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Issue 42, October 24, 2017

CDC Science Clips: Volume 9, Issue 42, October 23, 2017

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

  1. Top Articles of the Week

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

    The names of CDC authors are indicated in bold text.
    • Communicable Diseases
      • A rapid review of eHealth interventions addressing the continuum of HIV care (2007-2017)
        Henny KD, Wilkes AL, McDonald CM, Denson DJ, Neumann MS.
        AIDS Behav. 2017 Oct 05.
        National HIV prevention goals call for interventions that address Continuum of HIV Care (CoC) for persons living with HIV. Electronic health (eHealth) can leverage technology to rapidly develop and disseminate such interventions. We conducted a qualitative review to synthesize (a) technology types, (b) CoC outcomes, (c) theoretical frameworks, and (d) behavior change mechanisms. This rapid review of eHealth, HIV-related articles (2007-2017) focused on technology-based interventions that reported CoC-related outcomes. Forty-five studies met inclusion criteria. Mobile texting was the most commonly reported technology (44.4%, k = 20). About 75% (k = 34) of studies showed proven or preliminary efficacy for improving CoC-related outcomes. Most studies (60%, k = 27) focused on medication adherence; 20% (k = 9) measured virologic suppression. Many eHealth interventions with preliminary or proven efficacy relied on mobile technology and integrated knowledge/cognition as behavior change mechanisms. This review identified gaps in development and application of eHealth interventions regarding CoC.

      • [No abstract]

    • Food Safety
      • Increasing campylobacter infections, outbreaks, and antimicrobial resistance in the United States, 2004-2012
        Geissler AL, Bustos Carrillo F, Swanson K, Patrick ME, Fullerton KE, Bennett C, Barrett K, Mahon BE.
        Clin Infect Dis. 2017 Jul 20.
        Background: Campylobacteriosis, a leading cause of foodborne illness in the United States, was not nationally notifiable until 2015. Data describing national patterns and trends are limited. We describe the epidemiology of Campylobacter infections in the United States during 2004-2012. Methods: We summarized laboratory-confirmed campylobacteriosis data from the Nationally Notifiable Disease Surveillance System, National Outbreak Reporting System, National Antimicrobial Resistance Monitoring System, and Foodborne Diseases Active Surveillance Network. Results: During 2004-2012, 303520 culture-confirmed campylobacteriosis cases were reported. Average annual incidence rate (IR) was 11.4 cases/100000 persons, with substantial variation by state (range, 3.1-47.6 cases/100000 persons). IRs among patients aged 0-4 years were more than double overall IRs. IRs were highest among males in all age groups. IRs in western states and rural counties were higher (16.2/100000 and 14.2/100000, respectively) than southern states and metropolitan counties (6.8/100000 and 11.0/100000, respectively). Annual IRs increased 21% from 10.5/100000 during 2004-2006 to 12.7/100000 during 2010-2012, with the greatest increases among persons aged >60 years (40%) and in southern states (32%). The annual median number of Campylobacter outbreaks increased from 28 in 2004-2006 to 56 in 2010-2012; in total, 347 were reported. Antimicrobial susceptibility testing of isolates from 4793 domestic and 1070 travel-associated infections revealed that, comparing 2004-2009 to 2010-2012, ciprofloxacin resistance increased among domestic infections (12.8% vs 16.1%). Conclusions: During 2004-2012, incidence of campylobacteriosis, outbreaks, and clinically significant antimicrobial resistance increased. Marked demographic and geographic differences exist. Our findings underscore the importance of national surveillance and understanding of risk factors to guide and target control measures.

    • Healthcare Associated Infections
      • Approach to the investigation and management of patients with Candida auris, an emerging multidrug-resistant yeast
        Tsay S, Kallen A, Jackson BR, Chiller TM, Vallabhaneni S.
        Clin Infect Dis. 2017 Aug 17.
        Candida auris is an emerging, multidrug-resistant yeast that can spread in healthcare settings. It can cause invasive infections with high mortality and is difficult to identify using traditional yeast identification methods. C. auris has been reported in over a dozen countries, and as of July 2017, 99 clinical cases have been reported in the United States;.C. auris can colonize skin and persist in the healthcare environment, allowing for transmission between patients. Prompt investigation and aggressive interventions, including notification of public health agencies, implementation of contact precautions, thorough environmental cleaning and disinfection, infection control assessments, contact tracing and screening contacts to assess for colonization, and retrospective review of microbiology records and prospective surveillance for cases at laboratories are all needed to limit the spread of C. auris. This review summarizes the current recommended approach to manage cases of C. auris and control transmission of C. auris in healthcare facilities.

    • Immunity and Immunization
      • Adenovirus vector-based multi-epitope vaccine provides partial protection against H5, H7, and H9 avian influenza viruses
        Hassan AO, Amen O, Sayedahmed EE, Vemula SV, Amoah S, York I, Gangappa S, Sambhara S, Mittal SK.
        PLoS One. 2017 ;12(10):e0186244.
        The emergence of H5, H7, and H9 avian influenza virus subtypes in humans reveals their pandemic potential. Although human-to-human transmission has been limited, the genetic reassortment of the avian and human/porcine influenza viruses or mutations in some of the genes resulting in virus replication in the upper respiratory tract of humans could generate novel pandemic influenza viruses. Current vaccines do not provide cross protection against antigenically distinct strains of the H5, H7, and H9 influenza viruses. Therefore, newer vaccine approaches are needed to overcome these potential threats. We developed an egg-independent, adenovirus vector-based, multi-epitope (ME) vaccine approach using the relatively conserved immunogenic domains of the H5N1 influenza virus [M2 ectodomain (M2e), hemagglutinin (HA) fusion domain (HFD), T-cell epitope of nucleoprotein (TNP). and HA alpha-helix domain (HalphaD)]. Our ME vaccine induced humoral and cell-mediated immune responses and caused a significant reduction in the viral loads in the lungs of vaccinated mice that were challenged with antigenically distinct H5, H7, or H9 avian influenza viruses. These results suggest that our ME vaccine approach provided broad protection against the avian influenza viruses. Further improvement of this vaccine will lead to a pre-pandemic vaccine that may lower morbidity, hinder transmission, and prevent mortality in a pandemic situation before a strain-matched vaccine becomes available.

    • Maternal and Child Health
      • Risk comparison for prenatal use of analgesics and selected birth defects, National Birth Defects Prevention Study 1997-2011
        Interrante JD, Ailes EC, Lind JN, Anderka M, Feldkamp ML, Werler MM, Taylor LG, Trinidad J, Gilboa SM, Broussard CS.
        Ann Epidemiol. 2017 Sep 20.
        PURPOSE: To compare the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or opioids to the use of acetaminophen without NSAIDs or opioids with respect to associations with birth defects. METHODS: We used data from the National Birth Defects Prevention Study (1997-2011). Exposure was self-reported maternal analgesic use from the month before through the third month of pregnancy (periconceptional). Adjusted odds ratios (aORs) were calculated to examine associations with 16 birth defects. RESULTS: Compared to acetaminophen, mothers reporting NSAIDs were significantly more likely to have offspring with gastroschisis, hypospadias, cleft palate, cleft lip with cleft palate, cleft lip without cleft palate, anencephaly, spina bifida, hypoplastic left heart syndrome, pulmonary valve stenosis, and tetralogy of Fallot (aOR range, 1.2-1.6). Opioids were associated with tetralogy of Fallot, perimembranous ventricular septal defect, and ventricular septal defect with atrial septal defect (aOR range, 1.8-2.3), whereas use of both opioids and NSAIDs was associated with gastroschisis, cleft palate, spina bifida, hypoplastic left heart syndrome, and pulmonary valve stenosis (aOR range, 2.0-2.9). CONCLUSIONS: Compared to periconceptional use of acetaminophen, selected birth defects occurred more frequently among infants of women using NSAIDs and/or opioids. However, we could not definitely determine whether these risks relate to the drugs or to indications for treatment.

    • Physical Activity
      • Cerebral hemodynamics and executive function during exercise and recovery in normobaric hypoxia
        Stavres J, Gerhart HD, Kim JH, Glickman EL, Seo Y.
        Aerosp Med Hum Perform. 2017 Oct 01;88(10):911-917.
        BACKGROUND: Hypoxia and exercise each exhibit opposing effects on executive function, and the mechanisms for this are not entirely clear. This study examined the influence of cerebral oxygenation and perfusion on executive function during exercise and recovery in normobaric hypoxia (NH) and normoxia (N). METHODS: There were 18 subjects who completed cycling trials in NH (12.5% FIo2) and N (20.93% FIo2). Right prefrontal cortex (PFC) oxyhemoglobin (O2Hb) and middle cerebral artery blood velocity (MCAbv) were collected during executive function challenges [mathematical processing and running memory continuous performance task (RMCPT)] at baseline, following 30 min of acclimation, during 20 min of cycling (60% Vo2max), and at 1, 15, 30, and 45 min following exercise. RESULTS: Results indicated effects of time for Math, RMCPT, and O2Hb; but not for MCAbv. Results also indicated effects of condition for O2Hb. Math scores were improved by 8.0% during exercise and remained elevated at 30 min of recovery (12.5%), RMCPT scores significantly improved at all time points (7.5-11.9%), and O2Hb increased by 662.2% and 440.9% during exercise in N and NH, respectively, and remained elevated through 15 min of recovery in both conditions. DISCUSSION: These results support the influence of PFC oxygenation and perfusion on executive function during exercise and recovery in N and NH.Stavres J, Gerhart HD, Kim J-H, Glickman EL, Seo Y. Cerebral hemodynamics and executive function during exercise and recovery in normobaric hypoxia. Aerosp Med Hum Perform 2017; 88(10):911-917.

    • Substance Use and Abuse
      • Surveillance of nicotine and pH in cigarette and cigar filler
        Lawler TS, Stanfill SB, deCastro BR, Lisko JG, Duncan BW, Richter P, Watson CH.
        Tob Regul Sci. 2017 Apr;3(Suppl 1):101-116.
        OBJECTIVE: We examined differences between nicotine concentrations and pH in cigarette and cigar tobacco filler. METHODS: Nicotine and pH levels for 50 cigarette and 75 cigar brands were measured. Non-mentholated and mentholated cigarette products were included in the analysis along with several cigar types as identified by the manufacturer: large cigars, pipe tobacco cigars, cigarillos, mini cigarillos, and little cigars. RESULTS: There were significant differences found between pH and nicotine for cigarette and cigar tobacco products. Mean nicotine concentrations in cigarettes (19.2 mg/g) and large cigars (15.4 mg/g) were higher than the other cigars types, especially the pipe tobacco cigars (8.79 mg/g). The mean pH for cigarettes was pH 5.46. Large cigars had the highest mean pH value (pH 6.10) and pipe tobacco cigars had the lowest (pH 5.05). CONCLUSIONS: Although cigarettes are the most common combustible tobacco product used worldwide, cigar use remains popular. Our research provides a means to investigate the possibility of distinguishing the 2 tobacco product types and offers information on nicotine and pH across a wide range of cigarette and cigar varieties that may be beneficial to help establish tobacco policies and regulations across product types.

    • Zoonotic and Vectorborne Diseases
      • Fatal Rocky Mountain spotted fever along the United States-Mexico Border, 2013-2016
        Drexler NA, Yaglom H, Casal M, Fierro M, Kriner P, Murphy B, Kjemtrup A, Paddock CD.
        Emerg Infect Dis. 2017 Oct;23(10):1621-1626.
        Rocky Mountain spotted fever (RMSF) is an emerging public health concern near the US-Mexico border, where it has resulted in thousands of cases and hundreds of deaths in the past decade. We identified 4 patients who had acquired RMSF in northern Mexico and subsequently died at US healthcare facilities. Two patients sought care in Mexico before being admitted to US-based hospitals. All patients initially had several nonspecific signs and symptoms, including fever, headache, nausea, vomiting, or myalgia, but deteriorated rapidly without receipt of a tetracycline-class antimicrobial drug. Each patient experienced respiratory failure late in illness. Although transborder cases are not common, early recognition and prompt initiation of appropriate treatment are vital for averting severe illness and death. Clinicians on both sides of the US-Mexico border should consider a diagnosis of RMSF for patients with rapidly progressing febrile illness and recent exposure in northern Mexico.

      • Pathogenesis and sexual transmission of Spondweni and Zika viruses
        McDonald EM, Duggal NK, Brault AC.
        PLoS Negl Trop Dis. 2017 Oct 06;11(10):e0005990.
        The Spondweni serogroup of viruses (Flaviviridae, Flavivirus) is comprised of Spondweni virus (SPONV) and Zika virus (ZIKV), which are mosquito-borne viruses capable of eliciting human disease. Numerous cases of ZIKV sexual transmission in humans have been documented following the emergence of the Asian genotype in the Americas. The African ZIKV genotype virus was previously implicated in the first reported case of ZIKV sexual transmission. Reports of SPONV infection in humans have been associated with non-specific febrile illness, but no association with sexual transmission has been reported. In order to assess the relative efficiency of sexual transmission of different ZIKV strains and the potential capacity of SPONV to be sexually transmitted, viral loads in the male reproductive tract and in seminal fluids were assessed in interferon alpha/beta and -gamma receptor deficient (AG129) mice. Male mice were inoculated subcutaneously with Asian genotype ZIKV strains PRVABC59 (Puerto Rico, 2015), FSS13025 (Cambodia, 2010), or P6-740 (Malaysia, 1966); African genotype ZIKV strain DakAr41524 (Senegal, 1984); or SPONV strain SAAr94 (South Africa, 1955). Infectious virus was detected in 60-72% of ejaculates collected from AG129 mice inoculated with ZIKV strains. In contrast, only 4% of ejaculates from SPONV-inoculated AG129 males were found to contain infectious virus, despite viral titers in the testes that were comparable to those of ZIKV-inoculated mice. Based on these results, future studies should be undertaken to assess the role of viral genetic determinants and host tropism that dictate the differential sexual transmission potential of ZIKV and SPONV.

  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. Association between urinary sodium and potassium excretion and blood pressure among adults in the United States: National Health and Nutrition Examination Survey, 2014
        Jackson SL, Cogswell ME, Zhao L, Terry AL, Wang CY, Wright J, Coleman King SM, Bowman B, Chen TC, Merritt RK, Loria CM.
        Circulation. 2017 Oct 11.
        Background -Higher levels of sodium and lower levels of potassium intake are associated with higher blood pressure. However, the shape and magnitude of these associations can vary by study participant characteristics or intake assessment method. Twenty-four hour urinary excretion of sodium and potassium are unaffected by recall errors and represent all sources of intake, and were collected for the first time in a nationally representative US survey. Our objective was to assess the associations of blood pressure and hypertension with 24-hour urinary excretion of sodium and potassium among US adults. Methods -Cross-sectional data from 766 participants aged 20-69 years with complete blood pressure and 24-hour urine collections in the 2014 National Health and Nutrition Examination Survey, a nationally-representative survey of the US noninstitutionalized population. Usual 24-hour urinary electrolyte excretion (sodium, potassium, and their ratio) was estimated from up to two collections on non-consecutive days, adjusting for day-to-day variability in excretion. Outcomes included systolic and diastolic blood pressure from the average of 3 measures and hypertension status, based on average blood pressure >/=140/90 and anti-hypertensive medication use. Results -After multivariable adjustment, each 1000 mg difference in usual 24-hour sodium excretion was directly associated with systolic (4.58 mmHg, 95% confidence interval 2.64,6.51) and diastolic (2.25 mmHg, 95% CI 0.83,3.67) blood pressures. Each 1000 mg difference in potassium excretion was inversely associated with systolic blood pressure (-3.72 mmHg, 95% CI -6.01,-1.42). Each 0.5 unit difference in sodium-to-potassium ratio was directly associated with systolic blood pressure (1.72 mmHg, 95% CI 0.76, 2.68). Hypertension was linearly associated with progressively higher sodium and lower potassium excretion; compared with the lowest quartiles of excretion, the adjusted odds of hypertension for the highest quartiles were 4.22 (95% CI 1.36, 13.15) for sodium, and 0.38 (95% CI 0.17, 0.87) for potassium, respectively, P<0.01 for trends. Conclusions -These cross-sectional results show a strong dose-response association between urinary sodium excretion and blood pressure, and an inverse association between urinary potassium excretion and blood pressure, in a nationally representative sample of US adults.

      2. Evaluating the completeness of the national ALS registry, United States
        Kaye WE, Wagner L, Wu R, Mehta P.
        Amyotroph Lateral Scler Frontotemporal Degener. 2017 Oct 11:1-6.
        Our objective was to evaluate the completeness of the United States National ALS Registry (Registry). We compared persons with ALS who were passively identified by the Registry with those actively identified in the State and Metropolitan Area ALS Surveillance project. Cases in the two projects were matched using a combination of identifiers, including, partial social security number, name, date of birth, and sex. The distributions of cases from the two projects that matched/did not match were compared and Chi-square tests conducted to determine statistical significance. There were 5883 ALS cases identified by the surveillance project. Of these, 1116 died before the Registry started, leaving 4767 cases. We matched 2720 cases from the surveillance project to those in the Registry. The cases identified by the surveillance project that did not match cases in the Registry were more likely to be non-white, Hispanic, less than 65 years of age, and from western states. The methods used by the Registry to identify ALS cases, i.e. national administrative data and self-registration, worked well but missed cases. These findings suggest that developing strategies to identify and promote the Registry to those who were more likely to be missing, e.g. non-white and Hispanic, could be beneficial to improving the completeness of the Registry.

      3. Preventive Medicine supplement issue on noncommunicable disease risk factors in developing countries: Policy perspectives
        Kostova D, Chaloupka FJ, Frieden TR, Henning K, Paul J, Osewe PL, Asma S.
        Prev Med. 2017 Oct 05.

        [No abstract]

      4. Exposure to perchlorate, nitrate and thiocyanate, and prevalence of diabetes mellitus
        Liu G, Zong G, Dhana K, Hu Y, Blount BC, Morel-Espinosa M, Sun Q.
        Int J Epidemiol. 2017 Sep 11.
        Background: It is known that perchlorate, nitrate and thiocyanate have the property of inhibiting sodium iodide symporter. Animal studies have suggested that these compounds, especially perchlorate, might also interfere with insulin secretion. However, the association between their exposure and diabetes risk is largely unknown in humans. Methods: Among 11 443 participants (mean age 42.3 years) from the National Health and Nutritional Examination Survey 2001-14, urinary perchlorate, nitrate and thiocyanate were measured by using ion chromatography coupled with electrospray tandem mass spectrometry. Diabetes was defined as self-reported doctor diagnosis, use of oral hypoglycaemic medication or insulin, fasting plasma glucose >/= 126 mg/dl or glycated haemoglobin A1c (HbA1c) >/= 6.5%. Results: The median (interquartile range) levels of urinary perchlorate, nitrate and thiocyanate were 3.32 (1.84, 5.70) mug/l, 46.4 (27.9, 72.0) mg/l and 1.23 (0.59, 2.78) mg/l, respectively. Higher levels of urinary perchlorate were associated with elevated levels of fasting glucose, HbA1c, insulin and homeostatic model assessment of insulin resistance (all P trend < 0.001). After multivariate adjustment including urinary creatinine, smoking status and body mass index (BMI), higher urinary perchlorate, but not nitrate or thiocyanate, was associated with an increased prevalence of diabetes mellitus. Comparing extreme quintiles, the odds ratio (95% confidence interval) of diabetes was 1.53 (1.21, 1.93; P trend < 0.001) for perchlorate, 1.01 (0.77, 1.32; P trend = 0.44) for nitrate and 0.98 (0.73, 1.31; P trend = 0.64) for thiocyanate. When urinary perchlorate, nitrate and thiocyanate were further mutually adjusted, the results did not materially change. Similar results were observed when analyses were stratified by smoking status, as well as by age, gender, kidney function and BMI. Conclusions: Higher urinary perchlorate levels are associated with an increased prevalence of diabetes mellitus, independent of traditional risk factors. Future prospective studies are needed to confirm these findings.

      5. Inpatient glucose values: Determining the nondiabetic range and use in identifying patients at high risk for diabetes
        Rhee MK, Safo SE, Jackson SL, Xue W, Olson DE, Long Q, Barb D, Haw JS, Tomolo AM, Phillips LS.
        Am J Med. 2017 Oct 06.
        BACKGROUND: Many individuals with diabetes remain undiagnosed, leading to delays in treatment and higher risk for subsequent diabetes complications. Despite recommendations for diabetes screening in high risk groups, the optimal approach is not known. We evaluated the utility of inpatient glucose levels as an opportunistic screening tool for identifying patients at high risk for diabetes. METHODS: We retrospectively examined 462,421 patients in the national VA healthcare system, hospitalized on medical/surgical services in 2000-2010, for >/=3 days, with >/=2 inpatient random plasma glucose (RPG) measurements. All had continuity of care – >/=1 primary care visit and >/=1 glucose measure within 2 years before hospitalization and yearly for >/=3 years after discharge. Glucose levels during hospitalization and incidence of diabetes within 3 years after discharge in patients without diabetes were evaluated. RESULTS: Patients had mean age 65.0 years, BMI 29.9, and were 96% male, 71% white, and 18% black. Preexisting diabetes was present in 39.4%, 1.3% were diagnosed during hospitalization, 8.1% diagnosed <5 years post-discharge, and 51.3% never diagnosed (NonDM). The NonDM group had the lowest mean hospital RPG (112 mg/dl [6.2 mmol/L]). Having at least two RPGs >140 mg/dl (>7.8 mmol/L), the 95th percentile of NonDM hospital glucose, provided 81% specificity for identifying incident diabetes <3 years post-discharge. CONCLUSIONS: Screening for diabetes could be considered in patients with at least two hospital glucoses at/above the 95th percentile of the nondiabetic range (141 mg/dl [7.8 mmol/L]).

      6. A comparison of fecal immunochemical and high-sensitivity guaiac tests for colorectal cancer screening
        Shapiro JA, Bobo JK, Church TR, Rex DK, Chovnick G, Thompson TD, Zauber AG, Lieberman D, Levin TR, Joseph DA, Nadel MR.
        Am J Gastroenterol. 2017 Oct 10.
        OBJECTIVES: Annual testing using either a high-sensitivity guaiac fecal occult blood test (HS-gFOBT) or a fecal immunochemical test (FIT) is recommended for screening average-risk people for colorectal cancer. We compared the performance characteristics of the HS-gFOBT Hemoccult II SENSA and two FITs (InSure FIT and OC FIT-CHEK) for detecting advanced colorectal neoplasia. METHODS: The study included 1,006 asymptomatic patients, aged 50-75 years, who were scheduled to receive a screening colonoscopy at gastroenterology practices in the Minneapolis and Indianapolis metropolitan areas. Each participant was asked to complete all three stool tests before their colonoscopy. Each test’s performance characteristics were evaluated using the screening colonoscopic results as the reference standard. RESULTS: Sensitivity for detecting advanced colorectal neoplasia was highest for InSure FIT (26.3%, 95% confidence interval (CI) 15.9-40.7), followed by OC FIT-CHEK (15.1%, 95% CI 6.7-26.1) and Hemoccult II SENSA (7.4%, 95% CI 1.9-17.0). InSure FIT was statistically significantly more sensitive than both OC FIT-CHEK (absolute difference in sensitivity=11.2%, 95% CI 0.4-24.2) and Hemoccult II SENSA (difference in sensitivity=18.9%, 95% CI 10.2-32.6). Specificities were relatively high for all tests (between 96.8% and 98.6%). CONCLUSIONS: Our results suggest that some FITs are more sensitive than the HS-gFOBT Hemoccult II SENSA, but these results need to be confirmed in larger asymptomatic populations. Comparisons between the FITs examined in this study and other FITs are needed to determine the best tests for population screening.Am J Gastroenterol advance online publication, 10 October 2017; doi:10.1038/ajg.2017.285.

    • Communicable Diseases
      1. Prenatal screening for and prevalence of hepatitis B surface antigen in pregnant women and prevention of transmission to infants born to infected mothers – Guam, 2014
        Abara WE, Cha S, Malik T, DeSimone MS, Schillie S, Collier M, Schumann B, Klemme M, Kamb M.
        J Pediatric Infect Dis Soc. 2017 Sep 05.
        Background: Perinatal transmission is the major mode of hepatitis B virus (HBV) transmission and drives HBV endemicity in the US territory of Guam. We assessed correlates of prenatal hepatitis B surface antigen (HBsAg) screening and HBsAg positivity among pregnant women and evaluated the care of infants of HBsAg-positive women. Methods: Demographic and clinical data were abstracted from the maternal medical records of 966 randomly selected live infants born in 2014. Frequencies were calculated, and prevalence ratios (PRs) and 95% confidence intervals (CIs) were estimated using Poisson regression. Results: Among the mothers of the 966 infants, 78.2% were Pacific Islanders, 56.9% were >25 years old (born before universal infant hepatitis B vaccination in Guam), 89.0% received prenatal care (PNC), 96.7% underwent prenatal HBsAg screening, and 2.0% were HBsAg positive. Approximately 15% of the women who did not have PNC were not screened for HBsAg. Receipt of PNC was associated with HBsAg screening (adjusted PR, 1.13 [95% CI, 1.04-1.23]), and HBsAg positivity was associated with a maternal age of >25 years (adjusted PR, 6.80 [95% CI, 1.32-35.08]). All 18 infants of the HBsAg-positive mothers received hepatitis B vaccine, and 17 (94.4%) received hepatitis B immunoglobulin. Conclusion: Although the prenatal HBsAg screening prevalence in this sample was high, the maternal HBsAg prevalence among women in this sample was more than 14 times and 2 times the prevalence among US-born Pacific Islander/Asian women and all women in the continental United States, respectively. Improving access to PNC, ensuring that all pregnant women in Guam (especially those born before universal hepatitis B vaccination) are screened for HBsAg, and adopting postexposure prophylaxis for infants of HBsAg-positive mothers as standard clinical practice are important for preventing perinatal HBV transmission and reducing HBV endemicity.

      2. International travelers with infectious diseases determined by pathology results, Centers for Disease Control and Prevention – United States, 1995-2015
        Angelo KM, Barbre K, Shieh WJ, Kozarsky PE, Blau DM, Sotir MJ, Zaki SR.
        Travel Med Infect Dis. 2017 Oct 06.
        BACKGROUND: The failure to consider travel-related diagnoses, the lack of diagnostic capacity for specialized laboratory testing, and the declining number of autopsies may affect the diagnosis and management of travel-related infections. Pre- and post-mortem pathology can help determine causes of illness and death in international travelers. METHODS: We conducted a retrospective review of biopsy and autopsy specimens sent to the Infectious Diseases Pathology Branch laboratory (IDPBL) at the Centers for Disease Control and Prevention (CDC) for diagnostic testing from 1995-2015. Cases were included if the specimen submitted for diagnosis was from a traveler with prior international travel during the disease incubation period and the cause of illness or death was unknown at the time of specimen submission. RESULTS: Twenty-one travelers, six (29%) with biopsy specimens and 15 (71%) with autopsy specimens, met the inclusion criteria. Among the 15 travelers who underwent autopsies, the most common diagnoses were protozoal infections (7 travelers; 47%), including five malaria cases, followed by viral infections (6 travelers; 40%). CONCLUSIONS: Biopsy or autopsy specimens can assist in diagnosing infectious diseases in travelers, especially from pathogens not endemic in the U.S. CDC’s IDPBL provides a useful resource for clinicians considering infectious diseases in returned travelers.

      3. Antibody banding patterns of the Enzyme-linked Immunoelectrotransfer Blot (EITB) and brain imaging findings in patients with neurocysticercosis
        Arroyo G, Rodriguez S, Lescano AG, Alroy K, Bustos JA, Santivanez S, Gonzales I, Saavedra H, Pretell EJ, Gonzalez AE, Gilman RH, Tsang VC, Garcia HH.
        Clin Infect Dis. 2017 Sep 04.
        Background: The enzyme-linked immunoelectrotransfer blot (EITB) assay is the reference serological test for neurocysticercosis (NCC). A positive result on EITB does not always correlate with the presence of active infections in the central nervous system (CNS), and patients with a single viable brain cyst may be EITB negative. Nonetheless, EITB antibody banding patterns appears to be related with the expression of three protein families of Taenia solium, and in turn with the characteristics of NCC in the CNS (type, stage and burden of viable cysts). Methods: We evaluated EITB antibody banding patterns and brain imaging findings of 548 NCC cases. Similar banding patterns were grouped into homogeneous classes using latent class analysis. The association between classes and brain imaging findings was assessed. Results: Four classes were identified. Class 1 (patients negative or only positive to the GP50 band, related to the protein family of the same name) was associated with non-viable or single viable parenchymal cysticerci; class 2 (patients positive to bands GP42-39 and GP24, related to the T24-42 protein family, with or without anti-GP50 antibodies) was associated with intraparenchymal viable and non-viable infections; classes 3 and 4 (positive to GP50, GP42-39 and GP24 but also responding to low molecular weight bands GP21, GP18, GP14 and GP13, related to the 8kDa protein family) were associated with extraparenchymal and intraparenchymal multiple viable cysticerci. Conclusions/significance: EITB antibody banding patterns correlate with brain imaging findings and complement imaging information for the diagnosis of NCC and for staging NCC patients.

      4. Pediatric norovirus GII.4 infections in Nicaragua, 1999-2015
        Bucardo F, Reyes Y, Becker-Dreps S, Bowman N, Gruber JF, Vinje J, Espinoza F, Paniagua M, Balmaseda A, Svensson L, Nordgren J.
        Infect Genet Evol. 2017 Oct 02;55:305-312.
        OBJECTIVES: Investigate clinical and epidemiological factors of pediatric GII.4 norovirus infections in children with acute gastroenteritis (AGE) in Nicaragua between 1999 and 2015. METHODS: We retrospectively analyzed laboratory and epidemiologic data from 1,790 children</=7years with AGE from 6 hospitals in Nicaragua (n=538), and 3 community clinics (n=919) and households (n=333) in Leon, between 1999 and 2015. Moreover, asymptomatic children from community clinics (n=162) and households (n=105) were enrolled. Norovirus was detected by real-time PCR and genotyped by sequencing the N-terminal and shell region of the capsid gene. RESULTS: Norovirus was found in 19% (n=338) and 12% (n=32) of children with and without AGE, respectively. In total, 20 genotypes including a tentatively new genotype were detected. Among children with AGE, the most common genotypes were GII.4 (53%), GII.14 (7%), GII.3 (6%) and GI.3 (6%). In contrast, only one (1.4%) GII.4 was found in asymptomatic children. The prevalence of GII.4 infections was significantly higher in children between 7 and 12months of age. The prevalence of GII.4 was lowest in households (38%), followed by community clinics (50%) and hospitals (75%). Several different GII.4 variants were detected and their emergence followed the global temporal trend. CONCLUSIONS: Overall our study found the predominance of pediatric GII.4 norovirus infections in Nicaragua mostly occurring in children between 7 and 12months of age, implicating GII.4 as the main norovirus vaccine target.

      5. Programmatic evaluation of an algorithm for intensified TB case finding and isoniazid preventive therapy for people living with HIV in Thailand and Vietnam
        Cowger T, Thai LH, Duong BD, Danyuttapolchai J, Kittimunkong S, Nhung NV, Nhan DT, Monkongdee P, Thoa CK, Khanh VT, Nateniyom S, Ntb Y, Ngoc DV, Thinh T, Whitehead S, Pevzner ES.
        J Acquir Immune Defic Syndr. 2017 Oct 04.
        BACKGROUND: Tuberculosis (TB) screening affords clinicians opportunities to diagnose or exclude TB disease and initiate Isoniazid Preventive Therapy (IPT) for people living with HIV (PLHIV). METHODS: We implemented an algorithm to diagnose or rule out TB among PLHIV in eleven HIV clinics in Thailand and Vietnam. We assessed algorithm yield and uptake of IPT and factors associated with TB disease among PLHIV. RESULTS: A total of 1,448 PLHIV not yet on antiretroviral therapy (ART) were enrolled and screened for TB. Overall, 634 (44%) screened positive and 119 (8%) were diagnosed with TB; of these, 40% (48/119) were diagnosed by a positive culture following a negative sputum smear microscopy. In total, 55% of those eligible (263/477) started on IPT and of those, 75% (196/263) completed therapy. The prevalence of TB disease we observed in this study was 8.2% (8,218 per 100,000 persons): 46 and 25 times the prevalence of TB in the general population in Thailand and Vietnam, respectively. Several factors were independently associated with TB disease including being underweight (aOR [95% CI]: 2.3 [1.2, 2.6]) and using injection drugs (aOR [95% CI]: 2.9 [1.3, 6.3]). CONCLUSIONS: The high yield of TB disease diagnosed among PLHIV screened with the algorithm, and higher burden among PLHIV who inject drugs, underscores the need for innovative, tailored approaches to TB screening and prevention. As countries adopt Test-and-Start for ART, TB screening, sensitive TB diagnostics, and IPT should be included in differentiated-care models for HIV to improve diagnosis and prevention of TB among PLHIV.

      6. HIV care outcomes among Hispanics or Latinos with diagnosed HIV infection – United States, 2015
        Gant Z, Dailey A, Hu X, Johnson AS.
        MMWR Morb Mortal Wkly Rep. 2017 Oct 13;66(40):1065-1072.
        Data from CDC’s National HIV Surveillance System (NHSS)* are used to monitor progress toward achieving national goals set forth in the Division of HIV/AIDS Prevention’s Strategic Plan (1) and other federal directivesdagger for human immunodeficiency virus (HIV) testing, care, and treatment outcomes and HIV-related disparities in the United States. Recent data indicate that Hispanics or Latinos section sign are disproportionately affected by HIV infection. Hispanics or Latinos living with diagnosed HIV infection have lower levels of care and viral suppression than do non-Hispanic whites but higher levels than those reported among blacks or African Americans (2). The annual rate of diagnosis of HIV infection among Hispanics or Latinos is three times that of non-Hispanic whites (3), and a recent study found increases in incidence of HIV infection among Hispanic or Latino men who have sex with men (4). Among persons with HIV infection diagnosed through 2013 who were alive at year-end 2014, 70.2% of Hispanics or Latinos received any HIV medical care compared with 76.1% of non-Hispanic whites (2). CDC used NHSS data to describe HIV care outcomes among Hispanics or Latinos. Among male Hispanics or Latinos with HIV infection diagnosed in 2015, fewer males with infection attributed to heterosexual contact (34.6%) had their infection diagnosed at an early stage (stage 1 = 12.0%, stage 2 = 22.6%) than males with infection attributed to male-to-male sexual contact (60.9%: stage 1 = 25.2%, stage 2 = 35.7%). The percentage of Hispanics or Latinos linked to care after diagnosis of HIV infection increased with increasing age; females aged 45-54 years with infection attributed to injection drug use (IDU) accounted for the lowest percentage (61.4%) of persons linked to care. Among Hispanics or Latinos living with HIV infection, care and viral suppression were lower among selected age groups of Hispanic or Latino males with HIV infection attributed to IDU than among males with infection attributed to male-to-male sexual contact and male-to-male sexual contact and IDU. Intensified efforts to develop and implement effective interventions and public health strategies that increase engagement in care and viral suppression among Hispanics or Latinos (3,5), particularly those who inject drugs, are needed to achieve national HIV prevention goals.

      7. OBJECTIVES: To describe how select Social Determinants of Health (SDH) are associated with the burden of hepatitis B virus (HBV) infection among foreign-born persons residing in the United States. METHODS: Multivariate logistic regression was used to examine the Racial and Ethnic Approaches to Community Health (REACH) 2010 Risk Factor Survey data to investigate the independent relationship between SDH and HBV testing and access to care. RESULTS: HBV infected persons with insurance were more likely to see a physician than those without. Respondents worried about money to pay rent or mortgage were more likely to report HBV infection than individuals who reported they never worry. Compared to English speakers, Spanish-speakers were less likely to report HBV infection, Vietnamese-speakers were more likely to see a physician for HBV infection, and Khmer-speakers were less likely to be tested. CONCLUSIONS: Health insurance coverage, worries about paying rent, and language of interview all differentially affect HBV testing and linkages to care among foreign-born persons. Multi-sectorial stakeholder collaborative efforts should integrate resources to provide culturally sensitive health promotion campaigns which may improve HBV related outcomes.

      8. Burden of pneumonia-associated hospitalizations – United States, 2001-2014
        Hayes BH, Haberling DL, Kennedy J, Varma JK, Fry AM, Vora NM.
        Chest. 2017 Oct 07.
        BACKGROUND: The epidemiology of pneumonia has likely evolved in recent years, reflecting an aging population, changes in population immunity, and socioeconomic disparities. METHODS: Using the National (Nationwide) Inpatient Sample (NIS), estimated numbers and rates of pneumonia-associated hospitalizations for 2001-2014 were calculated. A pneumonia-associated hospitalization was defined as one in which the discharge record listed a principal diagnosis of pneumonia or a secondary diagnosis of pneumonia if the principal diagnosis was respiratory failure or sepsis. RESULTS: There were an estimated 20,361,181 (SE: 95,601) pneumonia-associated hospitalizations in the United States during 2001-2014 (average annual age-adjusted pneumonia-associated hospitalization rate of 464.8 per 100,000 population [95% CI: 462.5-467.1]). The average annual age-adjusted pneumonia-associated hospitalization rate decreased over the study period. In-hospital death occurred in 7.4% (SE: 0.03) of pneumonia-associated hospitalizations. Non-Hispanic American Indian/Alaskan Natives and non-Hispanic blacks had the highest average annual age-adjusted rates of pneumonia-associated hospitalization of all race/ethnicities at 439.2 (95% CI: 415.9-462.5) and 438.6 (95% CI: 432.5-444.7) per 100,000 population, respectively. During 2001-2014, the proportion of pneumonia-associated hospitalizations co-listing an immunocompromising condition increased from 18.7% (SE: 0.2) in 2001 to 29.5% (SE: 0.2) in 2014. Total charges for pneumonia-associated hospitalizations in 2014 were over $84 billion. CONCLUSIONS: Pneumonia is a major cause of morbidity and mortality in the United States. Differences in rates and outcomes of pneumonia-associated hospitalizations between sociodemographic groups warrant further investigation. The immunocompromised population has emerged as a group experiencing a disproportionate burden of pneumonia-associated hospitalizations.

      9. Intestinal carriage of third-generation cephalosporin-resistant and extended-spectrum beta-lactamase-producing enterobacteriaceae in healthy US children
        Islam S, Selvarangan R, Kanwar N, McHenry R, Chappell JD, Halasa N, Wikswo ME, Payne DC, Azimi PH, McDonald LC, Gomez-Duarte OG.
        J Pediatric Infect Dis Soc. 2017 Jun 15.
        Background: The epidemiology of antibiotic-resistant Enterobacteriaceae intestinal carriage in healthy US children has not been well characterized. Methods: Children between 14 days and 14 years of age were enrolled during well-child visits in Oakland, California, Kansas City, Kansas, and Nashville, Tennessee, between December 2013 and March 2015. Data on recent antibiotic use by the child and travel and hospitalization history of all members of each child’s household were obtained with a risk-factor survey. Stool specimens collected from the subjects were screened for extended-spectrum beta-lactamase-producing (ESBL-P) bacteria using CHROMagar ESBL medium. Putative ESBL-P Escherichia coli and Klebsiella colonies underwent phenotypic confirmation by double-disk synergy testing; confirmed third-generation cephalosporin-resistant (3GCR) isolates underwent additional antibiotic-susceptibility testing. Results: In 519 subjects, the overall 3GCR Enterobacteriaceae carriage rate was 4.4% (n = 23) and ranged from 3.4% to 5.1% among the study sites. The ESBL-P Enterobacteriaceae carriage rate was 3.5% (n = 18). The rates of 3GCR Enterobacteriaceae carriage was highest in 1 to <2 year olds at 6.5%, and was 5.2% in <5 year-olds vs 1.7% in >/=5-year-olds (P = .11). 3GCR and ESBL-P Enterobacteriaceae carriage was associated with international travel within the previous year; 11.1% of ESBL-P Enterobacteriaceae carriers reported this history compared with 1.6% of noncarriers (P = .004). No other queried factor was found to increase risk. Of the 24 analyzed 3GCR isolates, 58% were multidrug resistant. Conclusions: The 3GCR Enterobacteriaceae carriage rate exceeds 5% in healthy US children <5 years of age. International travel within the previous year increased the risk of 3GCR and ESBL-P Enterobacteriaceae carriage. In contrast, we found no differences in the rates of hospitalization or recent antibiotic exposure between carriers and noncarriers. Young children, who have the highest prevalence of colonization, might be a sentinel population to study to gain a better understanding of community sources of antibiotic-resistant Enterobacteriaceae.

      10. HIV drug resistance in African infants and young children newly diagnosed with HIV: a multicounty analysis
        Jordan MR, Penazzato M, Cournil A, Vubil A, Jani I, Hunt G, Carmona S, Maphalala G, Mthethwa N, Watera C, Kaleebu P, Chakanyuka Musanhu C, Mtapuri-Zinyowera S, Dzangare J, Peeters M, Yang C, Parkin N, Bertagnolio S.
        Clin Infect Dis. 2017 Aug 08.
        Background: Prevention of mother-to-child transmission (PMTCT) of HIV programs have been scaled-up in many low- and middle-income countries; however, HIV drug resistance (HIVDR) data amongst HIV-1-infected young children remain limited. Methods: Surveys of pre-treatment HIVDR amongst children younger than 18 months of age who were diagnosed with HIV through Early Infant Diagnosis were conducted in five sub-Saharan African countries (Mozambique, Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following World Health Organization guidance. De-identified demographic and clinical data were used to explore risk factors associated with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. Results: Among the 1,450 genotypes analyzed, 1,048 had accompanying demographic and clinical data. The median age of children was 4 months; 50.4% were female. HIV from 54.1 % showed resistance to one or more antiretroviral drug, with 53.0% and 8.8% having resistance to one or more NNRTI or nucleoside reverse transcriptase inhibitor, respectively. NNRTI resistance was particularly high in children exposed to antiretroviral drugs through PMTCT; adjusted odds ratios 1.8 (95% confidence interval (CI): 1.3 – 2.6) for maternal exposure only and 2.4 (CI: 1.6 – 3.6) for neonatal exposure only. Conclusions: Protease inhibitor-based regimens in children younger than three years are currently recommended by WHO but the implementation of this recommendation is suboptimal. These results reinforce the urgent need to overcome barriers to scale-up of pediatric protease inhibitor-based regimens in sub-Saharan Africa and underscore the need to accelerate the study and approval of integrase inhibitors for use in young children.

      11. Prolonged excretion of poliovirus among individuals with primary immunodeficiency disorder: An analysis of the World Health Organization Registry
        Macklin G, Liao Y, Takane M, Dooling K, Gilmour S, Mach O, Kew OM, Sutter RW.
        Front Immunol. 2017 ;8:1103.
        Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93%) prolonged excretors and 7/101 (7%) chronic excretors. We documented an increase in incidence in recent decades, with a shift toward middle-income countries, and a predominance of poliovirus type 2 in 73/101 (72%) cases. The median length of excretion was 1.3 years (95% confidence interval: 1.0, 1.4) and 90% of individuals stopped excreting after 3.7 years. Common variable immunodeficiency syndrome and residence in high-income countries were risk factors for long-term excretion. The changing epidemiology of cases, manifested by the greater incidence in recent decades and a shift to from high- to middle-income countries, highlights the expanding risk of poliovirus transmission after oral poliovirus vaccine cessation. To better quantify and reduce this risk, more sensitive surveillance and effective antiviral therapies are needed.

      12. Rural men who have sex with men (MSM) are heavily affected by HIV, and many lack culturally competent HIV prevention resources. Rural MSM may find sexual partners on the internet, which may also be a way to deliver prevention services to them. To understand the differences between rural and urban MSM with respect to HIV risk factors and behaviors and the utilization of online HIV prevention services, we used data from the 2012 Web-Based HIV Behavioral Survey (WHBS). Using WHBS data collected between June and August 2012, we compared the characteristics of MSM with positive or unknown HIV infection status who had sex with a male in the past 12 months, from rural vs urban areas using Chi square tests and median tests. We used logistic regression and calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) to compare self-reported HIV risk behaviors, HIV/STI testing behaviors, use of prevention services, and perceived discrimination. Of the 8166 MSM included in our analysis, 3583 (44%) were from rural areas, and 4583 (56%) were from urban areas. Compared to urban MSM, rural MSM were less likely to ever test for HIV (aPR = 0.94, CI 0.92-0.95), to be tested for HIV in the last year (aPR = 0.83, CI 0.79-0.87), or to receive free condoms (aPR = 0.83, CI 0.79-0.86) or individual prevention counseling in the past year (aPR = 0.86, CI 0.78-0.95). Rural MSM were less likely to have been tested in the last year for syphilis, gonorrhea, or chlamydia (aPR = 0.70, CI 0.62-0.78; aPR = 0.72, CI 0.64-0.81; aPR = 0.75, CI 0.67-0.85, respectively). Rural MSM also reported perceiving less tolerance of gays and bisexuals within their community (aPR = 0.80, CI 0.77-0.84). HIV prevalence is lower among MSM in rural areas compared to MSM in urban areas, but rural MSM report that they are more likely to face intolerance and are less likely to use basic HIV prevention services compared to urban MSM. Therefore, this hard-to-reach population could benefit from prevention services offered through the internet.

      13. Uptake of antibiotic stewardship programs in U.S. acute care hospitals: Findings from the 2015 National Healthcare Safety Network Annual Hospital Survey
        O’Leary EN, van Santen KL, Webb AK, Pollock DA, Edwards JR, Srinivasan A.
        Clin Infect Dis. 2017 Jul 29.
        To assess uptake of the Centers for Disease Control and Prevention’s Core Elements of Hospital Antibiotic Stewardship Programs, we analyzed stewardship practices as reported in the 2015 National Healthcare Safety Network’s Annual Hospital Survey. Hospital uptake of all 7 core elements increased from 40.9% in 2014 to 48.1% in 2015.

      14. Increases in ocular syphilis – North Carolina, 2014-2015
        Oliver SE, Cope AB, Rinsky JL, Williams C, Liu G, Hawks S, Peterman TA, Markowitz L, Fleischauer AT, Samoff E.
        Clin Infect Dis. 2017 Jul 13.
        Background: Ocular syphilis is an inflammatory eye disease due to Treponema pallidum infection. In the United States, syphilis rates have increased since 2000; clusters of ocular syphilis were reported in 2015. We investigated ocular syphilis in North Carolina to describe the epidemiology and clinical course of disease. Methods: We reviewed syphilis cases reported to North Carolina during 2014-2015 and abstracted information from health department interviews for cases with ocular symptoms and no other defined etiology. To assess duration and severity of ocular symptoms, we also reviewed medical records and conducted structured interviews. We compared the prevalence of ocular manifestations among reported syphilis cases by demographic and clinical characteristics. Results: Among 4232 syphilis patients, 63 (1.5%) had ocular syphilis: 21 in 2014 and 42 in 2015, a 100% increase. Total syphilis cases increased 35% through 2015. No patient with ocular syphilis named another ocular syphilis patient as a sex partner. Patients presented in all syphilis stages; 24 (38%) were diagnosed in primary or secondary syphilis. Ocular manifestations were more prevalent among syphilis patients who were male, aged >/=40 years, white, and infected with human immunodeficiency virus. No risk behaviors were associated with ocular syphilis. Among 39 interviewed patients, 34 (87%) reported reduced vision during infection; 12 (31%) reported residual visual symptoms posttreatment. Conclusions: In North Carolina, ocular syphilis increased from 2014 to 2015 and may be due to increased recognition of ocular manifestations, or a true increase in ocular syphilis. Many ocular syphilis patients experienced vision loss; however, most improved posttreatment.

      15. Syphilis
        Peeling RW, Mabey D, Kamb ML, Chen XS, Radolf JD, Benzaken AS.
        Nat Rev Dis Primers. 2017 Oct 12;3:17073.
        Treponema pallidum subspecies pallidum (T. pallidum) causes syphilis via sexual exposure or via vertical transmission during pregnancy. T. pallidum is renowned for its invasiveness and immune-evasiveness; its clinical manifestations result from local inflammatory responses to replicating spirochaetes and often imitate those of other diseases. The spirochaete has a long latent period during which individuals have no signs or symptoms but can remain infectious. Despite the availability of simple diagnostic tests and the effectiveness of treatment with a single dose of long-acting penicillin, syphilis is re-emerging as a global public health problem, particularly among men who have sex with men (MSM) in high-income and middle-income countries. Syphilis also causes several hundred thousand stillbirths and neonatal deaths every year in developing nations. Although several low-income countries have achieved WHO targets for the elimination of congenital syphilis, an alarming increase in the prevalence of syphilis in HIV-infected MSM serves as a strong reminder of the tenacity of T. pallidum as a pathogen. Strong advocacy and community involvement are needed to ensure that syphilis is given a high priority on the global health agenda. More investment is needed in research on the interaction between HIV and syphilis in MSM as well as into improved diagnostics, a better test of cure, intensified public health measures and, ultimately, a vaccine.

      16. ICTV virus taxonomy profile: Hepeviridae
        Purdy MA, Harrison TJ, Jameel S, Meng XJ, Okamoto H, Van der Poel WH, Smith DB.
        J Gen Virol. 2017 Oct 12.
        The family Hepeviridae includes enterically transmitted small non-enveloped positive-sense RNA viruses. It includes the genera Piscihepevirus, whose members infect fish, and Orthohepevirus, whose members infect mammals and birds. Members of the genus Orthohepevirus include hepatitis E virus, which is responsible for self-limiting acute hepatitis in humans and several mammalian species; the infection may become chronic in immunocompromised individuals. Extrahepatic manifestations of Guillain-Barre syndrome, neuralgic amyotrophy, glomerulonephritis and pancreatitis have been described in humans. Avian hepatitis E virus causes hepatitis-splenomegaly syndrome in chickens. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Hepeviridae, which is available at www.ictv.global/report/hepeviridae.

      17. Incidence of norovirus-associated diarrhea and vomiting disease among children and adults in a community cohort in the Peruvian Amazon basin
        Romero C, Tinoco YO, Loli S, Razuri H, Soto G, Silva M, Galvan P, Kambhampati A, Parashar UD, Kasper MR, Bausch DG, Simons MP, Lopman B.
        Clin Infect Dis. 2017 Sep 01;65(5):833-839.
        Background: Data on norovirus epidemiology among all ages in community settings are scarce, especially from tropical settings. Methods: We implemented active surveillance in 297 households in Peru from October 2012 to August 2015 to assess the burden of diarrhea and acute gastroenteritis (AGE) due to norovirus in a lower-middle-income community. During period 1 (October 2012-May 2013), we used a “traditional” diarrhea case definition (>/=3 loose/liquid stools within 24 hours). During period 2 (June 2013-August 2015), we used an expanded case definition of AGE (by adding >/=2 vomiting episodes without diarrhea or 1-2 vomiting episodes plus 1-2 loose/liquid stools within 24 hours). Stool samples were tested for norovirus by reverse-transcription polymerase chain reaction. Results: During period 1, overall diarrhea and norovirus-associated diarrhea incidence was 37.2/100 person-years (PY) (95% confidence interval [CI], 33.2-41.7) and 5.7/100 PY (95% CI, 3.9-8.1), respectively. During period 2, overall AGE and norovirus-associated AGE incidence was 51.8/100 PY (95% CI, 48.8-54.9) and 6.5/100 PY (95% CI, 5.4-7.8), respectively. In both periods, children aged <2 years had the highest incidence of norovirus. Vomiting without diarrhea occurred among norovirus cases in participants <15 years old, but with a higher proportion among children <2 years, accounting for 35% (7/20) of all cases in this age group. Noroviruses were identified in 7% (23/335) of controls free of gastroenteric symptoms. Conclusions: Norovirus was a significant cause of AGE in this community, especially among children <2 years of age. Inclusion of vomiting in the case definition resulted in a 20% improvement for detection of norovirus cases.

      18. Factors associated with all-cause mortality among patients with multidrug-resistant tuberculosis – United States, 1993-2013
        Salinas JL, Armstrong LR, Silk BJ, Haddad MB, Cegielski JP.
        Clin Infect Dis. 2017 Jul 29.
        We assessed characteristics associated with all-cause mortality among U.S. patients with multidrug-resistant tuberculosis. Mortality decreased from 31% during 1993-2002 to 11% during 2003-2013. Directly observed therapy coverage increased from 74% to 95% and was protective against all-cause mortality after accounting for demographics, clinical characteristics, HIV status, and period of treatment.

      19. Burden of influenza in 4 ecologically distinct regions of Peru: Household active surveillance of a community cohort, 2009-2015
        Tinoco YO, Azziz-Baumgartner E, Uyeki TM, Razuri HR, Kasper MR, Romero C, Silva ME, Simons MP, Soto GM, Widdowson MA, Gilman RH, Bausch DG, Montgomery JM.
        Clin Infect Dis. 2017 Aug 09.
        Background: There are limited data on the burden of disease posed by influenza in low- and middle-income countries. Furthermore, most estimates of influenza disease burden worldwide rely on passive sentinel surveillance at health clinics and hospitals that lack accurate population denominators. Methods: We documented influenza incidence, seasonality, health-system utilization with influenza illness, and vaccination coverage through active community-based surveillance in 4 ecologically distinct regions of Peru over 6 years. Approximately 7200 people in 1500 randomly selected households were visited 3 times per week. Naso- and oropharyngeal swabs were collected from persons with influenza-like illness and tested for influenza virus by real-time reverse-transcription polymerase chain reaction. Results: We followed participants for 35353 person-years (PY). The overall incidence of influenza was 100 per 1000 PY (95% confidence interval [CI], 97-104) and was highest in children aged 2-4 years (256/1000 PY [95% CI, 236-277]). Seasonal incidence trends were similar across sites, with 61% of annual influenza cases occurring during the austral winter (May-September). Of all participants, 44 per 1000 PY (95% CI, 42-46) sought medical care, 0.7 per 1000 PY (95% CI, 0.4-1.0) were hospitalized, and 1 person died (2.8/100000 PY). Influenza vaccine coverage was 27% among children aged 6-23 months and 26% among persons aged >/=65 years. Conclusions: Our results indicate that 1 in 10 persons develops influenza each year in Peru, with the highest incidence in young children. Active community-based surveillance allows for a better understanding of the true burden and seasonality of disease that is essential to plan the optimal target groups, timing, and cost of national influenza vaccination programs.

    • Community Health Services
      1. Public health and vulnerable populations: Morbidity and mortality among people ever incarcerated in New York city jails, 2001 to 2005
        Levanon Seligson A, Parvez FM, Lim S, Singh T, Mavinkurve M, Harris TG, Kerker BD.
        J Correct Health Care. 2017 Jan 01:1078345817727527.
        The health of people ever incarcerated in New York City (NYC) jails during 2001 to 2005 was characterized by matching jail, shelter, mortality, sexually transmitted infection, HIV, and tuberculosis (TB) data from the NYC Departments of Health and Mental Hygiene, Correction, and Homeless Services. Compared with nonincarcerated people and those living in the lowest income NYC neighborhoods, those ever incarcerated had higher HIV prevalence and HIV case rates. Ever-incarcerated females also had higher rates of gonorrhea and syphilis than nonincarcerated females. Ever-incarcerated people who used the single adult homeless shelter system had higher HIV, gonorrhea, and TB case rates and all-cause mortality rates than ever-incarcerated people without shelter use, when adjusting for other variables. People ever incarcerated in NYC jails are at risk for conditions of public health importance. Sex-specific jail- and community-based interventions are needed.

    • Environmental Health
      1. Per- and polyfluoroalkyl substances in sera from children 3 to 11 years of age participating in the National Health and Nutrition Examination Survey 2013-2014
        Ye X, Kato K, Wong LY, Jia T, Kalathil A, Latremouille J, Calafat AM.
        Int J Hyg Environ Health. 2017 Sep 29.
        Several per- and polyfluoroalkyl substances (PFAS) have been measured in U.S. National Health and Nutrition Examination Survey (NHANES) participants 12 years of age and older since 1999-2000, but PFAS data using NHANES individual samples among children younger than 12 years do not exist. To obtain the first nationally representative PFAS exposure data in U.S. children, we quantified serum concentrations of 14 PFAS including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), in a nationally representative subsample of 639 3-11year old participants in NHANES 2013-2014. We used on-line solid-phase extraction coupled to isotope dilution-high performance liquid chromatography-tandem mass spectrometry; limits of detection were 0.1ng/mL for all analytes. We calculated geometric mean concentrations, determined weighted Pearson correlations, and used linear regression to evaluate associations of sex, age (3-5 vs 6-11 years), race/ethnicity (Hispanic vs non-Hispanic), household income, and body mass index with concentrations of PFAS detected in more than 60% of participants. We detected PFOS, PFOA, PFHxS, and PFNA in all children at concentrations similar to those of NHANES 2013-2014 adolescents and adults, suggesting prevalent exposure to these PFAS or their precursors among U.S. 3-11year old children, most of whom were born after the phase out of PFOS in the United States in 2002. PFAS concentration differences by sex, race/ethnicity, and age suggest lifestyle differences that may impact exposure, and highlight the importance of identifying exposure sources and of studying the environmental fate and transport of PFAS.

    • Epidemiology and Surveillance
      1. Keeping up with a world in motion: Screening strategies for migrating populations
        Cookson ST, Maloney SA.
        Clin Infect Dis. 2017 Oct 15;65(8):1410-1411.

        [No abstract]

    • Genetics and Genomics
      1. Thorough molecular characterization of reference viruses supports the detection of emerging human pathogens as well as studies of evolutionary relationships. However, full characterization of the tripartite RNA genomes of many viruses of the clinically important family Peribunyaviridae remains incomplete, making it difficult to identify emerging strains. Here, we report the full genome sequences of nine viruses belonging to the California serogroup and describe multi-segment analyses of these and previously published California serogroup strain data to determine the role of segment reassortment in the evolution of this serogroup. Phylogenetic trees from the small, medium, and large segments suggest long term, independent evolution of the majority of strains. However, trees from each segment were not entirely congruent and evidence of reassortment among some strains is presented. Of unique interest, the L segment phylogeny reveals divergent branching patterns for encephalitic versus non-encephalitic viruses in both major clades of the California serogroup.

    • Health Economics
      1. Antibiotic expenditures by medication, class, and health care setting in the United States, 2010-2015
        Suda KJ, Hicks LA, Roberts RM, Hunkler RJ, Matusiak LM, Schumock GT.
        Clin Infect Dis. 2017 Aug 25.
        BACKGROUND: Improving antibiotic use has the potential to decrease health care costs by reducing the incidence of antibiotic-resistant infections, antibiotic-associated adverse events, and expenditures due to unnecessary prescriptions. Antibiotic expenditures in 2009 totaled $10.7 billion in the United States. Since then, national and local antibiotic stewardship initiatives have grown. The purpose of this study was to assess trends in antibiotic expenditures by health care setting in the United States between 2010 and 2015. METHODS: Systemic (non-topical) antibiotic expenditures from January 2010 to December 2015 were extracted from the QuintilesIMS National Sales Perspectives database. These data represent a statistically valid projection of U.S. medication purchases. Regression analyses evaluated trends in expenditures over the study period. RESULTS: Antibiotic expenditures totaled $56.0 billion over the six-year period; the majority (59.1%) of expenditures were associated with the outpatient setting. Overall antibiotic expenditures in 2015 ($8.8 billion) were 16.6% lower than in 2010 ($10.6 billion). Antibiotic expenditures similarly decreased in the community by 25.5% (p=0.05), but outpatient clinics and mail service pharmacy expenditures experienced significant growth (148% and 67% increase, respectively; p<0.01 for both). In 2015, 16.5% of antibiotic expenditures in the community were for parenteral formulations, an increase of 25%. CONCLUSIONS: From 2010 to 2015 antibiotic expenditures decreased. The majority of antibiotic expenditures were in the outpatient setting, specifically community pharmacies. Expenditures for intravenous agents in the community are increasing and may represent increased use. These results reinforce the importance of antibiotic stewardship efforts across the spectrum of healthcare.

    • Immunity and Immunization
      1. We compared acute gastroenteritis (AGE)-related hospitalization rates among children <5 years of age during the pre-rotavirus vaccine (2000-2006) and post-rotavirus vaccine (2008-2013) periods to estimate national reductions in AGE-related hospitalizations and associated costs. We estimate that between 2008 and 2013, AGE-related hospitalizations declined by 382000, and $1.228 billion in medical costs were averted.

      2. Reduced severity of pertussis in persons with age-appropriate pertussis vaccination – United States, 2010-2012
        McNamara LA, Skoff T, Faulkner A, Miller L, Kudish K, Kenyon C, Bargsten M, Zansky S, Sullivan AD, Martin S, Briere E.
        Clin Infect Dis. 2017 Sep 01;65(5):811-818.
        Background: In 2012, >48000 pertussis cases were reported in the United States. Many cases occurred in vaccinated persons, showing that pertussis vaccination does not prevent all pertussis cases. However, pertussis vaccination may have an impact on disease severity. Methods: We analyzed data on probable and confirmed pertussis cases reported through Enhanced Pertussis Surveillance (Emerging Infections Program Network) between 2010 and 2012. Surveillance data were collected through physician and patient interview and vaccine registries. We assessed whether having received an age-appropriate number of pertussis vaccines (AAV) (for persons aged >/=3 months) was associated with reduced odds of posttussive vomiting, a marker of more clinically significant illness, or of severe pertussis (seizure, encephalopathy, pneumonia, and/or hospitalization). Adjusted odds ratios were calculated using multivariable logistic regression. Results: Among 9801 pertussis patients aged >/=3 months, 77.6% were AAV. AAV status was associated with a 60% reduction in odds of severe disease in children aged 7 months-6 years in multivariable logistic regression and a 30% reduction in odds of posttussive vomiting in persons aged 19 months-64 years. Conclusions: Serious pertussis symptoms and complications are less common among AAV pertussis patients, demonstrating that the positive impact of pertussis vaccination extends beyond decreasing risk of disease.

      3. The Household Influenza Vaccine Effectiveness Study: Lack of antibody response and protection following receipt of 2014-2015 influenza vaccine
        Petrie JG, Malosh RE, Cheng CK, Ohmit SE, Martin ET, Johnson E, Truscon R, Eichelberger MC, Gubareva LV, Fry AM, Monto AS.
        Clin Infect Dis. 2017 Jul 20.
        Background: Antigenically drifted A(H3N2) viruses circulated extensively during the 2014-2015 influenza season. Vaccine effectiveness (VE) was low and not significant among outpatients but in a hospitalized population was 43%. At least one study paradoxically observed increased A(H3N2) infection among those vaccinated 3 consecutive years. Methods: We followed a cohort of 1341 individuals from 340 households. VE against laboratory-confirmed influenza was estimated. Hemagglutination-inhibition and neuraminidase-inhibition antibody titers were determined in subjects >/=13 years. Results: Influenza A(H3N2) was identified in 166 (12%) individuals and B(Yamagata) in 34 (2%). VE against A(H3N2) was -3% (95% confidence interval [CI]: -55%, 32%) and similarly ineffective between age groups; increased risk of infection was not observed among those vaccinated in 2 or 3 previous years. VE against influenza B(Yamagata) was 57% (95% CI: -3%, 82%) but only significantly protective in children <9 years (87% [95% CI: 43%, 97%]). Less than 20% of older children and adults had >/=4-fold antibody titer rise against influenza A(H3N2) and B antigens following vaccination; responses were surprisingly similar for antigens included in the vaccine and those similar to circulating viruses. Antibody against A/Hong Kong/4801/14, similar to circulating 2014-2015 A(H3N2) viruses and included in the 2016-2017 vaccine, did not significantly predict protection. Conclusions: Absence of VE against A(H3N2) was consistent with circulation of antigenically drifted viruses; however, generally limited antibody response following vaccination is concerning even in the context of antigenic mismatch. Although 2014-2015 vaccines were not effective in preventing A(H3N2) infection, no increased susceptibility was detected among the repeatedly vaccinated.

      4. Vaccination coverage for selected vaccines, exemption rates, and provisional enrollment among children in kindergarten – United States, 2016-17 school year
        Seither R, Calhoun K, Street EJ, Mellerson J, Knighton CL, Tippins A, Underwood JM.
        MMWR Morb Mortal Wkly Rep. 2017 Oct 13;66(40):1073-1080.
        State and local school vaccination requirements help protect students and communities against vaccine-preventable diseases (1). CDC reports vaccination coverage and exemption data for children attending kindergarten (kindergartners) collected by federally funded immunization programs in the United States.* The typical age range for kindergartners is 4-6 years. Although vaccination requirements vary by state (the District of Columbia [DC] is counted as a state in this report.), the Advisory Committee on Immunization Practices recommends that children in this age range have received, among other vaccinations, 5 doses of diphtheria, tetanus, and acellular pertussis vaccine (DTaP), 2 doses of measles, mumps, and rubella vaccine (MMR), and 2 doses of varicella vaccine (2). This report summarizes 2016-17 school year MMR, DTaP, and varicella vaccination coverage reported by immunization programs in 49 states, exemptions in 50 states, and kindergartners provisionally enrolled or within a grace period in 27 states. Median vaccination coveragedagger was 94.5% for the state-required number of doses of DTaP; 94.0% for 2 doses of MMR; and 93.8% for 2 doses of varicella vaccine. The median percentage of kindergartners with an exemption from at least one vaccine section sign was 2.0%, similar to 2015-16 (1.9%). Median grace period and provisional enrollment was 2.0%. Vaccination coverage remains consistently high and exemptions low at state and national levels. Local-level vaccination coverage data provide opportunities for immunization programs to identify schools, districts, counties, or regions susceptible to vaccine-preventable diseases and for schools to address undervaccination through implementation of existing state and local vaccination policies (1) to protect communities through increased coverage.

      5. Mumps outbreak in a highly vaccinated university-affiliated setting before and after a measles-mumps-rubella (MMR) vaccination campaign-Iowa, July 2015-May 2016
        Shah M, Quinlisk P, Weigel A, Riley J, James L, Patterson J, Hickman C, Rota PA, Schicker R, Clemmons N, Kalas N, Cardemil C.
        Clin Infect Dis. 2017 Aug 16.
        Background: In response to a mumps outbreak at the University of Iowa and surrounding community, university, state, and local health officials implemented a vaccination campaign targeting students <25 years of age with an additional dose of measles-mumps-rubella (MMR) vaccine. Over 4,700 vaccine campaign doses were administered; 97% were documented third doses. We describe the epidemiology of the outbreak before and after the campaign, focusing on cases in university students. Methods: Mumps cases were identified from reportable disease databases and university health system records. Detailed information on student cases was obtained from interviews, medical chart abstractions, university and state vaccination records, and state public health laboratory results. Pre- and post-campaign incidence among students, university faculty/staff, and community members <25 vs. >/=25 years old were compared using Fisher’s exact test. Multivariable regression modeling was performed to identify variables associated with a positive mumps polymerase chain reaction test. Results: Of 453 cases in the county, 301 (66%) occurred in university students. Student cases were primarily undergraduates (90%) and highly vaccinated (86% had 2 MMR doses, and 12% had 3 MMR doses). Fewer cases occurred in students after the campaign (75; 25%) than before (226; 75%). Cases in the target group (students <25 years of age) declined 9% post-campaign (p = 0.01). A positive mumps PCR test was associated with the presence of parotitis and early sample collection, and inversely associated with recent receipt of MMR vaccine. Conclusions: Following a large additional dose MMR vaccination campaign, fewer mumps cases occurred overall and in the target population.

    • Laboratory Sciences
      1. Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using Standard Reference Material 1950 metabolites in frozen human plasma
        Bowden JA, Heckert A, Ulmer CZ, Jones CM, Koelmel JP, Abdullah L, Ahonen L, Alnouti Y, Armando A, Asara JM, Bamba T, Barr JR, Bergquist J, Borchers CH, Brandsma J, Breitkopf SB, Cajka T, Cazenave-Gassiot A, Checa A, Cinel MA, Colas RA, Cremers S, Dennis EA, Evans JE, Fauland A, Fiehn O, Gardner MS, Garrett TJ, Gotlinger KH, Han J, Huang Y, Neo AH, Hyotylainen T, Izumi Y, Jiang H, Jiang H, Jiang J, Kachman M, Kiyonami R, Klavins K, Klose C, Kofeler HC, Kolmert J, Koal T, Koster G, Kuklenyik Z, Kurland IJ, Leadley M, Lin K, Maddipati KR, McDougall D, Meikle PJ, Mellett NA, Monnin C, Moseley MA, Nandakumar R, Oresic M, Patterson RE, Peake D, Pierce JS, Post M, Postle AD, Pugh R, Qui Y, Quehenberger O, Ramrup P, Rees J, et al .
        J Lipid Res. 2017 Oct 06.
        As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950 Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each lab using a different lipidomics workflow. A total of 1527 unique lipids were measured across all laboratories, and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and inter-laboratory quality control and method validation. These analyses were performed using non-standardized laboratory-independent workflows. The consensus locations were also compared to a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

      2. Comparison of platforms for testing antibody responses against the Chlamydia trachomatis Antigen Pgp3
        Gwyn S, Cooley G, Goodhew B, Kohloff S, Banniettis N, Wiegand R, Martin DL.
        Am J Trop Med Hyg. 2017 Sep 25.
        Antibody responses to Chlamydia trachomatis (CT) antigens may be useful tools for surveillance of trachoma by estimating cumulative prevalence of infection within a population. Data were compared from three different platforms-multiplex bead array (MBA), enzyme-linked immunosorbent assay (ELISA), and lateral flow assay (LFA)-measuring antibody responses against the CT antigen protein plasmid gene product 3 (Pgp3). Sensitivity was defined as the proportion of specimens testing antibody positive from a set of dried blood spots from Tanzanian 1-9-year olds who were positive for CT nucleic acid of all nucleic acid amplification test (NAAT)-positive individuals (N = 103). The sensitivity of the LFA could not be determined because of the use of dried blood spots for this test; this specimen type has yet to be adapted to LFA. Specificity was defined as the proportion of sera from U.S. and Bolivian 1-9-year olds that had previously tested negative by the Chlamydia microimmunofluorescence (MIF) assay testing negative to Pgp3-specific antibodies (N = 154). The sensitivity for MBA and ELISA was the same-93.2 (95% confidence interval [CI]: 88.3-98.1). Specificity ranged across platforms from 96.1 (95% CI: 91.8-98.2) to 99.4% (95% CI: 98.2-100). ELISA performance was similar regardless of whether the plates were precoated or freshly coated with antigen. Sensitivity and specificity of control panels were similar if the cutoff was determined using receiver operator curves or a finite mixture model, but the cutoffs themselves differed by approximately 0.5 OD using the different methodologies. These platforms show good sensitivity and specificity and show good agreement between tests at a population level, but indicate variability for ELISA outcomes depending on the cutoff determination methodology.

      3. Inactivated H7 influenza virus vaccines protect mice despite inducing only low levels of neutralizing antibodies
        Kamal RP, Blanchfield K, Belser JA, Music N, Tzeng WP, Holiday C, Burroughs A, Sun X, Maines TR, Levine MZ, York IA.
        J Virol. 2017 Oct 15;91(20).
        Avian influenza viruses of the H7 hemagglutinin (HA) subtype present a significant public health threat, as evidenced by the ongoing outbreak of human A(H7N9) infections in China. When evaluated by hemagglutination inhibition (HI) and microneutralization (MN) assays, H7 viruses and vaccines are found to induce lower level of neutralizing antibodies (nAb) than do their seasonal counterparts, making it difficult to develop and evaluate prepandemic vaccines. We have previously shown that purified recombinant H7 HA appear to be poorly immunogenic in that they induce low levels of HI and MN antibodies. In this study, we immunized mice with whole inactivated reverse genetics reassortant (RG) viruses expressing HA and neuraminidase (NA) from 3 different H7 viruses [A/Shanghai/2/2013(H7N9), A/Netherlands/219/2003(H7N7), and A/New York/107/2003(H7N2)] or with human A(H1N1)pdm09 (A/California/07/2009-like) or A(H3N2) (A/Perth16/2009) viruses. Mice produced equivalent titers of antibodies to all viruses as measured by enzyme-linked immunosorbent assay (ELISA). However, the antibody titers induced by H7 viruses were significantly lower when measured by HI and MN assays. Despite inducing very low levels of nAb, H7 vaccines conferred complete protection against homologous virus challenge in mice, and the serum antibodies directed against the HA head region were capable of mediating protection. The apparently low immunogenicity associated with H7 viruses and vaccines may be at least partly related to measuring antibody titers with the traditional HI and MN assays, which may not provide a true measure of protective immunity associated with H7 immunization. This study underscores the need for development of additional correlates of protection for prepandemic vaccines.IMPORTANCE H7 avian influenza viruses present a serious risk to human health. Preparedness efforts include development of prepandemic vaccines. For seasonal influenza viruses, protection is correlated with antibody titers measured by hemagglutination inhibition (HI) and virus microneutralization (MN) assays. Since H7 vaccines typically induce low titers in HI and MN assays, they have been considered to be poorly immunogenic. We show that in mice H7 whole inactivated virus vaccines (WIVs) were as immunogenic as seasonal WIVs, as they induced similar levels of overall serum antibodies. However, a larger fraction of the antibodies induced by H7 WIV was nonneutralizing in vitro Nevertheless, the H7 WIV completely protected mice against homologous viral challenge, and antibodies directed against the HA head were the major contributor toward immune protection. Vaccines against H7 avian influenza viruses may be more effective than HI and virus neutralization assays suggest, and such vaccines may need other methods for evaluation.

      4. Potential toxicity and underlying mechanisms associated with pulmonary exposure to iron oxide nanoparticles: Conflicting literature and unclear risk
        Kornberg TG, Stueckle TA, Antonini JA, Rojanasakul Y, Castranova V, Yang Y, Wang L.
        Nanomaterials (Basel). 2017 Oct 06;7(10).
        Fine/micron-sized iron oxide particulates are incidentally released from a number of industrial processes, including iron ore mining, steel processing, welding, and pyrite production. Some research suggests that occupational exposure to these particulates is linked to an increased risk of adverse respiratory outcomes, whereas other studies suggest that iron oxide is biologically benign. Iron oxide nanoparticles (IONPs), which are less than 100 nm in diameter, have recently surged in use as components of novel drug delivery systems, unique imaging protocols, as environmental catalysts, and for incorporation into thermoplastics. However, the adverse outcomes associated with occupational exposure to IONPs remain relatively unknown. Relevant in vivo studies suggest that pulmonary exposure to IONPs may induce inflammation, pulmonary fibrosis, genotoxicity, and extra-pulmonary effects. This correlates well with in vitro studies that utilize relevant dose, cell type(s), and meaningful end points. A majority of these adverse outcomes are attributed to increased oxidative stress, most likely caused by particle internalization, dissolution, release of free iron ions, and disruption of iron homeostasis. However, because the overall toxicity profile of IONPs is not well understood, it is difficult to set safe exposure limit recommendations that would be adequate for the protection of at-risk workers. This review article will focus on known risks following IONPs exposure supported by human, animal, and cell culture-based studies, the potential challenges intrinsic to IONPs toxicity assessment, and how these may contribute to the poorly characterized IONPs toxicity profile.

      5. Direct measurement of aerosol glass fiber alignment in a DC electric field
        Ku BK, Deye G, Turkevich LA.
        Aerosol Science and Technology. 2017 .
        We report non-conducting aerosol fiber (i.e., glass fiber) alignment in a DC electric field. Direct observation of fiber orientation state is demonstrated and quantitative analysis of fiber alignment is made using phase contrast microscopy in four different conditions; i) dry air and naturally charged fibers, ii) humid and naturally charged, iii) humid and neutralized (Boltzmann charge distribution) and iv) humid and neutralized with an electrostatic precipitator upstream electrodes (i.e., non-charged). The glass fiber aerosols generated by a vortex shaking method were conditioned using a Po-210 neutralizer or humidifier and were provided into a test unit where cylindrical or parallel plate electrodes are used and high voltage is applied to them. Fibers were collected on a filter immediately downstream from the electrodes and their images were taken through an optical microscope to visualize the fiber orientation and measure the alignment angles and lengths of the fibers. The results showed that under all four conditions tested, airborne glass fibers could be aligned to the electric field with different alignment quality, indicating that the glass fibers can be polarized in a steady electric field. In humid air, the fiber alignment along the field direction was observed to be much better and the number of uniform background particles (i.e., randomly oriented fibers) in angular distributions is smaller than that in dry air. Also, it was found that charged fibers in humid air could be better aligned with negligible uniform background than neutralized and non-charged fibers. Possible mechanisms about humidity and charge effects on enhanced fiber alignment are discussed to support the observations. The results indicate that the enhancement of alignment in an electric field would be possible in humid air for other non-conducting fibrous particles having surface chemistry similar to glass fibers.

      6. The recently developed Crimean-Congo hemorrhagic fever virus (CCHFV) reverse genetics systems have paved the way for experiments looking to identify and characterize the roles played by viral and cellular proteins in the CCHFV life cycle. In particular, the development of the noninfectious minigenome and virus-like particle (VLP) systems is a tremendous technological advance, as these systems allow for precisely targeting proteins or nucleic acids and measuring the effects these mutations or treatments have on viral life cycle stages. Importantly, these systems can be used at low-containment levels. Presented are the materials and methods currently available to study CCHFV transcription, replication, and translation in the context of a minigenome or VLP.

    • Maternal and Child Health
      1. Injuries in children with autism spectrum disorder: Study to Explore Early Development (SEED)
        DiGuiseppi C, Levy SE, Sabourin KR, Soke GN, Rosenberg S, Lee LC, Moody E, Schieve LA.
        J Autism Dev Disord. 2017 Oct 11.
        This study examined caregiver-reported medically-attended injuries among 30-68 month old children with autism spectrum disorder (ASD) compared to general population (POP) and non-ASD developmental disorders (DD) controls in the Study to Explore Early Development. Injuries were common in ASD cases (32.3%) as well as POP (30.2%) and DD (27.8%) controls; most resulted in an emergency visit or hospitalization. After accounting for sociodemographic, health, IQ and behavior differences, odds of injury in ASD cases were significantly higher than DD controls but similar to POP controls. Attention problems mediated the relationships. Clinicians caring for children with both ASD and attention problems should consider providing targeted safety advice. Differences in injury risk between children with ASD vs. other developmental disorders need further study.

      2. Are lower TSH cutoffs in neonatal screening for congenital hypothyroidism warranted?
        Lain S, Trumpff C, Grosse SD, Olivieri A, Van Vliet G.
        Eur J Endocrinol. 2017 Nov;177(5):D1-d12.
        When newborn screening (NBS) for congenital hypothyroidism (CH) using thyroid-stimulating hormone (TSH) as a primary screening test was introduced, typical TSH screening cutoffs were 20-50 U/L of whole blood. Over the years, lowering of TSH cutoffs has contributed to an increased prevalence of detected CH. However, a consensus on the benefit deriving from lowering TSH cutoffs at screening is lacking. The present paper outlines arguments both for and against the lowering of TSH cutoffs at NBS. It includes a review of recently published evidence from Australia, Belgium and Italy. A section focused on economic implications of lowering TSH cutoffs is also provided. One issue that bears further examination is the extent to which mild iodine deficiency at the population level might affect the association of neonatal TSH values with cognitive and developmental outcomes. A debate on TSH cutoffs provides the opportunity to reflect on how to make NBS for CH more effective and to guarantee optimum neurocognitive development and a good quality of life to babies with mild as well as with severe CH. All authors of this debate article agree on the need to establish optimal TSH cutoffs for screening programs in various settings and to ensure the benefits of screening and access to care for newborns worldwide.

    • Mining
      1. Regional- to reservoir-scale evaluation of CO2 storage resource estimates of coal seams
        Zhang Q, Ellett KM, Rupp JA, Mastalerz M, Karacan CO.
        Energy Procedia. 2017 2017/07/01/;114(Supplement C):5346-5355.
        Unmineable coal seams are an important target for investigating the economic viability of carbon capture and storage technology owing to their potential for simultaneous CO2 storage and enhanced coalbed methane production. As such, recent developments in integrated system models are aiming to explicitly incorporate coal seam storage and enhanced methane production into their economic analyses, however, such implementation currently relies on fairly uncertain prospective resource estimates derived from regional-scale analyses. In this paper, we evaluate the uncertainty of such prospective resource estimates, both for CO2 storage and for CO2 utilization potential (i.e., enhanced coalbed methane production from CO2 injection) via comparison to results from more detailed, local-scale reservoir simulations at numerous locations. Reservoir-scale simulations incorporate the dynamic system response to CO2 injection, whereas regional-scale prospective resource estimates rely on volumetric calculations of original gas-in-place from static geological models combined with assumed recovery factors. Results based on a case study of 12 different locations in the Illinois Basin, USA suggest that prospective resource estimates for CO2 storage may be systematically biased towards over-estimation. By developing a set of low-, mid-, and high-range estimates from model simulations, a total of 36 comparisons were made to the prospective resource estimates, of which 35 showed significantly lower results for the model-based estimates. Model sensitivity testing of variable CO2 injection rates indicated that the requirement to maintain reservoir pressure below the fracture gradient threshold is in part responsible for the lower limit of storage resource estimates obtained from the reservoir simulation results versus the prospective resource methodology which neglects such processes. In terms of enhanced methane recovery, results were far more comparable between the two methods for the low- and mid-range set of estimates, whereas the high-range estimates were still notably larger using the prospective resource methodology. We conclude that utilizing prospective resource estimates of enhanced coalbed methane potential in integrated system models appears feasible for the more conservative range of estimates, whereas CO2 storage estimates of coal seams are likely to produce overly optimistic results in the system model. We also note that for the Illinois Basin case study, both the modelling results and the regional-scale results indicate that a significant amount of additional well drilling beyond the existing coalbed methane infrastructure would need to be conducted in order for coal seams to be a viable alternative to other options in the region such as oil and gas reservoirs and deep saline formations.

    • Occupational Safety and Health
      1. Occupational exposure to disinfectants and asthma control in US nurses
        Dumas O, Wiley AS, Quinot C, Varraso R, Zock JP, Henneberger PK, Speizer FE, Le Moual N, Camargo CA.
        Eur Respir J. 2017 Oct;50(4).
        Disinfectant use has been associated with adverse respiratory effects among healthcare workers. However, the specific harmful agents have not been elucidated. We examined the association between occupational exposure to disinfectants and asthma control in the Nurses’ Health Study II, a large cohort of female nurses.Nurses with asthma were invited in 2014 to complete two questionnaires on their current occupation and asthma (response rate 80%). Asthma control was defined by the Asthma Control Test (ACT). Exposure to major disinfectants was evaluated by a job-task-exposure matrix (JTEM).Analyses included 4102 nurses with asthma (mean age 58 years). Asthma control was poor (ACT score 16-19) in 12% of nurses and very poor (ACT score </=15) in 6% of nurses. Use of disinfectants to clean medical instruments (19% exposed) was associated with poorly (OR 1.37; 95% CI 1.05-1.79) and very poorly (OR 1.88, 95% CI 1.38-2.56) controlled asthma (ptrend=0.004, after adjustment for potential confounders). Using JTEM estimates, exposure to formaldehyde, glutaraldehyde, hypochlorite bleach, hydrogen peroxide and enzymatic cleaners was associated with poor asthma control (all ptrend<0.05); exposure to quaternary ammonium compounds and alcohol was not.Use of several disinfectants was associated with poor asthma control. Our findings suggest targets for future efforts to prevent worsening of asthma control in healthcare workers.

      2. Recommendations for a clinical decision support system for work-related asthma in primary care settings
        Harber P, Redlich CA, Hines S, Filios M, Storey E.
        J Occup Environ Med. 2017 Oct 11.
        OBJECTIVE: Describe a recommended clinical decision support approach for work-related asthma for incorporation in electronic health records for primary care health care providers. METHODS: Subject matter experts convened by the American Thoracic Society reviewed available guidelines and published literature to develop specific recommendations. RESULTS: It is important to recognize possible work-related asthma among persons with new-onset or worsening asthma. The work group recommends incorporating three simple questions about temporal relations between asthma symptoms and work in EHR systems and identified specific clinical conditions to trigger this intervention. Patients with positive responses to the three questions should have the asthma diagnosis documented and have further evaluation, education, and possible referral. CONCLUSIONS: An effective CDS system for improving recognition of work-related asthma may help reduce morbidity and mortality of asthma in adults.

      3. Site-specific solid cancer mortality following exposure to ionizing radiation: a cohort study of workers (INWORKS)
        Richardson DB, Cardis E, Daniels RD, Gillies M, Haylock R, Leuraud K, Laurier D, Moissonnier M, Schubauer-Berigan MK, Thierry-Chef I, Kesminiene A.
        Epidemiology. 2017 Oct 04.
        BACKGROUND: There is considerable scientific interest in associations between protracted low-dose exposure to ionizing radiation and the occurrence of specific types of cancer. METHODS: Associations between ionizing radiation and site-specific solid cancer mortality were examined among 308,297 nuclear workers employed in France, the United Kingdom, and the United States. Workers were monitored for external radiation exposure and follow-up encompassed 8.2 million person-years. Radiation-mortality associations were estimated using a maximum likelihood method and using a Markov chain Monte Carlo method, the latter used to fit a hierarchical regression model to stabilize estimates of association. RESULTS: The analysis included 17,957 deaths due to solid cancer, the most common being lung, prostate, and colon cancer. Using a maximum likelihood method to quantify associations between radiation dose and site-specific cancer, we obtained positive point estimates for oral, esophagus, stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura, bone and connective tissue, skin, ovary, testis, and thyroid cancer; in addition, we obtained negative point estimates for cancer of the liver and gallbladder, prostate, bladder, kidney, and brain. Most of these estimated coefficients exhibited substantial imprecision. Employing a hierarchical model for stabilization had little impact on the estimated associations for the most commonly observed outcomes, but for less frequent cancer types the stabilized estimates tended to take less extreme values and have greater precision than estimates obtained without such stabilization. CONCLUSIONS: The results provide further evidence regarding associations between low-dose radiation exposure and cancer.

      4. Translation research in occupational safety and health: A proposed framework
        Schulte PA, Cunningham TR, Nickels L, Felknor S, Guerin R, Blosser F, Chang CC, Check P, Eggerth D, Flynn M, Forrester C, Hard D, Hudson H, Lincoln J, McKernan LT, Pratap P, Stephenson CM, Van Bogaert D, Menger-Ogle L.
        Am J Ind Med. 2017 Oct 09.
        Translation research in occupational safety and health is the application of scientific investigative approaches to study how the outputs of basic and applied research can be effectively translated into practice and have an impact. This includes the study of the ways in which useful knowledge and interventions are disseminated, adopted, implemented, and institutionalized. In this paper, a 4-stage framework (Development, Testing, Institutionalization, and Evaluation) is presented. Translation research can be used to enhance the use and impact of occupational safety and health knowledge and interventions to protect workers. This type of research has not received much attention in the occupational safety and health field. However, in contemporary society, it is critical to know how to make an impact with the findings and outputs of basic and applied research. This paper provides a novel framework for consideration of how to advance and prioritize translation research for occupational safety and health.

    • Parasitic Diseases
      1. Methodological considerations for use of routine health information system data to evaluate malaria program impact in an era of declining malaria transmission
        Ashton RA, Bennett A, Yukich J, Bhattarai A, Keating J, Eisele TP.
        Am J Trop Med Hyg. 2017 Sep;97(3_Suppl):46-57.
        Coverage of malaria control interventions is increasing dramatically across endemic countries. Evaluating the impact of malaria control programs and specific interventions on health indicators is essential to enable countries to select the most effective and appropriate combination of tools to accelerate progress or proceed toward malaria elimination. When key malaria interventions have been proven effective under controlled settings, further evaluations of the impact of the intervention using randomized approaches may not be appropriate or ethical. Alternatives to randomized controlled trials are therefore required for rigorous evaluation under conditions of routine program delivery. Routine health management information system (HMIS) data are a potentially rich source of data for impact evaluation, but have been underused in impact evaluation due to concerns over internal validity, completeness, and potential bias in estimates of program or intervention impact. A range of methodologies were identified that have been used for impact evaluations with malaria outcome indicators generated from HMIS data. Methods used to maximize internal validity of HMIS data are presented, together with recommendations on reducing bias in impact estimates. Interrupted time series and dose-response analyses are proposed as the strongest quasi-experimental impact evaluation designs for analysis of malaria outcome indicators from routine HMIS data. Interrupted time series analysis compares the outcome trend and level before and after the introduction of an intervention, set of interventions or program. The dose-response national platform approach explores associations between intervention coverage or program intensity and the outcome at a subnational (district or health facility catchment) level.

      2. Albendazole and ivermectin for the control of soil-transmitted helminths in an area with high prevalence of Strongyloides stercoralis and hookworm in northwestern Argentina: A community-based pragmatic study
        Echazu A, Juarez M, Vargas PA, Cajal SP, Cimino RO, Heredia V, Caropresi S, Paredes G, Arias LM, Abril M, Gold S, Lammie P, Krolewiecki AJ.
        PLoS Negl Trop Dis. 2017 Oct 09;11(10):e0006003.
        BACKGROUND: Recommendations for soil-transmitted helminth (STH) control give a key role to deworming of school and pre-school age children with albendazole or mebendazole; which might be insufficient to achieve adequate control, particularly against Strongyloides stercoralis. The impact of preventive chemotherapy (PC) against STH morbidity is still incompletely understood. The aim of this study was to assess the effectiveness of a community-based program with albendazole and ivermectin in a high transmission setting for S. stercoralis and hookworm. METHODOLOGY: Community-based pragmatic trial conducted in Tartagal, Argentina; from 2012 to 2015. Six communities (5070 people) were enrolled for community-based PC with albendazole and ivermectin. Two communities (2721 people) were re-treated for second and third rounds. STH prevalence, anemia and malnutrition were explored through consecutive surveys. Anthropometric assessment of children, stool analysis, complete blood count and NIE-ELISA serology for S. stercoralis were performed. PRINCIPAL FINDINGS: STH infection was associated with anemia and stunting in the baseline survey that included all communities and showed a STH prevalence of 47.6% (almost exclusively hookworm and S. stercoralis). Among communities with multiple interventions, STH prevalence decreased from 62% to 23% (p<0.001) after the first PC; anemia also diminished from 52% to 12% (p<0.001). After two interventions S. stercoralis seroprevalence declined, from 51% to 14% (p<0.001) and stunting prevalence decreased, from 19% to 12% (p = 0.009). CONCLUSIONS: Hookworm’ infections are associated with anemia in the general population and nutritional impairment in children. S. stercoralis is also associated with anemia. Community-based deworming with albendazole and ivermectin is effective for the reduction of STH prevalence and morbidity in communities with high prevalence of hookworm and S. stercoralis.

      3. Impact evaluation of malaria control interventions on morbidity and all-cause child mortality in Rwanda, 2000-2010
        Eckert E, Florey LS, Tongren JE, Salgado SR, Rukundo A, Habimana JP, Hakizimana E, Munguti K, Umulisa N, Mulindahabi M, Karema C.
        Am J Trop Med Hyg. 2017 Sep;97(3_Suppl):99-110.
        The impressive decline in child mortality that occurred in Rwanda from 1996-2000 to 2006-2010 coincided with a period of rapid increase of malaria control interventions such as indoor residual spraying (IRS); insecticide-treated net (ITN) distribution and use, and improved malaria case management. The impact of these interventions was examined through ecological correlation analysis, and robust decomposition analysis of contextual factors on all-cause child mortality. Child mortality fell 61% during the evaluation period and prevalence of severe anemia in children 6-23 months declined 71% between 2005 and 2010. These changes in malaria morbidity and mortality occurred concurrently with a substantial increase in vector control activities. ITN use increased among children under five, from 4% to 70%. The IRS program began in 2007 and covered 1.3 million people in the highest burden districts by 2010. At the same time, diagnosis and treatment with an effective antimalarial expanded nationally, and included making services available to children under the age of 5 at the community level. The percentage of children under 5 who sought care for a fever increased from 26% in 2000 to 48% in 2010. Multivariable models of the change in child mortality between 2000 and 2010 using nationally representative data reveal the importance of increasing ITN ownership in explaining the observed mortality declines. Taken as a whole, the evidence supports the conclusion that malaria control interventions contributed to the observed decline in child mortality in Rwanda from 2000 to 2010, even in a context of improving socioeconomic, maternal, and child health conditions.

      4. Impact of insecticide-treated net ownership on all-cause child mortality in Malawi, 2006-2010
        Florey LS, Bennett A, Hershey CL, Bhattarai A, Nielsen CF, Ali D, Luhanga M, Taylor C, Eisele TP, Ye Y.
        Am J Trop Med Hyg. 2017 Sep;97(3_Suppl):65-75.
        Insecticide-treated nets (ITNs) have been shown to be highly effective at reducing malaria morbidity and mortality in children. However, there are limited studies that assess the association between increasing ITN coverage and child mortality over time, at the national level, and under programmatic conditions. Two analytic approaches were used to examine this association: a retrospective cohort analysis of individual children and a district-level ecologic analysis. To evaluate the association between household ITN ownership and all-cause child mortality (ACCM) at the individual level, data from the 2010 Demographic and Health Survey (DHS) were modeled in a Cox proportional hazards framework while controlling for numerous environmental, household, and individual confounders through the use of exact matching. To evaluate population-level association between ITN ownership and ACCM between 2006 and 2010, program ITN distribution data and mortality data from the 2006 Multiple Indicator Cluster Survey and the 2010 DHS were aggregated at the district level and modeled using negative binomial regression. In the Cox model controlling for household, child and maternal health factors, children between 1 and 59 months in households owning an ITN had significantly lower mortality compared with those without an ITN (hazard ratio = 0.75, 95% confidence interval [CI] = 0.62-90). In the district-level model, higher ITN ownership was significantly associated with lower ACCM (incidence rate ratio = 0.77; 95% CI = 0.60-0.98). These findings suggest that increasing ITN ownership may have contributed to the decline in ACCM during 2006-2010 in Malawi and represent a novel use of district-level data from nationally representative surveys.

      5. Implementing impact evaluations of malaria control interventions: Process, lessons learned, and recommendations
        Hershey CL, Bhattarai A, Florey LS, McElroy PD, Nielsen CF, Ye Y, Eckert E, Franca-Koh AC, Shargie E, Komatsu R, Smithson P, Thwing J, Mihigo J, Herrera S, Taylor C, Shah J, Mouzin E, Yoon SS, Salgado SR.
        Am J Trop Med Hyg. 2017 Sep;97(3_Suppl):20-31.
        As funding for malaria control increased considerably over the past 10 years resulting in the expanded coverage of malaria control interventions, so did the need to measure the impact of these investments on malaria morbidity and mortality. Members of the Roll Back Malaria (RBM) Partnership undertook impact evaluations of malaria control programs at a time when there was little guidance in terms of the process for conducting an impact evaluation of a national-level malaria control program. The President’s Malaria Initiative (PMI), as a member of the RBM Partnership, has provided financial and technical support for impact evaluations in 13 countries to date. On the basis of these experiences, PMI and its partners have developed a streamlined process for conducting the evaluations with a set of lessons learned and recommendations. Chief among these are: to ensure country ownership and involvement in the evaluations; to engage stakeholders throughout the process; to coordinate evaluations among interested partners to avoid duplication of efforts; to tailor the evaluation to the particular country context; to develop a standard methodology for the evaluations and a streamlined process for completion within a reasonable time; and to develop tailored dissemination products on the evaluation for a broad range of stakeholders. These key lessons learned and resulting recommendations will guide future impact evaluations of malaria control programs and other health programs.

      6. Malaria control interventions contributed to declines in malaria parasitemia, severe anemia, and all-cause mortality in children less than 5 years of age in Malawi, 2000-2010
        Hershey CL, Florey LS, Ali D, Bennett A, Luhanga M, Mathanga DP, Salgado SR, Nielsen CF, Troell P, Jenda G, Ye Y, Bhattarai A.
        Am J Trop Med Hyg. 2017 Sep;97(3_Suppl):76-88.
        Malaria control intervention coverage increased nationwide in Malawi during 2000-2010. Trends in intervention coverage were assessed against trends in malaria parasite prevalence, severe anemia (hemoglobin < 8 g/dL), and all-cause mortality in children under 5 years of age (ACCM) using nationally representative household surveys. Associations between insecticide-treated net (ITN) ownership, malaria morbidity, and ACCM were also assessed. Household ITN ownership increased from 27.4% (95% confidence interval [CI] = 25.9-29.0) in 2004 to 56.8% (95% CI = 55.6-58.1) in 2010. Similarly intermittent preventive treatment during pregnancy coverage increased from 28.2% (95% CI = 26.7-29.8) in 2000 to 55.0% (95% CI = 53.4-56.6) in 2010. Malaria parasite prevalence decreased significantly from 60.5% (95% CI = 53.0-68.0) in 2001 to 20.4% (95% CI = 15.7-25.1) in 2009 in children aged 6-35 months. Severe anemia prevalence decreased from 20.4% (95% CI: 17.3-24.0) in 2004 to 13.1% (95% CI = 11.0-15.4) in 2010 in children aged 6-23 months. ACCM decreased 41%, from 188.6 deaths per 1,000 live births (95% CI = 179.1-198.0) during 1996-2000, to 112.1 deaths per 1,000 live births (95% CI = 105.8-118.5) during 2006-2010. When controlling for other covariates in random effects logistic regression models, household ITN ownership was protective against malaria parasitemia in children (odds ratio [OR] = 0.81, 95% CI = 0.72-0.92) and severe anemia (OR = 0.82, 95% CI = 0.72-0.94). After considering the magnitude of changes in malaria intervention coverage and nonmalaria factors, and given the contribution of malaria to all-cause mortality in malaria-endemic countries, the substantial increase in malaria control interventions likely improved child survival in Malawi during 2000-2010.

      7. Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes
        Kapisi J, Kakuru A, Jagannathan P, Muhindo MK, Natureeba P, Awori P, Nakalembe M, Ssekitoleko R, Olwoch P, Ategeka J, Nayebare P, Clark TD, Rizzuto G, Muehlenbachs A, Havlir DV, Kamya MR, Dorsey G, Gaw SL.
        Malar J. 2017 Oct 05;16(1):400.
        BACKGROUND: Malaria in pregnancy has been associated with maternal morbidity, placental malaria, and adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of malaria during pregnancy, measures of placental malaria, and birth outcomes. METHODS: This is a nested observational study of data from a randomized controlled trial of intermittent preventive therapy during pregnancy among 282 participants with assessment of placental malaria and delivery outcomes. HIV-uninfected pregnant women were enrolled at 12-20 weeks of gestation. Symptomatic malaria during pregnancy was measured using passive surveillance and monthly detection of asymptomatic parasitaemia using loop-mediated isothermal amplification (LAMP). Placental malaria was defined as either the presence of parasites in placental blood by microscopy, detection of parasites in placental blood by LAMP, or histopathologic evidence of parasites or pigment. Adverse birth outcomes assessed included low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) infants. RESULTS: The 282 women were divided into three groups representing increasing malaria burden during pregnancy. Fifty-two (18.4%) had no episodes of symptomatic malaria or asymptomatic parasitaemia during the pregnancy, 157 (55.7%) had low malaria burden (0-1 episodes of symptomatic malaria and < 50% of samples LAMP+), and 73 (25.9%) had high malaria burden during pregnancy (>/= 2 episodes of symptomatic malaria or >/= 50% of samples LAMP+). Women with high malaria burden had increased risks of placental malaria by blood microscopy and LAMP [aRR 14.2 (1.80-111.6) and 4.06 (1.73-9.51), respectively], compared to the other two groups combined. Compared with women with no malaria exposure during pregnancy, the risk of placental malaria by histopathology was higher among low and high burden groups [aRR = 3.27 (1.32-8.12) and aRR = 7.07 (2.84-17.6), respectively]. Detection of placental parasites by any method was significantly associated with PTB [aRR 5.64 (1.46-21.8)], and with a trend towards increased risk for LBW and SGA irrespective of the level of malaria burden during pregnancy. CONCLUSION: Higher malaria burden during pregnancy was associated with placental malaria and together with the detection of parasites in the placenta were associated with increased risk for adverse birth outcomes. Trial Registration Current Controlled Trials Identifier NCT02163447.

      8. Seroprevalence of antibodies to Toxocara species in the United States and associated risk factors, 2011- 2014
        Liu EW, Chastain HM, Shin SH, Wiegand R, Kruszon-Moran D, Handali S, Jones JL.
        Clin Infect Dis. 2017 Sep 04.
        Background: Toxocariasis results from infection with larval stages of a dog and cat intestinal nematode and causes human morbidity. The current US estimate of Toxocara exposure is 13.9% (NHANES III 1988-1994). Methods: We used a multiplex bead based assay (Tc-CTL-1MBA) with purified Toxocara canis antigen to estimate Toxocara antibody seroprevalence in serum of 13,509 persons six years and older from the National Health and Nutrition Examination Survey (NHANES), 2011-2014 and identified seropositivity risk factors. We tested a subset of 500 samples with the previously used T. canis enzyme immunoassay to estimate seroprevalence had prior samples been tested by Tc-CTL-1MBA. Results: The age standardized estimate of Toxocara seroprevalence was 5.0% (95% confidence interval [CI], 4.2%-5.8%), lower than previously reported even adjusting for increased Tc-CTL-1MBA specificity. Risk factors for seropositivity from multiple logistic regression were older age (odds ratio [OR], 2.1; 95%CI, 1.1-3.9 in persons 50-59 years old; OR, 1.7; 95%CI, 1.0-2.8 in persons 60-69; and OR, 2.6; 95%CI, 1.5-4.7 in persons >/=70 versus persons 6-11), non-Hispanic Black race/Hispanic origin (OR, 1.4; 95%CI, 1.0-2.0) versus non-Hispanic White, male sex (OR, 1.9; 95%CI, 1.6-2.2), living below poverty level (OR, 1.9; 95%CI, 1.4-2.6), households with >/=0.5 persons per room (OR, 1.3; 95%CI, 1.0-1.6), less than college education (OR, 1.9; 95%CI, 1.5-2.4), and birth outside the United States (OR, 3.6; 95%CI, 2.6-5.1). Conclusions: Toxocara seroprevalence estimates in 2011-14 were lower than in a study from NHANES III, 1988-94, but seropositivity risk factors remained the same and should continue to be the focus of prevention efforts.

      9. Absence of Loa loa microfilaremia among newly arrived Congolese refugees in Texas
        Montour J, Lee D, Snider C, Jentes ES, Stauffer W.
        Am J Trop Med Hyg. 2017 Sep 05.
        The Centers for Disease Control and Prevention recommends that refugees at risk of Loa loa infection be tested for microfilaria before treatment with ivermectin. We report observational results of this approach in African refugees in Texas. Daytime blood smears were performed for microfilaria on at-risk African refugees who arrived in Texas from July 1, 2014 through December 30, 2016. Clinics were asked if there were any adverse events reported among those who received ivermectin. Of the 422 persons screened, 346 (82%) were born in L. loa-endemic countries, with 332 (96%) of these being born in the Democratic Republic of Congo. No smears detected microfilaria, and all received presumptive ivermectin with no reports of significant adverse events. In this investigation, the prevalence of significant microfilarial load in sub-Saharan African refugees appeared to be low, and ivermectin treatment was safe and well tolerated.

      10. Can the collection of expired long-lasting insecticidal nets reduce their coverage and use? Sociocultural aspects related to LLIN life cycle management and use in four districts in Madagascar
        Ramanantsoa A, Wilson-Barthes M, Rahenintsoa R, Hoibak S, Ranaivoharimina H, Rahelimalala MD, Rakotomanga A, Finlay A, Muela Ribera J, Peeters Grietens K.
        Malar J. 2017 Oct 10;16(1):404.
        BACKGROUND: There is growing awareness of the likely impact increased numbers of LLINs will have on the environment, if not disposed of or recycled appropriately. As part of a World Health Organization (WHO) and United Nations Environment Programme (UNEP) pilot study to assess environmentally-sound and cost-effective LLIN recycling strategies, the USAID-Deliver Project collected 22,559 used bed nets in Madagascar. A social science study was conducted to provide data on socio-cultural factors related to collection and replacement of LLINs, including impact on primary and other net uses. METHODS: Ethnographic exploratory research was carried out following the pilot USAID-Deliver net collection and recycling campaign in Betioky, Tsihombe, Fenerive Est and Ambanja districts of Madagascar, triangulating participant observation, interviewing and group discussions. Sampling was theoretical and data analysis was a continuous and iterative process concurrent to data collection. Final analysis was conducted using NVivo10. RESULTS: The following themes emerged as contributing to the success of collecting expired LLINs in the community for recycling purposes: (i) net adequacy and preference: characteristic differences between collected and newly distributed nets lead to communities’ reticence to relinquish old nets before confirming new nets were appropriate for intended use. Where newly distributed nets failed to meet local requirements, this was expected to increase alternative uses and decrease household turn over. (ii) Net collection strategies: the net collection campaign brought net use out of the private sphere and into the public arena. Net owners reported feeling ashamed when presenting damaged nets in public for collection, leading to reduced net relinquishment. (iii) Net lifecycle: communities perceived nets as being individually owned and economic value was attributed both to good-condition nets for sleeping and to worn nets for alternative/secondary purposes. Collecting nets at the stage of waste rather than at their prescribed end of life was locally acceptable. CONCLUSION: The collection of LLINs for recycling/disposal can lead to lower coverage under certain conditions. Collecting used LLINs may be appropriate under the following conditions: (i) nets are collected at the stage of waste; (ii) new nets are in line with community preferences; and (iii) collection strategies have been agreed upon within the community prior to replacement activities. Any collection/recycling of old LLINs should be based on in-depth understanding of the local context and include participatory processes to prevent reduced coverage.

      11. [No abstract]

      12. Declines in malaria burden and all-cause child mortality following increases in control interventions in Senegal, 2005-2010
        Thwing J, Eckert E, Dione DA, Tine R, Faye A, Ye Y, Ndiop M, Cisse M, Ndione JA, Diouf MB, Ba M.
        Am J Trop Med Hyg. 2017 Sep;97(3_Suppl):89-98.
        Malaria is endemic in Senegal. The national malaria control strategy focuses on achieving universal coverage for major interventions, with a goal of reaching preelimination status by 2018. Senegal began distribution of insecticide-treated nets (ITNs) and introduced artemisinin-based combination therapy in 2006, then introduced rapid diagnostic tests in 2007. We evaluated the impact of these efforts using a plausibility design based on malaria’s contribution to all-cause under-five mortality (ACCM) and considering other contextual factors which may influence ACCM. Between 2005 and 2010, household ownership of ITNs increased from 20% to 63%, and the proportion of people sleeping under an ITN the night prior to the survey increased from 6% to 29%. Malaria parasite prevalence declined from 6% to 3% from 2008 to 2010 among children under five. Some nonmalaria indicators of child health improved, for example, increase of complete vaccination coverage from 58% to 64%; however, nutritional indicators deteriorated, with an increase in stunting from 16% to 26%. Although economic indicators improved, environmental conditions favored an increase in malaria transmission. ACCM decreased 40% between 2005 and 2010, from 121 (95% confidence interval [CI] 113-129) to 72 (95% CI 66-77) per 1,000, and declines were greater among age groups, epidemiologic zones, and wealth quintiles most at risk for malaria. After considering coverage of malaria interventions, trends in malaria morbidity, effects of contextual factors, and trends in ACCM, it is plausible that malaria control interventions contributed to a reduction in malaria mortality and to the impressive gains in child survival in Senegal.

      13. Assessing bed net damage: comparisons of three measurement methods for estimating the size, shape, and distribution of holes on bed nets
        Vanden Eng JL, Mathanga DP, Landman K, Mwandama D, Minta AA, Shah M, Sutcliffe J, Chisaka J, Lindblade KA, Steinhardt L.
        Malar J. 2017 Oct 10;16(1):405.
        BACKGROUND: Measuring the physical condition of long-lasting insecticidal nets (LLINs) under field conditions is of great importance for malaria control programmes to guide decisions on how frequently to replace LLINs. Current guidelines by the World Health Organization Pesticide Evaluation Scheme (WHOPES) propose a proportionate hole index (pHI) for assessing LLIN condition by counting the number of holes the size of a thumb, fist, head, and larger than a head. However, this method does not account for irregular hole shapes or exact hole sizes which could result in inaccurate decisions about when to replace LLINs. METHODS: LLINs were collected during a 2013 health facility-based malaria case control study in Machinga District, Malawi. To evaluate the accuracy of the pHI, the physical condition of 277 LLINs was estimated by the WHOPES method and then compared with two more thorough measurement methods: image analysis of digital photographs of each LLIN side; and for 10 nets, ruler measurements of the length, width, and location of each hole. Total hole counts and areas per net were estimated by each method, and detailed results of hole shapes and composite pictures of hole locations were generated using image analysis. RESULTS: The WHOPES method and image analysis resulted in similar estimates of total hole counts, each with a median of 10 (inter-quartile range (IQR) 4-24 and 4-23, respectively; p = 0.004); however, estimated hole areas were significantly larger using the WHOPES method (median 162 cm2, IQR 28-793) than image analysis (median 13 cm2, IQR 3-101; p < 0.0001). The WHOPES method classified fewer LLINs in ‘good condition’ compared to image analysis (42% vs 74%). The ruler method detected significantly more holes than image analysis did (p = 0.002) in 10 LLINs; however, total hole area was not significantly different (p = 0.16). Most holes were not circular but roughly 2-5 times longer in one direction. The lower quarter of LLIN sides was found to have the most holes. CONCLUSIONS: The WHOPES method overestimated total hole area, likely because holes are elongated rather than circular, suggesting further adjustments to the pHI formula may be warranted when considering LLIN replacement strategies.

      14. Framework for evaluating the health impact of the scale-up of malaria control interventions on all-cause child mortality in sub-Saharan Africa
        Ye Y, Eisele TP, Eckert E, Korenromp E, Shah JA, Hershey CL, Ivanovich E, Newby H, Carvajal-Velez L, Lynch M, Komatsu R, Cibulskis RE, Moore Z, Bhattarai A.
        Am J Trop Med Hyg. 2017 Sep;97(3_Suppl):9-19.
        Concerted efforts from national and international partners have scaled up malaria control interventions, including insecticide-treated nets, indoor residual spraying, diagnostics, prompt and effective treatment of malaria cases, and intermittent preventive treatment during pregnancy in sub-Saharan Africa (SSA). This scale-up warrants an assessment of its health impact to guide future efforts and investments; however, measuring malaria-specific mortality and the overall impact of malaria control interventions remains challenging. In 2007, Roll Back Malaria’s Monitoring and Evaluation Reference Group proposed a theoretical framework for evaluating the impact of full-coverage malaria control interventions on morbidity and mortality in high-burden SSA countries. Recently, several evaluations have contributed new ideas and lessons to strengthen this plausibility design. This paper harnesses that new evaluation experience to expand the framework, with additional features, such as stratification, to examine subgroups most likely to experience improvement if control programs are working; the use of a national platform framework; and analysis of complete birth histories from national household surveys. The refined framework has shown that, despite persisting data challenges, combining multiple sources of data, considering potential contributions from both fundamental and proximate contextual factors, and conducting subnational analyses allows identification of the plausible contributions of malaria control interventions on malaria morbidity and mortality.

    • Substance Use and Abuse
      1. Effect of a high dosage opioid prior authorization policy on prescription opioid use, misuse, and overdose outcomes
        Hartung DM, Kim H, Ahmed SM, Middleton L, Keast S, Deyo RA, Zhang K, McConnell KJ.
        Subst Abus. 2017 Oct 10:0.
        BACKGROUND: High dosage opioid use is a risk factor for opioid-related overdose commonly cited in guidelines, recommendations, and policies. In 2012, the Oregon Medicaid program developed a prior authorization policy for opioid prescriptions above 120 mg per day morphine equivalent dose (MED). This study aimed to evaluate the effects of that policy on utilization, prescribing patterns, and health outcomes. Methods: Using administrative claims data from Oregon and a control state (Colorado) between 2011 and 2013, we used difference-in-differences analyses to examine changes in utilization, measures of high risk opioid use, and overdose after introduction of the policy. We also evaluated opioid utilization in a cohort of individuals who were high dosage opioid users before the policy. Results: Following implementation of Oregon’s high dosage policy, the monthly probability of an opioid fill over 120 mg MED declined significantly by 1.7 percentage points (95% confidence interval [CI]; -2.0% to -1.4%), whereas it increased significantly by 1.0 percentage points (95% CI 0.4% to 1.7%) for opioid fills < 61 mg MED. Fills of medications used to treat neuropathic pain also increased by 1.2 percentage points (95% CI 0.7% to 1.8%). The monthly probability of multiple pharmacy use declined by 0.1 percentage points (-0.2% to -0.0) following the prior authorization, but there were no significant changes in ED encounters or hospitalizations for opioid overdose. Among individuals who were using a high dosage opioid before the policy, there was a 20.3 percentage point (95% CI -15.3% to -25.3%) decline in estimated probability of having a high dosage fill after the policy. Conclusions: Oregon’s prior authorization policy was effective at reducing high dosage opioid prescriptions. While multiple pharmacy use also declined, we found no impact on opioid overdose.

    • Zoonotic and Vectorborne Diseases
      1. Notes from the field: Multiple cases of Seoul virus infection in a household with infected pet rats – Tennessee, December 2016-April 2017
        Fill MA, Mullins H, May AS, Henderson H, Brown SM, Chiang CF, Patel NR, Klena JD, de St Maurice A, Knust B, Nichol ST, Dunn JR, Schaffner W, Jones TF.
        MMWR Morb Mortal Wkly Rep. 2017 Oct 13;66(40):1081-1082.

        [No abstract]

      2. Outbreak of influenza A(H7N2) among cats in an animal shelter with cat-to-human transmission – New York City, 2016
        Lee CT, Slavinski S, Schiff C, Merlino M, Daskalakis D, Liu D, Rakeman JL, Misener M, Thompson C, Leung YL, Varma JK, Fry A, Havers F, Davis T, Newbury S, Layton M.
        Clin Infect Dis. 2017 Jul 28.
        We describe the first case of cat-to-human transmission of influenza A(H7N2), an avian-lineage influenza A virus, that occurred during an outbreak among cats in New York City animal shelters. We describe the public health response and investigation.

      3. Favipiravir and ribavirin treatment of epidemiologically linked cases of Lassa fever
        Raabe VN, Kann G, Ribner BS, Morales A, Varkey JB, Mehta AK, Lyon GM, Vanairsdale S, Faber K, Becker S, Eickmann M, Strecker T, Brown S, Patel K, De Leuw P, Schuettfort G, Stephan C, Rabenau H, Klena JD, Rollin PE, McElroy A, Stroher U, Nichol S, Kraft CS, Wolf T.
        Clin Infect Dis. 2017 Sep 01;65(5):855-859.
        Two patients with Lassa fever are described who are the first human cases treated with a combination of ribavirin and favipiravir. Both patients survived but developed transaminitis and had prolonged detectable virus RNA in blood and semen, suggesting that the possibility of sexual transmission of Lassa virus should be considered.

      4. Chikungunya detection during dengue outbreak in Sumatra, Indonesia: Clinical manifestations and virological profile
        Sasmono RT, Perkasa A, Yohan B, Haryanto S, Yudhaputri FA, Hayati RF, Ma’roef CN, Ledermann JP, Aye Myint KS, Powers AM.
        Am J Trop Med Hyg. 2017 Sep 25.
        Chikungunya fever (CHIK) is an acute viral infection caused by infection with chikungunya virus (CHIKV). The disease affects people in areas where certain Aedes species mosquito vectors are present, especially in tropical and subtropical countries. Indonesia has witnessed CHIK disease since the early 1970s with sporadic outbreaks occurring throughout the year. The CHIK clinical manifestation, characterized by fever, headache, and joint pain, is similar to that of dengue (DEN) disease. During a molecular study of a DEN outbreak in Jambi, Sumatra, in the early 2015, DEN-negative samples were evaluated for evidence of CHIKV infection. Among 103 DEN-negative samples, eight samples were confirmed (7.8%) as positive for CHIK by both molecular detection and virus isolation. The mean age of the CHIK patients was 21.3 +/- 9.1 (range 11-35 years). The clinical manifestations of the CHIK patients were mild and mimicked DEN, with fever and headache as the main symptoms. Only three out of eight patients presented with classical joint pain. Sequencing of the envelope glycoprotein E1 gene and phylogenetic analysis identified all CHIKV isolates as belonging to the Asian genotype. Overall, our study confirms sustained endemic CHIKV transmission and the presence of multiple arboviruses circulating during a DEN outbreak in Indonesia. The co-circulation of arboviruses poses a public health threat and is likely to cause misdiagnosis and underreporting of CHIK in DEN-endemic areas such as Indonesia.

      5. Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne orthonairovirus, causes a severe hemorrhagic disease in humans (Crimean-Congo hemorrhagic fever, CCHF). Currently, no vaccines are approved to prevent CCHF; treatment is limited to supportive care and the use of ribavirin, the therapeutic benefits of which remain unclear. CCHF is part of WHO’s priority list of infectious diseases warranting further research and development. To aid in the identification of new antiviral compounds, we generated a recombinant CCHFV expressing a reporter protein, allowing us to quantify virus inhibition by measuring the reduction in fluorescence in infected cells treated with candidate compounds. The screening assay was readily adaptable to high-throughput screening (HTS) of compounds using Huh7 cells, with a signal-to-noise ratio of 50:1, and Z’-factors > 0.6 in both 96- and 384-well formats. A screen of candidate nucleoside analog compounds identified 2′-deoxy-2′-fluorocytidine (EC50 = 61 +/- 18 nM) as having 200 x the potency of ribavirin (EC50 = 12.5 +/- 2.6 muM), as well as 17 x the potency of T-705 (favipiravir), another compound with reported anti-CCHFV activity (EC50 = 1.03 +/- 0.16 muM). Furthermore, we also determined that 2′-deoxy-2′-fluorocytidine acts synergistically with T-705 to inhibit CCHFV replication without causing cytotoxicity. The incorporation of this reporter virus into the high-throughput screening assay described here will allow more rapid identification of effective therapeutic options to combat this emerging human pathogen.

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