive strains; with sof-negative strains demonstrating differential seasonal preference for infection, consistent with the recently demonstrated differential seasonal preference based on phylogenetic clustering of full-length M proteins. This might relate to the differences in GAS strain compositions found in different geographic settings and could further inform prevention strategies.

      3. Chromosome and large linear plasmid sequences of a Borrelia miyamotoi strain isolated from Ixodes pacificus ticks from CaliforniaExternal
        Kingry LC, Replogle A, Dolan M, Sexton C, Padgett KA, Schriefer ME.
        Genome Announc. 2017 Sep 14;5(37).

        Borrelia miyamotoi, a relapsing fever group spirochete, is an emerging tick-borne pathogen. It has been identified in ixodid ticks across the Northern Hemisphere, including the West Coast of the United States. We describe the chromosome and large linear plasmid sequence of a B. miyamotoi isolate cultured from a California field-collected Ixodes pacificus tick.

      4. Preliminary characterization of MEDLE-2, a protein potentially involved in the invasion of Cryptosporidium parvumExternal
        Li B, Wu H, Li N, Su J, Jia R, Jiang J, Feng Y, Xiao L.
        Front Microbiol. 2017 ;8:1647.

        Cryptosporidium spp. are important causes of diarrhea in humans, ruminants, and other mammals. Comparative genomic analysis indicated that genetically related and host-adapted Cryptosporidium species have different numbers of subtelomeric genes encoding the Cryptosporidium-specific MEDLE family of secreted proteins, which could contribute to differences in host specificity. In this study, a Cryptosporidium parvum-specific member of the protein family MEDLE-2 encoded by cgd5_4590 was cloned and expressed in Escherichia coli. Immunofluorescent staining with antibodies generated from the recombinant protein showed the expression of the protein in sporozoites and development stages. In vitro neutralization assay with the antibodies partially blocked the invasion of sporozoites. These results support the potential involvement of MEDLE-2 in the invasion of host cells.

      5. Complete genome sequences of Bordetella pertussis isolates with novel pertactin-deficient deletionsExternal
        Weigand MR, Peng Y, Cassiday PK, Loparev VN, Johnson T, Juieng P, Nazarian EJ, Weening K, Tondella ML, Williams MM.
        Genome Announc. 2017 Sep 14;5(37).

        Clinical isolates of the respiratory pathogen Bordetella pertussis in the United States have become predominantly deficient for the acellular vaccine immunogen pertactin through various independent mutations. Here, we report the complete genome sequences for four B. pertussis isolates that harbor novel deletions responsible for pertactin deficiency.

    • Global Health
      1. What proportion of international travellers acquire a travel-related illness? A review of the literatureExternal
        Angelo KM, Kozarsky PE, Ryan ET, Chen LH, Sotir MJ.
        J Travel Med. 2017 Sep 01;24(5).

        Introduction: As international travel increases, travellers may be at increased risk of acquiring infectious diseases not endemic in their home countries. Many journal articles and reference books related to travel medicine cite that between 22-64% of international travellers become ill during or after travel; however, this information is minimal, outdated and limited by poor generalizability. We aim to provide a current and more accurate estimate of the proportion of international travellers who acquire a travel-related illness. Methods: We identified studies via PubMed or travel medicine experts, published between January 1, 1976-December 31, 2016 that included the number of international travellers acquiring a travel-related illness. We excluded studies that focused on a single disease or did not determine a rate based on the total number of travellers. We abstracted information on traveller demographics, trip specifics, study enrollment and follow-up and number of ill travellers and their illnesses. Results: Of 743 studies, nine met the inclusion criteria. The data sources were from North America (four studies) and Europe (five studies). Most travellers were tourists, the most frequent destination regions were Asia and Africa, and the median trip duration ranged from 8-21 days. Six studies enrolled participants at the travellers’ pre-travel consultation. All studies collected data through either extraction from the medical record, weekly diaries, or pre- and post-travel questionnaires. Data collection timeframes varied by study. Between 6-87% of travellers became ill across all studies. Four studies provided the best estimate: between 43-79% of travellers who frequently visited developing nations (e.g. India, Tanzania, and Kenya) became ill; travellers most frequently reported diarrhoea. Conclusion: This is the most comprehensive assessment available on the proportion of international travellers that develop a travel-related illness. Additional cohort studies would provide needed data to more precisely determine the rates of illness in international travellers. Keywords: International travel, travel, illness.

      2. [No abstract]

    • Health Disparities
      1. Relatively little research has attempted to disentangle the individual and neighborhood conditions underlying health disparities. To address this, survey data were collected from 1,107 residents living in one of the 114 census tracts. Results from a multilevel structural equation model found an individual’s perceptions of the social and built environment were significantly associated with their current physical health, mental health, and perceived stress. Associations between household income and poor physical health were more pronounced for participants who lived in low-income neighborhoods compared to participants who lived in high-income neighborhoods. Additionally, Black residents reported significantly better mental health than White residents when they lived in high-income neighborhoods, while Black residents who lived in low-income neighborhoods reported significantly more stress than White residents in low-income neighborhoods. Results of this study advance scientific understanding of social determinants of health and may aid in the development of programs and policies.

    • Healthcare Associated Infections
      1. Transmission of donor-derived Trypanosoma cruzi and subsequent development of Chagas disease in a lung transplant recipientExternal
        Corey AB, Sonetti D, Maloney JD, Montgomery SP, Rademacher BL, Taylor LJ, Smith JA, Striker R.
        Case Rep Infect Dis. 2017 ;2017:5381072.

        Donor infection status should be considered when accepting an organ for transplant. Here we present a case of Chagas disease developing after a lung transplant where the donor was known to be Trypanosoma cruzi antibody positive. The recipient developed acute Trypanosoma cruzi infection with reactivation after treatment. Chagas disease-positive donors are likely to be encountered in the United States; donor targeted screening is needed to guide decisions regarding organ transplant and posttransplant monitoring.

      2. Acanthamoeba granulomatous amoebic encephalitis after pediatric hematopoietic stem cell transplantExternal
        Coven SL, Song E, Steward S, Pierson CR, Cope JR, Ali IK, Ardura MI, Hall MW, Chung MG, Bajwa RP.
        Pediatr Transplant. 2017 Sep 17.

        Acanthamoeba encephalitis is a rare, often fatal condition, particularly after HSCT, with 9 reported cases to date in the world literature. Our case was originally diagnosed with ALL at age 3 years, and after several relapses underwent HSCT at age 9 years. At 17 years of age, he was diagnosed with secondary AML for which he underwent a second allogeneic HSCT. He presented with acute-onset worsening neurological deficits on day +226 after the second transplant and a post-mortem diagnosis of Acanthamoeba encephalitis was established, with the aid of the CDC.

    • Immunity and Immunization
      1. Association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in 2010-11 and 2011-12External
        Donahue JG, Kieke BA, King JP, DeStefano F, Mascola MA, Irving SA, Cheetham TC, Glanz JM, Jackson LA, Klein NP, Naleway AL, Weintraub E, Belongia EA.
        Vaccine. 2017 Sep 25;35(40):5314-5322.

        INTRODUCTION: Inactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB). METHODS: We conducted a case-control study over two influenza seasons (2010-11, 2011-12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1-28days before the SAB. RESULTS: The overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1-3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1-28days was 3.7 (95% CI 1.4-9.4) in 2010-11 and 1.4 (95% CI 0.6-3.3) in 2011-12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1-28days was 7.7 (95% CI 2.2-27.3); the aOR was 1.3 (95% CI 0.7-2.7) among women not vaccinated in the previous season. This effect modification was observed in each season. CONCLUSION: SAB was associated with influenza vaccination in the preceding 28days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.

      2. Birth outcomes following immunization of pregnant women with pandemic H1N1 influenza vaccine 2009-2010External
        Eaton A, Lewis N, Fireman B, Hansen J, Baxter R, Gee J, Klein NP.
        Vaccine. 2017 Sep 13.

        BACKGROUND: Following the H1N1 influenza pandemic in 2009, pregnant women were recommended to receive both seasonal (TIV) and H1N1 influenza vaccines. This study presents incidence of adverse birth and pregnancy outcomes among a population of pregnant women immunized with TIV and H1N1 vaccines at Kaiser Permanente Northern California during 2009-2010. METHODS: We telephone surveyed pregnant Kaiser Permanente Northern California members to assess non-medically-attended reactions following H1N1, TIV or both vaccines during 2009-2010 (n=5365) in a separate study. Here we assessed preterm birth (<37weeks), very preterm birth (<32weeks), low birth weight (<2500 g, LBW), very low birth weight (<1500g), small for gestational age, spontaneous abortions, stillbirths and congenital anomalies among this cohort by comparing incidence and 95% confidence intervals between the following immunization groups: TIV only, H1N1 only, H1N1 prior to TIV immunization, TIV prior to H1N1 and both immunizations given at the same time. RESULTS: Results did not vary significantly between groups. Comparing H1N1 with TIV, incidence were similar for preterm births (6.37vs 6.28/100 births), very preterm births (5.30vs 8.29/1000 births), LBW (4.19vs 2.90/100 births), very LBW (4.54vs 5.52/1000 births), small for gestational age (9.99vs 9.24/1000 births), spontaneous abortion (7.10vs 6.83/1000 pregnancies), stillbirths (7.10vs 4.57/1000 pregnancies), and congenital anomalies (2.67vs 2.43/100 births). CONCLUSIONS: Although constrained by small sample size, complex vaccine groups, and differential vaccine availability during 2009-2010, this study found no difference in adverse birth outcomes between H1N1 vaccine and TIV.

      3. A comparative cost analysis of the Vaccination Program for US-bound RefugeesExternal
        Joo H, Maskery B, Mitchell T, Leidner A, Klosovsky A, Weinberg M.
        Vaccine. 2017 Sep 14.

        BACKGROUND: Vaccination Program for US-bound Refugees (VPR) currently provides one or two doses of some age-specific Advisory Committee on Immunization Practices (ACIP)-recommended vaccines to US-bound refugees prior to departure. METHODS: We quantified and compared the full vaccination costs for refugees using two scenarios: (1) the baseline of no VPR and (2) the current situation with VPR. Under the first scenario, refugees would be fully vaccinated after arrival in the United States. For the second scenario, refugees would receive one or two doses of selected vaccines before departure and complete the recommended vaccination schedule after arrival in the United States. We evaluated costs for the full vaccination schedule and for the subset of vaccines provided by VPR by four age-stratified groups; all costs were reported in 2015 US dollars. We performed one-way and probabilistic sensitivity analyses and break-even analyses to evaluate the robustness of results. RESULTS: Vaccination costs with the VPR scenario were lower than costs of the scenario without the VPR for refugees in all examined age groups. Net cost savings per person associated with the VPR were ranged from $225.93 with estimated Refugee Medical Assistance (RMA) or Medicaid payments for domestic costs to $498.42 with estimated private sector payments. Limiting the analyses to only the vaccines included in VPR, the average costs per person were 56% less for the VPR scenario with RMA/Medicaid payments. Net cost savings with the VPR scenario were sensitive to inputs for vaccination costs, domestic vaccine coverage rates, and revaccination rates, but the VPR scenario was cost savings across a range of plausible parameter estimates. CONCLUSIONS: VPR is a cost-saving program that would also reduce the risk of refugees arriving while infected with a vaccine preventable disease.

      4. Cross-reactive antibody responses to novel H5Nx influenza viruses following homologous and heterologous prime-boost vaccination with a prepandemic stockpiled A(H5N1) vaccine in humansExternal
        Levine MZ, Holiday C, Liu F, Jefferson S, Gillis E, Bellamy AR, Tumpey T, Katz JM.
        J Infect Dis. 2017 Sep 15;216(suppl_4):S555-s559.

        Recently, novel highly pathogenic avian influenza H5Nx viruses (clade caused outbreaks in US poultry. We evaluated the potential of a stockpiled A(H5N1) A/Anhui/1/2005 (clade 2.3.4) vaccine to elicit cross-reactive antibody responses to these emerging viruses. Sera from subjects who received 2 doses of MF59-adjuvanted A/Anhui/1/2005, or 1 dose of MF59-adjuvanted A/Anhui/1/2005 following priming with a clade 1 vaccine were characterized by microneutralization assays and modified hemagglutination inhibition (HI) assays. Only heterologous prime-boost vaccination induced modest cross-reactive HI antibody responses to H5Nx viruses. Heterologous prime-boost may provide a more effective vaccination strategy to broaden the antibody responses to emerging viruses.

      5. Current safety issues with quadrivalent meningococcal conjugate vaccinesExternal
        Myers TR, McNeil MM.
        Hum Vaccin Immunother. 2017 Sep 21:0.

        Invasive meningococcal disease, although rare, can present as sudden, life-threatening disease with high risk of mortality or severe long-term sequelae. The main prevention strategy for invasive meningococcal disease in the United States is the routine vaccination of adolescents and other persons at increased risk of meningococcal disease with quadrivalent meningococcal conjugate vaccines. Two such vaccines are currently licensed and available in the United States, Menactra(R) (Sanofi Pasteur) and Menveo(R) (Glaxo Smith Kline), and usage in the adolescent population have steadily increased since their introduction. Although early reports raised concerns about a possible association of Menactra with Guillain-Barre syndrome, a comprehensive safety review determined that if such risk existed it was no more than 0.66 cases per 1 million vaccinations. More recently, a study found an elevated risk of Bell’s palsy when Menveo was administered concomitantly with other vaccines but no association was found when the vaccine was administered alone. In this commentary, we describe the current state of knowledge with respect to the safety of quadrivalent meningococcal conjugate vaccines, and we identify potential areas for safety research for these vaccines.

      6. Prevalence of human papillomavirus among females after vaccine introduction – National Health and Nutrition Examination Survey, United States, 2003-2014External
        Oliver SE, Unger ER, Lewis R, McDaniel D, Gargano JW, Steinau M, Markowitz LE.
        J Infect Dis. 2017 Sep 01;216(5):594-603.

        Background: Human papillomavirus (HPV) vaccine was recommended in 2006 for routine vaccination of US females aged 11-12 years. Most vaccine used through 2014 was quadrivalent vaccine (4vHPV), which prevents HPV-6, -11, -16, and -18 infection. To evaluate vaccine impact, we measured HPV prevalence in the National Health and Nutrition Examination Survey (NHANES). Methods: We analyzed HPV DNA types detected in self-collected cervicovaginal specimens and demographic, sexual behavior, and self-reported vaccination data from females 14-34 years old. We estimated HPV prevalence in the prevaccine (2003-2006) and vaccine eras (2007-2010 and 2011-2014). Results: Among 14- to 19-year-olds, 4vHPV-type prevalence decreased from 11.5% (95% confidence interval [CI], 9.1%-14.4%) in 2003-2006 to 3.3% (95% CI, 1.9%-5.8%) in 2011-2014, when >/=1-dose coverage was 55%. Among 20- to 24-year-olds, prevalence decreased from 18.5% (95% CI, 14.9%-22.8%) in 2003-2006 to 7.2% (95% CI, 4.7%-11.1%) in 2011-2014, when >/=1-dose coverage was 43%. Compared to 2003-2006, 4vHPV prevalence in sexually active 14- to 24-year-olds in 2011-2014 decreased 89% among those vaccinated and 34% among those unvaccinated. Vaccine effectiveness was 83%. Conclusions: Within 8 years of vaccine introduction, 4vHPV-type prevalence decreased 71% among 14- to 19-year-olds and 61% among 20- to 24-year-olds. Estimated vaccine effectiveness was high. The decrease in 4vHPV-type prevalence among unvaccinated females suggests herd protection.

      7. Updated estimation of the impact of a Japanese encephalitis immunization program with live, attenuated SA 14-14-2 vaccine in NepalExternal
        Upreti SR, Lindsey NP, Bohara R, Choudhary GR, Shakya S, Gautam M, Giri JN, Fischer M, Hills SL.
        PLoS Negl Trop Dis. 2017 Sep;11(9):e0005866.

        BACKGROUND: Japanese encephalitis (JE) is a mosquito-borne disease that is associated with considerable morbidity and mortality in many Asian countries. The objective of this study was to describe the impact of the JE immunization program using SA 14-14-2 JE vaccine implemented in Nepal during 2006 through 2011. A previous assessment after the initial program implementation phase described a significantly lower post-campaign JE incidence compared to expected incidence; however, the previous evaluation had limited post-campaign data for some districts. METHODOLOGY/PRINCIPAL FINDINGS: JE and acute encephalitis syndrome (AES) data gathered through Nepal’s routine surveillance system from 2004 through 2014 were analyzed to assess the impact of the JE immunization program implemented in 31 districts. Expected incidence rates were determined by calculating the incidence of cases per 100,000 person-years in each district before the vaccination campaigns. This rate was applied to the relevant population after the vaccination campaigns, which provided the expected number of cases had the campaign not occurred. The observed incidence rate was the number of reported cases per 100,000 person-years post-campaign. Expected and observed JE and AES cases and incidence rates were compared. The post-campaign JE incidence rate of 0.7 cases per 100,000 was 78% (95% CI 76%-79%) lower than expected had no campaign occurred and an estimated 3,011 (95% CI 2,941-3,057) JE cases were prevented. The post-vaccination AES incidence of 5.5 cases per 100,000 was 59% (58%-60%) lower than the expected and an estimated 9,497 (95% CI 9,268-9,584) AES cases were prevented. CONCLUSIONS/SIGNIFICANCE: This analysis strengthens previous findings of the substantial impact of Nepal’s JE immunization program using SA 14-14-2 JE vaccine.

      8. Vaccine approaches conferring cross-protection against influenza virusesExternal
        Vemula SV, Sayedahmed EE, Sambhara S, Mittal SK.
        Expert Rev Vaccines. 2017 Sep 19:1-14.

        INTRODUCTION: Annual vaccination is one of the most efficient and cost-effective strategies to prevent and control influenza epidemics. Most of the currently available influenza vaccines are strong inducers of antibody responses against viral surface proteins, hemagglutinin (HA) and neuraminidase (NA), but are poor inducers of cell-mediated immune responses against conserved internal proteins. Moreover, due to the high variability of viral surface proteins because of antigenic drift or antigenic shift, many of the currently licensed vaccines confer little or no protection against drift or shift variants. Areas covered: Next generation influenza vaccines that can induce humoral immune responses to receptor-binding epitopes as well as broadly neutralizing conserved epitopes, and cell-mediated immune responses against highly conserved internal proteins would be effective against variant viruses as well as a novel pandemic influenza until circulating strain-specific vaccines become available. Here we discuss vaccine approaches that have the potential to provide broad spectrum protection against influenza viruses. Expert commentary: Based on current progress in defining cross-protective influenza immunity, it seems that the development of a universal influenza vaccine is feasible. It would revolutionize the strategy for influenza pandemic preparedness, and significantly impact the shelf-life and protection efficacy of seasonal influenza vaccines.

    • Injury and Violence
      1. Rural and urban differences in passenger-vehicle-occupant deaths and seat belt use among adults – United States, 2014External
        Beck LF, Downs J, Stevens MR, Sauber-Schatz EK.
        MMWR Surveill Summ. 2017 Sep 22;66(17):1-13.

        PROBLEM/CONDITION: Motor-vehicle crashes are a leading cause of death in the United States. Compared with urban residents, rural residents are at an increased risk for death from crashes and are less likely to wear seat belts. These differences have not been well described by levels of rurality. REPORTING PERIOD: 2014. DESCRIPTION OF SYSTEMS: Data from the Fatality Analysis Reporting System (FARS) and the Behavioral Risk Factor Surveillance System (BRFSS) were used to identify passenger-vehicle-occupant deaths from motor-vehicle crashes and estimate the prevalence of seat belt use. FARS, a census of U.S. motor-vehicle crashes involving one or more deaths, was used to identify passenger-vehicle-occupant deaths among adults aged >/=18 years. Passenger-vehicle occupants were defined as persons driving or riding in passenger cars, light trucks, vans, or sport utility vehicles. Death rates per 100,000 population, age-adjusted to the 2000 U.S. standard population and the proportion of occupants who were unrestrained at the time of the fatal crash, were calculated. BRFSS, an annual, state-based, random-digit-dialed telephone survey of the noninstitutionalized U.S. civilian population aged >/=18 years, was used to estimate prevalence of seat belt use. FARS and BRFSS data were analyzed by a six-level rural-urban designation, based on the U.S. Department of Agriculture 2013 rural-urban continuum codes, and stratified by census region and type of state seat belt enforcement law (primary or secondary). RESULTS: Within each census region, age-adjusted passenger-vehicle-occupant death rates per 100,000 population increased with increasing rurality, from the most urban to the most rural counties: South, 6.8 to 29.2; Midwest, 5.3 to 25.8; West, 3.9 to 40.0; and Northeast, 3.5 to 10.8. (For the Northeast, data for the most rural counties were not reported because of suppression criteria; comparison is for the most urban to the second-most rural counties.) Similarly, the proportion of occupants who were unrestrained at the time of the fatal crash increased as rurality increased. Self-reported seat belt use in the United States decreased with increasing rurality, ranging from 88.8% in the most urban counties to 74.7% in the most rural counties. Similar differences in age-adjusted death rates and seat belt use were observed in states with primary and secondary seat belt enforcement laws. INTERPRETATION: Rurality was associated with higher age-adjusted passenger-vehicle-occupant death rates, a higher proportion of unrestrained passenger-vehicle-occupant deaths, and lower seat belt use among adults in all census regions and regardless of state seat belt enforcement type. PUBLIC HEALTH ACTIONS: Seat belt use decreases and age-adjusted passenger-vehicle-occupant death rates increase with increasing levels of rurality. Improving seat belt use remains a critical strategy to reduce crash-related deaths in the United States, especially in rural areas where seat belt use is lower and age-adjusted death rates are higher than in urban areas. States and communities can consider using evidence-based interventions to reduce rural-urban disparities in seat belt use and passenger-vehicle-occupant death rates.

      2. Perceptions of alcohol-impaired driving and the blood alcohol concentration standard in the United StatesExternal
        Eby D, Molnar L, Kostyniuk LP, St. Louis RL, Zanier N, Lepkowski J, Bergen G.
        J Safety Res. 2017 ;63:73-81.

        Introduction Although the number of alcohol-impaired driving (AID) fatalities has declined over the past several years, AID continues to be a serious public health problem. The purpose of this effort was to gain a better understanding of the U.S. driving population’s perceptions and thoughts about the impacts of lowering the blood alcohol concentration (BAC) driving standard below.08% on AID, health, and other outcomes. Methods A questionnaire was administered to a nationally representative sample of licensed drivers in the U.S. (n = 1011) who were of age 21 or older on driving habits, alcohol consumption habits, drinking and driving habits, attitudes about drinking and driving, experiences with and opinions of drinking and driving laws, opinions about strategies to reduce drinking and driving, general concerns about traffic safety issues, and demographics. Results One-third of participants supported lowering the legal BAC standard, and participants rated a BAC standard of.05% to be moderately acceptable on average. 63.9% indicated that lowering 30 the BAC to.05% would have no effect on their decisions to drink and drive. Nearly 60% of respondents lacked accurate knowledge of their state’s BAC standard. Conclusions Public support for lowering the BAC standard was moderate and was partially tied to beliefs about the impacts of a change in the BAC standard. The results suggest that an opportunity for better educating the driving population about existing AID policy and the implications for lowering the BAC level on traffic injury prevention. Practical applications The study results are useful for state traffic safety professionals and policy makers to have a better understanding of the public’s perceptions of and thoughts about BAC standards. There is a clear need for more research into the effects of lowering the BAC standard on crashes, arrests, AID behavior, and alcohol-related behaviors.

      3. [No abstract]

    • Laboratory Sciences
      1. Molecular epidemiology of cryptosporidiosis in ChinaExternal
        Feng Y, Xiao L.
        Front Microbiol. 2017 ;8:1701.

        Molecular epidemiology of cryptosporidiosis is an active research area in China. The use of genotyping and subtyping tools in prevalence studies has led to the identification of unique characteristics of Cryptosporidium infections in humans and animals. Human cryptosporidiosis in China is exemplified by the high diversity of Cryptosporidium spp. at species and subtype levels, with dominant C. hominis and C. parvum subtypes being rarely detected in other countries. Similarly, preweaned dairy calves, lambs, and goat kids are mostly infected with non-pathogenic Cryptosporidium species (C. bovis in calves and C. xiaoi in lambs and goat kids), with C. parvum starting to appear in dairy calves as a consequence of concentrated animal feeding operations. The latter Cryptosporidium species is dominated by IId subtypes, with IIa subtypes largely absent from the country. Unlike elsewhere, rodents in China appear to be commonly infected with C. parvum IId subtypes, with identical subtypes being found in these animals, calves, other livestock, and humans. In addition to cattle, pigs and chickens appear to be significant contributors to Cryptosporidium contamination in drinking water sources, as reflected by the frequent detection of C. suis, C. baileyi, and C. meleagridis in water samples. Chinese scientists have also made significant contributions to the development of new molecular epidemiological tools for Cryptosporidium spp. and improvements in our understanding of the mechanism involved in the emergence of hyper-transmissible and virulent C. hominis and C. parvum subtypes. Despite this progress, coordinated research efforts should be made to address changes in Cryptosporidium transmission because of rapid economic development in China and to prevent the introduction and spread of virulent and zoonotic Cryptosporidium species and subtypes in farm animals.

      2. Analytic validation of immunohistochemical assays: A comparison of laboratory practices before and after introduction of an evidence-based guidelineExternal
        Fitzgibbons PL, Goldsmith JD, Souers RJ, Fatheree LA, Volmar KE, Stuart LN, Nowak JA, Astles JR, Nakhleh RE.
        Arch Pathol Lab Med. 2017 Sep;141(9):1247-1254.

        CONTEXT: – Laboratories must demonstrate analytic validity before any test can be used clinically, but studies have shown inconsistent practices in immunohistochemical assay validation. OBJECTIVE: – To assess changes in immunohistochemistry analytic validation practices after publication of an evidence-based laboratory practice guideline. DESIGN: – A survey on current immunohistochemistry assay validation practices and on the awareness and adoption of a recently published guideline was sent to subscribers enrolled in one of 3 relevant College of American Pathologists proficiency testing programs and to additional nonsubscribing laboratories that perform immunohistochemical testing. The results were compared with an earlier survey of validation practices. RESULTS: – Analysis was based on responses from 1085 laboratories that perform immunohistochemical staining. Of 1057 responses, 65.4% (691) were aware of the guideline recommendations before this survey was sent and 79.9% (550 of 688) of those have already adopted some or all of the recommendations. Compared with the 2010 survey, a significant number of laboratories now have written validation procedures for both predictive and nonpredictive marker assays and specifications for the minimum numbers of cases needed for validation. There was also significant improvement in compliance with validation requirements, with 99% (100 of 102) having validated their most recently introduced predictive marker assay, compared with 74.9% (326 of 435) in 2010. The difficulty in finding validation cases for rare antigens and resource limitations were cited as the biggest challenges in implementing the guideline. CONCLUSIONS: – Dissemination of the 2014 evidence-based guideline validation practices had a positive impact on laboratory performance; some or all of the recommendations have been adopted by nearly 80% of respondents.

      3. Background: Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including influenza infection, but no studies have addressed the potential influences of PEM on the immunogenicity and protective efficacy of avian influenza A(H5N1) vaccine. Methods: We investigated the role of PEM on vaccine-mediated protection after a lethal challenge with recombinant A(H5N1) virus using isocaloric diets providing either adequate protein (AP; 18% protein) or very low protein (VLP; 2% protein) in an established murine model of influenza vaccination. Results: We demonstrated that mice maintained on a VLP diet succumb to lethal challenge at greater rates than mice maintained on an AP diet, despite comparable immunization regimens. Importantly, there was no virus-induced mortality in both VLP and AP groups of mice when either group was immunized with adjuvanted low-dose A(H5N1) subvirion vaccine. Conclusions: Our results suggest that adjuvanted vaccination in populations where PEM is endemic may be one strategy to boost vaccination-promoted immunity and improve outcomes associated with highly pathogenic A(H5N1).

      4. Effect of priming with seasonal influenza A(H3N2) virus on the prevalence of cross-reactive hemagglutination-inhibition antibodies to swine-origin A(H3N2) variantsExternal
        Liu F, Veguilla V, Gross FL, Gillis E, Rowe T, Xu X, Tumpey TM, Katz JM, Levine MZ, Lu X.
        J Infect Dis. 2017 Sep 15;216(suppl_4):S539-s547.

        Background: Recent outbreaks of swine-origin influenza A(H3N2) variant (H3N2v) viruses have raised public health concerns. Previous studies indicated that older children and young adults had the highest levels of hemagglutination-inhibition (HI) antibodies to 2010-2011 H3N2v viruses. However, newly emerging 2013 H3N2v have acquired antigenic mutations in the hemagglutinin at amino acid position 145 (N145K/R). We estimated the levels of serologic cross-reactivity among humans primed with seasonal influenza A(H3N2) (sH3N2), using postinfection ferret antisera. We also explored age-related HI antibody responses to 2012-2013 H3N2v viruses. Methods: Human and ferret antisera were tested in HI assays against 1 representative 2012 H3N2v (145N) and 2 2013 H3N2v (145K/R) viruses, together with 9 sH3N2 viruses circulating since 1968. Results: Low levels of cross-reactivity between the H3N2v and sH3N2 viruses from the 1970s-1990s were observed using postinfection ferret antisera. The overall seroprevalence among the sH3N2-primed population against 2012-2013 H3N2v viruses was >50%, and age-related seroprevalence was observed. Seroprevalence was significantly higher to 2013 H3N2v than to 2012 H3N2v viruses among some children likely to have been primed with A/Sydney/5/97-like (145K) or A/Wuhan/359/95-like viruses (145K). Conclusions: A single substitution (N145K/R) was sufficient to affect seropositivity to H3N2v viruses in some individuals. Insight into age-related antibody responses to newly emerging H3N2v viruses is critical for risk assessment and pandemic preparedness.

      5. The fate of inhaled nanoparticles: Detection and measurement by enhanced dark-field microscopyExternal
        Mercer RR, Scabilloni JF, Wang L, Battelli LA, Antonini JM, Roberts JR, Qian Y, Sisler JD, Castranova V, Porter DW, Hubbs AF.
        Toxicol Pathol. 2017 Jan 01:192623317732321.

        Assessing the potential health risks for newly developed nanoparticles poses a significant challenge. Nanometer-sized particles are not generally detectable with the light microscope. Electron microscopy typically requires high-level doses, above the physiologic range, for particle examination in tissues. Enhanced dark-field microscopy (EDM) is an adaption of the light microscope that images scattered light. Nanoparticles scatter light with high efficiency while normal tissues do not. EDM has the potential to identify the critical target sites for nanoparticle deposition and injury in the lungs and other organs. This study describes the methods for EDM imaging of nanoparticles and applications. Examples of EDM application include measurement of deposition and clearance patterns. Imaging of a wide variety of nanoparticles demonstrated frequent situations where nanoparticles detected by EDM were not visible by light microscopy. EDM examination of colloidal gold nanospheres (10-100 nm diameter) demonstrated a detection size limit of approximately 15 nm in tissue sections. EDM determined nanoparticle volume density was directly proportional to total lung burden of exposed animals. The results confirm that EDM can determine nanoparticle distribution, clearance, transport to lymph nodes, and accumulation in extrapulmonary organs. Thus, EDM substantially improves the qualitative and quantitative microscopic evaluation of inhaled nanoparticles.

      6. Assessment of molecular, antigenic, and pathological features of canine influenza A(H3N2) viruses that emerged in the United StatesExternal
        Pulit-Penaloza JA, Simpson N, Yang H, Creager HM, Jones J, Carney P, Belser JA, Yang G, Chang J, Zeng H, Thor S, Jang Y, Killian ML, Jenkins-Moore M, Janas-Martindale A, Dubovi E, Wentworth DE, Stevens J, Tumpey TM, Davis CT, Maines TR.
        J Infect Dis. 2017 Sep 15;216(suppl_4):S499-s507.

        Background: A single subtype of canine influenza virus (CIV), A(H3N8), was circulating in the United States until a new subtype, A(H3N2), was detected in Illinois in spring 2015. Since then, this CIV has caused thousands of infections in dogs in multiple states. Methods: In this study, genetic and antigenic properties of the new CIV were evaluated. In addition, structural and glycan array binding features of the recombinant hemagglutinin were determined. Replication kinetics in human airway cells and pathogenesis and transmissibility in animal models were also assessed. Results: A(H3N2) CIVs maintained molecular and antigenic features related to low pathogenicity avian influenza A(H3N2) viruses and were distinct from A(H3N8) CIVs. The structural and glycan array binding profile confirmed these findings and revealed avian-like receptor-binding specificity. While replication kinetics in human airway epithelial cells was on par with that of seasonal influenza viruses, mild-to-moderate disease was observed in infected mice and ferrets, and the virus was inefficiently transmitted among cohoused ferrets. Conclusions: Further adaptation is needed for A(H3N2) CIVs to present a likely threat to humans. However, the potential for coinfection of dogs and possible reassortment of human and other animal influenza A viruses presents an ongoing risk to public health.

      7. Development of a cigarette tobacco filler standard reference materialExternal
        Sander LC, Pritchett JS, Daniels YC, Wood LJ, Lang BE, Wise SA, Yen JH, Johnson TL, Walters MJ, Phillips T, Holman MR, Lee GE, Lisko JG, Lane B, Valentin-Blasini L, Watson C.
        Anal Chem. 2017 Sep 20.

        A new tobacco filler Standard Reference Material (SRM) has been issued by the National Institute of Standards and Technology (NIST) in September 2016 with certified and reference mass fraction values for nicotine, N-nitrosonornicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and volatiles. The constituents have been determined by multiple analytical methods with measurements at NIST and at the Centers for Disease Control and Prevention, and with confirmatory measurements by commercial laboratories. This effort highlights the development of the first SRM for reduced nicotine and reduced tobacco-specific nitrosamines with certified values for composition.

      8. Analytic validation of immunohistochemistry assays: New benchmark data from a survey of 1085 laboratoriesExternal
        Stuart LN, Volmar KE, Nowak JA, Fatheree LA, Souers RJ, Fitzgibbons PL, Goldsmith JD, Astles JR, Nakhleh RE.
        Arch Pathol Lab Med. 2017 Sep;141(9):1255-1261.

        CONTEXT: – A cooperative agreement between the College of American Pathologists (CAP) and the United States Centers for Disease Control and Prevention was undertaken to measure laboratories’ awareness and implementation of an evidence-based laboratory practice guideline (LPG) on immunohistochemical (IHC) validation practices published in 2014. OBJECTIVE: – To establish new benchmark data on IHC laboratory practices. DESIGN: – A 2015 survey on IHC assay validation practices was sent to laboratories subscribed to specific CAP proficiency testing programs and to additional nonsubscribing laboratories that perform IHC testing. Specific questions were designed to capture laboratory practices not addressed in a 2010 survey. RESULTS: – The analysis was based on responses from 1085 laboratories that perform IHC staining. Ninety-six percent (809 of 844) always documented validation of IHC assays. Sixty percent (648 of 1078) had separate procedures for predictive and nonpredictive markers, 42.7% (220 of 515) had procedures for laboratory-developed tests, 50% (349 of 697) had procedures for testing cytologic specimens, and 46.2% (363 of 785) had procedures for testing decalcified specimens. Minimum case numbers were specified by 85.9% (720 of 838) of laboratories for nonpredictive markers and 76% (584 of 768) for predictive markers. Median concordance requirements were 95% for both types. For initial validation, 75.4% (538 of 714) of laboratories adopted the 20-case minimum for nonpredictive markers and 45.9% (266 of 579) adopted the 40-case minimum for predictive markers as outlined in the 2014 LPG. The most common method for validation was correlation with morphology and expected results. Laboratories also reported which assay changes necessitated revalidation and their minimum case requirements. CONCLUSIONS: – Benchmark data on current IHC validation practices and procedures may help laboratories understand the issues and influence further refinement of LPG recommendations.

      9. SOX9 regulates cancer stem-like properties and metastatic potential of single-walled carbon nanotube-exposed cellsExternal
        Voronkova MA, Luanpitpong S, Rojanasakul LW, Castranova V, Dinu CZ, Riedel H, Rojanasakul Y.
        Sci Rep. 2017 Sep 14;7(1):11653.

        Engineered nanomaterials hold great promise for the future development of innovative products but their adverse health effects are a major concern. Recent studies have indicated that certain nanomaterials, including carbon nanotubes (CNTs), may be carcinogenic. However, the underlying mechanisms behind their potential malignant properties remain unclear. In this study, we linked SOX9, a stem cell associated transcription factor, to the neoplastic-like properties of human lung epithelial cells chronically exposed to a low-dose of single-walled carbon nanotubes (SWCNTs). We found that SOX9 is upregulated in SWCNT-exposed cells, which is consistent with their abilities to induce tumor formation and metastasis in vivo. We therefore hypothesized that SOX9 overexpression may be responsible for the neoplastic-like phenotype observed in our model. Indeed, SOX9 knockdown inhibited anchorage-independent cell growth in vitro and lung colonization in vivo in a mouse xenograft model. SOX9 depletion also suppressed the formation of cancer stem-like cells (CSCs), as determined by tumor sphere formation and aldehyde dehydrogenase (ALDH) activity (Aldefluor) assays. Furthermore, SOX9 knockdown suppressed tumor metastasis and the expression of the stem cell marker ALDH1A1. Taken together, our findings provide a mechanistic insight into SWCNT-induced carcinogenesis and the role of SOX9 in CSC regulation and metastasis.

    • Maternal and Child Health
      1. Reporting newborn audiologic results to state EHDI programsExternal
        Chung W, Beauchaine KL, Grimes A, O’Hollearn T, Mason C, Ringwalt S.
        Ear Hear. 2017 Sep/Oct;38(5):638-642.

        OBJECTIVES: All US states and territories have an Early Hearing Detection and Intervention (EHDI) program to facilitate early hearing evaluation and intervention for infants who are deaf or hard of hearing. To ensure efficient coordination of care, the state EHDI programs rely heavily on audiologists’ prompt reporting of a newborn’s hearing status. Several states have regulations requiring mandatory reporting of a newborn’s hearing status. This is an important public health responsibility of pediatric audiologists. Reasons for failing to report vary. DESIGN: The Early Hearing Detection and Intervention-Pediatric Audiology Links to Services (EHDI) facility survey was used to inform reporting compliance of audiology facilities throughout the United States. The survey was disseminated via articles, newsletters, and call-to-action notices to audiologists. RESULTS: Among 1024 facilities surveyed, 88 (8.6%) reported that they did not report newborn’s hearing findings to their state EHDI program. Not knowing how to report to the state EHDI program was the most frequently chosen reason (60%). However, among the 936 facilities that were compliant with the reporting requirements, 51 estimated that they reported less than two-third of all hearing evaluation results (5.4%). Some facilities did not report a normal-hearing result and some failed to report because they assumed another facility would report the hearing results. CONCLUSIONS: Survey results indicated that audiologists were compliant reporting hearing results to the state EHDI programs. However, there is room for improvement. Regular provider outreach and training by the state EHDI program is necessary to ensure those who are not reporting will comply and to clarify reporting requirements for those who are already compliant.

      2. Maternal dietary L-arginine and adverse birth outcomes in Dar es Salaam, TanzaniaExternal
        Darling AM, McDonald CR, Urassa WS, Kain KC, Mwiru RS, Fawzi WW.
        Am J Epidemiol. 2017 Sep 01;186(5):603-611.

        The amino acid arginine is a physiological precursor to nitric oxide, which is a key mediator of embryonic survival, fetal growth, and pregnancy maintenance. We evaluated the association between consumption of the amino acid arginine and the rate of adverse birth outcomes using data from a double-blind, randomized, placebo-controlled micronutrient supplementation trial among pregnant women in Dar es Salaam, Tanzania (2001-2004). Dietary intakes of arginine were assessed using repeated 24-hour recalls that were administered throughout pregnancy. Participants (n = 7,591) were monitored by research midwives throughout follow-up to assess pregnancy outcomes. Cubic-restricted splines and multivariable log-Poisson regression with empirical standard errors were used to estimate the continuous and categorical associations between arginine intake and adverse birth outcomes. Compared with women within the lowest quintile of arginine intake, those within the highest quintile had 0.79 times the risk of preterm birth before 37 weeks (95% confidence interval: 0.63, 1.00; P = 0.03). The continuous associations of arginine intake with preterm birth before 37 weeks and with preterm birth before 34 weeks were characterized by an initial rapid decrease in risk with increasing intake (P for nonlinearity < 0.01). Arginine intake was not associated with fetal loss or giving birth to infants who were born small for their gestational ages. This data suggest that the association between dietary arginine intake and preterm birth warrants further investigation.

      3. Autism spectrum disorder among US children (2002-2010): Socioeconomic, racial, and ethnic disparitiesExternal
        Durkin MS, Maenner MJ, Baio J, Christensen D, Daniels J, Fitzgerald R, Imm P, Lee LC, Schieve LA, Van Naarden Braun K, Wingate MS, Yeargin-Allsopp M.
        Am J Public Health. 2017 Sep 21:e1-e9.

        OBJECTIVES: To describe the association between indicators of socioeconomic status (SES) and the prevalence of autism spectrum disorder (ASD) in the United States during the period 2002 to 2010, when overall ASD prevalence among children more than doubled, and to determine whether SES disparities account for ongoing racial and ethnic disparities in ASD prevalence. METHODS: We computed ASD prevalence and 95% confidence intervals (CIs) from population-based surveillance, census, and survey data. We defined SES categories by using area-level education, income, and poverty indicators. We ascertained ASD in 13 396 of 1 308 641 8-year-old children under surveillance. RESULTS: The prevalence of ASD increased with increasing SES during each surveillance year among White, Black, and Hispanic children. The prevalence difference between high- and low-SES groups was relatively constant over time (3.9/1000 [95% CI = 3.3, 4.5] in 2002 and 4.1/1000 [95% CI = 3.6, 4.6] in the period 2006-2010). Significant racial/ethnic differences in ASD prevalence remained after stratification by SES. CONCLUSIONS: A positive SES gradient in ASD prevalence according to US surveillance data prevailed between 2002 and 2010, and racial and ethnic disparities in prevalence persisted during this time among low-SES children. (Am J Public Health. Published online ahead of print September 21, 2017: e1-e9. doi:10.2105/AJPH.2017.304032).

      4. Employer-sponsored plan expenditures for infants born pretermExternal
        Grosse SD, Waitzman NJ, Yang N, Abe K, Barfield WD.
        Pediatrics. 2017 Sep 21.

        BACKGROUND: Care for infants born preterm or with major birth defects is costly. Specific estimates of financial burden for different payers are lacking, in part because use of administrative data to identify preterm infants and costs is challenging. METHODS: We used private health insurance claims data and billing codes to identify live births during 2013 and calculated first-year expenditures for employer-sponsored health plans for infants born preterm, both overall and stratified by major birth defects. RESULTS: We conservatively estimated that 7.7% of insured infants born preterm accounted for 37% of $2.0 billion spent by participating plans on the care of infants born during 2013. With a mean difference in plan expenditures of approximately $47 100 per infant, preterm births cost the included plans an extra $600 million during the first year of life. Extrapolating to the national level, we projected aggregate employer-sponsored plan expenditures of $6 billion for infants born preterm during 2013. Infants with major birth defects accounted for 5.8% of preterm births but 24.5% of expenditures during infancy. By using an alternative algorithm to identify preterm infants, it was revealed that incremental expenditures were higher: $78 000 per preterm infant and $14 billion nationally. CONCLUSION: Preterm births (especially in conjunction with major birth defects) represent a substantial burden on payers, and efforts to mitigate this burden are needed. In addition, researchers need to conduct studies using linked vital records, birth defects surveillance, and administrative data to accurately and longitudinally assess per-infant costs attributable to preterm birth and the interaction of preterm birth with major birth defects.

      5. Combined prenatal pesticide exposure and folic acid intake in relation to autism spectrum disorderExternal
        Schmidt RJ, Kogan V, Shelton JF, Delwiche L, Hansen RL, Ozonoff S, Ma CC, McCanlies EC, Bennett DH, Hertz-Picciotto I, Tancredi DJ, Volk HE.
        Environ Health Perspect. 2017 Sep 08;125(9):097007.

        BACKGROUND: Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. OBJECTIVE: We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). METHODS: Participants were California children born from 2000-2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case-control study at age 2-5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003-2011. High vs. low daily FA intake was dichotomized at 800mug (median). Mothers’ addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. RESULTS: High FA intake (>/=800mug) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with <800mug FA and any indoor pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (>/=6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models. CONCLUSIONS: In this study population, associations between pesticide exposures and ASD were attenuated among those with high versus low FA intake during the first month of pregnancy. Confirmatory and mechanistic studies are needed.

      6. Maternal exposure to nitrogen dioxide, intake of methyl nutrients and congenital heart defects in offspringExternal
        Stingone JA, Luben TJ, Carmichael SL, Aylsworth AS, Botto LD, Correa A, Gilboa SM, Langlois PH, Nembhard WN, Richmond-Bryant J, Shaw GM, Olshan AF.
        Am J Epidemiol. 2017 May 18.

        Nutrients that regulate methylation processes may modify susceptibility to the effects of air pollutants. Data from the National Birth Defects Prevention Study, 1997-2006, were used to estimate associations between maternal exposure to nitrogen dioxide (NO2), dietary intake of methyl nutrients and the odds of congenital heart defects in offspring. NO2 concentrations, a marker of traffic-related air pollution, averaged across post-conception weeks 2-8, were assigned to 6160 non-diabetic mothers of cases and controls using inverse distance-squared weighting of air monitors within 50 km of maternal residence. Intake of choline, folate, methionine, and vitamins B6 and B12 were assessed using a food frequency questionnaire. Hierarchical regression models, which accounted for similarities across defects, were constructed and relative excess risks due to interaction were calculated. Relative to women with the lowest NO2 exposure and high methionine intake, women with the highest NO2 exposure and lowest methionine intake had the greatest odds of offspring with a perimembranous ventricular septal defect (Odds Ratio: 3.23, 95% Confidence Interval, 1.74, 6.01; Relative Excess Risk due to Interaction: 2.15, 95% Confidence Interval, 0.39, 3.92). Considerable departure from additivity was not observed for other defects. These results provide modest evidence of interaction between nutrition and NO2 exposure during pregnancy.

      7. Understanding the natural progression of spina bifida: Prospective studyExternal
        Thibadeau J, Reeder MR, Andrews J, Ong K, Feldkamp ML, Rice S, Alriksson-Schmidt A.
        JMIR Res Protoc. 2017 Sep 14;6(9):e180.

        BACKGROUND: Spina bifida (SB) is monitored through birth defects surveillance across the United States and in most developed countries. Although much is known about the management of SB and its many comorbid conditions in affected individuals, there are few systematic, longitudinal studies on population-based cohorts of children or adults. The natural history of SB across the life course of persons with this condition is not well documented. Earlier identification of comorbidities and secondary conditions could allow for earlier intervention that might enhance the developmental trajectory for children with SB. OBJECTIVE: The purpose of this project was to assess the development, health, and condition progression by prospectively studying children who were born with SB in Arizona and Utah. In addition, the methodology used to collect the data would be evaluated and revised as appropriate. METHODS: Parents of children with SB aged 3-6 years were eligible to participate in the study, in English or Spanish. The actual recruitment process was closely documented. Data on medical history were collected from medical records; family functioning, child behaviors, self-care, mobility and functioning, and health and well-being from parent reports; and neuropsychological data from testing of the child. RESULTS: In total, 152 individuals with SB were identified as eligible and their parents were contacted by site personnel for enrollment in the study. Of those, 45 (29.6%) declined to participate and 6 (3.9%) consented but did not follow through. Among 101 parents willing to participate, 81 (80.2%) completed the full protocol and 20 (19.8%) completed the partial protocol. Utah enrolled 72.3% (73/101) of participants, predominately non-Hispanic (60/73, 82%) and male (47/73, 64%). Arizona enrolled 56% (28/50) of participants they had permission to contact, predominately Hispanic (18/28, 64%) and male (16/28, 57%). CONCLUSIONS: We observed variance by site for recruitment, due to differences in identification and ascertainment of eligible cases and the required institutional review board processes. Restriction in recruitment and the proportion of minorities likely impacted participation rates in Arizona more than Utah.

    • Mining
      1. Characterization of airborne float coal dust emitted during continuous mining, longwall mining and belt transportExternal
        Shahan MR, Seaman CE, Beck TW, Colinet JF, Mischler SE.
        Mining Engineering. 2017 ;69(9):61-66.

        Float coal dust is produced by various mining methods, carried by ventilating air and deposited on the floor, roof and ribs of mine airways. It deposited, float dust is re-entrained during a methane explosion. Without sufficient inert rock dust quantities, this float coal dust can propagate an explosion throughout mining entries. Consequently, controlling float coaf dust is of critical interest to mining operations. Rock dusting, which is the adding of inert material to airway surfaces, is the main control technique currently used by the coal mining industry to reduce the float coal dust explosion hazard. To assist the industry in reducing this hazard, the Pittsburgh Mining Research Division of the U.S. National Institute for Occupational Safety and Health initiated a project to investigate methods and technologies to reduce float ooal dust in underground coal mines through prevention, capture and suppression prior to deposition. Field characterization studies were performed to determine quantitatively the sources, types and amounts of dust produced during various coal mining processes. The operations chosen for study were a continuous miner section, a longwall section and a coal-handling facility. For each of these operations, the primary dust sources were confirmed to be the continuous mining machine, longwall shearer and conveyor belt transfer points, respectively. Respirable and total airborne float dust samples were collected and analyzed for each operation, and the ratio of total airborne float coal dust to respirable dust was calculated. During the continuous mining process, the ratio of total airborne float ooal dust to respirable dust ranged from 10.3 to 13.6. The ratios measured on the longwall face were between 1B.5 and 21.5. The total airborne float coal dust to respirable dust ratio observed during belt transport ranged between 7.5 and 21.8.

    • Occupational Safety and Health
      1. OBJECTIVE: The aim of this study was to examine prevalence of obesity (body mass index of 30 or higher), no leisure-time physical activity in the past 30 days (no LTPA), and short sleep duration (averaging less than 7 hours of sleep per 24-hour period) among 22 occupational groups. METHODS: We analyzed 2013 and 2014 Behavioral Risk Factor Surveillance System (BRFSS) data from 29 states, controlling for sex, age, race/ethnicity, and education. RESULTS: By occupation, prevalence ranged from 16.1% to 35.8% for obesity, 11.3% to 28.7% for no LTPA, and 31.4% to 42.9% for short sleep. Only Transportation & Material Moving ranked among the top five occupations for all three risk factors. Obesity and no LTPA varied significantly by sex for several occupations. CONCLUSION: Prevalence of obesity, no LTPA, and short sleep varied by occupation and affected more than one in five U.S. workers.

      2. Respiratory and ocular symptoms among employees of an indoor waterpark resort – Ohio, 2016External
        Chiu SK, Burton NC, Dunn KH, de Perio MA.
        MMWR Morb Mortal Wkly Rep. 2017 Sep 22;66(37):986-989.

        In July 2015, a municipal health department in Ohio received complaints of respiratory and ocular symptoms from patrons of an indoor waterpark resort. In response, the health department conducted an online survey in August 2015 through which 19 (68%) patron and employee respondents reported eye burning, nose irritation, difficulty breathing, and vomiting. On August 11, 2015, the health department requested a health hazard evaluation by CDC’s National Institute for Occupational Safety and Health to characterize the prevalence of symptoms among employees and determine the etiology of work-related symptoms. In January 2016, CDC investigators performed a cross-sectional epidemiologic study, environmental sampling, and ventilation system assessment (1). Findings suggested that chlorine disinfection byproducts and environmental conditions contributed to a higher prevalence of work-related respiratory and ocular symptoms among employees in the waterpark compared with employees in other resort areas. Recommendations included servicing the ventilation system, changing work practices to decrease the amount of disinfection byproduct precursors, and responding promptly to employee reports of symptoms.

      3. Exploring associations between state education initiatives and teachers’ sleep: A social-ecological approachExternal
        Fujishiro K, Farley AN, Kellemen M, Swoboda CM.
        Soc Sci Med. 2017 Sep 12;191:151-159.

        Social policies that are not specifically aimed at impacting health can still have health consequences. State education reforms, such as standardized testing and stringent accountability for schools and teachers, may affect teacher health by changing their working conditions. This study explores associations between state education initiatives and teachers’ sleep, an important predictor of productivity and chronic health conditions. The Behavioral Risk Factor Surveillance System 2013 and 2014 data sets provided sleep and demographic data for 7836 teachers in 29 states in the United States. We linked the teacher data to state education reform data from the U.S. Department of Education. Logistic regression was used to estimate odds ratios (ORs) of reporting inadequate sleep (i.e., <6.5 h and <5.5 h) associated with state education policies after adjusting for demographic characteristics. Teachers had significantly higher odds of reporting inadequate sleep if their state financed professional development, sanctioned or rewarded schools based on student performance, and regulated classroom materials for state-wide common core standards (ORs ranging from 1.25 to 1.84). More strictly defined inadequate sleep (<5.5 h) had generally higher ORs than less strict definition (<6.5 h). The Race-to-the-Top award, a US federal grant designed to encourage states to implement reforms through regulations and legislations, was also associated with inadequate sleep (OR = 1.41, p < 0.01, for <6.5 h; OR = 1.55, p < 0.01, for <5.5 h). Although this exploratory study did not have district- and school-level implementation data, the results suggest that some state education policies may have impacts on teacher sleep. Consequences of education reform for teacher health deserve more attention.

      4. Characterizing the interrelationships of prescription opioid and benzodiazepine drugs with worker health and workplace hazardsExternal
        Kowalski-McGraw M, Green-McKenzie J, Pandalai SP, Schulte PA.
        J Occup Environ Med. 2017 Sep 19.

        OBJECTIVE: Prescription opioid and benzodiazepine drug use, which has risen significantly, can affect worker health. Exploration of the scientific literature assessed (1) interrelationships of such drug use, occupational risk factors, and illness and injury, and (2) occupational and personal risk factor combinations that can affect their use. METHODS: The scientific literature from 2000 to 2015 was searched to determine any interrelationships. RESULTS: Evidence for eight conceptual models emerged based on the search yield of 133 articles. These models summarize interrelationships among prescription opioid and benzodiazepine use with occupational injury and illness. Factors associated with the use of these drugs included fatigue, impaired cognition, falls, motor vehicle crashes, and the use of multiple providers. CONCLUSION: Prescription opioid and benzodiazepine drugs may be both a personal risk factor for work-related injury and a consequence of workplace exposures.

      5. Current asthma and asthma-like symptoms among workers at a Veterans Administration Medical CenterExternal
        Kurth L, Virji MA, Storey E, Framberg S, Kallio C, Fink J, Laney AS.
        Int J Hyg Environ Health. 2017 Sep 05.

        INTRODUCTION: Healthcare workers are at increased risk for respiratory disorders. The purpose of our respiratory health survey was to estimate the prevalence of current asthma and asthma-like symptoms and their association with workplace exposures and tasks among healthcare workers at a Veterans Administration (VA) Medical Center. MATERIAL AND METHODS: Information on respiratory health and work characteristics, including tasks performed, products used, and exposures, were collected by questionnaire from a convenience sample of workers employed at the VA Medical Center during 2012-2014. Associations of asthma and asthma-like symptoms with cleaning and disinfecting tasks and products as well as exposure to dampness and molds, and construction dust were evaluated using log-binomial regression. RESULTS: The prevalence of current asthma was 17.6% and almost half of all workers reported asthma-like symptoms. We observed elevated prevalence of current asthma among the VA healthcare workers compared to the U.S. general and working adult populations. Asthma and asthma-like symptoms were significantly associated with mold, dampness, and construction material exposures; cleaning and disinfecting products; and cleaning or disinfecting tasks. CONCLUSIONS: Workplace exposures and tasks associated with current asthma and asthma-like symptoms were identified but further research is needed to investigate the temporal association between workplace exposures and current asthma and asthma-like symptoms.

    • Parasitic Diseases
      1. Acute malaria infection after atovaquone-proguanil prophylaxisExternal
        Minta AA, Tan KR, Mace KE, Arguin PM.
        J Travel Med. 2017 Mar 01;24(2).

        [No abstract]

    • Reproductive Health
      1. Trends in contraceptive use according to HIV status among privately insured women in the United StatesExternal
        Haddad LB, Monsour M, Tepper NK, Whiteman MK, Kourtis AP, Jamieson DJ.
        Am J Obstet Gynecol. 2017 Sep 01.

        BACKGROUND: There is limited information on the patterns and trends of contraceptive use among women living with HIV, compared with noninfected women in the United States. Further, little is known about whether antiretroviral therapy correlates with contraceptive use. Such information is needed to help identify potential gaps in care and to enhance unintended pregnancy prevention efforts. OBJECTIVE: We sought to compare contraceptive method use among HIV-infected and noninfected privately insured women in the United States, and to evaluate the association between antiretroviral therapy use and contraceptive method use. STUDY DESIGN: We used a large US nationwide health care claims database to identify girls and women ages 15-44 years with prescription drug coverage. We used diagnosis, procedure, and National Drug Codes to assess female sterilization and reversible prescription contraception use in 2008 and 2014 among women continuously enrolled in the database during 2003 through 2008 or 2009 through 2014, respectively. Women with no codes were classified as using no method; these may have included women using nonprescription methods, such as condoms. We calculated prevalence of contraceptive use by HIV infection status, and by use of antiretroviral therapy among those with HIV. We used multivariable polytomous logistic regression to calculate unadjusted and adjusted odds ratios and 95% confidence intervals for female sterilization, long-acting reversible contraception, and short-acting hormonal contraception compared to no method. RESULTS: While contraceptive use increased among HIV-infected and noninfected women from 2008 through 2014, in both years, a lower proportion of HIV-infected women used prescription contraceptive methods (2008: 17.5%; 2014: 28.9%, compared with noninfected women (2008: 28.8%; 2014: 39.8%, P < .001 for both). Controlling for demographics, chronic medical conditions, pregnancy history, and cohort year, HIV-infected women compared to HIV-noninfected women had lower odds of using long-acting reversible contraception (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86 compared to no method) or short-acting hormonal contraception method (adjusted odds ratio, 0.59; 95% confidence interval, 0.50-0.70 compared to no method). In 2014, HIV-infected women using antiretroviral therapy were significantly more likely to use no method (76.8% vs 64.1%), and significantly less likely to use short-acting hormonal contraception (11.0% vs 22.7%) compared to HIV-infected women not using antiretroviral therapy. Those receiving antiretroviral therapy had lower odds of using short-acting hormonal contraception compared to no method (adjusted odds ratio, 0.45; 95% confidence interval, 0.32-0.63). There was no significant difference in female sterilization by HIV status or antiretroviral therapy use. CONCLUSION: Despite the safety of reversible contraceptives for women with HIV, use of prescription contraception continues to be lower among privately insured HIV-infected women compared to noninfected women, particularly among those receiving antiretroviral therapy.

      2. Assessing the use of assisted reproductive technology in the United States by non-United States residentsExternal
        Levine AD, Boulet SL, Berry RM, Jamieson DJ, Alberta-Sherer HB, Kissin DM.
        Fertil Steril. 2017 Aug 31.

        OBJECTIVE: To study cross-border reproductive care (CBRC) by assessing the frequency and nature of assisted reproductive technology (ART) care that non-U.S. residents receive in the United States. DESIGN: Retrospective study of ART cycles reported to the Centers for Disease Control and Prevention’s National ART Surveillance System (NASS) from 2006 to 2013. SETTING: Private and academic ART clinics. PATIENT(S): Patients who participated in ART cycles in the United States from 2006 to 2013. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Frequency and trend of ART use in the U.S. by non-U.S. residents, countries of residence for non-U.S. residents, differences by residence status for specific ART treatments received, and the outcomes of these ART cycles. RESULT(S): A total of 1,271,775 ART cycles were reported to NASS from 2006 to 2013. The percentage of ART cycles performed for non-U.S. residents increased from 1.2% (n = 1,683) in 2006 to 2.8% (n = 5,381) in 2013 (P<.001), with treatment delivered to residents of 147 countries. Compared with resident cycles, non-U.S. resident cycles had higher use of oocyte donation (10.6% vs. 42.6%), gestational carriers (1.6% vs. 12.4%), and preimplantation genetic diagnosis or screening (5.3% vs. 19.1%). U.S. resident and non-U.S. resident cycles had similar embryo transfer and multiple birth rates. CONCLUSION(S): This analysis showed that non-U.S. resident cycles accounted for a growing share of all U.S. ART cycles and made higher use of specialized treatment techniques. This study provides important baseline data on CBRC in the U.S. and may also prove to be useful to organizations interested in improving access to fertility treatments.

      3. CDC’s U.S. Medical Eligibility Criteria for Contraceptive Use (U.S. MEC) (first published in 2010 and updated in 2016) provides evidence-based guidance for the safe use of contraceptive methods among U.S. women with certain characteristics or medical conditions (1), and is adapted from global guidance from the World Health Organization (WHO) and kept up to date based on continual review of published literature (2).* CDC recently evaluated the evidence and the updated WHO guidance on the risk for human immunodeficiency virus (HIV) acquisition among women using hormonal contraception.dagger After careful review, CDC adopted the updated WHO guidance for inclusion in the U.S. MEC guidance; this guidance states that the advantages of progestin-only injectable contraceptive use (including depot medroxyprogesterone acetate [DMPA]) by women at high risk for HIV infection outweigh the theoretical or proven risks (U.S. MEC category 2). The guidance also includes an accompanying updated clarification, which states that “there continues to be evidence of a possible increased risk of acquiring HIV among progestin-only injectable users. Uncertainty exists about whether this is due to methodological issues with the evidence or a real biological effect. In many settings, unintended pregnancies and/or pregnancy-related morbidity and mortality are common, and progestin-only injectables are among the few types of methods widely available. Women should not be denied the use of progestin-only injectables because of concerns about the possible increased risk. Women considering progestin-only injectables should be advised about these concerns, about the uncertainty over whether there is a causal relationship, and about how to minimize their risk of acquiring HIV.” Recommendations for other hormonal contraceptive methods (including combined hormonal methods, implants, and progestin-only pills) remain the same; there is no restriction for their use among women at high risk for HIV infection (U.S. MEC category 1).

    • Substance Use and Abuse
      1. BACKGROUND: Internalized homonegativity may promote substance use among U.S. men who have sex with men only (MSMO) and men who have sex with men and women (MSMW). However, studies have produced mixed findings, used non-representative samples, and not adequately examined MSMW. OBJECTIVES: We investigated (1) internalized homonegativity in relation to substance use and (2) the extent of temporal change in internalized homonegativity among MSMO and MSMW. METHODS: Using merged 2002, 2006-2010, and 2011-2013 cycles of the National Survey of Family Growth-a nationally representative U.S. sample of persons aged 15-44 years-we acquired subsamples of MSMO (n = 419) and MSMW (n = 195). Rao-Scott chi-square tests examined internalized homonegativity in relation to past-month binge drinking and use of marijuana. These tests examined past-year use of any illicit substance, cocaine, crack, injection drugs, and methamphetamine. Multivariable logistic regression models controlled for covariates. Rao-Scott chi-square tests examined temporal changes in internalized homonegativity. RESULTS: Among MSMO, internalized homonegativity was associated with increased odds of using any illicit substance, cocaine, and methamphetamine. Among MSMW, however, internalized homonegativity was associated with decreased odds of using any illicit substance, cocaine, crack, injection drugs, and methamphetamine. The proportion of MSMO and MSMW who expressed internalized homonegativity did not significantly change during 2002-2013. Conclusions/Importance: Internalized homonegativity may be positively associated with substance use among MSMO, but negatively associated with substance use among MSMW. Future studies should seek to better understand internalized homonegativity and other determinants of substance use among MSMO and MSMW.

      2. Biomarkers of exposure to new and emerging tobacco delivery productsExternal
        Schick SF, Blount BC, Jacob PR, Saliba NA, Bernert JT, El Hellani A, Jatlow P, Pappas RS, Wang L, Foulds J, Ghosh A, Hecht SS, Gomez JC, Martin JR, Mesaros C, Srivastava S, St Helen G, Tarran R, Lorkiewicz PK, Blair IA, Kimmel HL, Doerschuk CM, Benowitz NL, Bhatnagar A.
        Am J Physiol Lung Cell Mol Physiol. 2017 Sep 01;313(3):L425-l452.

        Accurate and reliable measurements of exposure to tobacco products are essential for identifying and confirming patterns of tobacco product use and for assessing their potential biological effects in both human populations and experimental systems. Due to the introduction of new tobacco-derived products and the development of novel ways to modify and use conventional tobacco products, precise and specific assessments of exposure to tobacco are now more important than ever. Biomarkers that were developed and validated to measure exposure to cigarettes are being evaluated to assess their use for measuring exposure to these new products. Here, we review current methods for measuring exposure to new and emerging tobacco products, such as electronic cigarettes, little cigars, water pipes, and cigarillos. Rigorously validated biomarkers specific to these new products have not yet been identified. Here, we discuss the strengths and limitations of current approaches, including whether they provide reliable exposure estimates for new and emerging products. We provide specific guidance for choosing practical and economical biomarkers for different study designs and experimental conditions. Our goal is to help both new and experienced investigators measure exposure to tobacco products accurately and avoid common experimental errors. With the identification of the capacity gaps in biomarker research on new and emerging tobacco products, we hope to provide researchers, policymakers, and funding agencies with a clear action plan for conducting and promoting research on the patterns of use and health effects of these products.

      3. Age at pubertal onset in girls and tobacco smoke exposure during pre- and postnatal susceptibility windowsExternal
        Windham GC, Lum R, Voss R, Wolff M, Pinney SM, Teteilbaum SL, Sosnoff CS, Dobraca D, Biro F, Hiatt RA, Greenspan LC, Galvez M, Kushi LH.
        Epidemiology. 2017 Sep;28(5):719-727.

        BACKGROUND: Tobacco smoke contains known hormonally active chemicals and reproductive toxicants. Several studies have examined prenatal maternal smoking and offspring age at menarche, but few examined earlier pubertal markers, nor accounted for exposure during childhood. Our objective was to examine pre- and postnatal smoke exposure in relation to timing of early pubertal events. METHODS: An ethnically diverse cohort of 1239 girls was enrolled at age 6-8 years old for a longitudinal study of puberty at three US sites. Girls participated in annual or semi-annual exams to measure anthropometry and Tanner breast and pubic hair stages. Prenatal and current tobacco smoke exposures, as well as covariates, were obtained from parent questionnaire. Cotinine was measured in urine collected at enrollment. Using accelerated failure time models, we calculated adjusted time ratios for age at pubertal onset (maturation stages 2 or higher) and smoke exposure. RESULTS: Girls with higher prenatal (>/=5 cigarettes per day) or secondhand smoke exposure had earlier pubic hair development than unexposed (adjusted time ratio: 0.92 [95% CI = 0.87, 0.97] and 0.94 [95% CI = 0.90, 0.97], respectively). Including both exposures in the same model yielded similar associations. Higher urinary cotinine quartiles were associated with younger age at breast and pubic hair onset in unadjusted models, but not after adjustment. CONCLUSIONS: Greater prenatal and childhood secondhand smoke exposure were associated with earlier onset of pubic hair, but not breast, development. These exposures represent modifiable risk factors for early pubertal development that should be considered for addition to the extensive list of adverse effects from tobacco smoke.

    • Zoonotic and Vectorborne Diseases
      1. H7 subtype influenza viruses represent a persistent public health threat because of their continued detection in poultry and ability to cause human infection. An outbreak of highly pathogenic avian influenza H7N7 virus in Italy during 2013 resulted in 3 cases of human conjunctivitis. We determined the pathogenicity and transmissibility of influenza A/Italy/3/2013 virus in mouse and ferret models and examined the replication kinetics of this virus in several human epithelial cell types. The moderate virulence observed in mammalian models and the capacity for transmission in a direct contact model underscore the need for continued study of H7 subtype viruses.

      2. Mild respiratory illness among young children caused by highly pathogenic avian influenza A (H5N1) virus infection in Dhaka, Bangladesh, 2011External
        Chakraborty A, Rahman M, Hossain MJ, Khan SU, Haider MS, Sultana R, Ali Rimi N, Islam MS, Haider N, Islam A, Sultana Shanta I, Sultana T, Al Mamun A, Homaira N, Goswami D, Nahar K, Alamgir AS, Rahman M, Mahbuba Jamil K, Azziz-Baumgartner E, Simpson N, Shu B, Lindstrom S, Gerloff N, Davis CT, Katz JM, Mikolon A, Uyeki TM, Luby SP, Sturm-Ramirez K.
        J Infect Dis. 2017 Sep 15;216(suppl_4):S520-s528.

        Background: In March 2011, a multidisciplinary team investigated 2 human cases of highly pathogenic avian influenza A(H5N1) virus infection, detected through population-based active surveillance for influenza in Bangladesh, to assess transmission and contain further spread. Methods: We collected clinical and exposure history of the case patients and monitored persons coming within 1 m of a case patient during their infectious period. Nasopharyngeal wash specimens from case patients and contacts were tested with real-time reverse-transcription polymerase chain reaction, and virus culture and isolates were characterized. Serum samples were tested with microneutralization and hemagglutination inhibition assays. We tested poultry, wild bird, and environmental samples from case patient households and surrounding areas for influenza viruses. Results: Two previously healthy case patients, aged 13 and 31 months, had influenzalike illness and fully recovered. They had contact with poultry 7 and 10 days before illness onset, respectively. None of their 57 contacts were subsequently ill. Clade highly pathogenic avian influenza H5N1 viruses were isolated from the case patients and from chicken fecal samples collected at the live bird markets near the patients’ dwellings. Conclusion: Identification of H5N1 cases through population-based surveillance suggests possible additional undetected cases throughout Bangladesh and highlights the importance of surveillance for mild respiratory illness among populations frequently exposed to infected poultry.

      3. Highly pathogenic avian influenza A(H5N1) viruses at the animal-human interface in Vietnam, 2003-2010External
        Creanga A, Hang NL, Cuong VD, Nguyen HT, Phuong HV, Thanh LT, Thach NC, Hien PT, Tung N, Jang Y, Balish A, Dang NH, Duong MT, Huong NT, Hoa DN, Tho ND, Klimov A, Kapella BK, Gubareva L, Kile JC, Hien NT, Mai LQ, Davis CT.
        J Infect Dis. 2017 Sep 15;216(suppl_4):S529-s538.

        Mutation and reassortment of highly pathogenic avian influenza A(H5N1) viruses at the animal-human interface remain a major concern for emergence of viruses with pandemic potential. To understand the relationship of H5N1 viruses circulating in poultry and those isolated from humans, comprehensive phylogenetic and molecular analyses of viruses collected from both hosts in Vietnam between 2003 and 2010 were performed. We examined the temporal and spatial distribution of human cases relative to H5N1 poultry outbreaks and characterized the genetic lineages and amino acid substitutions in each gene segment identified in humans relative to closely related viruses from avian hosts. Six hemagglutinin clades and 8 genotypes were identified in humans, all of which were initially identified in poultry. Several amino acid mutations throughout the genomes of viruses isolated from humans were identified, indicating the potential for poultry viruses infecting humans to rapidly acquire molecular markers associated with mammalian adaptation and antiviral resistance.

      4. Effect of counselling on health-care-seeking behaviours and rabies vaccination adherence after dog bites in Haiti, 2014-15: a retrospective follow-up surveyExternal
        Etheart MD, Kligerman M, Augustin PD, Blanton JD, Monroe B, Fleurinord L, Millien M, Crowdis K, Fenelon N, Wallace RM.
        Lancet Glob Health. 2017 Oct;5(10):e1017-e1025.

        BACKGROUND: Haiti has an integrated bite case management (IBCM) programme to counsel animal-bite victims on the risk of rabies and appropriate treatment, as well as the Haiti Animal Rabies Surveillance Program (HARSP) to examine the animals. We assessed the usefulness of the IBCM programme to promote best practices for rabies prophylaxis after exposure in a low-income rabies-endemic setting. METHODS: We did a retrospective follow-up survey of randomly selected bite victims who were counselled by Haiti’s IBCM programme between May 15, 2014, and Sept 15, 2015. We classified participants by HARSP decisions of confirmed, probable, suspected, or non-rabies exposures. We compared health-care outcomes in people who sought medical care before IBCM counselling with those in people who sought care after counselling. We used decision trees to estimate the probability of actions taken in the health-care system, and thereby human deaths. FINDINGS: During the study period, 1478 dog bites were reported to HARSP for assessment. 37 (3%) were confirmed exposures, 76 (5%) probable exposures, 189 (13%) suspected exposures, and 1176 (80%) non-rabies exposures. 115 of these cases were followed up in the survey. IBCM counselling was associated with a 1.2 times increase in frequency of bite victims seeking medical care and of 2.4 times increase in vaccination uptake. We estimated that there would be four human rabies deaths among the 1478 people assessed by IBCM during the survey period, and 11 in the absence of this programme, which would equate to a 65% decrease in rabies deaths. Among three people dead at the time of the follow-up survey, one was deemed to be due to rabies after a probable rabies exposure. INTERPRETATION: Adherence to medical providers’ recommendations might be improved through counselling provided by IBCM programmes. FUNDING: None.

      5. A DNA vaccine for Crimean-Congo hemorrhagic fever protects against disease and death in two lethal mouse modelsExternal
        Garrison AR, Shoemaker CJ, Golden JW, Fitzpatrick CJ, Suschak JJ, Richards MJ, Badger CV, Six CM, Martin JD, Hannaman D, Zivcec M, Bergeron E, Koehler JW, Schmaljohn CS.
        PLoS Negl Trop Dis. 2017 Sep 18;11(9):e0005908.

        Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus capable of causing a severe hemorrhagic fever disease in humans. There are currently no licensed vaccines to prevent CCHFV-associated disease. We developed a DNA vaccine expressing the M-segment glycoprotein precursor gene of CCHFV and assessed its immunogenicity and protective efficacy in two lethal mouse models of disease: type I interferon receptor knockout (IFNAR-/-) mice; and a novel transiently immune suppressed (IS) mouse model. Vaccination of mice by muscle electroporation of the M-segment DNA vaccine elicited strong antigen-specific humoral immune responses with neutralizing titers after three vaccinations in both IFNAR-/- and IS mouse models. To compare the protective efficacy of the vaccine in the two models, groups of vaccinated mice (7-10 per group) were intraperitoneally (IP) challenged with a lethal dose of CCHFV strain IbAr 10200. Weight loss was markedly reduced in CCHFV DNA-vaccinated mice as compared to controls. Furthermore, whereas all vector-control vaccinated mice succumbed to disease by day 5, the DNA vaccine protected >60% of the animals from lethal disease. Mice from both models developed comparable levels of antibodies, but the IS mice had a more balanced Th1/Th2 response to vaccination. There were no statistical differences in the protective efficacies of the vaccine in the two models. Our results provide the first comparison of these two mouse models for assessing a vaccine against CCHFV and offer supportive data indicating that a DNA vaccine expressing the glycoprotein genes of CCHFV elicits protective immunity against CCHFV.

      6. Drug susceptibility evaluation of an influenza A(H7N9) virus by analyzing recombinant neuraminidase proteinsExternal
        Gubareva LV, Sleeman K, Guo Z, Yang H, Hodges E, Davis CT, Baranovich T, Stevens J.
        J Infect Dis. 2017 Sep 15;216(suppl_4):S566-s574.

        Background: Neuraminidase (NA) inhibitors are the recommended antiviral medications for influenza treatment. However, their therapeutic efficacy can be compromised by NA changes that emerge naturally and/or following antiviral treatment. Knowledge of which molecular changes confer drug resistance of influenza A(H7N9) viruses (group 2NA) remains sparse. Methods: Fourteen amino acid substitutions were introduced into the NA of A/Shanghai/2/2013(H7N9). Recombinant N9 (recN9) proteins were expressed in a baculovirus system in insect cells and tested using the Centers for Disease Control and Prevention standardized NA inhibition (NI) assay with oseltamivir, zanamivir, peramivir, and laninamivir. The wild-type N9 crystal structure was determined in complex with oseltamivir, zanamivir, or sialic acid, and structural analysis was performed. Results: All substitutions conferred either reduced or highly reduced inhibition by at least 1 NA inhibitor; half of them caused reduced inhibition or highly reduced inhibition by all NA inhibitors. R292K conferred the highest increase in oseltamivir half-maximal inhibitory concentration (IC50), and E119D conferred the highest zanamivir IC50. Unlike N2 (another group 2NA), H274Y conferred highly reduced inhibition by oseltamivir. Additionally, R152K, a naturally occurring variation at the NA catalytic residue of A(H7N9) viruses, conferred reduced inhibition by laninamivir. Conclusions: The recNA method is a valuable tool for assessing the effect of NA changes on drug susceptibility of emerging influenza viruses.

      7. Human infections with novel influenza A viruses are of global public health concern, and antiviral medications have a potentially important role in treatment and prevention of human illness. Initial guidance was developed by the U.S. Centers for Disease Control and Prevention after the emergence of human infections with avian influenza A(H5N1) and has evolved over time, with identification of influenza A(H7N9) virus infections in humans, as well as detection of avian influenza viruses in birds in the United States. This commentary describes the historical context and current guidance for the use of influenza antiviral medications for treatment and post-exposure chemoprophylaxis of human infections with novel influenza A viruses associated with severe human illness, or with the potential to cause severe human disease, and provides the scientific rationale behind current recommendations.

      8. Zoonotic infection of Brazilian primate workers with New World simian foamy virusExternal
        Muniz CP, Cavalcante LT, Jia H, Zheng H, Tang S, Augusto AM, Pissinatti A, Fedullo LP, Santos AF, Soares MA, Switzer WM.
        PLoS One. 2017 ;12(9):e0184502.

        Simian foamy viruses (SFVs) are retroviruses present in nearly all nonhuman primates (NHPs), including Old World primates (OWP) and New World primates (NWP). While all confirmed human infections with SFV are from zoonotic transmissions originating from OWP, little is known about the zoonotic transmission potential of NWP SFV. We conducted a longitudinal, prospective study of 56 workers occupationally exposed to NWP in Brazil. Plasma from these workers was tested using Western blot (WB) assays containing NWP SFV antigens. Genomic DNA from blood and buccal swabs was analyzed for the presence of proviral SFV sequences by three nested PCR tests and a new quantitative PCR assay. Exposure histories were obtained and analyzed for associations with possible SFV infection. Ten persons (18%) tested seropositive and two persons were seroindeterminate (3.6%) for NWP SFV. Six persons had seroreactivity over 2-3 years suggestive of persistent infection. All SFV NWP WB-positive workers reported at least one incident involving NWP, including six reporting NWP bites. NWP SFV viral DNA was not detected in the blood or buccal swabs from all 12 NWP SFV seroreactive workers. We also found evidence of SFV seroreversion in three workers suggestive of possible clearance of infection. Our findings suggest that NWP SFV can be transmitted to occupationally-exposed humans and can elicit specific humoral immune responses but infection remains well-controlled resulting in latent infection and may occasionally clear.

      9. Essential medications for patients with suspected or confirmed Ebola virus disease in resource-limited environmentsExternal
        Pierce WF, Ready SD, Chapman JT, Kulick C, Shields A, Wang J, Andrews K, Childs RW, Bell C, Kosyak A, Pham J.
        Mil Med. 2017 Sep;182(9):e2006-e2016.

        BACKGROUND: In 2014, the U.S. Public Health Service (USPHS) Commissioned Corps deployed to Monrovia, Liberia, to operate a 25-bed Ebola treatment unit (ETU) constructed by the U.S. Military. The ETU was named the Monrovia Medical Unit (MMU) and was constructed from an U.S. Air Force Expeditionary Medical Support (EMEDS) unit with modifications on the basis of consultation from Medecins Sans Frontieres, the World Health Organization, and expert panels from the U.S. Department of Defense and Department of Health and Human Services. From November 12, 2014, to April 30, 2015, 42 patients (18 confirmed Ebola virus disease [EVD] and 24 suspected EVD) from nine countries were treated by USPHS providers at the MMU. The medications used in the MMU were primarily procured from the EMEDS 25-bed pharmacy cache. However, specific formulary additions were made for treatment of EVD. METHODS: Using the MMU pharmacy dispensing data, we compared and contrasted the medications used in the MMU with recommendations in published EVD treatment guidelines for austere settings. FINDINGS: After comparing and contrasting the MMU pharmacy dispensing data with publications with EVD medication recommendations applicable to resource-limited settings, 101 medications were included in the USPHS Essential Medications for the Management of EVD List (EML) for an austere, isolated clinical environment. DISCUSSION/IMPACT/RECOMMENDATIONS: Because Ebola outbreaks often occur in remote areas, proactive planning, improved preparedness, and optimal patient care for EVD are needed, especially in the context of austere environments with a scarcity of resources. We developed the EML to assist in the planning for future Ebola outbreaks in a remote clinical environment and to provide a list of medications that have been used in an ETU. The EML is a comprehensive medication list that builds on the existing publications with EVD treatment recommendations applicable to supply-constrained clinical environments. As well, it is a resource for the provision of medications when evaluating donations, procurement, and may help inform estimates for product inventory requirements for an ETU. We hope the EML will improve readiness and enhance the capabilities of local and regional international responders.

      10. Zika virus disease-associated Guillain-Barre syndrome – Barranquilla, Colombia 2015-2016External
        Salinas JL, Walteros DM, Styczynski A, Garzon F, Quijada H, Bravo E, Chaparro P, Madero J, Acosta-Reyes J, Ledermann J, Arteta Z, Borland E, Burns P, Gonzalez M, Powers AM, Mercado M, Solano A, Sejvar JJ, Ospina ML.
        J Neurol Sci. 2017 15 Oct;381:272-277.

        Background An outbreak of Guillain-Barre syndrome (GBS), a disorder characterized by acute, symmetric limb weakness with decreased or absent deep-tendon reflexes, was reported in Barranquilla, Colombia, after the introduction of Zika virus in 2015. We reviewed clinical data for GBS cases in Barranquilla and performed a case-control investigation to assess the association of suspect and probable Zika virus disease with GBS. Methods We used the Brighton Collaboration Criteria to confirm reported GBS patients in Barranquilla during October 2015-April 2016. In April 2016, two neighborhood and age range-matched controls were selected for each confirmed GBS case-patient. We obtained demographics and antecedent symptoms in the 2-month period before GBS onset for case-patients and the same period for controls. Sera were collected for Zika virus antibody testing. Suspected Zika virus disease was defined as a history of rash and >= 2 other Zika-related symptoms (fever, arthralgia, myalgia, or conjunctivitis). Probable Zika virus disease was defined as suspected Zika virus disease with laboratory evidence of a recent Zika virus or flavivirus infection. Conditional logistic regression adjusted for sex and race/ethnicity was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results We confirmed 47 GBS cases. Incidence increased with age (10-fold higher in those >= 60 years versus those < 20 years). We interviewed 40 case-patients and 79 controls. There was no significant difference in laboratory evidence of recent Zika virus or flavivirus infection between case-patients and controls (OR: 2.2; 95% CI: 0.9-5.1). GBS was associated with having suspected (OR: 3.0, 95% CI: 1.1-8.6) or probable Zika virus disease (OR: 4.6, CI: 1.1-19.0). Conclusions Older individuals and those with suspected and probable Zika virus disease had higher odds of developing GBS. Key points We confirmed a Guillain-Barre syndrome (GBS) outbreak in Barranquilla, Colombia, during October 2015-April 2016. A case-control investigation using neighborhood controls showed an association of suspected and probable Zika virus disease with GBS.

      11. Risk of human infections with highly pathogenic H5N2 and low pathogenic H7N1 avian influenza strains during outbreaks in ostriches in South AfricaExternal
        Venter M, Treurnicht FK, Buys A, Tempia S, Samudzi R, McAnerney J, Jacobs CA, Thomas J, Blumberg L.
        J Infect Dis. 2017 Sep 15;216(suppl_4):S512-s519.

        Background: Risk factors for human infection with highly pathogenic (HP) and low-pathogenic (LP) avian influenza (AI) H5N2 and H7N1 were investigated during outbreaks in ostriches in the Western Cape province, South Africa. Methods: Serum surveys were conducted for veterinarians, farmworkers, and laboratory and abattoir workers involved in 2 AI outbreaks in the Western Cape province: (1) controlling and culling of 42000 ostriches during (HPAI)H5N2 outbreaks in ostriches (2011) (n = 207); (2) movement control during (LPAI)H7N1 outbreaks in 2012 (n = 66). A third serosurvey was conducted on state veterinarians from across the country in 2012 tasked with disease control in general (n = 37). Antibodies to H5 and H7 were measured by means of hemagglutination inhibition and microneutralization assays, with microneutralization assay titers >40 considered positive. Results: Two of 207 (1%) participants were seropositive for H5 and 4 of 207 (2%) for H7 in 2011, compared with 1 of 66 (1.5%) and 8 of 66 (13%) in 2012. Although individuals in all professions tested seropositive, abattoir workers (10 of 97; 10.3%) were significantly more at risk of influenza A(H7N1) infection (P = .001) than those in other professions (2 of 171;1.2%). Among state veterinarians, 4 of 37(11%) were seropositive for H7 and 1 of 37 (2.7%) for H5. Investigations of (LP)H7N1-associated fatalities in wild birds and quarantined exotic birds in Gauteng, AI outbreaks in poultry in KwaZulu-Natal, and ostriches in Western Cape province provide possible exposure events. Conclusion: (LPAI)H7N1 strains pose a greater infection-risk than (HPAI)H5N2 strains to persons involved in control of outbreaks in infected birds, with ostrich abattoir workers at highest risk.

      12. The global threat of animal influenza viruses of zoonotic concern: Then and nowExternal
        Widdowson MA, Bresee JS, Jernigan DB.
        J Infect Dis. 2017 Sep 15;216(suppl_4):S493-s498.

        Animal influenza viruses can reassort or mutate to infect and spread sustainably among people and cause a devastating worldwide pandemic. Since the first evidence of human infection with an animal influenza virus, in 1958, 16 different novel, zoonotic influenza A virus subtype groups in 29 countries, Taiwan, and Hong Kong have caused human infections, with differing severity and frequency. The frequency of novel influenza virus detection is increasing, and human infections with influenza A(H5N1) and A(H7N9) viruses are now annual seasonal occurrences in Asia. The study of the epidemiology and virology of animal influenza viruses is key to understanding pandemic risk and informing preparedness. This supplement brings together select recent articles that look at the risk of emergence and transmission of and approaches to prevent novel influenza virus infections.

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