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CDC Science Clips: Volume 9, Issue 24, June 20, 2017

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

  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs).
    • CDC Public Health Grand Rounds:
      Hearing Health RSS Word feed
      1. Vital Signs: Noise-induced hearing loss among adults – United States 2011-2012
        Carroll YI, Eichwald J, Scinicariello F, Hoffman HJ, Deitchman S, Radke MS, Themann CL, Breysse P.
        MMWR Morb Mortal Wkly Rep. 2017 Feb 10;66(5):139-144.
        INTRODUCTION: The 2016 National Academies of Sciences report “Hearing Health Care for Adults: Priorities for Improving Access and Affordability” included a call to action for government agencies to strengthen efforts to collect, analyze, and disseminate population-based data on hearing loss in adults. METHODS: CDC analyzed the most recent available data collected both by questionnaire and audiometric tests of adult participants aged 20-69 years in the 2011-2012 National Health and Nutrition Examination Survey (NHANES) to determine the presence of audiometric notches indicative of noise-induced hearing loss. Prevalence of both unilateral and bilateral audiometric notches and their association with sociodemographics and self-reported exposure to loud noise were calculated. RESULTS: Nearly one in four adults (24%) had audiometric notches, suggesting a high prevalence of noise-induced hearing loss. The prevalence of notches was higher among males. Almost one in four U.S. adults who reported excellent or good hearing had audiometric notches (5.5% bilateral and 18.0% unilateral). Among participants who reported exposure to loud noise at work, almost one third had a notch. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Noise-induced hearing loss is a significant, often unrecognized health problem among U.S. adults. Discussions between patients and personal health care providers about hearing loss symptoms, tests, and ways to protect hearing might help with early diagnosis of hearing loss and provide opportunities to prevent harmful noise exposures. Avoiding prolonged exposure to loud environments and using personal hearing protection devices can prevent noise-induced hearing loss.

      2. Effectiveness of “Dangerous Decibels,” a school-based hearing loss prevention program
        Griest SE, Folmer RL, Martin WH.
        Am J Audiol. 2007 Dec;16(2):S165-81.
        PURPOSE: To evaluate the effectiveness of the “Dangerous Decibels” educational program in increasing students’ knowledge and positively changing their attitudes and intended behaviors related to hearing and hearing loss prevention. METHOD: Baseline questionnaires were completed by 478 4th-grade students and 550 7th-grade students. Approximately half of the students in each grade received a 35-min interactive classroom presentation on hearing and hearing loss prevention. The remaining students served as comparison groups. Students who received the curriculum filled out questionnaires immediately after the presentation. All students filled out follow-up questionnaires 3 months after baseline. RESULTS: Fourth-grade students who participated in the Dangerous Decibels presentation exhibited significant improvements in knowledge and attitudes related to hearing and hearing loss prevention. These improvements were maintained 3 months after the presentation. Seventh-grade students also experienced long-term improvements in their knowledge base. However, attitudes and intended behaviors in 7th graders returned to baseline levels 3 months postpresentation. CONCLUSION: The Dangerous Decibels hearing loss prevention program was effective at producing long-term improvements in the knowledge base of 4th- and 7th-grade students. Future studies should include components on peer pressure and should incorporate repeated, multimodality interventions to increase the likelihood of long-term improvement in adolescents.

      3. Prevalence of noise-induced hearing-threshold shifts and hearing loss among US youths
        Henderson E, Testa MA, Hartnick C.
        Pediatrics. 2011 Jan;127(1):e39-46.
        OBJECTIVE: We investigated trends in noise-induced threshold shifts (NITSs), high-frequency hearing loss (HFHL), and low-frequency hearing loss (LFHL). METHODS: A total of 4310 adolescents 12 to 19 years of age completed audiometric testing during National Health and Nutrition Examination Surveys in 1988-1994 and 2005-2006. NITS criteria were audiometric patterns of decreased 3- to 6-kHz thresholds but preserved 0.5- to 1-kHz and 8-kHz thresholds; HFHL and LFHL criteria were high and low pure-tone averages, respectively, of >15 dB HL. RESULTS: There were no significant increases in NITSs (odds ratio [OR]: 0.81 [95% confidence interval [CI]: 0.53-1.22]; P = .29), HFHL (OR: 1.21 [95% CI: 0.87-1.69]; P = .25), or LFHL (OR: 1.37 [95% CI: 0.77-2.45]; P = .28) between survey periods. However, a significant increase in the prevalence of NITSs occurred among female youths (11.6% [95% CI: 9.0%-14.1%] vs 16.7% [95% CI: 13.2%-20.3%]; P < .0001). The overall prevalence of exposure to loud noise or listening to music through headphones in the previous 24 hours increased from 19.8% (95% CI: 17.6%-22.1%) to 34.8% (95% CI: 31.0%-38.5%; P < .0001). In 2005-2006, female youths had a similar prevalence of exposure to recreational noise (23.6% [95% CI: 19.6%-27.6%] vs 27.7% [95% CI: 23.6%-31.8%]; P < .0001) and a lower prevalence of hearing-protection use (3.4% [95% CI: 1.6%-5.3%] vs 10.3% [95% CI: 7.3%-13.2%]; P < .0001) compared with male youths. CONCLUSIONS: Increased exposure to recreational noise and minimal use of hearing protection might have lead to an increase in NITS prevalence among female youths.

      4. Declining prevalence of hearing loss in US adults aged 20 to 69 years
        Hoffman HJ, Dobie RA, Losonczy KG, Themann CL, Flamme GA.
        JAMA Otolaryngol Head Neck Surg. 2017 Mar 01;143(3):274-285.
        Importance: As the US population ages, effective health care planning requires understanding the changes in prevalence of hearing loss. Objective: To determine if age- and sex-specific prevalence of adult hearing loss has changed during the past decade. Design, Setting, and Participants: We analyzed audiometric data from adults aged 20 to 69 years from the 2011-2012 cycle of the US National Health and Nutrition Examination Survey, a cross-sectional, nationally representative interview and examination survey of the civilian, noninstitutionalized population, and compared them with data from the 1999-2004 cycles. Logistic regression was used to examine unadjusted, age- and sex-adjusted, and multivariable-adjusted associations with demographic, noise exposure, and cardiovascular risk factors. Data analysis was performed from April 28 to June 3, 2016. Interventions: Audiometry and questionnaires. Main Outcomes and Measures: Speech-frequency hearing impairment (HI) defined by pure-tone average of thresholds at 4 frequencies (0.5, 1, 2, and 4 kHz) greater than 25 decibels hearing level (HL), and high-frequency HI defined by pure-tone average of thresholds at 3 frequencies (3, 4, and 6 kHz) greater than 25 decibels HL. Results: Based on 3831 participants with complete threshold measurements (1953 men and 1878 women; mean [SD] age, 43.6 [14.4] years), the 2011-2012 nationally weighted adult prevalence of unilateral and bilateral speech-frequency HI was 14.1% (27.7 million) compared with 15.9% (28.0 million) for the 1999-2004 cycles; after adjustment for age and sex, the difference was significant (odds ratio [OR], 0.70; 95% CI, 0.56-0.86). Men had nearly twice the prevalence of speech-frequency HI (18.6% [17.8 million]) as women (9.6% [9.7 million]). For individuals aged 60 to 69 years, speech-frequency HI prevalence was 39.3% (95% CI, 30.7%-48.7%). In adjusted multivariable analyses for bilateral speech-frequency HI, age was the major risk factor (60-69 years: OR, 39.5; 95% CI, 10.5-149.4); however, male sex (OR, 1.8; 95% CI, 1.1-3.0), non-Hispanic white (OR, 2.3; 95% CI, 1.3-3.9) and non-Hispanic Asian race/ethnicity (OR, 2.1; 95% CI, 1.1-4.2), lower educational level (less than high school: OR, 4.2; 95% CI, 2.1-8.5), and heavy use of firearms (>/=1000 rounds fired: OR, 1.8; 95% CI, 1.1-3.0) were also significant risk factors. Additional associations for high-frequency HI were Mexican-American (OR, 2.0; 95% CI, 1.3-3.1) and other Hispanic race/ethnicity (OR, 2.4; 95% CI, 1.4-4.0) and the combination of loud and very loud noise exposure occupationally and outside of work (OR, 2.4; 95% CI, 1.4-4.2). Conclusions and Relevance: Adult hearing loss is common and associated with age, other demographic factors (sex, race/ethnicity, and educational level), and noise exposure. Age- and sex-specific prevalence of HI continues to decline. Despite the benefit of delayed onset of HI, hearing health care needs will increase as the US population grows and ages.

      5. Evaluation of smartphone sound measurement applications
        Kardous CA, Shaw PB.
        J Acoust Soc Am. 2014 Apr;135(4):El186-92.
        This study reports on the accuracy of smartphone sound measurement applications (apps) and whether they can be appropriately employed for occupational noise measurements. A representative sample of smartphones and tablets on various platforms were acquired, more than 130 iOS apps were evaluated but only 10 apps met our selection criteria. Only 4 out of 62 Android apps were tested. The results showed two apps with mean differences of 0.07 dB (unweighted) and -0.52 dB (A-weighted) from the reference values. Two other apps had mean differences within +/-2 dB. The study suggests that certain apps may be appropriate for use in occupational noise measurements.

      6. Randomized trial of four noise-induced hearing loss and tinnitus prevention interventions for children
        Martin WH, Griest SE, Sobel JL, Howarth LC.
        Int J Audiol. 2013 Feb;52 Suppl 1:S41-9.
        OBJECTIVE: To evaluate the effectiveness of four NIHL prevention interventions at improving knowledge, attitudes, and intended behaviors regarding sound exposure and appropriate use of hearing protective strategies in children. DESIGN: A randomized trial of the four interventions with a non-intervention comparison group. Questionnaires were completed prior to, immediately after, and three months after each intervention. STUDY: Interventions included: (1) A classroom presentation by older-peer educators, (2) A classroom presentation by health professionals, (3). Exploration of a museum exhibition, and (4). Exploration of an internet-based virtual museum. A comparison group received no intervention. STUDY SAMPLE: Fifty-three fourth grade classrooms (1120 students) participated in the study. RESULTS: All interventions produced significant improvements but the number of improvements decreased over time. In terms of effectiveness, the classroom programs were more effective than the internet-based virtual exhibit, which was more effective than the visit to the museum exhibition. Self-reported exposures indicated that as many as 94.5% of participants were at risk for NIHL. CONCLUSIONS: Interpersonal, interactive educational interventions such as the classroom program are more effective and have longer impact than self-directed learning experiences for NIHL and tinnitus prevention, however each may have an important role in promoting hearing health in elementary school students.

      7. Program sustainability: Hearing loss and tinnitus prevention in American Indian communities
        Martin WH, Sobel JL, Griest SE, Howarth LC, Becker TM.
        Am J Prev Med. 2017 Mar;52(3s3):S268-s270.
        INTRODUCTION: An important goal of any health promotion effort is to have it maintained in delivery and effectiveness over time. The purpose of this study was to establish a community-based noise-induced hearing loss and tinnitus prevention program in three different types of American Indian communities and evaluate them for evidence of long-term sustainability. METHODS: The target population was fourth- and fifth-grade students from three different models of American Indian communities. The evidenced-based Dangerous Decibels(R) program was adapted to include local media, classroom education, family and community outreach, and web-based activities. Sustainability was attempted by promoting funding stability, political support, partnerships, organizational capacity, program adaptation, program evaluation, communications, public health impacts, and strategic planning. RESULTS: Currently, there is evidence suggesting that the hearing health promotion program is self-sustaining in all three American Indian communities. The intervention was effective at changing knowledge, attitudes, beliefs, and behaviors in the target population, but program adoption and self-sustenance faced challenges that required patience, persistence, and creativity by the program team. Components of the intervention continue to be delivered by local members of each community. CONCLUSIONS: Critical factors that led to self-sustaining programs included approval of community leaders and engagement of community members in the design, administration, and evaluation of the effort; use of a well-developed, evidence-based intervention; and high-level training of local participants who could confidently and effectively continue delivering the program following a gradual transition to independence.

      8. PURPOSE: To ascertain whether current pure-tone school hearing screening criteria used across the United States are adequate for the early identification of noise-induced hearing loss (NIHL) in adolescents. METHOD: School-based pure-tone hearing screening protocols were collected, reviewed, and consolidated from 46 state agencies. A retrospective categorical analysis of air-conduction audiometric thresholds from a computerized database of 9th-grade (n = 376) and 12th-grade (n = 265) students from a suburban high school was conducted. The database analysis was designed to determine whether each screening protocol would identify high-frequency notched audiometric configurations suggestive of NIHL when using the noise notch criteria described by A. S. Niskar et al. (2001). RESULTS: All of the school-based hearing screening criteria identified significantly (p <or= .05) fewer students with a high-frequency notch (HFN) than the noise notch protocol regardless of screening decibel level specified. Over half of the school-based hearing screening protocols used in the United States will identify only 22% of the students with an HFN and consequently would fail to detect a potential NIHL. CONCLUSIONS: Currently implemented school-based hearing screening guidelines are nonstandardized and inadequate for the early identification of NIHL. This denies the majority of students the opportunity to receive early intervention and to prevent further progression of NIHL. It is necessary to identify, standardize, and implement effective and efficient screening or monitoring programs for the early detection and prevention of NIHL in adolescents.

      9. Auditory risk estimates for youth target shooting
        Meinke DK, Murphy WJ, Finan DS, Lankford JE, Flamme GA, Stewart M, Soendergaard J, Jerome TW.
        Int J Audiol. 2014 Mar;53 Suppl 2:S16-25.
        OBJECTIVE: To characterize the impulse noise exposure and auditory risk for youth recreational firearm users engaged in outdoor target shooting events. The youth shooting positions are typically standing or sitting at a table, which places the firearm closer to the ground or reflective surface when compared to adult shooters. DESIGN: Acoustic characteristics were examined and the auditory risk estimates were evaluated using contemporary damage-risk criteria for unprotected adult listeners and the 120-dB peak limit suggested by the World Health Organization (1999) for children. STUDY SAMPLE: Impulses were generated by 26 firearm/ammunition configurations representing rifles, shotguns, and pistols used by youth. Measurements were obtained relative to a youth shooter’s left ear. RESULTS: All firearms generated peak levels that exceeded the 120 dB peak limit suggested by the WHO for children. In general, shooting from the seated position over a tabletop increases the peak levels, LAeq8 and reduces the unprotected maximum permissible exposures (MPEs) for both rifles and pistols. Pistols pose the greatest auditory risk when fired over a tabletop. CONCLUSION: Youth should utilize smaller caliber weapons, preferably from the standing position, and always wear hearing protection whenever engaging in shooting activities to reduce the risk for auditory damage.

      10. Assessment of noise exposure for indoor and outdoor firing ranges
        Murphy WJ, Tubbs RL.
        J Occup Environ Hyg. 2007 Sep;4(9):688-97.
        The National Institute for Occupational Safety and Health (NIOSH) received an employee request for a health hazard evaluation of a Special Weapons Assault Team (SWAT) in January 2002. The department was concerned about noise exposures and potential hearing damage from weapons training on their indoor and outdoor firing ranges. NIOSH investigators conducted noise sampling with an acoustic mannequin head and 1/4 -inch microphone to characterize the noise exposures that officers might experience during small arms qualification and training when wearing a variety of hearing protection devices provided by the department. The peak sound pressure levels for the various weapons ranged from 156 to 170 decibels (dB SPL), which are greater than the recommended allowable 140 dB SPL exposure guideline from NIOSH. The earplugs, ear muffs, and customized SWAT team hearing protectors provided between 25 and 35 dB of peak reduction. Double hearing protection (plugs plus muffs) added 15-20 dB of peak reduction.

      11. Economic impact of hearing loss and reduction of noise-induced hearing loss in the United States
        Neitzel RL, Swinburn TK, Hammer MS, Eisenberg D.
        J Speech Lang Hear Res. 2017 Jan 01;60(1):182-189.
        Purpose: Hearing loss (HL) is pervasive and debilitating, and noise-induced HL is preventable by reducing environmental noise. Lack of economic analyses of HL impacts means that prevention and treatment remain a low priority for public health and environmental investment. Method: This article estimates the costs of HL on productivity by building on established estimates for HL prevalence and wage and employment differentials between those with and without HL. Results: We estimate that HL affects more than 13% of the working population. Not all HL can be prevented or treated, but if the 20% of HL resulting from excessive noise exposure were prevented, the economic benefit would be substantial-we estimate a range of $58 billion to $152 billion annually, with a core estimate of $123 billion. We believe this is a conservative estimate, because consideration of additional costs of HL, including health care and special education, would likely further increase the benefits associated with HL prevention. Conclusion: HL is costly and warrants additional emphasis in public and environmental health programs. This study represents an important first step in valuing HL prevention-in particular, prevention of noise-induced HL-where new policies and technologies appear promising.

      12. An ecological approach to hearing-health promotion in workplaces
        Reddy R, Welch D, Ameratunga S, Thorne P.
        Int J Audiol. 2017 May;56(5):316-327.
        OBJECTIVE: To develop and assess use, acceptability and feasibility of an ecological hearing conservation programme for workplaces. DESIGN: A school-based public health hearing preservation education programme (Dangerous Decibels(R)) was adapted for workplaces using the Multi-level Approach to Community Health (MATCH) Model. The programme was delivered in small manufacturing companies and evaluated using a questionnaire before the training and at one week and two-months after training. STUDY SAMPLE: Workers (n = 56) from five small manufacturing companies were recruited. RESULTS: There was a significant improvement in knowledge, attitudes and behaviour of workers at the intrapersonal level; in behaviour motivation and safety culture at the interpersonal and organisational levels; and an overall improvement in hearing-health behaviour after two months post-intervention. CONCLUSIONS: The developed programme offers a simple, interactive and theory-based intervention that is well accepted and effective in promoting positive hearing-health behaviour in workplaces.
      13. Stewart M, Meinke D, Flamme G, Murphy W, Finan D, Lankford J, Tasko S.
        National Hearing Conservation Association. 2017 .

        [No abstract]

      14. Shooting habits of youth recreational firearm users
        Stewart M, Meinke DK, Snyders JK, Howerton K.
        Int J Audiol. 2014 Mar;53 Suppl 2:S26-34.
        OBJECTIVE: This study surveyed youth recreational firearm users (YRFUs) regarding shooting habits, reported use of hearing protection devices (HPDs), self-assessed auditory status, and attitudes about firearm noise and hearing loss. DESIGN: A descriptive study using a 28-item survey administered by personal interview. STUDY SAMPLE: Two-hundred and ten youth aged 10 to 17 years responded. RESULTS: Seventy-eight percent of those surveyed began shooting before the age of ten. The majority reported using large caliber firearms capable of rapid fire for both hunting and target practice. Most youths in this study were not aware of, and therefore, were not utilizing HPDs specifically designed for the shooting sports. Ten percent of subjects reported constant tinnitus and 45% notice tinnitus occurred or worsened after shooting. Although the majority of YRFUs reported good or perfect hearing, a small percentage (4-5%) of youth reported having only ‘fair” hearing. CONCLUSION: YRFUs are putting themselves at risk beginning at a young age for noise-induced hearing loss (NIHL) and tinnitus based on self-reported shooting habits and inconsistent use of HPDs during both target practice and hunting activities. This research highlights the need for early education and intervention efforts to minimize the risk of NIHL in youth.

      15. [No abstract]

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions RSS Word feed
      1. Design of the subpopulations and intermediate outcome measures in COPD (SPIROMICS) AIR study
        Hansel NN, Paulin LM, Gassett AJ, Peng RD, Alexis N, Fan VS, Bleecker E, Bowler R, Comellas AP, Dransfield M, Han MK, Kim V, Krishnan JA, Pirozzi C, Cooper CB, Martinez F, Woodruff PG, Breysse PJ, Graham Barr R, Kaufman JD.
        BMJ Open Respiratory Research. 2017 01 May;4 (1) (no pagination)(e000186).
        Introduction Population-based epidemiological evidence suggests that exposure to ambient air pollutants increases hospitalisations and mortality from chronic obstructive pulmonary disease (COPD), but less is known about the impact of exposure to air pollutants on patient-reported outcomes, morbidity and progression of COPD. Methods and analysis The Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) Air Pollution Study (SPIROMICS AIR) was initiated in 2013 to investigate the relation between individual-level estimates of short-term and long-term air pollution exposures, day-to-day symptom variability and disease progression in individuals with COPD. SPIROMICS AIR builds on a multicentre study of smokers with COPD, supplementing it with state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, ozone, sulfur dioxide and black carbon. In the parent study, approximately 3000 smokers with and without airflow obstruction are being followed for up to 3 years for the identification of intermediate biomarkers which predict disease progression. Subcohorts undergo daily symptom monitoring using comprehensive daily diaries. The air monitoring and modelling methods employed in SPIROMICS AIR will provide estimates of individual exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand the health effects of short-term and long-term exposures to air pollution on COPD morbidity, including exacerbation risk, patient-reported outcomes and disease progression. Ethics and dissemination The institutional review boards of all the participating institutions approved the study protocols. The results of the trial will be presented at national and international meetings and published in peer-reviewed journals. Copyright ? Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved.

      2. The effects of joint disease, inhibitors and other complications on health-related quality of life among males with severe haemophilia A in the United States
        Soucie JM, Grosse SD, Siddiqi AE, Byams V, Thierry J, Zack MM, Shapiro A, Duncan N.
        Haemophilia. 2017 Jun 02.
        INTRODUCTION: Health-related quality of life (HRQoL) is reduced among persons with haemophilia. Little is known about how HRQoL varies with complications of haemophilia such as inhibitors and joint disease. Estimates of preference-based HRQoL measures are needed to model the cost-effectiveness of prevention strategies. AIM: We examined the characteristics of a national sample of persons with severe haemophilia A for associations with two preference-based measures of HRQoL. METHODS: We analysed utility weights converted from EuroQol 5 Dimensions (EQ-5D) and the Short Form 6 Dimensions (SF-6D) scores from 1859 males aged >/=14 years with severe haemophilia A treated at 135 US haemophilia treatment centres in 2005-2011. Bivariate and regression analyses examined age-group-specific associations of HRQoL with inhibitor status, overweight/obesity, number of bleeds, viral infections, indicators of liver and joint disease, and severe bleeding at the time of the first HRQoL measurement. RESULTS: Overall mean HRQoL utility weight values were 0.71 using the SF-6D and 0.78 using the EQ-5D. All studied patient characteristics except for overweight/obesity were significantly associated with HRQoL in bivariate analyses. In a multivariate analysis, only joint disease was significantly associated with utility weights from both HRQoL measures and across all age groups. After adjustment for joint disease and other variables, the presence of an inhibitor was not significantly associated with HRQoL scores from either of the standardized assessment tools. CONCLUSION: Clinically significant complications of haemophilia, especially joint disease, are strongly associated with HRQoL and should be accounted for in studies of preference-based health utilities for people with haemophilia.

      3. Multi-site clinical assessment of myalgic encephalomyelitis/Chronic Fatigue Syndrome (MCAM): Design and implementation of a prospective/retrospective rolling cohort study
        Unger ER, Lin JS, Tian H, Natelson BH, Lange G, Vu D, Blate M, Klimas NG, Balbin EG, Bateman L, Allen A, Lapp CW, Springs W, Kogelnik AM, Phan CC, Danver J, Podell RN, Fitzpatrick T, Peterson DL, Gottschalk CG, Rajeevan MS.
        Am J Epidemiol. 2017 Apr 15;185(8):617-626.
        In the Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM), we relied on expert clinician diagnoses to enroll patients from 7 specialty clinics in the United States in order to perform a systematic collection of data on measures of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Healthy persons and those with other illnesses that share some features with ME/CFS were enrolled in comparison groups. The major objectives were to: 1) use standardized questionnaires to measure illness domains of ME/CFS and to evaluate patient heterogeneity overall and between clinics; 2) describe the course of illness, identify the measures that best correlate with meaningful clinical differences, and assess the performances of questionnaires as patient/person-reported outcome measures; 3) describe prescribed medications, orders for laboratory and other tests, and management tools used by expert clinicians to care for persons with ME/CFS; 4) collect biospecimens for future hypothesis testing and for evaluation of morning cortisol profiles; and 5) identify measures that best distinguish persons with ME/CFS from those in the comparison groups and detect subgroups of persons with ME/CFS who may have different underlying causes. Enrollment began in 2012 and is planned to continue in multiple stages through 2017. We present the MCAM methods in detail, along with an initial description of the 471 patients with ME/CFS who were enrolled in stage 1.

    • Communicable Diseases RSS Word feed
      1. Prevalence, incidence and correlates of HSV-2 infection in an HIV incidence adolescent and adult cohort study in western Kenya
        Akinyi B, Odhiambo C, Otieno F, Inzaule S, Oswago S, Kerubo E, Ndivo R, Zeh C.
        PLoS One. 2017 ;12(6):e0178907.
        BACKGROUND: Herpes simplex virus type 2 (HSV-2) infections are associated with increased risk of HIV transmission. We determined HSV-2 prevalence, incidence and associated risk factors, incidence among persons with indeterminate results, and prevalence of HSV-2/HIV co-infection among young adults (18-34 years) and adolescents (16-17 years) enrolled in an HIV incidence cohort study in western Kenya. METHODS: Participants (n = 1106; 846 adults) were screened and those HIV-1 negative were enrolled and followed-up quarterly for one year. HSV-2 was assessed using the Kalon enzyme immunoassay. HSV-2 incidence was calculated separately among HSV-2 seronegative participants and those indeterminate at baseline. Logistic regression was used to estimate the odds of HSV-2 infection and Poisson regression was used to assess HSV-2 incidence and associated factors. RESULTS: Overall, HSV-2 prevalence was 26.6% [95% confidence interval (CI): 23.9-29.4] and was higher in adults (31.5% [95% CI: 28.3-34.9]) than adolescents (10.7% [95% CI: 7.1-15.3]). Factors associated with prevalent HSV-2 included female gender, increasing age, HIV infection, history of sexually transmitted infection, low level of education, multiple sexual partners, and being married, divorced, separated or widowed. Overall HSV-2 incidence was 4.0 per 100 person-years (/100PY) 95% CI: 2.7-6.1 and was higher in adults (4.5/100PY) and females (5.1/100PY). In multivariable analysis only marital status was associated with HSV-2 incidence. Among 45 participants with indeterminate HSV-2 results at baseline, 22 seroconverted, resulting in an incidence rate of 53.2 /100PY [95% CI: 35.1-80.9]. Inclusion of indeterminate results almost doubled the overall incidence rate to 7.8 /100 PY [95% CI: 5.9-10.5]. Prevalence of HIV/HSV-2 co-infection was higher in female adults than female adolescents (17.1 [95% CI: 13.6-21.0] versus 3.4 [95% CI: 1.1-7.8]). CONCLUSION: The high incidence rate among persons with indeterminate results underscores the public health concerns for HSV-2 spread and underreporting of the HSV-2 burden. Careful consideration is needed when interpreting HSV-2 serology results in these settings.

      2. Density of upper respiratory colonization with Streptococcus pneumoniae and its role in the diagnosis of pneumococcal pneumonia among children aged <5 years in the PERCH Study
        Baggett HC, Watson NL, Deloria Knoll M, Brooks WA, Feikin DR, Hammitt LL, Howie SR, Kotloff KL, Levine OS, Madhi SA, Murdoch DR, Scott JA, Thea DM, Antonio M, Awori JO, Baillie VL, DeLuca AN, Driscoll AJ, Duncan J, Ebruke BE, Goswami D, Higdon MM, Karron RA, Moore DP, Morpeth SC, Mulindwa JM, Park DE, Paveenkittiporn W, Piralam B, Prosperi C, Sow SO, Tapia MD, Zaman K, Zeger SL, O’Brien KL.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S317-s327.
        Background.: Previous studies suggested an association between upper airway pneumococcal colonization density and pneumococcal pneumonia, but data in children are limited. Using data from the Pneumonia Etiology Research for Child Health (PERCH) study, we assessed this potential association. Methods.: PERCH is a case-control study in 7 countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. Cases were children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia. Controls were randomly selected from the community. Microbiologically confirmed pneumococcal pneumonia (MCPP) was confirmed by detection of pneumococcus in a relevant normally sterile body fluid. Colonization density was calculated with quantitative polymerase chain reaction analysis of nasopharyngeal/oropharyngeal specimens. Results.: Median colonization density among 56 cases with MCPP (MCPP cases; 17.28 x 106 copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 0.75 x 106) and controls (0.60 x 106) (each P < .001). The optimal density for discriminating MCPP cases from controls using the Youden index was >6.9 log10 copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site. The threshold was lower (>/=4.4 log10 copies/mL) when MCPP cases were distinguished from controls who received antibiotics before specimen collection. Among the 4035 non-MCPP cases, 500 (12%) had pneumococcal colonization density >6.9 log10 copies/mL; above this cutoff was associated with alveolar consolidation at chest radiography, very severe pneumonia, oxygen saturation <92%, C-reactive protein >/=40 mg/L, and lack of antibiotic pretreatment (all P< .001). Conclusions.: Pneumococcal colonization density >6.9 log10 copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies. Our findings do not support its use for individual diagnosis in a clinical setting.

      3. Standardization of clinical assessment and sample collection across all PERCH study sites
        Crawley J, Prosperi C, Baggett HC, Brooks WA, Deloria Knoll M, Hammitt LL, Howie SR, Kotloff KL, Levine OS, Madhi SA, Murdoch DR, O’Brien KL, Thea DM, Awori JO, Bunthi C, DeLuca AN, Driscoll AJ, Ebruke BE, Goswami D, Hidgon MM, Karron RA, Kazungu S, Kourouma N, Mackenzie G, Moore DP, Mudau A, Mwale M, Nahar K, Park DE, Piralam B, Seidenberg P, Sylla M, Feikin DR, Scott JA.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S228-s237.
        Background.: Variable adherence to standardized case definitions, clinical procedures, specimen collection techniques, and laboratory methods has complicated the interpretation of previous multicenter pneumonia etiology studies. To circumvent these problems, a program of clinical standardization was embedded in the Pneumonia Etiology Research for Child Health (PERCH) study. Methods.: Between March 2011 and August 2013, standardized training on the PERCH case definition, clinical procedures, and collection of laboratory specimens was delivered to 331 clinical staff at 9 study sites in 7 countries (The Gambia, Kenya, Mali, South Africa, Zambia, Thailand, and Bangladesh), through 32 on-site courses and a training website. Staff competency was assessed throughout 24 months of enrollment with multiple-choice question (MCQ) examinations, a video quiz, and checklist evaluations of practical skills. Results.: MCQ evaluation was confined to 158 clinical staff members who enrolled PERCH cases and controls, with scores obtained for >86% of eligible staff at each time-point. Median scores after baseline training were >/=80%, and improved by 10 percentage points with refresher training, with no significant intersite differences. Percentage agreement with the clinical trainer on the presence or absence of clinical signs on video clips was high (>/=89%), with interobserver concordance being substantial to high (AC1 statistic, 0.62-0.82) for 5 of 6 signs assessed. Staff attained median scores of >90% in checklist evaluations of practical skills. Conclusions.: Satisfactory clinical standardization was achieved within and across all PERCH sites, providing reassurance that any etiological or clinical differences observed across the study sites are true differences, and not attributable to differences in application of the clinical case definition, interpretation of clinical signs, or in techniques used for clinical measurements or specimen collection.

      4. Bayesian estimation of pneumonia etiology: Epidemiologic considerations and applications to the Pneumonia Etiology Research for Child Health Study
        Deloria Knoll M, Fu W, Shi Q, Prosperi C, Wu Z, Hammitt LL, Feikin DR, Baggett HC, Howie SR, Scott JA, Murdoch DR, Madhi SA, Thea DM, Brooks WA, Kotloff KL, Li M, Park DE, Lin W, Levine OS, O’Brien KL, Zeger SL.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S213-s227.
        In pneumonia, specimens are rarely obtained directly from the infection site, the lung, so the pathogen causing infection is determined indirectly from multiple tests on peripheral clinical specimens, which may have imperfect and uncertain sensitivity and specificity, so inference about the cause is complex. Analytic approaches have included expert review of case-only results, case-control logistic regression, latent class analysis, and attributable fraction, but each has serious limitations and none naturally integrate multiple test results. The Pneumonia Etiology Research for Child Health (PERCH) study required an analytic solution appropriate for a case-control design that could incorporate evidence from multiple specimens from cases and controls and that accounted for measurement error. We describe a Bayesian integrated approach we developed that combined and extended elements of attributable fraction and latent class analyses to meet some of these challenges and illustrate the advantage it confers regarding the challenges identified for other methods.

      5. Evaluation of pneumococcal load in blood by polymerase chain reaction for the diagnosis of pneumococcal pneumonia in young children in the PERCH Study
        Deloria Knoll M, Morpeth SC, Scott JA, Watson NL, Park DE, Baggett HC, Brooks WA, Feikin DR, Hammitt LL, Howie SR, Kotloff KL, Levine OS, O’Brien KL, Thea DM, Ahmed D, Antonio M, Awori JO, Baillie VL, Chipeta J, Deluca AN, Dione M, Driscoll AJ, Higdon MM, Jatapai A, Karron RA, Mazumder R, Moore DP, Mwansa J, Nyongesa S, Prosperi C, Seidenberg P, Siludjai D, Sow SO, Tamboura B, Zeger SL, Murdoch DR, Madhi SA.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S357-s367.
        Background.: Detection of pneumococcus by lytA polymerase chain reaction (PCR) in blood had poor diagnostic accuracy for diagnosing pneumococcal pneumonia in children in 9 African and Asian sites. We assessed the value of blood lytA quantification in diagnosing pneumococcal pneumonia. Methods.: The Pneumonia Etiology Research for Child Health (PERCH) case-control study tested whole blood by PCR for pneumococcus in children aged 1-59 months hospitalized with signs of pneumonia and in age-frequency matched community controls. The distribution of load among PCR-positive participants was compared between microbiologically confirmed pneumococcal pneumonia (MCPP) cases, cases confirmed for nonpneumococcal pathogens, nonconfirmed cases, and controls. Receiver operating characteristic analyses determined the “optimal threshold” that distinguished MCPP cases from controls. Results.: Load was available for 290 of 291 cases with pneumococcal PCR detected in blood and 273 of 273 controls. Load was higher in MCPP cases than controls (median, 4.0 x 103 vs 0.19 x 103 copies/mL), but overlapped substantially (range, 0.16-989.9 x 103 copies/mL and 0.01-551.9 x 103 copies/mL, respectively). The proportion with high load (>/=2.2 log10 copies/mL) was 62.5% among MCPP cases, 4.3% among nonconfirmed cases, 9.3% among cases confirmed for a nonpneumococcal pathogen, and 3.1% among controls. Pneumococcal load in blood was not associated with respiratory tract illness in controls (P = .32). High blood pneumococcal load was associated with alveolar consolidation on chest radiograph in nonconfirmed cases, and with high (>6.9 log10 copies/mL) nasopharyngeal/oropharyngeal load and C-reactive protein >/=40 mg/L (both P < .01) in nonconfirmed cases but not controls. Conclusions.: Quantitative pneumococcal PCR in blood has limited diagnostic utility for identifying pneumococcal pneumonia in individual children, but may be informative in epidemiological studies.

      6. Safety of induced sputum collection in children hospitalized with severe or very severe pneumonia
        DeLuca AN, Hammitt LL, Kim J, Higdon MM, Baggett HC, Brooks WA, Howie SR, Deloria Knoll M, Kotloff KL, Levine OS, Madhi SA, Murdoch DR, Scott JA, Thea DM, Amornintapichet T, Awori JO, Chuananon S, Driscoll AJ, Ebruke BE, Hossain L, Jahan Y, Kagucia EW, Kazungu S, Moore DP, Mudau A, Mwananyanda L, Park DE, Prosperi C, Seidenberg P, Sylla M, Tapia MD, Zaman SM, O’Brien KL.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S301-s308.
        Background.: Induced sputum (IS) may provide diagnostic information about the etiology of pneumonia. The safety of this procedure across a heterogeneous population with severe pneumonia in low- and middle-income countries has not been described. Methods.: IS specimens were obtained as part a 7-country study of the etiology of severe and very severe pneumonia in hospitalized children <5 years of age. Rigorous clinical monitoring was done before, during, and after the procedure to record oxygen requirement, oxygen saturation, respiratory rate, consciousness level, and other evidence of clinical deterioration. Criteria for IS contraindications were predefined and serious adverse events (SAEs) were reported to ethics committees and a central safety monitor. Results.: A total of 4653 IS procedures were done among 3802 children. Thirteen SAEs were reported in relation to collection of IS, or 0.34% of children with at least 1 IS specimen collected (95% confidence interval, 0.15%-0.53%). A drop in oxygen saturation that required supplemental oxygen was the most common SAE. One child died after feeding was reinitiated 2 hours after undergoing sputum induction; this death was categorized as “possibly related” to the procedure. Conclusions.: The overall frequency of SAEs was very low, and the nature of most SAEs was manageable, demonstrating a low-risk safety profile for IS collection even among severely ill children in low-income-country settings. Healthcare providers should monitor oxygen saturation and requirements during and after IS collection, and assess patients prior to reinitiating feeding after the IS procedure, to ensure patient safety.

      7. Effect of point-of-care CD4 cell count results on linkage to care and antiretroviral initiation during a home-based HIV testing campaign: a non-blinded, cluster-randomised trial
        Desai MA, Okal DO, Rose CE, Ndivo R, Oyaro B, Otieno FO, Williams T, Chen RT, Zeh C, Samandari T.
        Lancet HIV. 2017 May 31.
        BACKGROUND: HIV disease staging with referral laboratory-based CD4 cell count testing is a key barrier to the initiation of antiretroviral treatment (ART). Point-of-care CD4 cell counts can improve linkage to HIV care among people living with HIV, but its effect has not been assessed with a randomised controlled trial in the context of home-based HIV counselling and testing (HBCT). METHODS: We did a two-arm, cluster-randomised, controlled efficacy trial in two districts of western Kenya with ongoing HBCT. Housing compounds were randomly assigned (1:1) to point-of-care CD4 cell counts (366 compounds with 417 participants) or standard-of-care (318 compounds with 353 participants) CD4 cell counts done at one of three referral laboratories serving the study catchment area. In each compound, we enrolled people with HIV not engaged in care in the previous 6 months. All participants received post-test counselling and referral for HIV care. Point-of-care test participants received additional counselling on the result, including ART eligibility if CD4 was less than 350 cells per muL, the cutoff in Kenyan guidelines. Participants were interviewed 6 months after enrolment to ascertain whether they sought HIV care, verified through chart reviews at 23 local clinics. The prevalence of loss to follow-up at 6 months (LTFU) was listed as the main outcome in the study protocol. We analysed linkage to care at 6 months (defined as 1-LTFU) as the primary outcome. All analyses were by intention to treat. This trial is registered at, number NCT02515149. FINDINGS: We enrolled 770 participants between July 1, 2013, and Feb 28, 2014. 692 (90%) had verified linkage to care status and 78 (10%) were lost to follow-up. Of 371 participants in the point-of-care group, 215 (58%) had linked to care within 6 months versus 108 (34%) of 321 in the standard-of-care group (Cox proportional multivariable hazard ratio [HR] 2.14, 95% CI 1.67-2.74; log rank p<0.0001). INTERPRETATION: Point-of-care CD4 cell counts in a resource-limited HBCT setting doubled linkage to care and thereby improved ART initiation. Given the substantial economic and logistic hindrances to providing ART for all people with HIV in resource-limited settings in the near term, point of care CD4 cell counts might have a role in prioritising care and improving linkage to care. FUNDING: US Centers for Disease Control and Prevention.

      8. First newborn baby to receive experimental therapies survives Ebola virus disease
        Dornemann J, Burzio C, Ronsse A, Sprecher A, De Clerck H, Van Herp M, Kolie MC, Yosifiva V, Caluwaerts S, McElroy AK, Antierens A.
        J Infect Dis. 2017 Jan 15;215(2):171-174.
        A neonate born to an Ebola virus-positive woman was diagnosed with Ebola virus infection on her first day of life. The patient was treated with monoclonal antibodies (ZMapp), a buffy coat transfusion from an Ebola survivor, and the broad-spectrum antiviral GS-5734. On day 20, a venous blood specimen tested negative for Ebola virus by quantitative reverse-transcription polymerase chain reaction. The patient was discharged in good health on day 33 of life. Further follow-up consultations showed age-appropriate weight gain and neurodevelopment at the age of 12 months. This patient is the first neonate documented to have survived congenital infection with Ebola virus.

      9. The effect of antibiotic exposure and specimen volume on the detection of bacterial pathogens in children with pneumonia
        Driscoll AJ, Deloria Knoll M, Hammitt LL, Baggett HC, Brooks WA, Feikin DR, Kotloff KL, Levine OS, Madhi SA, O’Brien KL, Scott JA, Thea DM, Howie SR, Adrian PV, Ahmed D, DeLuca AN, Ebruke BE, Gitahi C, Higdon MM, Kaewpan A, Karani A, Karron RA, Mazumder R, McLellan J, Moore DP, Mwananyanda L, Park DE, Prosperi C, Rhodes J, Saifullah M, Seidenberg P, Sow SO, Tamboura B, Zeger SL, Murdoch DR.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S368-s377.
        Background.: Antibiotic exposure and specimen volume are known to affect pathogen detection by culture. Here we assess their effects on bacterial pathogen detection by both culture and polymerase chain reaction (PCR) in children. Methods.: PERCH (Pneumonia Etiology Research for Child Health) is a case-control study of pneumonia in children aged 1-59 months investigating pathogens in blood, nasopharyngeal/oropharyngeal (NP/OP) swabs, and induced sputum by culture and PCR. Antibiotic exposure was ascertained by serum bioassay, and for cases, by a record of antibiotic treatment prior to specimen collection. Inoculated blood culture bottles were weighed to estimate volume. Results.: Antibiotic exposure ranged by specimen type from 43.5% to 81.7% in 4223 cases and was detected in 2.3% of 4863 controls. Antibiotics were associated with a 45% reduction in blood culture yield and approximately 20% reduction in yield from induced sputum culture. Reduction in yield of Streptococcus pneumoniae from NP culture was approximately 30% in cases and approximately 32% in controls. Several bacteria had significant but marginal reductions (by 5%-7%) in detection by PCR in NP/OP swabs from both cases and controls, with the exception of S. pneumoniae in exposed controls, which was detected 25% less frequently compared to nonexposed controls. Bacterial detection in induced sputum by PCR decreased 7% for exposed compared to nonexposed cases. For every additional 1 mL of blood culture specimen collected, microbial yield increased 0.51% (95% confidence interval, 0.47%-0.54%), from 2% when volume was </=1 mL to approximately 6% for >/=3 mL. Conclusions.: Antibiotic exposure and blood culture volume affect detection of bacterial pathogens in children with pneumonia and should be accounted for in studies of etiology and in clinical management.

      10. Standardization of laboratory methods for the PERCH Study
        Driscoll AJ, Karron RA, Morpeth SC, Bhat N, Levine OS, Baggett HC, Brooks WA, Feikin DR, Hammitt LL, Howie SR, Knoll MD, Kotloff KL, Madhi SA, Scott JA, Thea DM, Adrian PV, Ahmed D, Alam M, Anderson TP, Antonio M, Baillie VL, Dione M, Endtz HP, Gitahi C, Karani A, Kwenda G, Maiga AA, McClellan J, Mitchell JL, Morailane P, Mugo D, Mwaba J, Mwansa J, Mwarumba S, Nyongesa S, Panchalingam S, Rahman M, Sawatwong P, Tamboura B, Toure A, Whistler T, O’Brien KL, Murdoch DR.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S245-s252.
        The Pneumonia Etiology Research for Child Health study was conducted across 7 diverse research sites and relied on standardized clinical and laboratory methods for the accurate and meaningful interpretation of pneumonia etiology data. Blood, respiratory specimens, and urine were collected from children aged 1-59 months hospitalized with severe or very severe pneumonia and community controls of the same age without severe pneumonia and were tested with an extensive array of laboratory diagnostic tests. A standardized testing algorithm and standard operating procedures were applied across all study sites. Site laboratories received uniform training, equipment, and reagents for core testing methods. Standardization was further assured by routine teleconferences, in-person meetings, site monitoring visits, and internal and external quality assurance testing. Targeted confirmatory testing and testing by specialized assays were done at a central reference laboratory.

      11. Chest radiograph findings in childhood pneumonia cases from the multisite PERCH Study
        Fancourt N, Deloria Knoll M, Baggett HC, Brooks WA, Feikin DR, Hammitt LL, Howie SR, Kotloff KL, Levine OS, Madhi SA, Murdoch DR, Scott JA, Thea DM, Awori JO, Barger-Kamate B, Chipeta J, DeLuca AN, Diallo M, Driscoll AJ, Ebruke BE, Higdon MM, Jahan Y, Karron RA, Mahomed N, Moore DP, Nahar K, Naorat S, Ominde MS, Park DE, Prosperi C, Wa Somwe S, Thamthitiwat S, Zaman SM, Zeger SL, O’Brien KL.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S262-s270.
        Background: Chest radiographs (CXRs) are frequently used to assess pneumonia cases. Variations in CXR appearances between epidemiological settings and their correlation with clinical signs are not well documented. Methods: The Pneumonia Etiology Research for Child Health project enrolled 4232 cases of hospitalized World Health Organization (WHO)-defined severe and very severe pneumonia from 9 sites in 7 countries (Bangladesh, the Gambia, Kenya, Mali, South Africa, Thailand, and Zambia). At admission, each case underwent a standardized assessment of clinical signs and pneumonia risk factors by trained health personnel, and a CXR was taken that was interpreted using the standardized WHO methodology. CXRs were categorized as abnormal (consolidation and/or other infiltrate), normal, or uninterpretable. Results: CXRs were interpretable in 3587 (85%) cases, of which 1935 (54%) were abnormal (site range, 35%-64%). Cases with abnormal CXRs were more likely than those with normal CXRs to have hypoxemia (45% vs 26%), crackles (69% vs 62%), tachypnea (85% vs 80%), or fever (20% vs 16%) and less likely to have wheeze (30% vs 38%; all P < .05). CXR consolidation was associated with a higher case fatality ratio at 30-day follow-up (13.5%) compared to other infiltrate (4.7%) or normal (4.9%) CXRs. Conclusions: Clinically diagnosed pneumonia cases with abnormal CXRs were more likely to have signs typically associated with pneumonia. However, CXR-normal cases were common, and clinical signs considered indicative of pneumonia were present in substantial proportions of these cases. CXR-consolidation cases represent a group with an increased likelihood of death at 30 days post-discharge.

      12. Standardized interpretation of chest radiographs in cases of pediatric pneumonia from the PERCH Study
        Fancourt N, Deloria Knoll M, Barger-Kamate B, de Campo J, de Campo M, Diallo M, Ebruke BE, Feikin DR, Gleeson F, Gong W, Hammitt LL, Izadnegahdar R, Kruatrachue A, Madhi SA, Manduku V, Matin FB, Mahomed N, Moore DP, Mwenechanya M, Nahar K, Oluwalana C, Ominde MS, Prosperi C, Sande J, Suntarattiwong P, O’Brien KL.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S253-s261.
        Background.: Chest radiographs (CXRs) are a valuable diagnostic tool in epidemiologic studies of pneumonia. The World Health Organization (WHO) methodology for the interpretation of pediatric CXRs has not been evaluated beyond its intended application as an endpoint measure for bacterial vaccine trials. Methods.: The Pneumonia Etiology Research for Child Health (PERCH) study enrolled children aged 1-59 months hospitalized with WHO-defined severe and very severe pneumonia from 7 low- and middle-income countries. An interpretation process categorized each CXR into 1 of 5 conclusions: consolidation, other infiltrate, both consolidation and other infiltrate, normal, or uninterpretable. Two members of a 14-person reading panel, who had undertaken training and standardization in CXR interpretation, interpreted each CXR. Two members of an arbitration panel provided additional independent reviews of CXRs with discordant interpretations at the primary reading, blinded to previous reports. Further discordance was resolved with consensus discussion. Results.: A total of 4172 CXRs were obtained from 4232 cases. Observed agreement for detecting consolidation (with or without other infiltrate) between primary readers was 78% (kappa = 0.50) and between arbitrators was 84% (kappa = 0.61); agreement for primary readers and arbitrators across 5 conclusion categories was 43.5% (kappa = 0.25) and 48.5% (kappa = 0.32), respectively. Disagreement was most frequent between conclusions of other infiltrate and normal for both the reading panel and the arbitration panel (32% and 30% of discordant CXRs, respectively). Conclusions.: Agreement was similar to that of previous evaluations using the WHO methodology for detecting consolidation, but poor for other infiltrates despite attempts at a rigorous standardization process.

      13. Is higher viral load in the upper respiratory tract associated with severe pneumonia? Findings From the PERCH Study
        Feikin DR, Fu W, Park DE, Shi Q, Higdon MM, Baggett HC, Brooks WA, Deloria Knoll M, Hammitt LL, Howie SR, Kotloff KL, Levine OS, Madhi SA, Scott JA, Thea DM, Adrian PV, Antonio M, Awori JO, Baillie VL, DeLuca AN, Driscoll AJ, Ebruke BE, Goswami D, Karron RA, Li M, Morpeth SC, Mwaba J, Mwansa J, Prosperi C, Sawatwong P, Sow SO, Tapia MD, Whistler T, Zaman K, Zeger SL, O’ Brien KL, Murdoch DR.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S337-s346.
        Background.: The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization-defined severe and very severe pneumonia and age-matched community controls. Methods.: In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. Results.: The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. Conclusions.: Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia.

      14. The enduring challenge of determining pneumonia etiology in children: Considerations for future research priorities
        Feikin DR, Hammitt LL, Murdoch DR, O’Brien KL, Scott JA.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S188-s196.
        Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations.

      15. A comparison of postelimination measles epidemiology in the United States, 2009-2014 versus 2001-2008
        Fiebelkorn AP, Redd SB, Gastanaduy PA, Clemmons N, Rota PA, Rota JS, Bellini WJ, Wallace GS.
        J Pediatric Infect Dis Soc. 2017 Mar 01;6(1):40-48.
        Background: Measles, a vaccine-preventable disease that can cause severe complications, was declared eliminated from the United States in 2000. The last published summary of US measles epidemiology was during 2001-2008. We summarized US measles epidemiology during 2009-2014. Methods: We compared demographic, vaccination, and virologic data on confirmed measles cases reported to the Centers for Disease Control and Prevention during January 1, 2009-December 31, 2014 and January 1, 2001-December 31, 2008. Results: During 2009-2014, 1264 confirmed measles cases were reported in the United States, including 275 importations from 58 countries and 66 outbreaks. The annual median number of cases and outbreaks during this period was 130 (range, 55-667 cases) and 10 (range, 4-23 outbreaks), respectively, compared with an annual median of 56 cases (P = .08) and 4 outbreaks during 2001-2008 (P = .04). Among US-resident case-patients during 2009-2014, children aged 12-15 months had the highest measles incidence (65 cases; 8.3 cases/million person-years), and infants aged 6-11 months had the second highest incidence (86 cases; 7.3 cases/million person-years). During 2009-2014, 865 (74%) of 1173 US-resident case-patients were unvaccinated and 188 (16%) had unknown vaccination status; of 917 vaccine-eligible US-resident case-patients, 600 (65%) were reported as having philosophical or religious objections to vaccination. Conclusions: Although the United States has maintained measles elimination since 2000, measles outbreaks continue to occur globally, resulting in imported cases and potential spread. The annual median number of cases and outbreaks more than doubled during 2009-2014 compared with the earlier postelimination years. To maintain elimination, it will be necessary to maintain high 2-dose vaccination coverage, continue case-based surveillance, and monitor the patterns and rates of vaccine exemption.

      16. Notes from the field: Two cases of Legionnaires’ disease in newborns after water births – Arizona, 2016
        Granseth G, Bhattarai R, Sylvester T, Prasai S, Livar E.
        MMWR Morb Mortal Wkly Rep. 2017 Jun 09;66(22):590-591.

        [No abstract]

      17. Addressing the analytic challenges of cross-sectional pediatric pneumonia etiology data
        Hammitt LL, Feikin DR, Scott JA, Zeger SL, Murdoch DR, O’Brien KL, Deloria Knoll M.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S197-s204.
        Despite tremendous advances in diagnostic laboratory technology, identifying the pathogen(s) causing pneumonia remains challenging because the infected lung tissue cannot usually be sampled for testing. Consequently, to obtain information about pneumonia etiology, clinicians and researchers test specimens distant to the site of infection. These tests may lack sensitivity (eg, blood culture, which is only positive in a small proportion of children with pneumonia) and/or specificity (eg, detection of pathogens in upper respiratory tract specimens, which may indicate asymptomatic carriage or a less severe syndrome, such as upper respiratory infection). While highly sensitive nucleic acid detection methods and testing of multiple specimens improve sensitivity, multiple pathogens are often detected and this adds complexity to the interpretation as the etiologic significance of results may be unclear (ie, the pneumonia may be caused by none, one, some, or all of the pathogens detected). Some of these challenges can be addressed by adjusting positivity rates to account for poor sensitivity or incorporating test results from controls without pneumonia to account for poor specificity. However, no classical analytic methods can account for measurement error (ie, sensitivity and specificity) for multiple specimen types and integrate the results of measurements for multiple pathogens to produce an accurate understanding of etiology. We describe the major analytic challenges in determining pneumonia etiology and review how the common analytical approaches (eg, descriptive, case-control, attributable fraction, latent class analysis) address some but not all challenges. We demonstrate how these limitations necessitate a new, integrated analytical approach to pneumonia etiology data.

      18. Should controls with respiratory symptoms be excluded from case-control studies of pneumonia etiology? Reflections from the PERCH Study
        Higdon MM, Hammitt LL, Deloria Knoll M, Baggett HC, Brooks WA, Howie SR, Kotloff KL, Levine OS, Madhi SA, Murdoch DR, Scott JA, Thea DM, Driscoll AJ, Karron RA, Park DE, Prosperi C, Zeger SL, O’Brien KL, Feikin DR.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S205-s212.
        Many pneumonia etiology case-control studies exclude controls with respiratory illness from enrollment or analyses. Herein we argue that selecting controls regardless of respiratory symptoms provides the least biased estimates of pneumonia etiology. We review 3 reasons investigators may choose to exclude controls with respiratory symptoms in light of epidemiologic principles of control selection and present data from the Pneumonia Etiology Research for Child Health (PERCH) study where relevant to assess their validity. We conclude that exclusion of controls with respiratory symptoms will result in biased estimates of etiology. Randomly selected community controls, with or without respiratory symptoms, as long as they do not meet the criteria for case-defining pneumonia, are most representative of the general population from which cases arose and the least subject to selection bias.

      19. Association of C-reactive protein with bacterial and respiratory syncytial virus-associated pneumonia among children aged <5 years in the PERCH Study
        Higdon MM, Le T, O’Brien KL, Murdoch DR, Prosperi C, Baggett HC, Brooks WA, Feikin DR, Hammitt LL, Howie SR, Kotloff KL, Levine OS, Scott JA, Thea DM, Awori JO, Baillie VL, Cascio S, Chuananon S, DeLuca AN, Driscoll AJ, Ebruke BE, Endtz HP, Kaewpan A, Kahn G, Karani A, Karron RA, Moore DP, Park DE, Rahman MZ, Salaudeen R, Seidenberg P, Somwe SW, Sylla M, Tapia MD, Zeger SL, Deloria Knoll M, Madhi SA.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S378-s386.
        Background.: Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods.: We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for “confirmed” bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to “RSV pneumonia” (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Results.: Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP >/=40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP >/=40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP >/=100 mg/L substantially improved specificity over CRP >/=40 mg/L, though at a loss to sensitivity. Conclusions.: Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study.

      20. Shiga toxin-producing Escherichia coli (STEC) causes an estimated 265 000 infections in the United States annually. Of emerging non-O157:H7 STEC serotypes, O26 is the most commonly recognized. During an outbreak of STEC O26 in Oregon in 2015, we used syndromic surveillance data to supplement case finding by laboratory reporting. From 157 records retrieved by querying syndromic surveillance data, we detected 4 confirmed and 5 suspected cases. However, none of the suspected cases were confirmed by stool culture, and by the time that the data were being analyzed, the confirmed cases were already known to investigators. Syndromic surveillance data can potentially supplement case finding during outbreaks of foodborne disease. To be an effective case-finding strategy, timely completion of all steps, including collecting specimens from suspected cases, should be performed in real time.

      21. Retinol binding protein and vitamin D were measured in children aged <5 years hospitalized with lower respiratory tract infection and respiratory syncytial virus and/or human metapneumovirus detections. Low vitamin levels were observed in 50% of the children and were associated with significantly elevated risk of the need for intensive care unit admission and invasive mechanical ventilation.

      22. OBJECTIVES: Drug-susceptibility testing (DST) of Mycobacterium tuberculosis is necessary for identifying drug-resistant tuberculosis, administering effective treatment regimens, and preventing the spread of drug-resistant tuberculosis. DST is recommended for all culture-confirmed cases of tuberculosis. We examined trends in delayed and unreported DST results in the Centers for Disease Control and Prevention’s National Tuberculosis Surveillance System. METHODS: We analyzed culture-confirmed tuberculosis cases reported to the National Tuberculosis Surveillance System during 1993-2014 for annual trends in initial DST reporting for first-line antituberculosis drugs and trends in on-time, delayed, and unreported results. We defined on-time reporting as DST results received during the same calendar year in which the patient’s case was reported or </=4 months after the calendar year ended and delayed reporting as DST results received after the calendar year. We compared cases with on-time, delayed, and unreported DST results by patient and tuberculosis program characteristics. RESULTS: The proportion of cases with reported results for all first-line antituberculosis drugs increased during 1993-2011. Reporting of pyrazinamide results was lower than reporting of other drugs. However, during 2000-2012, of 134 787 tuberculosis cases reported to the National Tuberculosis Surveillance System, reporting was on time for 125 855 (93.4%) cases, delayed for 5332 (4.0%) cases, and unreported for 3600 (2.7%) cases. CONCLUSIONS: Despite increases in the proportion of cases with on-time DST results, delayed and unreported results persisted. Carefully assessing causes for delayed and unreported DST results should lead to more timely reporting of drug-resistant tuberculosis.

      23. Coccidioidomycosis: An underreported cause of death-Arizona, 2008-2013
        Jones JM, Koski L, Khan M, Brady S, Sunenshine R, Komatsu KK.
        Med Mycol. 2017 Jun 08.
        In Arizona during 1997-2013, coccidioidomycosis increased from 21 to 90 cases/100,000 population, but coccidioidomycosis-associated deaths remained stable at 3-6 deaths/million population. We used the capture-recapture method by using death certificates and hospital discharge data to more fully estimate the total number of coccidioidomycosis-attributable deaths and compared this with published estimates. Death certificates were included if any cause of death included coccidioidomycosis; hospital discharge data deaths were included if any discharge diagnosis included coccidioidomycosis and laboratory confirmation. Among deaths during 2008-2013, we identified 529 coccidioidomycosis-attributable deaths from death certificates and 560 from hospital discharge data, with 251 deaths identified in both databases. Capture-recapture estimated 1,178 total coccidioidomycosis-attributable deaths, compared with 164 deaths (underlying cause of death) or 529 deaths (any cause of death) on death certificates. Coccidioidomycosis-attributable deaths are underreported from two- to sevenfold on Arizona death certificates, demonstrating an education need for death certifiers to document coccidioidomycosis mortality.

      24. Forgotten but not gone: Update on measles infection for hospitalists
        Kobaidze K, Wallace G.
        J Hosp Med. 2017 Jun;12(6):472-476.
        Measles (rubeola) continues to be endemic and epidemic in many regions of the world. Measles is primarily a disease of childhood, but it can also affect adult populations, and therefore it is important that both adult and pediatric hospitalist physicians be able to recognize it. Although the disease is rarely encountered in the United States, measles infection can spread rapidly across vulnerable populations. In addition, infected adults can develop complications that may require hospitalization for treatment. This review summarizes the typical clinical course and complications of measles infection, along with recommendations for diagnosis and management for both adult and pediatric hospitalists. Journal of Hospital Medicine 2017;12:472-476.

      25. Pharmacodynamic optimization for treatment of invasive Candida auris infection
        Lepak AJ, Zhao M, Berkow EL, Lockhart SR, Andes DR.
        Antimicrob Agents Chemother. 2017 Jun 05.
        Candida auris is an emerging, multidrug-resistant threat. The pharmacodynamics of three antifungal classes against nine C. auris strains was explored using a murine invasive candidiasis model. The total drug median PD target associated with net stasis was a fluconazole AUC/MIC of 26, amphotericin B Cmax/MIC of 0.9, and micafungin AUC/MIC of 54. The micafungin PD targets for C. auris were >/=20-fold lower than other Candida species in this animal model. Clinically relevant micafungin exposures produced the most killing among the three classes.

      26. Prevalence of hepatitis B antiviral drug resistance variants in North American patients with chronic hepatitis B not receiving antiviral treatment
        Lok AS, Ganova-Raeva L, Cloonan Y, Punkova L, Lin HS, Lee WM, Ghany MG.
        J Viral Hepat. 2017 Jun 05.
        Antiviral drug resistance HBV variants (HBV-DR) occur spontaneously in chronic hepatitis B (CHB) patients and after exposure to nucleos(t)ide analogues (NUCs). We determined the prevalence of HBV-DR variants among participants of the Hepatitis B Research Network (HBRN) Cohort Study conducted at 21 sites in the United States (US) and Canada. Samples obtained from 1342 CHB participants aged >/=18 years, and who were currently not receiving NUCs, were tested for HBV-DR variants by Sanger sequencing. In addition, next generation sequencing (NGS) was used to characterize HBV-DR variants from 66 participants with and 66 participants with no prior NUC exposure matched for HBV genotype and HBV DNA level. Half the participants were men, 75% Asian, 26% HBeAg-positive. Primary HBV-DR variants were detected by Sanger sequencing in 16 (1.2%) participants: 2/142 (1.4%) with and 14/1200 (1.2%) without prior NUC exposure; only 1 of these 16 had a secondary variant. In total, 23 (1.7%) participants had secondary variants, including 1 with prior NUC experience. In the subset of 132 participants, NGS detected HBV-DR variants in a higher proportion of participants: primary variants in 18 (13.6%) [8 (12.1%) with, and 10 (15.2%) without prior NUC therapy], and secondary variants in 10 (7.6%) participants. Based on Sanger sequencing, prevalence of primary HBV-DR variants is low (1.2%) among adults with CHB in US/Canada. The similar low prevalence of HBV-DR variants in participants with and without NUC treatment suggests transmission of these variants is uncommon.

      27. Thailand national guidelines for the prevention of mother-to-child transmission of HIV 2017

        Lolekha R, Chokephaibulkit K, Phanuphak N, Chaithongwongwatthana S, Kietiburanakul S, Chetchotisakd P, Boonsuk S.
        Asian Biomedicine. 2017 April;11(2):145-159.
        Background: Thailand validated the elimination of mother-to-child transmission (MTCT) of HIV in June 2016 (meeting World Health Organization target < 2%). The Thailand National HIV Guidelines Working Group issued a new version of its national Prevention of MTCT guidelines in December 2016 aimed to reduce MTCT rate to less than 1% by 2020. Objectives: To organize national stakeholders for a new MTCT of HIV to further reduce MTCT of HIV Methods: The US CDC, Division of Global HIV/AIDS, medical scores, the Thai Red Cross AIDS Research Centers, and the Ministry of Public Health collaborated to develop Thailand National Guidelines for prevention of MTCT of HIV Results: The guidelines included recommending initiation antepartum highly active antiretroviral therapy (HAART) containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC) plus efavirenz (EFV) regardless of CD4 cell count as soon as HIV is diagnosed for antiretroviral treatment (ART) naive HIV-infected pregnant women. An alternative regimen is TDF or zidovudine (AZT) plus 3TC plus lopinavir/ritonavir (LPV/r) for the HIV-infected pregnant woman suspected to have NNRTI resistance. Treatment should be started immediately irrespective of gestational age and continue after delivery for life. Raltegravir is recommended in addition to HAART regimen for HIV-infected pregnant women who present late at ANC (gestational age (GA) >= 32 weeks) or those who have viral load (VL) > 1000 copies/mL at GA > 32 weeks. HIV-infected pregnant women who conceive while receiving HAART should continue this effective treatment regimen during pregnancy. HIV-infected pregnant women who present in labor and do not receiving HAART should receive single-dose nevira pine (SD-NVP) immediately along with oral AZT, initiate and continue HAART for life. Infants born to HIV-infected mothers are categorized into two groups (high risk vs. standard risk) based on their risk for MTCT. High MTCT risk is defined as an infant whose mother has VL > 50 copies/mL at GA > 36 weeks or has received HAART less than 12 weeks prior to delivery, or has poor ART adherence. These infants should be initiated AZT plus 3TC plus NVP for six weeks after delivery. Infants with standard MTCT risk should receive AZT syrup for 4 weeks. Exclusive formula feeding is recommended for all HIV-exposed infants. Conclusions: In addition to ARV therapy, other coordinated care are essential to further reduce MTCT of HIV in Thailand.

      28. Increasing availability of prevention to communities disproportionately affected by HIV
        McCree DH, Purcell DW, Cleveland JC, Brooks JT.
        Am J Public Health. 2017 Jul;107(7):1027-1028.

        [No abstract]

      29. The incremental value of repeated induced sputum and gastric aspirate samples for the diagnosis of pulmonary tuberculosis in young children with acute community-acquired pneumonia
        Moore DP, Higdon MM, Hammitt LL, Prosperi C, DeLuca AN, Da Silva P, Baillie VL, Adrian PV, Mudau A, Deloria Knoll M, Feikin DR, Murdoch DR, O’Brien KL, Madhi SA.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S309-s316.
        Background.: Mycobacterium tuberculosis (Mtb) contributes to the pathogenesis of childhood acute community-acquired pneumonia in settings with a high tuberculosis burden. The incremental value of a repeated induced sputum (IS) sample, compared with a single IS or gastric aspirate (GA) sample, is not well known. Methods.: Two IS samples were obtained for Mtb culture from children enrolled as cases in the Pneumonia Etiology Research for Child Health (PERCH) study in South Africa. Nonstudy attending physicians requested GA if pulmonary tuberculosis was clinically suspected. We compared the Mtb yield of 2 IS samples to that of 1 IS sample and GA samples. Results: . Twenty-seven (3.0%) culture-confirmed pulmonary tuberculosis cases were identified among 906 children investigated with IS and GA samples for Mtb. Results from 2 IS samples were available for 719 children (79.4%). Of 12 culture-confirmed pulmonary tuberculosis cases identified among children with >/=2 IS samples, 4 (33.3%) were negative at the first IS sample. In head-to-head comparisons among children with both GA and IS samples collected, the yield of 1 GA sample (8 of 427; 1.9%) was similar to that of 1 IS sample (5 of 427, 1.2%), and the yield of 2 GA samples (10 of 300; 3.3%) was similar to that of 2 IS samples (5 of 300; 1.7%). IS samples identified 8 (42.1%) of the 19 culture-confirmed pulmonary tuberculosis cases that were identified through submission of IS and GA samples. Conclusions.: A single IS sample underestimated the presence of Mtb in children hospitalized with severe or very severe pneumonia. Detection of Mtb is enhanced by combining 2 IS with GA sample collections in young children with acute severe pneumonia.

      30. Detection of pneumococcal DNA in blood by polymerase chain reaction for diagnosing pneumococcal pneumonia in young children from low- and middle-income countries
        Morpeth SC, Deloria Knoll M, Scott JA, Park DE, Watson NL, Baggett HC, Brooks WA, Feikin DR, Hammitt LL, Howie SR, Kotloff KL, Levine OS, Madhi SA, O’Brien KL, Thea DM, Adrian PV, Ahmed D, Antonio M, Bunthi C, DeLuca AN, Driscoll AJ, Githua LP, Higdon MM, Kahn G, Karani A, Karron RA, Kwenda G, Makprasert S, Mazumder R, Moore DP, Mwansa J, Nyongesa S, Prosperi C, Sow SO, Tamboura B, Whistler T, Zeger SL, Murdoch DR.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S347-s356.
        Background.: We investigated the performance of polymerase chain reaction (PCR) on blood in the diagnosis of pneumococcal pneumonia among children from 7 low- and middle-income countries. Methods.: We tested blood by PCR for the pneumococcal autolysin gene in children aged 1-59 months in the Pneumonia Etiology Research for Child Health (PERCH) study. Children had World Health Organization-defined severe or very severe pneumonia or were age-frequency-matched community controls. Additionally, we tested blood from general pediatric admissions in Kilifi, Kenya, a PERCH site. The proportion PCR-positive was compared among cases with microbiologically confirmed pneumococcal pneumonia (MCPP), cases without a confirmed bacterial infection (nonconfirmed), cases confirmed for nonpneumococcal bacteria, and controls. Results.: In PERCH, 7.3% (n = 291/3995) of cases and 5.5% (n = 273/4987) of controls were blood pneumococcal PCR-positive (P < .001), compared with 64.3% (n = 36/56) of MCPP cases and 6.3% (n = 243/3832) of nonconfirmed cases (P < .001). Blood pneumococcal PCR positivity was higher in children from the 5 African countries (5.5%-11.5% among cases and 5.3%-10.2% among controls) than from the 2 Asian countries (1.3% and 1.0% among cases and 0.8% and 0.8% among controls). Among Kilifi general pediatric admissions, 3.9% (n = 274/6968) were PCR-positive, including 61.7% (n = 37/60) of those with positive blood cultures for pneumococcus. Discussion.: The utility of pneumococcal PCR on blood for diagnosing childhood pneumococcal pneumonia in the 7 low- and middle-income countries studied is limited by poor specificity and by poor sensitivity among MCPP cases.

      31. The diagnostic utility of induced sputum microscopy and culture in childhood pneumonia
        Murdoch DR, Morpeth SC, Hammitt LL, Driscoll AJ, Watson NL, Baggett HC, Brooks WA, Deloria Knoll M, Feikin DR, Kotloff KL, Levine OS, Madhi SA, O’Brien KL, Scott JA, Thea DM, Adrian PV, Ahmed D, Alam M, Awori JO, DeLuca AN, Higdon MM, Karron RA, Kwenda G, Machuka EM, Makprasert S, McLellan J, Moore DP, Mwaba J, Mwarumba S, Park DE, Prosperi C, Sangwichian O, Sissoko S, Tapia MD, Zeger SL, Howie SR.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S280-s288.
        Background.: Sputum microscopy and culture are commonly used for diagnosing the cause of pneumonia in adults but are rarely performed in children due to difficulties in obtaining specimens. Induced sputum is occasionally used to investigate lower respiratory infections in children but has not been widely used in pneumonia etiology studies. Methods.: We evaluated the diagnostic utility of induced sputum microscopy and culture in patients enrolled in the Pneumonia Etiology Research for Child Health (PERCH) study, a large study of community-acquired pneumonia in children aged 1-59 months. Comparisons were made between induced sputum samples from hospitalized children with radiographically confirmed pneumonia and children categorized as nonpneumonia (due to the absence of prespecified clinical and laboratory signs and absence of infiltrate on chest radiograph). Results.: One induced sputum sample was available for analysis from 3772 (89.1%) of 4232 suspected pneumonia cases enrolled in PERCH. Of these, sputum from 2608 (69.1%) met the quality criterion of <10 squamous epithelial cells per low-power field, and 1162 (44.6%) had radiographic pneumonia. Induced sputum microscopy and culture results were not associated with radiographic pneumonia, regardless of prior antibiotic use, stratification by specific bacteria, or interpretative criteria used. Conclusions.: The findings of this study do not support the culture of induced sputum specimens as a diagnostic tool for pneumonia in young children as part of routine clinical practice.

      32. Microscopic analysis and quality assessment of induced sputum from children with pneumonia in the PERCH Study
        Murdoch DR, Morpeth SC, Hammitt LL, Driscoll AJ, Watson NL, Baggett HC, Brooks WA, Deloria Knoll M, Feikin DR, Kotloff KL, Levine OS, Madhi SA, O’Brien KL, Scott JA, Thea DM, Ahmed D, Awori JO, DeLuca AN, Ebruke BE, Higdon MM, Jorakate P, Karron RA, Kazungu S, Kwenda G, Hossain L, Makprasert S, Moore DP, Mudau A, Mwaba J, Panchalingam S, Park DE, Prosperi C, Salaudeen R, Toure A, Zeger SL, Howie SR.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S271-s279.
        Background.: It is standard practice for laboratories to assess the cellular quality of expectorated sputum specimens to check that they originated from the lower respiratory tract. The presence of low numbers of squamous epithelial cells (SECs) and high numbers of polymorphonuclear (PMN) cells are regarded as indicative of a lower respiratory tract specimen. However, these quality ratings have never been evaluated for induced sputum specimens from children with suspected pneumonia. Methods.: We evaluated induced sputum Gram stain smears and cultures from hospitalized children aged 1-59 months enrolled in a large study of community-acquired pneumonia. We hypothesized that a specimen representative of the lower respiratory tract will contain smaller quantities of oropharyngeal flora and be more likely to have a predominance of potential pathogens compared to a specimen containing mainly saliva. The prevalence of potential pathogens cultured from induced sputum specimens and quantity of oropharyngeal flora were compared for different quantities of SECs and PMNs. Results.: Of 3772 induced sputum specimens, 2608 (69%) had <10 SECs per low-power field (LPF) and 2350 (62%) had >25 PMNs per LPF, measures traditionally associated with specimens from the lower respiratory tract in adults. Using isolation of low quantities of oropharyngeal flora and higher prevalence of potential pathogens as markers of higher quality, <10 SECs per LPF (but not >25 PMNs per LPF) was the microscopic variable most associated with high quality of induced sputum. Conclusions.: Quantity of SECs may be a useful quality measure of induced sputum from young children with pneumonia.

      33. Mycoplasma hominis Infections transmitted through amniotic tissue product
        Novosad SA, Basavaraju SV, Annambhotla P, Mohr M, Halpin A, Foy L, Chmielewski R, Winchell JM, Benitez AJ, Morrison SS, Johnson T, Crabb DM, Ratliff AE, Waites K, Kuehnert MJ.
        Clin Infect Dis. 2017 May 31.
        Background: Mycoplasma hominis is a commensal genitourinary tract organism that can cause infections outside the genitourinary tract. We investigated a cluster of M. hominis surgical site infections in patients who underwent spine surgery, all associated with amniotic tissue linked to a common donor. Methods: Laboratory tests of tissue product from the donor, including culture, quantitative real-time PCR (qPCR), and whole genome sequencing were performed. Use of this amniotic tissue product was reviewed. A multi-state investigation to identify additional cases and locate any unused products was conducted. Results: Twenty-seven tissue product vials from a donor were distributed to facilities in seven states; at least 20 vials from this donor were used in 14 patients. Of these, 4/14 (29%) developed surgical site infections, including two M. hominis infections. M. hominis was detected by culture and qPCR in two unused vials from the donor. Sequencing indicated >99% similarity between patient and unopened vial isolates. For five of 27 (19%) vials, the final disposition could not be confirmed. Conclusions: M. hominis was transmitted through amniotic tissue from a single donor to two recipients. Current routine donor screening and product testing does not detect all potential pathogens. Clinicians should be aware that M. hominis can cause surgical site infections, and may not be detected by routine clinical cultures. The lack of a standardized system to track tissue products in healthcare facilities limits the ability of public health agencies to respond to outbreaks and investigate other adverse events associated with these products.

      34. Introduction to the epidemiologic considerations, analytic methods, and foundational results from the Pneumonia Etiology Research for Child Health Study
        O’Brien KL, Baggett HC, Brooks WA, Feikin DR, Hammitt LL, Howie SR, Deloria Knoll M, Kotloff KL, Levine OS, Madhi SA, Murdoch DR, Scott JA, Thea DM, Zeger SL.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S179-s184.

        [No abstract]

      35. Colonization density of the upper respiratory tract as a predictor of pneumonia-Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii
        Park DE, Baggett HC, Howie SR, Shi Q, Watson NL, Brooks WA, Deloria Knoll M, Hammitt LL, Kotloff KL, Levine OS, Madhi SA, Murdoch DR, O’Brien KL, Scott JA, Thea DM, Ahmed D, Antonio M, Baillie VL, DeLuca AN, Driscoll AJ, Fu W, Gitahi CW, Olutunde E, Higdon MM, Hossain L, Karron RA, Maiga AA, Maloney SA, Moore DP, Morpeth SC, Mwaba J, Mwenechanya M, Prosperi C, Sylla M, Thamthitiwat S, Zeger SL, Feikin DR.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S328-s336.
        Background.: There is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii. Methods.: In 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR). Differences in median colonization density were evaluated using the Wilcoxon rank-sum test. Density cutoffs were determined using receiver operating characteristic curves. Cases with a pathogen identified from lung aspirate culture or PCR, pleural fluid culture or PCR, blood culture, and immunofluorescence for P. jirovecii defined microbiologically confirmed cases for the given pathogens. Results.: Higher densities of H. influenzae were observed in both microbiologically confirmed cases and chest radiograph (CXR)-positive cases compared to controls. Staphylococcus aureus and P. jirovecii had higher densities in CXR-positive cases vs controls. A 5.9 log10 copies/mL density cutoff for H. influenzae yielded 86% sensitivity and 77% specificity for detecting microbiologically confirmed cases; however, densities overlapped between cases and controls and positive predictive values were poor (<3%). Informative density cutoffs were not found for S. aureus and M. catarrhalis, and a lack of confirmed case data limited the cutoff identification for P. jirovecii. Conclusions.: There is evidence for an association between H. influenzae colonization density and H. influenzae-confirmed pneumonia in children; the association may be particularly informative in epidemiologic studies. Colonization densities of M. catarrhalis, S. aureus, and P. jirovecii are unlikely to be of diagnostic value in clinical settings.

      36. We conducted a systematic review and meta-analysis of the association between serosorting and HIV infection among HIV-negative men who have sex with men (MSM). Compared to no condomless anal sex (i.e., consistent condom use or no anal sex), serosorting was associated with increased HIV risk (RR = 1.64, 95% CI 1.37-1.96). Compared to condomless discordant anal sex, serosorting was associated with reduced HIV risk (RR = 0.46, 95% CI 0.33-0.65). Serosorting may be an important harm reduction strategy when condoms are not consistently used, but can be harmful if HIV-negative MSM who consistently use condoms shift to using serosorting as their primary prevention strategy. The protective effects of serosorting and ways in which MSM are operationalizing serosorting are becoming more complex as additional factors affecting risk are considered (e.g., durable viral load suppression, PrEP). Understanding the potential risk and benefit of serosorting continues to be important, particularly within the context of other prevention strategies.

      37. High rate of treatment completion in program settings with 12-dose weekly isoniazid and rifapentine (3HP) for latent Mycobacterium tuberculosis infection
        Sandul AL, Nwana N, Holcombe JM, Lobato MN, Marks S, Webb R, Wang SH, Stewart B, Griffin P, Hunt G, Shah N, Marco A, Patil N, Mukasa L, Moro RN, Jereb J, Mase S, Chorba T, Bamrah-Morris S, Ho CS.
        Clin Infect Dis. 2017 May 30.
        Background: RCTs demonstrated the newest LTBI regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), as efficacious as 9 months of isoniazid (9H) with a greater completion rate (82% versus 69%); however, 3HP has not been assessed in routine health care settings. Methods: Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions (ADRs), and factors associated with treatment discontinuation. Results: Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children 2-17 years had the highest completion rate, 94.5% (155/164). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% CI, 0.23-0.85]; P = .014), and highest in persons >/=65 years (RR, 1.72 [95% CI, 1.25-2.35] P = .001). In multivariable analyses, discontinuation was lowest among contacts of patients with TB disease (adjusted relative risk [ARR], 0.68 [95% CI, 0.52-0.89]; P = .005), and students (ARR, 0.45 [95% CI, 0.21-0.98]; P = .044); highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P=.013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). ADRs were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions: Completion of 3HP in routine health care settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

      38. Using a programmatic mapping approach to plan for HIV prevention and harm reduction interventions for people who inject drugs in three South African cities
        Scheibe A, Shelly S, Lambert A, Schneider A, Basson R, Medeiros N, Padayachee K, Savva H, Hausler H.
        Harm Reduct J. 2017 Jun 07;14(1):35.
        BACKGROUND: Stigma, criminalisation and a lack of data on drug use contribute to the “invisibility” of people who inject drugs (PWID) and make HIV prevention and treatment service delivery challenging. We aimed to confirm locations where PWID congregate in Cape Town, eThekwini and Tshwane (South Africa) and to estimate PWID population sizes within selected electoral wards in these areas to inform South Africa’s first multi-site HIV prevention project for PWID. METHODS: Field workers (including PWID peers) interviewed community informants to identify suspected injecting locations in selected electoral wards in each city and then visited these locations and interviewed PWID. Interviews were used to gather information about the accessibility of sterile injecting equipment, location coordinates and movement patterns. We used the Delphi method to obtain final population size estimates for the mapped wards based on estimates from wisdom of the crowd methods, the literature and programmatic data. RESULTS: Between January and April 2015, we mapped 45 wards. Tshwane teams interviewed 39 PWID in 12 wards, resulting in an estimated number of accessible PWID ranging from 568 to 1431. In eThekwini, teams interviewed 40 PWID in 15 wards with an estimated number of accessible PWID ranging from 184 to 350. The Cape Town team interviewed 61 PWID in 18 wards with an estimated number of accessible PWID ranging between 398 and 503. Sterile needles were only available at one location. Almost all needles were bought from pharmacies. Between 80 and 86% of PWID frequented more than one location per day. PWID who reported movement visited a median of three locations a day. CONCLUSIONS: Programmatic mapping led by PWID peers can be used effectively to identify and reach PWID and build relationships where access to HIV prevention commodities for PWID is limited. PWID reported limited access to sterile injecting equipment, highlighting an important HIV prevention need. Programmatic mapping data show that outreach programmes should be flexible and account for the mobile nature of PWID populations. The PWID population size estimates can be used to develop service delivery targets and as baseline measures.

      39. Vital Signs: Health care-associated Legionnaires’ disease surveillance data from 20 states and a large metropolitan area – United States, 2015
        Soda EA, Barskey AE, Shah PP, Schrag S, Whitney CG, Arduino MJ, Reddy SC, Kunz JM, Hunter CM, Raphael BH, Cooley LA.
        MMWR Morb Mortal Wkly Rep. 2017 Jun 09;66(22):584-589.
        BACKGROUND: Legionnaires’ disease, a severe pneumonia, is typically acquired through inhalation of aerosolized water containing Legionella bacteria. Legionella can grow in the complex water systems of buildings, including health care facilities. Effective water management programs could prevent the growth of Legionella in building water systems. METHODS: Using national surveillance data, Legionnaires’ disease cases were characterized from the 21 jurisdictions (20 U.S. states and one large metropolitan area) that reported exposure information for >/=90% of 2015 Legionella infections. An assessment of whether cases were health care-associated was completed; definite health care association was defined as hospitalization or long-term care facility residence for the entire 10 days preceding symptom onset, and possible association was defined as any exposure to a health care facility for a portion of the 10 days preceding symptom onset. All other Legionnaires’ disease cases were considered unrelated to health care. RESULTS: A total of 2,809 confirmed Legionnaires’ disease cases were reported from the 21 jurisdictions, including 85 (3%) definite and 468 (17%) possible health care-associated cases. Among the 21 jurisdictions, 16 (76%) reported 1-21 definite health care-associated cases per jurisdiction. Among definite health care-associated cases, the majority (75, 88%) occurred in persons aged >/=60 years, and exposures occurred at 72 facilities (15 hospitals and 57 long-term care facilities). The case fatality rate was 25% for definite and 10% for possible health care-associated Legionnaires’ disease. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Exposure to Legionella from health care facility water systems can result in Legionnaires’ disease. The high case fatality rate of health care-associated Legionnaires’ disease highlights the importance of case prevention and response activities, including implementation of effective water management programs and timely case identification.

      40. Uptake of and factors associated with direct-acting antiviral therapy among patients in the Chronic Hepatitis Cohort Study, 2014 to 2015
        Spradling PR, Xing J, Rupp LB, Moorman AC, Gordon SC, Lu M, Teshale EH, Boscarino JA, Schmidt MA, Daida YG, Holmberg SD.
        J Clin Gastroenterol. 2017 Jun 05.
        BACKGROUND: Limited information is available describing the uptake of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection among patients in general US health care settings. We determined the proportion of HCV-infected patients in the Chronic Hepatitis Cohort Study prescribed DAAs in 2014, who initiated treatment and identified characteristics associated with treatment initiation. METHODS: Uptake was defined as the proportion of HCV-infected patients with at least 1 clinical encounter in 2013 who were prescribed a DAA regimen during 2014 and initiated the regimen by August 2015. Using multivariable analysis, we examined demographic and clinical characteristics associated with receipt of DAAs. RESULTS: The cohort comprised 9508 patients; 544 (5.7%) started a DAA regimen. Higher annual income [adjusted odds ratios (aOR) 2.3 for income>$50K vs. <$30K], higher Fibrosis-4 score (aORs, 2.1, 2.0, and 1.4 for Fibrosis-4, >5.88, 3.25 to 5.88, 2.0 to 3.25, respectively, vs. <2.0), genotype 2 infection (aOR 2.2 vs. genotype 1), pre-2014 treatment failure (aOR 2.0 vs. treatment-naive), and human immunodeficiency virus (HIV) coinfection (aOR 1.8 vs. HCV monoinfection) were associated with DAA initiation. Black race/ethnicity (aOR 0.7 vs. whites) and Medicaid coverage (aOR 0.5 vs. private insurance) were associated with noninitiation. Sex, age, comorbidity, previous liver transplant, and duration of follow-up were not associated with receipt of DAAs. CONCLUSIONS: Among patients in these general US health care settings, uptake of DAA therapy was low in 2014, and especially so among minority and Medicaid patients. Systemic efforts to improve access to DAAs for all patients are essential to reduce morbidity and mortality from HCV infection.

      41. Limited utility of polymerase chain reaction in induced sputum specimens for determining the causes of childhood pneumonia in resource-poor settings: Findings from the Pneumonia Etiology Research for Child Health (PERCH) Study
        Thea DM, Seidenberg P, Park DE, Mwananyanda L, Fu W, Shi Q, Baggett HC, Brooks WA, Feikin DR, Howie SR, Knoll MD, Kotloff KL, Levine OS, Madhi SA, O’Brien KL, Scott JA, Antonio M, Awori JO, Baillie VL, DeLuca AN, Driscoll AJ, Higdon MM, Hossain L, Jahan Y, Karron RA, Kazungu S, Li M, Moore DP, Morpeth SC, Ofordile O, Prosperi C, Sangwichian O, Sawatwong P, Sylla M, Tapia MD, Zeger SL, Murdoch DR, Hammitt LL.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S289-s300.
        Background.: Sputum examination can be useful in diagnosing the cause of pneumonia in adults but is less well established in children. We sought to assess the diagnostic utility of polymerase chain reaction (PCR) for detection of respiratory viruses and bacteria in induced sputum (IS) specimens from children hospitalized with severe or very severe pneumonia. Methods.: Among children aged 1-59 months, we compared organism detection by multiplex PCR in IS and nasopharyngeal/oropharyngeal (NP/OP) specimens. To assess whether organism presence or density in IS specimens was associated with chest radiographic evidence of pneumonia (radiographic pneumonia), we compared prevalence and density in IS specimens from children with radiographic pneumonia and children with suspected pneumonia but without chest radiographic changes or clinical or laboratory findings suggestive of pneumonia (nonpneumonia group). Results.: Among 4232 cases with World Health Organization-defined severe or very severe pneumonia, we identified 1935 (45.7%) with radiographic pneumonia and 573 (13.5%) with nonpneumonia. The organism detection yield was marginally improved with IS specimens (96.2% vs 92.4% for NP/OP specimens for all viruses combined [P = .41]; 96.9% vs 93.3% for all bacteria combined [P = .01]). After accounting for presence in NP/OP specimens, no organism was detected more frequently in the IS specimens from the radiographic pneumonia compared with the nonpneumonia cases. Among high-quality IS specimens, there were no statistically significant differences in organism density, except with cytomegalovirus, for which there was a higher quantity in the IS specimens from cases with radiographic pneumonia compared with the nonpneumonia cases (median cycle threshold value, 27.9 vs 28.5, respectively; P = .01). Conclusions.: Using advanced molecular methods with IS specimens provided little additional diagnostic information beyond that obtained with NP/OP swab specimens.

      42. Perceived message effectiveness to evaluate updated concepts for a national HIV testing campaign for African American women

        Uhrig JD, Leeks KD, Stryker JE, Shadle J, Bann CM.
        J Commun Healthc. 2017 :1-11.
        The U.S. Centers for Disease Control and Prevention launched Take Charge. Take the Test.?, a national, communication campaign focused on the overarching goal of increasing HIV testing among African American women in March 2012. We surveyed 200 members of the campaign?s priority audience to inform selection of updated concepts for the campaign. Two of the potential concepts (Love Yourself More and Look Out for Yourself) were updated versions of the original campaign concepts, and three (Control of My Life, Personal Potential, and Strong Sisters) were newly developed. Look Out for Yourself and Love Yourself More had the highest mean ratings on the perceived effectiveness scale (PES) and were not significantly different from each other. Control of My Life had the third highest mean rating on the PES and was not significantly different from Love Yourself More. All three concepts were rated significantly higher than Personal Potential and Strong Sisters (P?<?0.01). Across all concepts, prior intentions to get tested in the next 6 months was a positive, statistically significant predictor of the PES (P?<?0.001). Higher perceived effectiveness was significantly associated with agreement that the concept motivated the respondent to get tested for HIV across all five concepts (P?<?0.001). The findings support framing HIV testing as a matter of personal responsibility and emphasizing the importance of getting tested so that women can be there to participate in their children?s lives as effective messaging strategies for African American women.

      43. Data management and data quality in PERCH, a large international case-control study of severe childhood pneumonia
        Watson NL, Prosperi C, Driscoll AJ, Higdon MM, Park DE, Sanza M, DeLuca AN, Awori JO, Goswami D, Hammond E, Hossain L, Johnson C, Kamau A, Kuwanda L, Moore DP, Neyzari O, Onwuchekwa U, Parker D, Sapchookul P, Seidenberg P, Shamsul A, Siazeele K, Srisaengchai P, Sylla M, Levine OS, Murdoch DR, O’Brien KL, Wolff M, Deloria Knoll M.
        Clin Infect Dis. 2017 Jun 15;64(suppl_3):S238-s244.
        The Pneumonia Etiology Research for Child Health (PERCH) study is the largest multicountry etiology study of pediatric pneumonia undertaken in the past 3 decades. The study enrolled 4232 hospitalized cases and 5325 controls over 2 years across 9 research sites in 7 countries in Africa and Asia. The volume and complexity of data collection in PERCH presented considerable logistical and technical challenges. The project chose an internet-based data entry system to allow real-time access to the data, enabling the project to monitor and clean incoming data and perform preliminary analyses throughout the study. To ensure high-quality data, the project developed comprehensive quality indicator, data query, and monitoring reports. Among the approximately 9000 cases and controls, analyzable laboratory results were available for >/=96% of core specimens collected. Selected approaches to data management in PERCH may be extended to the planning and organization of international studies of similar scope and complexity.

      44. Ebola virus disease contact tracing activities, lessons learned and best practices during the Duport Road outbreak in Monrovia, Liberia, November 2015
        Wolfe CM, Hamblion EL, Schulte J, Williams P, Koryon A, Enders J, Sanor V, Wapoe Y, Kwayon D, Blackey D, Laney AS, Weston EJ, Dokubo EK, Davies-Wayne G, Wendland A, Daw VT, Badini M, Clement P, Mahmoud N, Williams D, Gasasira A, Nyenswah TG, Fallah M.
        PLoS Negl Trop Dis. 2017 Jun 02;11(6):e0005597.
        BACKGROUND: Contact tracing is one of the key response activities necessary for halting Ebola Virus Disease (EVD) transmission. Key elements of contact tracing include identification of persons who have been in contact with confirmed EVD cases and careful monitoring for EVD symptoms, but the details of implementation likely influence their effectiveness. In November 2015, several months after a major Ebola outbreak was controlled in Liberia, three members of a family were confirmed positive for EVD in the Duport Road area of Monrovia. The cluster provided an opportunity to implement and evaluate modified approaches to contact tracing. METHODS: The approaches employed for improved contact tracing included classification and risk-based management of identified contacts (including facility based isolation of some high risk contacts, provision of support to persons being monitored, and school-based surveillance for some persons with potential exposure but not listed as contacts), use of phone records to help locate missing contacts, and modifications to data management tools. We recorded details about the implementation of these approaches, report the overall outcomes of the contact tracing efforts and the challenges encountered, and provide recommendations for management of future outbreaks. RESULTS: 165 contacts were identified (with over 150 identified within 48 hours of confirmation of the EVD cases) and all initially missing contacts were located. Contacts were closely monitored and promptly tested if symptomatic; no contacts developed disease. Encountered challenges related to knowledge gaps among contact tracing staff, data management, and coordination of contact tracing activities with efforts to offer Ebola vaccine. CONCLUSIONS: The Duport Road EVD cluster was promptly controlled. Missing contacts were effectively identified, and identified contacts were effectively monitored and rapidly tested. There is a persistent risk of EVD reemergence in Liberia; the experience controlling each cluster can help inform future Ebola control efforts in Liberia and elsewhere.

    • Disease Reservoirs and Vectors RSS Word feed
      1. Ebola virus field sample collection
        Amman BR, Schuh AJ, Towner JS.
        Methods Mol Biol. 2017 ;1628:373-393.
        Sampling wildlife for ebolaviruses presents the researcher with a multitude of challenges, foremost of which is safety. Throughout the methods described in this chapter, personal safety and personal protective equipment (PPE) will be reiterated for each methodology. The methods described here are those used to successfully detect and isolate marburgviruses from their natural reservoir, Rousettus aegyptiacus, and therefore should be applicable for diagnostic testing for ebolaviruses via RT-PCR, ELISA, and IHC techniques.Although an ebolavirus natural reservoir has yet to be identified, the majority of disease ecologists believe the reservoir to belong to the order Chiroptera (bats). The methods presented in this chapter are presented with bats as an example, but all of these methods would be applicable to other species of wildlife with few or no modifications.

      2. International workshop on insecticide resistance in vectors of arboviruses, December 2016, Rio de Janeiro, Brazil
        Corbel V, Fonseca DM, Weetman D, Pinto J, Achee NL, Chandre F, Coulibaly MB, Dusfour I, Grieco J, Juntarajumnong W, Lenhart A, Martins AJ, Moyes C, Ng LC, Raghavendra K, Vatandoost H, Vontas J, Muller P, Kasai S, Fouque F, Velayudhan R, Durot C, David JP.
        Parasit Vectors. 2017 Jun 02;10(1):278.
        Vector-borne diseases transmitted by insect vectors such as mosquitoes occur in over 100 countries and affect almost half of the world’s population. Dengue is currently the most prevalent arboviral disease but chikungunya, Zika and yellow fever show increasing prevalence and severity. Vector control, mainly by the use of insecticides, play a key role in disease prevention but the use of the same chemicals for more than 40 years, together with the dissemination of mosquitoes by trade and environmental changes, resulted in the global spread of insecticide resistance. In this context, innovative tools and strategies for vector control, including the management of resistance, are urgently needed. This report summarizes the main outputs of the first international workshop on Insecticide resistance in vectors of arboviruses held in Rio de Janeiro, Brazil, 5-8 December 2016. The primary aims of this workshop were to identify strategies for the development and implementation of standardized insecticide resistance management, also to allow comparisons across nations and across time, and to define research priorities for control of vectors of arboviruses. The workshop brought together 163 participants from 28 nationalities and was accessible, live, through the web (> 70,000 web-accesses over 3 days).

      3. The role of ticks in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus: A review of published field and laboratory studies
        Gargili A, Estrada-Pena A, Spengler JR, Lukashev A, Nuttall PA, Bente DA.
        Antiviral Res. 2017 Jun 01;144:93-119.
        This manuscript is part of a series of reviews that aim to cover published research on Crimean-Congo hemorrhagic fever (CCHF) and its etiological agent, CCHF virus (CCHFV). The virus is maintained and transmitted in a vertical and horizontal transmission cycle involving a variety of wild and domestic vertebrate species that act as amplification hosts, without showing signs of illness. These vertebrates have traditionally been considered reservoirs of CCHFV, but in fact they develop only a transient viremia, while the virus can persist in ticks for their entire lifespan, and can also be transmitted vertically to the next generation. As a result, ticks are now considered to be both the vector and the reservoir for the virus. CCHFV has been detected in a wide range of tick species, but only a few have been proven to be vectors and reservoirs, mainly because most published studies have been performed under a broad variety of conditions, precluding definitive characterization. This article reviews the published literature, summarizes current knowledge of the role of ticks in CCHFV maintenance and transmission and provides guidance for how to fill the knowledge gaps. Special focus is given to existing data on tick species in which vertical passage has been demonstrated under natural or experimental conditions. At the same time, we identify earlier reports that used unreliable methods and perceptions to ascribe a vector role to some species of ticks, and have contributed to confusion regarding viral transmission. We also examine epidemiological pathways of CCHFV circulation and discuss priority areas for future research.

    • Environmental Health RSS Word feed
      1. Bacteria in a water-damaged building: associations of actinomycetes and non-tuberculous mycobacteria with respiratory health in occupants
        Park JH, Cox-Ganser JM, White SK, Laney AS, Caulfield SM, Turner WA, Sumner AD, Kreiss K.
        Indoor Air. 2017 Jan;27(1):24-33.
        We examined microbial correlates of health outcomes in building occupants with a sarcoidosis cluster and excess asthma. We offered employees a questionnaire and pulmonary function testing and collected floor dust and liquid/sludge from drain tubing traps of heat pumps that were analyzed for various microbial agents. Forty-nine percent of participants reported any symptom reflecting possible granulomatous disease (shortness of breath on exertion, flu-like achiness, or fever and chills) weekly in the last 4 weeks. In multivariate regressions, thermophilic actinomycetes (median = 529 CFU/m2 ) in dust were associated with FEV1 /FVC [coefficient = -2.8 per interquartile range change, P = 0.02], percent predicted FEF25-75% (coefficient = -12.9, P = 0.01), and any granulomatous disease-like symptom [odds ratio (OR) = 3.1, 95% confidence interval (CI) = 1.45-6.73]. Mycobacteria (median = 658 CFU/m2 ) were positively associated with asthma symptoms (OR = 1.5, 95% CI = 0.97-2.43). Composite score (median = 11.5) of total bacteria from heat pumps was negatively associated with asthma (0.8, 0.71-1.00) and positively associated with FEV1 /FVC (coefficient = 0.44, P = 0.095). Endotoxin (median score = 12.0) was negatively associated with two or more granulomatous disease-like symptoms (OR = 0.8, 95% CI = 0.67-0.98) and asthma (0.8, 0.67-0.96). Fungi or (1–>3)-beta-D-glucan in dust or heat pump traps was not associated with any health outcomes. Thermophilic actinomycetes and non-tuberculous mycobacteria may have played a role in the occupants’ respiratory outcomes in this water-damaged building.

    • Genetics and Genomics RSS Word feed
      1. Genome-wide association study to identify variants associated with vaso-occlusive pain in sickle cell anemia
        Chaturvedi S, Bhatnagar P, Bean CJ, Steinberg MH, Milton JN, Casella JF, Barron-Casella E, Arking DE, DeBaun MR.
        Blood. 2017 Jun 05.

        [No abstract]

      2. Invasive serotype 35B pneumococci including an expanding serotype switch lineage, United States, 2015-2016
        Chochua S, Metcalf BJ, Li Z, Walker H, Tran T, McGee L, Beall B.
        Emerg Infect Dis. 2017 Jun;23(6):922-930.
        We used whole-genome sequencing to characterize 199 nonvaccine serotype 35B pneumococcal strains that caused invasive pneumococcal disease (IPD) in the United States during 2015-2016 and related these findings to previous serotype 35B IPD data obtained by Active Bacterial Core surveillance. Penicillin-nonsusceptible 35B IPD increased during post-pneumococcal 7-valent conjugate vaccine years (2001-2009) and increased further after implementation of pneumococcal 13-valent conjugate vaccine in 2010. This increase was caused primarily by the 35B/sequence type (ST) 558 lineage. 35B/ST558 and vaccine serotype 9V/ST156 lineages were implicated as cps35B donor and recipient, respectively, for a single capsular switch event that generated emergent 35B/ST156 progeny in 6 states during 2015-2016. Three additional capsular switch 35B variants were identified, 2 of which also involved 35B/ST558 as cps35B donor. Spread of 35B/ST156 is of concern in view of past global predominance of pathogenic ST156 vaccine serotype strains. Protection against serotype 35B should be considered in next-generation pneumococcal vaccines.

      3. Neisseria genomics: current status and future perspectives
        Harrison OB, Schoen C, Retchless AC, Wang X, Jolley KA, Bray JE, Maiden MC.
        Pathog Dis. 2017 Jun 07.
        High-throughput whole genome sequencing has unlocked a multitude of possibilities enabling members of the Neisseria genus to be examined with unprecedented detail, including the human pathogens Neisseria meningitidis and Neisseria gonorrhoeae. To maximise the potential benefit of this for public health, it is becoming increasingly important to ensure that this plethora of data are adequately stored, disseminated and made readily accessible. Investigations facilitating cross-species comparisons as well as the analysis of global datasets will allow differences among and within species and across geographic locations and different times to be identified, improving our understanding of the distinct phenotypes observed. Recent advances in high-throughput platforms that measure the transcriptome, proteome and/or epigenome are also becoming increasingly employed to explore the complexities of Neisseria biology. An integrated approach to the analysis of these is essential to fully understand the impact these may have in the Neisseria genus. This article reviews the current status of some of the tools available for next generation sequence analysis at the dawn of the ‘post-genomic’ era.

      4. Efficient detection of viral transmissions with Next-Generation Sequencing data
        Rytsareva I, Campo DS, Zheng Y, Sims S, Thankachan SV, Tetik C, Chirag J, Chockalingam SP, Sue A, Aluru S, Khudyakov Y.
        BMC Genomics. 2017 May 24;18(Suppl 4):372.
        BACKGROUND: Hepatitis C is a major public health problem in the United States and worldwide. Outbreaks of hepatitis C virus (HCV) infections associated with unsafe injection practices, drug diversion, and other exposures to blood are difficult to detect and investigate. Molecular analysis has been frequently used in the study of HCV outbreaks and transmission chains; helping identify a cluster of sequences as linked by transmission if their genetic distances are below a previously defined threshold. However, HCV exists as a population of numerous variants in each infected individual and it has been observed that minority variants in the source are often the ones responsible for transmission, a situation that precludes the use of a single sequence per individual because many such transmissions would be missed. The use of Next-Generation Sequencing immensely increases the sensitivity of transmission detection but brings a considerable computational challenge because all sequences need to be compared among all pairs of samples. METHODS: We developed a three-step strategy that filters pairs of samples according to different criteria: (i) a k-mer bloom filter, (ii) a Levenhstein filter and (iii) a filter of identical sequences. We applied these three filters on a set of samples that cover the spectrum of genetic relationships among HCV cases, from being part of the same transmission cluster, to belonging to different subtypes. RESULTS: Our three-step filtering strategy rapidly removes 85.1% of all the pairwise sample comparisons and 91.0% of all pairwise sequence comparisons, accurately establishing which pairs of HCV samples are below the relatedness threshold. CONCLUSIONS: We present a fast and efficient three-step filtering strategy that removes most sequence comparisons and accurately establishes transmission links of any threshold-based method. This highly efficient workflow will allow a faster response and molecular detection capacity, improving the rate of detection of viral transmissions with molecular data.

    • Health Economics RSS Word feed
      1. Cost projections for implementation of safety interventions to prevent transfusion-transmitted Zika virus infection in the United States
        Ellingson KD, Sapiano MR, Haass KA, Savinkina AA, Baker ML, Henry RA, Berger JJ, Kuehnert MJ, Basavaraju SV.
        Transfusion. 2017 Jun;57 Suppl 2:1625-1633.
        BACKGROUND: In August 2016, the Food and Drug Administration advised US blood centers to screen all whole blood and apheresis donations for Zika virus (ZIKV) with an individual-donor nucleic acid test (ID-NAT) or to use approved pathogen reduction technology (PRT). The cost of implementing this guidance nationally has not been assessed. STUDY DESIGN AND METHODS: Scenarios were constructed to characterize approaches to ZIKV screening, including universal ID-NAT, risk-based seasonal allowance of minipool (MP) NAT by state, and universal MP-NAT. Data from the 2015 National Blood Collection and Utilization Survey (NBCUS) were used to characterize the number of donations nationally and by state. For each scenario, the estimated cost per donor ($3-$9 for MP-NAT, $7-$13 for ID-NAT) was multiplied by the estimated number of relevant donations from the NBCUS. Cost of PRT was calculated by multiplying the cost per unit ($50-$125) by the number of units approved for PRT. Prediction intervals for costs were generated using Monte Carlo simulation methods. RESULTS: Screening all donations in the 50 states and DC for ZIKV by ID-NAT would cost $137 million (95% confidence interval [CI], $109-$167) annually. Allowing seasonal MP-NAT in states with lower ZIKV risk could reduce NAT screening costs by 18% to 25%. Application of PRT to all platelet (PLT) and plasma units would cost $213 million (95% CI, $156-$304). CONCLUSION: Universal ID-NAT screening for ZIKV will cost US blood centers more than $100 million annually. The high cost of PRT for apheresis PLTs and plasma could be mitigated if, once validated, testing for transfusion transmissible pathogens could be eliminated.

      2. HUD Housing Assistance associated with lower uninsurance rates and unmet medical need
        Simon AE, Fenelon A, Helms V, Lloyd PC, Rossen LM.
        Health Aff (Millwood). 2017 Jun 01;36(6):1016-1023.
        To investigate whether receiving US Department of Housing and Urban Development (HUD) housing assistance is associated with improved access to health care, we analyzed data on nondisabled adults ages 18-64 who responded to the 2004-12 National Health Interview Survey that were linked with administrative data from HUD for the period 2002-14. To account for potential selection bias, we compared access to care between respondents who were receiving HUD housing assistance at the time of the survey interview (current recipients) and those who received HUD assistance within twenty-four months of completing the survey interview (future recipients). Receiving assistance was associated with lower uninsurance rates: 31.8 percent of current recipients were uninsured, compared to 37.2 percent of future recipients. Rates of unmet need for health care due to cost were similarly lower for current recipients than for future recipients. No effect of receiving assistance was observed on having a usual source of care. These findings provide evidence that supports the effectiveness of housing assistance in improving health care access.

      3. Evaluation of unintended social and economic consequences of an unplanned school closure in rural Illinois
        Tsai V, Khan NM, Shi J, Rainey J, Gao H, Zheteyeva Y.
        J Sch Health. 2017 Jul;87(7):546-553.
        BACKGROUND: School closure is one of the primary measures considered during severe influenza pandemics and other emergencies. However, prolonged school closures may cause unintended adverse consequences to schools, students, and their families. A better understanding of these consequences will inform prepandemic planning, and help public health and education authorities in making informed decisions when considering school closures. METHODS: We conducted a household survey and interviewed school officials following an 8-day long closure of a school district in rural Illinois. We described household responses regarding difficulties of school closure, and summarized main themes from school official interviews. RESULTS: A total of 208 (27%) household surveys were completed and returned. This school closure caused difficulties to 36 (17%) households; uncertain duration of closure, childcare arrangements, and lost pay were the most often reported difficulties. Having 1 adult in the household losing pay and household income below $25,000 were significantly associated with overall difficulty during this school closure. Concern about student health and safety was the most frequent theme in school administrator interviews. CONCLUSIONS: Whereas the majority of responding households did not report difficulties during this school closure, households with 1 adult losing pay during the closure reported incurring additional expenses for childcare.

    • Immunity and Immunization RSS Word feed
      1. Penicillin resistance of nonvaccine type pneumococcus before and after PCV13 introduction, United States
        Andam CP, Worby CJ, Gierke R, McGee L, Pilishvili T, Hanage WP.
        Emerg Infect Dis. 2017 Jun;23(6):1012-1015.
        Introduction of 13-valent pneumococcal conjugate vaccine in the United States was not associated with a significant change in prevalence of penicillin resistance in nonvaccine type serotypes because of the variable success of highly resistant serotypes. Differences in regional serotype distribution and serotype-specific resistance contributed to geographic heterogeneity of penicillin resistance.

      2. Innate immune factors in mothers’ breast milk and their lack of association with rotavirus vaccine immunogenicity in Nicaraguan infants
        Becker-Dreps S, Choi WS, Stamper L, Vilchez S, Velasquez DE, Moon SS, Hudgens MG, Jiang B, Permar SR.
        J Pediatric Infect Dis Soc. 2017 Mar 01;6(1):87-90.
        To better understand underlying causes of lower rotavirus vaccine effectiveness in low-middle income countries (LMICs), we measured innate antiviral factors in Nicaraguan mothers’ milk and immune response to the first dose of the pentavalent rotavirus vaccine in corresponding infants. No relationship was found between concentrations of innate factors and rotavirus vaccine response.

      3. Japanese encephalitis surveillance and immunization – Asia and Western Pacific Regions, 2016
        Heffelfinger JD, Li X, Batmunkh N, Grabovac V, Diorditsa S, Liyanage JB, Pattamadilok S, Bahl S, Vannice KS, Hyde TB, Chu SY, Fox KK, Hills SL, Marfin AA.
        MMWR Morb Mortal Wkly Rep. 2017 Jun 09;66(22):579-583.
        Japanese encephalitis (JE) virus is the most important vaccine-preventable cause of encephalitis in the Asia-Pacific region. The World Health Organization (WHO) recommends integration of JE vaccination into national immunization schedules in all areas where the disease is a public health priority (1). This report updates a previous summary of JE surveillance and immunization programs in Asia and the Western Pacific in 2012 (2). Since 2012, funding for JE immunization has become available through the GAVI Alliance, three JE vaccines have been WHO-prequalified,* and an updated WHO JE vaccine position paper providing guidance on JE vaccines and vaccination strategies has been published (1). Data for this report were obtained from a survey of JE surveillance and immunization practices administered to health officials in countries with JE virus transmission risk, the 2015 WHO/United Nations Children’s Fund Joint Reporting Form on Immunization, notes and reports from JE meetings held during 2014-2016, published literature, and websites. In 2016, 22 (92%) of 24 countries with JE virus transmission risk conducted JE surveillance, an increase from 18 (75%) countries in 2012, and 12 (50%) countries had a JE immunization program, compared with 11 (46%) countries in 2012. Strengthened JE surveillance, continued commitment, and adequate resources for JE vaccination should help maintain progress toward prevention and control of JE.

    • Injury and Violence RSS Word feed
      1. CDC’s efforts to improve traumatic brain injury surveillance

        Bell JM, Breiding MJ, DePadilla L.
        J Safety Res. 2017 .
        Introduction: Youth sports concussion has become a prominent public health issue due to growing concern about the risk of long-term health effects. Method: A broad spectrum of stakeholders has convened to propose solutions, including a committee of the National Academy of Sciences (NAS) who systematically examined the issue and, in a 2014 report, made a series of recommendations to better address this public health problem. Results: Among these recommendations, the NAS committee called for CDC to develop a plan for a comprehensive surveillance system to better quantify the incidence and outcomes of youth sports concussion among children 5 to 21. years of age. Since the release of the NAS report, CDC has taken action to address this recommendation and, in the process, develop strategies to improve traumatic brain injury (TBI) surveillance more broadly. The challenges outlined by the NAS committee with respect to producing comprehensive incidence estimates of youth sports concussion are not exclusive to youth sports concussion, but also apply to TBI surveillance overall. In this commentary, we will discuss these challenges, the process CDC has undertaken to address them and describe our plan for improving TBI and youth sports concussion surveillance.

      2. Advancing the public’s health by scaling innovations in clinical quality
        Malcarney MB, Horton K, Seiler N, Hastings D.
        Public Health Rep. 2017 Jan 01.

        [No abstract]

    • Laboratory Sciences RSS Word feed
      1. Changes in vaginal community state types reflect major shifts in the microbiome
        Brooks JP, Buck GA, Chen G, Diao L, Edwards DJ, Fettweis JM, Huzurbazar S, Rakitin A, Satten GA, Smirnova E, Waks Z, Wright ML, Yanover C, Zhou YH.
        Microb Ecol Health Dis. 2017 ;28(1):1303265.
        Background: Recent studies of various human microbiome habitats have revealed thousands of bacterial species and the existence of large variation in communities of microorganisms in the same habitats across individual human subjects. Previous efforts to summarize this diversity, notably in the human gut and vagina, have categorized microbiome profiles by clustering them into community state types (CSTs). The functional relevance of specific CSTs has not been established. Objective: We investigate whether CSTs can be used to assess dynamics in the microbiome. Design: We conduct a re-analysis of five sequencing-based microbiome surveys derived from vaginal samples with repeated measures. Results: We observe that detection of a CST transition is largely insensitive to choices in methods for normalization or clustering. We find that healthy subjects persist in a CST for two to three weeks or more on average, while those with evidence of dysbiosis tend to change more often. Changes in CST can be gradual or occur over less than one day. Upcoming CST changes and switches to high-risk CSTs can be predicted with high accuracy in certain scenarios. Finally, we observe that presence of Gardnerella vaginalis is a strong predictor of an upcoming CST change. Conclusion: Overall, our results show that the CST concept is useful for studying microbiome dynamics.

      2. Multicenter performance assessment of Carba NP test
        Cunningham SA, Limbago B, Traczewski M, Anderson K, Hackel M, Hindler J, Sahm D, Alyanak E, Lawsin A, Gulvik CA, de Man TJ, Mandrekar JN, Schuetz AN, Jenkins S, Humphries R, Palavecino E, Vasoo S, Patel R.
        J Clin Microbiol. 2017 Jun;55(6):1954-1960.
        Eighty Gram-negative bacilli (54 Enterobacteriaceae and 26 nonfermenting Gram-negative bacilli) obtained from multiple institutions in the United States were distributed in a blinded manner to seven testing laboratories to compare their performance of a test for detection of carbapenemase production, the Carba NP test. The Carba NP test was performed by all laboratories, following the Clinical and Laboratory Standards Institute (CLSI) procedure. Site-versus-site comparisons demonstrated a high level of consistency for the Carba NP assay, with just 3/21 site comparisons yielding a difference in sensitivity (P < 0.05). Previously described limitations with blaOXA-48-like carbapenemases and blaOXA carbapenemases associated with Acinetobacter baumannii were noted. Based on these data, we demonstrate that the Carba NP test, when implemented with the standardized CLSI methodology, provides reproducible results across multiple sites for detection of carbapenemases.

      3. Continued decline in blood collection and transfusion in the United States-2015
        Ellingson KD, Sapiano MR, Haass KA, Savinkina AA, Baker ML, Chung KW, Henry RA, Berger JJ, Kuehnert MJ, Basavaraju SV.
        Transfusion. 2017 Jun;57 Suppl 2:1588-1598.
        BACKGROUND: In 2011 and 2013, the National Blood Collection and Utilization Survey (NBCUS) revealed declines in blood collection and transfusion in the United States. The objective of this study was to describe blood services in 2015. STUDY DESIGN AND METHODS: The 2015 NBCUS was distributed to all US blood collection centers, all hospitals performing at least 1000 surgeries annually, and a 40% random sample of hospitals performing 100 to 999 surgeries annually. Weighting and imputation were used to generate national estimates for units of blood and components collected, deferred, distributed, transfused, and outdated. RESULTS: Response rates for the 2015 NBCUS were 78.4% for blood collection centers and 73.9% for transfusing hospitals. In 2015, 12,591,000 units of red blood cells (RBCs) (95% confidence interval [CI], 11,985,000-13,197,000 units of RBCs) were collected, and 11,349,000 (95% CI, 10,592,000-11,747,000) were transfused, representing declines since 2013 of 11.6% and 13.9%, respectively. Total platelet units distributed (2,436,000; 95% CI, 2,230,000-2,642,000) and transfused (1,983,000; 95% CI, 1,816,000 = 2,151,000) declined by 0.5% and 13.1%, respectively, since 2013. Plasma distributions (3,714,000; 95% CI, 3,306,000-4,121,000) and transfusions (2,727,000; 95% CI, 2,594,000-2,859,000) in 2015 declined since 2013. The median price paid per unit in 2015-$211 for leukocyte-reduced RBCs, $524 for apheresis platelets, and $54 for fresh frozen plasma-was less for all components than in 2013. CONCLUSIONS: The 2015 NBCUS findings suggest that continued declines in demand for blood products resulted in fewer units collected and distributed Maintaining a blood inventory sufficient to meet routine and emergent demands will require further monitoring and understanding of these trends.

      4. Isolation of azole-resistant Aspergillus fumigatus from the environment in the south-eastern USA
        Hurst SF, Berkow EL, Stevenson KL, Litvintseva AP, Lockhart SR.
        J Antimicrob Chemother. 2017 Jun 01.
        Background: Azole resistance in isolates of the fungus Aspergillus fumigatus has been associated with agricultural use of azole fungicides. Environmental isolation of resistant isolates has been reported in Asia, Africa, Europe and South America. Objectives: To determine whether A. fumigatus isolates containing TR 34 /L98H or TR 46 /Y121F/T289A can be found in fields in the USA treated with agricultural azoles. Methods: Crop debris was collected and screened for A. fumigatus . All A. fumigatus isolates were screened for azole resistance. The CYP51A gene of azole-resistant isolates was sequenced. The population structure of a subset of isolates was determined using microsatellite typing. Results: This article identifies azole-resistant A. fumigatus isolates containing the TR 34 /L98H mutation in an experimental peanut field that had been treated with azole fungicides. Conclusions: These findings suggest the development of resistance to azole antifungals in A. fumigatus may be present where agricultural azoles are used in the USA.

      5. Supplemental findings from the National Blood Collection and Utilization Surveys, 2013 and 2015
        Sapiano MR, Savinkina AA, Ellingson KD, Haass KA, Baker ML, Henry RA, Berger JJ, Kuehnert MJ, Basavaraju SV.
        Transfusion. 2017 Jun;57 Suppl 2:1599-1624.

        [No abstract]

      6. Potential applications and human biosafety of nanomaterials used in nanomedicine
        Su H, Wang Y, Gu Y, Bowman L, Zhao J, Ding M.
        J Appl Toxicol. 2017 Jun 06.
        With the rapid development of nanotechnology, potential applications of nanomaterials in medicine have been widely researched in recent years. Nanomaterials themselves can be used as image agents or therapeutic drugs, and for drug and gene delivery, biological devices, nanoelectronic biosensors or molecular nanotechnology. As the composition, morphology, chemical properties, implant sites as well as potential applications become more and more complex, human biosafety of nanomaterials for clinical use has become a major concern. If nanoparticles accumulate in the human body or interact with the body molecules or chemical components, health risks may also occur. Accordingly, the unique chemical and physical properties, potential applications in medical fields, as well as human biosafety in clinical trials are reviewed in this study. Finally, this article tries to give some suggestions for future work in nanomedicine research.

      7. Rapid and sensitive detection of botulinum neurotoxins (BoNTs), which cause botulism, is essential in a public health emergency or bioterrorism event. We have previously developed a mass spectrometry (MS)-based functional method, Endopep-MS assay, for the fast detection and differentiation of all BoNT serotypes by affinity enriching the toxin and detecting the serotype-specific cleavage products of peptide substrates derived from the in vivo targets. To improve the performance of the Endopep-MS assay, we report here the further optimization of the peptide substrate for the detection of serotype A botulinum neurotoxins. An increased substrate cleavage was achieved by extending the original peptide N-terminus with optimized amino acid sequence, increasing the detection sensitivity of the method. In addition, the resistance of the substrate to nonspecific hydrolysis was dramatically improved by selectively substituting amino acids at the scissile bond and various other positions of the extended peptide. Moreover, incorporating the N-terminal hydrophobic residues dramatically improved the relative intensity of the cleavage products in the mass spectra. This allowed easy detection of the cleavage products, further enhancing the performance of the assay. The limit of detection for spiked serum sample was enhanced from 0.5 to 0.1 mouseLD50 and from 0.5 to 0.2 mouseLD50 for spiked stool. Graphical abstract Mass spectra of optimized and old peptide substrates with BoNT/A.

      8. Global and national laboratory networks support high quality surveillance for measles and rubella
        Xu W, Zhang Y, Wang H, Zhu Z, Mao N, Mulders MN, Rota PA.
        Int Health. 2017 May 01;9(3):184-189.
        Laboratory networks are an essential component of disease surveillance systems because they provide accurate and timely confirmation of infection. WHO coordinates global laboratory surveillance of vaccine preventable diseases, including measles and rubella. The more than 700 laboratories within the WHO Global Measles and Rubella Laboratory Network (GMRLN) supports surveillance for measles, rubella and congenial rubella syndrome in 191 counties. This paper describes the overall structure and function of the GMRLN and highlights the largest of the national laboratory networks, the China Measles and Rubella Laboratory Network.

      9. Ebola virus (EBOV) disease is a severe, acute human syndrome associated with high case fatality rates. Immune responses to EBOV are thought to be at least partially responsible for disease pathogenesis and must therefore be investigated to get a better understanding of underlying mechanisms of pathogenesis. Syrian hamsters are susceptible to EBOV infection and develop a disease more consistent with human EBOV disease than other rodent disease models. Quantitative RT-PCR (qRT-PCR) is ideal for monitoring immune responses during EBOV infection in low- to medium-throughput applications. A relatively straightforward protocol for monitoring immune responses, based on information gleaned from experimental EBOV infection of hamsters, is presented.

    • Occupational Safety and Health RSS Word feed
      1. Occupational allergy

        Anderson S, Long C, Dotson G.
        Eur Med J. 2017 ;2(2):65-71.
        An estimated 11 million workers in the USA are potentially exposed to agents that can become a cause of allergic diseases such as occupational asthma and allergic contact dermatitis, which can adversely affect health and well-being. Hundreds of chemicals (e.g. metals, epoxy and acrylic resins, rubber additives, and chemical intermediates) and proteins (e.g. natural rubber latex, plant proteins, mould, animal dander) present in virtually every industry have been identified as causes of allergic disease. In general, allergens can be classified as low molecular weight (chemical) allergens and high molecular weight (protein) allergens. These agents are capable of inducing immunological responses that are both immunoglobulin E and non-immunoglobulin E-mediated. Interestingly, the same chemical can induce diverse immune responses in different individuals. As new hazards continue to emerge, it is critical to understand the immunological mechanisms of occupational allergic disease. Specific understanding of these mechanisms has direct implications in hazard identification, hazard communication, and risk assessment. Such efforts will ultimately assist in the development of risk management strategies capable of controlling workplace exposures to allergens to prevent the induction of sensitisation in na?ve individuals and inhibit elicitation of allergic responses. The purpose of this short review is to give a brief synopsis of the incidence, agents, mechanisms, and research needs related to occupational allergy.

      2. Lessons learned from surface wipe sampling for lead in three workplaces
        Beaucham C, Ceballos D, King B.
        J Occup Environ Hyg. 2017 Jun 02:0.
        Surface wipe sampling in the occupational environment is a technique widely used by industrial hygienists. Although several organizations have promulgated standards for sampling lead and other metals, uncertainty still exists when trying to determine an appropriate wipe sampling strategy and how to interpret sampling results. Investigators from the National Institute for Occupational Safety and Health (NIOSH) Health Hazard Evaluation Program have used surface wipe sampling as part of their exposure assessment sampling strategies in a wide range of workplaces. This manuscript discusses wipe sampling for measuring lead on surfaces in three facilities: (1) a battery recycling facility, (2) a firing range and gun store, and (3) an electronic scrap recycling facility. We summarize our findings from the facilities and what we learned by integrating wipe sampling into our sampling plan. Wiping sampling demonstrated lead in non-production surfaces in all three workplaces and that the potential that employees were taking lead home to their families existed. We also found that the presence of metals such as tin can interfere with the colorimetric results. We also discuss the advantages and disadvantages of colorimetric analysis of surface wipe samples and the challenges we faced when interpreting wipe sampling results.

      3. The Centers for Disease Control and Prevention: Findings from The National Healthy Worksite Program
        Lang J, Cluff L, Payne J, Matson-Koffman D, Hampton J.
        J Occup Environ Med. 2017 Jun 07.
        OBJECTIVE: To evaluate employers’ implementation of evidence-based interventions, and changes in employees’ behaviors associated with participating in the national healthy worksite program (NHWP). METHODS: NHWP recruited 100 small and mid-sized employers and provided training and support for 18 months. Outcome measures were collected with an employer questionnaire, an employee survey, and biometric data at baseline and 18 months later. RESULTS: The 41 employers who completed the NHWP implemented significantly more evidence-based interventions and had more comprehensive worksite health promotion programs after participating. Employees made significant improvements in physical activity and nutritional behaviors, but did not significantly improve employee weight. CONCLUSIONS: Training and technical support can help small and mid-sized employers implement evidence-based health interventions to promote positive employee behavior changes. A longer follow up period may be needed to assess whether NHWP led to improvements in clinical outcomes.

      4. Non-chemical risk assessment for lifting and low back pain based on Bayesian threshold models
        Pandalai SP, Wheeler MW, Lu ML.
        Saf Health Work. 2017 Jun;8(2):206-211.
        BACKGROUND: Self-reported low back pain (LBP) has been evaluated in relation to material handling lifting tasks, but little research has focused on relating quantifiable stressors to LBP at the individual level. The National Institute for Occupational Safety and Health (NIOSH) Composite Lifting Index (CLI) has been used to quantify stressors for lifting tasks. A chemical exposure can be readily used as an exposure metric or stressor for chemical risk assessment (RA). Defining and quantifying lifting nonchemical stressors and related adverse responses is more difficult. Stressor-response models appropriate for CLI and LBP associations do not easily fit in common chemical RA modeling techniques (e.g., Benchmark Dose methods), so different approaches were tried. METHODS: This work used prospective data from 138 manufacturing workers to consider the linkage of the occupational stressor of material lifting to LBP. The final model used a Bayesian random threshold approach to estimate the probability of an increase in LBP as a threshold step function. RESULTS: Using maximal and mean CLI values, a significant increase in the probability of LBP for values above 1.5 was found. CONCLUSION: A risk of LBP associated with CLI values > 1.5 existed in this worker population. The relevance for other populations requires further study.

    • Parasitic Diseases RSS Word feed
      1. Surveillance for sulfadoxine-pyrimethamine resistant malaria parasites in the Lake and Southern Zones, Tanzania, using pooling and next-generation sequencing
        Ngondi JM, Ishengoma DS, Doctor SM, Thwai KL, Keeler C, Mkude S, Munishi OM, Willilo RA, Lalji S, Kaspar N, Kitojo C, Paxton LA, Hathaway NJ, Bailey JA, Juliano JJ, Meshnick SR, Gutman J.
        Malar J. 2017 Jun 05;16(1):236.
        BACKGROUND: Malaria in pregnancy (MiP) remains a major public health challenge in areas of high malaria transmission. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended to prevent the adverse consequences of MiP. The effectiveness of SP for IPTp may be reduced in areas where the dhps581 mutation (a key marker of high level SP resistance) is found; this mutation was previously reported to be common in the Tanga Region of northern Tanzania, but there are limited data from other areas. The frequency of molecular markers of SP resistance was investigated in malaria parasites from febrile patients at health centres (HC) in seven regions comprising the Lake and Southern Zones of mainland Tanzania as part of the ongoing efforts to generate national-wide data of SP resistance. METHODS: A cross-sectional survey was conducted in the outpatient departments of 14 HCs in seven regions from April to June, 2015. 1750 dried blood spot (DBS) samples were collected (117 to 160 per facility) from consenting patients with positive rapid diagnostic tests for malaria, and no recent (within past 2 months) exposure to SP or related drugs. DNA was extracted from the DBS, pooled by HC, and underwent pooled targeted amplicon deep sequencing to yield estimates of mutated parasite allele frequency at each locus of interest. RESULTS: The dhps540 mutation was common across all 14 sites, ranging from 55 to 98.4% of sequences obtained. Frequency of the dhps581 mutation ranged from 0 to 2.4%, except at Kayanga HC (Kagera Region, Lake Zone) where 24.9% of sequences obtained were mutated. The dhfr164 mutation was detected only at Kanyanga HC (0.06%). CONCLUSION: By pooling DNA extracts, the allele frequency of mutations in 14 sites could be directly determined on a single deep-sequencing run. The dhps540 mutant was very common at all locations. Surprisingly, the dhps581 was common at one health center, but rare in all the others, suggesting that there is geographic micro-heterogeneity in mutant distribution and that accurate surveillance requires inclusion of multiple sites. A better understanding of the effect of the dhps581 mutant on the efficacy of IPTp-SP is needed.

      2. Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: study design and methodology for a cluster randomized controlled trial
        Samuels AM, Awino N, Odongo W, Abong’o B, Gimnig J, Otieno K, Shi YP, Were V, Allen DR, Were F, Sang T, Obor D, Williamson J, Hamel MJ, Patrick Kachur S, Slutsker L, Lindblade KA, Kariuki S, Desai M.
        Malar J. 2017 Jun 07;16(1):240.
        Most human Plasmodium infections in western Kenya are asymptomatic and are believed to contribute importantly to malaria transmission. Elimination of asymptomatic infections requires active treatment approaches, such as mass testing and treatment (MTaT) or mass drug administration (MDA), as infected persons do not seek care for their infection. Evaluations of community-based approaches that are designed to reduce malaria transmission require careful attention to study design to ensure that important effects can be measured accurately. This manuscript describes the study design and methodology of a cluster-randomized controlled trial to evaluate a MTaT approach for malaria transmission reduction in an area of high malaria transmission. Ten health facilities in western Kenya were purposively selected for inclusion. The communities within 3 km of each health facility were divided into three clusters of approximately equal population size. Two clusters around each health facility were randomly assigned to the control arm, and one to the intervention arm. Three times per year for 2 years, after the long and short rains, and again before the long rains, teams of community health volunteers visited every household within the intervention arm, tested all consenting individuals with malaria rapid diagnostic tests, and treated all positive individuals with an effective anti-malarial. The effect of mass testing and treatment on malaria transmission was measured through population-based longitudinal cohorts, outpatient visits for clinical malaria, periodic population-based cross-sectional surveys, and entomological indices.

    • Program Evaluation RSS Word feed
      1. The practice of health program evaluation
        Lewis SR.
        Health Promot Pract. 2017 Jun 01.
        The Practice of Health Program Evaluation provides an overview of the evaluation process for public health programs while diving deeper to address select advanced concepts and techniques. The book unfolds evaluation as a three-phased process consisting of identification of evaluation questions, data collection and analysis, and dissemination of results and recommendations. The text covers research design, sampling methods, as well as quantitative and qualitative approaches. Types of evaluation are also discussed, including economic assessment and systems research as relative newcomers. Aspects critical to conducting a successful evaluation regardless of type or research design are emphasized, such as stakeholder engagement, validity and reliability, and adoption of sound recommendations. The book encourages evaluators to document their approach by developing an evaluation plan, a data analysis plan, and a dissemination plan, in order to help build consensus throughout the process. The evaluative text offers a good bird’s-eye view of the evaluation process, while offering guidance for evaluation experts on how to navigate political waters and advocate for their findings to help affect change.

    • Public Health Leadership and Management RSS Word feed
      1. Implementing One Health as an integrated approach to health in Rwanda
        Nyatanyi T, Wilkes M, McDermott H, Nzietchueng S, Gafarasi I, Mudakikwa A, Kinani JF, Rukelibuga J, Omolo J, Mupfasoni D, Kabeja A, Nyamusore J, Nziza J, Hakizimana JL, Kamugisha J, Nkunda R, Kibuuka R, Rugigana E, Farmer P, Cotton P, Binagwaho A.
        BMJ Glob Health. 2017 Jan;2(1):e000121.
        It is increasingly clear that resolution of complex global health problems requires interdisciplinary, intersectoral expertise and cooperation from governmental, non-governmental and educational agencies. ‘One Health’ refers to the collaboration of multiple disciplines and sectors working locally, nationally and globally to attain optimal health for people, animals and the environment. One Health offers the opportunity to acknowledge shared interests, set common goals, and drive toward team work to benefit the overall health of a nation. As in most countries, the health of Rwanda’s people and economy are highly dependent on the health of the environment. Recently, Rwanda has developed a One Health strategic plan to meet its human, animal and environmental health challenges. This approach drives innovations that are important to solve both acute and chronic health problems and offers synergy across systems, resulting in improved communication, evidence-based solutions, development of a new generation of systems-thinkers, improved surveillance, decreased lag time in response, and improved health and economic savings. Several factors have enabled the One Health movement in Rwanda including an elaborate network of community health workers, existing rapid response teams, international academic partnerships willing to look more broadly than at a single disease or population, and relative equity between female and male health professionals. Barriers to implementing this strategy include competition over budget, poor communication, and the need for improved technology. Given the interconnectedness of our global community, it may be time for countries and their neighbours to follow Rwanda’s lead and consider incorporating One Health principles into their national strategic health plans.

    • Reproductive Health RSS Word feed
      1. Disparities in assisted reproductive technology utilization by race and ethnicity, United States, 2014: A commentary
        Dieke AC, Zhang Y, Kissin DM, Barfield WD, Boulet SL.
        J Womens Health (Larchmt). 2017 Jun 06.
        Disparities in infertility and access to infertility treatments, such as assisted reproductive technology (ART), by race/ethnicity, have been reported. However, identifying disparities in ART usage may have been hampered by missing race/ethnicity information in ART surveillance. We review infertility prevalence and treatment disparities, use recent data to examine ART use in the United States by race/ethnicity and residency in states with mandated insurance coverage for in vitro fertilization (IVF), and discuss approaches for reducing disparities. We used 2014 National ART Surveillance System (NASS) data to calculate rates of ART procedures per million women 15-44 years of age, a proxy measure of ART utilization, for Census-defined racial/ethnic groups in the United States; rates were further stratified by the presence of insurance mandates for IVF treatment. Missing race/ethnicity data (35.6% of cycles) were imputed. Asian/Pacific Islander (A/PI) women had the highest rates of ART utilization at 5883 ART procedures per million women 15-44 years of age in 2014, whereas American Indian/Alaska Native non-Hispanic women had the lowest rates at 807 per million, compared with other racial/ethnic groups. In each racial/ethnic category, ART utilization rates were higher for women in states with an insurance mandate for IVF treatment versus those without. In 2014, A/PI women had the highest rates of ART utilization. ART utilization for all racial/ethnic groups was higher in states with insurance mandates for IVF than those without, although disparities were still evident. Although mandates may increase access to infertility treatments, they are not sufficient to eliminate these disparities.

      2. Use of clinical performance measures for contraceptive care in Iowa, 2013
        Frederiksen BN, Kane DJ, Rivera M, Wheeler D, Gavin L.
        Contraception. 2017 May 31.
        OBJECTIVES: To assess feasibility of calculating clinical performance measures for contraceptive care for National Quality Forum submission: the percentage of women aged 15-44 provided: 1) a most or moderately effective contraceptive method (MME), and 2) a long-acting reversible contraceptive (LARC) method. METHODS: We used 2013 Iowa Department of Public Health (IDPH) Title X and Iowa Medicaid data. We stratified Title X data by age and Medicaid data by age and benefit type (family planning waiver (FPW) vs. general Medicaid), and examined variation by residence, public health region, and health plan based on program interest. FINDINGS: Among women attending IDPH Title X clinics in 2013 (N=11,584), 86% of women ages 15-20years and 83% of women ages 21-44years were provided MME; 20% of women ages 15-20years and 20% of women ages 21-44years were provided LARC. Estimates varied across Title X sub-recipient agencies, which receive federal funds from IDPH. Among Medicaid FPW clients (N=30,013), 79% of women ages 15-20years and 73% of women ages 21-44years were provided MME; 12% of women ages 15-20years and 11% of women ages 21-44years were provided LARC. Among general Medicaid clients (N=14,737), 40% of women ages 15-20years and 28% of women ages 21-44years were provided MME; 5% of women ages 15-20years and 5% of women ages 21-44years were provided LARC. CONCLUSION: A high percentage of IDPH Title X and FPW clients were provided a MME method. No reporting entity had a LARC percentage less than 1-2%. IMPLICATIONS: Measure calculation using Title X and Medicaid data is feasible and can potentially be used to identify ways to increase access to contraceptive methods.

      3. Urinary triclosan concentrations and diminished ovarian reserve among women undergoing treatment in a fertility clinic
        Minguez-Alarcon L, Christou G, Messerlian C, Williams PL, Carignan CC, Souter I, Ford JB, Calafat AM, Hauser R.
        Fertil Steril. 2017 Jun 02.
        OBJECTIVE: To investigate the association between urinary triclosan concentrations and antral follicle count (AFC), a well-accepted marker of ovarian reserve, among women from a fertility center. DESIGN: Prospective cohort study. SETTING: Hospital fertility center. PATIENT(S): A total of 109 women. INTERVENTION(S): Urinary triclosan concentrations quantified by online solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry. MAIN OUTCOME MEASURE(S): AFC through transvaginal ultrasonography on the third day of an unstimulated menstrual cycle or on the third day of a progesterone withdrawal bleed. RESULT(S): The geometric mean of the specific gravity-adjusted urinary triclosan concentrations for the 225 samples provided by the 109 women was 13.0 mug/L (95% confidence interval [CI], 8.9, 19.1). Women had median (with interquartile range) AFC of 13 (8, 18). The specific gravity-adjusted urinary triclosan concentrations were inversely associated with AFC (-4%; 95% CI, -7%, -1%). Women with triclosan concentrations above the median had lower AFC compared with those whose triclosan concentrations were equal to or below the median, with an adjusted difference of -3.2 (95% CI, -3.9, -1.6) among those with a body mass index <25 kg/m2 and -1.8 (95% CI, -3.2, -0.3) among those who were <35 years old. CONCLUSION(S): Specific gravity-adjusted urinary triclosan concentrations were inversely associated with AFC in women seeking care at a fertility center. This association was modified by age and body mass index, with the younger and leaner women showing larger decreases in AFC.

    • Statistics as Topic RSS Word feed
      1. Statistical literacy and knowledge is needed to read and understand the public health literature. The purpose of this study was to quantify basic and advanced statistical methods used in public health research. We randomly sampled 216 published articles from seven top tier general public health journals. Studies were reviewed by two readers and a standardized data collection form completed for each article. Data were analyzed with descriptive statistics and frequency distributions. Results were summarized for statistical methods used in the literature, including descriptive and inferential statistics, modeling, advanced statistical techniques, and statistical software used. Approximately 81.9% of articles reported an observational study design and 93.1% of articles were substantively focused. Descriptive statistics in table or graphical form were reported in more than 95% of the articles, and statistical inference reported in more than 76% of the studies reviewed. These results reveal the types of statistical methods currently used in the public health literature. Although this study did not obtain information on what should be taught, information on statistical methods being used is useful for curriculum development in graduate health sciences education, as well as making informed decisions about continuing education for public health professionals.

      2. A nonparametric multiple imputation approach for missing categorical data
        Zhou M, He Y, Yu M, Hsu CH.
        BMC Med Res Methodol. 2017 Jun 06;17(1):87.
        BACKGROUND: Incomplete categorical variables with more than two categories are common in public health data. However, most of the existing missing-data methods do not use the information from nonresponse (missingness) probabilities. METHODS: We propose a nearest-neighbour multiple imputation approach to impute a missing at random categorical outcome and to estimate the proportion of each category. The donor set for imputation is formed by measuring distances between each missing value with other non-missing values. The distance function is calculated based on a predictive score, which is derived from two working models: one fits a multinomial logistic regression for predicting the missing categorical outcome (the outcome model) and the other fits a logistic regression for predicting missingness probabilities (the missingness model). A weighting scheme is used to accommodate contributions from two working models when generating the predictive score. A missing value is imputed by randomly selecting one of the non-missing values with the smallest distances. We conduct a simulation to evaluate the performance of the proposed method and compare it with several alternative methods. A real-data application is also presented. RESULTS: The simulation study suggests that the proposed method performs well when missingness probabilities are not extreme under some misspecifications of the working models. However, the calibration estimator, which is also based on two working models, can be highly unstable when missingness probabilities for some observations are extremely high. In this scenario, the proposed method produces more stable and better estimates. In addition, proper weights need to be chosen to balance the contributions from the two working models and achieve optimal results for the proposed method. CONCLUSIONS: We conclude that the proposed multiple imputation method is a reasonable approach to dealing with missing categorical outcome data with more than two levels for assessing the distribution of the outcome. In terms of the choices for the working models, we suggest a multinomial logistic regression for predicting the missing outcome and a binary logistic regression for predicting the missingness probability.

    • Substance Use and Abuse RSS Word feed
      1. Evaluation of a web-based training in smoking cessation counseling targeting U.S. eye-care professionals
        Asfar T, Lee DJ, Lam BL, Murchison AP, Mayro EL, Owsley C, McGwin G, Gower EW, Friedman DS, Saaddine J.
        Health Educ Behav. 2017 Jun 01:1090198117709883.
        BACKGROUND: Smoking causes blindness-related diseases. Eye-care providers are uniquely positioned to help their patients quit smoking. AIMS: Using a pre-/postevaluation design, this study evaluated a web-based training in smoking cessation counseling targeting eye-care providers. METHOD: The training was developed based on the 3A1R protocol: “Ask about smoking, Advise to quit, Assess willingness to quit, and Refer to tobacco quitlines,” and made available in the form of a web-based video presentation. Providers ( n = 654) at four academic centers were invited to participate. Participants completed pretraining, posttraining, and 3-month follow-up surveys. Main outcomes were self-reported improvement in their motivation, confidence, and counseling practices at 3-month follow-up. Generalized linear mixed models for two time-points (pretraining and 3-month) were conducted for these outcomes. RESULTS: A total of 113 providers (54.0% males) participated in the study (17.7% response rate). At the 3-month evaluation, 9.8% of participants reported improvement in their motivation. With respect to the 3A1R, 8% reported improvement in their confidence for Ask, 15.5% for Advise, 28.6% for Assess, and 37.8% for Refer. Similarly, 25.5% reported improvement in their practices for Ask, 25.5% for Advise, 37.2% for Assess, and 39.4% for Refer to tobacco quitlines ( p < .001 for all except for Refer confidence p = .05). DISCUSSION: Although participation rate was low, the program effectively improved providers’ smoking cessation counseling practices. CONCLUSIONS: Including training in smoking cessation counseling in ophthalmology curriculums, and integrating the 3A1R protocol into the electronic medical records systems in eye-care settings, might promote smoking cessation practices in these settings.

      2. Hospitalizations for endocarditis and associated health care costs among persons with diagnosed drug dependence – North Carolina, 2010-2015
        Fleischauer AT, Ruhl L, Rhea S, Barnes E.
        MMWR Morb Mortal Wkly Rep. 2017 Jun 09;66(22):569-573.
        Opioid dependence and overdose have increased to epidemic levels in the United States. The 2014 National Survey on Drug Use and Health estimated that 4.3 million persons were nonmedical users of prescription pain relievers (1). These users are 40 times more likely than the general population to use heroin or other injection drugs (2). Furthermore, CDC estimated a near quadrupling of heroin-related overdose deaths during 2002-2014 (3). Although overdose contributes most to drug-associated mortality, infectious complications of intravenous drug use constitute a major cause of morbidity leading to hospitalization (4). In addition to infections from hepatitis C virus (HCV) and human immunodeficiency virus (HIV), injecting drug users are at increased risk for acquiring invasive bacterial infections, including endocarditis (5,6). Evidence that hospitalizations for endocarditis are increasing in association with the current opioid epidemic exists (7-9). To examine trends in hospitalizations for endocarditis among persons in North Carolina with drug dependence during 2010-2015, data from the North Carolina Hospital Discharge database were analyzed. The incidence of hospital discharge diagnoses for drug dependence combined with endocarditis increased more than twelvefold from 0.2 to 2.7 per 100,000 persons per year over this 6-year period. Correspondingly, hospital costs for these patients increased eighteenfold, from $1.1 million in 2010 to $22.2 million in 2015. To reduce the risk for morbidity and mortality related to opioid-associated endocarditis, public health programs and health care systems should consider collaborating to implement syringe service programs, harm reduction strategies, and opioid treatment programs.

      3. Despite the 2009 implementation of a tobacco tax increase in Thailand, smoking rates remained unchanged between 2009 and 2011. Prior evidence has linked cigarette tax increases to compensatory behaviours aimed at lowering the cost of smoking, such as switching to lower-priced cigarette brands. Using data from 2009 and 2011 Global Adult Tobacco Surveys in Thailand, we estimated unadjusted changes in cigarette prices paid, cigarette affordability, and consumption of cigarettes in three price categories classified as upper-, middle-, and lower-priced brand tiers (or price tertiles). We used ordered logit regression to analyse the correlates of price-tier choice and to estimate the change in price-tier consumption adjusted for demographic and region characteristics. Between 2009 and 2011, real cigarette prices increased, but the affordability of cigarettes remained unchanged overall. There was a significant reduction in the consumption of cigarette brands in the top price-tier overall, accompanied by increases in the consumption of brands in the bottom and middle price-tiers, depending on the region. Adjusted estimates from the logit models indicate that, on average, the proportion of smokers selecting brands from upper- and middle price-tiers decreased while consumption of lower price-tier brands increased during the study period. The estimated shifts in consumption from more expensive to less expensive cigarette brands and the overall lack of change in cigarette affordability in Thailand between 2009 and 2011 are both factors that may have contributed to the observed lack of change in smoking rates after the 2009 tax increase.

      4. Trends in sales of flavored and menthol tobacco products in the United States during 2011-2015
        Kuiper NM, Gammon D, Loomis B, Falvey K, Wang TW, King BA, Rogers T.
        Nicotine Tob Res. 2017 Jun 01.
        Introduction: Flavors can mask the harshness of tobacco and make it appealing to young people. This study assessed flavored and menthol tobacco product sales at the national and state levels. Methods: Universal Product Code (UPC) tobacco sales data collected by Nielsen were combined for convenience stores and all-outlets-combined during October 22, 2011-January 9, 2016. Products were characterized as flavored, menthol, or non-flavored/non-menthol. Total unit sales, and the proportion of flavored and menthol unit sales, were assessed nationally and by state for seven tobacco products. Joinpoint Regression was used to assess trends in average monthly percentage change. Results: Nationally, the proportion of flavored and menthol sales in 2015 was as follows: cigarettes (32.5% menthol), large cigars (26.1% flavored), cigarillos (47.5% flavored, 0.2% menthol), little cigars (21.8% flavored, 19.4% menthol), chewing tobacco (1.4% flavored, 0.7% menthol), moist snuff (3.0% flavored, 57.0% menthol), and snus (88.5% menthol). From 2011-2015, sales increased for flavored cigarillos and chewing tobacco, as well as for menthol cigarettes, little cigars, moist snuff and snus. Sales decreased for flavored large cigars, moist snuff and snus, and for menthol chewing tobacco. State-level variations were observed by product; for example, flavored little cigar sales ranged from 4.4% (Maine) to 69.3% (Utah) and flavored cigarillo sales ranged from 26.6% (Maine) to 63.0% (Maryland). Conclusions: Menthol and flavored sales have increased since 2011, particularly for the products with the highest number of units sold, and significant state variation exists. Efforts to restrict flavored tobacco product sales could reduce overall U.S. tobacco consumption. Implications: Flavors in tobacco products can mask the harshness of tobacco and make these products more appealing to young people. This is the first study to assess national and state-level trends in flavored and menthol tobacco product sales. These findings underscore the importance of population-based interventions to address flavored tobacco product use at the national, state, and local levels. Additionally, further monitoring of flavored and menthol tobacco product sales can inform potential future regulatory efforts at the national, state, and local levels.

    • Veterinary Medicine RSS Word feed
      1. Assessment of the immunogenicity of rabies vaccine preserved by vaporization and delivered to the duodenal mucosa of gray foxes (Urocyon cinereoargenteus)
        Smith TG, Wu X, Ellison JA, Wadhwa A, Franka R, Langham GL, Skinner BL, Hanlon CA, Bronshtein VL.
        Am J Vet Res. 2017 Jun;78(6):752-756.
        OBJECTIVE To assess the immunogenicity of thermostable live-attenuated rabies virus (RABV) preserved by vaporization (PBV) and delivered to the duodenal mucosa of a wildlife species targeted for an oral vaccination program. ANIMALS 8 gray foxes (Urocyon cinereoargenteus). PROCEDURES Endoscopy was used to place RABV PBV (n = 3 foxes), alginate-encapsulated RABV PBV (3 foxes), or nonpreserved RABV (2 foxes) vaccine into the duodenum of foxes. Blood samples were collected weekly to monitor the immune response. Saliva samples were collected weekly and tested for virus shedding by use of a conventional reverse-transcriptase PCR assay. Foxes were euthanized 28 days after vaccine administration, and relevant tissues were collected and tested for presence of RABV. RESULTS 2 of 3 foxes that received RABV PBV and 1 of 2 foxes that received nonpreserved RABV seroconverted by day 28. None of the 3 foxes receiving alginate-encapsulated RABV PBV seroconverted. No RABV RNA was detected in saliva at any of the time points, and RABV antigen or RNA was not detected in any of the tissues obtained on day 28. None of the foxes displayed any clinical signs of rabies. CONCLUSIONS AND CLINICAL RELEVANCE Results for this study indicated that a live-attenuated RABV vaccine delivered to the duodenal mucosa can induce an immune response in gray foxes. A safe, potent, thermostable RABV vaccine that could be delivered orally to wildlife or domestic animals would enhance current rabies control and prevention efforts.

    • Zoonotic and Vectorborne Diseases RSS Word feed
      1. Severe neurologic disorders in 2 fetuses with Zika virus infection, Colombia
        Acosta-Reyes J, Navarro E, Herrera MJ, Goenaga E, Ospina ML, Parra E, Mercado M, Chaparro P, Beltran M, Gunturiz ML, Pardo L, Valencia C, Huertas S, Rodriguez J, Ruiz G, Valencia D, Haddad LB, Tinker SC, Moore CA, Baquero H.
        Emerg Infect Dis. 2017 Jun;23(6):982-984.
        We report the results of pathologic examinations of 2 fetuses from women in Colombia with Zika virus infection during pregnancy that revealed severe central nervous system defects and potential associated abnormalities of the eye, spleen, and placenta. Amniotic fluid and tissues from multiple fetal organs tested positive for Zika virus.

      2. Longitudinal monitoring of Cryptosporidium species in pre-weaned dairy calves on five farms in Shanghai, China
        Cai M, Guo Y, Pan B, Li N, Wang X, Tang C, Feng Y, Xiao L.
        Vet Parasitol. 2017 Jul 15;241:14-19.
        In pre-weaned dairy calves, the zoonotic and pathogenic species Cryptosporidium parvum is the dominant Cryptosporidium species in most industrialized nations. In several studies in China, however, C. bovis has been the dominant one. To further examine the distribution of Cryptosporidium species in pre-weaned dairy calves in China, 818 fecal specimens were collected from five farms in Shanghai, with repeated samplings (up to five times) on each farm. PCR-restriction fragment length polymorphism (RFLP) analysis of the small subunit rRNA gene was used to detect and genotype Cryptosporidium spp. Cryptosporidium parvum was subtyped by sequence analysis of the 60kDa glycoprotein gene. Cryptosporidium occurrence on farms varied between 25.0% (Farm 2) and 55.0% (Farm 4), with a mean infection rate of 37.0%. Three Cryptosporidium species were detected, including C. bovis (193/303 or 63.7%), C. parvum (72/303 or 23.8%) and C. ryanae (32/303 or 10.6%). Concurrent infection of C. bovis and C. ryanae was detected in six (1.9%) animals. During the first two samplings, C. bovis was the dominant species on four farms and C. parvum was detected on only one farm (Farm 1). One of the study farms (Farm 3) started to have C. parvum at the third sampling. C. parvum was associated with the occurrence of moderate or watery diarrhea, while C. bovis was not. All C. parvum were subtype IIdA19G1, which is dominant in China but rare elsewhere. Genotyping and subtyping results indicated that the introduction of C. parvum to Farm 3 was caused by brief housing of several bull calves from another farm. Data from the study suggest that C. parvum is still uncommon in pre-weaned dairy calves in China and measures should be developed to prevent its spread in the country.

      3. Measures taken to prevent Zika virus infection during pregnancy – Puerto Rico, 2016
        D’Angelo DV, Salvesen von Essen B, Lamias MJ, Shulman H, Hernandez-Virella WI, Taraporewalla AJ, Vargas MI, Harrison L, Ellington SR, Soto L, Williams T, Rodriguez A, Shapiro-Mendoza CK, Rivera B, Cox S, Pazol K, Rice ME, Dee DL, Romero L, Lathrop E, Barfield W, Smith RA, Jamieson DJ, Honein MA, Deseda C, Warner L.
        MMWR Morb Mortal Wkly Rep. 2017 Jun 09;66(22):574-578.
        Zika virus infection during pregnancy remains a serious health threat in Puerto Rico. Infection during pregnancy can cause microcephaly, brain abnormalities, and other severe birth defects (1). From January 1, 2016 through March 29, 2017, Puerto Rico reported approximately 3,300 pregnant women with laboratory evidence of possible Zika virus infection (2). There is currently no vaccine or intervention to prevent the adverse effects of Zika virus infection during pregnancy; therefore, prevention has been the focus of public health activities, especially for pregnant women (3). CDC and the Puerto Rico Department of Health analyzed data from the Pregnancy Risk Assessment Monitoring System Zika Postpartum Emergency Response (PRAMS-ZPER) survey conducted from August through December 2016 among Puerto Rico residents with a live birth. Most women (98.1%) reported using at least one measure to avoid mosquitos in their home environment. However, only 45.8% of women reported wearing mosquito repellent daily, and 11.5% reported wearing pants and shirts with long sleeves daily. Approximately one third (38.5%) reported abstaining from sex or using condoms consistently throughout pregnancy. Overall, 76.9% of women reported having been tested for Zika virus by their health care provider during the first or second trimester of pregnancy. These results can be used to assess and refine Zika virus infection prevention messaging and interventions for pregnant women and to reinforce measures to promote prenatal testing for Zika.

      4. Isolated case of Marburg virus disease, Kampala, Uganda, 2014
        Nyakarahuka L, Ojwang J, Tumusiime A, Balinandi S, Whitmer S, Kyazze S, Kasozi S, Wetaka M, Makumbi I, Dahlke M, Borchert J, Lutwama J, Stroher U, Rollin PE, Nichol ST, Shoemaker TR.
        Emerg Infect Dis. 2017 Jun;23(6):1001-1004.
        In September 2014, a single fatal case of Marburg virus was identified in a healthcare worker in Kampala, Uganda. The source of infection was not identified, and no secondary cases were identified. We describe the rapid identification, laboratory diagnosis, and case investigation of the third Marburg virus outbreak in Uganda.

      5. Seoul virus infection in humans, France, 2014-2016
        Reynes JM, Carli D, Bour JB, Boudjeltia S, Dewilde A, Gerbier G, Nussbaumer T, Jacomo V, Rapt MP, Rollin PE, Septfons A.
        Emerg Infect Dis. 2017 Jun;23(6):973-977.
        We report detection of Seoul virus in 3 patients in France over a 2-year period. These patients accounted for 3 of the 4 Seoul virus infections among 434 hantavirus infections (1.7%) reported during this time. More attention should be given to this virus in Europe where surveillance has been focused mostly on Puumala and Dobrava-Belgrade hantaviruses.

      6. Engaging community and faith-based organizations in the Zika response, United States, 2016
        Santibanez S, Lynch J, Paye YP, McCalla H, Gaines J, Konkel K, Ocasio Torres LJ, North WA, Likos A, Daniel KL.
        Public Health Rep. 2017 Jan 01:33354917710212.

        [No abstract]

      7. Novel influenza A viruses and pandemic threats
        Uyeki TM, Katz JM, Jernigan DB.
        Lancet. 2017 Jun 03;389(10085):2172-2174.

        [No abstract]

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