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CDC Science Clips: Volume 11, Issue 4, January 22, 2019

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

  1. Top Articles of the Week

    Selected weekly by a senior CDC scientist from the standard sections listed below.

    The names of CDC authors are indicated in bold text.
    • Communicable Diseases
      • Colonization factors among enterotoxigenic Escherichia coli isolates from children with moderate-to-severe diarrhea and from matched controls in the Global Enteric Multicenter Study (GEMS)
        Vidal RM, Muhsen K, Tennant SM, Svennerholm AM, Sow SO, Sur D, Zaidi AK, Faruque AS, Saha D, Adegbola R, Hossain MJ, Alonso PL, Breiman RF, Bassat Q, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ahmed S, Qureshi S, Quadri F, Hossain A, Das SK, Antonio M, Mandomando I, Nhampossa T, Acacio S, Omore R, Ochieng JB, Oundo JO, Mintz ED, O’Reilly CE, Berkeley LY, Livio S, Panchalingam S, Nasrin D, Farag TH, Wu Y, Sommerfelt H, Robins-Browne RM, Del Canto F, Hazen TH, Rasko DA, Kotloff KL, Nataro JP, Levine MM.
        PLoS Negl Trop Dis. 2019 Jan 4;13(1):e0007037.
        BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) encoding heat-stable enterotoxin (ST) alone or with heat-labile enterotoxin (LT) cause moderate-to-severe diarrhea (MSD) in developing country children. The Global Enteric Multicenter Study (GEMS) identified ETEC encoding ST among the top four enteropathogens. Since the GEMS objective was to provide evidence to guide development and implementation of enteric vaccines and other interventions to diminish diarrheal disease morbidity and mortality, we examined colonization factor (CF) prevalence among ETEC isolates from children age <5 years with MSD and from matched controls in four African and three Asian sites. We also assessed strength of association of specific CFs with MSD. METHODOLOGY/PRINCIPAL FINDINGS: MSD cases enrolled at healthcare facilities over three years and matched controls were tested in a standardized manner for many enteropathogens. To identify ETEC, three E. coli colonies per child were tested by polymerase chain reaction (PCR) to detect genes encoding LT, ST; confirmed ETEC were examined by PCR for major CFs (Colonization Factor Antigen I [CFA/I] or Coli Surface [CS] antigens CS1-CS6) and minor CFs (CS7, CS12, CS13, CS14, CS17, CS18, CS19, CS20, CS21, CS30). ETEC from 806 cases had a single toxin/CF profile in three tested strains per child. Major CFs, components of multiple ETEC vaccine candidates, were detected in 66.0% of LT/ST and ST-only cases and were associated with MSD versus matched controls by conditional logistic regression (p</=0.006); major CFs detected in only 25.0% of LT-only cases weren’t associated with MSD. ETEC encoding exclusively CS14, identified among 19.9% of 291 ST-only and 1.5% of 259 LT/ST strains, were associated with MSD (p = 0.0011). No other minor CF exhibited prevalence >/=5% and significant association with MSD. CONCLUSIONS/SIGNIFICANCE: Major CF-based efficacious ETEC vaccines could potentially prevent up to 66% of pediatric MSD cases due to ST-encoding ETEC in developing countries; adding CS14 extends coverage to ~77%.

    • Health Economics
      • OBJECTIVE: To provide guidance on selecting the most appropriate price index for adjusting health expenditures or costs for inflation. DATA SOURCES: Major price index series produced by federal statistical agencies. STUDY DESIGN: We compare the key characteristics of each index and develop suggestions on specific indexes to use in many common situations and general guidance in others. DATA COLLECTION/EXTRACTION METHODS: Price series and methodological documentation were downloaded from federal websites and supplemented with literature scans. PRINCIPAL FINDINGS: The gross domestic product implicit price deflator or the overall Personal Consumption Expenditures (PCE) index is preferable to the Consumer Price Index (CPI-U) to adjust for general inflation, in most cases. The Personal Health Care (PHC) index or the PCE health-by-function index is generally preferred to adjust total medical expenditures for inflation. The CPI medical care index is preferred for the adjustment of consumer out-of-pocket expenditures for inflation. A new, experimental disease-specific Medical Care Expenditure Index is now available to adjust payments for disease treatment episodes. CONCLUSIONS: There is no single gold standard for adjusting health expenditures for inflation. Our discussion of best practices can help researchers select the index best suited to their study.

    • Immunity and Immunization
      • A parenteral inactivated rotavirus vaccine (IRV) in development could address three problems with current live oral rotavirus vaccines (ORV): their lower efficacy in low and middle-income countries (LMICs), lingering concerns about their association with intussusception, and their requirement for a separate supply chain with large volume cold storage. Adding a new parenteral IRV to the current schedule of childhood immunizations would be more acceptable if it could be combined with another injectable vaccine such as inactivated polio vaccine (IPV). Current plans for polio eradication call for phasing out oral polio vaccine (OPV) and transitioning to IPV, initially in LMICs as a single dose booster after two doses of OPV and ultimately as a two dose schedule. Today in many LMICs, IPV is administered as a standalone vaccine, which involves a separate cold chain and is relatively costly. We therefore tested in two animal models formulations of IPV with IRV to determine whether co-administration might interfere with the immune response to each product and spare antigen dose for both vaccines. Our results demonstrate that IRV when adjuvanted with alum and administered alone or in combination with IPV did not impair the immune responses to either rotavirus or poliovirus serotypes 1, 2 and 3. Similarly, IPV when formulated and administered alone or together with IRV induced comparable levels of neutralizing antibody to poliovirus type 1, 2 and 3. Furthermore, comparable antibody titers were observed in animals vaccinated with low, middle or high dose of IPV or IRV in combination. This dose sparing and the lack of interference between IPV and IRV administered together represent another step to support the further development of this novel combination vaccine for children.

    • Injury and Violence
    • Laboratory Sciences
      • In-ear and on-body measurements of impulse-noise exposure
        Davis SK, Calamia PT, Murphy WJ, Smalt CJ.
        Int J Audiol. 2019 Jan 5:1-9.
        Accurate quantification of noise exposure in military environments is challenging due to movement of listeners and noise sources, spectral and temporal noise characteristics, and varied use of hearing protection. This study evaluates a wearable recording device designed to measure on-body and in-ear noise exposure, specifically in an environment with significant impulse noise resulting from firearms. A commercial audio recorder was augmented to obtain simultaneous measurements inside the ear canal behind an integrated hearing protector, and near the outer ear. Validation measurements, conducted with an acoustic test fixture and shock tube, indicated high impulse peak insertion loss with a proper fit of the integrated hearing protector. The recording devices were worn by five subjects during a live-fire data collection at Marine Corps Base Quantico where Marines fired semi-automatic rifles. The field test demonstrated the successful measurement of high-level impulse waveforms with the on-body and in-ear recording system. Dual channels allowed for instantaneous fit estimates for the hearing protection component, and the device worked as intended in terms of hearing protection and noise dosimetry. Accurate measurements of noise exposure and hearing protector fit should improve the ability to model and assess the risks of noise-induced hearing loss.

    • Nutritional Sciences
      • Systematic review and Bayesian meta-analysis of the dose-response relationship between folic acid intake and changes in blood folate concentrations
        Crider KS, Devine O, Qi YP, Yeung LF, Sekkarie A, Zaganjor I, Wong E, Rose CE, Berry RJ.
        Nutrients. 2019 Jan 2;11(1).
        The threshold for population-level optimal red blood cell (RBC) folate concentration among women of reproductive age for the prevention of neural tube defects has been estimated at 906 nmol/L; however, the dose-response relationship between folic acid intake and blood folate concentrations is uncharacterized. To estimate the magnitude of blood folate concentration increase in response to specific dosages of folic acid under steady-state conditions (as could be achieved with food fortification), a systematic review of the literature and meta-analysis was conducted. Of the 14,002 records we identified, 533 were selected for full-text review, and data were extracted from 108 articles. The steady-state concentrations (homeostasis) of both serum/plasma and RBC folate concentrations were estimated using a Bayesian meta-analytic approach and one-compartment physiologically-based pharmacokinetic models. RBC folate concentrations increased 1.78 fold (95% credible interval (CI): 1.66, 1.93) from baseline to steady-state at 375(-)570 microg folic acid/day, and it took a median of 36 weeks of folic acid intake (95% CI: 27, 52) to achieve steady-state RBC folate concentrations. Based on regression analysis, we estimate that serum/plasma folate concentrations increased 11.6% (95% CI: 8.4, 14.9) for every 100 microg/day folic acid intake. These results will help programs plan and monitor folic acid fortification programs.

    • Occupational Safety and Health
      • Leadership is a critical component to an organization’s embedded safety culture and influences the ways that health and safety is enacted on site. Empirical research has demonstrated that by improving leadership, safety outcomes are likely to improve as well. Worker perceptions are shaped through leader-employee interactions over time. However, few details are known about social support dimensions (i.e., emotional, informational, and tangible support) offered by supervisors and what kind of impact this communication has on miners’ safety culture perceptions and performance. In order to study leadership communication in a high-risk environment, this study utilized pre- and post-interview data collected with 20 managers and 48 workers to identify positive and negative instances of social support and its implications on worker performance. Findings show that emotional support, although helpful in motivating miner compliance and proactivity, was harder to tailor and to be received as intended. Informational support not only had the largest impact on miners’ behaviors but was also carried out by miners through support to their coworkers. Finally, tangible support in the form of supervisor assistance had a larger impact on worker behavior than offering incentives or other tangible rewards. By demonstrating the communication offered and desired within these three support dimensions – informational, emotional, and tangible – practitioners can see what is lacking in their organization and whether a shift is needed to balance supportive communication.

      • A tolerability assessment of new respiratory protective devices developed for health care personnel: A randomized simulated clinical study
        Radonovich LJ, Wizner K, LaVela SL, Lee ML, Findley K, Yorio P.
        PLoS One. 2019 ;14(1):e0209559.
        BACKGROUND: U.S. health care personnel (HCP) have reported that some respiratory protective devices (RPD) commonly used in health care have suboptimal tolerability. Between 2012 and 2016, the U.S. National Institute for Occupational Safety and Health, and the Veterans Health Administration collaborated with two respirator manufacturers, Company A and B, to bring new RPD with improved tolerability to the U.S. health care marketplace. The purpose of this study was to compare the tolerability of four new prototype RPD to two models commonly used in U.S. health care delivery. METHODS: A randomized, simulated workplace study was conducted to compare self-reported tolerability of four new prototype RPD (A1, A2, B1, and B2) worn by HCP and two N95 control respirators commonly used in U.S. health care delivery, the 1870 and 1860, manufactured by 3M Corporation. A new survey tool, the Respirator Comfort, Wearing Experience, and Function Instrument (R-COMFI), developed previously in part for the current study, was used as the primary outcome metric. With a maximum total score of 47, lower R-COMFI scores reflected better self-reported tolerability. Poisson regression analyses were used to estimate prototype relative risks compared to controls. RESULTS: Conducted between 2014 and 2015 in two inpatient care rooms at the North Florida/South Georgia Veterans Health System, among 383 participants who enrolled, 335 (87.5%) completed the study. Mean total R-COMFI scores for the 3M 1870, 3M 1860, and prototypes A1, A2, B1, and B2 were 8.26, 9.36, 5.79, 7.70, 6.09, and 5.71, respectively. Compared to the 3M 1870, total R-COMFI unadjusted relative risks (RR) and 95 percent confidence intervals (CI) were A1 (RR 0.70, CI 0.60, 0.82), A2 (RR 0.93, CI 0.82, 1.06), B1 (RR 0.74, CI 0.64, 0.85), and B2 (RR 0.69, CI 0.60, 0.80). Compared to the 3M 1860, prototype total R-COMFI unadjusted RR and 95 percent CI were A1 (RR 0.62, CI 0.53, 0.72), A2 (RR 0.82, CI 0.73, 0.93), B1 (RR 0.65, CI 0.57, 0.74), and B2 (RR 0.61, CI 0.53, 0.70). Similarly, models adjusted for demographic characteristics showed that prototypes A1, B1, and B2 significantly improved tolerability scores compared to both controls, while prototype A2 was significantly improved compared to the 3M 1860. CONCLUSIONS: Compared to the 3M 1870 and 3M 1860, two RPDs commonly used in U.S. health care delivery, tolerability improved for three of four newly developed prototypes in this simulated workplace study. The R-COMFI tool, used in this study to assess tolerability, should be useful for future comparative studies of RPD.

    • Substance Use and Abuse
      • Curiosity about and susceptibility toward hookah smoking among middle and high school students
        Gentzke AS, Wang B, Robinson JN, Phillips E, King BA.
        Prev Chronic Dis. 2019 Jan 10;16:E04.
        INTRODUCTION: Hookah smoking has increased among young people. Curiosity and susceptibility may be associated with experimentation or established use. Because tobacco use behaviors are established primarily during adolescence, our objective was to examine factors that may increase the risk of future tobacco product use among youth. METHODS: We analyzed data from the 2016 National Youth Tobacco Survey, a nationally representative survey of US students. Analyses were restricted to youth who had never smoked a hookah and stratified by their ever having used other tobacco products. The prevalence of hookah curiosity and susceptibility was assessed by sociodemographic characteristics, perceptions of harmfulness and addictiveness of hookahs, and peer use of hookahs. Associations between covariates and curiosity and susceptibility were assessed by using multivariable-adjusted regression. RESULTS: Overall, 29.1% of students reported any hookah curiosity or susceptibility. Curiosity was reported by 14.6% of those who never used tobacco products and by 45.9% of those who ever used tobacco products. Hookah susceptibility was reported by 15.6% of never-users and 52.5% of ever-users. Regardless of ever having used other tobacco products, odds of curiosity and susceptibility were higher among students with perceptions of reduced hookah harmfulness and addictiveness and among those who perceived high levels of hookah use among peers. CONCLUSION: Nearly 3 in 10 youth who never smoked a hookah (6.9 million) reported hookah curiosity or susceptibility, and prevalence was highest among those who had ever used other tobacco products. These findings reinforce the importance of educating youth about the dangers of all tobacco products and dispel misperceptions about the harmfulness and addictiveness of hookah smoking. Continued surveillance of youth curiosity, susceptibility, and use of hookahs can inform public health policy and practice.

    • Zoonotic and Vectorborne Diseases
      • Adaptive immune responses in humans during Nipah virus acute and convalescent phases of infection
        Arunkumar G, Devadiga S, McElroy AK, Prabhu S, Sheik S, Abdulmajeed J, Robin S, Sushama A, Jayaram A, Nittur S, Shakir M, Kumar KG, Radhakrishnan C, Sakeena K, Vasudevan J, Reena KJ, Sarita RL, Klena JD, Spiropoulou CF, Laserson KF, Nichol ST.
        Clin Infect Dis. 2019 Jan 7.
        Background: Nipah virus (NiV) is one of ten potential causes of imminent public health emergencies of international concern. We investigated the NiV outbreak that occurred in May 2018 in Kerala, India. Here we describe the longitudinal characteristics of cell-mediated and humoral immune responses to NiV infection during the acute and convalescent phases in two human survivors. Methods: Serial blood samples were obtained from the only two survivors of the NiV outbreak in Kerala. We used flow cytometry to determine the absolute T lymphocyte and B lymphocyte counts and the phenotypes of both T and B cells. We also detected and quantitated the humoral immune response to NiV by virus-specific IgM and IgG ELISA. Results: Absolute numbers of T lymphocytes remained within normal limits throughout the period of illness studied in both survivors. However, a marked elevation of activated CD8 T cells was observed in both cases. Over 30% of total CD8 T cells expressed Ki67, indicating active proliferation. Proliferating (Ki-67+) CD8 T cells expressed high levels of granzyme B and PD-1, consistent with the profile of acute effector cells. Total B lymphocyte, activated B cell, and plasmablast counts were also elevated in NiV survivors. These individuals developed detectable NiV-specific IgM and IgG antibodies within a week of disease onset. Clearance of NiV RNA from blood preceded the appearance of virus-specific IgG and coincided with the peak of activated CD8 T cells. Conclusion: We describe for the first time longitudinal kinetic data on the activation status of human B and T cell populations during acute Nipah virus infection. While marked CD8 T cell activation was observed with effector characteristics, activated CD4 T cells were less prominent.

      • Monkeypox re-emergence in Africa: a call to expand the concept and practice of One Health
        Reynolds MG, Doty JB, McCollum AM, Olson VA, Nakazawa Y.
        Expert Rev Anti Infect Ther. 2019 Jan 9.
        INTRODUCTION: Monkeypox is a re-emerging viral zoonosis that occurs naturally in heavily-forested regions of West and Central Africa. Inter-human transmission of monkeypox virus, although limited, drives outbreaks, particularly in household and healthcare settings. But the available evidence suggests that without repeated zoonotic introductions, human infections would eventually cease to occur. Therefore, interrupting virus transmission from animals to humans is key to combatting this disease. Such efforts, however, are hindered by an incomplete understanding of the maintenance and transmission dynamics of the virus in its natural reservoir host(s). Areas covered: Herein we review laboratory and field studies examining the susceptibility of various animal taxa to monkeypox virus infection, and note the competence of various species to serve as reservoirs or transmission hosts. In addition, we discuss early socio-ecologic theories of monkeypox virus transmission in rural settings and review current modes of ecologic investigation-including ecologic niche modeling, and ecologic sampling-in light of their potential to identify specific animal species and features of the environment that are associated with heightened risk for human disease. Expert opinion: The role of disease ecology and scientific research in ongoing disease prevention efforts should be reinforced, particularly for wildlife-associated zoonoses such as monkeypox. Such efforts alongside those aimed at nurturing ‘One Health’ collaborations may ultimately hold the greatest promise for reducing human infections with this pathogen.

  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. Systems modelling as an approach for understanding and building consensus on non-communicable diseases (NCD) management in Cambodia
        Ansah JP, Islam AM, Koh V, Ly V, Kol H, Matchar DB, Loun C, Loun M.
        BMC Health Serv Res. 2019 Jan 3;19(1):2.
        BACKGROUND: This paper aims to demonstrate how systems modeling methodology of Group Model Building (GMD) can be applied for exploring and reaching consensus on non-communicable disease (NCD) management. This exercise was undertaken as a first step for developing a quantitative simulation model for generating credible estimates to make an investment case for the prevention and management of NCDs. METHODS: Stakeholder engagement was facilitated through the use of a Group Model Building (GMB) approach. This approach combines various techniques in order to gain a whole system perspective. RESULTS: A conceptual qualitative model framework that connects prevention-via risk factors reduction-screening and treatment of non-communicable diseases (NCDs) was developed with stakeholders that draws on stakeholders personal experiences, beliefs, and perceptions through a moderated interactions to gain in-depth understanding of NCDs management. CONCLUSION: Managing NCDs in Cambodia will require concerted effort to tackle NCD risk factors, identifying individuals with NCDs through screening and providing adequate and affordable consistent care to improve health and outcomes of NCDs.

      2. Prevalence of tuberculosis disease among adult US-bound refugees with chronic kidney disease
        Bardenheier BH, Pavkov ME, Winston CA, Klosovsky A, Yen C, Benoit S, Gravenstein S, Posey DL, Phares CR.
        J Immigr Minor Health. 2019 Jan 5.
        The association between chronic kidney disease (CKD) and tuberculosis disease (TB) has been recognized for decades. Recently CKD prevalence is increasing in low- to middle-income countries with high TB burden. Using data from the required overseas medical exam and the recommended US follow-up exam for 444,356 US-bound refugees aged >/= 18 during 2009-2017, we ran Poisson regression to assess the prevalence of TB among refugees with and without CKD, controlling for sex, age, diabetes, tobacco use, body mass index ( kg/m(2)), prior residence in camp or non-camp setting, and region of birth country. Of the 1117 (0.3%) with CKD, 21 (1.9%) had TB disease; of the 443,239 who did not have CKD, 3380 (0.8%) had TB. In adjusted analyses, TB was significantly higher among those with than without CKD (prevalence ratio 1.93, 95% CI: 1.26, 2.98, p < 0.01). Healthcare providers attending to refugees need to be aware of this association.

      3. Urinary biomarkers of carcinogenic exposure among cigarette, waterpipe and smokeless tobacco users and never users of tobacco in the Golestan Cohort Study
        Etemadi A, Poustchi H, Chang CM, Blount BC, Calafat AM, Wang L, De Jesus VR, Pourshams A, Shakeri R, Shiels MS, Inoue-Choi M, Ambrose BK, Christensen CH, Wang B, Murphy G, Ye X, Bhandari D, Feng J, Xia B, Sosnoff CS, Kamangar F, Brennan P, Boffetta P, Dawsey SM, Abnet CC, Malekzadeh R, Freedman ND.
        Cancer Epidemiol Biomarkers Prev. 2019 Jan 8.
        BACKGROUND: How carcinogen exposure varies across users of different, particularly non-cigarette, tobacco products remains poorly understood. METHODS: We randomly selected 165 participants of Golestan Cohort Study from northeastern Iran: 60 never users of any tobacco, 35 exclusive cigarette, 40 exclusive (78% daily) waterpipe, and 30 exclusive smokeless tobacco (nass) users. We measured concentrations of 39 biomarkers of exposure in 4 chemical classes in baseline urine samples: tobacco alkaloids, tobacco-specific nitrosamines (TSNAs), polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). We also quantified the same biomarkers in a second urine sample, obtained five years later, among continuing cigarette smokers and never tobacco users. RESULTS: Nass users had the highest concentrations of tobacco alkaloids. All tobacco users had elevated TSNA concentrations which correlated with nicotine dose. In both cigarette and waterpipe smokers, PAH and VOC biomarkers were higher than never tobacco users and nass users, and highly correlated with nicotine dose. PAH biomarkers of phenanthrene and pyrene, and two VOC metabolites (phenylmercapturic acid and phenylglyoxylic acid) were higher in waterpipe smokers than all other groups. PAH biomarkers among Golestan never tobacco users were comparable to those in U.S. cigarette smokers. All biomarkers had moderate to good correlations over five years, particularly in continuing cigarette smokers. CONCLUSION: We observed two patterns of exposure biomarkers that differentiated the use of the combustible products (cigarettes and waterpipe) from the smokeless product. Environmental exposure from non-tobacco sources appeared to contribute to the presence of high levels of PAH metabolites in the Golestan Cohort.

      4. Referrals and management strategies for pediatric obesity – DocStyles Survey 2017
        Imoisili OE, Goodman AB, Dooyema CA, Park S, Harrison M, Lundeen EA, Blanck H.
        Front Pediatr. 2018 ;6:367.
        Background: Childhood obesity care management options can be delivered in community-, clinic-, and hospital-settings. The referral practices of clinicians to these various settings have not previously been characterized beyond the local level. This study describes the management strategies and referral practices of clinicians caring for pediatric patients with obesity and associated clinician characteristics in a geographically diverse sample. Methods: This cross-sectional study used data from the DocStyles 2017 panel-based survey of 891 clinicians who see pediatric patients. We used multivariable logistic regression to estimate associations between the demographic and practice characteristics of clinicians and types of referrals for the purposes of pediatric weight management. Results: About half of surveyed clinicians (54%) referred <25% of their pediatric patients with obesity for the purposes of weight management. Only 15% referred most (>/=75%) of their pediatric patients with obesity for weight management. Referral types included clinical referrals, behavioral referrals, and weight management program (WMP) referrals. Within these categories, the percentage referrals ranged from 19% for behavioral/mental health professionals to 72% for registered dieticians. Among the significant associations, female clinicians had higher odds of referral to community and clinical WMP; practices in the Northeast had higher odds of referral to subspecialists, dieticians, mental health professionals, and clinical WMP; and clinics having >/=15 well child visits per week were associated with higher odds of referral to subspecialists, mental health professionals, and health educators. Not having an affiliation with teaching hospitals and serving low-income patients were associated with lower odds of referral to mental health professionals, and community and clinical WMP. Compared to pediatricians, family practitioners, internists, and nurse practitioners had higher odds of providing referrals to mental health professionals and to health educators. Conclusion: This study helps characterize the current landscape of referral practices and management strategies of clinicians who care for pediatric patients with obesity. Our data provide insight into the clinician, clinical practice, and reported patient characteristics associated with childhood obesity referral types. Understanding referral patterns and management strategies may help improve care for children with obesity and their families.

      5. Using machine learning and an ensemble of methods to predict kidney transplant survival
        Mark E, Goldsman D, Gurbaxani B, Keskinocak P, Sokol J.
        PLoS One. 2019 ;14(1):e0209068.
        We used an ensemble of statistical methods to build a model that predicts kidney transplant survival and identifies important predictive variables. The proposed model achieved better performance, measured by Harrell’s concordance index, than the Estimated Post Transplant Survival model used in the kidney allocation system in the U.S., and other models published recently in the literature. The model has a five-year concordance index of 0.724 (in comparison, the concordance index is 0.697 for the Estimated Post Transplant Survival model, the state of the art currently in use). It combines predictions from random survival forests with a Cox proportional hazards model. The rankings of importance for the model’s variables differ by transplant recipient age. Better survival predictions could eventually lead to more efficient allocation of kidneys and improve patient outcomes.

      6. Urinary phthalate biomarker concentrations and postmenopausal breast cancer risk
        Reeves KW, Santana MD, Manson JE, Hankinson SE, Zoeller RT, Bigelow C, Sturgeon SR, Spiegelman D, Tinker L, Luo J, Chen B, Meliker J, Bonner MR, Cote ML, Cheng TD, Calafat AM.
        J Natl Cancer Inst. 2019 Jan 10.
        Background: Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking. Methods: We conducted a nested case-control study within the Women’s Health Initiative (WHI) prospective cohort (N = 419 invasive cases and 838 controls). Controls were matched 2:1 to cases on age, enrollment date, follow-up time, and WHI study group. We quantified thirteen phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios and 95% confidence intervals (OR, 95% CI) for breast cancer risk associated with each phthalate biomarker over up to 19 years of follow-up. Results: Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (e.g. 4th vs 1st quartile of diethylhexyl phthalate OR 1.03, 95% CI 0.91 – 1.17). Results were generally similar in analyses restricted to disease subtypes, to non-users of postmenopausal hormone therapy, stratified by body mass index, or to cases diagnosed within three, five, or ten years. Conclusions: In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer.

      7. Establishing baseline cervical cancer screening coverage – India, 2015-2016
        Van Dyne EA, Hallowell BD, Saraiya M, Senkomago V, Patel SA, Agrawal S, Ghosh A, Saraf D, Mehrotra R, Dhillon PK.
        MMWR Morb Mortal Wkly Rep. 2019 Jan 11;68(1):14-19.
        Cervical cancer is the second leading cause of new cancer cases and cancer-related deaths among women in India, with an estimated 96,922 new cases and 60,078 deaths each year.* Despite the availability of effective low-cost screening options in India, limited access to screening and treatment services, diagnosis at a later stage, and low investment in health care infrastructure all contribute to the high number of deaths (1). In 2016 the Ministry of Health and Family Welfare of India recommended cervical cancer screening using visual inspection with acetic acid every 5 years for women aged 30-65 years (per World Health Organization [WHO] guidelines) (2,3). To establish a baseline for cervical cancer screening coverage, survey data were analyzed to estimate the percentage of women aged 30-49 years who had ever been screened for cervical cancer (defined as ever having had a cervix examination). Cervical cancer screening was estimated using data from the Fourth National Family Health Survey(dagger) (NFHS-4), a nationally representative survey conducted at the district level during 2015-2016, which included 699,686 Indian women aged 15-49 years. Lifetime cervical cancer screening prevalence was low (29.8%) and varied by geographic region, ranging from 10.0% in the Northeast Region to 45.2% in the Western Region. Prevalence of screening was higher among women with higher levels of education and household wealth, those who had ever been married, and urban residents. This screening prevalence can be used as a baseline indicator for cervical cancer screening in India in accordance with the WHO Noncommunicable Diseases Global Monitoring Framework during state-based programmatic rollout and program evaluation (4).

    • Communicable Diseases
      1. Trends in hepatitis B and hepatitis C seroprevalence among blood donors – Haiti, 2005-2014
        Baptiste AE, Chevalier MS, Polo E, Noel E, Hulland EN, Archer WR.
        ISBT Sci Ser. 2018 May;13(2):150-157.
        Background and Objectives: Data on the seroprevalence of viral hepatitis are limited in Haiti; consequently, the epidemiology is poorly described. This study aims to provide a descriptive analysis of hepatitis B virus (HBV) and hepatitis C virus (HCV) seroprevalence of blood donations in Haiti. Materials and Methods: Using Haiti’s National Blood Safety Program and Haitian Red Cross reports from 2005 to 2014, we analysed the results of screening tests of donor serum samples to assess HBV and HCV seroprevalence among adults aged 17 to 65 years. Results: A total of 198 758 donor samples were screened from 2005 to 2014, of which 0.56% were positive for antibody to hepatitis C virus (anti-HCV) and 3.80% were positive for hepatitis B surface antigen. Over the 10-year study period, anti-HCV seroprevalence among blood donors increased by 31% from 0.66% to 0.86% (95% CI: 1.01-1.70); however, this trend was not uniform over time, with a significant decrease from 0.66% in 2005 to 0.39% in 2009 (95% CI: 0.43- 0.82) and 0.43% in 2012 (95% CI: 0.50-0.90). Conversely, HBV decreased significantly by 13% from 3.95% in 2005 to 3.42% in 2014 (95% CI: 0.77-0.97), a trend that was also observed in 2012 and 2013. Conclusion: The significant, uniform decrease in HBV seroprevalence in more recent years may represent the positive impact of public health interventions in preventing the transmission of blood-borne infections. More research is needed to understand why the trends in HCV transmission are non-uniform and to investigate the significant increase in more recent years.

      2. Emergence of extensively drug-resistant Salmonella typhi infections among travelers to or from Pakistan – United States, 2016-2018
        Chatham-Stephens K, Medalla F, Hughes M, Appiah GD, Aubert RD, Caidi H, Angelo KM, Walker AT, Hatley N, Masani S, Nash J, Belko J, Ryan ET, Mintz E, Friedman CR.
        MMWR Morb Mortal Wkly Rep. 2019 Jan 11;68(1):11-13.
        In February 2018, a typhoid fever outbreak caused by Salmonella enterica serotype Typhi (Typhi), resistant to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporins, was reported in Pakistan. During November 2016-September 2017, 339 cases of this extensively drug-resistant (XDR) Typhi strain were reported in Pakistan, mostly in Karachi and Hyderabad; one travel-associated case was also reported from the United Kingdom (1). More cases have been detected in Karachi and Hyderabad as surveillance efforts have been strengthened, with recent reports increasing the number of cases to 5,372 (2). In the United States, in response to the reports from Pakistan, enhanced surveillance identified 29 patients with typhoid fever who had traveled to or from Pakistan during 2016-2018, including five with XDR Typhi. Travelers to areas with endemic disease, such as South Asia, should be vaccinated against typhoid fever before traveling and follow safe food and water practices. Clinicians should be aware that most typhoid fever infections in the United States are fluoroquinolone nonsusceptible and that the XDR Typhi outbreak strain associated with travel to Pakistan is only susceptible to azithromycin and carbapenems.

      3. A multiplex HIV incidence assay for inferring recent HIV-1 transmission and time of infection
        Curtis KA, Campbell EM, Hanson DL, Rudolph DL, Duwve J, Blosser S, Gentry J, Lovchik J, Peters PJ, Owen SM, Switzer WM.
        J Acquir Immune Defic Syndr. 2019 Jan 7.
        BACKGROUND: Laboratory assays for determining recent HIV-1 infection are an important public health tool for aiding in the estimation of HIV incidence. Some incidence assay analytes are remarkably predictive of time since seroconversion and may be useful for additional applications, such as predicting recent transmission events during HIV outbreaks and informing prevention strategies. METHODS: Plasma samples (n= 154) from a recent HIV-1 outbreak in a rural community in Indiana were tested with the customized HIV-1 Multiplex assay, based on the Bio-Rad Bio-Plex platform, which measures antibody response to HIV envelope antigens, gp120, gp160, and gp41. Assay cutoffs for each analyte were established to determine whether an individual seroconverted within 30, 60, or 90 days of the sample collection date. Additionally, a novel bioinformatics method was implemented to infer infection dates of persons newly diagnosed with HIV during the outbreak. RESULTS: Sensitivity/specificity of the HIV-1 Multiplex assay for predicting seroconversion within 30, 60, 90 days, based on a training data set, was 90.5%/95.4%, 94.1%/90%, 89.4%/82.9%, respectively. Of 154 new diagnoses in Indiana between December 2014 and August 2016, the majority (71%) of recent infections (</=3 months since seroconversion) were identified between February and May 2016. The epidemiologic curve derived from the bioinformatics analysis indicated HIV transmission began as early as 2010, grew exponentially in 2014, and leveled off in April 2015. CONCLUSION: The HIV-1 Multiplex assay has the potential to identify and monitor trends in recent infection during an epidemic to assess the efficacy of programmatic or treatment interventions.

      4. Kenya tuberculosis prevalence survey 2016: Challenges and opportunities of ending TB in Kenya
        Enos M, Sitienei J, Ong’ang’o J, Mungai B, Kamene M, Wambugu J, Kipruto H, Manduku V, Mburu J, Nyaboke D, Ngari F, Omesa E, Omale N, Mwirigi N, Okallo G, Njoroge J, Githiomi M, Mwangi M, Kirathe D, Kiplimo R, Ndombi A, Odeny L, Mailu E, Kandie T, Maina M, Kasera K, Mulama B, Mugi B, Weyenga H.
        PLoS One. 2018 ;13(12):e0209098.
        BACKGROUND: We aimed to determine the prevalence of pulmonary TB amongst the adult population (>/=15 years) in 2016 in Kenya. METHOD: A nationwide cross-sectional survey where participants first underwent TB symptom screening and chest x-ray. Subsequently, participants who reported cough >2weeks and/or had a chest x-ray suggestive of TB, submitted sputum specimen for laboratory examination by smear microscopy, culture and Xpert MTB/RIF. RESULT: The survey identified 305 prevalent TB cases translating to a prevalence of 558 [95%CI 455-662] per 100,000 adult population. The highest disease burden was reported among people aged 25-34 years (716 [95% CI 526-906]), males (809 [(95% CI 656-962]) and those who live in urban areas (760 [95% CI 539-981]). Compared to the reported TB notification rate for Kenya in 2016, the prevalence to notification ratio was 2.5:1. The gap between the survey prevalence and notification rates was highest among males, age groups 25-34, and the older age group of 65 years and above. Only 48% of the of the survey prevalent cases reported cough >2weeks. In addition, only 59% of the identified cases had the four cardinal symptoms for TB (cough >/=2 weeks, fever, night sweat and weight loss. However, 88.2% had an abnormal chest x-ray suggestive of TB. The use of Xpert MTB/RIF identified 77.7% of the cases compared to smear microscopy’s 46%. Twenty-one percent of the survey participants with respiratory symptoms reported to have sought prior health care at private clinics and chemists. Among the survey prevalent cases who reported TB related symptoms, 64.9% had not sought any health care prior to the survey. CONCLUSION: This survey established that TB prevalence in Kenya is higher than had been estimated, and about half of the those who fall ill with the disease each year are missed.

      5. Performance of the Syphilis Health Check in clinic and laboratory-based settings
        Fakile YF, Brinson M, Mobley V, Park IU, Gaynor AM.
        Sex Transm Dis. 2019 Jan 8.
        BACKGROUND: In this study, we evaluate the performance of the Syphilis Health Check (SHC) in clinical and laboratory settings using fingerstick whole-blood and serum. METHODS: Fingerstick whole-blood and serum specimens from adult patients (n=562) without prior syphilis history presenting at two county health department STD clinics in North Carolina were tested. Fingerstick specimens were tested with the SHC in clinic, and serum specimens were tested at the North Carolina State Laboratory of Public Health with: 1) qualitative rapid plasma reagin (RPR), 2) treponemal EIA and 3) SHC. Sensitivity and specificity were calculated with 95% confidence intervals. RESULTS: The fingerstick whole-blood had a sensitivity of 100% (7/7) and specificity of 95.7% (531/555), compared to consensus reference testing – CRT (RPR and EIA reactive), but a sensitivity of 50% (8/16), and specificity of 95.9% (523/546), when compared to the treponemal EIA. Both laboratory-based SHC on serum and whole-blood SHC performed similarly, compared to CRT, and the treponemal EIA alone. Twenty-four specimens SHC reactive on whole-blood were nonreactive by CRT. In 8/24 of these cases STD clinic staff reported difficulty reading the test line for the SHC. Of the fingerstick whole-blood SHC reactive specimens, only 14/31 were also serum SHC reactive. CONCLUSION: The SHC on whole-blood appears to be sensitive at detecting patients likely to have syphilis, and could be an option for testing among high-risk populations. However, given challenges in interpreting SHC test results, adequate training of persons performing testing and ongoing quality assurance measures are key.

      6. Why we need pre-exposure prophylaxis: incident HIV and syphilis among men, and transgender women, who have sex with men, Bangkok, Thailand, 2005-2015
        Holtz TH, Wimonsate W, Mock PA, Pattanasin S, Chonwattana W, Thienkrua W, Sukwicha W, Curlin ME, Chitwarakorn A, Dunne EF.
        Int J STD AIDS. 2019 Jan 9:956462418814994.
        We describe incident human immunodeficiency virus (HIV) and syphilis trends in men who have sex with men (MSM) and transgender women (TGW) presenting for HIV voluntary counseling and testing (VCT) services and sexually transmitted infection (STI) management at the Silom Community Clinic, Bangkok, Thailand. Clients underwent rapid HIV testing and syphilis rapid plasma reagin (RPR) testing. For incidence analysis, we included clients with >1 follow-up visit. Initial negative HIV with subsequent positive HIV defined incident HIV infection; incident syphilis infection was defined as negative RPR followed by positive RPR (titer >/=1:8) and confirmatory anti- Treponema pallidum antibodies. Calculation of incidence using Poisson regression assumed a uniform probability distribution throughout the seroconversion interval. From 15 September 2005 to 31 December 2015, we tested 10,158 clients for HIV and 10,324 for syphilis. Overall, 7109 clients tested HIV-seronegative and contributed 7157 person-years (PY). Three-hundred forty-seven incident HIV infections resulted in an incidence rate of 4.8 per 100 PY (95% confidence interval [CI] 4.4-5.4). We found an inverted U-shape trend of HIV incidence over time with a peak of 6.4 per 100 PY in quarter 2/2011 ( p < 0.01) (Poisson with RCS function, p = 0.001). Overall, 8713 clients tested seronegative for syphilis and contributed 8623 PY. The incidence of syphilis infection was 4.4 per 100 PY (95% CI 3.9-4.8). Despite an apparent decline in HIV incidence among MSM and TGW attending VCT services, syphilis incidence rose and remained high. Evaluating temporal trends of HIV and syphilis incidence provides an opportunity to evaluate epidemic trajectories and target limited program funding. We recommend focused HIV and STI prevention interventions for MSM in Bangkok.

      7. Evaluation of a program to improve hand hygiene in Kenyan hospitals through production and promotion of alcohol-based Handrub – 2012-2014
        Ndegwa L, Hatfield KM, Sinkowitz-Cochran R, D’Iorio E, Gupta N, Kimotho J, Woodard T, Chaves SS, Ellingson K.
        Antimicrob Resist Infect Control. 2019 ;8:2.
        Although critical to prevent healthcare-associated infections, hand hygiene (HH) compliance is poor in resource-limited settings. In 2012, three Kenyan hospitals began onsite production of alcohol-based handrub (ABHR) and HH promotion. Our aim is to determine the impact of local production of ABHR on HH compliance and perceptions of ABHR. We observed 25,738 HH compliance opportunities and conducted 15 baseline and post-intervention focus group discussions. Hand Hygiene compliance increased from 28% (baseline) to 38% (post-intervention, p = 0.0003). Healthcare workers liked the increased accessibility of ABHR, but disliked its smell, feel, and sporadic availability. Onsite production and promotion of ABHR resulted in modest HH improvement. Enhancing the quality of ABHR and addressing logistical barriers could improve program impact.

      8. Outcomes of infants born to women with influenza A(H1N1)pdm09
        Newsome K, Alverson CJ, Williams J, McIntyre AF, Fine AD, Wasserman C, Lofy KH, Acosta M, Louie JK, Jones-Vessey K, Stanfield V, Yeung A, Rasmussen SA.
        Birth Defects Res. 2019 Jan 9.
        BACKGROUND: Pregnant women with influenza are more likely to have complications, but information on infant outcomes is limited. METHODS: Five state/local health departments collected data on outcomes of infants born to pregnant women with 2009 H1N1 influenza reported to the Centers for Disease Control and Prevention from April to December 2009. Collaborating sites linked information on pregnant women with confirmed 2009 H1N1 influenza, many who were severely ill, to their infants’ birth certificates. Collaborators also collected birth certificate data from two comparison groups that were matched with H1N1-affected pregnancies on month of conception, sex, and county of residence. RESULTS: 490 pregnant women with influenza, 1,451 women without reported influenza with pregnancies in the same year, and 1,446 pregnant women without reported influenza with prior year pregnancies were included. Women with 2009 H1N1 influenza admitted to an intensive care unit (ICU; n = 64) were more likely to deliver preterm infants (<37 weeks), low birth weight infants, and infants with Apgar scores <=6 at 5 min than women in comparison groups (adjusted relative risk, aRR = 3.9 [2.7, 5.6], aRR = 4.6 [2.9, 7.5], and aRR = 8.7 [3.6, 21.2], for same year comparisons, respectively). Women with influenza who were not hospitalized and hospitalized women not admitted to the ICU did not have significantly elevated risks for adverse infant outcomes. CONCLUSIONS: Severely ill women with 2009 H1N1 influenza during pregnancy were more likely to have adverse birth outcomes than women without influenza, providing more support for influenza vaccination during pregnancy.

      9. HIV testing uptake among the household contacts of multidrug-resistant tuberculosis index cases in eight countries
        Opollo VS, Wu X, Hughes MD, Swindells S, Gupta A, Hesseling A, Churchyard G, Kim S, Lando R, Dawson R, Mave V, Mendoza A, Gonzales P, Kumarasamy N, von Groote-Bidlingmaier F, Conradie F, Shenje J, Fontain SN, Garcia-Prats A, Asmelash A, Nedsuwan S, Mohapi L, Mngqibisa R, Garcia Ferreira AC, Okeyo E, Naini L, Jones L, Smith B, Shah NS.
        Int J Tuberc Lung Dis. 2018 Dec 1;22(12):1443-1449.
        SETTING: The household contacts (HHCs) of multidrug-resistant tuberculosis (MDR-TB) index cases are at high risk of tuberculous infection and disease progression, particularly if infected with the human immunodeficiency virus (HIV). HIV testing is important for risk assessment and clinical management. METHODS: This was a cross-sectional, multi-country study of adult MDR-TB index cases and HHCs. All adult and child HHCs were offered HIV testing if never tested or if HIV-negative >1 year previously when last tested. We measured HIV testing uptake and used logistic regression to evaluate predictors. RESULTS: A total of 1007 HHCs of 284 index cases were enrolled in eight countries. HIV status was known at enrolment for 226 (22%) HHCs; 39 (4%) were HIV-positive. HIV testing was offered to 769 (98%) of the 781 remaining HHCs; 544 (71%) agreed to testing. Of 535 who were actually tested, 26 (5%) were HIV-infected. HIV testing uptake varied by site (median 86%, range 0-100%; P < 0.0001), and was lower in children aged <18 years than in adults (59% vs. 78%; adjusted for site P < 0.0001). CONCLUSIONS: HIV testing of HHCs of MDR-TB index cases is feasible and high-yield, with 5% testing positive. Reasons for low test uptake among children and at specific sites-including sites with high HIV prevalence-require further study to ensure all persons at risk for HIV are aware of their status.

      10. Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis
        Rajasingham R, Meya DB, Greene GS, Jordan A, Nakawuka M, Chiller TM, Boulware DR, Larson BA.
        PLoS One. 2019 ;14(1):e0210105.
        BACKGROUND: Cryptococcal meningitis accounts for 15% of AIDS-related mortality. Cryptococcal antigen (CrAg) is detected in blood weeks before onset of meningitis, and CrAg positivity is an independent predictor of meningitis and death. CrAg screening for patients with advanced HIV and preemptive treatment is recommended by the World Health Organization, though implementation remains limited. Our objective was to evaluate costs and mortality reduction (lives saved) from a national CrAg screening program across Uganda. METHODS: We created a decision analytic model to evaluate CrAg screening. CrAg screening was considered for those with a CD4<100 cells/muL per national and international guidelines, and in the context of a national HIV test-and-treat program where CD4 testing was not available. Costs (2016 USD) were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were based on large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa. CrAg positive (CrAg+) persons could be: (a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or (b) symptomatic with meningitis with hospitalization. RESULTS: In the base case model for 1 million persons with a CD4 test annually, 128,000 with a CD4<100 cells/muL were screened, and 8,233 were asymptomatic CrAg+ and received preemptive therapy. Compared to no screening and treatment, CrAg screening and treatment in the base case cost $3,356,724 compared to doing nothing, and saved 7,320 lives, for a cost of $459 per life saved, with the $3.3 million in cost savings derived from fewer patients developing fulminant meningitis. In the scenario of a national HIV test-and-treat program, of 1 million HIV-infected persons, 800,000 persons were screened, of whom 640,000 returned to clinic, and 8,233 were incident CrAg positive (CrAg prevalence 1.4%). The total cost of a CrAg screening and treatment program was $4.16 million dollars, with 2,180 known deaths. Conversely, without CrAg screening, the cost of treating meningitis was $3.09 million dollars with 3,806 deaths. Thus, despite the very low CrAg prevalence of 1.4% in the general HIV-infected population, and inadequate retention-in-care, CrAg screening averted 43% of deaths from cryptococcal meningitis at a cost of $662 per death averted. CONCLUSION: CrAg screening and treatment programs are cost-saving and lifesaving, assuming preemptive treatment is 77% effective in preventing death, and could be adopted and implemented by ministries of health to reduce mortality in those with advanced HIV disease. Even within HIV test-and-treat programs where CD4 testing is not performed, and CrAg prevalence is only 1.4%, CrAg screening is cost-effective.

      11. The impact of screening and partner notification on chlamydia in the United States, 2000-2015: Evaluation of epidemiologic trends using a pair-formation transmission model
        Ronn MM, Tuite AR, Menzies NA, Wolf EE, Gift TL, Chesson HW, Torrone E, Berruti A, Mazzola E, Galer K, Hsu K, Salomon JA.
        Am J Epidemiol. 2019 Jan 4.
        Population-level effects of chlamydia control strategies on chlamydia transmission dynamics are difficult to quantify. In this study, we calibrated a novel sex- and age-stratified pair-formation transmission model of chlamydial infection to epidemiological data in the United States for 2000-2015. We used sex- and age-specific prevalence estimates from the National Health and Nutrition Examination Surveys, case report data from national chlamydia surveillance, and survey data from the Youth Risk Behavior Survey on the proportion of sexually active 15-18 year-old population. We were able to reconcile national prevalence estimates and case report data by allowing for changes over time in screening coverage and reporting completeness. In retrospective analysis, we found that in the absence of chlamydia screening and partner notification, chlamydia prevalence would be approximately twice as great in 2015 as currently estimated levels. Although chlamydia screening and partner notification were both found to reduce chlamydia burden, the relative magnitude of their estimated impact varied in our sensitivity analyses. The variation in the model predictions highlights the need for further data collection and research to improve our understanding of the natural history of chlamydia and the pathways through which prevention strategies affect transmission dynamics.

      12. Prognostic factors in 264 adults with invasive Scedosporium spp. and Lomentospora prolificans infection reported in the literature and FungiScope(R)
        Seidel D, Meissner A, Lackner M, Piepenbrock E, Salmanton-Garcia J, Stecher M, Mellinghoff S, Hamprecht A, Duran Graeff L, Kohler P, Cheng MP, Denis J, Chedotal I, Chander J, Pakstis DL, Los-Arcos I, Slavin M, Montagna MT, Caggiano G, Mares M, Trauth J, Aurbach U, Vehreschild M, Vehreschild JJ, Duarte RF, Herbrecht R, Wisplinghoff H, Cornely OA, Bachmann B, Borchert K, Burchardt A, Chakrabarti A, Christopeit M, Fasih N, Hekmat K, Hernandez Ruperez B, Kemmerling B, Kessel J, Jyoti Kindo A, Klimko N, Krause R, Lass-Florl C, Levesque E, Lockhart S, Steinmann J, Maritati A, Markiefka B, Martin Gomez MT, Meis J, Oksi J, Pagano L, Ramos Martinez A, Reischies F, Soler Palacin P, Vermeulen E.
        Crit Rev Microbiol. 2019 Jan 10:1-21.
        Invasive Scedosporium spp. and Lomentospora prolificans infections are an emerging threat in immunocompromised and occasionally in healthy hosts. Scedosporium spp. is intrinsically resistant to most, L. prolificans to all the antifungal drugs currently approved, raising concerns about appropriate treatment decisions. High mortality rates of up to 90% underline the need for comprehensive diagnostic workup and even more for new, effective antifungal drugs to improve patient outcome. For a comprehensive analysis, we identified cases of severe Scedosporium spp. and L. prolificans infections from the literature diagnosed in 2000 or later and the FungiScope((R)) registry. For 208 Scedosporium spp. infections solid organ transplantation (n = 58, 27.9%) and for 56 L. prolificans infection underlying malignancy (n = 28, 50.0%) were the most prevalent risk factors. L. prolificans infections frequently presented as fungemia (n = 26, 46.4% versus n = 12, 5.8% for Scedosporium spp.). Malignancy, fungemia, CNS and lung involvement predicted worse outcome for scedosporiosis and lomentosporiosis. Patients treated with voriconazole had a better overall outcome in both groups compared to treatment with amphotericin B formulations. This review discusses the epidemiology, prognostic factors, pathogen susceptibility to approved and investigational antifungals, and treatment strategies of severe infections caused by Scedosporium spp. and L. prolificans.

      13. Human bocavirus, coronavirus, and polyomavirus detected among patients hospitalised with severe acute respiratory illness in South Africa, 2012 to 2013
        Subramoney K, Hellferscee O, Pretorius M, Tempia S, McMorrow M, von Gottberg A, Wolter N, Variava E, Dawood H, Kahn K, Walaza S, Madhi SA, Cohen C, Venter M, Treurnicht FK.
        Health Sci Rep. 2018 Aug;1(8):e59.
        Aim: To investigate the prevalence of human bocavirus (hBoV), human coronaviruses (hCoV), and human polyomaviruses (hPyV) among patients with severe acute respiratory illness (SARI), in South Africa. Methods: The study included 680 South African patients randomly selected in age-defined categories from hospitalised patients enrolled through SARI surveillance during 2012 to 2013. A multiplex reverse transcription real-time polymerase chain reaction assay was used to detect hBoV; hCoV-OC43, hCoV-229E, hCoV-NL63, and hCoV-HKU1; and Washington University hPyV (hPyV-WU) and Karolinska Insitute hPyV (hPyV-KI), in respiratory tract specimens collected from patients with SARI. All respiratory specimens from patients enrolled through SARI surveillance were also routinely tested by multiplex reverse transcription real-time polymerase chain reaction for adenovirus; enterovirus; human metapneumovirus; parainfluenza virus types 1, 2, and 3; respiratory syncytial virus; rhinovirus; influenza A, and influenza B. Results: Human bocavirus, hCoV-229E, and hPyV-WU were detected in 3.7% (25/680), 4.1% (28/680), and 4.1% (28/680) of respiratory specimens, respectively. All other viruses were detected in <2% of specimens. Rhinovirus was the most common coinfecting virus (21.4%-60.7%), followed by adenovirus (21.4%-39.3%), and respiratory syncytial virus (10.7%-24.0%). Testing for the additional viruses (hBoV, hCoV, and hPyV) decreased the number of specimens that initially tested negative by 2.9% (20/680). Conclusion: Inclusion of laboratory tests for hBoV, hCoV-229E, and hPyV-WU in differential testing algorithms for surveillance and diagnostics for suspected cases of respiratory illness of unknown cause may improve our understanding of the etiology of SARI, especially in a country like South Africa with a high number of immune compromised persons.

      14. Brief Report: Cutaneous melanoma risk among people with HIV in the United States and Canada
        Yanik EL, Hernandez-Ramirez RU, Qin L, Lin H, Leyden W, Neugebauer RS, Horberg MA, Moore RD, Mathews WC, Justice AC, Hessol NA, Mayor AM, Gill MJ, Brooks JT, Sun J, Althoff KN, Engels EA, Silverberg MJ, Dubrow R.
        J Acquir Immune Defic Syndr. 2018 Aug 15;78(5):499-504.
        BACKGROUND: Cutaneous melanoma incidence may be modestly elevated in people with HIV (PWH) vs. people without HIV. However, little is known about the relationship of immunosuppression, HIV replication, and antiretroviral therapy (ART) with melanoma risk. METHODS: PWH of white race in the North American AIDS Cohort Collaboration on Research and Design were included. A standardized incidence ratio was calculated comparing risk with the white general population, standardizing by age, sex, and calendar period. Associations between melanoma incidence and current, lagged, and cumulative measures of CD4 count, HIV RNA level, and ART use were estimated with Cox regression, adjusting for established risk factors such as age and annual residential ultraviolet B (UVB) exposure. RESULTS: Eighty melanomas were diagnosed among 33,934 white PWH (incidence = 40.75 per 100,000 person-years). Incidence was not elevated compared with the general population [standardized incidence ratio = 1.15, 95% confidence interval (95% CI) = 0.91 to 1.43]. Higher melanoma incidence was associated with older age [adjusted hazard ratio (aHR) per decade increase = 1.50, 95% CI = 1.20 to 1.89] and higher UVB exposure (aHR for exposure >/=35 vs. <35 mW/m = 1.62, 95% CI = 0.99 to 2.65). Current, lagged, and cumulative CD4 and HIV RNA were not associated with melanoma incidence. Melanoma incidence was higher among people ART-treated for a larger proportion of time in the previous 720 days (aHR per 10% increase = 1.16, 95% CI = 1.03 to 1.30). CONCLUSIONS: These results suggest that HIV-induced immune dysfunction does not influence melanoma development. The association between ART and melanoma risk may be due to increased skin surveillance among PWH engaged in clinical care. Associations with age and UVB confirmed those established in the general population.

    • Disease Reservoirs and Vectors
      1. Fine-scale spatial and temporal dynamics of kdr haplotypes in Aedes aegypti from Mexico
        Grossman MK, Rodriguez J, Barreiro AM, Lenhart A, Manrique-Saide P, Vazquez-Prokopec GM.
        Parasit Vectors. 2019 Jan 9;12(1):20.
        BACKGROUND: As resistance to insecticides increases in disease vectors, it has become exceedingly important to monitor populations for susceptibility. Most studies of field populations of Aedes aegypti have largely characterized resistance patterns at the spatial scale of the city or country, which may not be completely informative given that insecticide application occurs at the scale of the house or city block. Phenotypic resistance to pyrethroids dominates in Ae. aegypti, and it has been partially explained by mutations in the voltage-gated sodium channel gene. Here, we assess community-level patterns of four knockdown resistance (kdr) haplotypes (C1534/I1016, F1534/I1016, C1534/V1016 and F1534/V1016) in Ae. aegypti in 24 randomly chosen city blocks from a city in Yucatan State, Mexico, during both the dry and wet season and over two years. RESULTS: Three of the four haplotypes, C1534/I1016, C1534/V1016 and F1534/V1016 were heterogeneous between city blocks at all four sampling time points, and the double mutant haplotype, C1534/I1016, showed a significant increase following the wet season. The F1534/I1016 haplotype was rarely detected, similar to other studies. However, when haplotype frequencies were aggregated to a coarser spatial scale, the differences in space and time were obscured. CONCLUSIONS: Our results provide empirical evidence that the selection of kdr alleles is occurring at fine spatial scales, indicating that future studies should include this scale to better understand evolutionary processes of resistance in natural populations.

    • Environmental Health
      1. Radon is a leading cause of lung cancer. Recommendations for radon testing in multi-family housing focus on testing a percentage of all units. There is considerable variability among recommendations as well as their implementation. We used the hypergeometric distribution to determine the probability of identifying one or more units with radon at or above 4.0 pCi/L for two prevalences (1:15, the U.S. average) and 1:3 (for states with many homes with radon >/=4.0 pCi/L) using two approaches. First, the distribution was used to evaluate the probability of finding one or more units with radon at or above 4.0 pCi/L when: 1) testing 10% or 25% of a range of ground-floor units, or 2) testing a varying percentage of units in 10-, 20-, or 30- ground-floor unit buildings. Second, the method was used to determine the number of units to be tested to identify one or more units with radon at or above 4.0 pCi/L with 95% probability given a range of total ground-floor units. Methods identified that that testing 10% or 25% of ground-floor units had low probability of identifying at least one unit with radon at or above 4.0 pCi/L, especially at low prevalence. At low prevalence (1:15), at least 10 units need to be tested in structures with 20 or fewer total units; at high prevalence (1:3), at least five units need to be tested in units with structures having 10 or fewer units to achieve 95% probability of identifying at least one unit with radon at or above 4.0 pCi/L. These findings indicate that recommendations for radon testing in multi-family housing may be improved by applying a well-established and more rigorous statistical approach than percentage-based testing to will more accurately characterize radon exposure to radon in multi-family housing units, which could improve lung cancer prevention efforts.

      2. Very low-level prenatal mercury exposure and behaviors in children: the HOME Study
        Patel NB, Xu Y, McCandless LC, Chen A, Yolton K, Braun J, Jones RL, Dietrich KN, Lanphear BP.
        Environ Health. 2019 Jan 9;18(1):4.
        BACKGROUND: Mercury is toxic to the developing brain, but the lowest concentration associated with the development of behavior problems is unclear. The purpose of this study was to examine the association between very low-level mercury exposure during fetal development and behavior problems in children. METHODS: We used data from 389 mothers and children in a prospective pregnancy and birth cohort study. We defined mean prenatal mercury concentration as the mean of total whole blood mercury concentrations in maternal samples collected at 16- and 26-weeks of gestation, delivery, and neonatal cord blood samples. We assessed parent-reported child behavior up to five times from two to 8 years of age using the Behavioral Assessment System for Children (BASC-2). At 8 years of age, we assessed self-reported child anxiety using the Spence Children’s Anxiety Scale (SCAS). We used multiple linear mixed models and linear regression models to estimate the association between mean prenatal mercury concentrations and child behavior and anxiety, respectively. RESULTS: The median prenatal total blood mercury concentrations was 0.67 mug/L. Overall, we did not find statistically significant associations between mean prenatal mercury concentrations and behavior problems scores, but a 2-fold increase in mercury concentrations at 16-weeks gestation was associated with 0.83 point (95% CI: 0.05, 1.62) higher BASC-2 anxiety scores. Maternal and cord blood mercury concentrations at delivery were associated with parent-reported anxiety at 8 years. CONCLUSION: We found limited evidence of an association between very-low level prenatal mercury exposure and behaviors in children, with an exception of anxiety.

      3. Prenatal exposure to select phthalates and phenols and associations with fetal and placental weight among male births in the EDEN Cohort (France)
        Philippat C, Heude B, Botton J, Alfaidy N, Calafat AM, Slama R.
        Environ Health Perspect. 2019 Jan;127(1):17002.
        BACKGROUND: The placenta performs crucial physiological functions to ensure normal fetal development. Few epidemiological studies investigated placental weight sensitivity to phthalates and phenols. OBJECTIVE: Our goal was to explore whether maternal exposure to select phthalates and phenols is associated with changes in placental weight at birth and in placental-to-birth weight ratio (PFR). METHODS: Placental weight and birth weight were available for 473 mother-son pairs in the EDEN (Etude des Determinants pre et postnatals du developpement et de la sante de l’Enfant) cohort for whom 9 phenols (4 parabens, 2 dichlorophenols, triclosan, benzophenone-3, bisphenol A) and 11 phthalate metabolites were measured in spot urine samples collected between weeks 23 and 29 of gestation. We used adjusted Elastic Net penalized regression models (ENET) to select biomarkers associated with placental weight, birth weight and PFR. Unpenalized effect estimates were then obtained by fitting linear regression models simultaneously adjusted for the ENET-selected biomarkers and a priori chosen confounders. RESULTS: The multipollutant ENET model for placental weight retained four biomarkers: triclosan and monocarboxy-isononyl phthalate (MCNP), which were negatively associated with placental weight, and benzophenone-3 and the sum of parabens, which were positively associated with this outcome. The ENET model for PFR retained two phthalate metabolites [MCNP and monocarboxy-isooctyl phthalate (MCOP)], which were negatively associated with this outcome. DISCUSSION: The positive association between the sum of parabens and placental weight was consistent with results of a previous study among 49 male births. Our results provide preliminary evidence of possible associations between other compounds such as triclosan, benzophenone-3, MCNP, and MCOP and both placental weight and PFR. These associations were not reported in previous studies and should be seen as hypothesis generating. Studies relying on repeated assessments of exposure in prospective mother-child cohorts are needed to substantiate the plausibility of the hypotheses generated by our results.

    • Genetics and Genomics
      1. Evolution of gene expression levels in the male reproductive organs of Anopheles mosquitoes
        Izquierdo A, Fahrenberger M, Persampieri T, Benedict MQ, Giles T, Catteruccia F, Emes RD, Dottorini T.
        Life Sci Alliance. 2019 Feb;2(1):e201800191.
        Modifications in gene expression determine many of the phenotypic differentiations between closely related species. This is particularly evident in reproductive tissues, where evolution of genes is more rapid, facilitating the appearance of distinct reproductive characteristics which may lead to species isolation and phenotypic variation. Large-scale, comparative analyses of transcript expression levels have been limited until recently by lack of inter-species data mining solutions. Here, by combining expression normalisation across lineages, multivariate statistical analysis, evolutionary rate, and protein-protein interaction analysis, we investigate ortholog transcripts in the male accessory glands and testes across five closely related species in the Anopheles gambiae complex. We first demonstrate that the differentiation by transcript expression is consistent with the known Anopheles phylogeny. Then, through clustering, we discover groups of transcripts with tissue-dependent expression patterns conserved across lineages, or lineage-dependent patterns conserved across tissues. The strongest associations with reproductive function, transcriptional regulatory networks, protein-protein subnetworks, and evolutionary rate are found for the groups of transcripts featuring large expression differences in lineage or tissue-conserved patterns.

    • Health Economics
      1. Number and cost of hospitalizations with principal and secondary diagnoses of tuberculosis, United States
        Aslam MV, Owusu-Edusei K, Marks SM, Asay GR, Miramontes R, Kolasa M, Winston CA, Dietz PM.
        Int J Tuberc Lung Dis. 2018 Dec 1;22(12):1495-1504.
        OBJECTIVE: To estimate the number and cost of hospitalizations with a diagnosis of active tuberculosis (TB) disease in the United States. METHODS: We analyzed the 2014 National In-Patient Sample using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes to identify hospitalizations with a principal (TB-PD) or any secondary discharge (TB-SD) TB diagnosis. We used a generalized linear model with log link and gamma distribution to estimate the cost per TB-PD and TB-SD episode adjusted for patient demographics, insurer, clinical elements, and hospital characteristics. RESULTS: We estimated 4985 TB-PD and 6080 TB-SD hospitalizations nationwide. TB-PD adjusted averaged $16 695 per episode (95%CI $16 168-$17 221). The average for miliary/disseminated TB ($22 498, 95%CI $21 067-$23 929) or TB of the central nervous system ($28 338, 95%CI $25 836-$30 840) was significantly greater than for pulmonary TB ($14 819, 95%CI $14 284-$15 354). The most common principal diagnoses for TB-SD were septicemia (n = 965 hospitalizations), human immunodeficiency virus infection (n = 610), pneumonia (n = 565), and chronic obstructive pulmonary disease and bronchiectasis (COPD-B, n = 150). The adjusted average cost per TB-SD episode was $15 909 (95%CI $15 337-$16 481), varying between $8687 (95%CI $8337-$9036) for COPD-B and $23 335 (95%CI $21 979-$24 690) for septicemia. TB-PD cost the US health care system $123.4 million (95%CI $106.3-$140.5) and TB-SD cost $141.9 million ($128.4-$155.5), of which Medicaid/Medicare covered respectively 67.2% and 69.7%. CONCLUSIONS: TB hospitalizations result in substantial costs within the US health care system.

    • Healthcare Associated Infections
      1. Notes from the Field: Respiratory syncytial virus infections in a neonatal intensive care unit – Louisiana, December 2017
        Washington EJ, Rose EB, Langley GE, Hand JP, Benowitz I, Gerber SI, Salinas AL, Terry AL, Tonzel JL, Sokol TM, Smith AT, Richardson GJ.
        MMWR Morb Mortal Wkly Rep. 2019 Jan 11;68(1):20-21.

        [No abstract]

    • Immunity and Immunization
      1. Rubella virus-associated cutaneous granulomatous disease: A unique complication in immune-deficient patients, not limited to DNA repair disorders
        Buchbinder D, Hauck F, Albert MH, Rack A, Bakhtiar S, Shcherbina A, Deripapa E, Sullivan KE, Perelygina L, Eloit M, Neven B, Perot P, Moshous D, Suarez F, Bodemer C, Bonilla FA, Vaz LE, Krol AL, Klein C, Seppanen M, Nugent DJ, Singh J, Ochs HD.
        J Clin Immunol. 2019 Jan 3.
        The association of immunodeficiency-related vaccine-derived rubella virus (iVDRV) with cutaneous and visceral granulomatous disease has been reported in patients with primary immunodeficiency disorders (PIDs). The majority of these PID patients with rubella-positive granulomas had DNA repair disorders. To support this line of inquiry, we provide additional descriptive data on seven previously reported patients with Nijmegen breakage syndrome (NBS) (n = 3) and ataxia telangiectasia (AT) (n = 4) as well as eight previously unreported patients with iVDRV-induced cutaneous granulomas and DNA repair disorders including NBS (n = 1), AT (n = 5), DNA ligase 4 deficiency (n = 1), and Artemis deficiency (n = 1). We also provide descriptive data on several previously unreported PID patients with iVDRV-induced cutaneous granulomas including cartilage hair hypoplasia (n = 1), warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (WHIM) syndrome (n = 1), MHC class II deficiency (n = 1), Coronin-1A deficiency (n = 1), X-linked severe combined immunodeficiency (X-SCID) (n = 1), and combined immunodeficiency without a molecular diagnosis (n = 1). At the time of this report, the median age of the patients with skin granulomas and DNA repair disorders was 9 years (range 3-18). Cutaneous granulomas have been documented in all, while visceral granulomas were observed in six cases (40%). All patients had received rubella virus vaccine. The median duration of time elapsed from vaccination to the development of cutaneous granulomas was 48 months (range 2-152). Hematopoietic cell transplantation was reported to result in scarring resolution of cutaneous granulomas in two patients with NBS, one patient with AT, one patient with Artemis deficiency, one patient with DNA Ligase 4 deficiency, one patient with MHC class II deficiency, and one patient with combined immunodeficiency without a known molecular etiology. Of the previously reported and unreported cases, the majority share the diagnosis of a DNA repair disorder. Analysis of additional patients with this complication may clarify determinants of rubella pathogenesis, identify specific immune defects resulting in chronic infection, and may lead to defect-specific therapies.

      2. Live attenuated and inactivated influenza vaccine effectiveness
        Chung JR, Flannery B, Ambrose CS, Begue RE, Caspard H, DeMarcus L, Fowlkes AL, Kersellius G, Steffens A, Fry AM.
        Pediatrics. 2019 Jan 7.
        BACKGROUND: Researchers in observational studies of vaccine effectiveness (VE) in which they compared quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) among children and adolescents have shown inconsistent results, and the studies have been limited by small samples. METHODS: We combined data from 5 US studies from 2013-2014 through 2015-2016 to compare the VE of LAIV4 and IIV against medically attended, laboratory-confirmed influenza among patients aged 2 to 17 years by influenza season, subtype, age group, and prior vaccination status. The VE of IIV or LAIV4 was calculated as 100% x (1 – odds ratio), comparing the odds of vaccination among patients who were influenza-positive to patients who were influenza-negative from adjusted logistic regression models. Relative effectiveness was defined as the odds of influenza comparingLAIV4 and IIV recipients. RESULTS: Of 17 173 patients aged 2 to 17 years, 4579 received IIV, 1979 received LAIV4, and 10 615 were unvaccinated. Against influenza A/H1N1pdm09, VE was 67% (95% confidence interval [CI]: 62% to 72%) for IIV and 20% (95% CI: -6% to 39%) for LAIV4. Results were similar when stratified by vaccination in the previous season. LAIV4 recipients had significantly higher odds of influenza A/H1N1pdm09 compared with IIV recipients (odds ratio 2.66; 95% CI: 2.06 to 3.44). LAIV4 and IIV had similar effectiveness against influenza A/H3N2 and B. Our overall findings were consistent when stratified by influenza season and age group. CONCLUSIONS: From this pooled individual patient-level data analysis, we found reduced effectiveness of LAIV4 against influenza A/H1N1pdm09 compared with IIV, which is consistent with published results from the individual studies included.

      3. Neutralization and hemagglutination-inhibition antibodies following influenza vaccination of HIV-infected and HIV-uninfected pregnant women
        Nunes MC, Weinberg A, Cutland CL, Jones S, Wang D, Dighero-Kemp B, Levine MZ, Wairagkar N, Madhi SA.
        PLoS One. 2018 ;13(12):e0210124.
        BACKGROUND: We previously reported that despite HIV-infected pregnant women had modest humoral immune responses to inactivated influenza vaccine (IIV) measured by hemagglutination-inhibition (HAI) assay, the observed vaccine efficacy against influenza disease was higher than predicted by HAI; suggesting that IIV may confer protection to HIV-infected individuals by additional mechanisms. We evaluated the response to IIV by microneutralization (MN) and HAI assays and correlated both methods in HIV-infected and HIV-uninfected pregnant women. METHODS: MN and HAI antibodies were measured pre-vaccination and approximately one-month post-vaccination in 80 HIV-infected and 75 HIV-uninfected women who received IIV. Geometric mean titers (GMTs), fold-change in titers and seroconversion rates were determined for the three influenza stains in the vaccine. RESULTS: After vaccination there were significant increases in MN and HAI GMTs for the three vaccine strains in both HIV-infected and HIV-uninfected women. HIV-infected women had, however, a lower immune response compared to HIV-uninfected. Fold-increases were 2 to 3-times higher for MN assay compared to HAI assay for the influenza-A strains. Also a higher percentage of women seroconverted by MN than by HAI assay for the influenza-A strains. There was high positive correlation between MN and HAI assays, except for the B/Victoria strain at pre-vaccination. CONCLUSIONS: In general, the MN assay was more sensitive than the HAI assay. Microneutralization antibodies might correlate better with protection against influenza infection.

      4. Effectiveness of trivalent inactivated influenza vaccine among community-dwelling older adults in Thailand: A two-year prospective cohort study
        Prasert K, Patumanond J, Praphasiri P, Siriluk S, Ditsungnoen D, Chittaganpich M, Dawood FS, Mott JA, Lindblade KA.
        Vaccine. 2019 Jan 4.
        BACKGROUND: We conducted a two-year prospective cohort study to measure the effectiveness of trivalent inactivated influenza vaccine (IIV3) to prevent laboratory-confirmed influenza among community-dwelling Thai adults aged >/=65years during 2015-16 and 2016-17 influenza seasons. METHODS: In 2015, we enrolled a cohort of 3220 participants. Trained health volunteers collected baseline data and followed participants for two years with weekly surveillance for new or worsened cough with self-collection of nasal swabs. Vaccine effectiveness (VE) was estimated as 100%x(1- rate ratio of rRT-PCR -confirmed influenza) among vaccinated versus unvaccinated participants. Propensity score stratification was used to reduce differences between vaccinated and unvaccinated participants associated with access to and receipt of IIV3. FINDINGS: During 2015-16 and 2016-17, 1666 (52%) and 1498 (48%) participants received IIV3, respectively. The overall incidence of influenza during the two seasons was 14.3/1000 person-years among vaccinated participants and 20.2/1000 person-years among unvaccinated participants. VE was -4% (95% confidence interval [CI], -83%-40%) during 2015-16 when there was poor antigenic match between the dominant circulating A/H3N2 viruses and the vaccine strain, and 50% (95% CI, 12-71%) during 2016-17 when circulating and vaccine strains were well-matched. Of all three influenza subtypes in both years, significant protection was observed only against Influenza A/H3N2 during 2016-17 (VE, 49%; 95% CI, 3-73%). INTERPRETATION: During a season with well-matched circulating and vaccine strains, IIV3 was moderately effective against laboratory-confirmed influenza among older adults in Thailand.

      5. The path to group A Streptococcus vaccines: WHO research and development technology roadmap and preferred product characteristics
        Vekemans J, Gouvea-Reis F, Kim JH, Excler JL, Smeesters PR, O’Brien KL, Van Beneden CA, Steer AC, Carapetis JR, Kaslow DC.
        Clin Infect Dis. 2019 Jan 8.
        Group A Streptococcus (GAS) infections result in a considerable under-appreciated burden of acute and chronic disease, globally. A 2018 World Health Assembly resolution calls for better control and prevention. Providing guidance on global health research needs is an important WHO activity, influencing prioritization of investments. Here, the role, status and directions in GAS vaccines research are discussed. WHO preferred product characteristics and a research and development technology roadmap, briefly presented, offer an actionable framework for vaccine development to regulatory and policy decision-making, availability and use. GAS vaccines should be considered for global prevention of the range of clinical manifestations and associated antibiotic use. Impediments related to antigen diversity, safety concerns, and the difficulty to establish vaccine efficacy against rheumatic heart disease are discussed. Demonstration of vaccine efficacy against pharyngitis and skin infections constitute key near-term strategic goals. Investments and collaborative partnerships to diversify and advance vaccine candidates are needed.

    • Informatics
      1. The effect of text message reminders to health workers on quality of care for malaria, pneumonia, and diarrhea in Malawi: A cluster-randomized, controlled trial
        Steinhardt LC, Mathanga D, Mwandama D, Nsona H, Moyo D, Gumbo A, Kobayashi M, Namuyinga R, Shah MP, Bauleni A, Troell P, Zurovac D, Rowe AK.
        Am J Trop Med Hyg. 2019 Jan 7.
        The use of mobile technologies in medicine, or mHealth, holds promise to improve health worker (HW) performance, but evidence is mixed. We conducted a cluster-randomized controlled trial to evaluate the effect of text message reminders to HWs in outpatient health facilities (HFs) on quality of care for malaria, pneumonia, and diarrhea in Malawi. After a baseline HF survey (2,360 patients) in January 2015, 105 HFs were randomized to three arms: 1) text messages to HWs on malaria case management; 2) text messages to HWs on malaria, pneumonia, and diarrhea case management (latter two for children < 5 years); and 3) control arm (no messages). Messages were sent beginning April 2015 twice daily for 6 months, followed by an endline HF survey (2,536 patients) in November 2015. An intention-to-treat analysis with difference-in-differences binomial regression modeling was performed. The proportion of patients with uncomplicated malaria managed correctly increased from 42.8% to 59.6% in the control arm, from 43.7% to 55.8% in arm 1 (effect size -4.7%-points, 95% confidence interval (CI): -18.2, 8.9, P = 0.50) and from 30.2% to 50.9% in arm 2 (effect size 3.9%-points, 95% CI: -14.1, 22.0, P = 0.67). Prescription of first-line antibiotics to children < 5 years with clinically defined pneumonia increased in all arms, but decreased in arm 2 (effect size -4.1%-points, 95% CI: -42.0, 33.8, P = 0.83). Prescription of oral rehydration solution to children with diarrhea declined slightly in all arms. We found no significant improvements in malaria, pneumonia, or diarrhea treatment after HW reminders, illustrating the importance of rigorously testing new interventions before adoption.

    • Injury and Violence
      1. Speak up! Prosocial intervention verbalizations predict successful bystander intervention for a laboratory analogue of sexual aggression
        Parrott DJ, Swartout KM, Tharp AT, Purvis DM, Topalli V.
        Sex Abuse. 2019 Jan 9:1079063218821121.
        This study evaluated a mechanism by which men’s self-efficacy to intervene increases their likelihood of preventing a laboratory analogue of sexual aggression (SA) via specific verbalizations and whether alcohol inhibits this mechanism. A sample of 78 male peer dyads were randomly assigned to consume an alcoholic or nonalcoholic beverage and complete a laboratory paradigm to assess bystander intervention to prevent SA toward a female who had ostensibly consumed an alcoholic or nonalcoholic beverage. Participants’ verbalizations during the task were subjected to quantitative analysis. Regardless of alcohol use, bystander self-efficacy increased the likelihood of successful bystander intervention via participants’ use of more prosocial verbalizations. Findings highlight prosocial verbalizations within the male peer context that may effectively prevent SA.

    • Laboratory Sciences
      1. Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity
        Dzimianski JV, Beldon BS, Daczkowski CM, Goodwin OY, Scholte FE, Bergeron E, Pegan SD.
        PLoS Pathog. 2019 Jan 10;15(1):e1007515.
        Post-translational modification of host and viral proteins by ubiquitin (Ub) and Ub-like proteins, such as interferon stimulated gene product 15 (ISG15), plays a key role in response to infection. Viruses have been increasingly identified that contain proteases possessing deubiquitinase (DUB) and/or deISGylase functions. This includes viruses in the Nairoviridae family that encode a viral homologue of the ovarian tumor protease (vOTU). vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins. There are currently about 40 known nairoviruses classified into fourteen species. Recent genomic characterization has revealed a high degree of diversity, with vOTUs showing less than 25% amino acids identities within the family. Previous investigations have been limited to only a few closely related nairoviruses, leaving it unclear what impact this diversity has on vOTU function. To probe the effects of vOTU diversity on enzyme activity and specificity, we assessed representative vOTUs spanning the Nairoviridae family towards Ub and ISG15 fluorogenic substrates. This revealed great variation in enzymatic activity and specific substrate preferences. A subset of the vOTUs were further assayed against eight biologically relevant di-Ub substrates, uncovering both common trends and distinct preferences of poly-Ub linkages by vOTUs. Four novel X-ray crystal structures were obtained that provide a biochemical rationale for vOTU substrate preferences and elucidate structural features that distinguish the vOTUs, including a motif in the Hughes orthonairovirus species that has not been previously observed in OTU domains. Additionally, structure-informed mutagenesis provided the first direct evidence of a second site involved in di-Ub binding for vOTUs. These results provide new insight into nairovirus evolution and pathogenesis, and further enhances the development of tools for therapeutic purposes.

      2. Toxin enzyme immunoassays detect Clostridioides difficile infection with greater severity and higher recurrence rates
        Guh AY, Hatfield KM, Winston LG, Martin B, Johnston H, Brousseau G, Farley MM, Wilson L, Perlmutter R, Phipps EC, Dumyati GK, Nelson D, Hatwar T, Kainer MA, Paulick AL, Karlsson M, Gerding DN, McDonald LC.
        Clin Infect Dis. 2019 Jan 7.
        Background: Few data suggest Clostridioides difficile infections (CDI) detected by toxin enzyme immunoassays (EIA) are more severe and have worse outcomes than those detected by nucleic acid amplification tests (NAAT) only. We compared toxin-positive and NAAT-positive only CDI across geographically-diverse sites. Methods: A case was defined as a positive C. difficile test in a person >/=1 year old with no positive tests in the prior 8 weeks. Cases were detected during 2014-15 by a testing algorithm (specimens initially tested by glutamate dehydrogenase [GDH] and toxin EIA; if discordant results, specimens were reflexed to NAAT) and classified as toxin-positive or NAAT-positive only. Medical charts were reviewed. Multivariable logistic regression models were used to compare CDI-related complications, recurrence, and 30-day mortality between the two groups. Results: Of 4878 cases, 2160 (44.3%) were toxin-positive and 2718 (55.7%) were NAAT-positive only. More toxin-positive than NAAT-positive only cases were aged >/=65 years (48.2% vs 38.0%; P<0.0001), had >/=3 unformed stool for >/=1 day (43.9% vs 36.6%; P<0.0001), and had white blood cells >/=15,000/microl (31.4% versus 21.4%; P<0.0001). In multivariable analysis, toxin-positivity was associated with recurrence (adjusted odds ratio [aOR]: 1.89, 95% CI: 1.61-2.23), but not with CDI-related complications (aOR: 0.91, 95% CI: 0.67-1.23) or 30-day mortality (aOR: 0.95; 95% CI: 0.73-1.24). Conclusions: Toxin-positive CDI is more severe, but there were no differences in adjusted CDI-related complication and mortality rates between toxin-positive and NAAT-positive only CDI that were detected by an algorithm that utilized an initial GDH screening test.

      3. Assessment of two personal breathing recording devices in a simulated healthcare environment
        Zhu J, He X, Guffey S, Bergman MS, Lee EG, Zhuang Z.
        J Int Soc Respir Prot. 2018 Dec;35(2):98-111.
        Background: In the field of respiratory protecting for healthcare workers (HCWs), no respiratory data are available recorded when HCWs are performing their work activities. The objective of this study was to assess the performance of two wearable breathing recording devices in a simulated healthcare environment. Methods: Breathing recording devices from two different manufactures “A” and “B” were assessed using 15 subjects while performing a series of simulated healthcare work activities (Patient assessment; Vitals; IV treatment; Changing linen; Carrying weight while walking; Normal breathing while standing). The minute volume (MV, L/min), mean inhalation flow (MIF, L/min), peak inhalation flow (PIF, L/min), breathing frequency (f, breaths/min), and tidal volume (TV, L/min) measured by each device were analyzed. Bland-Altman method was applied to explore the variability of devices A and B. Duncan’s multiple range test was used to investigate the differences among exercise-specific inspiratory flow rates. Results: The average MV, MIF and PIF reported by device A were 23, 54, and 82 L/min with 95% upper confidence intervals (CIs) of 25, 60 and 92 L/min; the mean differences of MV, MIF and PIF presented by the two units of device A were 0.9, 1.3, and 2.8 L/min, respectively. The average values and mean differences of MV, MIF and PIF found with device B were significantly higher than device A (P<0.05), showing a high variability. During non-speech activities, the PIF/MV and MIF/MV ratios were >3.14 and >2, while with speech, the ratios increased to >6 and >3. The f during speech (15 breaths/min) was significantly lower than non-speech activities (20-25 breaths/min). Among different simulated work activities, the PIF of “patient assessment” was the highest. Conclusions: This study demonstrated a novel approach to characterize respiratory flow for healthcare workers using an innovative wearable flow recording device. Data from this investigation could be useful in the development of future respirator test standards.

    • Maternal and Child Health
      1. Evaluation of state-mandated reporting of neonatal abstinence syndrome – six states, 2013-2017
        Jilani SM, Frey MT, Pepin D, Jewell T, Jordan M, Miller AM, Robinson M, St Mars T, Bryan M, Ko JY, Ailes EC, McCord RF, Gilchrist J, Foster S, Lind JN, Culp L, Penn MS, Reefhuis J.
        MMWR Morb Mortal Wkly Rep. 2019 Jan 11;68(1):6-10.
        From 2004 to 2014, the incidence of neonatal abstinence syndrome (NAS) in the United States increased 433%, from 1.5 to 8.0 per 1,000 hospital births. The latest national data from 2014 indicate that one baby was born with signs of NAS every 15 minutes in the United States (1). NAS is a drug withdrawal syndrome that most commonly occurs among infants after in utero exposure to opioids, although other substances have also been associated with NAS. Prenatal opioid exposure has also been associated with poor fetal growth, preterm birth, stillbirth, and possible specific birth defects (2-5). NAS surveillance has often depended on hospital discharge data, which historically underestimate the incidence of NAS and are not available in real time, thus limiting states’ ability to quickly direct public health resources (6,7). This evaluation focused on six states with state laws implementing required NAS case reporting for public health surveillance during 2013-2017 and reviews implementation of the laws, state officials’ reports of data quality before and after laws were passed, and advantages and challenges of legally mandating NAS reporting for public health surveillance in the absence of a national case definition. Using standardized search terms in an online legal research database, laws in six states mandating reporting of NAS from medical facilities to state health departments (SHDs) or from SHDs to a state legislative body were identified. SHD officials in these six states completed a questionnaire followed by a semistructured telephone interview to clarify open-text responses from the questionnaire. Variability was found in the type and number of surveillance data elements reported and in how states used NAS surveillance data. Following implementation, five states with identified laws reported receiving NAS case reports within 30 days of diagnosis. Mandated NAS case reporting allowed SHDs to quantify the incidence of NAS in their states and to inform programs and services. This information might be useful to states considering implementing mandatory NAS surveillance.

      2. Trends in multivitamin use among women of reproductive age: United States, 2006-2016
        Wong EC, Rose CE, Flores AL, Yeung LF.
        J Womens Health (Larchmt). 2019 Jan;28(1):37-45.
        BACKGROUND: Women of reproductive age can consume 0.4 milligrams of folic acid daily to reduce the risk of a neural tube defect (NTD)-affected pregnancy. Multivitamins (MVs) are one source of folic acid. MATERIALS AND METHODS: Using HealthStyles survey data (n = 9268), we assessed change in prevalence of MV use during 2006-2016 among women by age (18-24, 25-34, and 35-44 years), race/ethnicity (non-Hispanic [NH] white, NH black, Hispanic), and pregnancy status (trying to get pregnant, not pregnant nor trying to get pregnant, and pregnant) using log-binomial regression. RESULTS: Daily MV consumption decreased overall from 32.7% to 23.6% during 2006-2016 for women aged 18-44 years (p for trend <0.001). Age-specific decreases were seen in women aged 25-34 years (2006: 34.1%; 2016: 23.7%; p < 0.001) and 35-44 years (2006: 37.3%; 2016: 27.1%; p < 0.001). Decreases in daily MV intake were found among NH whites (2006: 35.4%; 2016: 24.9%; p < 0.001) and Hispanics (2006: 30.6%; 2016: 22.1%; p < 0.001), but remained unchanged among NH blacks (2006: 23.7%; 2016: 21.8%; p = 0.87). Daily MV intake remained unchanged for women trying to get pregnant (2006: 40.2%; 2012: 38.3%; p = 0.19), decreased for women not pregnant nor trying to get pregnant (2006: 31.3%; 2012: 21.3%; p < 0.001), and fluctuated for pregnant women (2006: 53.8%; 2012: 71.0%; p = 0.21). Prevalence of no MV consumption increased significantly across all age and race/ethnicity groups. CONCLUSIONS: Overall MV intake decreased for the past decade and varied by age, race/ethnicity, and pregnancy status. Innovative messaging and targeted interventions for increasing folic acid intake are needed to reduce NTDs.

    • Medicine
      1. [No abstract]

    • Mining
      1. This paper presents the results of a 2017 study conducted by the National Institute for Occupational Safety and Health (NIOSH), Pittsburgh Mining Research Division (PMRD), to evaluate the effects of longwall-induced subsurface deformations within a longwall abutment pillar under deep cover. The 2017 study was conducted in a southwestern Pennsylvania coal mine, which extracts 457 m-wide longwall panels under 361 m of cover. One 198 m-deep, in-place inclinometer monitoring well was drilled and installed over a 45 m by 84 m center abutment pillar. In addition to the monitoring well, surface subsidence measurements and underground coal pillar pressure measurements were conducted as the 457 m-wide longwall panel on the south side of the abutment pillar was being mined. Prior to the first longwall excavation, a number of simulations using FLAC3D? were conducted to estimate surface subsidence, increases in underground coal pillar pressure, and subsurface horizontal displacements in the monitoring well. Comparisons of the pre-mining FLAC3D simulation results and the surface, subsurface, and underground instrumentation results show that the measured in-place inclinometer casing deformations are in reasonable agreement with those predicted by the 3D finite difference models. The measured surface subsidence and pillar pressure are in excellent agreement with those predicted by the 3D models. Results from this 2017 research clearly indicate that, under deep cover, the measured horizontal displacements within the abutment pillar are approximately one order of magnitude smaller than those measured in a 2014 study under medium cover.

    • Nutritional Sciences
      1. Complementary feeding and bone health: a systematic review
        Obbagy JE, English LK, Wong YP, Butte NF, Dewey KG, Fox MK, Greer FR, Krebs NF, Scanlon KS, Stoody EE.
        Am J Clin Nutr. 2019 Jan 8.
        Background: Proper nutrition during infancy and toddlerhood is crucial for supporting healthy growth and development, including bone health. Complementary feeding is the process that starts when human milk or infant formula is complemented by other foods and beverages, beginning during late infancy and continuing to 24 mo of age. Objectives: This article aims to describe systematic reviews (SRs) conducted by the Nutrition Evidence Systematic Review team for the USDA and the Department of Health and Human Services Pregnancy and Birth to 24 Months Project to answer these questions: what is the relationship between 1) timing of introduction of complementary foods and beverages (CFBs) or 2) types and/or amounts of CFBs consumed and bone health? Methods: The literature was searched with the use of 4 databases (CINAHL, Cochrane, Embase, and PubMed) to identify articles published from January 1980 to July 2016 that addressed these topics and met predetermined criteria for inclusion. For each study, data were extracted and risk of bias was assessed. The evidence was qualitatively synthesized to develop a conclusion statement, and the strength of the evidence was graded. Results: Three articles addressed the timing of introduction of CFBs and bone health during childhood (through 18 y of age), and 2 addressed the types and/or amounts of CFBs consumed relative to bone health. Conclusions: Insufficient evidence was available to draw conclusions about the relationships between the timing of CFB introduction and types and/or amounts of CFBs consumed and bone health. Therefore, a grade was not assignable for these SRs. The ability to draw conclusions was limited by an overall lack of research, failure to adjust for several key confounding factors, and heterogeneity in studies with regard to methodology, subject populations, and results. Additional research is needed that addresses these gaps and limitations.

      2. Association of usual 24-h sodium excretion with measures of adiposity among adults in the United States: NHANES, 2014
        Zhao L, Cogswell ME, Yang Q, Zhang Z, Onufrak S, Jackson SL, Chen TC, Loria CM, Wang CY, Wright JD, Terry AL, Merritt R, Ogden CL.
        Am J Clin Nutr. 2019 Jan 8.
        Background: Both excessive sodium intake and obesity are risk factors for hypertension and cardiovascular disease. The association between sodium intake and obesity is unclear, with few studies assessing sodium intake using 24-h urine collection. Objectives: Our objective was to assess the association between usual 24-h sodium excretion and measures of adiposity among US adults. Methods: Cross-sectional data were analyzed from a sample of 730 nonpregnant participants aged 20-69 y who provided up to 2 complete 24-h urine specimens in the NHANES 2014 and had data on overweight or obesity [body mass index (kg/m2) >/=25] and central adiposity [waist circumference (WC): >88 cm for women, >102 cm for men]. Measurement error models were used to estimate usual sodium excretion, and multiple linear and logistic regression models were used to assess its associations with measures of adiposity, adjusting for sociodemographic, health, and dietary variables [i.e., energy intake or sugar-sweetened beverage (SSB) intake]. All analyses accounted for the complex survey sample design. Results: Unadjusted mean +/- SE usual sodium excretion was 3727 +/- 43.5 mg/d and 3145 +/- 55.0 mg/d among participants with and without overweight/obesity and 3653 +/- 58.1 mg/d and 3443 +/- 35.3 mg/d among participants with or without central adiposity, respectively. A 1000-mg/d higher sodium excretion was significantly associated with 3.8-units higher BMI (95% CI: 2.8, 4.8) and a 9.2-cm greater WC (95% CI: 6.9, 11.5 cm) adjusted for covariates. Compared with participants in the lowest quartile of sodium excretion, the adjusted prevalence ratios in the highest quartile were 1.93 (95% CI: 1.69, 2.20) for overweight/obesity and 2.07 (95% CI: 1.74, 2.46) for central adiposity. The associations also were significant when adjusting for SSBs, instead of energy, in models. Conclusions: Higher usual sodium excretion is associated with overweight/obesity and central adiposity among US adults.

    • Occupational Safety and Health
      1. The power of the crowd: Prospects and pitfalls for citizen science in occupational health
        Moore AC, Anderson AA, Long M, McKernan LT, Volckens J.
        J Occup Environ Hyg. 2019 Jan 8:1-11.

        [No abstract]

    • Occupational Safety and Health – Mining
      1. Testing a revised inlet for the personal dust monitor
        Mischler SE, Tuchman DP, Cauda EG, Colinet JF, Rubinstein EN.
        J Occup Environ Hyg. 2019 Jan 8:1-8.
        A person-wearable dust monitor that provides nearly real-time, mass-based readings of respirable dust was developed for use in underground coal mines. This personal dust monitor (PDM) combined dust sampling instrumentation with a cap lamp (and battery) into one belt-wearable unit, with the air inlet mounted on the cap lamp. However, obsolescence of belt-carried cap lamp and batteries in coal mining ensued and led end users to request that the cap lamp and battery be removed from the PDM. Removal of these components necessitated the design of a new air inlet to be worn on the miner’s lapel. The revised inlet was tested for dust collection equivalency against the original cap-mounted inlet design. Using calculated inlet respirable fractions and measured dust mass collection, the performance of the two inlets is shown to be similar. The new inlet requires a 1.02 factor for converting dust masses obtained from it to equivalent masses collected from the original inlet.

    • Parasitic Diseases
      1. Performance of antigen concentration thresholds for attributing fever to malaria among outpatients in Angola
        Plucinski MM, Rogier E, Dimbu R, Fortes F, Halsey ES, Aidoo M, Smith T.
        J Clin Microbiol. 2019 Jan 9.
        The density of malaria parasites is a key determinant in whether or not an infected individual develops fever. While the pyrogenic threshold for malaria parasite density has been well-studied, there is no analogous data on the level of antigen associated with fever during infection. Samples from 797 afebrile and 457 febrile outpatients from two provinces in Angola with known concentrations of histidine rich protein 2 (HRP2), aldolase, and lactate dehydrogenase (LDH) antigens were analyzed by Bayesian latent-class modeling to attribute malaria etiology to the fevers and to estimate the sensitivity and specificity of different antigen thresholds for detecting malaria fevers. Amongst patients positive for aldolase or LDH at levels detectable by a bead-based assay, concentrations of these two antigens did not differ between afebrile and febrile patients. In contrast, the concentration of HRP2 was substantially higher in febrile HRP2+ patients compared to afebrile HRP2+ patients. When considering HRP2 concentration, the malaria attributable fraction of fever was 0.092 in the Huambo province and 0.39 in Uige. Diagnostic tests detecting HRP2 with levels of detection in the 3,000-10,000 pg/muL range would provide ideal sensitivity and specificity for determining malaria etiology in febrile persons.

    • Reproductive Health
      1. Temporal differences in utilization of intracytoplasmic sperm injection among U.S. regions
        Boulet SL, Kissin DM.
        Obstet Gynecol. 2018 Nov;132(5):1302-1303.

        [No abstract]

      2. Smoking and clinical outcomes of assisted reproductive technologies
        Rockhill K, Tong VT, Boulet SL, Zhang Y, Jamieson DJ, Kissin DM.
        J Womens Health (Larchmt). 2019 Jan 7.
        BACKGROUND: Smoking near conception has adverse effects on pregnancy outcomes. We estimated the proportion of assisted reproductive technology (ART) cycles with smoking reported and associated clinical outcomes. METHODS: We used a retrospective cohort study (2009-2013) using national data of ART cycles in the United States. We compared patient characteristics, infertility diagnoses, and treatment procedures by self-reported smoking in the 3 months before treatment. Using multivariable logistic regression accounting for clustering by state, clinic, and patient, we assessed adjusted odds ratios (aOR) and 95% confidence intervals (CI) between smoking and clinical outcomes: cycle cancellations among all cycles (cycle stopped before retrieval of eggs or transfer of embryos), treatment outcomes (implantation, ectopic pregnancy, intrauterine pregnancy, and live birth) among cycles with >/=1 fresh embryo transferred, and pregnancy outcomes (miscarriage, stillbirth, and live birth) among intrauterine pregnancies. RESULTS: Smoking was reported in 1.9% of cycles. Higher proportions of cycles among smokers versus nonsmokers were younger, non-Hispanic White, multigravida women and had tubal factor and male factor infertility diagnoses; lower proportions had diagnoses of diminished ovarian reserve and unexplained infertility, and used donor eggs. Smoking was associated with higher adjusted odds of cycle cancellation with no embryo transfer (aOR: 1.10; 95% CI: 1.00-1.21) and cancellations before fresh oocyte retrieval or frozen embryo transfer (1.11; 1.02-1.21). Associations between other clinical outcomes were nonsignificant. CONCLUSIONS: Over 12,000 ART cycles in the United States were exposed to smoking during 2009-2013; smoking increased the odds of cycle cancellation. Providers should encourage women to quit smoking before ART treatments.

    • Substance Use and Abuse
      1. Mental health and substance use-related hospitalizations among women of reproductive age in Illinois and Wisconsin
        Bennett AC, Gibson C, Rohan AM, Howland JF, Rankin KM.
        Public Health Rep. 2018 Dec 3:33354918812807.
        INTRODUCTION:: Mental health and substance use are growing public health concerns, but established surveillance methods do not measure the burden of these conditions among women of reproductive age. We developed a standardized indicator from administrative data to identify inpatient hospitalizations related to mental health or substance use (MHSU) among women of reproductive age, as well as co-occurrence of mental health and substance use conditions among those hospitalizations. MATERIALS AND METHODS:: We used inpatient hospital discharge data from 2012-2014 for women aged 15-44 residing in Illinois and Wisconsin. We identified MHSU-related hospitalizations through the principal International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis and first-listed ICD-9-CM external cause of injury code (E code). We classified hospitalizations as related to 1 of 3 mutually exclusive categories: a mental disorder, a substance use disorder, or an acute MHSU-related event. We defined co-occurrence as the presence of both mental health and substance use codes in any available diagnosis or E-code field. RESULTS:: Of 1 173 758 hospitalizations of women of reproductive age, 150 318 (12.8%) were related to a mental disorder, a substance use disorder, or an acute MHSU-related event, for a rate of 135.6 hospitalizations per 10 000 women. Of MHSU-related hospitalizations, 115 163 (76.6%) were for a principal mental disorder, 22 466 (14.9%) were for a principal substance use disorder, and 12 709 (8.5%) were for an acute MHSU-related event; 42.4% had co-occurring mental health codes and substance use codes on the discharge record. PRACTICE IMPLICATIONS:: MHSU-related disorders and events are common causes of hospitalization for women of reproductive age, and nearly half of these hospitalizations involved co-occurring mental health and substance use diagnoses or events. This new indicator may improve public health surveillance by establishing a systematic and comprehensive method to measure the burden of MHSU-related hospitalizations among women of reproductive age.

      2. Smoking cessation attitudes and practices among cancer survivors – United States, 2015
        Gallaway MS, Glover-Kudon R, Momin B, Puckett M, Lunsford NB, Ragan KR, Rohan EA, Babb S.
        J Cancer Surviv. 2019 Jan 5.
        PURPOSE: The prevalence of smoking among cancer survivors is similar to the general population. However, there is little evidence on the prevalence of specific smoking cessation behaviors among adult cancer survivors. METHODS: The 2015 National Health Interview Survey (NHIS) data were analyzed to examine the prevalence of smoking cessation behaviors and use of treatments among cancer survivors. Weighted self-reported prevalence estimates and 95% confidence intervals were calculated using a sample of 2527 cancer survivors. RESULTS: Among this sample of US cancer survivors, 12% were current smokers, 37% were former smokers, and 51% were never smokers. Compared with former and never smokers, current smokers were younger (< 65 years), less educated, and less likely to report being insured or Medicaid health insurance (p < 0.01). More males were former smokers than current or never smokers. Current smokers reported wanting to quit (57%), a past year quit attempt (49%), or a health professional advised them to quit (66%). Current smokers reported the use of smoking cessation counseling (8%) or medication (38%). CONCLUSIONS: Even after a cancer diagnosis, about one in eight cancer survivors continued to smoke. All could have received advice to quit smoking by a health professional, but a third did not. IMPLICATIONS FOR CANCER SURVIVORS: Health professionals could consistently advise cancer survivors about the increased risks associated with continued smoking, provide them with cessation counseling and medications, refer them to other free cessation resources, and inform them of cessation treatments covered by their health insurance.

      3. Drug overdose deaths among women aged 30-64 years – United States, 1999-2017
        VanHouten JP, Rudd RA, Ballesteros MF, Mack KA.
        MMWR Morb Mortal Wkly Rep. 2019 Jan 11;68(1):1-5.
        The drug epidemic in the United States continues to evolve. The drug overdose death rate has rapidly increased among women (1,2), although within this demographic group, the increase in overdose death risk is not uniform. From 1999 to 2010, the largest percentage changes in the rates of overall drug overdose deaths were among women in the age groups 45-54 years and 55-64 years (1); however, this finding does not take into account trends in specific drugs or consider changes in age group distributions in drug-specific overdose death rates. To target prevention strategies to address the epidemic among women in these age groups, CDC examined overdose death rates among women aged 30-64 years during 1999-2017, overall and by drug subcategories (antidepressants, benzodiazepines, cocaine, heroin, prescription opioids, and synthetic opioids, excluding methadone). Age distribution changes in drug-specific overdose death rates were calculated. Among women aged 30-64 years, the unadjusted drug overdose death rate increased 260%, from 6.7 deaths per 100,000 population (4,314 total drug overdose deaths) in 1999 to 24.3 (18,110) in 2017. The number and rate of deaths involving antidepressants, benzodiazepines, cocaine, heroin, and synthetic opioids each increased during this period. Prescription opioid-related deaths increased between 1999 and 2017 among women aged 30-64 years, with the largest increases among those aged 55-64 years. Interventions to address the rise in drug overdose deaths include implementing the CDC Guideline for Prescribing Opioids for Chronic Pain (3), reviewing records of controlled substance prescribing (e.g., prescription drug monitoring programs, health insurance programs), and developing capacity of drug use disorder treatments and linkage to care, especially for middle-aged women with drug use disorders.

    • Zoonotic and Vectorborne Diseases
      1. Despite high-risk exposures, no evidence of zoonotic transmission during a canine outbreak of leptospirosis
        Guagliardo SA, Iverson SA, Reynolds L, Yaglom H, Venkat H, Galloway R, Levy C, Reindel A, Sylvester T, Kretschmer M, LaFerla Jenni M, Woodward P, Beatty N, Artus A, Klein R, Sunenshine R, Schafer IJ.
        Zoonoses Public Health. 2019 Jan 7.
        Leptospirosis is a bacterial zoonosis that affects many mammals, including humans and dogs; dogs can transmit the bacteria to humans, but the frequency of transmission and highest risk exposures are poorly understood. During 2016-2017, the Maricopa County Department of Public Health, Arizona Department of Health Services and Centers for Disease Control and Prevention investigated the zoonotic potential of a canine leptospirosis outbreak in the Phoenix metro area. We identified symptomatic persons exposed to canine leptospirosis cases by conducting active and passive surveillance. We tested dog owners (n = 9) and animal care providers (n = 109) for serological evidence of Leptospira spp. infection (via the microscopic agglutination test [MAT]) and interviewed these persons about their specific exposures to canine cases and general exposures to canine blood and urine. Through surveillance, seven symptomatic persons were identified; six were tested and all were negative by MAT, and of these six, four persons were negative by PCR (two did not have PCR testing). All serosurvey participants (n = 118) were also seronegative. Among animal care providers, bare skin contact with urine/blood from a canine case was reported by 23.2%; two persons reported dog urine splashing in their face. Veterinary technicians were more likely to have bare skin contact with blood from a canine case compared to veterinarians and boarding facility staff (p < 0.001). Infection control practices were inconsistent; when working with specimens from a canine leptospirosis case, 44.6% of participants reported always wearing gloves when working with urine (i.e., collecting specimens), and 54.5% always wore gloves when working with blood. Veterinary technicians were also most likely to engage in all activities involving potential urine/blood contact, such as conducting laboratory tests (p < 0.01). We therefore recommend that veterinary technicians specifically receive targeted education about infection control practices. Our results suggest that dog-to-human transmission of leptospirosis is uncommon.

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