Volume 10, Issue 12, April 3, 2018

CDC Science Clips: Volume 10, Issue 12, April 3, 2018

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

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

  1. CDC Vital Signs
    • Antibiotic Resistance
      1. *Carbapenem-resistant enterobacteriaceae: A strategic roadmap for infection controlExternal
        Friedman ND, Carmeli Y, Walton AL, Schwaber MJ.
        Infect Control Hosp Epidemiol. 2017 May;38(5):580-594.

        The incidence of carbapenem-resistant Enterobacteriaceae (CRE) has increased worldwide with great regional variability. Infections caused by these organisms are associated with crude mortality rates of up to 70%. The spread of CRE in healthcare settings is both an important medical problem and a major global public health threat. All countries are at risk of falling victim to the emergence of CRE; therefore, a preparedness plan is required to avoid the catastrophic natural course of this epidemic. Proactive and adequate preventive measures locally, regionally, and nationally are required to contain the spread of these bacteria. The keys to success in preventing the establishment of CRE endemicity in a region are early detection through targeted laboratory protocols and containment of spread through comprehensive infection control measures. This guideline provides a strategic roadmap for infection control measures based on the best available evidence and expert opinion, to enable preparation of a multifaceted preparedness plan to abort epidemics of CRE. Infect Control Hosp Epidemiol 2017;38:580-594.

      2. *The problem of carbapenemase-producing-carbapenem-resistant-Enterobacteriaceae detectionExternal
        Lutgring JD, Limbago BM.
        J Clin Microbiol. 2016 Mar;54(3):529-34.

        The emergence and spread of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are a significant clinical and public health concern. Reliable detection of CP-CRE is the first step in combating this problem. There are both phenotypic and molecular methods available for CP-CRE detection. There is no single detection method that is ideal for all situations.

      3. Guidance for control of infections with carbapenem-resistant or carbapenemase-producing Enterobacteriaceae in acute care facilitiesExternal
        Centers for Disease Control and Prevention .
        MMWR Morb Mortal Wkly Rep. 2009 Mar 20;58(10):256-60.

        Infection with carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae is emerging as an important challenge in health-care settings. Currently, carbapenem-resistant Klebsiella pneumoniae (CRKP) is the species of CRE most commonly encountered in the United States. CRKP is resistant to almost all available antimicrobial agents, and infections with CRKP have been associated with high rates of morbidity and mortality, particularly among persons with prolonged hospitalization and those who are critically ill and exposed to invasive devices (e.g., ventilators or central venous catheters). This report provides updated recommendations from CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC) for the control of CRE or carbapenemase-producing Enterobacteriaceae in acute care (inpatient) facilities. For all acute care facilities, CDC and HICPAC recommend an aggressive infection control strategy, including managing all patients with CRE using contact precautions and implementing Clinical and Laboratory Standards Institute (CLSI) guidelines for detection of carbapenemase production. In areas where CRE are not endemic, acute care facilities should 1) review microbiology records for the preceding 6-12 months to determine whether CRE have been recovered at the facility, 2) if the review finds previously unrecognized CRE, perform a point prevalence culture survey in high-risk units to look for other cases of CRE, and 3) perform active surveillance cultures of patients with epidemiologic links to persons from whom CRE have been recovered. In areas where CRE are endemic, an increased likelihood exists for imporation of CRE, and facilities should consider additional strategies to reduce rates of CRE. Acute care facilities should review these recommendations and implement appropriate strategies to limit the spread of these pathogens.

      4. Vital Signs: carbapenem-resistant EnterobacteriaceaeExternal
        Centers for Disease Control and Prevention .
        MMWR Morb Mortal Wkly Rep. 2013 Mar 8;62(9):165-70.

        BACKGROUND: Enterobacteriaceae are a family of bacteria that commonly cause infections in health-care settings as well as in the community. Among Enterobacteriaceae, resistance to broad-spectrum carbapenem antimicrobials has been uncommon. Over the past decade, however, carbapenem-resistant Enterobacteriaceae (CRE) have been recognized in health-care settings as a cause of difficult-to-treat infections associated with high mortality. METHODS: The percentage of acute-care hospitals reporting at least one CRE from health-care-associated infections (HAIs) in 2012 was estimated using data submitted to the National Healthcare Safety Network (NHSN) in 2012. The proportion of Enterobacteriaceae infections that were CRE was calculated using two surveillance systems: 1) the National Nosocomial Infection Surveillance system (NNIS) and NHSN (for 2001 and 2011, respectively) and 2) the Surveillance Network-USA (TSN) (for 2001 and 2010). Characteristics of CRE culture-positive episodes were determined using data collected as part of a population-based CRE surveillance project conducted by the Emerging Infections Program (EIP) in three states. RESULTS: In 2012, 4.6% of acute-care hospitals reported at least one CRE HAI (short-stay hospitals, 3.9%; long-term acute-care hospitals, 17.8%). The proportion of Enterobacteriaceae that were CRE increased from 1.2% in 2001 to 4.2% in 2011 in NNIS/NHSN and from 0% in 2001 to 1.4% in 2010 in TSN; most of the increase was observed in Klebsiella species (from 1.6% to 10.4% in NNIS/NHSN). In the EIP surveillance, 92% of CRE episodes occurred in patients with substantial health-care exposures. CONCLUSIONS: Carbapenem resistance among common Enterobacteriaceae has increased over the past decade; most CRE are associated with health-care exposures. IMPLICATIONS FOR PUBLIC HEALTH: Interventions exist that could slow the dissemination of CRE. Health departments are well positioned to play a leading role in prevention efforts by assisting with surveillance, situational awareness, and coordinating prevention efforts.

      5. Broad-spectrum, transmissible beta-lactamasesExternal
        Jacoby GA, Medeiros AA, O’Brien TF, Pinto ME, Jiang H.
        N Engl J Med. 1988 Sep 15;319(11):723-4.

        [No abstract]

      6. Evolution of antimicrobial resistance among Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae in Brooklyn, NYExternal
        Landman D, Bratu S, Kochar S, Panwar M, Trehan M, Doymaz M, Quale J.
        J Antimicrob Chemother. 2007 Jul;60(1):78-82.

        OBJECTIVES: To document resistance patterns of three important nosocomial pathogens, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae, present in hospitals in Brooklyn, NY. METHODS: Susceptibility profiles of pathogens gathered during a surveillance study in 2006 were analysed and compared with similar surveys performed in 1999 and 2001. MICs were determined according to CLSI standards, and selected isolates were screened by PCR for the presence of VIM, IMP and KPC beta-lactamases. RESULTS: For P. aeruginosa, susceptibility to most antimicrobials fell in 2001 and then reached a plateau. However, there was a progressive decrease in the number of patients with P. aeruginosa during the three surveys. While the total number of isolates of A. baumannii remained steady, there was a progressive decrease in susceptibility to most classes of antimicrobial agents, and approximately one-third had combined resistance to carbapenems, fluoroquinolones and aminoglycosides. There was a noticeable rise in the number of isolates of K. pneumoniae over the surveillance periods, suggesting that this has become the predominant pathogen in many medical centres. Over one-third of K. pneumoniae collected in 2006 carried the carbapenemase KPC, and 22% were resistant to all three classes of antimicrobial agents. CONCLUSIONS: Hospitals in our region have been beset with antimicrobial-resistant Gram-negative bacteria. K. pneumoniae has rapidly emerged as the most common multidrug-resistant pathogen. Improved therapeutic agents and methods of detection are needed to reduce transmission of these bacteria.

      7. In 2007, the Israel Ministry of Health initiated a nationwide intervention aimed at containing the spread of carbapenem-resistant Enterobacteriaceae (CRE), primarily manifested by the rapid dissemination of a single clone of Klebsiella pneumoniae. Data were gathered from acute and long-term care facilities, and ward-based mandatory guidelines for carrier isolation, patient and staff cohorting, and active surveillance were issued. Guidelines were issued to the microbiology laboratories delineating procedures for identifying CRE and carbapenemase production. A protocol for ruling out continued carriage in known carriers was established. Compliance with national guidelines was overseen via site visits at healthcare facilities, routine reporting of carrier census and isolation status, and the establishment of a network of communications to facilitate reporting on identified carriage, contact tracing and screening, and outbreak investigations. During the intervention, nosocomial CRE acquisition in acute care declined from a monthly high of 55.5 to an annual low of 4.8 cases per 100,000 patient-days (P < .001).

      8. Identical plasmid AmpC beta-lactamase genes and plasmid types in E. coli isolates from patients and poultry meat in the NetherlandsExternal
        Voets GM, Fluit AC, Scharringa J, Schapendonk C, van den Munckhof T, Leverstein-van Hall MA, Stuart JC.
        Int J Food Microbiol. 2013 Nov 1;167(3):359-62.

        The increasing prevalence of third-generation cephalosporin-resistant Enterobacteriaceae is a worldwide problem. Recent studies showed that poultry meat and humans share identical Extended-Spectrum Beta-Lactamase genes, plasmid types, and Escherichia coli strain types, suggesting that transmission from poultry meat to humans may occur. The aim of this study was to compare plasmid-encoded Ambler class C beta-lactamase (pAmpC) genes, their plasmids, and bacterial strain types between E. coli isolates from retail chicken meat and clinical isolates in the Netherlands. In total, 98 Dutch retail chicken meat samples and 479 third-generation cephalosporin non-susceptible human clinical E. coli isolates from the same period were screened for pAmpC production. Plasmid typing was performed using PCR-based replicon typing (PBRT). E coli strains were compared using Multi-Locus-Sequence-Typing (MLST). In 12 of 98 chicken meat samples (12%), pAmpC producing E. coli were detected (all blaCMY-2). Of the 479 human E. coli, 25 (5.2%) harboured pAmpC genes (blaCMY-2 n = 22, blaACT n = 2, blaMIR n = 1). PBRT showed that 91% of poultry meat isolates harboured blaCMY-2 on an IncK plasmid, and 9% on an IncI1 plasmid. Of the human blaCMY-2 producing isolates, 42% also harboured blaCMY-2 on an IncK plasmid, and 47% on an IncI1 plasmid. Thus, 68% of human pAmpC producing E. coli have the same AmpC gene (blaCMY-2) and plasmid type (IncI1 or IncK) as found in poultry meat. MLST showed one cluster containing one human isolate and three meat isolates, with an IncK plasmid. These findings imply that a foodborne transmission route of blaCMY-2 harbouring plasmids cannot be excluded and that further evaluation is required.

      9. Vital Signs: Preventing antibiotic-resistant infections in hospitals – United States, 2014External
        Weiner LM, Fridkin SK, Aponte-Torres Z, Avery L, Coffin N, Dudeck MA, Edwards JR, Jernigan JA, Konnor R, Soe MM, Peterson K, McDonald LC.
        MMWR Morb Mortal Wkly Rep. 2016 Mar 11;65(9):235-41.

        BACKGROUND: Health care-associated antibiotic-resistant (AR) infections increase patient morbidity and mortality and might be impossible to successfully treat with any antibiotic. CDC assessed health care-associated infections (HAI), including Clostridium difficile infections (CDI), and the role of six AR bacteria of highest concern nationwide in several types of health care facilities. METHODS: During 2014, approximately 4,000 short-term acute care hospitals, 501 long-term acute care hospitals, and 1,135 inpatient rehabilitation facilities in all 50 states reported data on specific infections to the National Healthcare Safety Network. National standardized infection ratios and their percentage reduction from a baseline year for each HAI type, by facility type, were calculated. The proportions of AR pathogens and HAIs caused by any of six resistant bacteria highlighted by CDC in 2013 as urgent or serious threats were determined. RESULTS: In 2014, the reductions in incidence in short-term acute care hospitals and long-term acute care hospitals were 50% and 9%, respectively, for central line-associated bloodstream infection; 0% (short-term acute care hospitals), 11% (long-term acute care hospitals), and 14% (inpatient rehabilitation facilities) for catheter-associated urinary tract infection; 17% (short-term acute care hospitals) for surgical site infection, and 8% (short-term acute care hospitals) for CDI. Combining HAIs other than CDI across all settings, 47.9% of Staphylococcus aureus isolates were methicillin resistant, 29.5% of enterococci were vancomycin-resistant, 17.8% of Enterobacteriaceae were extended-spectrum beta-lactamase phenotype, 3.6% of Enterobacteriaceae were carbapenem resistant, 15.9% of Pseudomonas aeruginosa isolates were multidrug resistant, and 52.6% of Acinetobacter species were multidrug resistant. The likelihood of HAIs caused by any of the six resistant bacteria ranged from 12% in inpatient rehabilitation facilities to 29% in long-term acute care hospitals. CONCLUSIONS: Although there has been considerable progress in preventing some HAIs, many remaining infections could be prevented with implementation of existing recommended practices. Depending upon the setting, more than one in four of HAIs excluding CDI are caused by AR bacteria. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Physicians, nurses, and health care leaders need to consistently and comprehensively follow all recommendations to prevent catheter- and procedure-related infections and reduce the impact of AR bacteria through antimicrobial stewardship and measures to prevent spread.

      10. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniaeExternal
        Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, Alberti S, Bush K, Tenover FC.
        Antimicrob Agents Chemother. 2001 Apr;45(4):1151-61.

        A Klebsiella pneumoniae isolate showing moderate to high-level imipenem and meropenem resistance was investigated. The MICs of both drugs were 16 microg/ml. The beta-lactamase activity against imipenem and meropenem was inhibited in the presence of clavulanic acid. The strain was also resistant to extended-spectrum cephalosporins and aztreonam. Isoelectric focusing studies demonstrated three beta-lactamases, with pIs of 7.2 (SHV-29), 6.7 (KPC-1), and 5.4 (TEM-1). The presence of bla(SHV) and bla(TEM) genes was confirmed by specific PCRs and DNA sequence analysis. Transformation and conjugation studies with Escherichia coli showed that the beta-lactamase with a pI of 6.7, KPC-1 (K. pneumoniae carbapenemase-1), was encoded on an approximately 50-kb nonconjugative plasmid. The gene, bla(KPC-1), was cloned in E. coli and shown to confer resistance to imipenem, meropenem, extended-spectrum cephalosporins, and aztreonam. The amino acid sequence of the novel carbapenem-hydrolyzing beta-lactamase, KPC-1, showed 45% identity to the pI 9.7 carbapenem-hydrolyzing beta-lactamase, Sme-1, from Serratia marcescens S6. Hydrolysis studies showed that purified KPC-1 hydrolyzed not only carbapenems but also penicillins, cephalosporins, and monobactams. KPC-1 had the highest affinity for meropenem. The kinetic studies also revealed that clavulanic acid and tazobactam inhibited KPC-1. An examination of the outer membrane proteins of the parent K. pneumoniae strain demonstrated that the strain does not express detectable levels of OmpK35 and OmpK37, although OmpK36 is present. We concluded that carbapenem resistance in K. pneumoniae strain 1534 is mainly due to production of a novel Bush group 2f, class A, carbapenem-hydrolyzing beta-lactamase, KPC-1, although alterations in porin expression may also play a role.

  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. Prevalence and causes of vision loss in high-income countries and in Eastern and Central Europe in 2015: magnitude, temporal trends and projectionsExternal
        Bourne RR, Jonas JB, Bron AM, Cicinelli MV, Das A, Flaxman SR, Friedman DS, Keeffe JE, Kempen JH, Leasher J, Limburg H, Naidoo K, Pesudovs K, Peto T, Saadine J, Silvester AJ, Tahhan N, Taylor HR, Varma R, Wong TY, Resnikoff S.
        Br J Ophthalmol. 2018 Mar 15.

        BACKGROUND: Within a surveillance of the prevalence and causes of vision impairment in high-income regions and Central/Eastern Europe, we update figures through 2015 and forecast expected values in 2020. METHODS: Based on a systematic review of medical literature, prevalence of blindness, moderate and severe vision impairment (MSVI), mild vision impairment and presbyopia was estimated for 1990, 2010, 2015, and 2020. RESULTS: Age-standardised prevalence of blindness and MSVI for all ages decreased from 1990 to 2015 from 0.26% (0.10-0.46) to 0.15% (0.06-0.26) and from 1.74% (0.76-2.94) to 1.27% (0.55-2.17), respectively. In 2015, the number of individuals affected by blindness, MSVI and mild vision impairment ranged from 70 000, 630 000 and 610 000, respectively, in Australasia to 980 000, 7.46 million and 7.25 million, respectively, in North America and 1.16 million, 9.61 million and 9.47 million, respectively, in Western Europe. In 2015, cataract was the most common cause for blindness, followed by age-related macular degeneration (AMD), glaucoma, uncorrected refractive error, diabetic retinopathy and cornea-related disorders, with declining burden from cataract and AMD over time. Uncorrected refractive error was the leading cause of MSVI. CONCLUSIONS: While continuing to advance control of cataract and AMD as the leading causes of blindness remains a high priority, overcoming barriers to uptake of refractive error services would address approximately half of the MSVI burden. New data on burden of presbyopia identify this entity as an important public health problem in this population. Additional research on better treatments, better implementation with existing tools and ongoing surveillance of the problem is needed.

      2. The Childhood Obesity Declines Project: A review of enacted policiesExternal
        Dooyema C, Jernigan J, Warnock AL, Dawkins-Lyn N, Harris C, Kauh T, Kettel Khan L, Ottley P, Young-Hyman D.
        Child Obes. 2018 Mar;14(S1):S22-s31.

        BACKGROUND: State- and local-level policies can influence children’s diet quality and physical activity (PA) behaviors. The goal of this article is to understand the enacted state and local policy landscape in four communities reporting declines in childhood obesity. METHODS AND RESULTS: State-level policies were searched within the CDC’s online Chronic Disease State Policy Tracking System. Local level policies were captured during key informant interviews in each of the sites. Policies were coded by setting [i.e., early care and education (ECE) also known as child care, school, community], jurisdictional level (i.e., state or local) and policy type (i.e., legislation or regulation). The time period for each site was unique, capturing enacted policies 5 years before the reported declines in childhood obesity in each of the communities. A total of 39 policies were captured across the 4 sites. The majority originated at the state level. Two policies pertaining to ECE, documented during key informant interviews, were found to be adopted at the local level. CONCLUSION: Similarities were noted between the four communities in the types of polices enacted. All four communities had state- and/or local-level policies that aimed to improve the nutrition environment and increase opportunities for PA in both the ECE and K-12 school settings. This article is a step in the process of determining what may have contributed to obesity declines in the selected communities.

      3. Impact of intensive lifestyle intervention on disability-free life expectancy: The Look AHEAD StudyExternal
        Gregg EW, Lin J, Bardenheier B, Chen H, Rejeski WJ, Zhuo X, Hergenroeder AL, Kritchevsky SB, Peters AL, Wagenknecht LE, Ip EH, Espeland MA.
        Diabetes Care. 2018 Mar 15.

        OBJECTIVE: The impact of weight loss intervention on disability-free life expectancy in adults with diabetes is unknown. We examined the impact of a long-term weight loss intervention on years spent with and without physical disability. RESEARCH DESIGN AND METHODS: Overweight or obese adults with type 2 diabetes age 45-76 years (n = 5,145) were randomly assigned to a 10-year intensive lifestyle intervention (ILI) or diabetes support and education (DSE). Physical function was assessed annually for 12 years using the SF-36. Annual incidence of physical disability, mortality, and disability remission were incorporated into a Markov model to quantify years of life spent active and physically disabled. RESULTS: Physical disability incidence was lower in the ILI group (6.0% per year) than in the DSE group (6.8% per year) (incidence rate ratio 0.88 [95% CI 0.81-0.96]), whereas rates of disability remission and mortality did not differ between groups. ILI participants had a significant delay in moderate or severe disability onset and an increase in number of nondisabled years (P < 0.05) compared with DSE participants. For a 60-year-old, this effect translates to 0.9 more disability-free years (12.0 years [95% CI 11.5-12.4] vs. 11.1 years [95% CI 10.6-11.7]) but no difference in total years of life. In stratified analyses, ILI increased disability-free years of life in women and participants without cardiovascular disease (CVD) but not in men or participants with CVD. CONCLUSIONS: Long-term lifestyle interventions among overweight or obese adults with type 2 diabetes may reduce long-term disability, leading to an effect on disability-free life expectancy but not on total life expectancy.

      4. Childhood Obesity Declines Project: Highlights of community strategies and policiesExternal
        Jernigan J, Kettel Khan L, Dooyema C, Ottley P, Harris C, Dawkins-Lyn N, Kauh T, Young-Hyman D.
        Child Obes. 2018 Mar;14(S1):S32-s39.

        BACKGROUND: The social ecological model (SEM) is a framework for understanding the interactive effects of personal and environmental factors that determine behavior. The SEM has been used to examine childhood obesity interventions and identify factors at each level that impact behaviors. However, little is known about how those factors interact both within and across levels of the SEM. METHODS: The Childhood Obesity Declines (COBD) project was exploratory, attempting to capture retrospectively policies and programs that occurred in four communities that reported small declines in childhood obesity. It also examined contextual factors that may have influenced initiatives, programs, or policies. Data collection included policy and program assessments, key informant interviews, and document reviews. These data were aggregated by the COBD project team to form a site report for each community (available at www.nccor.org/projects/obesity-declines ). These reports were used to develop site summaries that illustrate how policies, programs, and activities worked to address childhood obesity in each study site. RESULTS/CONCLUSIONS: Site summaries for Anchorage, AK; Granville County, NC; Philadelphia, PA; and New York City, NY, describe those policies and programs implemented across the levels of the SEM to address childhood obesity and examine interactions both across and within levels of the model to better understand what factors appear important for implementation success.

      5. Childhood Obesity Declines Project: An effort of the National Collaborative on Childhood Obesity Research to explore progress in four communitiesExternal
        Kauh TJ, Dawkins-Lyn N, Dooyema C, Harris C, Jernigan J, Kettel Khan L, Ottley P, Young-Hyman D.
        Child Obes. 2018 Mar;14(S1):S1-s4.

        BACKGROUND: Recent findings show that national childhood obesity prevalence overall is improving among some age groups, but that disparities continue to persist, particularly among populations that have historically been at higher risk of obesity and overweight. Over the past several years, many jurisdictions at the city or county level across the nation have also reported declines. Little evaluation has focused on understanding the factors that influence the implementation of efforts to reduce childhood obesity rates. This article summarizes the rationale, aims, and overall design of the Childhood Obesity Declines Project (COBD), which was the first of its kind to systematically study and document the what, how, when, and where of community-based obesity strategies in four distinct communities across the nation. METHODS: COBD was initiated by the National Collaborative on Childhood Obesity Research (NCCOR), was led by a subset of NCCOR advisors and a research team at ICF, and was guided by external advisors made up of researchers, decision makers, and other key stakeholders. The research team used an adapted version of the Systematic Screening and Assessment method to review and collect retrospective implementation data in four communities. RESULTS: COBD found that sites implemented strategies across the many levels and environments that impact children’s well being (akin to the social-ecological framework), building a Culture of Health in their communities. CONCLUSIONS: COBD demonstrates how collaboratives of major funders with the support of other experts and key stakeholders, can help to accelerate progress in identifying and disseminating strategies that promote healthy eating and physical activity.

      6. Childhood Obesity Declines Project: A different methodologyExternal
        Kettel Khan L, Ottley P, Harris C, Dawkins-Lyn N, Dooyema C, Jernigan J, Kauh T, Young-Hyman D.
        Child Obes. 2018 Mar;14(S1):S5-s11.

        BACKGROUND: The evidence for and our understanding of community-level strategies such as policies, system, and environmental changes that support healthy eating and active living is growing. However, researchers and evaluation scientists alike are still not confident in what to recommend for preventing or sustaining declines in the prevalence of obesity. METHODS: The Systematic Screening and Assessment (SSA) methodology was adapted as a retrospective process to confirm obesity declines and to better understand what and how policies and programs or interventions may contribute as drivers. The Childhood Obesity Declines (COBD) project’s adaptation of the SSA methodology consisted of the following components: (1) establishing and convening an external expert advisory panel; (2) identification and selection of sites reporting obesity declines; (3) confirmation and review of what strategies occurred and contextual factors were present during the period of the obesity decline; and (4) reporting the findings to sites and the field. RESULTS/DISCUSSION: The primary result of the COBD project is an in-depth examination of the question, “What happened and how did it happen in communities where the prevalence of obesity declined?” The primary aim of this article is to describe the project’s methodology and present its limitations and strengths. CONCLUSIONS: Exploration of the natural experiments such that occurred in Anchorage, Granville County, New York City, and Philadelphia is the beginning of our understanding of the drivers and contextual factors that may affect childhood obesity. This retrospective examination allows us to: (1) describe targeted interventions; (2) examine the timeline and summarize intervention implementation; (3) document national, state, local, and institutional policies; and (4) examine the influence of the reach and potential multisector layering of interventions.

      7. Objectives: To assess the association between sleep duration and health-related quality of life (HRQOL) among adults with or without chronic conditions. Methods: Using the 2014 Behavioral Risk Factor Surveillance System, we analyzed self-reported data from adult respondents aged >/=18 years with (n = 277,757, unhealthy group) and without (n = 172,052. healthy group) reported history of any of nine chronic conditions (coronary heart disease, stroke, cancer, chronic obstructive pulmonary disease, diabetes, asthma, arthritis, depression, chronic kidney disease). Multivariable logistic regressions were separately constructed to assess the associations between sleep duration and four self-reported HRQOL measures after adjustment for sociodemographics, leisure-time physical activity, body mass index, and smoking status among unhealthy and healthy adults. Results: The prevalence of poor/fair health, frequent physical distress, frequent mental distress, frequent activity limitation, and short sleep duration was 27.9%, 19.3%, 17.0%, 13.6%, and 38.3% in the unhealthy group and 6.9%, 4.0%, 5.3%, 2.1%, and 31.0% in the healthy group, respectively. U-shaped relationships of sleep duration to all four HRQOL indicators were observed among the unhealthy group and to poor/fair health, frequent mental distress, and frequent activity limitation among the healthy group. The relationships further varied by sex, age, race/ethnicity, and BMI category among the healthy group. Conclusions: Relationships between extreme sleep duration and HRQOLs were observed among both healthy and unhealthy groups. These results can help inform public awareness campaigns and physician-counseling regarding the importance of sleep for mental health and well-being.

      8. Objectives The objective of this study is to investigate differences in the diagnosis and management of systemic lupus erythematosus (SLE) by primary care and specialist physicians in a population-based registry. Methods This study includes individuals from the 2009 Indian Health Service lupus registry population with a diagnosis of SLE documented by either a primary care provider or specialist. SLE classification criteria, laboratory testing, and medication use at any time during the course of disease were determined by medical record abstraction. Results Of the 320 individuals with a diagnosis of SLE, 249 had the diagnosis documented by a specialist, with 71 documented by primary care. Individuals with a specialist diagnosis of SLE were more likely to have medical record documentation of meeting criteria for SLE by all criteria sets (American College of Rheumatology, 79% vs 22%; Boston Weighted, 82% vs 32%; and Systemic Lupus International Collaborating Clinics, 83% vs 35%; p < 0.001 for all comparisons). In addition, specialist diagnosis was associated with documentation of ever having been tested for anti-double-stranded DNA antibody and complement 3 and complement 4 ( p < 0.001). Documentation of ever receiving hydroxychloroquine was also more common with specialist diagnosis (86% vs 64%, p < 0.001). Conclusions Within the population studied, specialist diagnosis of SLE was associated with a higher likelihood of having SLE classification criteria documented, being tested for biomarkers of disease, and ever receiving treatment with hydroxychloroquine. These data support efforts both to increase specialist access for patients with suspected SLE and to provide lupus education to primary care providers.

      9. Design and analysis of group-randomized trials in cancer: A review of current practicesExternal
        Murray DM, Pals SL, George SM, Kuzmichev A, Lai GY, Lee JA, Myles RL, Nelson SM.
        Prev Med. 2018 Mar 15.

        The purpose of this paper is to summarize current practices for the design and analysis of group-randomized trials involving cancer-related risk factors or outcomes and to offer recommendations to improve future trials. We searched for group-randomized trials involving cancer-related risk factors or outcomes that were published or online in peer-reviewed journals in 2011-15. During 2016-17, in Bethesda MD, we reviewed 123 articles from 76 journals to characterize their design and their methods for sample size estimation and data analysis. Only 66 (53.7%) of the articles reported appropriate methods for sample size estimation. Only 63 (51.2%) reported exclusively appropriate methods for analysis. These findings suggest that many investigators do not adequately attend to the methodological challenges inherent in group-randomized trials. These practices can lead to underpowered studies, to an inflated type 1 error rate, and to inferences that mislead readers. Investigators should work with biostatisticians or other methodologists familiar with these issues. Funders and editors should ensure careful methodological review of applications and manuscripts. Reviewers should ensure that studies are properly planned and analyzed. These steps are needed to improve the rigor and reproducibility of group-randomized trials. The Office of Disease Prevention (ODP) at the National Institutes of Health (NIH) has taken several steps to address these issues. ODP offers an online course on the design and analysis of group-randomized trials. ODP is working to increase the number of methodologists who serve on grant review panels. ODP has developed standard language for the Application Guide and the Review Criteria to draw investigators’ attention to these issues. Finally, ODP has created a new Research Methods Resources website to help investigators, reviewers, and NIH staff better understand these issues.

      10. Childhood Obesity Declines Project: An exploratory study of strategies identified in communities reporting declinesExternal
        Ottley PG, Dawkins-Lyn N, Harris C, Dooyema C, Jernigan J, Kauh T, Kettel Khan L, Young-Hyman D.
        Child Obes. 2018 Mar;14(S1):S12-s21.

        BACKGROUND: Although childhood obesity rates have been high in the last few decades, recent national reports indicate a stabilization of rates among some subpopulations of children. This study examines the implementation of initiatives, policies, and programs (referred to as strategies) in four communities that experienced declines in childhood obesity between 2003 and 2012. METHODS AND RESULTS: The Childhood Obesity Decline project verified obesity declines and identified strategies that may have influenced and supported the decline in obesity. The project used an adaptation of the Systematic Screening and Assessment method to identify key informants in each site. Four settings were highlighted related to childhood: (1) communities, (2) schools, (3) early care and education, and (4) healthcare. The findings indicate that programs and policies were implemented across local settings (primarily in schools and early childhood settings) and at the state level, during a timeframe of supportive federal policies and initiatives. CONCLUSIONS: Multilevel approaches were aimed to improve the nutrition and physical activity environments where children spend most of their time. We hypothesized that other, more distal strategies amplified and reinforced the impact of the efforts that more directly targeted children. The simultaneous public health messaging and multilayered initiatives, supported by cross-sector partnerships and active, high-level champions, were identified as likely important contributors to success in attaining declines in rates of childhood obesity.

      11. The Childhood Obesity Declines Project: Implications for research and evaluation approachesExternal
        Young-Hyman D, Morris K, Kettel Khan L, Dawkins-Lyn N, Dooyema C, Harris C, Jernigan J, Ottley P, Kauh T.
        Child Obes. 2018 Mar;14(S1):S40-s44.

        BACKGROUND: Childhood obesity remains prevalent and is increasing in some disadvantaged populations. Numerous research, policy and community initiatives are undertaken to impact this pandemic. Understudied are natural experiments. The need to learn from these efforts is paramount. Resulting evidence may not be readily available to inform future research, community initiatives, and policy development/implementation. METHODS: We discuss the implications of using an adaptation of the Systematic Screening and Assessment (SSA) method to evaluate the Childhood Obesity Declines (COBD) project. The project examined successful initiatives, programs and policies in four diverse communities which were concurrent with significant declines in child obesity. In the context of other research designs and evaluation schemas, rationale for use of SSA is presented. Evidence generated by this method is highlighted and guidance suggested for evaluation of future studies of community-based childhood obesity prevention initiatives. Support for the role of stakeholder collaboratives, in particular the National Collaborative on Childhood Obesity Research, as a synergistic vehicle to accelerate research on childhood obesity is discussed. RESULTS/DISCUSSION: SSA mapped active processes and provided contextual understanding of multi-level/component simultaneous efforts to reduce rates of childhood obesity in community settings. Initiatives, programs and policies were not necessarily coordinated. And although direct attribution of intervention/initiative/policy components could not be made, the what, by who, how, to whom was temporally associated with statistically significant reductions in childhood obesity. CONCLUSIONS: SSA provides evidence for context and processes which are not often evaluated in other data analytic methods. SSA provides an additional tool to layer with other evaluation approaches.

    • Communicable Diseases
      1. Community-based mass treatment with azithromycin for the elimination of yaws in Ghana – Results of a pilot studyExternal
        Abdulai AA, Agana-Nsiire P, Biney F, Kwakye-Maclean C, Kyei-Faried S, Amponsa-Achiano K, Simpson SV, Bonsu G, Ohene SA, Ampofo WK, Adu-Sarkodie Y, Addo KK, Chi KH, Danavall D, Chen CY, Pillay A, Sanz S, Tun Y, Mitja O, Asiedu KB, Ballard RC.
        PLoS Negl Trop Dis. 2018 Mar;12(3):e0006303.

        INTRODUCTION: The WHO yaws eradication strategy consists of one round of total community treatment (TCT) of single-dose azithromycin with coverage of > 90%.The efficacy of the strategy to reduce the levels on infection has been demonstrated previously in isolated island communities in the Pacific region. We aimed to determine the efficacy of a single round of TCT with azithromycin to achieve a decrease in yaws prevalence in communities that are endemic for yaws and surrounded by other yaws-endemic areas. METHODS: Surveys for yaws seroprevalence and prevalence of skin lesions were conducted among schoolchildren aged 5-15 years before and one year after the TCT intervention in the Abamkrom sub-district of Ghana. We used a cluster design with the schools as the primary sampling unit. Among 20 eligible primary schools in the sub district, 10 were assigned to the baseline survey and 10 to the post-TCT survey. The field teams conducted a physical examination for skin lesions and a dual point-of-care immunoassay for non-treponemal and treponemal antibodies of all children present at the time of the visit. We also undertook surveys with non-probabilistic sampling to collect lesion swabs for etiology and macrolide resistance assessment. RESULTS: At baseline 14,548 (89%) of 16,287 population in the sub-district received treatment during TCT. Following one round of TCT, the prevalence of dual seropositivity among all children decreased from 10.9% (103/943) pre-TCT to 2.2% (27/1211) post-TCT (OR 0.19; 95%CI 0.09-0.37). The prevalence of serologically confirmed skin lesions consistent with active yaws was reduced from 5.7% (54/943) pre-TCT to 0.6% (7/1211) post-TCT (OR 0.10; 95% CI 0.25-0.35). No evidence of resistance to macrolides against Treponema pallidum subsp. pertenue was seen. DISCUSSION: A single round of high coverage TCT with azithromycin in a yaws affected sub-district adjoining other endemic areas is effective in reducing the prevalence of seropositive children and the prevalence of early skin lesions consistent with yaws one year following the intervention. These results suggest that national yaws eradication programmes may plan the gradual expansion of mass treatment interventions without high short-term risk of reintroduction of infection from contiguous untreated endemic areas.

      2. [No abstract]

      3. High human immunodeficiency virus incidence and prevalence and associated factors among adolescent sexual minority males – 3 cities, 2015External
        Balaji AB, An Q, Smith JC, Newcomb ME, Mustanski B, Prachand NG, Brady KA, Braunstein S, Paz-Bailey G.
        Clin Infect Dis. 2018 Mar 5;66(6):936-944.

        Background: Much has been written about the impact of human immunodeficiency virus (HIV) among young (13-24) sexual minority men (SMM). Evidence for concern is substantial for emerging adult (18-24 years) SMM. Data documenting the burden and associated risk factors of HIV among adolescent SMM (<18 years) remain limited. Methods: Adolescent SMM aged 13-18 years were recruited in 3 cities (Chicago, New York City, and Philadelphia) for interview and HIV testing. We used chi2 tests for percentages of binary variables and 1-way analysis of variance for means of continuous variables to assess differences by race/ethnicity in behaviors. We calculated estimated annual HIV incidence density (number of HIV infections per 100 person-years [PY] at risk). We computed Fisher’s exact tests to determine differences in HIV prevalence by selected characteristics. Results: Of 415 sexually active adolescent SMM with a valid HIV test result, 25 (6%) had a positive test. Estimated annual HIV incidence density was 3.4/100 PY; incidence density was highest for blacks, followed by Hispanics, then whites (4.1, 3.2, and 1.1/100 PY, respectively). Factors associated with higher HIV prevalence included black race; >/=4 male partners, condomless anal sex, and exchange sex in the past 12 months; and a recent partner who was older, black, HIV-infected, or had ever been in jail or prison (P < .05). Conclusions: HIV-related risk behaviors, prevalence, and estimated incidence density for adolescent SMM were high, especially for minority SMM. Our findings suggest that initiating intervention efforts early may be helpful in combating these trends.

      4. Evaluating a framework for tuberculosis screening among healthcare workers in clinical settings, Inner Mongolia, ChinaExternal
        Cheng S, Tollefson D, He G, Li Y, Guo H, Chai S, Gao F, Gao F, Han G, Ren L, Ren Y, Li J, Wang L, Varma JK, Hu D, Fan H, Zhao F, Bloss E, Wang Y, Rao CY.
        J Occup Med Toxicol. 2018 ;13:11.

        Background: Health care workers are at high risk for tuberculosis (TB). China, a high burden TB country, has no policy on medical surveillance for TB among healthcare workers. In this paper, we evaluate whether China’s national TB diagnostic guidelines could be used as a framework to screen healthcare workers for pulmonary TB disease in a clinical setting in China. Methods: Between April-August 2010, healthcare workers from 28 facilities in Inner Mongolia Autonomous Region, China were eligible for TB screening, comprised of symptom check, chest X-ray and tuberculin skin testing. Healthcare workers were categorized as having presumptive, confirmed, or clinically-diagnosed pulmonary TB, using Chinese national guidelines. Results: All healthcare workers (N=4347) were eligible for TB screening, of which 4285 (99%) participated in at least one TB screening test. Of the healthcare workers screened, 2% had cough for >/= 14 days, 3% had a chest X-ray consistent with TB, and 10% had a tuberculin skin test induration >/= 20 mm. Of these, 124 healthcare workers were identified with presumptive TB (i.e., cough for >/= 14 days in the past 4 weeks or x-ray consistent with TB). Twelve healthcare workers met the case definition for clinically-diagnosed pulmonary TB, but none were diagnosed with TB during the study period. Conclusion: A substantial proportion of healthcare workers in Inner Mongolia had signs, symptoms, or test results suggestive of TB disease that could have been identified using national TB diagnostic guidelines as a screening framework. However, achieving medical surveillance in China will require a framework that increases the ease, accuracy, and acceptance of TB screening in the medical community. Routine screening with improved diagnostics should be considered to detect tuberculosis disease among healthcare workers and reduce transmission in health care settings in China.

      5. No evidence of Mycobacterium tuberculosis in breast milk of 18 women with confirmed TB disease in Kisumu, KenyaExternal
        Click ES, Ouma GS, DeGruy K, Murithi W, Okonji JA, McCarthy KD, Musau S, Okumu A, Alexander H, Posey J, Cain KP.
        Int J Tuberc Lung Dis. 2018 Apr 1;22(4):464-465.

        [No abstract]

      6. Notes from the Field: Typhoid fever outbreak – Harare, Zimbabwe, October 2016-March 2017External
        Davis WW, Chonzi P, Masunda KP, Shields LM, Mukeredzi I, Manangazira P, Govore E, Aubert RD, Martin H, Gonese E, Ochieng JB, Juma B, Ali H, Allen K, Barr BA, Mintz E, Appiah GD.
        MMWR Morb Mortal Wkly Rep. 2018 Mar 23;67(11):342-343.

        [No abstract]

      7. Measles outbreak response decision-making under uncertainty: a retrospective analysisExternal
        Fonnesbeck CJ, Shea K, Carran S, Cassio de Moraes J, Gregory C, Goodson JL, Ferrari MJ.
        J R Soc Interface. 2018 Mar;15(140).

        Resurgent outbreaks of vaccine-preventable diseases that have previously been controlled or eliminated have been observed in many settings. Reactive vaccination campaigns may successfully control outbreaks but must necessarily be implemented in the face of considerable uncertainty. Real-time surveillance may provide critical information about at-risk population and optimal vaccination targets, but may itself be limited by the specificity of disease confirmation. We propose an integrated modelling approach that synthesizes historical demographic and vaccination data with real-time outbreak surveillance via a dynamic transmission model and an age-specific disease confirmation model. We apply this framework to data from the 1996-1997 measles outbreak in Sao Paulo, Brazil. To simulate the information available to decision-makers, we truncated the surveillance data to what would have been available at 1 or 2 months prior to the realized interventions. We use the model, fitted to real-time observations, to evaluate the likelihood that candidate age-targeted interventions could control the outbreak. Using only data available prior to the interventions, we estimate that a significant excess of susceptible adults would prevent child-targeted campaigns from controlling the outbreak and that failing to account for age-specific confirmation rates would underestimate the importance of adult-targeted vaccination.

      8. Two cases of fungal keratitis caused by Metarhizium anisopliaeExternal
        Goodman AL, Lockhart SR, Lysen CB, Westblade LF, Burnham CD, Burd EM.
        Med Mycol Case Rep. 2018 Sep;21:8-11.

        We present two cases of keratitis due to Metarhizium anisopliae in geographically separated areas of the United States. The isolates were microscopically similar but morphologically different and were identified by ribosomal DNA sequencing. Both isolates had low minimum inhibitory concentration (MIC) values to caspofungin and micafungin, but high MIC values to amphotericin B. The morphologic and antifungal susceptibility differences between the two isolates indicate possible polyphylogeny of the group.

      9. Bleeding and blood disorders in clients of voluntary medical male circumcision for HIV prevention – Eastern and Southern Africa, 2015-2016External
        Hinkle LE, Toledo C, Grund JM, Byams VR, Bock N, Ridzon R, Cooney C, Njeuhmeli E, Thomas AG, Odhiambo J, Odoyo-June E, Talam N, Matchere F, Msungama W, Nyirenda R, Odek J, Come J, Canda M, Wei S, Bere A, Bonnecwe C, Choge IA, Martin E, Loykissoonlal D, Lija GJ, Mlanga E, Simbeye D, Alamo S, Kabuye G, Lubwama J, Wamai N, Chituwo O, Sinyangwe G, Zulu JE, Ajayi CA, Balachandra S, Mandisarisa J, Xaba S, Davis SM.
        MMWR Morb Mortal Wkly Rep. 2018 Mar 23;67(11):337-339.

        Male circumcision reduces the risk for female-to-male human immunodeficiency virus (HIV) transmission by approximately 60% (1) and has become a key component of global HIV prevention programs in countries in Eastern and Southern Africa where HIV prevalence is high and circumcision coverage is low. Through September 2017, the President’s Emergency Plan for AIDS Relief (PEPFAR) had supported 15.2 million voluntary medical male circumcisions (VMMCs) in 14 priority countries in Eastern and Southern Africa (2). Like any surgical intervention, VMMC carries a risk for complications or adverse events. Adverse events during circumcision of males aged >/=10 years occur in 0.5% to 8% of procedures, though the majority of adverse events are mild (3,4). To monitor safety and service quality, PEPFAR tracks and reports qualifying notifiable adverse events. Data reported from eight country VMMC programs during 2015-2016 revealed that bleeding resulting in hospitalization for >/=3 days was the most commonly reported qualifying adverse event. In several cases, the bleeding adverse event revealed a previously undiagnosed or undisclosed bleeding disorder. Bleeding adverse events in men with potential bleeding disorders are serious and can be fatal. Strategies to improve precircumcision screening and performance of circumcisions on clients at risk in settings where blood products are available are recommended to reduce the occurrence of these adverse events or mitigate their effects (5).

      10. Subacute liver failure due to autochthonous hepatitis E virus infection in an elderly man in the United StatesExternal
        Landry ML, Kamili S, Jain D.
        Human Pathology: Case Reports. 2018 June;12:68-70.

        Hepatitis E virus (HEV) infection in immunocompetent individuals is uncommon in the United States. We report a case of elderly man who presented with jaundice, cholestatic hepatitis, and subacute liver failure with fatal outcome. The patient was started on steroids based on ANA positivity. Liver biopsy showed panlobular hepatitis with cholestasis. The histologic differential diagnosis included drug/toxic injury, biliary obstruction, and acute hepatitis C or hepatitis E. Drug/toxic injury was favored initially. However, subsequent serology was positive for anti-HEV IgM and IgG, and HEV RNA genotype 3 was detected in both serum and liver tissue. Awareness of autochthonous hepatitis E and its inclusion in the differential diagnosis is needed for early diagnosis and appropriate management.

      11. Adenovirus-associated acute conjunctivitis in Beijing, China, 2011-2013External
        Li J, Lu X, Jiang B, Du Y, Yang Y, Qian H, Liu B, Lin C, Jia L, Chen L, Wang Q.
        BMC Infect Dis. 2018 Mar 20;18(1):135.

        BACKGROUND: Human adenovirus (HAdV)-associated acute conjunctivitis is a common infectious disease and causes significant morbidity among residents in Beijing, China. However, little is known about the epidemiology and type distribution of acute adenoviral conjunctivitis in Beijing. METHODS: Acute conjunctivitis surveillance was conducted in 18 hospitals in Beijing from July through October during 2011-2013. HAdVs were detected by PCR from eye swab and types were determined by partial hexon and fiber gene sequencing. Risk factors associated with adenoviral conjunctivitis were analyzed. RESULTS: Of 876 conjunctivitis cases, 349 (39.8%) were HAdV positive. HAdV detection was most common in conjunctivitis patients aged 18-40 years; patients with contact history with a conjunctivitis case; patients with specimen collected on days 4-6 post symptom onset and patients who worked in food service as catering attendants. Fifteen types were identified among adenoviral conjunctivitis cases. Five HAdV types (HAdV-4, – 37, – 53, – 64 and – 8) accounted for 81.1% of all adenoviral conjunctivitis cases. HAdV-37, – 4 and – 53 were the most common types associated with adenoviral conjunctivitis in 2011, 2012 and 2013, respectively. CONCLUSION: Multiple HAdV types were associated with acute conjunctivitis in Beijing. Predominant types associated with adenoviral conjunctivitis circulating in Beijing varied from year to year.

      12. Towards elimination of hepatitis C virus infection in childrenExternal
        Nwaohiri A, Schillie S, Bulterys M, Kourtis AP.
        The Lancet Child and Adolescent Health. 2018 ;2(4):243.

        [No abstract]

      13. OBJECTIVE: Since the implementation of a series of blood donation safety improvements in Kenya, information about seroprevalence and determinants of transfusion transmissible infections among voluntary blood donors especially in high HIV burden regions of Homabay, Kisumu and Siaya counties remain scanty. A cross-sectional study examining HIV, syphilis, hepatitis B and C virus sero-markers and associated determinants was conducted among voluntary blood donors. Their demographic characteristics and previous risk exposure were recorded in a pre-donation questionnaire, while blood samples collected were screened for hepatitis B, hepatitis C, human immunodeficiency viruses by ELISA and RPR (syphilis), then confirmed using CMIA. RESULTS: Overall TTIs seroprevalence was 114 (9.4%), distributed among HIV, HBV, HCV and syphilis at 14 (1.15%), 42 (3.46%), 39 (3.21%) and 19 (1.56%), respectively, with co-infections of 3 (0.25%). There were no significant differences in proportions distributions among demographic variables. However, high risk sex was significantly associated with higher odds of HBV infections [> 1 partner vs. 0-1 partner; odd ratio (OR) 2.60; 95% confidence interval (CI) 1.098-6.86; p = 0.046]. In conclusion, a substantial percentage of blood donors still harbor transfusion transmissible infections despite recent safety improvements with greater majority cases caused by HBV infections arising from previous exposure to high risk sex.

      14. Seroprevalence of HPV 6, 11, 16 and 18 and correlates of exposure in unvaccinated women aged 16-64 years in Puerto RicoExternal
        Ortiz AP, Tortolero-Luna G, Romaguera J, Perez CM, Gonzalez D, Munoz C, Gonzalez L, Marrero E, Suarez E, Palesfky JM, Panicker G, Unger ER.
        Papillomavirus Res. 2018 Mar 16.

        BACKGROUND: To understand risk factors for HPV exposure in Puerto Rican women, we evaluated HPV 6, 11, 16, and 18 serology in women aged living in the San Juan metropolitan area. METHODS: As part of a cross-sectional study, a population-based sample of 524 HPV unvaccinated Hispanic women ages 16-64 years completed face-to-face and computer assisted interviews and provided blood and self-collected anal and cervical specimens. Serology used multiplex virus-like particle based-IgG ELISA and HPV DNA was detected with L1-consensus PCR. RESULTS: 32% and 47% were seropositive to HPV types included in the bivalent (16/18) and quadrivalent (6/11/16/18) vaccines, respectively. Type-specific seroprevalence was HPV6 – 29%, HPV11 – 18%, HPV16 – 23%, and HPV18 – 17%; seroprevalence was high in the youngest age-group (16-19: 26-37%). HPV seropositivity was associated with having >/= 3 lifetime sexual partners (OR=2.5, 95% CI=1.7-3.9) and detection of anogenital HPV DNA (OR=1.8, 95% CI=1.2-2.6). CONCLUSIONS: The high cumulative exposure of HPV vaccine types 6/11/16/18 in this Hispanic population was influenced by factors related to HPV exposure through sexual behavior. High seroprevalence in the youngest age-group indicates early age of exposure to HPV in Puerto Rico, highlighting the need for HPV vaccination starting prior to age 16.

      15. OBJECTIVE: It is unknown if human papillomavirus (HPV) serum antibody responses vary by anatomic site of infection. We aimed to assess the seroprevalence for HPV 6, 11, 16 and 18 in association with HPV DNA detection in different anatomic sites among women. METHODS: This cross sectional population-based study analyzed data from 524 women aged 16-64 years living in the San Juan metropolitan area of Puerto Rico (PR). Questionnaires were used to assess demographic and lifestyle variables, while anogenital and blood samples were collected for HPV analysis. Logistic regression models were used to estimate the adjusted prevalence odds ratio (POR) in order to determine the association between HPV DNA infection status in the cervix and anus and serum antibody status, controlling for different potential confounders. RESULTS: Overall, 46.9% of women had detectable antibodies to one or more types whereas 8.7% had HPV DNA for one or more of these types detected in cervix (4.0%) or anus (6.5%). Women with cervical HPV detection tended to be more HPV seropositive than women without cervical detection (adjusted POR (95%CI): 2.41 (0.90, 6.47), p=0.078); however the type-specific association between cervical DNA and serum antibodies was only significant for HPV 18 (adjusted POR (95% CI): 5.9 (1.03, 33.98)). No significant association was detected between anal HPV and seropositivity (p>0.10). CONCLUSION: Differences in the anatomic site of infection could influence seroconversion, however, longitudinal studies will be required for further evaluation. This information will be instrumental in advancing knowledge of immune mechanisms involved in anatomic site response.

      16. Low body mass index and latent tuberculous infection: a systematic review and meta-analysisExternal
        Saag LA, LaValley MP, Hochberg NS, Cegielski JP, Pleskunas JA, Linas BP, Horsburgh CR.
        Int J Tuberc Lung Dis. 2018 Apr 1;22(4):358-365.

        BACKGROUND: The well-documented association between underweight and increased incidence of active tuberculosis (TB) has not been extended to incidence or prevalence of latent tuberculous infection (LTBI). DESIGN: After identifying studies that reported a categorical measure of body mass index (BMI) and used the tuberculin skin test (TST) or QuantiFERON(R)-TB Gold In-Tube (QFT) to measure LTBI, a maximum likelihood random-effects model was used to examine the pooled association between LTBI and low BMI (<18.5 kg/m2), compared with 1) normal BMI (18.5-25 kg/m2) and 2) a complementary group of all others, i.e., non-underweight subjects (BMI >/=18.5 kg/m2). RESULTS: Among studies using TST, the odds ratios (ORs) showed a slight, non-statistically significant decrease in the odds of TST positivity in underweight persons compared with both groups (non-underweight, OR 0.88, 95%CI 0.73-1.05; normal weight, OR 0.96, 95%CI 0.77-1.20). Among studies using QFT, the OR suggested slightly decreased, yet non-significant, odds of QFT positivity in underweight compared with non-underweight subjects (OR 0.92, 95%CI 0.68-1.26), and significantly decreased odds of QFT positivity in underweight compared with normal weight subjects (OR 0.84, 95%CI 0.73-0.98). CONCLUSION: These results suggest that underweight persons are not at an increased risk of LTBI. Screening this population for LTBI would not increase the yield of identified LTBI.

      17. Operational research within a Global Fund supported tuberculosis project in India: why, how and its contribution towards change in policy and practiceExternal
        Sagili KD, Satyanarayana S, Chadha SS, Wilson NC, Kumar AM, Moonan PK, Oeltmann JE, Chadha VK, Nagaraja SB, Ghosh S, Lo TQ, Volkmann T, Willis M, Shringarpure K, Reddy RC, Kumar P, Nair SA, Rao R, Yassin M, Mwangala P, Zachariah R, Tonsing J, Harries AD, Khaparde S.
        Glob Health Action. 2018 ;11(1):1445467.

        BACKGROUND: The Global Fund encourages operational research (OR) in all its grants; however very few reports describe this aspect. In India, Project Axshya was supported by a Global Fund grant to improve the reach and visibility of the government Tuberculosis (TB) services among marginalised and vulnerable communities. OR was incorporated to build research capacity of professionals working with the national TB programme and to generate evidence to inform policies and practices. OBJECTIVES: To describe how Project Axshya facilitated building OR capacity within the country, helped in addressing several TB control priority research questions, documented project activities and their outcomes, and influenced policy and practice. METHODS: From September 2010 to September 2016, three key OR-related activities were implemented. First, practical output-oriented modular training courses were conducted (n = 3) to build research capacity of personnel involved in the TB programme, co-facilitated by The Union, in collaboration with the national TB programme, WHO country office and CDC, Atlanta. Second, two large-scale Knowledge, Attitude and Practice (KAP) surveys were conducted at baseline and mid-project to assess the changes pertaining to TB knowledge, attitudes and practices among the general population, TB patients and health care providers over the project period. Third, studies were conducted to describe the project’s core activities and outcomes. RESULTS: In the training courses, 44 participant teams were supported to develop research protocols on topics of national priority, resulting in 28 peer-reviewed scientific publications. The KAP surveys and description of project activities resulted in 14 peer-reviewed publications. Of the published papers at least 12 have influenced change in policy or practice. CONCLUSIONS: OR within a Global Fund supported TB project has resulted in building OR capacity, facilitating research in areas of national priority and influencing policy and practice. We believe this experience will provide guidance for undertaking OR in Global Fund projects.

      18. HIV incidence, HIV prevalence, and undiagnosed HIV infections in men who have sex with men, United StatesExternal
        Singh S, Song R, Johnson AS, McCray E, Hall HI.
        Ann Intern Med. 2018 Mar 20.

        Background: HIV infection is a persistent health concern in the United States, and men who have sex with men (MSM) continue to be the most affected population. Objective: To estimate HIV incidence and prevalence and the percentage of undiagnosed HIV infections overall and among MSM. Design: Cross-sectional analysis. Setting: National HIV Surveillance System. Participants: Persons aged 13 years and older with diagnosed HIV infection. Measurements: Data on HIV diagnoses and the first CD4 test result after diagnosis were used to model HIV incidence and prevalence and the percentage of undiagnosed HIV infections from 2008 to 2014 on the basis of a well-characterized CD4 depletion model. Results: Modeled HIV incidence decreased 14.8% overall, from 45 200 infections in 2008 to 38 500 in 2015, and among all transmission risk groups except MSM. The incidence of HIV increased 3.1% (95% CI, 1.6% to 4.5%) per year among Hispanic/Latino MSM (6300 infections in 2008, 7900 in 2015), decreased 2.7% (CI, -3.8% to -1.5%) per year among white MSM (8800 infections in 2008, 7100 in 2015), and remained stable among black MSM at about 10 000 infections. The incidence decreased by 3.0% (CI, -4.2% to -1.8%) per year among MSM aged 13 to 24 years and by 4.7% (CI, -6.2% to -3.1%) per year among those aged 35 to 44 years. Among MSM aged 25 to 34 years, HIV incidence increased 5.7% (CI, 4.4% to 7.0%) per year, from 6900 infections in 2008 to 10 000 in 2015. The percentage of undiagnosed HIV infections was higher among black, Hispanic/Latino, and younger MSM than white and older MSM, respectively. Limitation: Assumptions of the CD4 depletion model and variability of CD4 values. Conclusion: Expansion of HIV screening to reduce undiagnosed infections and increased access to care and treatment to achieve viral suppression are critical to reduce HIV transmission. Access to prevention methods, such as condoms and preexposure prophylaxis, also is needed, particularly among MSM of color and young MSM. Primary Funding Source: None.

      19. Tuberculosis – United States, 2017External
        Stewart RJ, Tsang CA, Pratt RH, Price SF, Langer AJ.
        MMWR Morb Mortal Wkly Rep. 2018 Mar 23;67(11):317-323.

        In 2017, a total of 9,093 new cases of tuberculosis (TB) were provisionally* reported in the United States, representing an incidence rate of 2.8 cases per 100,000 population. The case count decreased by 1.8% from 2016 to 2017, and the rate declined by 2.5% over the same period. These decreases are consistent with the slight decline in TB seen over the past several years (1). This report summarizes provisional TB surveillance data reported to CDC’s National Tuberculosis Surveillance System for 2017 and in the last decade. The rate of TB among non-U.S.-born persons in 2017 was 15 times the rate among U.S.-born persons. Among non-U.S.-born persons, the highest TB rate among all racial/ethnic groups was among Asians (27.0 per 100,000 persons), followed by non-Hispanic blacks (blacks; 22.0). Among U.S.-born persons, most TB cases were reported among blacks (37.1%), followed by non-Hispanic whites (whites; 29.5%). Previous studies have shown that the majority of TB cases in the United States are attributed to reactivation of latent TB infection (LTBI) (2). Ongoing efforts to prevent TB transmission and disease in the United States remain important to continued progress toward TB elimination. Testing and treatment of populations most at risk for TB disease and LTBI, including persons born in countries with high TB prevalence and persons in high-risk congregate settings (3), are major components of this effort.

      20. Community-acquired pneumonia visualized on CT scans but not chest radiographs: Pathogens, severity, and clinical outcomesExternal
        Upchurch CP, Grijalva CG, Wunderink RG, Williams DJ, Waterer GW, Anderson EJ, Zhu Y, Hart EM, Carroll F, Bramley AM, Jain S, Edwards KM, Self WH.
        Chest. 2018 Mar;153(3):601-610.

        BACKGROUND: The clinical significance of pneumonia visualized on CT scan in the setting of a normal chest radiograph is uncertain. METHODS: In a multicenter prospective surveillance study of adults hospitalized with community-acquired pneumonia (CAP), we compared the presenting clinical features, pathogens present, and outcomes of patients with pneumonia visualized on a CT scan but not on a concurrent chest radiograph (CT-only pneumonia) and those with pneumonia visualized on a chest radiograph. All patients underwent chest radiography; the decision to obtain CT imaging was determined by the treating clinicians. Chest radiographs and CT images were interpreted by study-dedicated thoracic radiologists blinded to the clinical data. RESULTS: The study population included 2,251 adults with CAP; 2,185 patients (97%) had pneumonia visualized on chest radiography, whereas 66 patients (3%) had pneumonia visualized on CT scan but not on concurrent chest radiography. Overall, these patients with CT-only pneumonia had a clinical profile similar to those with pneumonia visualized on chest radiography, including comorbidities, vital signs, hospital length of stay, prevalence of viral (30% vs 26%) and bacterial (12% vs 14%) pathogens, ICU admission (23% vs 21%), use of mechanical ventilation (6% vs 5%), septic shock (5% vs 4%), and inhospital mortality (0 vs 2%). CONCLUSIONS: Adults hospitalized with CAP who had radiological evidence of pneumonia on CT scan but not on concurrent chest radiograph had pathogens, disease severity, and outcomes similar to patients who had signs of pneumonia on chest radiography. These findings support using the same management principles for patients with CT-only pneumonia and those with pneumonia seen on chest radiography.

      21. Spatial-temporal trend for mother-to-child transmission of HIV up to infancy and during pre-Option B+ in western Kenya, 2007-13Cdc-pdfExternal
        Waruru A, Achia TN, Muttai H, Ng’ang’a L, Zielinski-Gutierrez E, Ochanda B, Katana A, Young PW, Tobias JL, Juma P, De Cock KM, Tylleskar T.
        PeerJ. 2018 ;2018(3).

        Introduction: Using spatial-temporal analyses to understand coverage and trends in elimination of mother-to-child transmission of HIV (e-MTCT) efforts may be helpful in ensuring timely services are delivered to the right place. We present spatial-temporal analysis of seven years of HIV early infant diagnosis (EID) data collected from 12 districts in western Kenya from January 2007 to November 2013, during pre-Option B+ use. Methods: We included in the analysis infants up to one year old. We performed trend analysis using extended Cochran-Mantel-Haenszel stratified test and logistic regression models to examine trends and associations of infant HIV status at first diagnosis with: early diagnosis ( < 8 weeks after birth), age at specimen collection, infant ever having breastfed, use of single dose nevirapine, and maternal antiretroviral therapy status. We examined these covariates and fitted spatial and spatial-temporal semiparametric Poisson regression models to explain HIVinfection rates using R-integrated nested Laplace approximation package. We calculated new infections per 100,000 live births and used Quantum GIS to map fitted MTCT estimates for each district in Nyanza region. Results: Median age was two months, interquartile range 1.5-5.8 months. Unadjusted pooled positive rate was 11.8% in the seven-years period and declined from 19.7% in 2007 to 7.0% in 2013, p < 0.01. Uptake of testing </= 8 weeks after birth was under 50% in 2007 and increased to 64.1% by 2013, p < 0.01. By 2013, the overall standardized MTCTrate was 447 infections per 100,000 live births. Based on Bayesian deviance information criterion comparisons, the spatial-temporal model with maternal and infant covariates was best in explaining geographical variation in MTCT. Discussion: Improved EID uptake and reduced MTCT rates are indicators of progress towards e-MTCT. Cojoined analysis of time and covariates in a spatial context provides a robust approach for explaining differences in programmatic impact over time. Conclusion: During this pre-Option B+ period, the prevention of mother to child transmission program in this region has not achieved e-MTCT target of </= 50 infections per 100,000 live births. Geographical disparities in program achievements may signify gaps in spatial distribution of e-MTCT efforts and could indicate areas needing further resources and interventions.

    • Community Health Services
      1. School health implementation tools: a mixed methods evaluation of factors influencing their useExternal
        Leeman J, Wiecha JL, Vu M, Blitstein JL, Allgood S, Lee S, Merlo C.
        Implement Sci. 2018 Mar 20;13(1):48.

        BACKGROUND: The U.S. Centers for Disease Control and Prevention (CDC) develops tools to support implementation of evidence-based interventions for school health. To advance understanding of factors influencing the use of these implementation tools, we conducted an evaluation of state, school district, and local school staffs’ use of four CDC tools to support implementation of physical activity, nutrition, health education, and parent engagement. Two frameworks guided the evaluation: Interactive Systems Framework (ISF) for Dissemination and Implementation and Consolidated Framework for Implementation Research (CFIR). METHODS: The evaluation applied a mixed methods, cross-sectional design that included online surveys (n = 69 state staff from 43 states), phone interviews (n = 13 state staff from 6 states), and in-person interviews (n = 90 district and school staff from 8 districts in 5 states). Descriptive analyses were applied to surveys and content analysis to interviews. RESULTS: The survey found that the majority of state staff surveyed was aware of three of the CDC tools but most were knowledgeable and confident in their ability to use only two. These same two tools were the ones for which states were most likely to have provided training and technical assistance in the past year. Interviews provided insight into how tools were used and why use varied, with themes organized within the ISF domain “support strategies” (e.g., training, technical assistance) and four CFIR domains: (1) characteristics of tools, (2) inner setting, (3) outer setting, and (4) individuals. Overall, tools were valued for the credibility of their source (CDC) and evidence strength and quality. Respondents reported that tools were too complex for use by school staff. However, if tools were adaptable and compatible with inner and outer setting factors, state and district staff were willing and able to adapt tools for school use. CONCLUSIONS: Implementation tools are essential to supporting broad-scale implementation of evidence-based interventions. This study illustrates how CFIR and ISF might be applied to evaluate factors influencing tools’ use and provides recommendations for designing tools to fit within the multi-tiered systems involved in promoting, supporting, and implementing evidence-based interventions in schools. Findings have relevance for the design of implementation tools for use by other multi-tiered systems.

    • Disease Reservoirs and Vectors
      1. Detection and characterization of a novel spotted fever group Rickettsia genotype in Haemaphysalis leporispalustris from California, USAExternal
        Eremeeva ME, Weiner LM, Zambrano ML, Dasch GA, Hu R, Vilcins I, Castro MB, Bonilla DL, Padgett KA.
        Ticks Tick Borne Dis. 2018 Mar 1.

        The rabbit tick, Haemaphysalis leporispalustris Packard, is known for its association with Rickettsia rickettsii as it harbors both virulent and avirulent strains of this pathogen. In this manuscript we report findings and preliminary characterization of a novel spotted fever group rickettsia (SFGR) in rabbit ticks from California, USA. Rickettsia sp. CA6269 (proposed “Candidatus Rickettsia lanei”) is most related to known R. rickettsii isolates but belongs to its own well-supported branch different from those of all R. rickettsii including strain Hlp2 and from Rickettsia sp. 364D (also known as R. philipii) and R. peacockii. This SFGR probably exhibits both transovarial and transstadial survival since it was found in both questing larvae and nymphs. Although this rabbit tick does not frequently bite humans, its role in maintenance of other rickettsial agents and this novel SFGR warrant further investigation.

    • Environmental Health
      1. Associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic diseases among children aged 6 and 7yearsExternal
        Buckley JP, Quiros-Alcala L, Teitelbaum SL, Calafat AM, Wolff MS, Engel SM.
        Environ Int. 2018 Mar 15;115:79-88.

        BACKGROUND: Prenatal environmental phenol and phthalate exposures may alter immune or inflammatory responses leading to respiratory and allergic disease. OBJECTIVES: We estimated associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic outcomes among children in the Mount Sinai Children’s Environmental Health Study. METHODS: We quantified urinary biomarkers of benzophenone-3, bisphenol A, paradichlorobenzene (as 2,5-dichlorophenol), triclosan, and 10 phthalate metabolites in third trimester maternal samples and assessed asthma, wheeze, and atopic skin conditions via parent questionnaires at ages 6 and 7years (n=164 children with 240 observations). We used logistic regression to estimate covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per standard deviation difference in natural log biomarker concentrations and examined effect measure modification by child’s sex. RESULTS: Associations of prenatal 2,5-dichlorophenol (all outcomes) and bisphenol A (asthma outcomes) were modified by child’s sex, with increased odds of outcomes among boys but not girls. Among boys, ORs for asthma diagnosis per standard deviation difference in biomarker concentration were 3.00 (95% CI: 1.36, 6.59) for 2,5-dichlorophenol and 3.04 (95% CI: 1.38, 6.68) for bisphenol A. Wheeze in the past 12months was inversely associated with low molecular weight phthalate metabolites among girls only (OR: 0.27, 95% CI: 0.13, 0.59) and with benzophenone-3 among all children (OR: 0.65, 95% CI: 0.44, 0.96). CONCLUSIONS: Prenatal bisphenol A and paradichlorobenzene exposures were associated with pediatric respiratory outcomes among boys. Future studies may shed light on biological mechanisms and potential sexually-dimorphic effects of select phenols and phthalates on respiratory disease development.

      2. Air quality awareness among U.S. adults with respiratory and heart diseaseExternal
        Mirabelli MC, Boehmer TK, Damon SA, Sircar KD, Wall HK, Yip FY, Zahran HS, Garbe PL.
        Am J Prev Med. 2018 Mar 15.

        INTRODUCTION: Poor air quality affects respiratory and cardiovascular health. Information about health risks associated with outdoor air quality is communicated to the public using air quality alerts. This study was conducted to assess associations of existing respiratory and heart disease with three aspects of air quality awareness: awareness of air quality alerts, discussing with a health professional strategies to reduce air pollution exposure, and avoiding busy roads to reduce air pollution exposure when walking, biking, or exercising outdoors. METHODS: During 2014-2016, a total of 12,599 U.S. adults participated in summer waves of the ConsumerStyles surveys and self-reported asthma, emphysema/chronic obstructive pulmonary disease, heart disease, and each aspect of air quality awareness. In 2017, associations between each health condition and air quality awareness were estimated using log binomial and multinomial regression. RESULTS: Overall, 49% of respondents were aware of air quality alerts, 3% discussed with a health professional strategies to reduce air pollution exposure, and 27% always/usually avoided busy roads to reduce air pollution exposure. Asthma was associated with increased prevalence of awareness of air quality alerts (prevalence ratio=1.11, 95% CI=1.04, 1.20), discussing with a health professional (prevalence ratio=4.88, 95% CI=3.74, 6.37), and always/usually avoiding busy roads to reduce air pollution exposure (prevalence ratio=1.13, 95% CI=1.01, 1.27). Heart disease was not associated with air quality awareness. CONCLUSIONS: Existing respiratory disease, but not heart disease, was associated with increased air quality awareness. These findings reveal important opportunities to raise awareness of air quality alerts and behavior changes aimed at reducing air pollution exposure among adults at risk of exacerbating respiratory and heart diseases.

      3. Within-day, between-day, and between-week variability of urinary concentrations of phenol biomarkers in pregnant womenExternal
        Vernet C, Philippat C, Calafat AM, Ye X, Lyon-Caen S, Siroux V, Schisterman EF, Slama R.
        Environ Health Perspect. 2018 Mar 16;126(3):037005.

        BACKGROUND: Toxicology studies have shown adverse effects of developmental exposure to industrial phenols. Evaluation in humans is challenged by potentially marked within-subject variability of phenol biomarkers in pregnant women, which is poorly characterized. OBJECTIVES: We aimed to characterize within-day, between-day, and between-week variability of phenol urinary biomarker concentrations during pregnancy. METHODS: In eight French pregnant women, we collected all urine voids over a 1-wk period (average, 60 samples per week per woman) at three occasions (15+/-2, 24+/-2, and 32+/-1 gestational weeks) in 2012-2013. Aliquots of each day and of the whole week were pooled within-subject. We assayed concentrations of 10 phenols in these pools, and, for two women, in all spot (unpooled) samples collected during a 1-wk period. We characterized variability using intraclass correlation coefficients (ICCs) with spot samples (within-day variability), daily pools (between-day variability), and weekly pools (between-week variability). RESULTS: For most biomarkers, the within-day variability was high (ICCs between 0.03 and 0.50). The between-day variability, based on samples pooled within each day, was much lower, with ICCs >0.60 except for bisphenol S (0.14, 95% confidence interval [CI]: 0.00, 0.39). The between-week variability differed between compounds, with triclosan and bisphenol S having the lowest ICCs (<0.3) and 2,5-dichlorophenol the highest (ICC >0.9). CONCLUSION: During pregnancy, phenol biomarkers showed a strong within-day variability, while the variability between days of a given week was more limited. One biospecimen is not enough to efficiently characterize exposure; collecting biospecimens during a single week may be enough to represent well the whole pregnancy exposure for some but not all phenols.

    • Food Safety
      1. Statistical adjustment of culture-independent diagnostic tests for trend analysis in the Foodborne Diseases Active Surveillance Network (FoodNet), USAExternal
        Gu W, Dutta V, Patrick M, Bruce BB, Geissler A, Huang J, Fitzgerald C, Henao O.
        Int J Epidemiol. 2018 Mar 19.

        Background: Culture-independent diagnostic tests (CIDTs) are increasingly used to diagnose Campylobacter infection in the Foodborne Diseases Active Surveillance Network (FoodNet). Because CIDTs have different performance characteristics compared with culture, which has been used historically and is still used to diagnose campylobacteriosis, adjustment of cases diagnosed by CIDT is needed to compare with culture-confirmed cases for monitoring incidence trends. Methods: We identified the necessary parameters for CIDT adjustment using culture as the gold standard, and derived formulas to calculate positive predictive values (PPVs). We conducted a literature review and meta-analysis to examine the variability in CIDT performance and Campylobacter prevalence applicable to FoodNet sites. We then developed a Monte Carlo method to estimate test-type and site-specific PPVs with their associated uncertainties. Results: The uncertainty in our estimated PPVs was largely derived from uncertainty about the specificity of CIDTs and low prevalence of Campylobacter in tested samples. Stable CIDT-adjusted incidences of Campylobacter cases from 2012 to 2015 were observed compared with a decline in culture-confirmed incidence. Conclusions: We highlight the lack of data on the total numbers of tested samples as one of main limitations for CIDT adjustment. Our results demonstrate the importance of adjusting CIDTs for understanding trends in Campylobacter incidence in FoodNet.

      2. Preliminary incidence and trends of infections with pathogens transmitted commonly through food – Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2006-2017External
        Marder EP, Griffin PM, Cieslak PR, Dunn J, Hurd S, Jervis R, Lathrop S, Muse A, Ryan P, Smith K, Tobin-D’Angelo M, Vugia DJ, Holt KG, Wolpert BJ, Tauxe R, Geissler AL.
        MMWR Morb Mortal Wkly Rep. 2018 Mar 23;67(11):324-328.

        Despite ongoing food safety measures in the United States, foodborne illness continues to be a substantial health burden. The 10 U.S. sites of the Foodborne Diseases Active Surveillance Network (FoodNet)* monitor cases of laboratory-diagnosed infections caused by nine pathogens transmitted commonly through food. This report summarizes preliminary 2017 data and describes changes in incidence since 2006. In 2017, FoodNet reported 24,484 infections, 5,677 hospitalizations, and 122 deaths. Compared with 2014-2016, the 2017 incidence of infections with Campylobacter, Listeria, non-O157 Shiga toxin-producing Escherichia coli (STEC), Yersinia, Vibrio, and Cyclospora increased. The increased incidences of pathogens for which testing was previously limited might have resulted from the increased use and sensitivity of culture-independent diagnostic tests (CIDTs), which can improve incidence estimates (1). Compared with 2006-2008, the 2017 incidence of infections with Salmonella serotypes Typhimurium and Heidelberg decreased, and the incidence of serotypes Javiana, Infantis, and Thompson increased. New regulatory requirements that include enhanced testing of poultry products for Salmonella(dagger) might have contributed to the decreases. The incidence of STEC O157 infections during 2017 also decreased compared with 2006-2008, which parallels reductions in isolations from ground beef.( section sign) The declines in two Salmonella serotypes and STEC O157 infections provide supportive evidence that targeted control measures are effective. The marked increases in infections caused by some Salmonella serotypes provide an opportunity to investigate food and nonfood sources of infection and to design specific interventions.

    • Genetics and Genomics
      1. The expanded use of next generation sequencing tools has led to an explosion in the rate of discovery of novel viral agents and has had a measured effect on the capacity to genetically identify the presence of previously described viruses in new geographic environments and within different hosts and vectors. For example, more than 30 flaviviruses (Flavivirus; Flaviviridae) with the capacity to infect only mosquitoes have been described in the last 10 years. By contrast, only two such viruses had been described in the previous 33 years.(1) This burgeoning expansion of the known virome has largely outpaced the scientific capacity for characterizing these agents in any detail. Furthermore, many of the methodologies used for rapid genetic detection (such as placing mosquitoes directly in nucleic acid extraction buffers and the use of FTA cards for blood samples) preclude the isolation of the agents.

      2. The evolution of resistance to antibiotics provides a timely and relevant topic for teaching undergraduate students evolutionary biology. Here, we present a module incorporating modified sequencing data from eight antibiotic resistant pathogen outbreaks in hospital settings with bioinformatics and phylogenetic analyses. This module uses whole genome sequencing data from hospital outbreaks investigated by the Centers for Disease Control and Prevention to provide examples of antibiotic resistance spread. Students work in groups to analyze outbreak data to identify the bacterial species and antibiotic resistance genes, to infer a phylogenetic tree examining relatedness among isolates, and to determine a possible source of the outbreak. Students then compile their results in individual reports and provide recommendations for preventing the further spread of antibiotic resistant organisms. In addition to providing genomic outbreak data, we include a teaching concepts guide discussing three integral components of the module: how evolutionary biology concepts of natural selection and competition impact antibiotic resistance; outbreak investigation information to aid in phylogenetic analysis and creation of recommendations; and instructions for the bioinformatics protocol. Completion of this module provides students an opportunity to think critically about the evolution of resistance, practice bioinformatics techniques, and relate evolutionary biology to current events.

    • Health Economics
      1. Economic analysis of CDC’s culture- and smear-based tuberculosis instructions for Filipino immigrantsExternal
        Maskery B, Posey DL, Coleman MS, Asis R, Zhou W, Painter JA, Wingate LT, Roque M, Cetron MS.
        Int J Tuberc Lung Dis. 2018 Apr 1;22(4):429-436.

        SETTING: In 2007, the US Centers for Disease Control and Prevention (CDC) revised its tuberculosis (TB) technical instructions for panel physicians who administer mandatory medical examinations among US-bound immigrants. Many US-bound immigrants come from the Philippines, a high TB prevalence country. OBJECTIVE: To quantify economic and health impacts of smear- vs. culture-based TB screening. DESIGN: Decision tree modeling was used to compare three Filipino screening programs: 1) no screening, 2) smear-based screening, and 3) culture-based screening. The model incorporated pre-departure TB screening results from Filipino panel physicians and CDC databases with post-arrival follow-up outcomes. Costs (2013 $US) were examined from societal, immigrant, US Public Health Department and hospitalization perspectives. RESULTS: With no screening, an annual cohort of 35 722 Filipino immigrants would include an estimated 450 TB patients with 264 hospitalizations, at a societal cost of US$9.90 million. Culture-based vs. smear-based screening would result in fewer imported cases (80.9 vs. 310.5), hospitalizations (19.7 vs. 68.1), and treatment costs (US$1.57 million vs. US$4.28 million). Societal screening costs, including US follow-up, were greater for culture-based screening (US$5.98 million) than for smear-based screening (US$3.38 million). Culture-based screening requirements increased immigrant costs by 61% (US$1.7 million), but reduced costs for the US Public Health Department (22%, US$750 000) and of hospitalization (70%, US$1 020 000). CONCLUSION: Culture-based screening reduced imported TB and US costs among Filipino immigrants.

      2. Cost and cost-effectiveness of a demand creation intervention to increase uptake of voluntary medical male circumcision in Tanzania: Spending more to spend lessExternal
        Torres-Rueda S, Wambura M, Weiss HA, Plotkin M, Kripke K, Chilongani J, Mahler H, Kuringe E, Makokha M, Hellar A, Schutte C, Kazaura KJ, Simbeye D, Mshana G, Larke N, Lija G, Changalucha J, Vassall A, Hayes R, Grund JM, Terris-Prestholt F.
        J Acquir Immune Defic Syndr. 2018 Mar 19.

        BACKGROUND: Although voluntary medical male circumcision (VMMC) reduces the risk of HIV acquisition, demand for services is lower among men in most at-risk age groups (ages 20-34 years). A randomised controlled trial was conducted to assess the effectiveness of locally-tailored demand creation activities (including mass media, community mobilisation and targeted service delivery) in increasing uptake of campaign-delivered VMMC among men aged 20-34 years. We conducted an economic evaluation to understand the intervention’s cost and cost-effectiveness. SETTING: Tanzania (Njombe and Tabora regions). METHODS: Cost data were collected on surgery, demand creation activities and monitoring and supervision related to VMMC implementation across clusters in both trial arms, as well as start-up activities for the intervention arm. The Decision Makers’ Program Planning Tool was used to estimate the number of HIV infections averted and related cost savings given total VMMCs per cluster. Disability-adjusted life years were calculated and used to estimate incremental cost-effectiveness ratios. RESULTS: Client load was higher in the intervention arms than in the control arms: 4394 v. 2901, respectively, in Tabora and 1797 v. 1025 in Njombe. Despite additional costs of tailored demand creation, demand increased more than proportionally: mean costs per VMMC in the intervention arms were $62 in Tabora and $130 in Njombe, and in the control arms $70 and $191, respectively. More infections were averted in the intervention arm than in the control arm in Tabora (123 v. 67, respectively) and in Njombe (164 v. 102, respectively). The intervention dominated the control as it was both less costly and more effective. Cost-savings were observed in both regions stemming from the antiretroviral treatment costs averted as a result of the VMMCs performed. CONCLUSION: Spending more to address local preferences as a way to increase uptake of VMMC can be cost-saving.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

    • Immunity and Immunization
      1. Rotavirus vaccines were introduced in the United States in 2006 and in the subsequent years have fundamentally altered seasonality and shifted disease from annual to biennial epidemics. We investigated whether season and year of birth have emerged as risk factors for rotavirus and affected vaccine performance. We constructed a retrospective birth cohort of US children <5 years using the 2001-2014 MarketScan Database. We evaluated the assocations of season of birth, even/odd year of birth and interactions with vaccination. We fit Cox proportional hazards models to estimate the hazard of rotavirus hospitalization by calendar year of birth, season of birth assessed for interaction with vaccination. After vaccine introduction, we observed monotonically decreasing rates of rotavirus hospitalization for each subsequent birth cohort, but a biennial incidence pattern by calendar year. In the post-vaccine period, children born odd calendar years had higher hazard of rotavirus hospitalization than even year births. Children born in winter had the highest hazard of hospitalization but also had the higher vaccine effectiveness than spring, summer or fall births. With the emergence of a strong biennial pattern of disease following vaccine introduction, the timing of a child’s birth has become a risk factor for rotavirus.

      2. Assessment of Tdap vaccination effectiveness in adolescents in integrated health-care systemsExternal
        Briere EC, Pondo T, Schmidt M, Skoff T, Shang N, Naleway A, Martin S, Jackson ML.
        J Adolesc Health. 2018 Mar 15.

        PURPOSE: Despite high national vaccination coverage with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines among U.S. adolescents, rates of adolescent pertussis disease are increasing. We estimated the duration of protection after Tdap vaccination and the possible effects of the change from whole-cell to acellular childhood pertussis vaccines in the United States during the 1990s. METHODS: We conducted a retrospective cohort analysis among 11- to 18-year-olds enrolled in two integrated health-care delivery systems during 2005-2012. Cases met the Council of State and Territorial Epidemiologists’ confirmed or probable definition or a polymerase chain reaction-positive suspect definition. We estimated vaccine effectiveness (VE) overall and by time since Tdap receipt. We stratified VE estimates by primary series pertussis vaccine received (based on birth year): mixed-vaccine cohort (1987-1997) and acellular vaccine cohort (1998-2001). RESULTS: The overall Tdap VE was 57% (95% confidence interval [CI]: 42%-68%); the VE in the mixed-vaccine and acellular cohorts was 65% (95% CI: 44%-78%) and 52% (95% CI: 30%-68%), respectively. Tdap VE within <2 years post vaccination (69%, 95% CI: 54%-79%) was significantly different from VE >/=2 years post vaccination (34%, 95% CI: 1%-55%, p value < .01). VE was significantly higher <2 years post vaccination compared with >/=2 years post vaccination in both mixed-vaccine (87%, 95% CI: 58%-96%, and 52%, 95% CI: 13%-73%; p value = .04) and acellular cohorts (62%, 95% CI: 41%-76%, and 21%, 95% CI: -30% to 52%; p value = .01). CONCLUSIONS: Although Tdap vaccination remains the best pertussis prevention method for adolescents, protection wanes within 2 years regardless of the type of childhood primary vaccine. Vaccines with longer duration of protection could decrease pertussis burden.

      3. Rotavirus vaccines and health care utilization for diarrhea in US children, 2001-2015External
        Getachew HB, Dahl RM, Lopman BA, Parashar UD.
        Pediatr Infect Dis J. 2018 Mar 14.

        BACKGROUND: Rotavirus vaccination was introduced in the United States in 2006. Our objectives were to examine reductions in diarrhea-associated health care utilization after rotavirus vaccine implementation and to assess direct vaccine effectiveness (VE) in US children. METHODS: Retrospective cohort study using claims data of US children under 5 years of age. We compared rates of diarrhea-associated health care utilization in prevaccine versus post-vaccine introduction years. We also examined vaccine effectiveness (VE) and duration of protection. RESULTS: Compared with the average rate of rotavirus-coded hospitalizations in the prevaccine years, overall vaccine rates were reduced by 75% in 2007-2008, 60% in 2008-2009, 94% in 2009-2010, 80% in 2010-2011, 97% in 2011-2012, 88% in 2012-2013, 98% in 2013-2014 and 92% in 2014-2015. RV5 adjusted VE was 88% against rotavirus-coded hospitalization among 3 to 11 months of age, 88% in 12 to 23 months of age, 87% in 24 to 35 months of age, 87% in 36 to 47 months of age, and 87% in 48 to 59 months of age. RV1 adjusted VE was 87% against rotavirus-coded hospitalization among 3 to 11 months of age, 86% in 12 to 23 months of age and 86% in 24 to 35 months of age. CONCLUSION: Implementation of rotavirus vaccines has substantially reduced diarrhea-associated health care utilization in US children under 5 years of age. Both vaccines provided good and enduring protection through the fourth year of life against rotavirus hospitalizations.

      4. Enhancing viral vaccine production using engineered knockout vero cell lines – A second lookExternal
        Hoeksema F, Karpilow J, Luitjens A, Lagerwerf F, Havenga M, Groothuizen M, Gillissen G, Lemckert AA, Jiang B, Tripp RA, Yallop C.
        Vaccine. 2018 Mar 16.

        The global adoption of vaccines to combat disease is hampered by the high cost of vaccine manufacturing. The work described herein follows two previous publications (van der Sanden et al., 2016; Wu et al., 2017) that report a strategy to enhance poliovirus and rotavirus vaccine production through genetic modification of the Vero cell lines used in large-scale vaccine manufacturing. CRISPR/Cas9 gene editing tools were used to knockout Vero target genes previously shown to play a role in polio- and rotavirus production. Subsequently, small-scale models of current industry manufacturing systems were developed and adopted to assess the increases in polio- and rotavirus output by multiple stable knockout cell lines. Unlike previous studies, the Vero knockout cell lines failed to achieve desired target yield increases. These findings suggest that additional research will be required before implementing the genetically engineered Vero cell lines in the manufacturing process for polio- and rotavirus vaccines to be able to supply vaccines at reduced prices.

      5. Assessment of poliovirus antibody seroprevalence in high risk areas for vaccine derived poliovirus transmission in MadagascarExternal
        Razafindratsimandresy R, Mach O, Heraud JM, Bernardson B, Weldon WC, Oberste MS, Sutter RW.
        Heliyon. 2018 Mar;4(3):e00563.

        Background: Vaccine-derived polioviruses (VDPV) outbreaks typically occur in areas of low poliovirus immunity. Madagascar successfully eradicated wild poliovirus in 1997; however, multiple VDPV outbreaks have occurred since then, and numerous vaccination campaigns have been carried out to control the VDPV outbreaks. We conducted a survey of poliovirus neutralizing antibodies among Malagasy children to assess performance of vaccination campaigns and estimate the risk of future VDPV outbreaks. Methods: This was a random community survey in children aged 6-11 months, 36-59 months and 5-14 years of age in high risk areas of Madagascar (Mahajanga, Toliara, Antsalova, and Midongy-atsimo); and in a reference area (Antananarivo). After obtaining informed consent, basic demographic and vaccination history, 2 mL of peripheral blood were collected. Neutralizing antibodies against all three poliovirus serotypes were detected by using a standard microneutralization assay. Results: There were 1500 children enrolled and 1496 (>99%) provided sufficient quantity of blood for analysis. Seroprevalence for poliovirus type 1 (PV1) was >90% in all age groups and study areas. PV2 seroprevalence ranged between 75-100%; it was lowest in the youngest age group in Midongy and Toliara. PV3 seroprevalence ranged between 79-100%. Seroprevalence in the reference area was not significantly different from polio high risk sites. Discussion: Madagascar achieved high population immunity. In order to preserve these gains, routine immunization needs to be strengthened. Currently, the risk of new VDPV emergences in Madagascar appears low.

      6. Impact of pentavalent rotavirus vaccine against severe rotavirus diarrhoea in The GambiaExternal
        Sanneh B, Papa Sey A, Shah M, Tate J, Sonko M, Jagne S, Jarju M, Sowe D, Taal M, Cohen A, Parashar U, Mwenda JM.
        Vaccine. 2018 Mar 12.

        INTRODUCTION: Rotavirus vaccines protect against the leading cause of severe childhood diarrhoea, and have been introduced in many low-income African countries. The Gambia introducedRotateq(R) (RV5) into their national immunization program in 2013. We revieweddata from an active rotavirus sentinel surveillancesitefor early evidence of vaccine impact. METHODS: We compared rotavirus prevalence in diarrhoeal stool in children< 5years of age admittedat the Edward Francis Small Teaching Hospital sentinel surveillance site before (2013) andafterRV5 introduction (2015-2016) in the Gambia. The rotavirus-percent positive was separately compared for all diarrhoealhospitalizations and for hospitalizations with severe symptoms. Rotavirus prevalence was compared annually for the pre-vaccine year of 2013 with post-vaccine years of 2015 and 2016 using chi-square or Fisher’s exact tests and the p-value to establish significant relationship was set at p<0.05. All analyses were completed in SAS 9.3 (SAS Analytics, North Carolina). RESULTS: Rotavirus prevalence among all diarrhoeahospitalizations decreased from 22% in 2013 to 11% in 2015 (p=0.04), while remaining unchanged in 2016 (18%, p=0.56). For hospitalizations that were clinically severe and/or treated with intravenous fluids (mean of 46 per year), the rotavirus prevalence decreased from 33% in 2013 to 8% in 2015 (p=0.04), and to 15% in 2016 (p=0.08). The children with age <1year accounted for 45% the population infected with rotavirus in both pre and post rotavirus vaccination periods. CONCLUSIONS: Rotavirus vaccine introduction in the Gambia could be among factors resulting in decreased diarrhea hospitalizations among children at the Edward Francis Small Teaching Hospital, particularly those with severe disease. These results support the continuation of rotavirus vaccine and additional monitoring of rotavirus hospitalization trends in the country.

      7. Assessing the potency and immunogenicity of inactivated poliovirus vaccine after exposure to freezing temperaturesExternal
        White JA, Estrada M, Weldon WC, Chumakov K, Kouiavskaia D, Fournier-Caruana J, Stevens E, Gary HE, Maes EF, Oberste MS, Snider CJ, Anand A, Chen D.
        Biologicals. 2018 Mar 14.

        According to manufacturers, inactivated poliovirus vaccines (IPVs) are freeze sensitive and require storage between 2 degrees C and 8 degrees C, whereas oral poliovirus vaccine requires storage at -20 degrees C. Introducing IPV into ongoing immunization services might result in accidental exposure to freezing temperatures and potential loss of vaccine potency. To better understand the effect of freezing IPVs, samples of single-dose vaccine vials from Statens Serum Institut (VeroPol) and multi-dose vaccine vials from Sanofi Pasteur (IPOL) were exposed to freezing temperatures mimicking what a vaccine vial might encounter in the field. D-antigen content was measured to determine the in vitro potency by ELISA. Immunogenicity testing was conducted for a subset of exposed IPVs using the rat model. Freezing VeroPol had no detectable effect on in vitro potency (D-antigen content) in all exposures tested. Freezing of the IPOL vaccine for 7 days at -20 degrees C showed statistically significant decreases in D-antigen content by ELISA in poliovirus type 1 (p<0.0001) and type 3 (p=0.048). Reduction of poliovirus type 2 potency also approached significance (p=0.062). The observed loss in D-antigen content did not affect immunogenicity in the rat model. Further work is required to determine the significance of the loss observed and the implications for vaccine handling policies and practices.

    • Injury and Violence
      1. Characteristics of and precipitating circumstances surrounding suicide among persons aged 10-17 years – Utah, 2011-2015External
        Annor FB, Zwald ML, Wilkinson A, Friedrichs M, Fondario A, Dunn A, Nakashima A, Gilbert LK, Ivey-Stephenson AZ.
        MMWR Morb Mortal Wkly Rep. 2018 Mar 23;67(11):329-332.

        In 2015, suicide was the third leading cause of death among persons aged 10-17 years (1), and in Utah, the age-adjusted suicide rate was consistently higher than the national rate during the past decade (2). In January 2017, the Utah Department of Health (UDOH) invited CDC to assist with an epidemiologic investigation of suicides among youths aged 10-17 years during 2011-2015 to identify precipitating factors. CDC analyzed data from the Utah Violent Death Reporting System (UTVDRS), National Vital Statistics System, and additional information collected in the field. During 2011-2015 in Utah, 150 youths died by suicide. Approximately three fourths of decedents were male (77.4%) and aged 15-17 years (75.4%). During this period, the unadjusted suicide rate per 100,000 youths in Utah increased 136.2%, from 4.7 per 100,000 population (2011) to 11.1 (2015), whereas among youths nationwide, the rate increased 23.5%, from 3.4 to 4.1. Among suicide decedents with circumstances data available, more than two thirds (68.3%) had multiple precipitating circumstances, including mental health diagnosis (35.2%), depressed mood (31.0%), recent crisis (55.3%), and history of suicidal ideation or attempt (29.6%). CDC’s technical package of policies, programs, and practices to prevent suicide supported by the best available evidence can be used as a suicide prevention resource (3).

      2. Introduction: This study assessed young athletes’ (ages 12 to 17) concussion attitudes and behaviors, particularly their self-reported experience learning about concussion and intentions to report a concussion and disparities in these experiences. Methods: We used data from Porter Novelli’s 2014 YouthStyles survey that is conducted each year to gather insights about American consumers. Results: Of the 1,005 respondents, 57% reported sports participation. Fourteen percent reported they may have had a previous concussion, and among them 41% reported having a concussion more than once while playing sports. Males (17.7%) were significantly more likely to report having a concussion than females (10.0%; x2 (1)=7.01, p=0.008). Fifty-five percent of respondents reported having learned about what to do if they think they may have a concussion, and 92% reported that they would tell their coach if they thought they sustained a concussion while playing youth or high school sports. Youth from higher income families ($75,000-$124,999) were significantly more likely than youth from lower income families (less than $35,000) to report that they learned about what do if they suspected that they had a concussion. Conclusion: Age of athlete, parental income level, athlete’s sex, and living in a metro versus non-metro area led to disparities in athletes’ concussion education. There is a need for increased access to concussion education and an emphasis on customizing concussion education efforts to meet the needs of different groups. Practical application: We identified athletes’ self-reported previously sustained concussions and predictors of education related to concussion. Further research is needed to explore the age, gender and income gaps in concussion education among athletes.

      3. Beyond residential mobility: A broader conceptualization of instability and its impact on victimization risk among childrenExternal
        Merrick MT, Henly M, Turner HA, David-Ferdon C, Hamby S, Kacha-Ochana A, Simon TR, Finkelhor D.
        Child Abuse Negl. 2018 Mar 17;79:485-494.

        Predictability in a child’s environment is a critical quality of safe, stable, nurturing relationships and environments, which promote wellbeing and protect against maltreatment. Research has focused on residential mobility’s effect on this predictability. This study augments such research by analyzing the impact of an instability index-including the lifetime destabilization factors (LDFs) of natural disasters, homelessness, child home removal, multiple moves, parental incarceration, unemployment, deployment, and multiple marriages–on childhood victimizations. The cross-sectional, nationally representative sample of 12,935 cases (mean age=8.6 years) was pooled from 2008, 2011, and 2014 National Surveys of Children’s Exposure to Violence (NatSCEV). Logistic regression models controlling for demographics, socio-economic status, and family structure tested the association between excessive residential mobility, alone, and with LDFs, and past year childhood victimizations (sexual victimization, witnessing community or family violence, maltreatment, physical assault, property crime, and polyvictimization). Nearly 40% of the sample reported at least one LDF. Excessive residential mobility was significantly predictive of increased odds of all but two victimizations; almost all associations were no longer significant after other destabilizing factors were included. The LDF index without residential mobility was significantly predictive of increased odds of all victimizations (AOR’s ranged from 1.36 to 1.69), and the adjusted odds ratio indicated a 69% increased odds of polyvictimization for each additional LDF a child experienced. The LDF index thus provides a useful alternative to using residential moves as the sole indicator of instability. These findings underscore the need for comprehensive supports and services to support stability for children and families.

    • Laboratory Sciences
      1. Multicenter validation of commercial antigenuria reagents to diagnose progressive disseminated histoplasmosis in people living with HIV/AIDS in two Latin American countriesExternal
        Caceres DH, Samayoa BE, Medina NG, Tobon AM, Guzman BJ, Mercado D, Restrepo A, Chiller T, Arathoon EE, Gomez BL.
        J Clin Microbiol. 2018 Mar 21.

        Histoplasmosis is an important cause of mortality in patients with AIDS, especially in countries with limited access to antiretroviral therapies and diagnostic tests. However, many disseminated infections in Latin America go undiagnosed. A simple, rapid method to detect Histoplasma capsulatum infection in endemic regions would dramatically decrease time to diagnosis and treatment, reducing morbidity and mortality. The aim of this study was to validate a commercial monoclonal Histoplasma galactomannan (HGM) ELISA (Immuno-Mycologics [IMMY], Norman, Oklahoma, USA) in two cohorts of people living with HIV/AIDS (PLHIV). We analyzed urine samples from 589 people (466 from Guatemala and 123 from Colombia), including 546 from PLHIV and 43 from non-PLHIV controls. Sixty-three of these people (35 from Guatemala and 28 from Colombia) had confirmed histoplasmosis by isolation of H. capsulatum Using the standard curve provided by the quantitative commercial test, sensitivity was 98% (95% CI, 95-100) and specificity was 97% (95% CI, 96-99) (cutoff=0.5 ng/mL). Semi-quantitative results, using a calibrator of 12.5 ng/mL of Histoplasma galactomannan to calculate an EIA Index Value (EIV) of the samples, showed a sensitivity of 95% (95% CI, 89-100%) and specificity of 98% (95% CI, 96-99%) (cutoff >/=2.6 EIV). This relatively simple-to-perform commercial antigenuria test showed a high performance, with reproducible results in both countries, suggesting that it can used to detect progressive disseminated histoplasmosis in PLHIV in a wide range of clinical laboratories in countries where histoplasmosis is endemic.

      2. Heterologous expression of three antigenic proteins from Angiostrongylus cantonensis: ES-7, Lec-5, and 14-3-3 in mammalian cellsExternal
        Cognato BB, Handali S, Morassutti AL, da Silva AJ, Graeff-Teixeira C.
        Mol Biochem Parasitol. 2018 Mar 16.

        Angiostrongylus cantonensis is a parasitic nematode and the main causative agent of human cerebral eosinophilic meningoencephalitis (EoM). A definitive diagnosis of EoM usually requires serologic or molecular analysis of the patient’s clinical sample. Currently, a 31kDa antigen is used in immunological tests for this purpose, however as a crude antigen preparation it may present cross-reactivity with other helminthic infections, especially echinococcosis. Heterologous expression studies using prokaryotic systems failed on producing antigenic proteins. The aim of this study was to express and purify three recombinant glycoproteins representing A. cantonensis antigens: ES-7, Lec-5, and 14-3-3, in Chinese hamster ovary (CHO) cells and ES-7 in human embryonic kidney (HEK) cells to develop a source of specific antigens to be used in the diagnosis of angiostrongyliasis. The potential diagnostic value of these three proteins was subsequently characterized in one- and two-dimensional electrophoresis and Western blot to dot blot analyses, with Angiostrongylus-positive sera, normal human sera (NHS), and a pool of Echinococcus-positive sera (included as a specificity control) used for detection. In addition, recognition of these three proteins following treatment with N-glycosidase F was examined. The ES-7 proteins that were expressed in HEK and CHO cells, and the Lec-5 protein that was expressed in CHO cells, were specifically recognized by A. cantonensis-positive sera in the 2D electrophoresis analysis. This recognition was shown to be dependent on the presence of glycidic portions, making mammalian cells a very promising source of heterologous expression antigenic proteins from Angiostrongylus.

      3. Initial public health laboratory response after Hurricane Maria – Puerto Rico, 2017External
        Concepcion-Acevedo J, Patel A, Luna-Pinto C, Pena RG, Cuevas Ruiz RI, Arbolay HR, Toro M, Deseda C, De Jesus VR, Ribot E, Gonzalez JQ, Rao G, De Leon Salazar A, Ansbro M, White BB, Hardy MC, Georgi JC, Stinnett R, Mercante AM, Lowe D, Martin H, Starks A, Metchock B, Johnston S, Dalton T, Joglar O, Stafford C, Youngblood M, Klein K, Lindstrom S, Berman L, Galloway R, Schafer IJ, Walke H, Stoddard R, Connelly R, McCaffery E, Rowlinson MC, Soroka S, Tranquillo DT, Gaynor A, Mangal C, Wroblewski K, Muehlenbachs A, Salerno RM, Lozier M, Sunshine B, Shapiro C, Rose D, Funk R, Pillai SK, O’Neill E.
        MMWR Morb Mortal Wkly Rep. 2018 Mar 23;67(11):333-336.

        Hurricane Maria made landfall in Puerto Rico on September 20, 2017, causing major damage to infrastructure and severely limiting access to potable water, electric power, transportation, and communications. Public services that were affected included operations of the Puerto Rico Department of Health (PRDOH), which provides critical laboratory testing and surveillance for diseases and other health hazards. PRDOH requested assistance from CDC for the restoration of laboratory infrastructure, surveillance capacity, and diagnostic testing for selected priority diseases, including influenza, rabies, leptospirosis, salmonellosis, and tuberculosis. PRDOH, CDC, and the Association of Public Health Laboratories (APHL) collaborated to conduct rapid needs assessments and, with assistance from the CDC Foundation, implement a temporary transport system for shipping samples from Puerto Rico to the continental United States for surveillance and diagnostic and confirmatory testing. This report describes the initial laboratory emergency response and engagement efforts among federal, state, and nongovernmental partners to reestablish public health laboratory services severely affected by Hurricane Maria. The implementation of a sample transport system allowed Puerto Rico to reinitiate priority infectious disease surveillance and laboratory testing for patient and public health interventions, while awaiting the rebuilding and reinstatement of PRDOH laboratory services.

      4. Understanding transport characteristics of airborne nanotubes and nanofibers is important for assessing their fate in the respiratory system. Typically, diffusion and aerodynamic diameters capture key deposition mechanisms of near-spherical particles such as diffusion and impaction in the submicrometer size range. For nonspherical particles with high aspect ratios, such as aerosolized carbon nanotubes, these diameters can vary widely, requiring their independent measurement. The objective of this study was to develop an approach to provide approximate estimates of aerodynamic- and diffusion-equivalent diameters of airborne carbon nanotubes (CNTs) and carbon nanofibers (CNFs) using their morphological characteristics obtained from electron micrographs. The as-received CNT and CNF materials were aerosolized using different techniques such as dry dispersion and nebulization. Mobility and aerodynamic diameters of test aerosol were directly deduced from tandem measurement of particle mobility and mass. The same test aerosol was mobility-classified and subsequently collected on a microscopy grid for transmission electron microscopy (TEM) analysis. TEM micrographs were used to obtain projected area, maximum projected length, and two-dimensional (2-D) radius of gyration of test particles. Estimates of the aerodynamic diameter and the diffusion diameter were obtained by applying the fractal theory developed for aerosol agglomerates of primary spherical particles. After accounting for the particle dynamic shape factor, estimated aerodynamic diameters agreed with those from the direct measurements (using tandem mobility-mass technique) within 30-40% for the agglomerates with relatively open structures while the diffusion diameters agreed within 40-50%. The uncertainty of these estimates mainly depends on degree of overlapping structures in the microscopy image and nonuniformity in tube diameter. The approach could be useful in calculating approximate airborne properties from microscopy images of CNT and CNF agglomerates with relatively open structures.

      5. Francisella tularensis, the causative agent of tularemia, is a HHS Tier 1 select agent. Tularemia is the most commonly reported human and animal infection caused by a bacterial select agent in the United States. Because of the rarity of disease, low clinical suspicion, and the organism’s low infectious dose, F. tularensis poses a hazard for unsuspecting laboratorians, particularly those who handle cultures outside a biological safety cabinet or without use of appropriate personal protective equipment (PPE). We examined Form 4s and Form 3s submitted to the Federal Select Agent Program between 2011 and 2015 to assess laboratory methods used in the identification of F. tularensis and categorize reported occupational exposures. Culture, which is used in a confirmatory identification, was the primary method used in clinical laboratories. Reported occupational exposures in clinical, veterinary, and reference laboratories occurred at a rate of 33.8, 14.0, and 0.4/100 isolates, respectively. The number of exposed workers in clinical, reference, veterinary, and research laboratories was 3.2, 2.4, 5.1, and 0.9 workers per reported incident, respectively. Most reported occupational exposures occurred in clinical laboratorians working on the bench at BSL-2 conditions with isolated cultures with no suspicion that the organism was F. tularensis; the fewest occurred in research laboratories at BSL-3 where occupational exposures were prevented by prior knowledge that the organism was F. tularensis and the PPE that was used in these laboratories.

      6. [No abstract]

      7. Flucytosine resistance in Cryptococcus gattii is indirectly mediated by the FCY2-FCY1-FUR1 pathwayExternal
        Vu K, Thompson GR, Roe CC, Sykes JE, Dreibe EM, Lockhart SR, Meyer W, Engelthaler DM, Gelli A.
        Med Mycol. 2018 Mar 15.

        Cryptococcosis is an opportunistic fungal infection caused by members of the two sibling species complexes: Cryptococcus neoformans and Cryptococcus gattii. Flucytosine (5FC) is one of the most widely used antifungals against Cryptococcus spp., yet very few studies have looked at the molecular mechanisms responsible for 5FC resistance in this pathogen. In this study, we examined 11 C. gattii clinical isolates of the major molecular type VGIII based on differential 5FC susceptibility and asked whether there were genomic changes in the key genes involved in flucytosine metabolism. Susceptibility assays and sequencing analysis revealed an association between a point mutation in the cytosine deaminase gene (FCY1) and 5FC resistance in two of the studied 5FC resistant C. gattii VGIII clinical isolates, B9322 and JS5. This mutation results in the replacement of arginine for histidine at position 29 and occurs within a variable stretch of amino acids. Heterologous expression of FCY1 and spot sensitivity assays, however, demonstrated that this point mutation did not have any effect on FCY1 activities and was not responsible for 5FC resistance. Comparative sequence analysis further showed that no changes in the amino acid sequence and no genomic alterations were observed within 1 kb of the upstream and downstream sequences of either cytosine permeases (FCY2-4) or uracil phosphoribosyltransferase (FUR1) genes in 5FC resistant and 5FC susceptible C. gattii VGIII isolates. The herein obtained results suggest that the observed 5FC resistance in the isolates B9322 and JS5 is due to changes in unknown protein(s) or pathway(s) that regulate flucytosine metabolism.

      8. Calibration approaches for the measurement of aerosol multielemental concentration using spark emission spectroscopyExternal
        Zheng L, Kulkarni P, Dionysiou DD.
        Journal of Analytical Atomic Spectrometry. 2018 ;33(3):404-412.

        A multivariate calibration approach, using partial least squares regression, has been developed for the measurement of aerosol elemental concentration. A training set consisting of 25 orthogonal aerosol samples with 9 factors (elements: Cr, Mn, Fe, Ni, Cu, Zn, Cd, Pb, and Ti) and 5 levels (elemental concentrations) was designed. Spectral information was obtained for each aerosol sample using aerosol spark emission spectroscopy (ASES) at a time resolution of 1 minute. Simultaneously, filter samples were collected for the determination of elemental concentration using an inductively coupled plasma mass spectrometry (ICP-MS) analysis. Two regression models, PLS1 and PLS2, were developed to predict mass concentration from spectral measurements. The prediction ability of the models improved substantially when only signature wavelengths were included instead of the entire spectrum. The PLS1 model with 45 selected spectral variables (PLS1-45 model) presented the lowest relative root mean square error of cross validation (RMSECV; 16-35%). The detection limits using the PLS1-45 model for the nine elements were in the range of 0.16-0.50 microg m-3. The performance of both multivariate and univariate regression models was tested for an unknown sample of welding fume aerosol. The multivariate model did not provide significantly better prediction compared to the univariate model. In spite of the difference in the matrices of the calibration aerosol and the unknown test aerosol, the results from the PLS model show good agreement with those from filter measurements. The relative root mean square error of prediction (RMSEP) obtained from the PLS1-45 model was 13% for Cr, 23% for Fe, 22% for Mn and 12% for Ni. The study shows that in spite of lower spectral resolution and lack of sample preparation, reliable and robust measurements can be obtained using the proposed calibration method based on PLS regression.

    • Maternal and Child Health
      1. Hearing trajectory in children with congenital cytomegalovirus infectionExternal
        Lanzieri TM, Chung W, Leung J, Caviness AC, Baumgardner JL, Blum P, Bialek SR, Demmler-Harrison G.
        Otolaryngol Head Neck Surg. 2018 Feb 1:194599818758247.

        Objectives To compare hearing trajectories among children with symptomatic and asymptomatic congenital cytomegalovirus infection through age 18 years and to identify brain abnormalities associated with sensorineural hearing loss (SNHL) in asymptomatic case patients. Study Design Longitudinal prospective cohort study. Setting Tertiary medical center. Subjects and Methods The study included 96 case patients (4 symptomatic and 92 asymptomatic) identified through hospital-based newborn cytomegalovirus screening from 1982 to 1992 and 72 symptomatic case patients identified through referrals from 1993 to 2005. We used growth curve modeling to analyze hearing thresholds (0.5-8 kHz) by ear with increasing age and Cox regression to determine abnormal findings on head computed tomography scan associated with SNHL (hearing threshold >/=25 dB in any audiometric frequency) among asymptomatic case patients. Results Fifty-six (74%) symptomatic and 20 (22%) asymptomatic case patients had SNHL: congenital/early-onset SNHL was diagnosed in 78 (51%) and 10 (5%) ears, respectively, and delayed-onset SNHL in 25 (17%) and 20 (11%) ears; 49 (32%) and 154 (84%) ears had normal hearing. In affected ears, all frequency-specific hearing thresholds worsened with age. Congenital/early-onset SNHL was significantly worse (severe-profound range, >70 dB) than delayed-onset SNHL (mild-moderate range, 26-55 db). Frequency-specific hearing thresholds were significantly different between symptomatic and asymptomatic case patients at 0.5 to 1 kHz but not at higher frequencies (2-8 kHz). Among asymptomatic case patients, white matter lucency was significantly associated with SNHL by age 5 years (hazard ratio, 4.4; 95% CI, 1.3-15.6). Conclusion Congenital/early-onset SNHL frequently resulted in severe to profound loss in symptomatic and asymptomatic case patients. White matter lucency in asymptomatic case patients was significantly associated with SNHL by age 5 years.

      2. Determining gestational age and preterm birth in rural Guatemala: A comparison of methodsExternal
        Weinstein JR, Thompson LM, Diaz Artiga A, Bryan JP, Arriaga WE, Omer SB, McCracken JP.
        PLoS One. 2018 ;13(3):e0193666.

        BACKGROUND: Preterm birth is the leading cause of death among children <5 years of age. Accurate determination of prematurity is necessary to provide appropriate neonatal care and guide preventive measures. To estimate the most accurate method to identify infants at risk for adverse outcomes, we assessed the validity of two widely available methods-last menstrual period (LMP) and the New Ballard (NB) neonatal assessment-against ultrasound in determining gestational age and preterm birth in highland Guatemala. METHODS: Pregnant women (n = 188) were recruited with a gestational age <20 weeks and followed until delivery. Ultrasound was performed by trained physicians and LMP was collected during recruitment. NB was performed on infants within 96 hours of birth by trained study nurses. LMP and NB accuracy at determining gestational age and identifying prematurity was assessed by comparing them to ultrasound. RESULTS: By ultrasound, infant mean gestational age at birth was 38.3 weeks (SD = 1.6) with 16% born at less than 37 gestation. LMP was more accurate than NB (mean difference of +0.13 weeks for LMP and +0.61 weeks for NB). However, LMP and NB estimates had low agreement with ultrasound-determined gestational age (Lin’s concordance<0.48 for both methods) and preterm birth (kappa<0.29 for both methods). By LMP, 18% were judged premature compared with 6% by NB. LMP underestimated gestational age among women presenting later to prenatal care (0.18 weeks for each additional week). Gestational age for preterm infants was overestimated by nearly one week using LMP and nearly two weeks using NB. New Ballard neuromuscular measurements were more predictive of preterm birth than those measuring physical criteria. CONCLUSION: In an indigenous population in highland Guatemala, LMP overestimated prematurity by 2% and NB underestimated prematurity by 10% compared with ultrasound estimates. New, simple and accurate methods are needed to identify preterm birth in resource-limited settings worldwide.

    • Parasitic Diseases
      1. Combination of indoor residual spraying with long-lasting insecticide-treated nets for malaria control in Zambezia, Mozambique: a cluster randomised trial and cost-effectiveness study protocolExternal
        Chaccour CJ, Alonso S, Zulliger R, Wagman J, Saifodine A, Candrinho B, Macete E, Brew J, Fornadel C, Kassim H, Loch L, Sacoor C, Varela K, Carty CL, Robertson M, Saute F.
        BMJ Glob Health. 2018 ;3(1):e000610.

        Background: Most of the reduction in malaria prevalence seen in Africa since 2000 has been attributed to vector control interventions. Yet increases in the distribution and intensity of insecticide resistance and higher costs of newer insecticides pose a challenge to sustaining these gains. Thus, endemic countries face challenging decisions regarding the choice of vector control interventions. Methods: A cluster randomised trial is being carried out in Mopeia District in the Zambezia Province of Mozambique, where malaria prevalence in children under 5 is high (68% in 2015), despite continuous and campaign distribution of long-lasting insecticide-treated nets (LLINs). Study arm 1 will continue to use the standard, LLIN-based National Malaria Control Programme vector control strategy (LLINs only), while study arm 2 will receive indoor residual spraying (IRS) once a year for 2 years with a microencapsulated formulation of pirimiphos-methyl (Actellic 300 CS), in addition to the standard LLIN strategy (LLINs+IRS). Prior to the 2016 IRS implementation (the first of two IRS campaigns in this study), 146 clusters were defined and stratified per number of households. Clusters were then randomised 1:1 into the two study arms. The public health impact and cost-effectiveness of IRS intervention will be evaluated over 2 years using multiple methods: (1) monthly active malaria case detection in a cohort of 1548 total children aged 6-59 months; (2) enhanced passive surveillance at health facilities and with community health workers; (3) annual cross-sectional surveys; and (4) entomological surveillance. Prospective microcosting of the intervention and provider and societal costs will be conducted. Insecticide resistance status pattern and changes in local Anopheline populations will be included as important supportive outcomes. Discussion: By evaluating the public health impact and cost-effectiveness of IRS with a non-pyrethroid insecticide in a high-transmission setting with high LLIN ownership, it is expected that this study will provide programmatic and policy-relevant data to guide national and global vector control strategies. Trial registration number: NCT02910934.

    • Substance Use and Abuse
      1. Self-identified tobacco use and harm perceptions among US youthExternal
        Agaku I, Odani S, Vardavas C, Neff L.
        Pediatrics. 2018 Mar 15.

        BACKGROUND: We investigated tobacco-related self-identity and risk perceptions among adolescent tobacco users. METHODS: Data were analyzed for 20 675 US sixth- to 12th-graders from the 2016 National Youth Tobacco Survey. Students who reported past-30-day use of a specific tobacco product or >/=2 products but denied having used “any tobacco product” in the past 30 days were classified as not self-identifying as tobacco users. Tobacco product harm perceptions were further assessed across products. Descriptive and multivariable logistic regression analyses were performed. RESULTS: Among past-30-day users of >/=1 specific tobacco product type, those denying having used any tobacco products in the past 30 days included single-product users of roll-your-own and/or pipe tobacco (82.2%), electronic cigarettes (e-cigarettes) (59.7%), cigars (56.6%), hookah (44.0%), smokeless tobacco (38.5%), and cigarettes (26.5%) as well as poly-tobacco users (12.7%). The odds of denying using any tobacco products were higher among those without symptoms of nicotine dependence than those with symptoms (adjusted odds ratio = 2.16); and those who access their tobacco products via social sources than those who bought them (adjusted odds ratio = 3.81; all P < .05). Among those believing “all tobacco products” were harmful, single-product users of the following believed their own product was not harmful: e-cigarettes (74.6%), hookah (56.0%), smokeless tobacco (41.8%), and cigarettes (15.5%). CONCLUSIONS: Many of those who used certain tobacco products exclusively did not self-identify as tobacco users. Increasing the sensitivity of questions used to assess youth tobacco use in surveys and clinical settings can mitigate nondisclosure or underreporting of true tobacco use status.

      2. Smoking increases HIV-related and non-HIV-related morbidity and mortality for persons with HIV infection. We estimated changes in cigarette smoking among adults with HIV and adults in the general U.S. population from 2009 to 2014 to inform HIV smoking cessation programs. Among HIV-positive adults, rates of current smoking declined from 37.6% (confidence interval [CI]: 34.7-40.6) in 2009 to 33.6% (CI: 29.8-37.8) in 2014. Current smoking among U.S. adults declined from 20.6% (CI: 19.9-21.3) in 2009 to 16.8% (CI: 16.2-17.4) in 2014. HIV-positive adults in care were significantly more likely to be current smokers compared with the general U.S. population; they were also less likely to quit smoking. For both HIV-positive adults in care and the general population, disparities were noted by racial/ethnic, educational level, and poverty-level subgroups. For most years, non-Hispanic blacks, those with less than high school education, and those living below poverty level were more likely to be current smokers and less likely to quit smoking compared with non-Hispanic whites, those with greater than high school education, and those living above poverty level, respectively. To decrease smoking-related causes of illness and death and to decrease HIV-related disparities, smoking cessation interventions are vital as part of routine care with HIV-positive persons. Clinicians who care for HIV-positive persons who smoke should utilize opportunities to discuss and implement smoking cessation strategies during routine clinical visits.

      3. Factors associated with concurrent heroin use among patients on methadone maintenance treatment in Vietnam: A 24-month retrospective analysis of a nationally representative sampleExternal
        Hoang T, Nguyen H, Shiraishi RW, Nguyen M, Bingham T, Nguyen D, Nguyen T, Duong H, Lyss S, Tran H.
        Int J Drug Policy. 2018 Mar 15;55:113-120.

        BACKGROUND: Methadone maintenance treatment (MMT) is highly effective for reducing heroin use and HIV transmission among people who inject opioids. We sought to measure and understand factors associated with continued heroin use, a critical factor affecting treatment outcome among MMT patients in Vietnam. METHOD: We collected data from medical charts of a nationally representative sample of patients who were on MMT from May 2008 to December 2013. We selected 10 MMT clinics using probability proportional to size and 50 patients/clinic by systematic random sampling. Concurrent heroin use was defined by self-report/positive urine test recorded in patient charts during month 3, 6, 12, and 24 after MMT initiation. We used multivariable logistic regression to identify factors associated with concurrent heroin use over the first 24 months in treatment. FINDINGS: All clients used heroin at baseline; concurrent heroin use was 55% at month 3; 19%, 14.6% and 15.2% at month 6, 12, and 24, respectively. Having no family emotional/financial support at baseline versus having this support (AOR=2.03; 95% confidence interval [CI]=1.17-3.53); using heroin for <15years versus >/=15 years at baseline (AOR=1.55; 95% CI=1.01-2.38); being HIV-infected/not on antiretroviral treatment (ART; AOR=1.79; 95% CI=1.07-2.98) or being HIV infected/on ART (AOR=2.39; 95% CI=1.61-3.55), versus not being HIV infected; baseline methamphetamine use versus non-use (AOR=2.68; 95% CI=1.08-6.65), were associated with increased odds of concurrent heroin use among patients. CONCLUSION: The association between concurrent heroin use among MMT patients and lack of family emotional/financial support, highlights the critical importance of these types of support for successful treatment. Association with shorter heroin use history suggests motivational enhancement may reduce concurrent heroin use. Living with HIV, whether on ART or not, is associated with increased concurrent heroin use and suggests safe injection commodities and education, and drug-drug interaction management, are needed for this subgroup. Though few MMT clients reported baseline methamphetamine use, its association with later heroin use suggests the need for effective methamphetamine use interventions.

      4. Annual total binge drinks consumed by U.S. adults, 2015External
        Kanny D, Naimi TS, Liu Y, Lu H, Brewer RD.
        Am J Prev Med. 2018 Apr;54(4):486-496.

        INTRODUCTION: Binge drinking (four or more drinks for women, five or more drinks for men on an occasion) accounts for more than half of the 88,000 U.S. deaths resulting from excessive drinking annually. Adult binge drinkers do so frequently and at high intensity; however, there are known disparities in binge drinking that are not well characterized by any single binge-drinking measure. A new measure of total annual binge drinks was used to assess these disparities at the state and national levels. METHODS: Behavioral Risk Factor Surveillance System 2015 data (analyzed in 2016) were used to estimate the prevalence, frequency, intensity, and total binge drinks among U.S. adults. Total annual binge drinks was calculated by multiplying annual binge-drinking episodes by binge-drinking intensity. RESULTS: In 2015, a total of 17.1% of U.S. adults (37.4 million) reported an annual average of 53.1 binge-drinking episodes per binge drinker, at an average intensity of 7.0 drinks per binge episode, resulting in 17.5 billion total binge drinks, or 467.0 binge drinks per binge drinker. Although binge drinking was more common among young adults (aged 18-34 years), half of the total binge drinks were consumed by adults aged >/=35 years. Total binge drinks per binge drinker were substantially higher among those with lower educational levels and household incomes than among those with higher educational levels and household incomes. CONCLUSIONS: U.S. adult binge drinkers consume about 17.5 billion total binge drinks annually, or about 470 binge drinks/binge drinker. Monitoring total binge drinks can help characterize disparities in binge drinking and help plan and evaluate effective prevention strategies.

      5. This study describes patterns of cigarette smoking (current, former, never) by sociodemographic, household, and chronic disease characteristics and correlates among US adults receiving housing assistance from the US Department of Housing and Urban Development (HUD) during 2007-2012. Estimates were generated from 4,771 adults by using National Health Interview Survey and HUD-linked data. Overall, 48.4% of HUD-assisted adults were never smokers, 33.0% were current smokers, and 18.6% were former smokers; smoking status varied by sex, age, race/ethnicity, whether children were living in the household, and chronic disease status. These estimates could inform tobacco control interventions to improve the health and well-being of HUD-assisted residents.

    • Zoonotic and Vectorborne Diseases
      1. Serological evidence of Orthopoxvirus circulation among equids, southeast BrazilExternal
        Borges IA, Reynolds MG, McCollum AM, Figueiredo PO, Ambrosio LL, Vieira FN, Costa GB, Matos AC, de Andrade Almeida VM, Ferreira PC, Lobato ZI, dos Reis JK, Kroon EG, Trindade GS.
        Frontiers in Microbiology. 2018 08 Mar;9 (MAR) (402).

        Since 1999 Vaccinia virus (VACV) outbreaks involving bovines and humans have been reported in Brazil; this zoonosis is known as Bovine Vaccinia (BV) and is mainly an occupational disease of milkers. It was only in 2008 (and then again in 2011 and 2014) however, that VACV was found causing natural infections in Brazilian equids. These reports involved only equids, no infected humans or bovines were identified, and the sources of infections remain unknown up to date. The peculiarities of Equine Vaccinia outbreaks (e.g., absence of human infection), the frequently shared environments, and fomites by equids and bovines in Brazilian farms and the remaining gaps in BV epidemiology incited a question over OPV serological status of equids in Brazil. For this report, sera from 621 equids – representing different species, ages, sexes and locations of origin within Minas Gerais State, southeast Brazil – were examined for the presence of anti-Orthopoxvirus (OPV) antibodies. Only 74 of these were sampled during an Equine Vaccinia outbreak, meaning some of these specific animals presented typical lesions of OPV infections. The majority of sera, however, were sampled from animals without typical signs of OPV infection and during the absence of reported Bovine or Equine Vaccinia outbreaks. Results suggest the circulation of VACV among equids of southeast Brazil even prior to the time of the first VACV outbreak in 2008. There is a correlation of OPVs outbreaks among bovines and equids although many gaps remain to our understanding of its nature. The data obtained may even be carefully associated to recent discussion over OPVs history. Moreover, data is available to improve the knowledge and instigate new researches regarding OPVs circulation in Brazil and worldwide.

      2. Fatal yellow fever in travelers to Brazil, 2018External
        Hamer DH, Angelo K, Caumes E, van Genderen PJ, Florescu SA, Popescu CP, Perret C, McBride A, Checkley A, Ryan J, Cetron M, Schlagenhauf P.
        MMWR Morb Mortal Wkly Rep. 2018 Mar 23;67(11):340-341.

        Yellow fever virus is a mosquito-borne flavivirus that causes yellow fever, an acute infectious disease that occurs in South America and sub-Saharan Africa. Most patients with yellow fever are asymptomatic, but among the 15% who develop severe illness, the case fatality rate is 20%-60%. Effective live-attenuated virus vaccines are available that protect against yellow fever (1). An outbreak of yellow fever began in Brazil in December 2016; since July 2017, cases in both humans and nonhuman primates have been reported from the states of Sao Paulo, Minas Gerais, and Rio de Janeiro, including cases occurring near large urban centers in these states (2). On January 16, 2018, the World Health Organization updated yellow fever vaccination recommendations for Brazil to include all persons traveling to or living in Espirito Santo, Sao Paulo, and Rio de Janeiro states, and certain cities in Bahia state, in addition to areas where vaccination had been recommended before the recent outbreak (3). Since January 2018, 10 travel-related cases of yellow fever, including four deaths, have been reported in international travelers returning from Brazil. None of the 10 travelers had received yellow fever vaccination.

      3. Eastern equine encephalitis virus in the United States, 2003-2016External
        Lindsey NP, Staples JE, Fischer M.
        Am J Trop Med Hyg. 2018 Mar 19.

        Eastern equine encephalitis virus (EEEV) is a mosquito-borne alphavirus found in the eastern United States. Eastern equine encephalitis virus disease in humans is rare but can result in severe, often fatal, illness. This report summarizes the national EEEV surveillance data for 2003 through 2016, including human disease cases and nonhuman infections. Over the 14-year period, 633 counties from 33 states reported EEEV activity; 88% of those counties reported EEEV activity only in nonhuman species. A total of 121 human cases of EEEV disease were reported, with a median of eight cases reported annually. The national average annual incidence of EEEV neuroinvasive disease was 0.03 cases per million population. States with the highest average annual incidence included New Hampshire, Massachusetts, Vermont, Maine, and Alabama. Eastern equine encephalitis virus neuroinvasive disease incidence was highest among males and among persons aged < 5 and > 60 years. Overall, 118 (98%) case patients were hospitalized and 50 (41%) died. The case fatality ratio was highest among case patients aged >/= 70 years. Nonhuman surveillance data indicate that the geographic range of EEEV is much greater than human cases alone might suggest. In areas where the virus circulates, health-care providers should consider EEEV infection in the differential diagnosis for meningitis and encephalitis. Providers are encouraged to report suspected cases to their public health department to facilitate diagnosis and consider interventions to mitigate the risk of further transmission. Because human vaccines against EEEV are not available, prevention depends on community efforts to reduce mosquito populations and personal protective measures to decrease exposure to mosquitoes.

      4. Fatal Powassan encephalitis (deer tick virus, lineage II) in a patient with fever and orchitis receiving rituximabExternal
        Solomon IH, Spera KM, Ryan SL, Helgager J, Andrici J, Zaki SR, Vaitkevicius H, Leon KE, Wilson MR, DeRisi JL, Koo S, Smirnakis SM, De Girolami U.
        JAMA Neurol. 2018 Mar 19.

        Importance: Powassan virus is a rare but increasingly recognized cause of severe neurological disease. Objective: To highlight the diagnostic challenges and neuropathological findings in a fatal case of Powassan encephalitis caused by deer tick virus (lineage II) in a patient with follicular lymphoma receiving rituximab, with nonspecific anti-GAD65 antibodies, who was initially seen with fever and orchiepididymitis. Design, Setting, and Participants: Comparison of clinical, radiological, histological, and laboratory findings, including immunohistochemistry, real-time polymerase chain reaction, antibody detection, and unbiased sequencing assays, in a single case report (first seen in December 2016) at an academic medical center. Exposure: Infection with Powassan virus. Main Outcomes and Measures: Results of individual assays compared retrospectively. Results: In a 63-year-old man with fatal Powassan encephalitis, serum and cerebrospinal fluid IgM antibodies were not detected via standard methods, likely because of rituximab exposure. Neuropathological findings were extensive, including diffuse leptomeningeal and parenchymal lymphohistiocytic infiltration, microglial proliferation, marked neuronal loss, and white matter microinfarctions most severely involving the cerebellum, thalamus, and basal ganglia. Diagnosis was made after death by 3 independent methods, including demonstration of Powassan virus antigen in brain biopsy and autopsy tissue, detection of viral RNA in serum and cerebrospinal fluid by targeted real-time polymerase chain reaction, and detection of viral RNA in cerebrospinal fluid by unbiased sequencing. Extensive testing for other etiologies yielded negative results, including mumps virus owing to prodromal orchiepididymitis. Low-titer anti-GAD65 antibodies identified in serum, suggestive of limbic encephalitis, were not detected in cerebrospinal fluid. Conclusions and Relevance: Owing to the rarity of Powassan encephalitis, a high degree of suspicion is required to make the diagnosis, particularly in an immunocompromised patient, in whom antibody-based assays may be falsely negative. Unbiased sequencing assays have the potential to detect uncommon infectious agents and may prove useful in similar scenarios.

      5. Human infection with avian influenza A(H7N2) virus-Virginia, 2002External
        Terebuh P, Adija A, Edwards L, Rowe T, Jenkins S, Kleene J, Fukuda K, Katz JM, Bridges CB.
        Influenza Other Respir Viruses. 2018 Feb 11.

        BACKGROUND: In March 2002, an outbreak of low-pathogenic avian influenza (LPAI) A(H7N2) was detected among commercial poultry operations in Virginia. METHODS: We performed a serosurvey of 80 government workers involved in efforts to control the outbreak. RESULTS: One study participant who assisted with disposal of infected birds tested positive for neutralizing antibodies to influenza A(H7N2) by microneutralization assay and H7-specific IgM antibodies by enzyme-linked immunosorbent assay (ELISA). The acute infection was temporally associated with an influenza-like illness that resolved without hospitalization. CONCLUSION: This study documents the earliest evidence of human infection with an H7 influenza virus of the North American lineage.

      6. Evaluation of a sequential enzyme immunoassay testing algorithm for Lyme disease demonstrates lack of test independence but high diagnostic specificityExternal
        Wormser GP, Molins CR, Levin A, Lipsett SC, Nigrovic LE, Schriefer ME, Branda JA.
        Diagn Microbiol Infect Dis. 2018 Feb 16.

        To diagnose Lyme disease, a two-tier testing algorithm is used in which supplemental IgM and IgG immunoblots to detect antibody to Borrelia burgdorferi are reflexively performed if a first-tier assay, such as a whole-cell sonicate-based enzyme immunoassay (WCS EIA), is reactive. Recent data suggest that equal specificity is found by substituting the C6 peptide EIA for immunoblots. In this study using 3956 control sera, we demonstrated that although this two-tier testing algorithm does significantly improve diagnostic specificity compared with each of the EIAs individually, the WCS EIA and the C6 peptide EIA are not independent tests. Therefore, when the C6 peptide EIA is used as the second-tier test, it should be regarded as a supplemental rather than a confirmatory test.

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

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