BACKGROUND: Characterizing acute and chronic hepatitis C virus (HCV) infection and HIV/HCV co-infection among persons who inject drugs (PWID) can inform elimination efforts. METHODS: During 2018 National HIV Behavioral Surveillance in 10 U.S. metropolitan statistical areas (MSAs), PWID were recruited using respondent-driven sampling and offered a survey, HIV testing, and HCV antibody and RNA testing. We examined prevalence and associated characteristics of HCV infection and HIV/HCV co-infection. Associations were assessed using log-linked Poisson regression models with robust standard errors accounting for clustering by recruitment chain and adjusting for MSA and network size. RESULTS: Overall, 44.2% had current HCV infection (RNA detected), with 3.9% classified as acute infection (HCV antibody non-reactive/RNA detected) and 40.3% as chronic (HCV antibody reactive/RNA detected). Four percent had HIV/HCV co-infection. Current HCV infection was significantly higher among PWID who were male, White, injected >1 time/day, shared syringes in past year, and shared injection equipment in past year. PWID who were transgender, injecting >5 years, and most often injected speedball (heroin and cocaine together) or stimulants alone were more likely to have HIV/HCV co-infection. Among PWID who never previously had HCV infection, 9.9% had acute HCV infection. Among PWID who started injecting ≤5 years ago, 41.5% had already acquired HCV infection. CONCLUSIONS: Acute and chronic HCV infections were substantial among a sample of PWID in 10 U.S. MSAs. Accessibility to HCV RNA testing, promoting safer practices, and intervening early with harm reduction programs for recent injection initiates will be critical to disease elimination efforts for PWID.

BACKGROUND Information is limited on messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection or attenuating disease when administered in real-world conditions.METHODS Prospective cohorts of 3,975 healthcare personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing during December 14 2020—April 10 2021. Self-collected mid-turbinate nasal swabs were tested by qualitative and quantitative reverse-transcription–polymerase-chain-reaction (RT-PCR). VE was calculated as 100%×(1−hazard ratio); adjusted VE was calculated using vaccination propensity weights and adjustments for site, occupation, and local virus circulation.RESULTS SARS-CoV-2 was detected in 204 (5.1%) participants; 16 were partially (≥14 days post-dose-1 to 13 days after dose-2) or fully (≥14 days post-dose-2) vaccinated, and 156 were unvaccinated; 32 with indeterminate status (<14 days after dose-1) were excluded. Adjusted mRNA VE of full vaccination was 91% (95% confidence interval [CI]=76%–97%) against symptomatic or asymptomatic SARS-CoV-2 infection; VE of partial vaccination was 81% (95% CI=64%-90%). Among partially or fully vaccinated participants with SARS-CoV-2 infection, mean viral RNA load (Log10 copies/mL) was 40% lower (95% CI=16%-57%), the risk of self-reported febrile COVID-19 was 58% lower (Risk Ratio=0.42, 95% CI=0.18-0.98), and 2.3 fewer days (95% CI=0.8-3.7) were spent sick in bed compared to unvaccinated infected participants.CONCLUSIONS Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infections when administered in real-world conditions and attenuated viral RNA load, febrile symptoms, and illness duration among those with breakthrough infection despite vaccination.Competing Interest StatementAllison L. Naleway reported funding from Pfizer for a meningococcal B vaccine study unrelated to the submitted work. Kurt T. Hegmann serves at the Editor of the American College of Occupational and Environmental Medicine evidence-based practice guidelines. Matthew S. These reported grants and personal fees from Reed Group and the American College of Occupational and Environmental Medicine, outside the submitted work. Other authors have reported no conflicts of interest.Funding StatementFunding provided in whole or in part by federal funds from the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention under contract numbers 75D30120R68013 awarded to Marshfield Clinic Research Laboratory, 75D30120C08379 to University of Arizona, and 75D30120C08150 awarded to Abt Associates, Inc.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was reviewed and approved by the University of Arizona IRB as the single IRB for this studyAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesSummary data will be available once all study objectives are met.

This paper describes the process for developing, validating and disseminating through a train-the-trainer (TOT) event a standardised curriculum for public health capacity building for points of entry (POE) staff across the 15-member state Economic Community of West African States (ECOWAS) that reflects both international standards and national guidelines.A five-phase process was used in developing the curriculum: phase (1) assessment of existing materials developed by the US Centers for Disease Control and Prevention (CDC), Africa CDC and the West African Economic and Monetary Union, (2) design of retained and new, harmonised content, (3) validation by the national leadership to produce final content, (4) implementation of the harmonised curriculum during a regional TOT, and (5) evaluation of the curriculum.Of the nine modules assessed in English and French, the technical team agreed to retain six harmonised modules providing materials for 10 days of intensive training. Following the TOT, most participants (n=28/30, 93.3%) indicated that the International Health Regulations and emergency management modules were relevant to their work and 96.7% (n=29/30) reported that the training should be cascaded to POE staff in their countries.The ECOWAS harmonised POE curriculum provides a set of training materials and expectations for national port health and POE staff to use across the region. This initiative contributes to reducing the effort required by countries to identify emergency preparedness and response capacity-building tools for border health systems in the Member States in a highly connected region.

The Democratic Republic of the Congo's (DRC) 10th known Ebola virus disease (EVD) outbreak occurred between August 1, 2018 and June 25, 2020, and was the largest EVD outbreak in the country's history. During this outbreak, the DRC Ministry of Health initiated traveller health screening at points of control (POC, locations not on the border) and points of entry (POE) to minimize disease translocation via ground and air travel. We sought to develop a model-based approach that could be applied in future outbreaks to inform decisions for optimizing POC and POE placement, and allocation of resources more broadly, to mitigate the risk of disease translocation associated with ground-level population mobility. We applied a parameter-free mobility model, the radiation model, to estimate likelihood of ground travel between selected origin locations (including Beni, DRC) and surrounding population centres, based on population size and drive-time. We then performed a road network route analysis and included estimated population movement results to calculate the proportionate volume of travellers who would move along each road segment; this reflects the proportion of travellers that could be screened at a POC or POE. For Beni, the road segments estimated to have the highest proportion of travellers that could be screened were part of routes into Uganda and Rwanda. Conversely, road segments that were part of routes to other population centres within the DRC were estimated to have relatively lower proportions. We observed a posteriori that, in many instances, our results aligned with locations that were selected for actual POC or POE placement through more time-consuming methods. This study has demonstrated that mobility models and simple spatial techniques can help identify potential locations for health screening at newly placed POC or existing POE during public health emergencies based on expected movement patterns. Importantly, we have provided methods to estimate the proportionate volume of travellers that POC or POE screening measures would assess based on their location. This is critical information in outbreak situations when timely decisions must be made to implement public health interventions that reach the most individuals across a network. © 2022 Elsevier Ltd

BACKGROUND: Households are common places for spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated factors associated with household transmission and acquisition of SARS-CoV-2. METHODS: Households with children age <18 years were enrolled into prospective, longitudinal cohorts and followed from August 2020 to August 2021 in Utah, September 2020 to August 2021 in New York City, and November 2020 to October 2021 in Maryland. Participants self-collected nasal swabs weekly and with onset of acute illness. Swabs were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. We assessed factors associated with SARS-CoV-2 acquisition using a multilevel logistic regression adjusted for household size and clustering and SARS-CoV-2 transmission using a logistic regression adjusted for household size. RESULTS: Among 2053 people (513 households) enrolled, 180 people (8.8%; in 76 households) tested positive for SARS-CoV-2. Compared with children age <12 years, the odds of acquiring infection were lower for adults age ≥18 years (adjusted odds ratio [aOR], 0.34; 95% CI, 0.14-0.87); however, this may reflect vaccination status, which protected against SARS-CoV-2 acquisition (aOR, 0.17; 95% CI, 0.03-0.91). The odds of onward transmission were similar between symptomatic and asymptomatic primary cases (aOR, 1.00; 95% CI, 0.35-2.93) and did not differ by age (12-17 years vs <12 years: aOR, 1.08; 95% CI, 0.20-5.62; ≥18 years vs <12 years: aOR, 1.70; 95% CI, 0.52-5.83). CONCLUSIONS: Adults had lower odds of acquiring SARS-CoV-2 compared with children, but this association might be influenced by coronavirus disease 2019 (COVID-19) vaccination, which was primarily available for adults and protective against infection. In contrast, all ages, regardless of symptoms and COVID-19 vaccination, had similar odds of transmitting SARS-CoV-2. Our findings underscore the importance of SARS-CoV-2 mitigation measures for persons of all ages.

The BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine was recommended by CDC's Advisory Committee on Immunization Practices for persons aged 12-15 years (referred to as adolescents in this report) on May 12, 2021, and for children aged 5-11 years on November 2, 2021 (1-4). Real-world data on vaccine effectiveness (VE) in these age groups are needed, especially because when the B.1.1.529 (Omicron) variant became predominant in the United States in December 2021, early investigations of VE demonstrated a decline in protection against symptomatic infection for adolescents aged 12-15 years and adults* (5). The PROTECT(†) prospective cohort of 1,364 children and adolescents aged 5-15 years was tested weekly for SARS-CoV-2, irrespective of symptoms, and upon COVID-19-associated illness during July 25, 2021-February 12, 2022. Among unvaccinated participants (i.e., those who had received no COVID-19 vaccine doses) with any laboratory-confirmed SARS-CoV-2 infection, those with B.1.617.2 (Delta) variant infections were more likely to report COVID-19 symptoms (66%) than were those with Omicron infections (49%). Among fully vaccinated children aged 5-11 years, VE against any symptomatic and asymptomatic Omicron infection 14-82 days (the longest interval after dose 2 in this age group) after receipt of dose 2 of the Pfizer-BioNTech vaccine was 31% (95% CI = 9%-48%), adjusted for sociodemographic characteristics, health information, frequency of social contact, mask use, location, and local virus circulation. Among adolescents aged 12-15 years, adjusted VE 14-149 days after dose 2 was 87% (95% CI = 49%-97%) against symptomatic and asymptomatic Delta infection and 59% (95% CI = 22%-79%) against Omicron infection. Fully vaccinated participants with Omicron infection spent an average of one half day less sick in bed than did unvaccinated participants with Omicron infection. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

BACKGROUND: Workers critical to emergency response and continuity of essential services during the coronavirus disease 2019 (COVID-19) pandemic are at a disproportionally high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Prospective cohort studies are needed to enhance understanding the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, identifying risk factors, assessing clinical outcomes, and determining the effectiveness of vaccination. OBJECTIVE: The Research on the Epidemiology of SARS-CoV-2 in Essential Response personnel (RECOVER) prospective cohort study was designed to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, examine risk factors for infection and clinical spectrum of illness, and assess effectiveness of vaccination among essential workers. METHODS: The RECOVER multi-site network was initiated in August 2020 and aims to enroll 3,000 healthcare personnel (HCP), first responders, and other essential and frontline workers (EFW) in six U.S. locations. Data on participant demographics, medical history, and vaccination history are collected at baseline and throughout the study. Active surveillance for symptoms of COVID-19-like illness (CLI), accessing medical care, and symptom duration are ascertained by text messages, e-mails, and direct participant or medical record reports. Participants self-collect a mid-turbinate nasal swab weekly, regardless of symptoms, and two additional respiratory specimens at the onset of CLI. Blood is collected upon enrollment, every three months, approximately 28 days after a reverse-transcription-polymerase-chain-reaction (RT-PCR)-confirmed SARS-CoV-2 infection, and 14-28 days after a dose of any COVID-19 vaccine. Beginning in February 2021, household members of RT-PCR-confirmed participants self-collect mid-turbinate nasal swabs daily for ten days. RESULTS: The study observation period began in August 2020 and is currently expected to continue through spring 2022. There are 2,623 actively enrolled RECOVER participants, including 252 participants who were found to be positive for SARS-CoV-2 by RT-PCR. Enrollment is ongoing at three of six study site locations. CONCLUSIONS: Data collected through the cohort are expected to provide important public health information for essential workers at high risk for occupational exposure to SARS-CoV-2 and allow early evaluation of COVID-19 vaccine effectiveness. INTERNATIONAL REGISTERED REPORT: DERR1-10.2196/31574.

BACKGROUND: Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in attenuating coronavirus disease 2019 (Covid-19) when administered in real-world conditions. METHODS: We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. From December 14, 2020, to April 10, 2021, the participants completed weekly SARS-CoV-2 testing by providing mid-turbinate nasal swabs for qualitative and quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis. The formula for calculating vaccine effectiveness was 100% × (1 - hazard ratio for SARS-CoV-2 infection in vaccinated vs. unvaccinated participants), with adjustments for the propensity to be vaccinated, study site, occupation, and local viral circulation. RESULTS: SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (≥14 days after dose 2), 11 partially vaccinated (≥14 days after dose 1 and <14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (<14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7). CONCLUSIONS: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination. (Funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention.).

Dengue is an ongoing health risk for Peace Corps Volunteers (PCVs) working in the tropics. On May 2019, the Peace Corps Office of Health Services notified the Centers for Disease Control and Prevention (CDC) of a dengue outbreak among PCVs in Timor-Leste. The purpose of this investigation was to identify the clinical, demographic, and epidemiological characteristics of PCVs with dengue and recommend dengue preventive measures. To identify PCVs with dengue and describe disease severity, the medical records of PCVs reporting fever during September 2018-June 2019 were reviewed. To identify factors associated with dengue virus (DENV) infection, we administered a questionnaire on demographics, travel history, and mosquito avoidance behaviors and collected blood specimens to detect the anti-DENV IgM antibody to diagnose recent infection. Of 35 PCVs in-country, 11 (31%) tested positive for dengue (NS1, IgM, PCR), eight requiring hospitalization and medical evacuation. Among 27 (77%) PCVs who participated in the investigation, all reported having been recently bitten by mosquitoes and 56% reported being bitten most often at home; only 16 (59%) reported having screens on bedroom windows. Nearly all (93%) PCVs reported using a bed net every night; fewer (70%) reported using mosquito repellent at least once a day. No behaviors were significantly associated with DENV infection. Raising awareness of dengue risk among PCVs and continuing to encourage mosquito avoidance behavior to prevent dengue is critical. Access to and use of measures to avoid mosquito bites should be improved or implemented. Peace Corps medical officers should continue to receive an annual refresher training on dengue clinical management.

Over 2 million mostly rural Americans are at risk of drinking water from private wells that contain arsenic (As) exceeding the U.S. Environmental Protection Agency (USEPA) Maximum Contaminant Level (MCL) of 10 micrograms per liter (mug/L). How well existing treatment technologies perform in real world situations, and to what extent they reduce health risks, are not well understood. This study evaluates the effectiveness of household As treatment systems in southern-central Maine (ME, n = 156) and northern New Jersey (NJ, n = 94) and ascertains how untreated well water chemistry and other factors influence As removal. Untreated and treated water samples, as well as a treatment questionnaire, were collected. Most ME households had point-of-use reverse-osmosis systems (POU RO), while in NJ, dual-tank point-of-entry (POE) whole house systems were popular. Arsenic treatment systems reduced well water arsenic concentrations ([As]) by up to two orders of magnitude, i.e. from a median of 71.7 to 0.8 mug/L and from a mean of 105 to 14.3 mug/L in ME, and from a median of 8.6 to 0.2 mug/L and a mean of 15.8 to 2.1 mug/L in NJ. More than half (53%) of the systems in ME reduced water [As] to below 1 mug/L, compared to 69% in NJ. The treatment system failure rates were 19% in ME (>USEPA MCL of 10 mug/L) and 16% in NJ (>NJ MCL of 5 mug/L). In both states, the higher the untreated well water [As] and the As(III)/As ratio, the higher the rate of treatment failure. POE systems failed less than POU systems, as did the treatment systems installed and maintained by vendors than those by homeowners. The 7-fold reduction of [As] in the treated water reduced skin cancer risk alone from 3765 to 514 in 1 million in ME, and from 568 to 75 in 1 million in NJ.

Biotin taken orally can interfere with some diagnostic immunoassays, including those for thyroid hormones, ferritin, and markers of infectious disease. Assays affected are ones that use streptavidin-biotin in their design. The goal of our study was to examine the effect of biotin concentrations of up to 1200 ng/ml on three serological assays performed on VITROS 3600 system, IgM anti-HAV, total anti-HAV, and IgM anti-HBc, by spiking serum samples with variable amounts of biotin. No false negative results were generated with either concentration of biotin for total anti-HAV (65/65). Likewise, biotin caused no false positive IgM anti-HAV results (59/59) with either concentration of biotin; however, 6.7% false negativity was found for IgM anti-HAV when samples were spiked with 1200 ng/mL of biotin. Conversely, 100% false positivity (30/30) was produced by biotin interference in total anti-HAV negative specimens with both concentrations of biotin. False negativity rate was 87.5% in IgM anti-Hbc positive samples when biotin levels were at 1200 ng/mL. These data show that individuals taking biotin-containing supplements may test false-positive in some serologic assays using streptavidin-biotin chemistries. Further studies are warranted to determine the extent of biotin interference resulting in false positive and negative results and their impact, if any, on surveillance and diagnostic settings. This article is protected by copyright. All rights reserved.

Background: Gastrointestinal (GI) illness is the most commonly reported health concern among Peace Corps Volunteers (PCVs) serving in Guatemala. This project identified water types and treatment and storage practices used by PCVs and measured select water quality parameters in their household water. Methods: A survey about water types and practices was conducted of PCVs in Guatemala. The water type most frequently consumed in the household ("primary drinking water") and other water types present in the household ("secondary water") were tested for free chlorine residual (FCR) and for the presence of Escherichia coli and total coliforms. A negative binomial regression model was used to analyze data on incidence of self-reported GI illness. Results: Tambo (commercially purified water in a 5-gal bottle) was the water type most frequently (64%) reported as primary drinking water in 39 PCV households. Most (74%) PCVs reported drinking water other than primary drinking water >/=1 day per week; the incidence rate of GI illness per PCV per month was significantly lower among PCVs who reported never consuming water other than primary drinking water compared to those who did (0.4 and 1.6 GI illnesses per PCV per month, respectively) (p < 0.05). E. coli was not detected in any primary drinking water sample, but was detected in 35% of secondary water samples. Total coliforms were detected in more than two-thirds of primary drinking water and secondary water samples. Nearly all water samples had an FCR of < 0.2 mg/L. Conclusions: Consuming primary drinking water exclusively likely contributes to reducing the rate of GI illness among PCVs. However, most PCVs reported drinking multiple water types, which may include contaminated secondary water types in the household. All water intended for consumption, including secondary sources within and outside the household, should be properly treated and safely stored.

INTRODUCTION: Historically, older people who inject drugs (PWID) have had the highest hepatitis C burden, however, young PWID account for recent increases in HCV infection. We assessed factors associated with past or present HCV infection (HCV antibody-positive) among young (</=35 years) and older PWID (>35 years). METHODS: Using Poisson regression, we calculated adjusted prevalence ratios (aPR) to examine socio-demographic and past 12-month injection risk behaviors associated with HCV infection. RESULTS: Of 4,094 PWID, 55.2% were HCV antibody-positive (anti-HCV). Among young PWID, anti-HCV prevalence was 42.1% and associated with </=high school diploma/GED (aPR=1.17, 95%CI=1.03-1.32), receptive syringe sharing (aPR=1.37, 95%CI=1.21-1.56), sharing injection equipment (aPR=1.16, 95%CI=1.01-1.35), arrest history (aPR=1.14, 95%CI=1.02-1.29), and injecting speedball (aPR=1.37, 95%CI=1.16-1.61). Among older PWID, anti-HCV prevalence was 62.2% and associated with </=high school diploma/GED (aPR= 1.08, 95%CI=1.02-1.15), sharing injection equipment (aPR=1.08, 95% CI=1.02-1.15), high injection frequency (aPR=1.16, 95%CI=1.01-1.34), and injecting speedball (aPR=1.09, 95%CI=1.01-1.16). CONCLUSION: Anti-HCV positivity prevalence is high and associated with risky injection practices. Almost half of young PWID were anti-HCV positive. Improving access to direct-acting antiviral treatment, syringe service programs, and medication-assisted therapy are critical to reducing HCV transmission risk and infection burden, particularly among young PWID who are more likely to be newly infected.

During September 29-October 6, 2017, the County of San Diego Public Health Services (COSD) was notified of two patients with suspected wound botulism and a history of using black tar heroin. On October 9, COSD, which had reported an average of one wound botulism case per year during 2001-2016, sent a health alert through the California Health Alert Network, notifying Southern California providers of these two patients, including their signs and symptoms and black tar heroin exposure. In collaboration with the California Department of Public Health, COSD conducted an investigation to identify additional cases, determine risk factors for illness, estimate cost of medical care, and develop recommendations to prevent further illness. By April 18, 2018, nine (eight confirmed and one probable) patients with wound botulism were identified, all of whom were hospitalized; one of the nine died. All nine were persons who inject drugs; seven specifically reported using black tar heroin and six practiced subcutaneous injection known as skin popping. Clinically compatible signs and symptoms included muscle weakness, difficulty swallowing, blurred vision, drooping eyelids, slurred speech, difficulty breathing, loss of facial expression, or descending paralysis. All patients were treated with heptavalent botulism antitoxin (BAT). Wound botulism is likely underrecognized because of its rarity and the overlapping signs and symptoms with opioid intoxication, overdose, and other neurologic syndromes including Guillain-Barre syndrome, the Miller Fisher variant of Guillain-Barre syndrome, and myasthenia gravis. Prompt diagnosis, administration of BAT, and provision of supportive care can help stop the progression of paralysis and be lifesaving.

BACKGROUND: Characteristics of US blood donors with recent (RBI) or occult (OBI) hepatitis B virus (HBV) infection are not well defined. METHODS: Donors with RBI and OBI were identified by nucleic acid and serologic testing among 34.4 million donations during 2009-2015. Consenting donors were interviewed and their HBV S-gene sequenced. RESULTS: The overall rate of HBV-infected donors was 7.95 per 100,000; of these, 0.35 per 100,000 and 1.70 per 100,000 were RBI and OBI, respectively. RBI (n = 120) and OBI (n = 583) donors constituted 26% of all HBV-infected (n = 2735) donors. Detection of HBV DNA in 92% of OBI donors required individual donation nucleic acid testing. Donors with OBI compared to RBI were older (mean age, 48 vs 39 years; p < 0.0001) with lower median viral loads (9 vs. 529 IU/mL; p < 0.0001). A higher proportion of OBI than RBI donors were born or resided in an endemic country (39% vs. 5%; p = 0.0078). Seventy-seven percent of all RBI and OBI donors had multiple sex partners, an HBV-risk factor. Of 40 RBI and 10 OBI donors whose S gene was sequenced, 33 (83%) and 6 (60%), respectively, carried HBV subgenotype A2; 18 (55%) and 2 (33%), respectively, shared an identical sequence. Infection with 1 or more putative HBV-immune-escape mutants was identified in 5 (50%) of OBI but no RBI donors. CONCLUSION: RBI and OBI continue to be identified at low rates, confirming the importance of comprehensive HBV DNA screening of US blood donations. HBV-infected donors require referral for care and evaluation and contact tracing; their HBV strains may provide important information on emergent genotypes.

Diagnosis of hepatitis C virus (HCV) infection is based on testing for antibodies to HCV (anti-HCV), hepatitis C core antigen (HCV cAg) and HCV RNA. To ensure quality control (QC) and quality assurance (QA), proficiency panels are provided by reference laboratories and various international organizations, requiring costly dry ice shipments to maintain specimen integrity. Alternative methods of specimen preservation and transport can save on shipping and handling and help in improving diagnostics by facilitating QA/QC of various laboratories especially in resource limited countries. Plasma samples positive for anti-HCV and HCV RNA were either dried using dried tube specimens (DTS) method or lyophilization for varying durations of time and temperature. Preservation of samples using DTS method resulted in loss of anti-HCV reactivity for low-positive samples and did not generate enough volume for HCV RNA testing. Lyophilized samples tested positive for anti-HCV even after storage at 4 degrees C and 25 degrees C for 12 weeks. Further, HCV RNA was detectable in 5 of 5 (100%) samples over the course of 12 week storage at 4, 25, 37 and 45 degrees C. In conclusion, lyophilization of specimens maintains integrity of plasma samples for testing for markers of HCV infection and can be a potent mode of sharing proficiency samples without incurring huge shipping costs and avoids challenges with dry ice shipments between donor and recipient laboratories.

INTRODUCTION: Recently, Salmonella enterica serovar Poona caused a multistate outbreak, with 245 out of 907 cases occurring in California. We report a comparison of pulsed-field gel electrophoresis (PFGE) results with whole genome sequencing (WGS) for genotyping of Salmonella Poona isolates. METHODS: CA Salmonella Poona isolates, collected from July to August 2015, were genotyped by PFGE using XbaI restriction enzyme. WGS was done using Nextera XT library kit with 2x300 bp or 2x250 bp sequencing chemistry on the Illumina MiSeq Sequencer. Reads were mapped to the de novo assembled serovar Poona draft genome (48 contigs, N50= 223,917) from the outbreak using CLCbio GW 8.0.2. The phylogenetic tree was generated based on hqSNPs calling. Genomes were annotated with CGE and PHAST online tools. In silico MLST was performed using the CGE online tool. RESULTS: Human (14) and cucumber (2) Salmonella Poona isolates exhibited 3 possibly related PFGE patterns (JL6X01.0018 [predominant], JL6X01.0375, JL6X01.0778). All isolates that were related by PFGE also clustered together according to the WGS. One isolate with a divergent PFGE pattern (JL6X01.0776) served as an outlier in the phylogenetic analysis and substantially differed from the outbreak clade by WGS. All outbreak isolates were assigned to MLST sequence type 447. The majority of the outbreak-related isolates possessed the same set of Salmonella Pathogenicity Islands with few variations. One outbreak isolate was sequenced and analyzed independently by CDC and CDPH laboratories; there was 0 SNP difference in results. Additional two isolates were sequenced by CDC and the raw data was processed through CDPH and CDC analysis pipelines. Both data analysis pipelines also generated concordant results. Discussion: PFGE and WGS results for the recent CA Salmonella enterica serovar Poona outbreak provided concordant assignment of the isolates to the outbreak cluster. WGS allowed more robust determination of genetic relatedness, provided information regarding MLST-type, pathogenicity genes, and bacteriophage content. WGS data obtained independently at two laboratories showed complete agreement.

Hepatitis E is a major public health problem in developing countries and is increasingly being recognized as a cause of substantial sporadic viral hepatitis infections in industrialized countries. Variable rates of hepatitis E seroprevalence have been reported from the same geographic regions depending on the assay used. In this study, we evaluated the performance characteristics of four assays which included two commercial assays, Wantai HEV-IgG ELISA kit (Wantai, China) and DS-EIA-ANTI-HEV-G kit (DSI, Italy), one NIH-developed immunoassay (NIH-55K, Kuniholm et al. 2009. JID 200:48-56) previously used in several major seroprevalence studies and one in-house western blot assay (CDC-WB). The limit of detection of IgG anti-HEV is 100 mIU/ml for Wantai assay, 200 mIU/ml for CDC-WB assay, 1000 mIU/ml for DSI assay and 40 mIU/ml for NIH-55K assay. Pairwise concordance between the four assays ranged from 56 to 87%. The concordance among all four assays was observed in 52% of the samples, while the concordance among three assays was observed in 37% of the samples. These data show a wide discordance between various IgG anti-HEV assays and warrant a comprehensive evaluation of all the assays using well characterized global serum reference panels.

OBJECTIVE: To describe the frequency, characteristics, and patient outcomes for women who accessed Emergency Medical Services (EMS) for obstetric emergencies at the ports of entry (POE) between El Paso, Texas, United States of America, and Ciudad Juarez, Chihuahua, Mexico. METHODS: A descriptive study of women 12-49 years of age for whom an EMS ambulance was called to an El Paso POE location from December 2008-April 2011 was conducted. Women were identified through surveillance of EMS records. EMS and emergency department (ED) records were abstracted for all women through December 2009 and for women with an obstetric emergency through April 2011. For obstetric patients admitted to the hospital, additional prenatal and birth characteristics were collected. Frequencies and proportions were estimated for each variable; differences between residents of the United States and Mexico were tested. RESULTS: During December 2008-December 2009, 47.6% (68/143) of women receiving EMS assistance at an El Paso POE had an obstetric emergency, nearly 20 times the proportion for Texas overall. During December 2008-April 2011, 60.1% (66/109) of obstetric patients with ED records were admitted to hospital and 52 gave birth before discharge. Preterm birth (23.1%; No. = 12), low birth weight (9.6%; No. = 5), birth in transit (7.7%; No. = 4), and postpartum hemorrhage (5.8%; No. = 3) were common; fewer than one-half the women (46.2%; No. = 24) had evidence of prenatal care. CONCLUSIONS: The high proportion of obstetric EMS transports and high prevalence of complications in this population suggest a need for binational risk reduction efforts.

We investigated the extent of lymphocytic choriomeningitis virus (LCMV) infection in employees and rodents at 3 commercial breeding facilities. Of 97 employees tested, 31 (32%) had IgM and/or IgG to LCMV, and aseptic meningitis was diagnosed in 4 employees. Of 1,820 rodents tested in 1 facility, 382 (21%) mice (Mus musculus) had detectable IgG, and 13 (0.7%) were positive by reverse transcription PCR; LCMV was isolated from 8. Rats (Rattus norvegicus) were not found to be infected. S-segment RNA sequence was similar to strains previously isolated in North America. Contact by wild mice with colony mice was the likely source for LCMV, and shipments of infected mice among facilities spread the infection. The breeding colonies were depopulated to prevent further human infections. Future outbreaks can be prevented with monitoring and management, and employees should be made aware of LCMV risks and prevention.

BACKGROUND: In vivo efficacy assessments of antimalarials are essential for ensuring effective case management. In Ethiopia, chloroquine (CQ) without primaquine is the first-line treatment for Plasmodium vivax in malarious areas, but artemether-lumefantrine (AL) is also commonly used. METHODS AND FINDINGS: In 2009, we conducted a 42-day efficacy study of AL or CQ for P. vivax in Oromia Regional State, Ethiopia. Individuals with P. vivax monoinfection were enrolled. Primary endpoint was day 28 cure rate. In patients with recurrent parasitemia, drug level and genotyping using microsatellite markers were assessed. Using survival analysis, uncorrected patient cure rates at day 28 were 75.7% (95% confidence interval (CI) 66.8-82.5) for AL and 90.8% (95% CI 83.6-94.9) for CQ. During the 42 days of follow-up, 41.6% (47/113) of patients in the AL arm and 31.8% (34/107) in the CQ arm presented with recurrent P. vivax infection, with the median number of days to recurrence of 28 compared to 35 days in the AL and CQ arm, respectively. Using microsatellite markers to reclassify recurrent parasitemias with a different genotype as non-treatment failures, day 28 cure rates were genotype adjusted to 91.1% (95% CI 84.1-95.1) for AL and to 97.2% (91.6-99.1) for CQ. Three patients (2.8%) with recurrent parasitemia by day 28 in the CQ arm were noted to have drug levels above 100 ng/ml. CONCLUSIONS: In the short term, both AL and CQ were effective and well-tolerated for P. vivax malaria, but high rates of recurrent parasitemia were noted with both drugs. CQ provided longer post-treatment prophylaxis than AL, resulting in delayed recurrence of parasitemia. Although the current policy of species-specific treatment can be maintained for Ethiopia, the co-administration of primaquine for treatment of P. vivax malaria needs to be urgently considered to prevent relapse infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT01052584.

BACKGROUND: Air travelers play a significant role in the spread of novel strains of influenza viruses; however, little is understood about the knowledge, attitudes, and practices of international air travelers toward pandemic influenza in relation to public health interventions and personal protective behaviors at overseas destinations. METHODS: Prior to the 2009 H1N1 influenza pandemic, we surveyed a convenience sample of 404 departing international travelers at Detroit Metropolitan Wayne County Airport. Presented with a hypothetical pandemic influenza scenario occurring overseas, the participants predicted their anticipated protective behaviors while abroad and recorded their attitudes toward potential screening measures at US ports of entry (POE). The survey also qualitatively explored factors that would influence compliance with health entry screening at POE. RESULTS: Those who perceived pandemic influenza to be serious were more likely to state that they would be comfortable with screening (p = 0.006), and if they had influenza-like illness (ILI) overseas, would be more willing to see a physician and delay return travel (p = 0.006 and 0.002, respectively). Other demographic variables, including age and race, were associated with protective behaviors in response to ILI. Travelers also identified diverse information requirements which would influence their behavior in response to entry screening, including characteristics of the pandemic, severity of illness, and screening operations. CONCLUSIONS: Demographic characteristics and perceived severity of illness are important factors that may influence the protective behaviors of travelers overseas. Our results indicate that educational material and advice directed to international travelers could be differentially tailored to traveler subpopulations.

BACKGROUND: In 2005, Ghana adopted artemisinin-based combination therapy (ACT) for primary treatment of falciparum malaria. A comprehensive study of the drug-resistance-associated mutations and their genetic lineages will lead to a better understanding of the evolution of antimalarial drug resistance in this region. METHODS: The pfcrt, pfmdr1, dhps, and dhfr mutations associated with chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) resistance and the microsatellite loci flanking these genes were genotyped in Plasmodium falciparum isolates from Ghana. RESULTS: The prevalence of mutations associated with both CQ and SP resistance was high in Ghana. However, we observed a decrease in prevalence of the pfcrt K76T mutation in northern Ghana after the change in drug policy from CQ to ACT. Analysis of genetic diversity and differentiation at microsatellite loci flanking all 4 genes indicated that they have been under strong selection, because of CQ and SP use. The triple-mutant pfcrt and dhfr alleles in Ghana were derived from Southeast Asia, whereas the double-mutant dhfr, dhps, and pfmdr1 alleles were of African lineage. CONCLUSION: Because of the possible role of pfmdr1 in amodiaquine and mefloquine resistance, demonstrating selection on pfmdr1 and defining lineages of resistant alleles in an African population holds great importance.

Assessing how natural selection, negative or positive, operates on genes with low polymorphism is challenging. We investigated the genetic diversity of orthologous genes encoding the rhoptry-associated protein 1 (RAP-1), a low polymorphic protein of malarial parasites that is involved in erythrocyte invasion. We applied evolutionary genetic methods to study the polymorphism in RAP-1 from Plasmodium falciparum (n=32) and Plasmodium vivax (n=6), the two parasites responsible for most human malaria morbidity and mortality, as well as RAP-1 orthologous in closely related malarial species found in non-human primates (NHPs). Overall, genes encoding RAP-1 are highly conserved in all Plasmodium spp. included in this investigation. We found no evidence for natural selection, positive or negative, acting on the gene encoding RAP-1 in P. falciparum or P. vivax. However, we found evidence that the orthologous genes in non-human primate parasites (Plasmodium cynomolgi, Plasmodium inui, and Plasmodium knowlesi) are under purifying (negative) selection. We discuss the importance of considering negative selection while studying genes encoding proteins with low polymorphism and how selective pressures may differ among orthologous genes in closely related malarial parasites species.

Treatment of Plasmodium falciparum is complicated by the emergence and spread of parasite resistance to many of the first line drugs used to treat malaria. Anti-malarial drug resistance has been associated with specific point mutations in several genes, suggesting that these single nucleotide polymorphisms can be useful in tracking the emergence of drug resistance. In India, P. falciparum can manifest itself as asymptomatic, mild, or severe malaria, with or without cerebral involvement. We tested whether chloroquine and antifolate drug resistant genotypes would be more commonly associated with cases of cerebral malaria than with cases of mild malaria in the province of Jabalpur, India by genotyping the genes dhps, dhfr, pfmdr-1, and pfcrt using pyrosequencing, direct sequencing, and real time PCR. Further, we used microsatellites surrounding the genes to determine the origins and spread of the drug resistant genotypes in this area. Resistance to chloroquine was essentially fixed with 95% of the isolates harboring the pfcrt K76T mutation. Resistant genotypes of dhfr, dhps, and pfmdr-1 were found in 94%, 17%, and 77% of the isolates, respectively. Drug resistant genotypes were equally likely to be associated with cerebral malaria as they were with cases of mild malaria. We found evidence of a selective sweep in pfcrt and, to a lesser degree, dhfr, indicating high levels of resistance to chloroquine and evolving resistance to pyrimethamine. Microsatellites surrounding pfcrt indicate that the resistant genotypes (SVMNT) were most similar to those found in Papua New Guinea.