Issue 40, October 10, 2017

CDC Science Clips: Volume 9, Issue 40, October 10, 2017

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

  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.
    • Chronic Diseases and Conditions
      • Financial and health barriers and caregiving-related difficulties among rural and urban caregiversExternal
        Bouldin ED, Shaull L, Andresen EM, Edwards VJ, McGuire LC.
        J Rural Health. 2017 Sep 23.

        PURPOSE: To assess whether financial or health-related barriers were more common among rural caregivers and whether rural caregivers experienced more caregiving-related difficulties than their urban peers. METHODS: We used data from 7,436 respondents to the Caregiver Module in 10 states from the 2011-2013 Behavioral Risk Factor Surveillance System. Respondents were classified as caregivers if they reported providing care to a family member or friend because of a long-term illness or disability. We classified respondents as living in a rural area if they lived outside of a Metropolitan Statistical Area (MSA). We defined a financial barrier as having an annual household income <$25,000 or not being able see a doctor when needed in the past year because of cost. We defined a health barrier as having multiple chronic health conditions, a disability, or fair or poor self-rated health. FINDINGS: Rural caregivers more frequently had financial barriers than urban caregivers (38.1% vs 31.0%, P = .0001), but the prevalence of health barriers was similar (43.3% vs 40.6%, P = .18). After adjusting for demographic differences, financial barriers remained more common among rural caregivers. Rural caregivers were less likely than their urban peers to report that caregiving created any difficulty in both unadjusted and adjusted models (adjusted prevalence ratio = 0.90; P < .001). CONCLUSIONS: Informal caregivers, particularly in rural areas, face financial barriers. Rural caregivers were less likely than urban caregivers to report caregiving-related difficulties. Rural caregivers’ coping strategies or skills in identifying informal supports may explain this difference, but additional research is needed to explore this hypothesis.

    • Communicable Diseases
      • HIV testing and sexual risks among migrant men who have sex with men: findings from a large cross-sectional study in Beijing, ChinaExternal
        Liu Y, Vermund SH, Ruan Y, Liu H, Zhang C, Yin L, Shao Y, Qian HZ.
        AIDS Care. 2017 Sep 25:1-9.

        Despite the exacerbating HIV transmission among migrant men who have sex with men (MSM) in China, few epidemiological studies explore their HIV testing/risk profiles. We sought to explore sociodemographic/behavioral correlates of HIV/syphilis and HIV testing among migrant MSM. A study was conducted among 3,588 HIV-uninfected MSM. Participants were recruited via short message services, peer referral, web-advertisement and community outreach. HIV/syphilis infections were lab-confirmed. Migrant MSM were more likely to be HIV-infected compared to local MSM. Among 2,699 migrant MSM, HIV testing was associated with older age, living longer in Beijing, having >/=10 lifetime male sexual partners (LMSPs), having insertive anal sex; while being unemployed/retired and having condomless receptive anal sex (CRAS) were associated with a lower odds of HIV testing. Being married, living longer in Beijing, ever testing for HIV and having sex with women were associated with lower HIV odds; while being unemployed/retired, having higher HIV perception, having >/= 10 LMSPs and having CRAS were associated a higher HIV odds. Increased likelihood of syphilis was associated with older age, being employed, higher HIV perception, having >/=10 LMSPs and having CRAS. Our study provides implications for targeted interventions to tackle HIV/STI risks and improve HIV testing among migrant Chinese MSM.

      • Multicountry validation of SAMBA – a novel molecular point-of-care test for HIV-1 detection in resource-limited settingExternal
        Ondiek J, Namukaya Z, Mtapuri-Zinyowera S, Balkan S, Elbireer A, Ushiro Lumb I, Kiyaga C, Goel N, Ritchie A, Ncube P, Omuomu K, Ndiege K, Kekitiinwa A, Mangwanya D, Fowler MG, Nadala L, Lee H.
        J Acquir Immune Defic Syndr. 2017 Oct 01;76(2):e52-e57.

        INTRODUCTION: Early diagnosis of HIV-1 infection and the prompt initiation of antiretroviral therapy are critical to achieving a reduction in the morbidity and mortality of infected infants. The Simple AMplification-Based Assay (SAMBA) HIV-1 Qual Whole Blood Test was developed specifically for early infant diagnosis and prevention of mother-to-child transmission programs implemented at the point-of-care in resource-limited settings. METHODS: We have evaluated the performance of this test run on the SAMBA I semiautomated platform with fresh whole blood specimens collected from 202 adults and 745 infants in Kenya, Uganda, and Zimbabwe. Results were compared with those obtained with the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HIV-1 assay as performed with fresh whole blood or dried blood spots of the same subjects, and discrepancies were resolved with alternative assays. RESULTS: The performance of the SAMBA and CAP/CTM assays evaluated at 5 laboratories in the 3 countries was similar for both adult and infant samples. The clinical sensitivity, specificity, positive predictive value, and negative predictive value for the SAMBA test were 100%, 99.2%, 98.7%, and 100%, respectively, with adult samples, and 98.5%, 99.8%, 99.7%, and 98.8%, respectively, with infant samples. DISCUSSION: Our data suggest that the SAMBA HIV-1 Qual Whole Blood Test would be effective for early diagnosis of HIV-1 infection in infants at point-of-care settings in sub-Saharan Africa.

      • Cross-sectional survey and surveillance for influenza viruses and MERS-CoV among Egyptian pilgrims returning from Hajj during 2012-2015External
        Refaey S, Amin MM, Roguski K, Azziz-Baumgartner E, Uyeki TM, Labib M, Kandeel A.
        Influenza Other Respir Viruses. 2017 Jan;11(1):57-60.

        BACKGROUND: Approximately 80 000 Egyptians participate in Hajj pilgrimage annually. The purpose of this study was to estimate influenza virus and MERS-CoV prevalence among Egyptian pilgrims returning from Hajj. STUDY: A cross-sectional survey among 3 364 returning Egyptian pilgrims from 2012 to 2015 was conducted. Nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected from all participants. Sputum specimens were collected from participants with respiratory symptoms and productive cough at the time of their interview. Specimens were tested for influenza viruses, and a convenience sample of NP/OP specimens was tested for MERS-CoV. Thirty percent of participants met the case definition for influenza-like illness (ILI), 14% tested positive for influenza viruses, and none tested positive for MERS-CoV. Self-reported influenza vaccination was 20%. CONCLUSIONS: High prevalence of reported ILI during pilgrimage and confirmed influenza virus on return from pilgrimage suggest a continued need for influenza prevention strategies for Egyptian Hajj pilgrims. An evaluation of the Ministry of Health and Population’s current risk communication campaigns to increase influenza vaccine use among pilgrims may help identify strategies to improve vaccine coverage.

      • Hepatitis C virus testing for case identification in persons born during 1945-1965: Results from three randomized controlled trialsExternal
        Yartel AK, Rein DB, Ann Brown K, Krauskopf K, Massoud OI, Jordan C, Kil N, Federman AD, Nerenz DR, Brady JE, Kruger DL, Smith BD.
        Hepatology. 2017 Sep 23.

        CDC and U.S. Preventive Services Task Force recommend one-time hepatitis C virus (HCV) testing for persons born during 1945-1965 (birth cohort). However, few studies estimate the effect of birth cohort (BC) testing implementation on HCV diagnoses in primary care settings. We aimed to determine the probability of identifying HCV infections in primary care using targeted BC testing compared with usual care at three academic medical centers. From December 2012 to March 2014, each center compared one of three distinct interventions to usual care using an independently-designed randomized controlled trial. Across centers, BC patients with no clinical documentation of previous HCV testing or diagnosis were randomly assigned to receive a one-time offering of HCV antibody (anti-HCV) testing via one of three independent implementation strategies (repeated-mailing outreach, EMR-integrated provider best practice alert [BPA], and direct patient-solicitation) or assigned to receive usual care. We estimated model-adjusted risk ratios (aRR) of anti-HCV positive (anti-HCV+) identification using BC testing versus usual care. In the repeated-mailing trial, 8,992 patients (intervention=2,993; control=5,999) were included in the analysis. The intervention was eight times as likely to identify anti-HCV+ patients compared with control (aRR 8.0, 95%CI 2.8-23.0; adjusted probabilities: intervention=0.27%; control=0.03%). In the BPA trial, data from 14,475 patients (BC=8,928; control=5,547) were analyzed. The intervention was 2.6 times as likely to identify anti-HCV+ patients versus control (aRR 2.6, 95%CI 1.1-6.4; adjusted probabilities: intervention=0.29%; control=0.11%). In the patient-solicitation trial, 8,873 patients (BC=4,307; control=4,566) were analyzed. The intervention was five times as likely to identify anti-HCV+ patients compared with control (aRR 5.3, 95%CI 2.3-12.3; adjusted probabilities: intervention=0.68%; control=0.11%). CONCLUSION: BC testing was effective in identifying previously undiagnosed HCV infections in primary care settings. This article is protected by copyright. All rights reserved.

    • Epidemiology and Surveillance
      • The 117 call alert system in Sierra Leone: from rapid Ebola notification to routine death reportingExternal
        Alpren C, Jalloh MF, Kaiser R, Diop M, Kargbo S, Castle E, Dafae F, Hersey S, Redd JT, Jambai A.
        BMJ Glob Health. 2017 ;2(3):e000392.

        A toll-free, nationwide phone alert system was established for rapid notification and response during the 2014-2015 Ebola epidemic in Sierra Leone. The system remained in place after the end of the epidemic under a policy of mandatory reporting and Ebola testing for all deaths, and, from June 2016, testing only in case of suspected Ebola. We describe the design, implementation and changes in the system; analyse calling trends during and after the Ebola epidemic; and discuss strengths and limitations of the system and its potential role in efforts to improve death reporting in Sierra Leone. Numbers of calls to report deaths of any cause (death alerts) and persons suspected of having Ebola (live alerts) were analysed by province and district and compared with numbers of Ebola cases reported by the WHO. Nearly 350 000 complete, non-prank calls were made to 117 between September 2014 and December 2016. The maximum number of daily death and live alerts was 9344 (October 2014) and 3031 (December 2014), respectively. Call volumes decreased as Ebola incidence declined and continued to decrease in the post-Ebola period. A national social mobilisation strategy was especially targeted to influential religious leaders, traditional healers and women’s groups. The existing infrastructure and experience with the system offer an opportunity to consider long-term use as a death reporting tool for civil registration and mortality surveillance, including rapid detection and control of public health threats. A routine social mobilisation component should be considered to increase usage.

    • Injury and Violence
      • The clinical implications of youth sports concussion laws: A reviewExternal
        Bell JM, Master CL, Lionbarger MR.
        Am J Lifestyle Med. 2017 ;20(10).

        The recent passage of state youth sports concussion laws across the country introduces clinical implications for health care professionals caring for student-athletes. Although the laws were established to provide protections for student-athletes and prevent adverse outcomes, efforts aimed at implementation have uncovered various challenges in concussion diagnosis and management. Some of the most salient issues include medical evaluation, return to play, and return to learn. For this reason, health care professionals play a pivotal role in determining the critical next steps after a student is removed from play with a suspected concussion. Also, state laws may influence an influx of concussion patients to health care facilities and, thereby, present various unforeseen challenges that can be mitigated with adequate clinical preparation. This is key to helping student-athletes recover and resume regular activities in sports, recreation, and education. This review describes the various components of state youth sports concussion laws relevant to clinical practice and nuances that health care professionals should appreciate in this context. Additionally, concussion tools and strategies that can be used in clinical practice are discussed.

    • Occupational Safety and Health
      • Objective: Positive associations between education and late-life cognition have been widely reported. This study examines whether occupational complexity mediates the relationship between education and late-life cognition, and whether the magnitude of mediation differs by race, gender, or education level. Methods: Data were from a population-based cohort of non-Hispanic Blacks and Whites aged >/=45 years (n = 7,357). Education was categorized as less than high school, high school, some college, and college or higher. Using linear regression, we estimated the direct effect of each successive increase in education on cognitive functioning and indirect effects via substantive complexity of work. Results: Occupational complexity significantly mediated 11%-22% of the cognitive gain associated with higher levels of education. The pattern of mediation varied between White men and all other race-gender groups: among White men, the higher the education, the greater the mediation effect by occupational complexity. Among Black men and women of both races, the higher the education, the smaller the mediation effect. Discussion: Higher levels of education may provide opportunity for intellectually engaging environments throughout adulthood in the form of complex work, which may protect late-life cognition. However, this protective effect of occupational complexity may not occur equally across race-gender subgroups.

      • Using systematic review in occupational safety and healthExternal
        Howard J, Piacentino J, MacMahon K, Schulte P.
        Am J Ind Med. 2017 Sep 25.

        Evaluation of scientific evidence is critical in developing recommendations to reduce risk. Healthcare was the first scientific field to employ a systematic review approach for synthesizing research findings to support evidence-based decision-making and it is still the largest producer and consumer of systematic reviews. Systematic reviews in the field of occupational safety and health are being conducted, but more widespread use and adoption would strengthen assessments. In 2016, NIOSH asked RAND to develop a framework for applying the traditional systematic review elements to the field of occupational safety and health. This paper describes how essential systematic review elements can be adapted for use in occupational systematic reviews to enhance their scientific quality, objectivity, transparency, reliability, utility, and acceptability.

    • Zoonotic and Vectorborne Diseases
      • Zika virus (ZIKV) has emerged as a major global public health concern in the last two years due to its link as a causative agent of human birth defects. Its rapid expansion into the Western Hemisphere as well as the ability to be transmitted from mother to fetus, through sexual transmission and possibly through blood transfusions has increased the need for a rapid and expansive public health response to this unprecedented epidemic. A non-invasive and rapid ZIKV diagnostic screening assay that can be performed in a clinical setting throughout pregnancy is vital for prenatal care of women living in areas of the world where exposure to the virus is possible. To meet this need we have developed a sensitive and specific reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay to detect ZIKV RNA in urine and serum with a simple visual detection. RT-LAMP results were shown to have a limit of detection 10-fold higher than qRT-PCR. As little as 1.2 RNA copies/mul was detected by RT-LAMP from a panel of 178 diagnostic specimens. The assay was shown to be highly specific for ZIKV RNA when tested with diagnostic specimens positive for dengue virus (DENV) and chikungunya virus (CHIKV). The assay described here illustrates the potential for a fast, reliable, sensitive and specific assay for the detection of ZIKV from urine or serum that can be performed in a clinical or field setting with minimal equipment and technological expertise.

  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.
    • Communicable Diseases
      1. Isolation of Candida auris from nine patients in Central America: Importance of accurate diagnosis and susceptibility testingExternal
        Arauz AB, Caceres DH, Santiago E, Armstrong P, Arosemena S, Ramos C, Espinosa-Bode A, Borace J, Hayer L, Cedeno I, Jackson BR, Sosa N, Berkow EL, Lockhart SR, Rodriguez-French A, Chiller T.
        Mycoses. 2017 Sep 25.

        Candida auris is an emerging multidrug-resistant (MDR) fungus associated with invasive infections and high mortality. This report describes nine patients from whom C. auris was isolated at a hospital in Panama City, Panama, the first such cases in Central America, and highlights the challenges of accurate identification and methods for susceptibility testing. This article is protected by copyright. All rights reserved.

      2. Salmonella epidemiology: A whirlwind of changeExternal
        Besser JM.
        Food Microbiology. 2017 .

        The field of infectious disease epidemiology for Salmonella and other enteric pathogens is undergoing some of the most profound changes since the time of Kauffman and White. Rapid advances in “big data” technologies such as genomics and metagenomics are making it possible to monitor and control salmonellosis in new and exciting ways. Epidemiological methods are becoming increasingly robust through the routine use of standardized hypothesis-generating questionnaires, iterative open-ended interviewing, informational trace-backs and new modeling techniques for describing the attribution of disease to food sources. In addition, Salmonella epidemiology is facing important challenges and new opportunities due to the rapid adoption of culture independent diagnostic test panels by clinical laboratories. Where is this unprecedented wave of change taking us? This chapter will examine emerging trends in Salmonella epidemiology, and take a peek into the not-so-distant future.

      3. Modifiable risk factors for typhoid intestinal perforations during a large outbreak of typhoid fever, Kampala Uganda, 2015External
        Bulage L, Masiira B, Ario AR, Matovu JK, Nsubuga P, Kaharuza F, Nankabirwa V, Routh J, Zhu BP.
        BMC Infect Dis. 2017 Sep 25;17(1):641.

        BACKGROUND: Between January and June, 2015, a large typhoid fever outbreak occurred in Kampala, Uganda, with 10,230 suspected cases. During the outbreak, area surgeons reported a surge in cases of typhoid intestinal perforation (TIP), a complication of typhoid fever. We conducted an investigation to characterize TIP cases and identify modifiable risk factors for TIP. METHODS: We defined a TIP case as a physician-diagnosed typhoid patient with non-traumatic terminal ileum perforation. We identified cases by reviewing medical records at all five major hospitals in Kampala from 2013 to 2015. In a matched case-control study, we compared potential risk factors among TIP cases and controls; controls were typhoid patients diagnosed by TUBEX TF, culture, or physician but without TIP, identified from the outbreak line-list and matched to cases by age, sex and residence. Cases and controls were interviewed using a standard questionnaire from 1st -23rd December 2015. We used conditional logistic regression to assess risk factors for TIP and control for confounding. RESULTS: Of the 88 TIP cases identified during 2013-2015, 77% (68/88) occurred between January and June, 2015; TIPs sharply increased in January and peaked in March, coincident with the typhoid outbreak. The estimated risk of TIP was 6.6 per 1000 suspected typhoid infections (68/10,230). The case-fatality rate was 10% (7/68). Cases sought care later than controls; Compared with 29% (13/45) of TIP cases and 63% (86/137) of controls who sought treatment within 3 days of onset, 42% (19/45) of cases and 32% (44/137) of controls sought treatment 4-9 days after illness onset (ORadj = 2.2, 95%CI = 0.83-5.8), while 29% (13/45) of cases and 5.1% (7/137) of controls sought treatment >/=10 days after onset (ORadj = 11, 95%CI = 1.9-61). 68% (96/141) of cases and 23% (23/100) of controls had got treatment before being treated at the treatment centre (ORadj = 9.0, 95%CI = 1.1-78). CONCLUSION: Delay in seeking treatment increased the risk of TIPs. For future outbreaks, we recommended aggressive community case-finding, and informational campaigns in affected communities and among local healthcare providers to increase awareness of the need for early and appropriate treatment.

      4. Implementing an isoniazid preventive therapy program for people living with HIV in ThailandExternal
        Danyuttapolchai J, Kittimunkong S, Nateniyom S, Painujit S, Klinbuayaem V, Maipanich N, Maokamnerd Y, Pevzner E, Whitehead S, Kanphukiew A, Monkongdee P, Martin M.
        PLoS One. 2017 ;12(9):e0184986.

        Treatment of people living with HIV (PLHIV) with latent tuberculosis (TB) infection using isoniazid preventive therapy (IPT) can reduce the risk of TB disease, however, the scale-up of IPT among PLHIV in Thailand and worldwide has been slow. To hasten the implementation of IPT in Thailand, we developed IPT implementation training curricula and tools for health care providers and implemented IPT services in seven large government hospitals. Of the 659 PLHIV enrolled, 272 (41.3%) reported symptoms of TB and 39 (14.3% of those with TB symptoms) were diagnosed with TB. A total of 346 (52.4%) participants were eligible for IPT; 318 (91.9%) of these participants opted to have a tuberculin skin test (TST) and 52 (16.3% of those who had a TST) had a positive TST result. Among the 52 participants with a positive TST, 46 (88.5%) initiated and 39 (75.0%) completed 9 months of IPT: physicians instructed three participants to stop IPT, two participants were lost to follow-up, one chose to stop therapy, and one developed TB. IPT can be implemented among PLHIV in Thailand and could reduce the burden of TB in the country.

      5. Comparison of boiling and chlorination on the quality of stored drinking water and childhood diarrhoea in Indonesian householdsExternal
        Fagerli K, Trivedi KK, Sodha SV, Blanton E, Ati A, Nguyen T, Delea KC, Ainslie R, Figueroa ME, Kim S, Quick R.
        Epidemiol Infect. 2017 Sep 25:1-9.

        We compared the impact of a commercial chlorination product (brand name Air RahMat) in stored drinking water to traditional boiling practices in Indonesia. We conducted a baseline survey of all households with children 1000 MPN/100 ml (RR 1.86, 95% CI 1.09-3.19) in stored water than in households without detectable E. coli. Although results suggested that Air RahMat water treatment was associated with lower E. coli contamination and diarrhoeal rates among children <5 years than water treatment by boiling, Air RahMat use remained low.

      6. Survey of poliovirus antibodies in Borno and Yobe States, North-Eastern NigeriaExternal
        Gofama MM, Verma H, Abdullahi H, Molodecky NA, Craig KT, Urua UA, Garba MA, Alhaji MA, Weldon WC, Oberste MS, Braka F, Muhammad AJ, Sutter RW.
        PLoS One. 2017 ;12(9):e0185284.

        BACKGROUND: Nigeria remains one of only three polio-endemic countries in the world. In 2016, after an absence of 2 years, wild poliovirus serotype 1 was again detected in North-Eastern Nigeria. To better guide programmatic action, we assessed the immunity status of infants and children in Borno and Yobe states, and evaluated the impact of recently introduced inactivated poliovirus vaccine (IPV) on antibody seroprevalence. METHODS AND FINDINGS: We conducted a facility-based study of seroprevalence to poliovirus serotypes 1, 2 and 3 among health-seeking patients in two sites each of Borno and Yobe States. Enrolment was conducted amongst children 6-9 and 36-47 months of age attending the paediatrics outpatient department of the selected hospitals in the two states between 11 January and 5 February 2016. Detailed demographic and immunization history of the child was taken and an assessment of the child’s health and nutritional state was conducted via physical examination. Blood was collected to test for levels of neutralizing antibody titres against the three poliovirus serotypes. The seroprevalence in the two age groups, potential determinants of seropositivity and the impact of one dose of IPV on humoral immunity were assessed. A total of 583 subjects were enrolled and provided sufficient quantities of serum for testing. Among 6-9-month-old infants, the seroprevalence was 81% (74-87%), 86% (79-91%), and 72% (65-79%) in Borno State, and 75% (67-81%), 74% (66-81%) and 69% (61-76%) in Yobe States, for serotypes-1, 2 and 3, respectively. Among children aged 36-47 months, the seroprevalence was >90% in both states for all three serotypes, with the exception of type 3 seroprevalence in Borno [87% (80-91%)]. Median reciprocal anti-polio neutralizing antibody titers were consistently >900 for serotypes 1 and 2 across age groups and states; with lower estimates for serotype 3, particularly in Borno. IPV received in routine immunization was found to be a significant determinant of seropositivity and anti-polio neutralizing antibodies among 6-9-month-old infants for serotypes 1 and 3, but demonstrated a non-significant positive association for serotype 2. Children receiving IPV through SIAs demonstrated significantly higher anti-polio neutralizing antibodies for serotypes 1 and 3. CONCLUSIONS: The seroprevalence to poliovirus remains suboptimal in both Borno and Yobe States in Nigeria. The low seroprevalence facilitated the continued transmission of both wild serotype 1 and serotype 2 circulating vaccine-derived poliovirus detected in Borno State in 2016. Further efforts are necessary to improve the immunity status of these populations to ensure sufficient population immunity to interrupt transmission.

      7. Influenza B virus outbreak at a religious residential school for boys in Northern Bangladesh, 2011External
        Haque F, Sturm-Ramirez K, Homaira N, Gurley ES, Hossain MJ, Hasan SM, Chowdhury S, Sarkar S, Khan AK, Rahman M, Rahman M, Luby SP.
        Influenza Other Respir Viruses. 2017 Mar;11(2):165-169.

        BACKGROUND: National media reported a febrile illness among dormitory residents of a boys’ religious school. We investigated the outbreak to identify cause. METHODS: Individuals with fever (>100 degrees F) and cough or sore throat between 1 and 13 August 2011 were influenza-like-illness (ILI) case-patients. We collected histories and specimens from hospitalized case-patients and visited campus to explore environmental context. RESULTS: All 28 case-patients were dormitory residents including 27 hospitalizations. Accommodation space per resident was <0.8 square metres. Nasal and oropharyngeal swabs from 22 case-patients were positive for influenza B virus using real-time reverse transcription polymerase chain reaction (rRT-PCR). CONCLUSIONS: Overcrowding likely facilitated transmission leading to this dormitory outbreak.

      8. Characteristics of US-born versus foreign-born Americans of African descent with chronic hepatitis BExternal
        Hassan MA, Kim WR, Li R, Smith CI, Fried MW, Sterling RK, Ghany MG, Wahed AS, Ganova-Raeva LM, Roberts LR, Lok AS.
        Am J Epidemiol. 2017 Aug 01;186(3):356-366.

        Hepatitis B virus (HBV) infection is more common in African Americans than in white Americans. We compared the epidemiologic, clinical, and virological characteristics of US-born African Americans (USAAs) to those of foreign-born African Americans (FBAAs) with chronic hepatitis B. The adult cohort study of the Hepatitis B Research Network enrolls patients with HBV infection from 21 clinical sites in the United States and Canada. A total of 237 (15%) of the adult participants with chronic HBV infection that were enrolled from January 20, 2011, to October 2, 2013, were of African descent, including 57 USAAs and 180 FBAAs (76%). Compared with FBAAs, USAAs were older and more likely to have acquired HBV through sexual exposure, to be HBeAg-positive, to have higher HBV DNA levels, and to be infected with HBV genotype A2. FBAAs from West Africa were more likely to have elevated serum alanine aminotransferase (72% vs. 50%; P < 0.01) and higher HBV DNA levels (median, 3.2 log10 IU/mL vs. 2.8 log10 IU/mL; P = 0.03) compared with East African FBAAs. The predominant HBV genotype among West African FBAAs was E (67%), whereas genotypes A (78%) and D (16%) were common in East African FBAAs. Significant differences were found between USAAs and FBAAs, highlighting the need for tailored strategies for prevention and management of chronic HBV infection for African Americans.

      9. CONSISE statement on the Reporting of Seroepidemiologic Studies for Influenza (ROSES-I statement): an extension of the STROBE statementExternal
        Horby PW, Laurie KL, Cowling BJ, Engelhardt OG, Sturm-Ramirez K, Sanchez JL, Katz JM, Uyeki TM, Wood J, Van Kerkhove MD.
        Influenza Other Respir Viruses. 2017 Jan;11(1):2-14.

        BACKGROUND: Population-based serologic studies are a vital tool for understanding the epidemiology of influenza and other respiratory viruses, including the early assessment of the transmissibility and severity of the 2009 influenza pandemic, and Middle East respiratory syndrome coronavirus. However, interpretation of the results of serologic studies has been hampered by the diversity of approaches and the lack of standardized methods and reporting. OBJECTIVE: The objective of the CONSISE ROSES-I statement was to improve the quality and transparency of reporting of influenza seroepidemiologic studies and facilitate the assessment of the validity and generalizability of published results. METHODS: The ROSES-I statement was developed as an expert consensus of the CONSISE epidemiology and laboratory working groups. The recommendations are presented in the familiar format of a reporting guideline. Because seroepidemiologic studies are a specific type of observational epidemiology study, the ROSES-I statement is built upon the STROBE guidelines. As such, the ROSES-I statement should be seen as an extension of the STROBE guidelines. RESULTS: The ROSES-I statement presents 42 items that can be used as a checklist of the information that should be included in the results of published seroepidemiologic studies, and which can also serve as a guide to the items that need to be considered during study design and implementation. CONCLUSIONS: We hope that the ROSES-I statement will contribute to improving the quality of reporting of seroepidemiologic studies.

      10. Clinical characteristics and factors associated with severe acute respiratory infection and influenza among children in Jingzhou, ChinaExternal
        Huai Y, Guan X, Liu S, Uyeki TM, Jiang H, Klena J, Huang J, Chen M, Peng Y, Yang H, Luo J, Zheng J, Peng Z, Huo X, Xiao L, Chen H, Zhang Y, Xing X, Feng L, Hu DJ, Yu H, Zhan F, Varma JK.
        Influenza Other Respir Viruses. 2017 Mar;11(2):148-156.

        BACKGROUND: Influenza is an important cause of respiratory illness in children, but data are limited on hospitalized children with laboratory-confirmed influenza in China. METHODS: We conducted active surveillance for severe acute respiratory infection (SARI; fever and at least one sign or symptom of acute respiratory illness) among hospitalized pediatric patients in Jingzhou, Hubei Province, from April 2010 to April 2012. Data were collected from enrolled SARI patients on demographics, underlying health conditions, clinical course of illness, and outcomes. Nasal swabs were collected and tested for influenza viruses by reverse transcription polymerase chain reaction. We described the clinical and epidemiological characteristics of children with influenza and analyzed the association between potential risk factors and SARI patients with influenza. RESULTS: During the study period, 15 354 children aged <15 years with signs and symptoms of SARI were enrolled at hospital admission. severe acute respiratory infection patients aged 5-15 years with confirmed influenza (H3N2) infection were more likely than children without influenza to have radiographic diagnosis of pneumonia (11/31, 36% vs 15/105, 14%. P<.05). Only 16% (1116/7145) of enrolled patients had received seasonal trivalent influenza vaccination within 12 months of hospital admission. Non-vaccinated influenza cases were more likely than vaccinated influenza cases to have pneumonia (31/133, 23% vs 37/256, 15%, P<.05). severe acute respiratory infection cases aged 5-15 years diagnosed with influenza were also more likely to have a household member who smoked cigarettes compared with SARI cases without a smoking household member (54/208, 26% vs 158/960, 16%, P<.05). CONCLUSIONS: Influenza A (H3N2) virus infection was an important contributor to pneumonia requiring hospitalization. Our results highlight the importance of surveillance in identifying factors for influenza hospitalization, monitoring adherence to influenza prevention and treatment strategies, and evaluating the disease burden among hospitalized pediatric SARI patients. Influenza vaccination promotion should target children.

      11. Respiratory syncytial virus hospitalization in middle-aged and older adultsExternal
        Malosh RE, Martin ET, Callear AP, Petrie JG, Lauring AS, Lamerato L, Fry AM, Ferdinands J, Flannery B, Monto AS.
        J Clin Virol. 2017 Sep 07;96:37-43.

        BACKGROUND: The importance of Respiratory Syncytial Virus (RSV) is increasingly recognized in hospitalized adults, but mainly in those >/= 65 years. OBJECTIVES: We sought to describe the epidemiology and clinical severity of RSV compared to influenza in hospitalized adults >/=18 years. STUDY DESIGN: Adults hospitalized with acute respiratory illnesses (ARI) of </=10days duration were prospectively enrolled from two Michigan hospitals during two influenza seasons. Collected specimens were tested for RSV and influenza by real-time, reverse transcription polymerase chain reaction (RT-PCR). Viral load and subtype were determined for RSV-positive specimens. We evaluated factors associated with RSV and outcomes of infection using multivariable logistic regression. RSV-positive patients were separately compared to two reference groups: RSV-negative and influenza-negative, and influenza-positive patients. RESULTS: RSV was detected in 84 (7%) of 1259 hospitalized individuals (55 RSV-B, 29 RSV-A). The highest prevalence was found in 50-64year olds (40/460; 8.7%); 98% of RSV cases in this age group had at least one chronic comorbidity. RSV detection was associated with obesity (OR: 1.71 95% CI: 0.99-3.06, p=0.03). Individuals with RSV were admitted to the hospital later in their illness and had a higher median Charlson comborbidity index (3 vs 2 p<0.001) compared to those with influenza. Clinical severity of RSV-associated hospitalizations was similar to influenza-associated hospitalizations. DISCUSSION: In this study we observed the highest frequency of RSV-associated hospitalizations among adult 50-64 years old; many of whom had chronic comorbidities. Our results suggest the potential benefit of including these individuals in future RSV vaccination strategies.

      12. Physician’s knowledge, attitudes, and practices regarding seasonal influenza, pandemic influenza, and highly pathogenic avian influenza A (H5N1) virus infections of humans in IndonesiaExternal
        Mangiri A, Iuliano AD, Wahyuningrum Y, Praptiningsih CY, Lafond KE, Storms AD, Samaan G, Ariawan I, Soeharno N, Kreslake JM, Storey JD, Uyeki TM.
        Influenza Other Respir Viruses. 2017 Jan;11(1):93-99.

        Indonesia has reported highest number of fatal human cases of highly pathogenic avian influenza (HPAI) A (H5N1) virus infection worldwide since 2005. There are limited data available on seasonal and pandemic influenza in Indonesia. During 2012, we conducted a survey of clinicians in two districts in western Java, Indonesia, to assess knowledge, attitudes, and practices (KAP) of clinical diagnosis, testing, and treatment of patients with seasonal influenza, pandemic influenza, or HPAI H5N1 virus infections. Overall, a very low percentage of physician participants reported ever diagnosing hospitalized patients with seasonal, pandemic, or HPAI H5N1 influenza. Use of influenza testing was low in outpatients and hospitalized patients, and use of antiviral treatment was very low for clinically diagnosed influenza patients. Further research is needed to explore health system barriers for influenza diagnostic testing and availability of antivirals for treatment of influenza in Indonesia.

      13. Incidence and etiology of hospitalized acute respiratory infections in the Egyptian DeltaExternal
        Rowlinson E, Dueger E, Mansour A, Azzazy N, Mansour H, Peters L, Rosenstock S, Hamid S, Said MM, Geneidy M, Abd Allah M, Kandeel A.
        Influenza Other Respir Viruses. 2017 Jan;11(1):23-32.

        INTRODUCTION: Acute Respiratory Infections (ARI) are responsible for nearly two million childhood deaths worldwide. A limited number of studies have been published on the epidemiology of viral respiratory pathogens in Egypt. METHODS: A total of 6113 hospitalized patients >1 month of age with suspected ARI were enrolled between June 23, 2009 and December 31, 2013. Naso- and oropharyngeal specimens were collected and tested for influenza A and B, respiratory syncytial virus, human metapneumovirus, adenovirus, and parainfluenza viruses 1-3. Blood specimens from children 1-11 months were cultured and bacterial growth was identified by polymerase chain reaction. Results from a healthcare utilization survey on the proportion of persons seeking care for ARI was used to calculate adjusted ARI incidence rates in the surveillance population. RESULTS: The proportion of patients with a viral pathogen detected decreased with age from 67% in patients age 1-11 months to 19% in patients >/=65 years of age. Influenza was the dominant viral pathogen detected in patients >/=1 year of age (13.9%). The highest incidence rates for hospitalized ARI were observed in children 1-11 months (1757.9-5537.5/100 000 population) and RSV was the most commonly detected pathogen in this age group. CONCLUSION: In this study population, influenza is the largest viral contributor to hospitalized ARIs and children 1-11 months of age experience a high rate of ARI hospitalizations. This study highlights a need for surveillance of additional viral pathogens and alternative detection methods for bacterial pathogens, which may reveal a substantial proportion of as yet unidentified etiologies in adults.

      14. OBJECTIVES: To assess the magnitude of active TB disease and latent TB infection (LTBI) in young adults of college age. PARTICIPANTS: Individuals who were aged 18-24 years in 2011 were used as a proxy for college students. METHODS: Active TB cases reported to the 2011 US National TB Surveillance System (NTSS) were included. LTBI prevalence was calculated from the 2011-2012 National Health and Nutrition Examination Survey. The 2011 American Community Survey was used to calculate population denominators. Analyses were stratified by nativity. RESULTS: Active TB disease incidence among persons aged 18-24 years was 2.82/100,000, 18.8/100,000 among foreign-born individuals and 0.9/100,000 among US-born individuals. In 2011, 878 TB cases were reported; 629 (71.6%) were foreign-born. LTBI prevalence among persons of 18-24 years was 2.5%: 8.7% and 1.3% among foreign-born and US-born, respectively. CONCLUSION: Active screening and treatment programs for foreign-born young adults could identify TB cases earlier and provide an opportunity for prevention efforts.

      15. Careers in infectious diseases: Public healthExternal
        Srinivasan A.
        J Infect Dis. 2017 Sep 15;216(suppl_5):S618-s619.

        Public health offers infectious disease physicians a variety of rewarding career options. Our training and skills make us well suited to a variety of roles in public health. This article summarizes some of the options for careers in public health and describes why ID physicians are so well suited to them.

      16. HIV testing among men in Curitiba, BrazilExternal
        Szwarcwald CL, Damacena GN, Miranda RL, Pascom AR, Junior AB.
        AIDS Care. 2017 Sep 21:1-3.

        In 2015, a community-wide intervention was launched in the city of Curitiba to evaluate the uptake of multiple HIV testing. A three-stage cluster sampling of 4800 men aged 15-64 years was selected in Curitiba. Logistic regression models were used to establish driving factors of HIV testing over the past 12 months. In the total sample, 49.5% have tested for HIV once in lifetime and 18.7% in the last 12 months. Among MSM, the proportions were much higher: 75.9% and 47.8% respectively. In the multivariate analysis, a significantly higher likelihood of HIV testing was found for young men (15-24 years), men with better educational level, those with more than 6 casual partners, and MSM compared to heterosexual men. The results indicate that the intervention to increase HIV diagnosis has substantially expanded MSM access to HIV testing.

      17. Antiretroviral prescription and viral suppression in a representative sample of HIV-infected persons in care in 4 large metropolitan areas of the United States, Medical Monitoring Project, 2011-2013External
        Wohl AR, Benbow N, Tejero J, Johnson C, Scheer S, Brady K, Gagner A, Hughes A, Eberhart M, Mattson C, Skarbinski J.
        J Acquir Immune Defic Syndr. 2017 Oct 01;76(2):158-170.

        BACKGROUND: Comparisons of antiretroviral therapy (ART) prescription and viral suppression among people in HIV care across US metropolitan areas are limited. Medical Monitoring Project, 2011-2013, data were used to describe and compare associations between sociodemographics and ART prescription and viral suppression for persons receiving HIV care. SETTING: Chicago, Los Angeles County (LAC), Philadelphia, and San Francisco in the United States. METHODS: Bivariate and multivariable methods were used. RESULTS: The proportion of patients prescribed ART (91%-93%) and virally suppressed (79%-88%) was consistent although more persons were virally suppressed in San Francisco compared with the other areas, and a smaller proportion was virally suppressed in Philadelphia compared with Chicago. In the combined cohort, persons aged 30-49 years were less likely than persons 50+ (adjusted prevalence ratio (aPR) -0.97, confidence interval (CI): 0.94 to 0.99); persons reporting non-injection drug use were less likely than non-users (aPR = 0.94, CI: 0.90 to 0.98); and Hispanics were more likely than whites (aPR – 1.04, CI: 1.01 to 1.08) to be prescribed ART. Blacks (aPR = 0.93; CI: 0.87 to 0.99) and homeless persons (aPR = 0.87; CI: 0.80 to 0.95) were less likely to be virally suppressed in the combined cohort. In LAC, persons aged 30-49 years were less likely than those 50+ to be prescribed ART (aPR = 0.94, CI: 0.90 to 0.98). Younger persons (18-29) (aPR = 0.77; CI: 0.60 to 0.99) and persons with less than a high school education (aPR = 0.80; CI: 0.67 to 0.95) in Philadelphia, blacks (aPR = 0.90; CI: 0.83 to 0.99) and men who have sex with women only (aPR = 0.89; CI: 0.80 to 0.99) in Chicago, and homeless individuals in LAC (aPR = 0.80; CI: 0.67 to 0.94) were less likely to be virally suppressed. CONCLUSION: Data highlight the need to increase ART prescription to achieve viral suppression among younger persons, noninjection drug users, blacks, and homeless persons in US metropolitan areas and underscores the importance of region-specific strategies for affected subgroups.

    • Disease Reservoirs and Vectors
      1. Stable transmission of Borrelia burgdorferi sensu stricto on the Outer Banks of North CarolinaExternal
        Levine JF, Apperson CS, Levin M, Kelly TR, Kakumanu ML, Ponnusamy L, Sutton H, Salger SA, Caldwell JM, Szempruch AJ.
        Zoonoses Public Health. 2017 Aug;64(5):337-354.

        The spirochaete (Borrelia burgdorferi) associated with Lyme disease was detected in questing ticks and rodents during a period of 18 years, 1991-2009, at five locations on the Outer Banks of North Carolina. The black-legged tick (Ixodes scapularis) was collected at varied intervals between 1991 and 2009 and examined for B. burgdorferi. The white-footed mouse (Peromyscus leucopus), house mouse (Mus musculus) marsh rice rat (Oryzomys palustris), marsh rabbit (Sylvilagus palustris), eastern cottontail (Sylvilagus floridanus) and six-lined racerunner (Cnemidophorus sexlineatus) were live-trapped, and their tissues cultured to isolate spirochaetes. Borrelia burgdorferi isolates were obtained from questing adult I. scapularis and engorged I. scapularis removed from P. leucopus, O. palustris and S. floridanus. The prevalence of B. burgdorferi infection was variable at different times and sites ranging from 7 to 14% of examined questing I. scapularis. Mitochondrial (16S) rRNA gene phylogenetic analysis from 65 adult I. scapularis identified 12 haplotypes in two major clades. Nine haplotypes were associated with northern/Midwestern I. scapularis populations and three with southern I. scapularis populations. Sixteen isolates obtained from tick hosts in 2005 were confirmed to be B. burgdorferi by amplifying and sequencing of 16S rRNA and 5S-23S intergenic spacer fragments. The sequences had 98-99% identity to B. burgdorferi sensu stricto strains B31, JD1 and M11p. Taken together, these studies indicate that B. burgdorferi sensu stricto is endemic in questing I. scapularis and mammalian tick hosts on the Outer Banks of North Carolina.

      2. Oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (RABORAL V-RG(R)): a global reviewExternal
        Maki J, Guiot AL, Aubert M, Brochier B, Cliquet F, Hanlon CA, King R, Oertli EH, Rupprecht CE, Schumacher C, Slate D, Yakobson B, Wohlers A, Lankau EW.
        Vet Res. 2017 Sep 22;48(1):57.

        RABORAL V-RG(R) is an oral rabies vaccine bait that contains an attenuated (“modified-live”) recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (V-RG). Approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (ORV) was released into the environment to immunize wildlife populations against rabies. V-RG is genetically stable, is not detected in the oral cavity beyond 48 h after ingestion, is not shed by vaccinates into the environment, and has been tested for thermostability under a range of laboratory and field conditions. Safety of V-RG has been evaluated in over 50 vertebrate species, including non-human primates, with no adverse effects observed regardless of route or dose. Immunogenicity and efficacy have been demonstrated under laboratory and field conditions in multiple target species (including fox, raccoon, coyote, skunk, raccoon dog, and jackal). The liquid vaccine is packaged inside edible baits (i.e., RABORAL V-RG, the vaccine-bait product) which are distributed into wildlife habitats for consumption by target species. Field application of RABORAL V-RG has contributed to the elimination of wildlife rabies from three European countries (Belgium, France and Luxembourg) and of the dog/coyote rabies virus variant from the United States of America (USA). An oral rabies vaccination program in west-central Texas has essentially eliminated the gray fox rabies virus variant from Texas with the last case reported in a cow during 2009. A long-term ORV barrier program in the USA using RABORAL V-RG is preventing substantial geographic expansion of the raccoon rabies virus variant. RABORAL V-RG has also been used to control wildlife rabies in Israel for more than a decade. This paper: (1) reviews the development and historical use of RABORAL V-RG; (2) highlights wildlife rabies control programs using the vaccine in multiple species and countries; and (3) discusses current and future challenges faced by programs seeking to control or eliminate wildlife rabies.

    • Genetics and Genomics
      1. Decoding noises in HIV computational genotypingExternal
        Jia M, Shaw T, Zhang X, Liu D, Shen Y, Ezeamama AE, Yang C, Zhang M.
        Virology. 2017 Sep 14;511:249-255.

        Lack of a consistent and reliable genotyping system can critically impede HIV genomic research on pathogenesis, fitness, virulence, drug resistance, and genomic-based healthcare and treatment. At present, mis-genotyping, i.e., background noises in molecular genotyping, and its impact on epidemic surveillance is unknown. For the first time, we present a comprehensive assessment of HIV genotyping quality. HIV sequence data were retrieved from worldwide published records, and subjected to a systematic genotyping assessment pipeline. Results showed that mis-genotyped cases occurred at 4.6% globally, with some regional and high-risk population heterogeneities. Results also revealed a consistent mis-genotyping pattern in gp120 in all studied populations except the group of men who have sex with men. Our study also suggests novel virus diversities in the mis-genotyped cases. Finally, this study reemphasizes the importance of implementing a standardized genotyping pipeline to avoid genotyping disparity and to advance our understanding of virus evolution in various epidemiological settings.

    • Health Economics
      1. Medical expenditures and earnings losses among US adults with arthritis in 2013External
        Murphy LB, Cisternas MG, Pasta DJ, Helmick CG, Yelin EH.
        Arthritis Care Res (Hoboken). 2017 Sep 26.

        OBJECTIVE: We estimated the economic impact of arthritis using 2013 US Medical Expenditure Panel Survey (MEPS) data. METHODS: We calculated arthritis-attributable and all-cause medical expenditures for adults age >/= 18 years and arthritis-attributable earnings losses among those 18-64 years who had ever worked. We calculated arthritis-attributable costs using multi-stage regression-based methods, and conducted sensitivity analyses to estimate costs for two other arthritis definitions in MEPS. RESULTS: In 2013, estimated total national arthritis-attributable medical expenditures were $139.8 billion (range= $135.9 – $157.5). Across expenditure categories, ambulatory care expenditures accounted for nearly half of arthritis-attributable expenditures. All-cause expenditures among adults with arthritis represented 51% of the $1.2 trillion national medical expenditures among all US adults in MEPS. Estimated total national arthritis-attributable earning losses were $163.7 billion (range= $163.7 – $170.0). The percentage with arthritis who worked in the past year was 7.2 percentage points lower than those without arthritis (76.8%; 95% CI= 75.0-78.6 and 84.0%; 95% CI= 82.5-85.5, respectively; adjusted for socio-demographics and chronic conditions). Total arthritis-attributable medical expenditures and earnings losses were $303.5 billion (range=$303.5 – $326.9). CONCLUSION: Total national arthritis-attributable medical care expenditures and earnings losses among adults with arthritis were $303.5 billion in 2013. High arthritis-attributable medical expenditures might be reduced by greater efforts to reduce pain and improve function. The high earnings losses were largely attributable to the substantially lower prevalence of working among those with arthritis compared with those without, signaling the need for interventions that keep people with arthritis in the work force. This article is protected by copyright. All rights reserved.

    • Healthcare Associated Infections
      1. Donor derived Kaposi’s sarcoma in a liver-kidney transplant recipientExternal
        Dollard SC, Douglas D, Basavaraju SV, Schmid DS, Kuehnert M, Aqel B.
        Am J Transplant. 2017 Sep 23.

        Human herpes virus 8 (HHV-8), also known as Kaposi’s sarcoma associated herpesvirus (KSHV), is an oncogenic virus that can cause Kaposi’s sarcoma (KS). KS can develop following organ transplantation through reactivation of the recipient’s latent HHV-8 infection, or less commonly through donor-derived infection which has higher risk for severe illness and mortality. We describe a case of probable donor-derived KS in the recipient of a liver-kidney transplant. The donor had multiple risk factors for HHV-8 infection. The KS was successfully treated by switching immunosuppression from tacrolimus to sirolimus. With an increasing number of human immunodeficiency virus (HIV)-positive persons seeking organ transplantation and serving as organ donors for HIV-positive recipients, HHV-8 prevalence among donors and recipients will likely increase and with that the risk for post-transplant KS. Pre-determination of HHV-8 status can be useful when considering organ donors and recipients with risk factors, although there are currently no validated commercial tests for HHV-8 antibody screening. This article is protected by copyright. All rights reserved.

    • Immunity and Immunization
      1. Influenza vaccination coverage among health care personnel – United States, 2016-17 influenza seasonExternal
        Black CL, Yue X, Ball SW, Fink R, de Perio MA, Laney AS, Williams WW, Lindley MC, Graitcer SB, Lu PJ, Devlin R, Greby SM.
        MMWR Morb Mortal Wkly Rep. 2017 Sep 29;66(38):1009-1015.

        The Advisory Committee on Immunization Practices (ACIP) recommends that all health care personnel (HCP) receive an annual influenza vaccination to reduce influenza-related morbidity and mortality among HCP and their patients and to reduce absenteeism among HCP (1-4). To estimate influenza vaccination coverage among HCP in the United States during the 2016-17 influenza season, CDC conducted an opt-in Internet panel survey of 2,438 HCP. Overall, 78.6% of survey respondents reported receiving vaccination during the 2016-17 season, similar to reported coverage in the previous three influenza seasons (5). Vaccination coverage continued to be higher among HCP working in hospitals (92.3%) and lower among HCP working in ambulatory (76.1%) and long-term care (LTC) (68.0%) settings. As in previous seasons, coverage was highest among HCP who were required by their employer to be vaccinated (96.7%) and lowest among HCP working in settings where vaccination was not required, promoted, or offered on-site (45.8%). Implementing workplace strategies found to improve vaccination coverage among HCP, including vaccination requirements or active promotion of on-site vaccinations at no cost, can help ensure that HCP and patients are protected against influenza (6).

      2. Influenza vaccination coverage among pregnant women – United States, 2016-17 influenza seasonExternal
        Ding H, Black CL, Ball S, Fink RV, Williams WW, Fiebelkorn AP, Lu PJ, Kahn KE, D’Angelo DV, Devlin R, Greby SM.
        MMWR Morb Mortal Wkly Rep. 2017 Sep 29;66(38):1016-1022.

        Pregnant women and their infants are at increased risk for severe influenza-associated illness (1), and since 2004, the Advisory Committee on Immunization Practices (ACIP) has recommended influenza vaccination for all women who are or might be pregnant during the influenza season, regardless of the trimester of the pregnancy (2). To assess influenza vaccination coverage among pregnant women during the 2016-17 influenza season, CDC analyzed data from an Internet panel survey conducted during March 28-April 7, 2017. Among 1,893 survey respondents pregnant at any time during October 2016-January 2017, 53.6% reported having received influenza vaccination before (16.2%) or during (37.4%) pregnancy, similar to coverage during the preceding four influenza seasons. Also similar to the preceding influenza season, 67.3% of women reported receiving a provider offer for influenza vaccination, 11.9% reported receiving a recommendation but no offer, and 20.7% reported receiving no recommendation; among these women, reported influenza vaccination coverage was 70.5%, 43.7%, and 14.8%, respectively. Among women who received a provider offer for vaccination, vaccination coverage differed by race/ethnicity, education, insurance type, and other sociodemographic factors. Use of evidence-based practices such as provider reminders and standing orders could reduce missed opportunities for vaccination and increase vaccination coverage among pregnant women.

      3. OBJECTIVE: Describe the Vaccine Safety Datalink’s (VSD) Guillain Barre Syndrome (GBS) surveillance following quadrivalent HPV vaccine (4vHPV) from 2006 through 2015. METHODS: Among 4vHPV vaccinated persons aged 9-26, ICD-9 coded GBS was identified in VSD’s electronic data. Medical records were reviewed and adjudicated to confirm GBS. We calculated incidence rates of confirmed GBS within 1-42days following 4vHPV with a one-sided 95% confidence interval. RESULTS: Following 2,773,185 4vHPV doses, we confirmed 1 case of GBS in a male and no cases among females. The incidence rate of medical record confirmed GBS within 42days following 4vHPV vaccine was 0.36 cases per million 4vHPV doses administered (1-sided 95% CI 1.71), which was less than the background rate. CONCLUSION: We found no evidence of an increased risk of GBS following 4vHPV. With an upper 95% confidence limit, we estimate that, if an increased risk exists, we would expect at most 1.08 additional cases of GBS per million people vaccinated with 4vHPV.

      4. Cost-effectiveness of a potential group B streptococcal vaccine for pregnant women in the United StatesExternal
        Kim SY, Nguyen C, Russell LB, Tomczyk S, Abdul-Hakeem F, Schrag SJ, Verani JR, Sinha A.
        Vaccine. 2017 Sep 23.

        BACKGROUND: In the U.S., intrapartum antibiotic prophylaxis (IAP) for pregnant women colonized with group B streptococcus (GBS) has reduced GBS disease in the first week of life (early-onset/EOGBS). Nonetheless, GBS remains a leading cause of neonatal sepsis, including 1000 late-onset (LOGBS) cases annually. A maternal vaccine under development could prevent EOGBS and LOGBS. METHODS: Using a decision-analytic model, we compared the public health impact, costs, and cost-effectiveness of five strategies to prevent GBS disease in infants: (1) no prevention; (2) currently recommended screening/IAP; (3) maternal GBS immunization; (4) maternal immunization with IAP when indicated for unimmunized women; (5) maternal immunization plus screening/IAP for all women. We modeled a pentavalent vaccine covering serotypes 1a, 1b, II, III, and V, which cause almost all GBS disease. RESULTS: In the base case, screening/IAP alone prevents 46% of EOGBS compared to no prevention, at a cost of $70,275 per quality-adjusted life-year (QALY) from a healthcare and $51,249/QALY from a societal perspective (2013 US$). At coverage rates typical of maternal vaccines in the U.S., a pentavalent vaccine alone would not prevent as much disease as screening/IAP until its efficacy approached 90%, but would cost less per QALY. At vaccine efficacy of >/=70%, maternal immunization together with IAP for unimmunized women would prevent more disease than screening/IAP, at a similar cost/QALY. CONCLUSIONS: GBS maternal immunization, with IAP as indicated for unvaccinated women, could be an attractive alternative to screening/IAP if a pentavalent vaccine is sufficiently effective. Coverage, typically low for maternal vaccines, is key to the vaccine’s public health impact.

      5. Estimating vaccine effectiveness in preventing laboratory-confirmed influenza in outpatient settings in South Africa, 2015External
        McAnerney JM, Walaza S, Tempia S, Blumberg L, Treurnicht FK, Madhi SA, Valley-Omar Z, Cohen C.
        Influenza Other Respir Viruses. 2017 Mar;11(2):177-181.

        Trivalent seasonal influenza vaccine effectiveness during the 2015 season in South Africa was assessed using a test-negative case control study design. Influenza A(H1N1)pdm09 was the dominant circulating strain. Overall influenza vaccine coverage was 3.2% (29/899). The vaccine effectiveness estimate, against any influenza virus infection, adjusted for age, underlying conditions and timing within season was 46.2% (95% CI: -23.5 to 76.5), and 53.6% (95% CI: -62.6 to 80.3) against influenza A(H1N1)pdm09.

      6. OBJECTIVES: Summary evidence of influenza vaccine effectiveness (IVE) against hospitalized influenza is lacking. We conducted a meta-analysis of studies reporting IVE against laboratory-confirmed hospitalized influenza among adults. METHODS: We searched Pubmed (January 2009 to November 2016) for studies that used test-negative design (TND) to enrol patients hospitalized with influenza-associated conditions. Two independent authors selected relevant articles. We calculated pooled IVE against any and (sub)type specific influenza among all adults, and stratified by age group (18-64 and 65 years and above) using random-effects models. RESULTS: We identified 3411 publications and 30 met our inclusion criteria. Between 2010-11 and 2014-15, the pooled seasonal IVE was 41% (95%CI:34;48) for any influenza (51% (95%CI:44;58) among people aged 18-64y and 37% (95%CI:30;44) among >/=65 years). IVE was 48% (95%CI:37;59),37% (95%CI:24;50) and 38% (95%CI:23;53) against influenza A(H1N1)pdm09, A(H3N2) and B, respectively. Among persons aged >/=65 year, IVE against A(H3N2) was 43% (95%CI:33;53) in seasons when circulating and vaccine strains were antigenically similar and 14% (95%CI:-3;30) when A(H3N2) variant viruses predominated. CONCLUSIONS: Influenza vaccines provided moderate protection against influenza-associated hospitalizations among adults. They seemed to provide low protection among elderly in seasons where vaccine and circulating A(H3N2) strains were antigenically variant.

      7. Epidemiology of childhood intussusception in Bangladesh: Findings from an active national hospital based surveillance system, 2012-2016External
        Satter SM, Aliabadi N, Yen C, Gastanaduy PA, Ahmed M, Mamun A, Islam K, Flora MS, Rahman M, Zaman K, Rahman M, Heffelfinger JD, Luby SP, Gurley ES, Parashar UD.
        Vaccine. 2017 Sep 20.

        INTRODUCTION: Rotavirus vaccines have significantly decreased the burden of diarrheal diseases in countries that have introduced them into their immunization programs. In some studies, there has been a small association between rotavirus vaccines and intussusception in post-marketing surveillance, highlighting the importance of tracking incidence before and after vaccine introduction. The objective of this study was to describe the epidemiology of intussusception among Bangladeshi children pre-vaccine introduction. METHODS: We conducted active, hospital-based surveillance for intussusception at 7 tertiary care hospitals with pediatric surgical facilities during July 2012 to September 2016. Hospitalized children under 2years of age were identified according to Brighton Collaboration level 1 criteria for intussusception. The frequency and proportion of intussusception among overall surgical admissions, as well as the demographic and clinical information of the cases is described. RESULTS: Overall 153 cases of intussusception among children <2years-old were identified at participating sites over the enrolment period, confirmed by Level 1 Brighton criteria. These cases represented 2% of all surgical admissions under 2years of age. One hundred twelve cases (73%) were male; the median age was 7months; and the median duration of hospitalization was 7days. One hundred forty-six (95%) children with intussusception required surgery, and 11 (7%) died. CONCLUSIONS: Confirmed cases of intussusception represented nearly 2% of pediatric surgical admissions at tertiary referral centers in Bangladesh during the study period and 7% of children with intussusception died. Given the high burden of rotavirus disease in Bangladesh, vaccine introduction is warranted, however, further studies after introduction of rotavirus vaccine are necessary to determine any association between vaccine and intussusception in this setting.

      8. Serological susceptibility to varicella among U.S. Immigration and Customs Enforcement detaineesExternal
        Varan AK, Lederman ER, Stous SS, Elson D, Freiman JL, Marin M, Lopez AS, Stauffer WM, Joseph RH, Waterman SH.
        J Correct Health Care. 2017 Jan 01:1078345817727287.

        U.S. Immigration and Customs Enforcement (ICE) is responsible for detaining unauthorized aliens during immigration proceedings. During 2014 to 2015, adult ICE detainees at a California facility were invited to complete a survey concerning self-reported varicella history and risk factors. Participants underwent serological testing for varicella-zoster virus (VZV) IgG; susceptible individuals were offered varicella vaccination. Among 400 detainees with available serology results, 48 (12%) were susceptible to varicella. Self-reported varicella history was negatively associated with susceptibility (adjusted odds ratio = 0.16; 95% confidence interval [0.07, 0.35]). Among 196 detainees reporting a positive history, 95% had VZV IgG levels suggestive of varicella immunity. Among 44 susceptible detainees offered vaccination, 86% accepted. Given relatively high varicella susceptibility, targeted screening and vaccination among ICE detainees lacking a positive history might reduce varicella transmission risks.

    • Injury and Violence
      1. Introduction: Ignition interlocks are effective in reducing alcohol-impaired driving recidivism for all offenders, including first-time offenders. Despite their effectiveness, interlock use among persons convicted of driving while intoxicated from alcohol (DWI) remains low. This cross-sectional survey of U.S. adults assessed public support for requiring ignition interlocks for all convicted DWI offenders including first-time offenders. The goal was to update results from a similar 2010 survey in light of new state requirements and increased interlock installations. Methods: Questions were included in the Porter Novelli FallStyles survey, which was fielded from September 28 to October 16, 2015. Participants were the 3,536 individuals who provided an opinion toward requiring ignition interlocks for all offenders. For analyses, opinion toward requiring interlocks for all offenders was dichotomized into ‘agree’ and ‘neutral/disagree.’ To handle missing data, 10 imputed datasets were created and pooled using fully conditional specification (FCS). Results: Fifty-nine percent of adults supported requiring interlocks for all DWI offenders. Multivariate analysis revealed that persons who did not report alcohol-impaired driving (AID) were 60% more likely to support requiring interlocks than those who reported AID. Having heard of interlocks also increased support. Support was generally consistent across demographic subgroups. Conclusions: Interlocks for all offenders have majority support nationwide in the current survey, consistent with previous reports. Support is lowest among those who have reported alcohol-impaired driving in the past 30. days. These results suggest that communities with higher levels of alcohol-impaired driving may be more resistant to requiring ignition interlocks for all convicted DWI offenders. Future studies should examine this association further. Practical applications: These results indicate that the majority of adults recognize DWI as a problem and support requiring interlocks for all offenders.

      2. Technology to augment early home visitation for child maltreatment prevention: A pragmatic randomized trialExternal
        Ondersma SJ, Martin J, Fortson B, Whitaker DJ, Self-Brown S, Beatty J, Loree A, Bard D, Chaffin M.
        Child Maltreat. 2017 Jan 01:1077559517729890.

        Early home visitation (EHV) for child maltreatment prevention is widely adopted but has received inconsistent empirical support. Supplementation with interactive software may facilitate attention to major risk factors and use of evidence-based approaches. We developed eight 20-min computer-delivered modules for use by mothers during the course of EHV. These modules were tested in a randomized trial in which 413 mothers were assigned to software-supplemented e-Parenting Program ( ePP), services as usual (SAU), or community referral conditions, with evaluation at 6 and 12 months. Outcomes included satisfaction, working alliance, EHV retention, child maltreatment, and child maltreatment risk factors. The software was well-received overall. At the 6-month follow-up, working alliance ratings were higher in the ePP condition relative to the SAU condition (Cohen’s d = .36, p < .01), with no differences at 12 months. There were no between-group differences in maltreatment or major risk factors at either time point. Despite good acceptability and feasibility, these findings provide limited support for use of this software within EHV. These findings contribute to the mixed results seen across different models of EHV for child maltreatment prevention.

      3. Characteristics of single vehicle crashes with a teen driver in South Carolina, 2005-2008External
        Shults RA, Bergen G, Smith TJ, Cook L, Kindelberger J, West B.
        Accid Anal Prev. 2017 Sep 22.

        OBJECTIVE: Teens’ crash risk is highest in the first years of independent driving. Circumstances surrounding fatal crashes have been widely documented, but less is known about factors related to nonfatal teen driver crashes. This study describes single vehicle nonfatal crashes involving the youngest teen drivers (15-17 years), compares these crashes to single vehicle nonfatal crashes among adult drivers (35-44 years) and examines factors related to nonfatal injury producing crashes for teen drivers. METHODS: Police crash data linked to hospital inpatient and emergency department data for 2005-2008 from the South Carolina Crash Outcomes Data Evaluation System (CODES) were analyzed. Nonfatal, single vehicle crashes involving passenger vehicles occurring on public roadways for teen (15-17 years) drivers were compared with those for adult (35-44 years) drivers on temporal patterns and crash risk factors per licensed driver and per vehicle miles traveled. Vehicle miles traveled by age group was estimated using data from the 2009 National Household Travel Survey. Multivariable log-linear regression analysis was conducted for teen driver crashes to determine which characteristics were related to crashes resulting in a minor/moderate injury or serious injury to at least one vehicle occupant. RESULTS: Compared with adult drivers, teen drivers in South Carolina had 2.5 times the single vehicle nonfatal crash rate per licensed driver and 11 times the rate per vehicle mile traveled. Teen drivers were nearly twice as likely to be speeding at the time of the crash compared with adult drivers. Teen driver crashes per licensed driver were highest during the afternoon hours of 3:00-5:59 pm and crashes per mile driven were highest during the nighttime hours of 9:00-11:59 pm. In 66% of the teen driver crashes, the driver was the only occupant. Crashes were twice as likely to result in serious injury when teen passengers were present than when the teen driver was alone. When teen drivers crashed while transporting teen passengers, the passengers were >5 times more likely to all be restrained if the teen driver was restrained. Crashes in which the teen driver was unrestrained were 80% more likely to result in minor/moderate injury and 6 times more likely to result in serious injury compared with crashes in which the teen driver was restrained. CONCLUSIONS: Despite the reductions in teen driver crashes associated with Graduated Driver Licensing (GDL), South Carolina’s teen driver crash rates remain substantially higher than those for adult drivers. Established risk factors for fatal teen driver crashes, including restraint nonuse, transporting teen passengers, and speeding also increase the risk of nonfatal injury in single vehicle crashes. As South Carolina examines strategies to further reduce teen driver crashes and associated injuries, the state could consider updating its GDL passenger restriction to either none or one passenger <21years and dropping the passenger restriction exemption for trips to and from school. Surveillance systems such as CODES that link crash data with health outcome data provide needed information to more fully understand the circumstances and consequences of teen driver nonfatal crashes and evaluate the effectiveness of strategies to improve teen driver safety.

      4. INTRODUCTION: The Monitoring the Future (MTF) survey provides nationally-representative annual estimates of licensure and driving patterns among U.S. teens. A previous study using MTF data reported substantial declines in the proportion of high school seniors that were licensed to drive and increases in the proportion of nondrivers following the recent U.S. economic recession. METHOD: To explore whether licensure and driving patterns among U.S. high school seniors have rebounded in the post-recession years, we analyzed MTF licensure and driving data for the decade of 2006-2015. We also examined trends in teen driver involvement in fatal and nonfatal injury crashes for that decade using data from the Fatality Analysis Reporting System and National Automotive Sampling System General Estimates System, respectively. RESULTS: During 2006-2015, the proportion of high school seniors that reported having a driver’s license declined by 9 percentage points (11%) from 81% to 72% and the proportion that did not drive during an average week increased by 8 percentage points (44%) from 18% to 26%. The annual proportion of black seniors that did not drive was consistently greater than twice the proportion of nondriving white seniors. Overall during the decade, 17- and 18-year-old drivers experienced large declines in fatal and nonfatal injury crashes, although crashes increased in both 2014 and 2015. CONCLUSIONS: The MTF data indicate that licensure and driving patterns among U.S. high school seniors have not rebounded since the economic recession. The recession had marked negative effects on teen employment opportunities, which likely influenced teen driving patterns. Possible explanations for the apparent discrepancies between the MTF data and the 2014 and 2015 increases in crashes are explored. PRACTICAL APPLICATIONS: MTF will continue to be an important resource for clarifying teen driving trends in relation to crash trends and informing strategies to improve teen driver safety.

    • Laboratory Sciences
      1. Peripheral clinic versus centralized laboratory-based Xpert MTB/RIF performance: Experience gained from a pragmatic, stepped-wedge trial in BotswanaExternal
        Agizew T, Boyd R, Ndwapi N, Auld A, Basotli J, Nyirenda S, Tedla Z, Mathoma A, Mathebula U, Lesedi C, Pals S, Date A, Alexander H, Kuebrich T, Finlay A.
        PLoS One. 2017 ;12(8):e0183237.

        BACKGROUND: In 2011, the Botswana National Tuberculosis Program adopted World Health Organization guidelines and introduced Xpert MTB/RIF (Xpert) assay to support intensified case finding among people living with HIV enrolling in care. An evaluation was designed to assess performance under operational conditions to inform the national Xpert scale-up. METHODS: Xpert was implemented from August 2012 through November 2014 with 13 GeneXpert instruments (GeneXpert) deployed in a phased approach over nine months: nine centralized laboratory and four point-of-care (POC) peripheral clinics. Clinicians and laboratorians were trained on the four-symptom tuberculosis screening algorithm and Xpert testing. We documented our experience with staff training and GeneXpert performance. Test results were extracted from GeneXpert software; unsuccessful tests were analysed in relation to testing sites and trends over time. RESULTS: During 276 instrument-months of operation a total of 3,630 tests were performed, of which 3,102 (85%) were successful with interpretable results. Mycobacterium tuberculosis complex was detected for 447 (14%); of these, 36 (8%) were rifampicin resistant. Of all 3,630 Xpert tests, 528 (15%) were unsuccessful; of these 361 (68%) were classified as “error”, 119 (23%) as “invalid” and 48 (9%) as “no result”. The total number of recorded error codes was 385 and the most common reasons were related to sample processing (211; 55%) followed by power supply (77; 20%) and cartridge/module related (54; 14%). Cumulative incidence of unsuccessful test was similar between POC (17%, 95% CI: 11-25%) and centralized laboratory-based GeneXpert instruments (14%, 95% CI: 11-17%; p = 0.140). CONCLUSIONS: Xpert introduction was successful in the Botswana setting. The incidence of unsuccessful test was similar by GeneXpert location (POC vs. centralized laboratory). However, unsuccessful test incidence (15%) in our settings was higher than previously reported and was mostly related to improper sample processing. Ensuring adequate training among Xpert testing staff is essential to minimize errors.

      2. Length, but not reactive edges, of cup-stack MWCNT is responsible for toxicity and acute lung inflammationExternal
        Hamilton RF, Tsuruoka S, Wu N, Wolfarth M, Porter DW, Bunderson-Schelvan M, Holian A.
        Toxicol Pathol. 2017 Jan 01:192623317732303.

        Multiwalled carbon nanotube (MWCNT) toxicity after inhalation has been associated with size, aspect ratio, rigidity, surface modification, and reactive oxygen species production. In this study, we investigated a series of cup-stacked MWCNT prepared as variants of the Creos 24PS. Mechanical chopping produced a short version (AR10) and graphitization to remove active reaction sites by extreme heat (2,800 degrees C; Creos 24HT) to test the contribution of length and alteration of potential reaction sites to toxicity. The 3 MWCNT variants were tested in vitro in a human macrophage-like cell model and with C57BL/6 alveolar macrophages for dose-dependent toxicity and NLRP3 inflammasome activation. The 24PS and 24HT variants showed significant dose-dependent toxicity and inflammasome activation. In contrast, the AR10 variant showed no toxicity or bioactivity at any concentration tested. The in vivo results reflected those observed in vitro, with the 24PS and 24HT variants resulting in acute inflammation, including elevated polymorphonuclear counts, Interleukin (IL)-18, cathepsin B, and lactate dehydrogenase in isolated lung lavage fluid from mice exposed to 40 microg MWCNT. Taken together, these data indicate that length, but not the absence of proposed reaction sites, on the MWCNT influences particle bioactivity.

      3. Many emerging viruses such as Ebola and Lassa occur in resource-limited areas of the world. The advent of multiplex immunoassays has facilitated the study of biomarkers of disease since only small amounts of clinical material are required; however, such assays are designed and validated for only plasma or serum. This is a significant impediment when studying infectious diseases in the context of an outbreak in a developing nation. Plasma or serum can be difficult to obtain in the field due to the need for additional processing of infectious materials. Evaluation of multiplex immunoassays using frozen and thawed human whole blood (WB) would permit additional analysis using a more readily available human clinical sample. In this study, frozen and thawed human WB was directly compared with frozen and thawed plasma from normal healthy donors in a series of multiplexed immunoassays for 59 different biomarkers. We demonstrate that most important biomarkers can be evaluated using thawed WB, which will facilitate the study of human cytokine and other biomarker responses to viruses emerging in resource-limited regions.

      4. Biomonitoring of exposure to polycyclic aromatic hydrocarbons (PAHs) typically uses measurement of metabolites of PAHs with four or less aromatic rings, such as 1-hydroxypyrene, even though interest may be in exposure to larger and carcinogenic PAHs, such as benzo[a]pyrene (B[a]P). An improved procedure for measuring two tetrol metabolites of B[a]P has been developed. Using 2 mL urine, the method includes enzymatic deconjugation of the tetrol conjugates, liquid-liquid extraction, activated carbon solid phase extraction (SPE) and Strata-X SPE, and gas chromatography-electron capture negative ionization-tandem mass spectrometric determination. Limits of detection were 0.026 pg/mL (benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, BPT I-1) and 0.090 pg/mL (benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol, BPT II-1). We quantified BPT I-1 and BPT II-1 in urine from a volunteer who consumed one meal containing high levels of PAHs (barbequed chicken). We also measured urinary concentrations of BPT I-1 and BPT II-1 in smokers and nonsmokers, and compared these concentrations with those of monohydroxy PAHs (OH-PAHs) and cotinine. Urinary elimination of BPT I-1 and BPT II-1 as a function of time after dietary exposure was similar to that observed previously for OH-PAHs. While the median BPT I-1 concentration in smokers’ urine (0.069 pg/mL) significantly differs from nonsmokers (0.043 pg/mL), BPT I-1 is only weakly correlated with cotinine. The urinary concentration of BPT I-1 shows a weaker relationship to tobacco smoke than metabolites of smaller PAHs, suggesting that other routes of exposure such as for example dietary routes may be of larger quantitative importance.

      5. Inhalation exposure to three-dimensional printer emissions stimulates acute hypertension and microvascular dysfunctionExternal
        Stefaniak AB, LeBouf RF, Duling MG, Yi J, Abukabda AB, McBride CR, Nurkiewicz TR.
        Toxicol Appl Pharmacol. 2017 Sep 20.

        Fused deposition modeling (FDM), or three-dimensional (3D) printing has become routine in industrial, occupational and domestic environments. We have recently reported that 3D printing emissions (3DPE) are complex mixtures, with a large ultrafine particulate matter component. We and others have reported that inhalation of xenobiotic particles in this size range is associated with an array of cardiovascular dysfunctions. Sprague-Dawley rats were exposed to 3DPE aerosols via nose-only exposure for ~3h. Twenty-four hours later, intravital microscopy was performed to assess microvascular function in the spinotrapezius muscle. Endothelium-dependent and -independent arteriolar dilation were stimulated by local microiontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). At the time of experiments, animals exposed to 3DPE inhalation presented with a mean arterial pressure of 125+/-4mmHg, and this was significantly higher than that for the sham-control group (94+/-3mmHg). Consistent with this pressor response in the 3DPE group, was an elevation of ~12% in resting arteriolar tone. Endothelium-dependent arteriolar dilation was significantly impaired after 3DPE inhalation across all iontophoretic ejection currents (0-27+/-15%, compared to sham-control: 15-120+/-21%). Endothelium-independent dilation was not affected by 3DPE inhalation. These alterations in peripheral microvascular resistance and reactivity are consistent with elevations in arterial pressure that follow 3DPE inhalation. Future studies must identify the specific toxicants generated by FDM that drive this acute pressor response.

      6. Sparse supervised classification methods predict and characterize nanomaterial exposures: Independent markers of MWCNT exposuresExternal
        Yanamala N, Orandle MS, Kodali VK, Bishop L, Zeidler-Erdely PC, Roberts JR, Castranova V, Erdely A.
        Toxicol Pathol. 2017 Jan 01:192623317730575.

        Recent experimental evidence indicates significant pulmonary toxicity of multiwalled carbon nanotubes (MWCNTs), such as inflammation, interstitial fibrosis, granuloma formation, and carcinogenicity. Although numerous studies explored the adverse potential of various CNTs, their comparability is often limited. This is due to differences in administered dose, physicochemical characteristics, exposure methods, and end points monitored. Here, we addressed the problem through sparse classification method, a supervised machine learning approach that can reduce the noise contained in redundant variables for discriminating among MWCNT-exposed and MWCNT-unexposed groups. A panel of proteins measured from bronchoalveolar lavage fluid (BAL) samples was used to predict exposure to various MWCNT and determine markers that are attributable to MWCNT exposure and toxicity in mice. Using sparse support vector machine-based classification technique, we identified a small subset of proteins clearly distinguishing each exposure. Macrophage-derived chemokine (MDC/CCL22), in particular, was associated with various MWCNT exposures and was independent of exposure method employed, that is, oropharyngeal aspiration versus inhalation exposure. Sustained expression of some of the selected protein markers identified also suggests their potential role in MWCNT-induced toxicity and proposes hypotheses for future mechanistic studies. Such approaches can be used more broadly for nanomaterial risk profiling studies to evaluate decisions related to dose/time-response relationships that could delineate experimental variables from exposure markers.

    • Maternal and Child Health
      1. Severe maternal morbidity at delivery and risk of hospital encounters within 6 weeks and 1 year postpartumExternal
        Harvey EM, Ahmed S, Manning SE, Diop H, Argani C, Strobino DM.
        J Womens Health (Larchmt). 2017 Sep 27.

        BACKGROUND: Little is known about the impact of severe maternal morbidity (SMM) after delivery. We examined the risk of rehospitalization in the first year postpartum among deliveries to women with and without SMM. MATERIALS AND METHODS: We used the Pregnancy to Early Life Longitudinal data system, in which vital birth/fetal death records were linked with hospital delivery discharge data and subsequent nondelivery hospitalization data, including observational stays (OSs) and in-patient stays (hospital discharge [HD]) for Massachusetts residents during 2002-2011. We excluded deliveries to women with preexisting chronic conditions: hypertension, diabetes, asthma, and autoimmune conditions for a final sample of 685,228 deliveries. Multivariable log binomial regression with generalized estimating equations modeled the relative risk (RR) of hospital encounters 6 weeks and 1 year postpartum. RESULTS: The rate of SMM was 99 per 10,000 deliveries. In the first year postpartum, 2.8% of deliveries to women without chronic medical conditions experienced at least one HD encounter and 1.0% at least one OS encounter. The adjusted relative risk (aRR) of any HD encounter for deliveries with SMM was 2.48 (95% confidence interval [CI]: 2.20-2.80) within 6 weeks postpartum and 2.04 (95% CI: 1.87-2.23) within 1 year. For OS encounters, aRRs among deliveries with SMM at delivery were 2.47 (95% CI: 1.94-3.14) in the first 6 weeks and 1.69 (95% CI: 1.43-2.01) in 1 year. CONCLUSIONS: In Massachusetts, SMM increased the risk of rehospitalization in the first year postpartum among deliveries to women without chronic medical conditions.

      2. Effects of prenatal micronutrient supplementation on spontaneous preterm birth: A double-blind randomized controlled trial in ChinaExternal
        Li Z, Mei Z, Zhang L, Li H, Zhang Y, Li N, Ye R, Ren A, Liu JM, Serdula MK.
        Am J Epidemiol. 2017 Aug 01;186(3):318-325.

        In this secondary analysis of data from a double-blind randomized controlled trial carried out in northern China, we aimed to assess the effect of prenatal supplementation with multiple micronutrients (MMN) or iron + folic acid (IFA), versus folic acid (FA) alone, on risk of spontaneous preterm birth (SPB) and the impact of supplementation timing on SPB. A total of 18,775 nulliparous pregnant women enrolled between 2006 and 2009 were randomly assigned to receive daily FA, IFA, or MMN from the period before 20 weeks’ gestation to delivery. The incidences of SPB for women consuming FA, IFA, and MMN were 5.7%, 5.6% and 5.1%, respectively. Compared with women given FA, the relative risks of SPB for those using MMN and IFA were 0.99 (95% confidence interval: 0.85, 1.16) and 0.89 (95% confidence interval: 0.79, 1.05), respectively. SPB incidence in women who started consuming FA, IFA, and MMN before the 12th week of gestation (4.6%, 4.2%, and 3.9%, respectively) was significantly reduced compared with starting supplement use on or after the 12th gestational week (6.9%, 7.2%, and 6.4%, respectively). Starting use of FA, IFA, or MMN supplements before the 12th week of gestation produced a 41%-45% reduction in risk of SPB. Early prenatal enrollment and micronutrient use during the first trimester of pregnancy appeared to be of particular importance for prevention of SPB, regardless of supplement group.

    • Nutritional Sciences
      1. Effective delivery of social and behavior change communication through a Care Group model in a supplementary feeding programExternal
        Wilner L, Suri DJ, Langlois BK, Walton SM, Rogers BL.
        J Health Popul Nutr. 2017 Sep 12;36(1):34.

        BACKGROUND: In 2014, an intervention aimed at increasing the oil in corn soy blend (CSB) porridge prepared by caregivers of children with moderate acute malnutrition was implemented in Southern Malawi. This analysis describes the flow of key messages delivered through the Care Group model during this intervention. METHODS: The intervention provided a supplementary food ration of CSB and oil and used a Care Group model in which healthcare workers were trained to deliver social and behavior change communication (SBCC) to care group volunteers who then delivered messages to caregivers of beneficiary children. Healthcare workers also delivered messages to caregivers directly. Interviews and focus groups were conducted with all three groups in order to determine the exchange of key messages about ingredient use, storage, and purpose, which were analyzed descriptively. RESULTS: Analysis of SBCC flow and information exchange showed that 100% of caregivers reported learning about the amounts of oil and CSB to use while preparing porridge and over 90% of caregivers, healthcare workers, and care group volunteers reported talking about it. Focus groups confirmed an effective flow of communication among these three groups. CONCLUSION: This analysis evaluated the flow of key SBCC messages through multiple, overlapping lines of communication among healthcare workers, care group volunteers, and caregivers; the effective transmission of these SBCC messages through this model may contribute to the success of a supplementary feeding intervention program. TRIAL REGISTRATION: The study was registered at ( NCT01873196 ).

    • Occupational Safety and Health
      1. Applying machine learning to workers’ compensation data to identify industry-specific ergonomic and safety prevention priorities: Ohio, 2001 to 2011External
        Meyers AR, Al-Tarawneh IS, Wurzelbacher SJ, Bushnell PT, Lampl MP, Bell JL, Bertke SJ, Robins DC, Tseng CY, Wei C, Raudabaugh JA, Schnorr TM.
        J Occup Environ Med. 2017 Sep 25.

        OBJECTIVE: This study leveraged a state workers’ compensation claims database and machine learning techniques to target prevention efforts by injury causation and industry. METHODS: Injury causation auto-coding methods were developed to code more than 1.2 million Ohio Bureau of Workers’ Compensation claims for this study. Industry groups were ranked for soft-tissue musculoskeletal claims that may have been preventable with biomechanical ergonomic (ERGO) or slip/trip/fall (STF) interventions. RESULTS: On the basis of the average of claim count and rate ranks for more than 200 industry groups, Skilled Nursing Facilities (ERGO) and General Freight Trucking (STF) were the highest risk for lost-time claims (>7 days). CONCLUSION: This study created a third, major causation-specific U.S. occupational injury surveillance system. These findings are being used to focus prevention resources on specific occupational injury types in specific industry groups, especially in Ohio. Other state bureaus or insurers may use similar methods.

    • Parasitic Diseases
      1. Cross-reactivity of the 31 kDa antigen of Angiostrongylus cantonensis – dealing with the immunodiagnosis of meningoencephalitisExternal
        Morassutti AL, Rascoe LN, Handali S, D. A. Silva AJ, Wilkins PP, Graeff-Teixeira C.
        Parasitology. 2017 Apr;144(4):459-463.

        The primary causative agent of eosinophilic meningoencephalitis (EoM) in endemic regions is the nematode Angiostrongylus cantonensis. The occurrence of EoM was previously restricted to countries in Southeast Asia and the Pacific Islands; however, more recently, it has been reported from other regions, including Brazil. The commonly used diagnosis is detection of specific antibody reactivity to the 31 kDa antigen, which is derived from female worm somatic extracts. Here we report the occurrence of cross-reactivity to this antigen in sera from other parasitic infections, especially those that may cause EoM, such as gnathostomiasis, toxocariasis, hydatidosis and strongyloidiasis. We also demonstrated that the cross-reactivity, in part, is dependent of the concentration of antigen used in Western blot assays. We discuss the importance of these findings on the interpretation of this test.

    • Physical Activity
      1. A youth compendium of physical activities: Activity codes and metabolic intensitiesExternal
        Butte NF, Watson KB, Ridley K, Zakeri IF, McMurray RG, Pfeiffer KA, Crouter SE, Herrmann SD, Bassett DR, Long A, Berhane Z, Trost SG, Ainsworth BE, Berrigan D, Fulton JE.
        Med Sci Sports Exerc. 2017 Sep 21.

        PURPOSE: A Youth Compendium of Physical Activities (Youth Compendium) was developed to estimate the energy costs of physical activities using data on youth only. METHODS: Based on a literature search and pooled data of energy expenditure measurements in youth, the energy costs of 196 activities were compiled in 16 activity categories to form a Youth Compendium of Physical Activities. To estimate the intensity of each activity, measured oxygen consumption (V[Combining Dot Above]O2) was divided by basal metabolic rate (Schofield age-, sex- and mass-specific equations) to produce a youth MET (METy). A mixed linear model was developed for each activity category to impute missing values for age ranges with no observations for a specific activity. RESULTS: This Youth Compendium consists of METy values for 196 specific activities classified into 16 major categories for four age groups, 6-9, 10-12, 13-15, and 16-18 years. METy values in this Youth Compendium were measured (51%) or imputed (49%) from youth data. CONCLUSION: This Youth Compendium of Physical Activities uses pediatric data exclusively, addresses the age-dependency of METy and imputes missing METy values and thus represents advancement in the physical activity research and practice. This Youth Compendium will be a valuable resource for stakeholders interested in evaluating interventions, programs, and policies designed to assess and encourage physical activity in youth.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

    • Reproductive Health
      1. Use of combined hormonal contraceptives among women with migraines and risk of ischemic strokeExternal
        Champaloux SW, Tepper NK, Monsour M, Curtis KM, Whiteman MK, Marchbanks PA, Jamieson DJ.
        Am J Obstet Gynecol. 2017 May;216(5):489.e1-489.e7.

        BACKGROUND: Migraine with aura and combined hormonal contraceptives are independently associated with an increased risk of ischemic stroke. However, little is known about whether there are any joint effects of migraine and hormonal contraceptives on risk of stroke. OBJECTIVE: We sought to estimate the incidence of stroke in women of reproductive age and examine the association among combined hormonal contraceptive use, migraine type (with or without aura), and ischemic stroke. STUDY DESIGN: This study used a nationwide health care claims database and employed a nested case-control study design. Females ages 15-49 years with first-ever stroke during 2006 through 2012 were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification inpatient services diagnosis codes. Four controls were matched to each case based on age. Migraine headache with and without aura was identified using inpatient or outpatient diagnosis codes. Current combined hormonal contraceptive use was identified using the National Drug Code from the pharmacy database. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals of ischemic stroke by migraine type and combined hormonal contraceptive use. RESULTS: From 2006 through 2012, there were 25,887 ischemic strokes among females ages 15-49 years, for a cumulative incidence of 11 strokes/100,000 females. Compared to those with neither migraine nor combined hormonal contraceptive use, the odds ratio of ischemic stroke was highest among those with migraine with aura using combined hormonal contraceptives (odds ratio, 6.1; 95% confidence interval, 3.1-12.1); odds ratios were also elevated for migraine with aura without combined hormonal contraceptive use (odds ratio, 2.7; 95% confidence interval, 1.9-3.7), migraine without aura and combined hormonal contraceptive use (odds ratio, 1.8; 95% confidence interval, 1.1-2.9), and migraine without aura without combined hormonal contraceptive use (odds ratio, 2.2; 95% confidence interval, 1.9-2.7). CONCLUSION: The joint effect of combined hormonal contraceptives and migraine with aura was associated with a 6-fold increased risk of ischemic stroke compared with neither risk factor. Use of combined hormonal contraceptives did not substantially further increase risk of ischemic stroke among women with migraine without aura. Determining migraine type is critical in assessing safety of combined hormonal contraceptives among women with migraine.

      2. Combined hormonal contraceptive (CHC) use among obese women and contraceptive effectiveness: a systematic reviewExternal
        Dragoman MV, Simmons KB, Paulen ME, Curtis KM.
        Contraception. 2017 Feb;95(2):117-129.

        OBJECTIVE: To evaluate from the literature whether combined hormonal contraception (CHC), including combined oral contraception pills (COCs), transdermal patch, vaginal ring or combined injectables, have different effectiveness or failure rates by body weight or body mass index (BMI). STUDY DESIGN: We searched PubMed and the Cochrane Library databases for all articles in all languages published between inception and February 2016, for evidence relevant to body weight or BMI, CHC use and contraceptive effectiveness. The quality of each individual study was assessed using the system for evaluating evidence developed by the United States Preventive Services Task Force. RESULTS: From 2874 articles, we identified 15 reports for inclusion, all of fair to poor quality. Fourteen studies measured the association of obesity status and contraceptive failure among COC users. Three fair quality and one poor quality study reported increased COC failure among a heterogeneous population of overweight and obese women compared with normal weight women, while eight fair quality and two poor quality studies did not find an association. Two fair quality studies reported on contraceptive transdermal patches. One pooled analysis described a higher proportion of pregnancies among women using the patch who weighed >/=90 kg; another secondary analysis suggested BMI>30 was associated with increased failure. No studies directly compared contraceptive effectiveness using the combined vaginal ring or combined injectable. CONCLUSION: Current available evidence addressing the risk of CHC failure in obese compared to normal weight women is limited to fair and poor quality studies. Studies of COCs show mixed results, though absolute differences in COC failure by body weight and BMI are small. Based on limited evidence, it appears that increasing body weight and BMI may contribute to decreasing contraceptive patch effectiveness.

      3. Nonoral combined hormonal contraceptives and thromboembolism: a systematic reviewExternal
        Tepper NK, Dragoman MV, Gaffield ME, Curtis KM.
        Contraception. 2017 Feb;95(2):130-139.

        BACKGROUND: Combined hormonal contraceptives (CHCs), containing estrogen and progestin, are associated with an increased risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE) compared with nonuse. Few studies have examined whether nonoral formulations (including the combined hormonal patch, combined vaginal ring and combined injectable contraceptives) increase the risk of thrombosis compared with combined oral contraceptives (COCs). OBJECTIVES: The objectives were to examine the risk of VTE and ATE among women using nonoral CHCs compared to women using COCs. METHODS: We searched the PubMed database for all English language articles published from database inception through May 2016. We included primary research studies that examined women using the patch, ring or combined injectables compared with women using levonorgestrel-containing or norgestimate-containing COCs. Outcomes of interest included VTE (deep venous thrombosis or pulmonary embolism) or ATE (acute myocardial infarction or ischemic stroke). We assessed the quality of each individual piece of evidence using the system developed by the United States Preventive Services Task Force. RESULTS: Eight studies were identified that met inclusion criteria. Of seven analyses from six studies examining VTE among patch users compared with levonorgestrel- or norgestimate-containing COC users, two found a statistically significantly elevated risk among patch users (risk estimates 2.2-2.3), one found an elevated risk that did not meet statistical significance (risk estimate 2.0), and four found no increased risk. Of three studies examining VTE among ring users compared with levonorgestrel COC users, one found a statistically significantly elevated risk among patch users (risk estimate 1.9) and two did not. Two studies did not find an increased risk for ATE among women using the patch compared with norgestimate COCs. We did not identify any studies examining combined injectable contraceptives. CONCLUSION: Limited Level II-2 good to fair evidence demonstrated conflicting results on whether women using the patch or the ring have a higher risk of VTE than women using COCs. Evidence did not demonstrate an increased risk of ATE among women using the patch. Overall, any potential elevated risk likely represents a small number of events on a population level. Additional studies with standard methodology are needed to further clarify any associations and better understand mechanisms of hormone-induced thrombosis among users of nonoral combined hormonal contraception.

    • Zoonotic and Vectorborne Diseases
      1. Compendium of measures to control Chlamydia psittaci infection among humans (psittacosis) and pet birds (avian chlamydiosis), 2017External
        Balsamo G, Maxted AM, Midla JW, Murphy JM, Wohrle R, Edling TM, Fish PH, Flammer K, Hyde D, Kutty PK, Kobayashi M, Helm B, Oiulfstad B, Ritchie BW, Stobierski MG, Ehnert K, Tully TN.
        J Avian Med Surg. 2017 Sep;31(3):262-282.

        Psittacosis, also known as parrot fever and ornithosis, is a bacterial infection that can cause severe pneumonia and other serious health problems in humans. It is caused by Chlamydia psittaci. Reclassification of the order Chlamydiales in 1999 into 2 genera (Chlamydia and Chlamydophila) was not wholly accepted or adopted. This resulted in a reversion to the single, original genus Chlamydia, which now encompasses all 9 species including Chlamydia psittaci. During 2003-2014, 112 human cases of psittacosis were reported to the Centers for Disease Control and Prevention through the Nationally Notifiable Diseases Surveillance System. While many types of birds can be infected by C psittaci, in general, the literature suggests that human cases can most often occur after exposure to infected parrot-type birds kept as pets, especially cockatiels, parakeets, and conures. In birds, C psittaci infection is referred to as avian chlamydiosis. Infected birds shed the bacteria through feces and nasal discharges, and humans become infected from exposure to these materials. This compendium provides information about psittacosis and avian chlamydiosis to public health officials, physicians, veterinarians, the pet bird industry, and others concerned with controlling these diseases and protecting public health. The recommendations in this compendium provide standardized procedures to control C psittaci infections. This document will be reviewed and revised as necessary, and the most current version replaces all previous versions. This document was last revised in 2010. Major changes in this version include a recommendation for a shorter treatment time for birds with avian chlamydiosis, additional information about diagnostic testing, including genotyping, clearer language associated with personal protective equipment recommended for those caring for confirmed or exposed birds, and incorporating a grading scale with recommendations generally based on the United States Preventive Services Task Force’s methods.

      2. Dengue is an important vector-borne pathogen found across much of the world. Many factors complicate our understanding of the relationship between infection with one of the four dengue virus serotypes, and the observed incidence of disease. One of the factors is a large proportion of infections appear to result in no or few symptoms, while others result in severe infections. Estimates of the proportion of infections that result in no symptoms (inapparent) vary widely from 8% to 100%, depending on study and setting. To investigate the sources of variation of these estimates, we used a flexible framework to combine data from multiple cohort studies and cluster studies (follow-up around index cases). Building on previous observations that the immune status of individuals affects their probability of apparent disease, we estimated the probability of apparent disease among individuals with different exposure histories. In cohort studies mostly assessing infection in children, we estimated the proportion of infections that are apparent as 0.18 (95% Credible Interval, CI: 0.16, 0.20) for primary infections, 0.13 (95% CI: 0.05, 0.17) for individuals infected in the year following a first infection (cross-immune period), and 0.41 (95% CI: 0.36, 0.45) for those experiencing secondary infections after this first year. Estimates of the proportion of infections that are apparent from cluster studies were slightly higher than those from cohort studies for both primary and secondary infections, 0.22 (95% CI: 0.15, 0.29) and 0.57 (95% CI: 0.49, 0.68) respectively. We attempted to estimate the apparent proportion by serotype, but current published data were too limited to distinguish the presence or absence of serotype-specific differences. These estimates are critical for understanding dengue epidemiology. Most dengue data come from passive surveillance systems which not only miss most infections because they are asymptomatic and often underreported, but will also vary in sensitivity over time due to the interaction between previous incidence and the symptomatic proportion, as shown here. Nonetheless the underlying incidence of infection is critical to understanding susceptibility of the population and estimating the true burden of disease, key factors for effectively targeting interventions. The estimates shown here help clarify the link between past infection, observed disease, and current transmission intensity.

      3. Extensive orf infection in a toddler with associated id reactionExternal
        Haddock ES, Cheng CE, Bradley JS, Hsu CH, Zhao H, Davidson WB, Barrio VR.
        Pediatr Dermatol. 2017 Sep 21.

        Orf is a zoonotic parapoxvirus typically transmitted to humans by a bite from goats or sheep. We present an unusual case of multiple orf lesions on the fingers of a 13-month-old child who was bitten by a goat and subsequently developed progressive swelling, blistering, and necrotic papulonodules of the hand followed by an additional diffuse, pruritic, papular rash. A primary diagnosis of orf infection was confirmed using real-time polymerase chain reaction, and the diffuse eruption was clinically consistent with an id reaction. Extensive necrosis and papular id reaction associated with orf rarely have been described.

      4. Knowledge and practices related to plague in an endemic area of UgandaExternal
        Kugeler KJ, Apangu T, Forrester JD, Griffith KS, Candini G, Abaru J, Okoth JF, Apio H, Ezama G, Okello R, Brett M, Mead P.
        Int J Infect Dis. 2017 Sep 18.

        BACKGROUND: Plague is a virulent zoonosis reported most commonly from sub-Saharan Africa. Early treatment with antibiotics is important to prevent mortality. Understanding knowledge gaps and common behaviors informs development of educational efforts to reduce plague mortality. METHODS: We conducted a multi-stage cluster-sampled survey of 420 households in the plague-endemic West Nile region of Uganda to assess knowledge of symptoms and causes of plague and healthcare-seeking practices. RESULTS: Most (84%) respondents were able to correctly describe plague symptoms; approximately 75% linked plague with fleas and dead rats. Most respondents indicated they would seek health care at a clinic for possible plague, however plague-like symptoms were reportedly common and in practice, persons sought care for those symptoms at a health clinic infrequently. CONCLUSIONS: Persons in the plague-endemic region of Uganda have a high level of understanding of plague, yet topics for targeted educational messages are apparent.

      5. Evaluation of bioMerieux’s dissociated Vidas Lyme IgM II and IgG II as a first-tier diagnostic assay for Lyme diseaseExternal
        Molins CR, Delorey MJ, Replogle A, Sexton C, Schriefer ME.
        J Clin Microbiol. 2017 Jun;55(6):1698-1706.

        The recommended laboratory diagnostic approach for Lyme disease is a standard two-tiered testing (STTT) algorithm where the first tier is typically an enzyme immunoassay (EIA) that if positive or equivocal is reflexed to Western immunoblotting as the second tier. bioMerieux manufactures one of the most commonly used first-tier EIAs in the United States, the combined IgM/IgG Vidas test (LYT). Recently, bioMerieux launched its dissociated first-tier tests, the Vidas Lyme IgM II (LYM) and IgG II (LYG) EIAs, which use purified recombinant test antigens and a different algorithm than STTT. The dissociated LYM/LYG EIAs were evaluated against the combined LYT EIA using samples from 471 well-characterized Lyme patients and controls. Statistical analyses were conducted to assess the performance of these EIAs as first-tier tests and when used in two-tiered algorithms, including a modified two-tiered testing (MTTT) approach where the second-tier test was a C6 EIA. Similar sensitivities and specificities were obtained for the two testing strategies (LYT versus LYM/LYG) when used as first-tier tests (sensitivity, 83 to 85%; specificity, 85 to 88%) with an observed agreement of 80%. Sensitivities of 68 to 69% and 76 to 77% and specificities of 97% and 98 to 99% resulted when the two EIA strategies were followed by Western immunoblotting and when used in an MTTT, respectively. The MTTT approach resulted in significantly higher sensitivities than did STTT. Overall, the LYM/LYG EIAs performed equivalently to the LYT EIA in test-to-test comparisons or as first-tier assays in STTT or MTTT with few exceptions.

      6. Improving dengue viral antigens detection in dengue patient serum specimens using a low pH glycine buffer treatmentExternal
        Shen WF, Galula JU, Chang GJ, Wu HC, King CC, Chao DY.
        J Microbiol Immunol Infect. 2017 Apr;50(2):167-174.

        BACKGROUND/PURPOSES: Early diagnosis of dengue virus (DENV) infection to monitor the potential progression to hemorrhagic fever can influence the timely management of dengue-associated severe illness. Nonstructural protein 1 (NS1) antigen detection in acute serum specimens has been widely accepted as an early diagnostic assay for dengue infection; however, lower sensitivity of the NS1 antigen-capture enzyme-linked immunosorbent assay (Ag-ELISA) in secondary dengue viral infection has been reported. METHODS: In this study, we developed two forms of Ag-ELISA capable of detecting E-Ag containing virion and virus-like particles, and secreted NS1 (sNS1) antigens, respectively. The temporal kinetics of viral RNA, sNS1, and E-Ag were evaluated based on the in vitro infection experiment. Meanwhile, a panel of 62 DENV-2 infected patients’ sera was tested. RESULTS: The sensitivity was 3.042 ng/mL and 3.840 ng/mL for sNS1 and E, respectively. The temporal kinetics of the appearance of viral RNA, E, NS1, and infectious virus in virus-infected tissue culture media suggested that viral RNAs and NS1 antigens could be detected earlier than E-Ag and infectious virus. Furthermore, a panel of 62 sera from patients infected by DENV Serotype 2 was tested. Treating clinical specimens with the dissociation buffer increased the detectable level of E from 13% to 92% and NS1 antigens from 40% to 85%. CONCLUSION: Inclusion of a low-pH glycine buffer treatment step in the commercially available Ag-ELISA is crucial for clinical diagnosis and E-containing viral particles could be a valuable target for acute DENV diagnosis, similar to NS1 detection.

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