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Volume 12, Issue, 8 March 10, 2020

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CDC Science Clips: Volume 12, Issue 8, March 10, 2020

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

This week, Science Clips is pleased to collaborate with CDC Vital Signs by featuring scientific articles from the latest issue on Colorectal Cancer Test Use. The articles marked with an asterisk are general review articles which may be of particular interest to clinicians and public health professionals seeking background information in this area.

The report consists of these components:

  1. CDC Vital Signs
    • Chronic Diseases and Conditions - Colorectal Cancer Test Use
      1. *Screening for colorectal cancer: Updated evidence report and systematic review for the US Preventive Services Task Forceexternal icon
        Lin JS, Piper MA, Perdue LA, Rutter CM, Webber EM, O'Connor E, Smith N, Whitlock EP.
        Jama. 2016 Jun 21;315(23):2576-94.
        IMPORTANCE: Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the United States. OBJECTIVE: To systematically review the effectiveness, diagnostic accuracy, and harms of screening for CRC. DATA SOURCES: Searches of MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2008, through December 31, 2014, with surveillance through February 23, 2016. STUDY SELECTION: English-language studies conducted in asymptomatic populations at general risk of CRC. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted. MAIN OUTCOMES AND MEASURES: Colorectal cancer incidence and mortality, test accuracy in detecting CRC or adenomas, and serious adverse events. RESULTS: Four pragmatic randomized clinical trials (RCTs) evaluating 1-time or 2-time flexible sigmoidoscopy (n = 458,002) were associated with decreased CRC-specific mortality compared with no screening (incidence rate ratio, 0.73; 95% CI, 0.66-0.82). Five RCTs with multiple rounds of biennial screening with guaiac-based fecal occult blood testing (n = 419,966) showed reduced CRC-specific mortality (relative risk [RR], 0.91; 95% CI, 0.84-0.98, at 19.5 years to RR, 0.78; 95% CI, 0.65-0.93, at 30 years). Seven studies of computed tomographic colonography (CTC) with bowel preparation demonstrated per-person sensitivity and specificity to detect adenomas 6 mm and larger comparable with colonoscopy (sensitivity from 73% [95% CI, 58%-84%] to 98% [95% CI, 91%-100%]; specificity from 89% [95% CI, 84%-93%] to 91% [95% CI, 88%-93%]); variability and imprecision may be due to differences in study designs or CTC protocols. Sensitivity of colonoscopy to detect adenomas 6 mm or larger ranged from 75% (95% CI, 63%-84%) to 93% (95% CI, 88%-96%). On the basis of a single stool specimen, the most commonly evaluated families of fecal immunochemical tests (FITs) demonstrated good sensitivity (range, 73%-88%) and specificity (range, 90%-96%). One study (n = 9989) found that FIT plus stool DNA test had better sensitivity in detecting CRC than FIT alone (92%) but lower specificity (84%). Serious adverse events from colonoscopy in asymptomatic persons included perforations (4/10,000 procedures, 95% CI, 2-5 in 10,000) and major bleeds (8/10,000 procedures, 95% CI, 5-14 in 10,000). Computed tomographic colonography may have harms resulting from low-dose ionizing radiation exposure or identification of extracolonic findings. CONCLUSIONS AND RELEVANCE: Colonoscopy, flexible sigmoidoscopy, CTC, and stool tests have differing levels of evidence to support their use, ability to detect cancer and precursor lesions, and risk of serious adverse events in average-risk adults. Although CRC screening has a large body of supporting evidence, additional research is still needed.

      2. *Effectiveness of interventions to increase screening for breast, cervical, and colorectal cancers: nine updated systematic reviews for the guide to community preventive servicesexternal icon
        Sabatino SA, Lawrence B, Elder R, Mercer SL, Wilson KM, DeVinney B, Melillo S, Carvalho M, Taplin S, Bastani R, Rimer BK, Vernon SW, Melvin CL, Taylor V, Fernandez M, Glanz K.
        Am J Prev Med. 2012 Jul;43(1):97-118.
        CONTEXT: Screening reduces mortality from breast, cervical, and colorectal cancers. The Guide to Community Preventive Services previously conducted systematic reviews on the effectiveness of 11 interventions to increase screening for these cancers. This article presents results of updated systematic reviews for nine of these interventions. EVIDENCE ACQUISITION: Five databases were searched for studies published during January 2004-October 2008. Studies had to (1) be a primary investigation of one or more intervention category; (2) be conducted in a country with a high-income economy; (3) provide information on at least one cancer screening outcome of interest; and (4) include screening use prior to intervention implementation or a concurrent group unexposed to the intervention category of interest. Forty-five studies were included in the reviews. EVIDENCE SYNTHESIS: Recommendations were added for one-on-one education to increase screening with fecal occult blood testing (FOBT) and group education to increase mammography screening. Strength of evidence for client reminder interventions to increase FOBT screening was upgraded from sufficient to strong. Previous findings and recommendations for reducing out-of-pocket costs (breast cancer screening); provider assessment and feedback (breast, cervical, and FOBT screening); one-on-one education and client reminders (breast and cervical cancer screening); and reducing structural barriers (breast cancer and FOBT screening) were reaffirmed or unchanged. Evidence remains insufficient to determine effectiveness for the remaining screening tests and intervention categories. CONCLUSIONS: Findings indicate new and reaffirmed interventions effective in promoting recommended cancer screening, including colorectal cancer screening. Findings can be used in community and healthcare settings to promote recommended care. Important research gaps also are described.

      3. Screening for colorectal cancer: US Preventive Services Task Force Recommendation Statementexternal icon
        Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Epling JW, Garcia FA, Gillman MW, Harper DM, Kemper AR, Krist AH, Kurth AE, Landefeld CS, Mangione CM, Owens DK, Phillips WR, Phipps MG, Pignone MP, Siu AL.
        Jama. 2016 Jun 21;315(23):2564-2575.
        IMPORTANCE: Colorectal cancer is the second leading cause of cancer death in the United States. In 2016, an estimated 134,000 persons will be diagnosed with the disease, and about 49,000 will die from it. Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years; the median age at death from colorectal cancer is 68 years. OBJECTIVE: To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for colorectal cancer. EVIDENCE REVIEW: The USPSTF reviewed the evidence on the effectiveness of screening with colonoscopy, flexible sigmoidoscopy, computed tomography colonography, the guaiac-based fecal occult blood test, the fecal immunochemical test, the multitargeted stool DNA test, and the methylated SEPT9 DNA test in reducing the incidence of and mortality from colorectal cancer or all-cause mortality; the harms of these screening tests; and the test performance characteristics of these tests for detecting adenomatous polyps, advanced adenomas based on size, or both, as well as colorectal cancer. The USPSTF also commissioned a comparative modeling study to provide information on optimal starting and stopping ages and screening intervals across the different available screening methods. FINDINGS: The USPSTF concludes with high certainty that screening for colorectal cancer in average-risk, asymptomatic adults aged 50 to 75 years is of substantial net benefit. Multiple screening strategies are available to choose from, with different levels of evidence to support their effectiveness, as well as unique advantages and limitations, although there are no empirical data to demonstrate that any of the reviewed strategies provide a greater net benefit. Screening for colorectal cancer is a substantially underused preventive health strategy in the United States. CONCLUSIONS AND RECOMMENDATIONS: The USPSTF recommends screening for colorectal cancer starting at age 50 years and continuing until age 75 years (A recommendation). The decision to screen for colorectal cancer in adults aged 76 to 85 years should be an individual one, taking into account the patient's overall health and prior screening history (C recommendation).

      4. The Guide to Community Preventive Servicesexternal icon
        Community Preventive Services Task Force
        Available at https://www.thecommunityguide.org/
        The Guide to Community Preventive Services (The Community Guide) is a collection of evidence-based findings of the Community Preventive Services Task Force (CPSTF). It is a resource to help you select interventions to improve health and prevent disease in your state, community, community organization, business, healthcare organization, or school.

      5. Patterns and trends in cancer screening in the United Statesexternal icon
        Hall IJ, Tangka FK, Sabatino SA, Thompson TD, Graubard BI, Breen N.
        Prev Chronic Dis. 2018 Jul 26;15:E97.
        INTRODUCTION: We examined the prevalence of cancer screening reported in 2015 among US adults, adjusted for important sociodemographic and access-to-care variables. By using data from the National Health Interview Survey (NHIS) for 2000 through 2015, we examined trends in prevalence of cancer screening that adhered to US Preventive Services Task Force screening recommendations in order to monitor screening progress among traditionally underserved population subgroups. METHODS: We analyzed NHIS data from surveys from 2000 through 2015 to estimate prevalence and trends in use of recommended screening tests for breast, cervical, colorectal, and prostate cancers. We used logistic regression and report predictive margins for population subgroups adjusted for various socioeconomic and demographic variables. RESULTS: Colorectal cancer screening was the only test that increased during the study period. We found disparities in prevalence of test use among subgroups for all tests examined. Factors that reduced the use of screening tests included no contact with a doctor in the past year, no usual source of health care, and no insurance coverage. CONCLUSION: Understanding use of cancer screening tests among different population subgroups is vital for planning public health interventions with potential to increase screening uptake and reduce disparities in cancer morbidity and mortality. Overarching goals of Healthy People 2020 are to "achieve health equity, eliminate disparities, and improve the health of all groups." Adjusted findings for 2015, compared with previous years, show persistent screening disparities, particularly among the uninsured, and progress for colorectal cancer screening only.

      6. Systematic review and meta-study synthesis of qualitative studies evaluating facilitators and barriers to participation in colorectal cancer screeningexternal icon
        Honein-AbouHaidar GN, Kastner M, Vuong V, Perrier L, Daly C, Rabeneck L, Straus S, Baxter NN.
        Cancer Epidemiol Biomarkers Prev. 2016 Jun;25(6):907-17.
        Screening reduces the incidence, morbidity, and mortality of colorectal cancer, yet participation tends to be low. We undertook a systematic review and meta-study synthesis of qualitative studies to identify facilitators and barriers to colorectal cancer screening participation. We searched major bibliographic databases for records published in all languages from inception to February 2015. Included primary studies that elicited views and perceptions towards colorectal cancer screening were appraised for relevance and quality. We used a two-stage synthesis to create an interpretation of colorectal cancer screening decisions grounded in primary studies; a thematic analysis to group themes and systematically compare studies and a meta-synthesis to generate an expanded theory of colorectal cancer screening participation. Ninety-four studies were included. The decision to participate in colorectal cancer screening depended on an individual's awareness of colorectal cancer screening. Awareness affected views of cancer, attitudes towards colorectal cancer screening modalities, and motivation for screening. Factors mediating awareness included public education to address misconceptions, primary care physician efforts to recommend screening, and the influence of friends and family. Specific barriers to participation in populations with lower participation rates included language barriers, logistical challenges to attending screening tests, and cultural beliefs. This study identifies key barriers, facilitators, and mediators to colorectal cancer screening participation. Cancer Epidemiol Biomarkers Prev; 25(6); 907-17. (c)2016 AACR.

      7. Adherence to colorectal cancer screening: a randomized clinical trial of competing strategiesexternal icon
        Inadomi JM, Vijan S, Janz NK, Fagerlin A, Thomas JP, Lin YV, Munoz R, Lau C, Somsouk M, El-Nachef N, Hayward RA.
        Arch Intern Med. 2012 Apr 9;172(7):575-82.
        BACKGROUND: Despite evidence that several colorectal cancer (CRC) screening strategies can reduce CRC mortality, screening rates remain low. This study aimed to determine whether the approach by which screening is recommended influences adherence. METHODS: We used a cluster randomization design with clinic time block as the unit of randomization. Persons at average risk for development of CRC in a racially/ethnically diverse urban setting were randomized to receive recommendation for screening by fecal occult blood testing (FOBT), colonoscopy, or their choice of FOBT or colonoscopy. The primary outcome was completion of CRC screening within 12 months after enrollment, defined as performance of colonoscopy, or 3 FOBT cards plus colonoscopy for any positive FOBT result. Secondary analyses evaluated sociodemographic factors associated with completion of screening. RESULTS: A total of 997 participants were enrolled; 58% completed the CRC screening strategy they were assigned or chose. However, participants who were recommended colonoscopy completed screening at a significantly lower rate (38%) than participants who were recommended FOBT (67%) (P < .001) or given a choice between FOBT or colonoscopy (69%) (P < .001). Latinos and Asians (primarily Chinese) completed screening more often than African Americans. Moreover, nonwhite participants adhered more often to FOBT, while white participants adhered more often to colonoscopy. CONCLUSIONS: The common practice of universally recommending colonoscopy may reduce adherence to CRC screening, especially among racial/ethnic minorities. Significant variation in overall and strategy-specific adherence exists between racial/ethnic groups; however, this may be a proxy for health beliefs and/or language. These results suggest that patient preferences should be considered when making CRC screening recommendations. Trial Registration clinicaltrials.gov Identifier: NCT00705731.

      8. Estimation of benefits, burden, and harms of colorectal cancer screening strategies: Modeling study for the US Preventive Services Task Forceexternal icon
        Knudsen AB, Zauber AG, Rutter CM, Naber SK, Doria-Rose VP, Pabiniak C, Johanson C, Fischer SE, Lansdorp-Vogelaar I, Kuntz KM.
        Jama. 2016 Jun 21;315(23):2595-609.
        IMPORTANCE: The US Preventive Services Task Force (USPSTF) is updating its 2008 colorectal cancer (CRC) screening recommendations. OBJECTIVE: To inform the USPSTF by modeling the benefits, burden, and harms of CRC screening strategies; estimating the optimal ages to begin and end screening; and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden. DESIGN, SETTING, AND PARTICIPANTS: Comparative modeling with 3 microsimulation models of a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis. EXPOSURES: Screening with sensitive guaiac-based fecal occult blood testing, fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy with or without stool testing, computed tomographic colonography (CTC), or colonoscopy starting at age 45, 50, or 55 years and ending at age 75, 80, or 85 years. Screening intervals varied by modality. Full adherence for all strategies was assumed. MAIN OUTCOMES AND MEASURES: Life-years gained compared with no screening (benefit), lifetime number of colonoscopies required (burden), lifetime number of colonoscopy complications (harms), and ratios of incremental burden and benefit (efficiency ratios) per 1000 40-year-olds. RESULTS: The screening strategies provided LYG in the range of 152 to 313 per 1000 40-year-olds. Lifetime colonoscopy burden per 1000 persons ranged from fewer than 900 (FIT every 3 years from ages 55-75 years) to more than 7500 (colonoscopy screening every 5 years from ages 45-85 years). Harm from screening was at most 23 complications per 1000 persons screened. Strategies with screening beginning at age 50 years generally provided more LYG as well as more additional LYG per additional colonoscopy than strategies with screening beginning at age 55 years. There were limited empirical data to support a start age of 45 years. For persons adequately screened up to age 75 years, additional screening yielded small increases in LYG relative to the increase in colonoscopy burden. With screening from ages 50 to 75 years, 4 strategies yielded a comparable balance of screening burden and similar LYG (median LYG per 1000 across the models): colonoscopy every 10 years (270 LYG); sigmoidoscopy every 10 years with annual FIT (256 LYG); CTC every 5 years (248 LYG); and annual FIT (244 LYG). CONCLUSIONS AND RELEVANCE: In this microsimulation modeling study of a previously unscreened population undergoing CRC screening that assumed 100% adherence, the strategies of colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT, and CTC every 5 years performed from ages 50 through 75 years provided similar LYG and a comparable balance of benefit and screening burden.

      9. Public health impact of achieving 80% colorectal cancer screening rates in the United States by 2018external icon
        Meester RG, Doubeni CA, Zauber AG, Goede SL, Levin TR, Corley DA, Jemal A, Lansdorp-Vogelaar I.
        Cancer. 2015 Jul 1;121(13):2281-5.
        BACKGROUND: The National Colorectal Cancer Roundtable, a national coalition of public, private, and voluntary organizations, has recently announced an initiative to increase colorectal cancer (CRC) screening rates in the United States to 80% by 2018. The authors evaluated the potential public health benefits of achieving this goal. METHODS: The authors simulated the 1980 through 2030 United States population of individuals aged 50 to 100 years using microsimulation modeling. Test-specific historical screening rates were based on National Health Interview Survey data for 1987 through 2013. The effects of increasing screening rates from approximately 58% in 2013 to 80% in 2018 were compared to a scenario in which the screening rate remained approximately constant. The outcomes were cancer incidence and mortality rates and numbers of CRC cases and deaths during short-term follow-up (2013-2020) and extended follow-up (2013-2030). RESULTS: Increasing CRC screening rates to 80% by 2018 would reduce CRC incidence rates by 17% and mortality rates by 19% during short-term follow-up and by 22% and 33%, respectively, during extended follow-up. These reductions would amount to a total of 277,000 averted new cancers and 203,000 averted CRC deaths from 2013 through 2030. CONCLUSIONS: Achieving the goal of increasing the uptake of CRC screening in the United States to 80% by 2018 may have a considerable public health impact by averting approximately 280,000 new cancer cases and 200,000 cancer deaths within <20 years. Cancer 2015;121:2281-2285. (c) 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

      10. Factors affecting adherence in a pragmatic trial of annual fecal immunochemical testing for colorectal cancerexternal icon
        Nielson CM, Vollmer WM, Petrik AF, Keast EM, Green BB, Coronado GD.
        J Gen Intern Med. 2019 Jun;34(6):978-985.
        BACKGROUND: Colorectal cancer screening by fecal immunochemical test (FIT) reduces the burden of colorectal cancer. However, effectiveness relies on annual adherence, which presents challenges for clinic staff and patients. OBJECTIVE: Describe FIT return rates and identify factors associated with FIT adherence over 2 years in a mailed FIT outreach program in federally qualified health centers. DESIGN: Observational study nested in the Strategies and Opportunities to Stop Colon Cancer in Priority Populations (STOP CRC) trial. Five thousand one hundred ninety-five patients had an initial FIT order and were followed for >/= 2 years (3574 also had a FIT order in the second year). MAIN MEASURES: FIT return percent in each year and patient- and neighborhood-level characteristics associated with FIT adherence. KEY RESULTS: Overall, the proportion of FIT orders that were completed was 46% in the patients' first year and 41% in the patients' second year. Of the 5195 patients with a FIT order in year 1, 3574 (69%) also had a FIT order in year 2 (71% of year 1 adherers and 67% of year 1 non-adherers, p = 0.009). Among those with a FIT order in the second year, the FIT return rate was about twice as high among those who were adherent in the first year (952/1674, or 57%) as among those who were not (531/1900, or 28%, p < 0.0001). Patient-level characteristics associated with higher odds of FIT return were a history of FIT screening at baseline, age over 65 (vs 50-65), no current tobacco use, recent receipt of a mammogram or flu vaccine, Asian ancestry (compared to non-Hispanic white), and non-English preference. The only neighborhood factor associated with lower FIT return rate was patient's larger residential city size. CONCLUSION: Our findings can inform the customization of programs to promote FIT return among patients who receive care at federally qualified health centers. TRIAL REGISTRATION: http://www.clinicaltrials.gov.


  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. OBJECTIVE: In an 8-week nonpharmacological pain intervention trial among older adults with lower extremity osteoarthritis (OA), we aimed to examine: a) the baseline frailty level of the participants; b) whether such intervention is more beneficial for baseline frailer older adults than for their counterparts with less frailty; and c) whether the intervention could also alter frailty. METHODS: Participants were randomly assigned to either chair yoga (CY) or health education program (HEP) groups and attended twice-weekly 45-minute CY or HEP sessions for 8weeks. Following a standard procedure, 82 variables were used to construct a frailty index (FI, 0-1). Primary outcomes were: Western Ontario and McMaster Universities (WOMAC) pain and pain interference. Linear mixed-effects models were used to evaluate the modifying effect of baseline frailty on the intervention effect of CY on primary outcomes. Similar models were used to evaluate the effect of CY on frailty. RESULTS: A total of 112 participants (n=63 CY, n=49 HEP; 75.3 [SD=7.5] years) with 85 females (75.9%) were included. The mean values of baseline FI for the CY and HEP groups were similar (0.428 [0.05] and 0.433 [0.05], P=0.355). Each 0.01 increment in baseline FI was associated with higher WOMAC pain (beta=0.28, P<0.001) and pain interference (beta=0.51, P<0.001). There was a significant interaction effect between intervention, time, and baseline FI (P=0.020 for WOMAC pain; P=0.010 for pain interference), indicating that participants with higher level of baseline FI had greater declines in WOMAC pain and pain interference. There was no significantly greater decline in FI for the CY group compared to the HEP group (between-group difference-0.01; P=0.509) and there were no significant trend changes in FI (P for interaction=0.605). CONCLUSIONS: Frailty modifies the intervention effect of CY on pain among older adults with lower extremity OA, underscoring the importance of assessing frailty to improve the management of pain in this population.

      2. Screening for lung cancer - 10 states, 2017external icon
        Richards TB, Soman A, Thomas CC, VanFrank B, Henley SJ, Gallaway MS, Richardson LC.
        MMWR Morb Mortal Wkly Rep. 2020 Feb 28;69(8):201-206.
        Lung cancer is the leading cause of cancer death in the United States; 148,869 lung cancer-associated deaths occurred in 2016 (1). Mortality might be reduced by identifying lung cancer at an early stage when treatment can be more effective (2). In 2013, the U.S. Preventive Services Task Force (USPSTF) recommended annual screening for lung cancer with low-dose computed tomography (CT) for adults aged 55-80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years (2).(dagger) This was a Grade B recommendation, which required health insurance plans to cover lung cancer screening as a preventive service.( section sign) To assess the prevalence of lung cancer screening by state, CDC used Behavioral Risk Factor Surveillance System (BRFSS) data( paragraph sign) collected in 2017 by 10 states. Overall, 12.7% adults aged 55-80 years met the USPSTF criteria for lung cancer screening. Among those meeting USPSTF criteria, 12.5% reported they had received a CT scan to check for lung cancer in the last 12 months. Efforts to educate health care providers and provide decision support tools might increase recommended lung cancer screening.

      3. PURPOSE: Cancer treatment may be affected by comorbidities; however, studies are limited. The purpose of this study is to examine the frequency of comorbidities at visits by patients with breast, prostate, colorectal, and lung cancer and to estimate frequency of a prescription for antineoplastic drugs being included in the treatment received at visits by patients with cancer and concomitant comorbidities. METHODS: We used nationally representative data on visits to office-based physicians from the 2010-2016 National Ambulatory Medical Care Survey and selected visits by adults with breast, prostate, colorectal, or lung cancer (n = 4,672). Nineteen comorbid conditions were examined. Descriptive statistics were calculated for visits by cancer patients with 0, 1, and >/= 2 comorbidities. RESULTS: From 2010-2016, a total of 10.2 million physician office visits were made annually by adult patients with breast, prostate, colorectal, or lung cancer. Among US visits by adult patients with breast, prostate, colorectal, or lung cancer, 56.3% were by patients with >/= 1 comorbidity. Hypertension was the most frequently observed comorbidity (37.7%), followed by hyperlipidemia (19.0%) and diabetes (12.3%). Antineoplastic drugs were prescribed in 33.5% of the visits and prescribed at a lower percentage among visits by cancer patients with COPD (21.3% versus 34.3% of visits by cancer patients without COPD) and heart disease (22.7% versus 34.2% of visits by cancer patients without heart disease). CONCLUSION: Our study provides information about comorbidities in cancer patients being treated by office-based physicians in an ambulatory setting.

    • Communicable Diseases
      1. Nutritional factors and infectious agents may contribute to paediatric growth deficits in low- and middle-income countries; however, the contribution of enteric pathogens is only beginning to be understood. We analysed the stool from children <5 years old from an open cohort, cluster-randomised controlled trial of a point-of-collection water chlorinator in urban Bangladesh. We compared the presence/absence of 15 enteric pathogens detected via multiplex, molecular methods in the stool with concurrent Z-scores/Z-score cut-offs (-2 standard deviations (s.d.)) for height-for-age (HAZ/stunting), weight-for-age (WAZ/underweight) and weight-for-height (WHZ/wasting), adjusted for sociodemographic and trial-related factors, and measured caregiver-reported diarrhoea. Enteric pathogen prevalence in the stool was high (88% had >/=1 enteric pathogen, most commonly Giardia spp. (40%), Salmonella enterica (33%), enterotoxigenic E. coli (28%) and Shigella spp. (27%)) while reported 7-day diarrhoea prevalence was 6%, suggesting high subclinical infection rates. Many children were stunted (26%) or underweight (24%). Adjusted models suggested Giardia spp. detection was associated with lower HAZ (-0.22 s.d., 95% CI -0.44 to 0.00; prevalence ratio for stunting: 1.39, 95% CI 0.94-2.06) and potentially lower WAZ. No pathogens were associated with reported diarrhoea in adjusted models. Giardia spp. carriage may be associated with growth faltering, but not diarrhoea, in this and similar low-income settings. Stool-based enteric pathogen detection provides a direct indication of previous exposure that may be useful as a broader endpoint of trials of environmental interventions.

      2. Case management and capacity building to enhance hepatitis C treatment uptake at community health centers in a large urban settingexternal icon
        Boodram B, Kaufmann M, Aronsohn A, Hamlish T, Peregrine Antalis E, Kim K, Wolf J, Rodriguez I, Millman AJ, Johnson D.
        Fam Community Health. 2020 Apr/Jun;43(2):150-160.
        An estimated 4.1 million people in the United States are infected with hepatitis C virus (HCV). In 2014, the Hepatitis C Community Alliance to Test and Treat (HepCCATT) collaborative was formed to address hepatitis C in Chicago. From 2014 to 2017, the HepCCATT Case Management Program case managed 181 HCV-infected people and performed on-site capacity building at a 6-site community health center (CHC) that produced codified protocols, which were translated into a telehealth program to build capacity within CHCs to deliver hepatitis C care. HepCCATT's innovative approach to addressing multilevel barriers is a potential model for increasing access to hepatitis C care and treatment.

      3. Viral rebound among persons with diagnosed HIV who achieved viral suppression, United Statesexternal icon
        Craw JA, Beer L, Tie Y, Jaenicke T, Shouse RL, Prejean J.
        J Acquir Immune Defic Syndr. 2020 Feb 7.
        BACKGROUND: Some persons who achieve viral suppression may later experience viral rebound, potentially putting them at risk for transmitting HIV. We estimate the prevalence of, and describe factors associated with, viral rebound among adults with diagnosed HIV in the United States who had >/=2 viral load tests in a 12-month period. SETTING: The Medical Monitoring Project (MMP) is an annual cross-sectional survey about the experiences and needs of adults with diagnosed HIV sampled from the National HIV Surveillance System (NHSS). METHODS: We analyzed interview and medical record data from three MMP cycles spanning June 2015-May 2018. We analyzed viral load results from the 12-month period before the interview among persons with >/=2 viral load tests who achieved viral suppression. Data were weighted based on known probabilities of selection, adjusted for patient nonresponse, and post-stratified to known population totals from NHSS. RESULTS: Among those with >/=2 viral load tests who achieved viral suppression, 7.5% demonstrated viral rebound. In multivariable analyses, viral rebound was higher among non-Hispanic blacks, persons ages 18-39, persons with public insurance, persons recently experiencing homelessness, persons with higher numbers of viral load tests, persons who missed HIV care appointments, and persons with sub-optimal adherence to antiretroviral therapy. CONCLUSIONS: Viral rebound varied by sociodemographic and clinical characteristics. HIV providers can monitor persons at greatest risk for viral rebound and link patients with ancillary services or evidence-based interventions to help them remain virally suppressed. Our findings can inform strategies and interventions implemented under the Ending the HIV Epidemic initiative.

      4. Ending the HIV epidemic in the United Statesexternal icon
        Demeke HB, McCray E, Dean HD.
        Am J Nurs. 2020 Mar;120(3):21-22.
        A new initiative aims to reduce new infections by 75% within five years.

      5. Identification of an emergent pathogen, Bartonella vinsonii, using next-generation sequencing in a patient with culture-negative endocarditisexternal icon
        Downey RD, Russo SM, Hauger SB, Murphey DK, Marx G, Huynh T, Denison AM, Quirt R, Bailey A, Fernandez M.
        J Pediatric Infect Dis Soc. 2020 Feb 24.
        Diagnosis and treatment of culture negative endocarditis remains a challenge. This report describes a rare cause of endocarditis in humans, Bartonella vinsonii, identified through next generation sequencing of plasma microbial cell-free DNA with confirmation of cardiac valve tissue infection through immunohistochemical staining and polymerase chain reaction.

      6. High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatmentexternal icon
        El Bouzidi K, Kemp SA, Datir RP, Murtala-Ibrahim F, Aliyu A, Kwaghe V, Frampton D, Roy S, Breuer J, Sabin CA, Ogbanufe O, Charurat ME, Bonsall D, Golubchik T, Fraser C, Dakum P, Ndembi N, Gupta RK.
        J Antimicrob Chemother. 2020 Feb 27.
        OBJECTIVES: HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa. METHODS: We studied a Nigerian cohort of recipients prior to and during receipt of second-line PI-based therapy, who were integrase inhibitor-naive. Illumina next-generation sequencing with target enrichment was used on stored plasma samples. Drug resistance was interpreted using the Stanford Resistance Database and the IAS-USA 2019 mutation lists. RESULTS: Of 115 individuals, 59.1% harboured CRF02_AG HIV-1 and 40.9% harboured subtype G HIV-1. Four participants had major IAS-USA integrase resistance-associated mutations detected at low levels (2%-5% frequency). Two had Q148K minority variants and two had R263K (one of whom also had L74I). L74I was detected in plasma samples at over 2% frequency in 40% (46/115). Twelve (26.1%) had low-level minority variants of between 2% and 20% of the viral population sampled. The remaining 34 (73.9%) had L74I present at >20% frequency. L74I was more common among those with subtype G infection (55.3%, 26/47) than those with CRF02_AG infection (29.4%, 20/68) (P = 0.005). CONCLUSIONS: HIV-1 subtypes circulating in West Africa appear to have very low prevalence of major integrase mutations, but significant prevalence of L74I. A combination of in vitro and clinical studies is warranted to understand the potential implications.

      7. Efficient transmission of viral gastroenteritis in Dutch householdsexternal icon
        Gastanaduy PA, Parashar UD.
        Lancet Infect Dis. 2020 Feb 20.

      8. What do the Universal Test and Treat trials tell us about the path to HIV epidemic control?external icon
        Havlir D, Lockman S, Ayles H, Larmarange J, Chamie G, Gaolathe T, Iwuji C, Fidler S, Kamya M, Floyd S, Moore J, Hayes R, Petersen M, Dabis F.
        J Int AIDS Soc. 2020 Feb;23(2):e25455.
        INTRODUCTION: Achieving HIV epidemic control globally will require new strategies to accelerate reductions in HIV incidence and mortality. Universal test and treat (UTT) was evaluated in four randomized population-based trials (BCPP/Ya Tsie, HPTN 071/PopART, SEARCH, ANRS 12249/TasP) conducted in sub-Saharan Africa (SSA) during expanded antiretroviral treatment (ART) eligibility by World Health Organization guidelines and the UNAIDS 90-90-90 campaign. DISCUSSION: These three-year studies were conducted in Botswana, Zambia, Uganda, Kenya and South Africa in settings with baseline HIV prevalence from 4% to 30%. Key observations across studies were: (1) Universal testing (implemented via a variety of home and community-based testing approaches) achieved >90% coverage in all studies. (2) When coupled with robust linkage to HIV care, rapid ART start and patient-centred care, UTT achieved among the highest reported population levels of viral suppression in SSA. Significant gains in population-level viral suppression were made in regions with both low and high baseline population viral load; however, viral suppression gains were not uniform across all sub-populations and were lower among youth. (3) UTT resulted in marked reductions in community HIV incidence when universal testing and robust linkage were present. However, HIV elimination targets were not reached. In BCPP and HPTN 071, annualized HIV incidence was approximately 20% to 30% lower in the intervention (which included universal testing) compared to control arms (no universal testing). In SEARCH (where both arms had universal testing), incidence declined 32% over three years. (4) UTT reduced HIV associated mortality by 23% in the intervention versus control communities in SEARCH, a study in which mortality was comprehensively measured. CONCLUSIONS: These trials provide strong evidence that UTT inclusive of universal testing increases population-level viral suppression and decreases HIV incidence and mortality faster than the status quo in SSA and should be adapted at a sub-country level as a public health strategy. However, more is needed, including integration of new prevention interventions into UTT, in order to reach UNAIDS HIV elimination targets.

      9. Mumps: An update on outbreaks, vaccine efficacy, and genomic diversityexternal icon
        Lam E, Rosen JB, Zucker JR.
        Clin Microbiol Rev. 2020 Mar 18;33(2).
        SUMMARYMumps is an acute viral infection characterized by inflammation of the parotid and other salivary glands. Persons with mumps are infectious from 2 days before through 5 days after parotitis onset, and transmission is through respiratory droplets. Despite the success of mumps vaccination programs in the United States and parts of Europe, a recent increase in outbreaks of mumps virus infections among fully vaccinated populations has been reported. Although the effectiveness of the mumps virus component of the measles-mumps-rubella (MMR) vaccine is suboptimal, a range of contributing factors has led to these outbreaks occurring in high-vaccination-coverage settings, including the intensity of exposure, the possibility of vaccine strain mismatch, delayed implementation of control measures due to the timeliness of reporting, a lack of use of appropriate laboratory tests (such as reverse transcription-PCR), and time since last vaccination. The resurgence of mumps virus infections among previously vaccinated individuals over the past decade has prompted discussions about new strategies to mitigate the risk of future outbreaks. The decision to implement a third dose of the MMR vaccine in response to an outbreak should be considered in discussions with local public health agencies. Traditional public health measures, including the isolation of infectious persons, timely contact tracing, and effective communication and awareness education for the public and medical community, should remain key interventions for outbreak control. Maintaining high mumps vaccination coverage remains key to U.S. and global efforts to reduce disease incidence and rates of complications.

      10. Advances in clinical trial design: Weaving tomorrow's TB treatmentsexternal icon
        Lienhardt C, Nunn A, Chaisson R, Vernon AA, Zignol M, Nahid P, Delaporte E, Kasaeva T.
        PLoS Med. 2020 Feb;17(2):e1003059.
        Christian Lienhardt and co-authors discuss the conclusions of the PLOS Medicine Collection on advances in clinical trial design for development of new tuberculosis treatments.

      11. A decade on: Follow-up findings of indigenous children with bronchiectasisexternal icon
        McCallum GB, Singleton RJ, Redding GJ, Grimwood K, Byrnes CA, Valery PC, Mobberley C, Oguoma VM, Eg KP, Morris PS, Chang AB.
        Pediatr Pulmonol. 2020 Feb 25.
        OBJECTIVE: The sole prospective longitudinal study of children with either chronic suppurative lung disease (CSLD) or bronchiectasis published in the current era was limited to a single center. We sought to extend this study by evaluating the longer-term clinical and lung function outcomes and their associated risk factors in Indigenous children of adolescents from Australia, Alaska, and New Zealand who participated in our previous CSLD or bronchiectasis studies during 2004-2010. METHODS: Between 2015 and 2018, we evaluated 131 out of 180 (72.8%) children of adolescents from the original studies at a single follow-up visit. We administered standardized questionnaires, reviewed medical records, undertook clinical examinations, performed spirometry, and scored available chest computed tomography scans. RESULTS: Participants were seen at a mean age of 12.3 years (standard deviation: 2.6) and a median of 9.0 years (range: 5.0-13.0) after their original recruitment. With increasing age, rates of acute lower respiratory infections (ALRI) declined, while lung function was mostly within population norms (median forced expiry volume in one-second = 90% predicted, interquartile range [IQR]: 81-105; forced vital capacity [FVC] = 98% predicted, IQR: 85-114). However, 43 out of 111 (38.7%) reported chronic cough episodes. Their overall global rating judged by symptoms, including ALRI frequency, examination findings, and spirometry was well (20.3%), stable (43.9%), or improved (35.8%). Multivariable regression identified household tobacco exposure and age at first ALRI-episode as independent risk factors associated with lower FVC% predicted values. CONCLUSION: Under our clinical care, the respiratory outcomes in late childhood or early adolescence are encouraging for these patient populations at high-risk of premature mortality. Prospective studies to further inform management throughout the life course into adulthood are now needed.

      12. Toward universal HIV treatment in Haiti: Time trends in ART retention following expanded ART eligibility in a national cohort from 2011-17external icon
        Puttkammer N, Parrish C, Desir Y, Hyppolite N, Wagenaar B, Joseph N, Hall L, Honore JG, Robin E, Perrin G, Francois K.
        J Acquir Immune Defic Syndr. 2020 Feb 14.
        BACKGROUND: The World Health Organization (WHO) recommends universal antiretroviral therapy (ART) for people living with HIV (PLWH), but evidence about effects of expanded ART access on ART retention in low-resource settings is limited. SETTING: Haiti's Ministry of Health endorsed universal ART for pregnant women in March 2013 (Option B+) and for all PLWH in July 2016. This study included 51,579 ART patients from 2011-17 at 94 hospitals and clinics in Haiti. METHODS: This observational, retrospective cohort study described time trends in 6-month ART retention using secondary data, and compared results during three time periods using an interrupted time series (ITS) model: pre-Option B+ (period 1: 1/11-2/13), Option B+ (period 2: 3/13-6/16), and Test and Start (T&S, period 3: 7/16-9/17). RESULTS: From the pre-Option B+ to the T&S period, the monthly count of new ART patients increased from 366/month to 877/month, and the proportion with same-day ART increased from 6.3% to 42.1% (p<0.001). The proportion retained on ART after 6 months declined from 78.4% to 75.0% (p<0.001). In the ITS model, ART retention improved by a rate of 1.4% per quarter during the T&S period after adjusting for patient characteristics (Adjusted Incidence Rate Ratio [aIRR]=1.014; 95% confidence interval [CI]: 1.002-1.026, p<0.001). However, patients with same-day ART were 14% less likely to be retained compared to those starting ART >30 days after HIV diagnosis (aIRR=0.86; 95% CI: 0.84-0.89, p<0.001). CONCLUSION: Achieving targets for HIV epidemic control will require increasing ART retention and reducing the disparity in retention for those with same-day ART.

      13. Prevalence of self-reported neurologic and ocular symptoms in early syphilis casesexternal icon
        Quilter LA, de Voux A, Amiya RM, Davies E, Hennessy RR, Kerani RP, Madera R, Matthias J, Pearson VM, Walters JK, Wilson C, Kidd S, Torrone E.
        Clin Infect Dis. 2020 Feb 26.
        BACKGROUND: Neurosyphilis, a complication of syphilis, can occur at any stage of infection. Measuring the prevalence of neurosyphilis is challenging and there are limited data on the prevalence of neurologic or ocular symptoms among patients with syphilis. We sought to describe the prevalence of neurologic and/or ocular symptoms among early syphilis (ES) cases and the clinical management of symptomatic cases enrolled in the STD Surveillance Network (SSuN) Neuro/Ocular Syphilis Surveillance project. METHODS: Persons diagnosed with ES were selected for interviews based on current health department protocols in five participating SSuN jurisdictions from November 2016-October 2017. All interviewed ES cases were screened for self-reported neurologic and/or ocular symptoms. Additional clinical information on diagnostic testing and treatment for cases concerning for neurosyphilis/ocular syphilis was obtained from providers. RESULTS: Among 9,123 patients with ES who were interviewed, 151 (1.7%, 95% CI: 1.4-1.9) reported >/=1 neurologic or ocular symptom. Of the 53 (35%) who underwent lumbar puncture (LP), 22 (42%) had documented abnormal cerebrospinal fluid, of which 21 (95%) were treated for neurosyphilis/ocular syphilis. Among the remaining 98 symptomatic patients with no documented LP (65%), 12 (12%) were treated for and/or clinically diagnosed with neurosyphilis/ocular syphilis. CONCLUSIONS: We observed a low prevalence of self-reported neurologic and/or ocular symptoms in interviewed ES cases. Approximately one-third of ES cases who self-reported symptoms underwent further recommended diagnostic evaluation. Understanding barriers to appropriate clinical evaluation is important to ensuring appropriate management of patients with possible neurologic and/or ocular manifestations of syphilis.

      14. Results of a pilot study of a mail-based human papillomavirus self-testing program for underscreened women from Appalachian Ohioexternal icon
        Reiter PL, Shoben AB, McDonough D, Ruffin MT, Steinau M, Unger ER, Paskett ED, Katz ML.
        Sex Transm Dis. 2019 Mar;46(3):185-190.
        BACKGROUND: Human papillomavirus (HPV) self-testing is an emerging cervical cancer screening strategy, yet few mail-based HPV self-testing programs have been implemented in the United States. We report the results of a pilot study of a mail-based program, the Health Outcomes through Motivation and Education Project. METHODS: In 2015 to 2016, we recruited 103 women from Appalachian Ohio who were aged 30 to 65 years and had not received a Papanicolaou (Pap) test in at least 3 years. Women were mailed an HPV self-test and randomized to receive either (a) self-test instructions developed by the device manufacturer and a standard information brochure about cervical cancer (control group) or (b) self-test instructions developed by the Health Outcomes through Motivation and Education Project and a photo story information brochure about cervical cancer (intervention group). Logistic regression compared study arms on HPV self-test return and receipt of a Pap test. RESULTS: Overall, 80 (78%) women returned their HPV self-test. Return was similar among the intervention and control groups (78% vs. 77%; odds ratio, 1.09; 95% confidence interval, 0.43-2.76). Among returners, 26% had an oncogenic HPV type detected in their sample. Women who returned their self-test reported high levels of satisfaction and positive experiences with the self-testing process. Few women overall received a Pap test (11%), and Pap testing was similar among the intervention and control groups (14% vs. 8%; odds ratio, 1.91; 95% confidence interval, 0.52-6.97). CONCLUSIONS: Mail-based HPV self-testing programs are a potentially promising strategy for reaching underscreened women in Appalachia. Efforts are needed to better understand how to optimize the success of such programs.

      15. Hospital discharge data underascertain enteric bacterial infections among childrenexternal icon
        Scallan Walter EJ, McLean HQ, Griffin PM.
        Foodborne Pathog Dis. 2020 Feb 24.
        Many enteric pathogens disproportionately infect children. Hospital discharge data can provide information on severe infections, including cost. However, the diagnosis must be recorded on the discharge record and coded accurately. We estimated the rate of underascertainment in hospital discharge data among children with culture-confirmed Campylobacter, Salmonella, and Escherichia coli O157 infections using linked laboratory and hospital discharge data from an integrated health care organization. We reviewed the International Classification of Diseases, 9th and 10th Revisions, Clinical Modification (ICD-9/10-CM) diagnosis codes on each patient's discharge record. We determined the percentage of patients who had a pathogen-specific diagnosis code (for Campylobacter, Salmonella, or E. coli O157) or nonspecific gastroenteritis code. We included the first admission or positive test and calculated the number of days between specimen submission (outpatient </=7 days before admission or inpatient) and hospital discharge. Of 65 hospitalized children with culture-confirmed Campylobacter (n = 30), Salmonella (n = 24), or E. coli O157 (n = 11) infections, 55% had that pathogen-specific diagnosis code listed on the discharge record (79% Salmonella, 54% E. coli O157, 37% Campylobacter). The discharge records of the 35 children with a specimen submitted for culture >/=3 days before discharge were 16 times more likely to have a pathogen-specific diagnosis than the records of the 30 children with a specimen submitted <3 days before discharge (83% vs. 23%; odds ratio 15.9, 95% confidence interval: 4.7-53.8). Overall, 34% of records of children with culture-confirmed infection had >/=1 nonspecific gastroenteritis code (Campylobacter 43%, Salmonella 29%, E. coli O157 18%), including 59% of those for children without a pathogen-specific diagnosis (Campylobacter 63%; Salmonella 60%; E. coli O157 40%). This study showed that hospital discharge data under-ascertain enteric illnesses in children even when the infections are culture confirmed, especially for infections that usually have a short length of stay.

      16. Fatal case of Legionnaires' disease after home exposure to Legionella pneumophila serogroup 3 - Wisconsin, 2018external icon
        Schumacher A, Kocharian A, Koch A, Marx J.
        MMWR Morb Mortal Wkly Rep. 2020 Feb 28;69(8):207-211.
        In January 2018, the Wisconsin Department of Health Services, Division of Public Health (DPH), received a report of a culture-confirmed case of Legionnaires' disease. The patient, who was immunocompromised, had died at a local hospital 10 days after being admitted. DPH and an infection preventionist from the hospital investigated to determine the source of the infection and prevent additional cases. Because the case was suspected to be nosocomial, health care facility water samples were tested for Legionella. When these samples were negative, water sources in the patient's home were tested. These tested positive for Legionella pneumophila, and the bacteria remained after an attempt to remediate. The patient and home isolates were identified as L. pneumophila serogroup 3, sequence type 93, by whole-genome multilocus sequence typing. A second resident of the home did not become ill. This case highlights the potential for immunocompromised persons and others at risk for Legionnaires' disease to be exposed to Legionella through home water systems containing the bacteria and demonstrates the difficulty of home remediation. This case also illustrates the role of lower respiratory tract specimens in the identification of less common Legionella infections (e.g., L. pneumophila serogroup 3) and confirmation of the infection source.

      17. Evidence of an association of increases in pre-exposure prophylaxis coverage with decreases in human immunodeficiency virus diagnosis rates in the United States, 2012-2016external icon
        Smith DK, Sullivan PS, Cadwell B, Waller LA, Siddiqi A, Mera-Giler R, Hu X, Hoover KW, Harris NS, McCallister S.
        Clin Infect Dis. 2020 Feb 25.
        BACKGROUND: Annual human immunodeficiency virus (HIV) diagnoses in the United States (US) have plateaued since 2013. We assessed whether there is an association between uptake of pre-exposure prophylaxis (PrEP) and decreases in HIV diagnoses. METHODS: We used 2012-2016 data from the US National HIV Surveillance System to estimate viral suppression (VS) and annual percentage change in diagnosis rate (EAPC) in 33 jurisdictions, and data from a national pharmacy database to estimate PrEP uptake. We used Poisson regression with random effects for state and year to estimate the association between PrEP coverage and EAPC: within jurisdictional quintiles grouped by changes in PrEP coverage, regressing EAPC on time; and among all jurisdictions, regressing EAPC on both time and jurisdictional changes in PrEP coverage with and without accounting for changes in VS. RESULTS: From 2012 to 2016, across the 10 states with the greatest increases in PrEP coverage, the EAPC decreased 4.0% (95% confidence interval [CI], -5.2% to -2.9%). On average, across the states and District of Columbia, EAPC for a given year decreased by 1.1% (95% CI, -1.77% to -.49%) for an increase in PrEP coverage of 1 per 100 persons with indications. When controlling for VS, the state-specific EAPC for a given year decreased by 1.3% (95% CI, -2.12% to -.57%) for an increase in PrEP coverage of 1 per 100 persons with indications. CONCLUSIONS: We found statistically significant associations between jurisdictional increases in PrEP coverage and decreases in EAPC independent of changes in VS, which supports bringing PrEP use to scale in the US to accelerate reductions in HIV infections.

      18. Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling studyexternal icon
        Wang X, Li Y, O'Brien KL, Madhi SA, Widdowson MA, Byass P, Omer SB, Abbas Q, Ali A, Amu A, Azziz-Baumgartner E, Bassat Q, Abdullah Brooks W, Chaves SS, Chung A, Cohen C, Echavarria M, Fasce RA, Gentile A, Gordon A, Groome M, Heikkinen T, Hirve S, Jara JH, Katz MA, Khuri-Bulos N, Krishnan A, de Leon O, Lucero MG, McCracken JP, Mira-Iglesias A, Moisi JC, Munywoki PK, Ourohire M, Polack FP, Rahi M, Rasmussen ZA, Rath BA, Saha SK, Simoes EA, Sotomayor V, Thamthitiwat S, Treurnicht FK, Wamukoya M, Yoshida LM, Zar HJ, Campbell H, Nair H.
        Lancet Glob Health. 2020 Feb 20.
        BACKGROUND: Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018. METHODS: We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and population-based childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries. FINDINGS: In 2018, among children under 5 years globally, there were an estimated 109.5 million influenza virus episodes (uncertainty range [UR] 63.1-190.6), 10.1 million influenza-virus-associated ALRI cases (6.8-15.1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 in-hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries. INTERPRETATION: A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries. FUNDING: WHO; Bill & Melinda Gates Foundation.

      19. Estimating the probability of diagnosis within one year of HIV acquisitionexternal icon
        Xia Q, Lim S, Wu B, Forgione LA, Crossa A, Balaji AB, Braunstein SL, Daskalakis DC, Tsoi BW, Harriman G, Torian LV, Song R.
        Aids. 2020 Feb 20.
        BACKGROUND: Early diagnosis of HIV is important for the prevention of ongoing transmission and development of HIV-related illness. The purpose of this study is to develop an outcome indicator to monitor the progress in early HIV diagnosis. METHODS: Persons diagnosed with HIV in New York City and their first CD4 test results were used to estimate the distribution of HIV diagnosis delay, based on a CD4 count depletion model. The distribution was then used to estimate the probability of diagnosis within 1 year of HIV acquisition, which is the number of cases diagnosed in a given calendar year for which diagnosis occurred within 1 year of acquisition divided by the number of incident cases in that calendar year. RESULTS: In 2012-2016, the estimated annual probability of diagnosis within 1 year of HIV acquisition in New York City was 43.0% [95% confidence interval (CI): 37.9-48.2%), 42.5% (95% CI: 36.8--48.3%), 42.8% (95% CI: 36.3--49.2%), 42.9% (95% CI: 35.4--50.3%), and 42.2% (95% CI: 33.1--51.2%), respectively. CONCLUSION: National and local health jurisdictions should consider using this new outcome indicator, the probability of diagnosis within 1 year of HIV acquisition, to monitor their progress in early HIV diagnosis.

    • Environmental Health
      1. Per- and polyfluoroalkyl substances and blood pressure in pre-diabetic adults-cross-sectional and longitudinal analyses of the Diabetes Prevention Program Outcomes Studyexternal icon
        Lin PD, Cardenas A, Hauser R, Gold DR, Kleinman KP, Hivert MF, Calafat AM, Webster TF, Horton ES, Oken E.
        Environ Int. 2020 Feb 20;137:105573.
        The relationship of plasma concentration of per- and polyfluoroalkyl substances (PFAS) with blood pressure (BP) is uncertain. This study examined cross-sectional and prospective associations of PFAS with BP and hypertension. We quantified plasma PFAS concentrations from 957 participants enrolled in the lifestyle and placebo arms of the Diabetes Prevention Program (DPP), a randomized controlled trial with approximately 15 years of follow-up. We used multivariable linear and logistic regressions to test cross-sectional associations of six PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), N-methyl-perfluorooctane sulfonamido acetic acid (MeFOSAA), and perfluorononanoic acid (PFNA), with BP and hypertension prevalence, respectively, at baseline. We used generalized linear mixed models to estimate longitudinal associations between baseline PFAS and the rate of BP changes, and Cox-Proportional hazard models to estimate risk of developing hypertension relative to baseline PFAS. Models were adjusted for baseline age, sex, race/ethnicity, treatment arm, educational attainment, income, marital status, smoking habit, alcohol drinking, and diet. We tested for effect modification by the treatment arm and sex, and accounted for multiple comparisons using the False-Discovery Rate (FDR). PFAS concentrations and hypertension prevalence within the study population (65.3% female, 57.7% White, 65.3% aged 40-59 years) were comparable to the general U.S. population. Cross-sectionally, we found small but statistically significant associations of baseline plasma concentrations of PFOA with systolic BP (beta per doubling: 1.49 mmHg, 95% CI: 0.29, 2.70); and MeFOSAA with hypertension (RR = 1.09 per doubling, 95% CI: 1.01, 1.19). Estimates were not statistically significant after FDR adjustment. Longitudinally, we observed null associations in the placebo arm, but some inverse associations of baseline PFOS and MeFOSAA with systolic BP in the lifestyle arm, perhaps due to regression toward the mean. Baseline PFAS concentrations also were not prospectively associated with hypertension risk. Overall, there were modest and mostly null associations of plasma PFAS concentrations with BP and hypertension.

      2. Dietary characteristics associated with plasma concentrations of per- and polyfluoroalkyl substances among adults with pre-diabetes: Cross-sectional results from the Diabetes Prevention Program Trialexternal icon
        Lin PD, Cardenas A, Hauser R, Gold DR, Kleinman KP, Hivert MF, Fleisch AF, Calafat AM, Sanchez-Guerra M, Osorio-Yanez C, Webster TF, Horton ES, Oken E.
        Environ Int. 2020 Feb 18;137:105217.
        Diet is assumed to be the main source of exposure to per- and polyfluoroalkyl substances (PFAS) in non-occupationally exposed populations, but studies on the diet-PFAS relationship in the United States are scarce. We extracted multiple dietary variables, including daily intakes of food group, diet scores, and dietary patterns, from self-reported dietary data collected at baseline (1996-1999) from adults with pre-diabetes enrolled in the Diabetes Prevention Program, and used linear regression models to evaluate relationships of each dietary variable with plasma concentrations of six PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (EtFOSAA), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA), perfluorononanoic acid (PFNA) adjusting for covariates. Participants (N=941, 65% female, 58% Caucasian, 68% married, 75% with higher education, 95% nonsmoker) had similar PFAS concentrations compared to the general U.S. population during 1999-2000. Using a single food group approach, fried fish, other fish/shellfish, meat and poultry had positive associations with most PFAS plasma concentrations. The strongest effect estimate detected was between fried fish and PFNA [13.6% (95% CI: 7.7, 19.9) increase in median concentration per SD increase]. Low-carbohydrate and high protein diet score had positive association with plasma PFHxS. Some food groups, mostly vegetables and fruits, and the Dietary Approaches to Stop Hypertension diet score had inverse associations with PFOS and MeFOSAA. A vegetable diet pattern was associated with lower plasma concentrations of MeFOSAA, while high-fat meat and low-fiber and high-fat grains diet patterns were associated with higher plasma concentrations of PFOS, PFHxS, MeFOSAA and PFNA. We summarized four major dietary characteristics associated with variations in PFAS plasma concentrations in this population. Specifically, consuming more meat/fish/shellfish (especially fried fish, and excluding Omega3-rich fish), low-fiber and high-fat bread/cereal/rice/pasta, and coffee/tea was associated with higher plasma concentrations while dietary patterns of vegetables, fruits and Omega-3 rich fish were associated with lower plasma concentrations of some PFAS.

      3. Associations between fine particulate matter, extreme heat events, and congenital heart defectsexternal icon
        Stingone JA, Luben TJ, Sheridan SC, Langlois PH, Shaw GM, Reefhuis J, Romitti PA, Feldkamp ML, Nembhard WN, Browne ML, Lin S.
        Environ Epidemiol. 2019 Dec;3(6):e071.
        Previous research reports associations between air pollution measured during pregnancy and the occurrence of congenital heart defects (CHDs) in offspring. The objective of this research was to assess if exposure to extreme heat events (EHEs) during pregnancy may modify this association. Methods: The study population consisted of 4,033 controls and 2,632 cases with dates of delivery between 1999 and 2007 who participated in the National Birth Defects Prevention Study, a multi-site case-control study in the United States. Daily data from the closest stationary fine particulate matter (PM2.5) monitor within 50 km from the maternal residence were averaged across weeks 3-8 post-conception. EHEs were defined as maximum ambient temperature in the upper 95th percentile for at least 2 consecutive days or the upper 90th percentile for 3 consecutive days. Logistic regression models were adjusted for maternal age, ethnicity, education, and average humidity. Relative excess risks due to interaction (RERI) were calculated. Results: Compared with women with low PM2.5 exposure and no exposure to an EHE, the odds of a ventricular septal defect in offspring associated with high PM2.5 exposure was elevated only among women who experienced an EHE (odds ratio [OR] 2.14 95% confidence interval [CI] 1.19, 3.38 vs. OR 0.97 95% CI 0.49, 1.95; RERI 0.82 95% CI -0.39, 2.17). The majority of observed associations and interactions for other heart defects were null and/or inconclusive due to lack of precision. Conclusions: This study provides limited evidence that EHEs may modify the association between prenatal exposure to PM2.5 and CHD occurrence.

    • Food Safety
      1. Outbreak of gastrointestinal anthrax following eating beef of suspicious origin: Isingiro District, Uganda, 2017external icon
        Nakanwagi M, Ario AR, Kwagonza L, Aceng FL, Mwesigye J, Bulage L, Buule J, Sendagala JN, Downing R, Zhu BP.
        PLoS Negl Trop Dis. 2020 Feb 27;14(2):e0008026.
        INTRODUCTION: Gastrointestinal anthrax is a rare but serious disease. In August 2017, Isingiro District, Uganda reported a cluster of >40 persons with acute-onset gastroenteritis. Symptoms included bloody diarrhoea. We investigated to identify the etiology and exposures, and to inform control measures. METHODS: We defined a suspected case as acute-onset of diarrhoea or vomiting during 15-31 August 2017 in a resident (aged>/=2 years) of Kabingo sub-county, Isingiro District; a confirmed case was a suspected case with a clinical sample positive for Bacillus anthracis by culture or PCR. We conducted descriptive epidemiology to generate hypotheses. In a case-control study, we compared exposures between case-patients and neighbourhood-matched controls. We used conditional logistic regression to compute matched odds ratios (MOR) for associations of illness with exposures. RESULTS: We identified 61 cases (58 suspected and 3 confirmed; no deaths). In the case-control study, 82% of 50 case-patients and 12% of 100 controls ate beef purchased exclusively from butchery X during the week before illness onset (MOR = 46, 95%CI = 4.7-446); 8.0% of case-patients and 3.0% of controls ate beef purchased from butchery X and elsewhere (MOR = 19, 95%CI = 1.0-328), compared with 6.0% of case-patients and 30% of controls who did not eat beef. B. anthracis was identified in two vomitus and one stool sample. Butchery X slaughtered a sick cow and sold the beef during case-patients' incubation period. CONCLUSION: This gastrointestinal anthrax outbreak occurred due to eating beef from butchery X. We recommended health education, safe disposal of the carcasses of livestock or game animals, and anthrax vaccination for livestock.

    • Health Disparities
      1. Disparities in shigellosis incidence by census tract poverty, crowding, and race/ethnicity in the United States, FoodNet, 2004-2014external icon
        Libby T, Clogher P, Wilson E, Oosmanally N, Boyle M, Eikmeier D, Nicholson C, McGuire S, Cieslak P, Golwalkar M, Geissler A, Vugia D.
        Open Forum Infect Dis. 2020 Feb;7(2):ofaa030.
        Background: Shigella causes an estimated 500 000 enteric illnesses in the United States annually, but the association with socioeconomic factors is unclear. Methods: We examined possible epidemiologic associations between shigellosis and poverty using 2004-2014 Foodborne Diseases Active Surveillance Network (FoodNet) data. Shigella cases (n = 21 246) were geocoded, linked to Census tract data from the American Community Survey, and categorized into 4 poverty and 4 crowding strata. For each stratum, we calculated incidence by sex, age, race/ethnicity, and FoodNet site. Using negative binomial regression, we estimated incidence rate ratios (IRRs) comparing the highest to lowest stratum. Results: Annual FoodNet Shigella incidence per 100 000 population was higher among children <5 years old (19.0), blacks (7.2), and Hispanics (5.6) and was associated with Census tract poverty (incidence rate ratio [IRR], 3.6; 95% confidence interval [CI], 3.5-3.8) and household crowding (IRR, 1.8; 95% CI, 1.7-1.9). The association with poverty was strongest among children and persisted regardless of sex, race/ethnicity, or geographic location. After controlling for demographic variables, the association between shigellosis and poverty remained significant (IRR, 2.3; 95% CI, 2.0-2.6). Conclusions: In the United States, Shigella infections are epidemiologically associated with poverty, and increased incidence rates are observed among young children, blacks, and Hispanics.

    • Healthcare Associated Infections
      1. Association between use of diagnostic tests and antibiotic prescribing for pharyngitis in the United Statesexternal icon
        Shapiro DJ, King LM, Fleming-Dutra KE, Hicks LA, Hersh AL.
        Infect Control Hosp Epidemiol. 2020 Feb 24:1-3.

    • Immunity and Immunization
      1. Since 2006, more than 100 countries have introduced rotavirus vaccine into their immunization programs. We reviewed published data on relative reductions of rotavirus hospitalizations, acute gastroenteritis (AGE) hospitalizations, and AGE deaths among children <5 years old. Articles published from 1 January 2006 to 31 December 2019 with at least 12 months of data before and after rotavirus vaccine introduction were included. Relative reductions were abstracted into a standardized form. Descriptive statistics are presented as medians and interquartile ranges (IQR). We reviewed 1827 total records and included 105 articles from 49 countries. Among children <5 years old, there was a median reduction of 59% (IQR: 46, 74) in rotavirus hospitalizations, 36% (IQR: 23, 47) in AGE hospitalizations, and 36% (IQR: 28, 46) AGE mortality. Reductions were larger in countries with low child mortality, among younger age groups, and in countries with higher coverage. The median percentage of specimens that tested positive for rotavirus among children <5 years old hospitalized for diarrhea was 40% (IQR: 28, 45) before rotavirus vaccine introduction and 20% (IQR: 20, 20) 4 years after introduction. Overall, we found sustained impact on rotavirus and AGE hospitalizations and deaths. These results should encourage countries still considering rotavirus vaccine implementation.

      2. Tetanus, diphtheria, and acellular pertussis and influenza vaccinations among women with a live birth, Internet Panel Survey, 2017-2018external icon
        Murthy NC, Black C, Kahn KE, Ding H, Ball S, Fink RV, Devlin R, D'Angelo D, Fiebelkorn AP.
        Infect Dis (Auckl). 2020 ;13:1178633720904099.
        Objectives: Pregnant women are at increased risk of complications from influenza, and infants are at increased risk of pertussis. Maternal influenza and Tdap (tetanus, diphtheria, and acellular pertussis) vaccination can reduce risk of these infections and related complications. Our objective was to estimate vaccination coverage with influenza and Tdap vaccines during pregnancy among women with a recent live birth. Methods: An opt-in Internet panel survey was conducted from March 28 to April 10, 2018 among pregnant and recently pregnant women. Respondents with a live birth from August 1, 2017 through the date in which the participant completed the survey were included in the analysis. Receipt of influenza vaccination since July 1, 2017 and Tdap vaccination during pregnancy were assessed by sociodemographic characteristics, receipt of a health care provider (HCP) recommendation and/or offer of vaccination, and vaccination-related knowledge, attitudes, and beliefs. Results: Less than a third (30.3%) of women with a live birth were unvaccinated during their pregnancy with both Tdap and influenza vaccines. Almost a third (32.8%) of the women reported being vaccinated with both vaccines. The majority (73.0%) of women reported receiving an HCP recommendation for both vaccines, and 54.2% of women were offered both vaccines by an HCP. Reasons for nonvaccination included negative attitudes toward influenza vaccine and lack of awareness about Tdap vaccination during pregnancy. Conclusions: Maternal Tdap and influenza vaccinations can prevent morbidity and mortality among infants and their mothers, yet many pregnant women are unvaccinated with either Tdap or influenza vaccines. Clinic-based education, along with interventions, such as standing orders and provider reminders, are strategies to increase maternal vaccination.

      3. Pediatricians' experiences with and perceptions of the Vaccines for Children Programexternal icon
        O'Leary ST, Allison MA, Vogt T, Hurley LP, Crane LA, Brtnikova M, McBurney E, Beaty BL, Crawford N, Lindley MC, Stokley SK, Kempe A.
        Pediatrics. 2020 Feb 21.
        BACKGROUND AND OBJECTIVES: The Vaccines for Children Program (VFC) provides vaccines for children who may not otherwise be vaccinated because of financial barriers. Pediatrician participation is crucial to the VFC's ongoing success. Our objectives were to assess, among a national sample of pediatricians, (1) VFC program participation, (2) perceived burden versus benefit of participation, and (3) knowledge and perception of a time-limited increased payment for VFC vaccine administration under the Patient Protection and Affordable Care Act. METHODS: An electronic and mail survey was conducted from June 2017 to September 2017. RESULTS: Response rate was 79% (372 of 471); 86% of pediatricians reported currently participating in the VFC; among those, 85% reported never having considered stopping, 10% considered it but not seriously, and 5% seriously considered it. Among those who had considered no longer participating (n = 47), the most commonly reported reasons included difficulty meeting VFC record-keeping requirements (74%), concern about action by the VFC for noncompliance (61%), and unpredictable VFC vaccine supplies (59%). Participating pediatricians rated, on a scale from -5 (high burden) to +5 (high benefit), their overall perception of the VFC: 63% reported +4 or +5, 23% reported +1 to +3, 5% reported 0, and 9% reported -1 to -5. Of pediatricians, 39% reported awareness of temporary increased payment for VFC vaccine administration. Among those, 10% reported that their practice increased the proportion of Medicaid and/or VFC-eligible patients served on the basis of this change. CONCLUSIONS: For most pediatricians, perceived benefits of VFC participation far outweigh perceived burdens. To ensure the program's ongoing success, it will be important to monitor factors influencing provider participation.

    • Injury and Violence
      1. Firearm homicide and suicide are the leading causes of violence-related injury deaths among U.S. youth. However, evaluations of the effectiveness of firearm violence prevention programs and strategies to reducing youth firearm violence are limited. To help inform and evaluate such efforts, this study aimed to identify risk and protective factors associated with youth firearm access, possession or carrying (for reasons other than hunting or target shooting) among a sample of U.S. urban youth in the Mountain West. Findings show the influence that youth violence risk (e.g., having friends engaged in delinquency; violence; drug sales; gang fights; exposure to violence; screening positive for violence risk) can have on youth firearm access, possession or carrying. Implications for prevention and intervention are discussed.

      2. Adverse childhood experiences (ACEs) are associated with mental health and substance use problems, but lesser known is how they interconnect. The objective of this study was to examine how internalizing and externalizing symptoms mediate the association of ACEs with prescription opioid misuse in order to understand how ACEs interconnect with mental health and substance use problems. Adults aged 18 or older from the National Epidemiological Survey on Alcohol and Related Conditions Wave 3 (NESARC-III) conducted in 2012-2013 were included (N=36,309). The prescription opioid misuse outcomes examined include prescription opioid misuse status, early-onset status of prescription opioid misuse, frequency of past-year prescription opioid misuse, and opioid use disorder. A natural effect model and regression analyses were used to conduct the mediation analyses. We found that respondents with higher ACE scores had greater odds of reporting past-year and lifetime prescription opioid misuse and DSM-V-diagnosed opioid use disorder as well as early onset of prescription opioid misuse (AORs range from 1.06 to 1.12). These associations are partially mediated by internalizing and externalizing symptoms. The findings suggest that internalizing and externalizing symptoms may be potential pathways through which ACEs are associated with prescription opioid misuse. Our results underscore the importance of preventing ACEs and reducing risk for internalizing and externalizing symptoms after exposure, which may reduce later prescription opioid misuse.

    • Laboratory Sciences
      1. An animal model of inhaled vitamin E acetate and EVALI-like lung injuryexternal icon
        Bhat TA, Kalathil SG, Bogner PN, Blount BC, Goniewicz ML, Thanavala YM.
        N Engl J Med. 2020 Feb 26.

      2. Influenza virus NS1- C/EBPbeta gene regulatory complex inhibits RIG-I transcriptionexternal icon
        Kumari R, Guo Z, Kumar A, Wiens M, Gangappa S, Katz JM, Cox NJ, Lal RB, Sarkar D, Fisher PB, Garcia-Sastre A, Fujita T, Kumar V, Sambhara S, Ranjan P, Lal SK.
        Antiviral Res. 2020 Feb 21:104747.
        Influenza virus non-structural protein 1 (NS1) counteracts host antiviral innate immune responses by inhibiting Retinoic acid inducible gene-I (RIG-I) activation. However, whether NS1 also specifically regulates RIG-I transcription is unknown. Here, we identify a CCAAT/Enhancer Binding Protein beta (C/EBPbeta) binding site in the RIG-I promoter as a repressor element, and show that NS1 promotes C/EBPbeta phosphorylation and its recruitment to the RIG-I promoter as a C/EBPbeta/NS1 complex. C/EBPbeta overexpression and siRNA knockdown in human lung epithelial cells resulted in suppression and activation of RIG-I expression respectively, implying a negative regulatory role of C/EBPbeta. Further, C/EBPbeta phosphorylation, its interaction with NS1 and occupancy at the RIG-I promoter was associated with RIG-I transcriptional inhibition. These findings provide an important insight into the molecular mechanism by which influenza NS1 commandeers RIG-I transcriptional regulation and suppresses host antiviral responses.

      3. Neutralization capacity of highly divergent type 2 vaccine-derived polioviruses from immunodeficient patientsexternal icon
        McDonald SL, Weldon WC, Wei L, Chen Q, Shaw J, Zhao K, Jorba J, Kew OM, Pallansch MA, Burns CC, Oberste MS.
        Vaccine. 2020 Feb 20.
        The use of the oral poliovirus vaccine (OPV) in developing countries has reduced the incidence of poliomyelitis by >99% since 1988 and is the primary tool for global polio eradication. Spontaneous reversions of the vaccine virus to a neurovirulent form can impede this effort. In persons with primary B-cell immunodeficiencies, exposure to OPV can result in chronic infection, mutation, and excretion of immunodeficiency-associated vaccine-derived polioviruses, (iVDPVs). These iVDPVs may have the potential for transmission in a susceptible population and cause paralysis. The extent to which sera from OPV recipients are able to neutralize iVDPVs with varying degrees of antigenic site substitutions is investigated here. We tested sera from a population immunized with a combination vaccine schedule (both OPV and inactivated polio vaccine) against a panel of iVDPVs and found that increases in amino acid substitution in the P1 capsid protein resulted in a decrease in the neutralizing capacity of the sera. This study underscores the importance of maintaining high vaccine coverage in areas of OPV use as well as active surveillance of those known to be immunocompromised.

      4. A DNA polymerization-independent role for mitochondrial DNA polymerase IC in African trypanosomesexternal icon
        Miller JC, Delzell SB, Concepcion-Acevedo J, Boucher MJ, Klingbeil MM.
        J Cell Sci. 2020 Feb 20.
        The mitochondrial DNA of Trypanosoma brucei and related parasites is a catenated network containing thousands of minicircles and tens of maxicircles called kinetoplast DNA (kDNA). Replication of the single nucleoid requires at least three DNA polymerases (POLIB, POLIC, and POLID) each having discrete localization near the kDNA during S phase. POLIB and POLID have roles in minicircle replication while the specific role of POLIC in kDNA maintenance is less clear. Here, we use an RNAi-complementation system to dissect the functions of the distinct POLIC domains: the conserved family A DNA polymerase domain (POLA) and the uncharacterized N-terminal region (UCR). While RNAi complementation with wild-type POLIC restored kDNA content and cell cycle localization, active site point mutations in the POLA domain impaired minicircle replication similarly to POLIB and POLID depletions. Complementation with POLA domain alone abolished POLIC foci formation and partially rescued the RNAi phenotype. Furthermore, we provide evidence of a crucial role for the UCR in cell cycle localization that facilitates proper distribution of progeny networks. This is the first report of a DNA polymerase that impacts mitochondrial nucleoid distribution.

      5. The utility of human immune system mice for high-containment viral hemorrhagic fever researchexternal icon
        Wozniak DM, Lavender KJ, Prescott J, Spengler JR.
        Vaccines (Basel). 2020 Feb 22;8(1).
        Human immune system (HIS) mice are a subset of humanized mice that are generated by xenoengraftment of human immune cells or tissues and/or their progenitors into immunodeficient mice. Viral hemorrhagic fevers (VHFs) cause severe disease in humans, typically with high case fatality rates. HIS mouse studies have been performed to investigate the pathogenesis and immune responses to VHFs that must be handled in high-containment laboratory facilities. Here, we summarize studies on filoviruses, nairoviruses, phenuiviruses, and hantaviruses, and discuss the knowledge gained from using various HIS mouse models. Furthermore, we discuss the complexities of designing and interpreting studies utilizing HIS mice while highlighting additional questions about VHFs that can still be addressed using HIS mouse models.

    • Medicine
      1. Slowing decline in blood collection and transfusion in the United States - 2017external icon
        Jones JM, Sapiano MR, Savinkina AA, Haass KA, Baker ML, Henry RA, Berger JJ, Basavaraju SV.
        Transfusion. 2020 Feb 21.
        INTRODUCTION: The National Blood Collection and Utilization Survey (NBCUS) has demonstrated declines in blood collection and transfusion in the United States since 2008, including declines of 11.6% in red blood cell (RBC) collections and 13.9% in RBC transfusions during 2013-2015. This study described the 2017 NBCUS results. METHODS: The 2017 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 2017 NBCUS were 88% for blood collection centers and 86% for transfusing hospitals. Compared with 2015, the number of RBC units collected during 2017 (12,211,000; 95% confidence interval [CI], 11,680,000-12,742,000) declined by 3.0%, and transfused RBC units (10,654,000, 95% CI, 10,314,000-10,995,000) declined by 6.1%. Distributed platelet (PLT) units (2,560,000; 95% CI, 2,391,000-2,730,000 units) increased by 5.1%, and transfused PLT units (1,937,000, 95% CI, 1,794,000-2,079,000) declined by 2.3%. Distributed plasma units (3,209,000; 95% CI, 2,879,000-3,539,000) declined by 13.6%, and transfused plasma units (2,374,000; 95% CI, 2,262,000-2,487,000) declined by 12.9%. CONCLUSION: The 2017 NBCUS suggests a continued but slowing decline in demand for RBCs. The decline in blood collection and use will likely continue. Despite decreasing demand and increasing manufacturing costs of blood products, the US blood industry has met the regular and emergent needs of the country.

    • Nutritional Sciences

    • Occupational Safety and Health
      1. Determinants of international variation in the prevalence of disabling wrist and hand painexternal icon
        Coggon D, Ntani G, Walker-Bone K, Felli VE, Harari F, Barrero LH, Felknor SA, Rojas M, Cattrell A, Serra C, Borchini R, Solidaki E, Merisalu E, Habib RR, Sadeghian F, Kadir MM, Peiris-John RJ, Matsudaira K, Nyantumbu-Mkhize B, Kelsall HL, Harcombe H.
        BMC Musculoskelet Disord. 2019 Sep 18;20(1):436.
        BACKGROUND: Previous research has indicated that wide international variation in the prevalence of disabling low back pain among working populations is largely driven by factors predisposing to musculoskeletal pain more generally. This paper explores whether the same applies to disabling wrist/hand pain (WHP). METHODS: Using data from the Cultural and Psychosocial Influences on Disability (CUPID) study, we focused on workers from 45 occupational groups (office workers, nurses and other workers) in 18 countries. Among 11,740 participants who completed a baseline questionnaire about musculoskeletal pain and potential risk factors, 9082 (77%) answered a further questionnaire after a mean interval of 14 months, including 1373 (15%) who reported disabling WHP in the month before follow-up. Poisson regression was used to assess associations of this outcome with baseline risk factors, including the number of anatomical sites other than wrist/hand that had been painful in the 12 months before baseline (taken as an index of general propensity to pain). RESULTS: After allowance for other risk factors, the strongest associations were with general pain propensity (prevalence rate ratio for an index >/=6 vs. 0: 3.6, 95% confidence interval 2.9-4.4), and risk rose progressively as the index increased. The population attributable fraction for a pain propensity index > 0 was 49.4%. The prevalence of disabling WHP by occupational group ranged from 0.3 to 36.2%, and correlated strongly with mean pain propensity index (correlation coefficient 0.86). CONCLUSION: Strategies to prevent disability from WHP among working populations should explore ways of reducing general propensity to pain, as well as improving the ergonomics of occupational tasks.

      2. The burden of respiratory abnormalities among workers at coffee roasting and packaging facilitiesexternal icon
        Harvey RR, Fechter-Leggett ED, Bailey RL, Edwards NT, Fedan KB, Virji MA, Nett RJ, Cox-Ganser JM, Cummings KJ.
        Front Public Health. 2020 ;8:5.
        Introduction: Respiratory hazards in the coffee roasting and packaging industry can include asthmagens such as green coffee bean and other dust and alpha-diketones such as diacetyl and 2,3-pentanedione that can occur naturally from roasting coffee or artificially from addition of flavoring to coffee. We sought to describe the burden of respiratory abnormalities among workers at 17 coffee roasting and packaging facilities. Methods: We completed medical surveys at 17 coffee roasting and packaging facilities that included interviewer-administered questionnaires and pulmonary function testing. We summarized work-related symptoms, diagnoses, and spirometry testing results among all participants. We compared health outcomes between participants who worked near flavoring and who did not. Results: Participants most commonly reported nose and eye symptoms, and wheeze, with a work-related pattern for some. Symptoms and pulmonary function tests were consistent with work-related asthma in some participants. About 5% of workers had abnormal spirometry and most improved after bronchodilator. Health outcomes were similar between employees who worked near flavoring and who did not, except employees who worked near flavoring reported more chronic bronchitis and ever receiving a diagnosis of asthma than those who did not work near flavoring. Conclusion: The symptoms and patterns likely represent overlapping health effects of different respiratory hazards, including green coffee bean and other dust that can contribute to work-related asthma, and diacetyl and 2,3-pentanedione that can contribute to obliterative bronchiolitis. Healthcare providers and occupational health and safety practitioners should be aware that workers at coffee roasting and packaging facilities are potentially at risk for occupational lung diseases.

    • Parasitic Diseases
      1. Artemether-lumefantrine efficacy for the treatment of uncomplicated Plasmodium falciparum infection in Choco, Colombia after 8 years as first-line treatmentexternal icon
        Olivera MJ, Guerra AP, Cortes LJ, Horth RZ, Padilla J, Novoa J, Ade MP, Ljolje D, Lucchi NW, Marquino W, Renteria M, Yurgaky W, Macedo de Oliveira A.
        Am J Trop Med Hyg. 2020 Feb 24.
        Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated Plasmodium falciparum infection in Colombia. To assess AL efficacy for uncomplicated falciparum malaria in Quibdo, Choco, Colombia, we conducted a 28-day therapeutic efficacy study (TES) following the WHO guidelines. From July 2018 to February 2019, febrile patients aged 5-65 years with microscopy-confirmed P. falciparum mono-infection and asexual parasite density of 250-100,000 parasites/microL were enrolled and treated with a supervised 3-day course of AL. The primary endpoint was adequate clinical and parasitological response (ACPR) on day 28. We attempted to use polymerase chain reaction (PCR) genotyping to differentiate reinfection and recrudescence, and conducted genetic testing for antimalarial resistance-associated genes. Eighty-eight patients consented and were enrolled: four were lost to follow-up or missed treatment doses. Therefore, 84 (95.5%) participants reached a valid endpoint: treatment failure or ACPR. No patient remained microscopy positive for malaria on day 3, evidence of delayed parasite clearance and artemisinin resistance. One patient had recurrent infection (12 parasites/microL) on day 28. Uncorrected ACPR rate was 98.8% (83/84) (95% CI: 93.5-100%). The recurrent infection sample did not amplify during molecular testing, giving a PCR-corrected ACPR of 100% (83/83) (95% CI: 95.7-100%). No P. falciparum kelch 13 polymorphisms associated with artemisinin resistance were identified. Our results support high AL efficacy for falciparum malaria in Choco. Because of the time required to conduct TESs in low-endemic settings, it is important to consider complementary alternatives to monitor antimalarial efficacy and resistance.

      2. Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors, and through transfusions, transplants, insect feces in food, and mother to child during gestation. An estimated 30% of infected persons will develop lifelong, potentially fatal cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment for Chagas disease in the United States, including the cost of commercially available benznidazole. We compare costs of testing and treatment for mothers and infants with the lifetime societal costs without testing and consequent morbidity and mortality due to lack of treatment or late treatment. We constructed a decision-analytic model, using one tree that shows the combined costs for every possible mother-child pairing. Savings per birth in a targeted screening program are $1,314, and with universal screening, $105 per birth. At current screening costs, universal screening results in $420 million in lifetime savings per birth-year cohort. We found that a congenital Chagas screening program in the United States is cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence greater than 0.06% compared with no screening program.

    • Physical Activity
      1. The updated Physical Activity Guidelines for Americans (2nd edition) removes the requirement that physical activity should occur in bouts lasting 10 minutes or more to count toward the minimum aerobic guideline. Using self-reported data from the 2017 Behavioral Risk Factor Surveillance System (N = 386,960), we examined differences in national physical activity estimates with and without this requirement. Overall, 1.9% of adults reported activities in short bouts (<10 minutes). When excluding short bouts, 29.9% were inactive, 20.7% were insufficiently active, and 49.4% were active. When including short bouts, 29.1% were inactive, 21.4% were insufficiently active, and 49.5% were active. Eliminating the 10-minute-bout requirement had little effect on physical activity estimates.

    • Reproductive Health
      1. Factors associated with local herb use during pregnancy and labor among women in Kigoma region, Tanzania, 2014-2016external icon
        Fukunaga R, Morof D, Blanton C, Ruiz A, Maro G, Serbanescu F.
        BMC Pregnancy Childbirth. 2020 Feb 21;20(1):122.
        BACKGROUND: Despite research suggesting an association between certain herb use during pregnancy and delivery and postnatal complications, herbs are still commonly used among pregnant women in sub-Sahara Africa (SSA). This study examines the factors and characteristics of women using local herbs during pregnancy and/or labor, and the associations between local herb use and postnatal complications in Kigoma, Tanzania. METHODS: We analyzed data from the 2016 Kigoma Tanzania Reproductive Health Survey (RHS), a regionally representative, population-based survey of reproductive age women (15-49 years). We included information on each woman's most recent pregnancy resulting in a live birth during January 2014-September 2016. We calculated weighted prevalence estimates and used multivariable logistic regression to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with use of local herbs during pregnancy and/or labor, as well as factors associated with postnatal complications. RESULTS: Of 3530 women, 10.9% (CI: 9.0-13.1) used local herbs during their last pregnancy and/or labor resulting in live birth. The most common reasons for taking local herbs included stomach pain (42.9%) and for the health of the child (25.5%). Adjusted odds of local herb use was higher for women reporting a home versus facility-based delivery (aOR: 1.6, CI: 1.1-2.2), having one versus three or more prior live births (aOR: 1.8, CI: 1.4-2.4), and having a household income in the lowest versus the highest wealth tercile (aOR: 1.4, CI: 1.1-1.9). Adjusted odds of postnatal complications were higher among women who used local herbs versus those who did not (aOR: 1.5, CI: 1.2-1.9), had four or more antenatal care visits versus fewer (aOR: 1.4, CI: 1.2-1.2), and were aged 25-34 (aOR: 1.1, CI: 1.0-1.3) and 35-49 (aOR: 1.3, CI: 1.0-1.6) versus < 25 years. CONCLUSIONS: About one in ten women in Kigoma used local herbs during their most recent pregnancy and/or labor and had a high risk of postnatal complications. Health providers may consider screening pregnant women for herb use during antenatal and delivery care as well as provide information about any known risks of complications from herb use.

    • Substance Use and Abuse
      1. INTRODUCTION: The National Youth Tobacco Survey (NYTS) has successfully monitored tobacco product use patterns and correlates since 1999 among US students in grades 6 through 12 using a scannable paper-and-pencil format. We conducted a study to determine the feasibility and potential benefits of administering an electronic version of the NYTS in school settings. METHODS: The pilot survey was administered by using 2 versions. Version 1 mimicked the scannable paper-and-pencil format with respect to design, formatting, and structure, but was administered on a tablet computer. Version 2 used an electronic survey design and formatting capabilities, which included programmed logic skips and tobacco product images. Chi-square and t tests were used to assess subgroup differences. Multivariable-adjusted logistic regression models were used to determine if the odds of ever and current tobacco product use differed between the 2 versions. RESULTS: In total, 2,769 students completed version 1 or version 2. Three-quarters of respondents reported a strong preference for using an electronic device to take the NYTS (74.7%). Compared with version 1, version 2 reduced the mean time to complete the survey by 15% (P < .01), reduced the number of questions students needed to answer by 30% (P < .01), and removed 1.9% of inconsistent survey responses. A significant difference was observed for ever e-cigarette use between versions 1 (22.2%) and 2 (29.5%; P < .0001). No significant differences in ever or current use were observed for other tobacco products. CONCLUSION: An electronic mode of administration is feasible and valid for conducting surveillance of tobacco product use among US youths.

      2. Emergency department visits attributed to adverse events involving benzodiazepines, 2016-2017external icon
        Moro RN, Geller AI, Weidle NJ, Lind JN, Lovegrove MC, Rose KO, Goring SK, McAninch JK, Dowell D, Budnitz DS.
        Am J Prev Med. 2020 Feb 11.
        INTRODUCTION: Characterization of emergency department visits attributed to adverse events involving benzodiazepines can be used to guide preventive interventions. This study describes U.S. emergency department visits attributed to adverse events involving benzodiazepines by intent, patient characteristics, and clinical manifestations. METHODS: Data from the 2016-2017 National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were analyzed in 2019 to calculate estimated annual numbers and rates of emergency department visits attributed to adverse events involving benzodiazepines, by intent of benzodiazepine use. RESULTS: Based on 6,148 cases, there were an estimated 212,770 (95% CI=167,163, 258,377) emergency department visits annually attributed to adverse events involving benzodiazepines. More than half were visits involving nonmedical use of benzodiazepines (119,008; 55.9%, 95% CI=50.0%, 61.9%), one third were visits involving self-harm with benzodiazepines (64,721; 30.4%, 95% CI=25.6%, 35.2%), and a smaller proportion of visits involved therapeutic use of benzodiazepines (29,041; 13.6%, 95% CI=11.4%, 15.9%). The estimated population rate of visits was highest for nonmedical use of benzodiazepines by patients aged 15-34 years (7.4 visits per 10,000 people). Among visits involving nonmedical use of benzodiazepines, 54.8% (95% CI=49.8%, 59.8%) were made by patients aged 15-34 years, 82.7% (95% CI=80.1%, 85.4%) involved concurrent use of other substances (illicit drugs, alcohol, prescription opioids, and/or other pharmaceuticals), and 24.2% (95% CI=17.7%, 30.6%) involved cardiorespiratory arrest or unresponsiveness. CONCLUSIONS: These findings support recommendations to assess for and address substance use disorder before initiating or continuing benzodiazepines and reinforce the need for validated self-harm risk assessment tools for clinicians.

      3. Mouth-level nicotine intake estimates from discarded filter butts to examine compensatory smoking in low nicotine cigarettesexternal icon
        Smith TT, Koopmeiners JS, Hatsukami DK, Tessier KM, Benowitz NL, Murphy SE, Strasser AA, Tidey JW, Blount BC, Valentin L, Bravo Cardenas R, Watson C, Pirkle JL, Donny EC.
        Cancer Epidemiol Biomarkers Prev. 2020 Feb 26.
        BACKGROUND: A mandated reduction in the nicotine content of cigarettes could reduce smoking rate and prevalence. However, one concern is that smokers may compensate by increasing the intensity with which they smoke each cigarette to obtain more nicotine. This study assessed whether smokers engage in compensatory smoking by estimating the mouth-level nicotine intake of low nicotine cigarettes smoked during a clinical trial. METHODS: Smokers were randomly assigned to receive cigarettes with one of five nicotine contents for 6 weeks. An additional group received a cigarette with the lowest nicotine content, but an increased tar yield. The obtained mouth-level nicotine intake from discarded cigarette butts for a subset of participants (51-70/group) was estimated using solanesol as described previously. A compensation index was calculated for each group to estimate the proportion of nicotine per cigarette recovered through changes in smoking intensity. RESULTS: There was no significant increase in smoking intensity for any of the reduced nicotine cigarettes as measured by the compensation index (an estimated 0.4% of the nicotine lost was recovered in the lowest nicotine group; 95% confidence interval, -0.1 to 1.2). There was a significant decrease in smoking intensity for very low nicotine content cigarettes with increased tar yield. CONCLUSIONS: Reductions in nicotine content did not result in compensatory changes in how intensively participants smoked research cigarettes. IMPACT: Combined with data from clinical trials showing a reduction in cigarettes smoked per day, these data suggest that a reduction in nicotine content is unlikely to result in increased smoke exposure.

      4. The impact of exclusive use of very low nicotine cigarettes on compensatory smoking: An inpatient crossover clinical trialexternal icon
        Smith TT, Koopmeiners JS, White CM, Denlinger-Apte RL, Pacek LR, De Jesus VR, Wang L, Watson C, Blount BC, Hatsukami DK, Benowitz NL, Donny EC, Carpenter MJ.
        Cancer Epidemiol Biomarkers Prev. 2020 Feb 26.
        BACKGROUND: The FDA is considering a mandated reduction in the nicotine content of cigarettes. Clinical trials have been limited by non-study cigarette use (noncompliance), which could mask compensation. The goal of this study was to assess whether compensation occurs when smokers provided with very low nicotine cigarettes cannot access normal nicotine cigarettes. METHODS: In a within-subjects, crossover design, current smokers (n = 16) were confined to a hotel for two 4-night hotel stays during which they were only able to access the research cigarettes provided. The hotel stays offered normal nicotine cigarettes or very low nicotine content (VLNC) cigarettes, in an unblinded design, available for "purchase" via a study bank. RESULTS: In the context of complete compliance with the study cigarettes (n = 16), there was not a significant increase during the VLNC condition for cigarettes smoked per day, expired carbon monoxide, or N-acetyl-S-(cyanoethyl)-l-cysteine (cyanoethyl-MA, metabolite of acrylonitrile). There was a significant nicotine x time interaction on urine N-acetyl-S-(3-hydroxypropyl)-l-cysteine (hydroxypropyl-MA, metabolite of acrolein), driven by an increase in the VLNC condition during the first 24 hours. By the end of the VLNC condition, there was no evidence of compensation across any measure of smoking or smoke exposure. CONCLUSIONS: Among current smokers who exclusively used VLNC cigarettes for 4 days, there was no significant compensatory smoking behavior. IMPACT: These data, combined with the larger body of work, suggest that a mandated reduction in nicotine content is unlikely to result in an increase in smoking behavior to obtain more nicotine.

    • Zoonotic and Vectorborne Diseases
      1. An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in Wuhan, Hubei Province, China in December 2019, and has spread throughout China and to 31 other countries and territories, including the United States (1). As of February 23, 2020, there were 76,936 reported cases in mainland China and 1,875 cases in locations outside mainland China (1). There have been 2,462 associated deaths worldwide; no deaths have been reported in the United States. Fourteen cases have been diagnosed in the United States, and an additional 39 cases have occurred among repatriated persons from high-risk settings, for a current total of 53 cases within the United States. This report summarizes the aggressive measures (2,3) that CDC, state and local health departments, multiple other federal agencies, and other partners are implementing to slow and try to contain transmission of COVID-19 in the United States. These measures require the identification of cases and contacts of persons with COVID-19 in the United States and the recommended assessment, monitoring, and care of travelers arriving from areas with substantial COVID-19 transmission. Although these measures might not prevent widespread transmission of the virus in the United States, they are being implemented to 1) slow the spread of illness; 2) provide time to better prepare state and local health departments, health care systems, businesses, educational organizations, and the general public in the event that widespread transmission occurs; and 3) better characterize COVID-19 to guide public health recommendations and the development and deployment of medical countermeasures, including diagnostics, therapeutics, and vaccines. U.S. public health authorities are monitoring the situation closely, and CDC is coordinating efforts with the World Health Organization (WHO) and other global partners. Interim guidance is available at https://www.cdc.gov/coronavirus/index.html. As more is learned about this novel virus and this outbreak, CDC will rapidly incorporate new knowledge into guidance for action by CDC, state and local health departments, health care providers, and communities.

      2. Comparison of knowledge, attitude, and practices of animal and human brucellosis between nomadic pastoralists and non-pastoralists in Kenyaexternal icon
        Njenga MK, Ogolla E, Thumbi SM, Ngere I, Omulo S, Muturi M, Marwanga D, Bitek A, Bett B, Widdowson MA, Munyua P, Osoro EM.
        BMC Public Health. 2020 Feb 24;20(1):269.
        BACKGROUND: The seroprevalence of brucellosis among nomadic pastoralists and their livestock in arid lands is reported to be over10-fold higher than non-pastoralists farmers and their livestock in Kenya. Here, we compared the seroprevalence of nomadic pastoralists and mixed farming with their knowledge of the disease and high-risk practices associated with brucellosis infection. METHODS: Across-sectional study was conducted in two counties - Kiambu County where farmers primarily practice smallholder livestock production and crop farming, and Marsabit County where farmers practice nomadic pastoral livestock production. Stratified random sampling was applied, in which sublocations were initially selected based on predominant livestock production system, before selecting households using randomly generated geographical coordinates. In each household, up to three persons aged 5 years and above were randomly selected, consented, and tested for Brucella spp IgG antibodies. A structured questionnaire was administered to the household head and selected individuals on disease knowledge and risky practices among the pastoralists and mixed farmers compared. Multivariable mixed effects logistic regression model was used to assess independent practices associated with human Brucella spp. IgG seropositivity. RESULTS: While the majority (74%) of pastoralist households had little to no formal education when compared to mixed (8%), over 70% of all households (pastoralists and mixed farmers) had heard of brucellosis and mentioned its clinical presentation in humans. However, fewer than 30% of all participants (pastoralists and mixed farmers) knew how brucellosis is transmitted between animals and humans or how its transmission can be prevented. Despite their comparable knowledge, significantly more seropositive pastoralists compared to mixed farmers engaged in risky practices including consuming unboiled milk (79.5% vs 1.7%, p < 0.001) and raw blood (28.3% vs 0.4%, p < 0.001), assisting in animal birth (43.0% vs 9.3%, p < 0.001), and handling raw hides (30.6% vs 5.5%, p < 0.001). , CONCLUSION: Nomadic pastoralists are more likely to engage in risky practices that promote Brucella Infection, probably because of their occupation and culture, despite having significant knowledge of the disease.

      3. Towards rabies elimination in the Asia-Pacific region: From theory to practiceexternal icon
        Rupprecht CE, Abela-Ridder B, Abila R, Amparo AC, Banyard A, Blanton J, Chanachai K, Dallmeier K, de Balogh K, Del Rio Vilas V, Ertl H, Freuling C, Hill R, Houillon G, Jakava-Viljanen M, Kasemsuwan S, Lechenet J, Nel L, Panichabhongse P, Rahman SA, Tantawichien T, Vandeputte J, Viriyabancha W, Vos A, Wallace R, Yale G, Yurachai O, Mueller T.
        Biologicals. 2020 Feb 20.
        Rabies is a major neglected zoonotic disease and causes a substantial burden in the Asian region. Currently, Pacific Oceania is free of rabies but enzootic areas throughout southeast Asia represent a major risk of disease introduction to this region. On September 25-26, 2019, researchers, government officials and related stakeholders met at an IABS conference in Bangkok, Thailand to engage on the topic of human rabies mediated by dogs. The objective of the meeting was focused upon snowballing efforts towards achieving substantial progress in rabies prevention, control and elimination within Asia by 2030, and thereby to safeguard the Pacific region. Individual sessions focused upon domestic animal, wildlife and human vaccination; the production and evaluation of quality, safety and efficacy of existing rabies biologics; and the future development of new products. Participants reviewed the progress to date in eliminating canine rabies by mass vaccination, described supportive methods to parenteral administration by oral vaccine application, considered updated global and local approaches at human prophylaxis and discussed the considerable challenges ahead. Such opportunities provide continuous engagement on disease management among professionals at a trans-disciplinary level and promote new applied research collaborations in a modern One Health context.

      4. BACKGROUND: Human rabies is a notifiable condition in Thailand, and 46 confirmed and probable cases were reported from 2010-2015; eleven were reported from Eastern Thailand. Although rabies is vaccine preventable, more than 90% of persons who died of rabies in Thailand either did not receive or inappropriately discontinued post-exposure prophylaxis (PEP). In 2012 Thailand launched a national animal rabies elimination program with the goal of elimination by 2020. One of the policies of this national program is to improve detection of animal rabies exposures, access to PEP, and adherence to vaccine schedules. To achieve this goal, several hospital-based electronic PEP surveillance systems have been instituted throughout Thailand. METHOD: Data from a voluntary, electronic hospital-based, rabies exposure and PEP surveillance system was analyzed from eight provinces in Eastern Thailand for the time period January 1 -December 31, 2015. The surveillance system collects data from all persons who present to an R36-integrated healthcare facility with a suspected rabies exposure, including characteristics of the biting animals, categorization of the rabies exposure, and adherence to PEP recommendations. The crude rate of healthcare seeking for a suspected rabies exposure was assessed by province, and a multivariable linear regression model was developed to determine the potential extent of undetected rabies exposures due to bite treatment at healthcare facilities that do not utilize the R36 system. Suspected rabies exposures were described by patient demographics, location of wound, and disposition of the offending animal. A comparison of adherence to intramuscular and intradermal vaccination regimens was performed and odds ratios were calculated for factors related to unadvised PEP discontinuation. RESULT: 6,204 suspected rabies exposures were reported from eight Eastern Thailand provinces, yielding a crude exposure rate of 106 reported rabies exposures per 100,000 population. When adjusted for under-detection due to non-participating hospitals and province-level demographic differences, the estimated suspected rabies exposure rate was 204/100,000. Dogs were the main source of exposure (77.8%) and children age <15 years and elderly age >60 years had the highest overall reported exposure rate (189.7 and 189.2/100,000). Adherence to either the intramuscular 5-dose or the intradermal 4-dose PEP regimen was low (15.8% and 46.5%, respectively); rabies immunoglobulin was received by only 15% of persons for whom it was indicated. Persons with rabies exposures were more likely to discontinue the vaccination series against medical advice if they were male, aged 16-45, if they received immunoglobulin, or if received the intramuscular regimen. CONCLUSION: When adjusting for number of reporting hospitals, province population density, number of hospitals per population and average family income, the expected report rate increased 1.9-fold, indicating that there is likely a high level of under-detection of persons seeking medical care for suspected rabies exposures. Expanded implementation of electronic surveillance systems will likely improve reporting and the epidemiologic knowledge of rabies exposures. Analysis of data collected from this system revealed very low rates of adherence to rabies vaccination recommendations. PEP adherence was better by the intradermal route, which provides more support for its use in situations where it is economically feasible.


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