This qualitative study takes place in an urban community that has high rates of HIV among Black youth. Six faith leaders were interviewed (five identified as Christian and one identified as Muslim). Three major themes arose from the interviews, including (1) the role of sex and HIV; (2) hindrances to sexual health conversations with youth; and (3) considering religious principles to prevent HIV in Black youth. Findings from this study can be used to inform an HIV-prevention curriculum for Black youth who identify strongly with their religion and spirituality and live in high HIV-risk communities. © 2024 by the authors.

BACKGROUND: Mechanisms underlying the pro gression of diabetic kidney disease to ESKD are not fully understood. METHODS: We performed global microRNA (miRNA) analysis on plasma from two cohorts consisting of 375 individuals with type 1 and type 2 diabetes with late diabetic kidney disease, and targeted proteomics analysis on plasma from four cohorts consisting of 746 individuals with late and early diabetic kidney disease. We examined structural lesions in kidney biopsy specimens from the 105 individuals with early diabetic kidney disease. Human umbilical vein endothelial cells were used to assess the effects of miRNA mimics or inhibitors on regulation of candidate proteins. RESULTS: In the late diabetic kidney disease cohorts, we identified 17 circulating miRNAs, represented by four exemplars (miR-1287-5p, miR-197-5p, miR-339-5p, and miR-328-3p), that were strongly associated with 10-year risk of ESKD. These miRNAs targeted proteins in the axon guidance pathway. Circulating levels of six of these proteins-most notably, EFNA4 and EPHA2-were strongly associated with 10-year risk of ESKD in all cohorts. Furthermore, circulating levels of these proteins correlated with severity of structural lesions in kidney biopsy specimens. In contrast, expression levels of genes encoding these proteins had no apparent effects on the lesions. In in vitro experiments, mimics of miR-1287-5p and miR-197-5p and inhibitors of miR-339-5p and miR-328-3p upregulated concentrations of EPHA2 in either cell lysate, supernatant, or both. CONCLUSIONS: This study reveals novel mechanisms involved in progression to ESKD and points to the importance of systemic factors in the development of diabetic kidney disease. Some circulating miRNAs and axon guidance pathway proteins represent potential targets for new therapies to prevent and treat this condition.

Underprioritization of mental health is a global problem and threatens the decades-long progress of the US President's Emergency Plan for AIDS Relief (PEPFAR) program. In recent years, mental health has become globally recognized as a part of universal healthcare, making this an opportune moment for the global community to integrate mental health services into routine programming. PEPFAR is well positioned to lead by example. We conceptualized 5 key strategies that might help serve as a framework to support mental health programming as part of PEPFAR's current 5-year strategic plan. PEPFAR and the global community have an opportunity to identify mental health service gaps and interweave global mental health priorities with actions to end the HIV and TB epidemics by 2030.

Tuberculosis (TB) is the leading cause of death among persons with HIV. In 2022, an estimated 167,000 TB-related deaths occurred globally among persons with HIV. TB preventive treatment (TPT) helps prevent TB disease and is recommended for persons at high risk for developing TB, including those with HIV. TPT, when taken with antiretroviral treatment (ART), can reduce TB-attributable deaths among persons with HIV. In 2018, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) program committed to offer one course of TPT to all eligible clients receiving ART. This analysis describes trends in TPT initiation and completion among PEPFAR-supported programs in 36 countries in Africa, Central and South America, and Asia during fiscal years (FYs) 2017-2023. Overall, TPT initiation rates peaked in FY19, a possible sign of programmatic saturation. TPT initiation among clients who had been on ART <6 months reached 59%, and overall completion rates up to 87% were reported. Approximately 13 million persons with HIV have completed TPT since FY17, but widespread adoption of shorter regimens, patient-centered approaches, and electronic medical record systems might be needed to ensure full TPT coverage. Through PEPFAR's partnership with national HIV programs, TPT has become the standard of care for persons with HIV.

In a broad sense, molecular epidemiology is the axis that unites insights at the molecular level and understanding of disease at the population level. It is also a partnership between epidemiologists and laboratory scientists in which investigations are conducted using the principles of both disciplines. A key trait of molecular epidemiology is to evaluate and establish the relationship between a biomarker and important exogenous and endogenous exposures, susceptibility, or disease, providing understanding that can be used in future research and public health and clinical practice. When potential solutions or interventions are identified, molecular epidemiology is also useful in developing and conducting clinical and intervention trials. It can then contribute to the translation of biomedical research into practical public health and clinical applications by addressing the medical and population implications of molecular phenomena in terms of reducing risk of disease. This chapter summarizes the contributions and research endeavours of molecular epidemiology and how they link with public health initiatives and clinical practice.

Viral metagenomics sequencing of fecal samples from outbreaks of acute gastroenteritis from the US revealed the presence of small circular ssDNA viral genomes encoding a replication initiator protein (Rep). Viral genomes were ∼2.5 kb in length, with bi-directionally oriented Rep and capsid (Cap) encoding genes and a stem loop structure downstream of Rep. Several genomes showed evidence of recombination. By digital screening of an in-house virome database (1.04 billion reads) using BLAST, we identified closely related sequences from cases of unexplained diarrhea in France. Deep sequencing and PCR detected such genomes in 7 of 25 US (28 percent) and 14 of 21 French outbreaks (67 percent). One of eighty-five sporadic diarrhea cases in the Gambia was positive by PCR. Twenty-two complete genomes were characterized showing that viruses from patients in the same outbreaks were closely related suggesting common origins. Similar genomes were also characterized from the stools of captive chimpanzees, a gorilla, a black howler monkey, and a lemur that were more diverse than the human stool-associated genomes. The name smacovirus is proposed for this monophyletic viral clade. Possible tropism include mammalian enteric cells or ingested food components such as infected plants. No evidence of viral amplification was found in immunodeficient mice orally inoculated with smacovirus-positive stool supernatants. A role for smacoviruses in diarrhea, if any, remains to be demonstrated.

BACKGROUND: The impact of work-related asthma (WRA) on quality of life (QoL) and work productivity remains largely neglected/uncertain despite its high prevalence. OBJECTIVE: To investigate the association of WRA with QoL and work productivity as compared with subjects with non-WRA and those without asthma and rhinitis. METHODS: A cross-sectional survey was carried out among workers during their periodic occupational health visit in Belgium. The Mini Asthma Quality of Life Questionnaire, the 8-item Medical Outcome Study Short Form instrument, and the Work Productivity and Activity Impairment-General Health questionnaire were administered. Survey participants were divided into 3 groups: (1) WRA (current asthma with ≥2 respiratory symptoms at work; n = 89); (2) non-WRA (current asthma without work-related respiratory symptoms; n = 119); and (3) the reference group (no asthma and no lower respiratory, nasal, or eye symptoms; n = 815). Associations of QoL and work productivity with WRA were evaluated by multivariable regression analyses. RESULTS: WRA and having poor asthma control were significantly associated with lower global Mini Asthma Quality of Life Questionnaire scores compared with non-WRA. Asthmatic subjects had significantly lower physical and mental health component scores of the 8-item Medical Outcome Study Short Form instrument and overall work productivity compared with the reference group, with greater impairment in workers with WRA than in those without WRA. Moreover, workers with WRA had higher percentages of doctor visits and income reduction because of respiratory symptoms than those with non-WRA. Work-related rhinitis and depression were associated with reduced QoL, independent of the effect of WRA. CONCLUSIONS: WRA should be managed comprehensively to reduce the worsening of QoL and work productivity of those affected.

The US President's Emergency Plan for AIDS Relief (PEPFAR) is the largest HIV program globally, serving roughly 58% of the estimated 28.7 million people with HIV (PWH) on antiretroviral therapy (ART) in 2021 [1,2]. Tuberculosis (TB) remains the leading cause of death among PWH; an estimated 46% of TB cases are undiagnosed at the time of death, emphasizing the challenge of TB detection among this population [3]. The WHO four-symptom screen at every clinical encounter is the primary TB case finding strategy implemented in PEPFAR. Recent program data show 87% of PWH were screened for TB symptoms and, among those, only 2.7% screened positive and were referred for further TB evaluation [2]. Although the expected rate of TB symptom positivity among PWH is debated, PEPFAR's yield is not yet optimal compared with reports from the literature ranging from 30% to 67% [4]. Poor case detection leads to PWH with undiagnosed, untreated, and unreported TB, which contributes to subsequent TB-attributable mortality among PWH. The extent of gaps in case detection and mortality have been difficult to quantify. | | We estimated the number of missed TB/HIV diagnoses and TB-attributable deaths in the populations PEPFAR serves using data from PEPFAR, WHO, and the Joint United Nations Programme on HIV/AIDS (UNAIDS) [1,5]. Data was analyzed for 2018–2021, reflecting data from before the COVID-19 pandemic through the most recently available year. WHO and UNAIDS reporting periods were aligned with PEPFAR data wherever possible. Country-level data was analyzed by year for the 32 countries where PEPFAR operated and reported TB data. All datasets were downloaded in April 2023 and analyzed in Tableau, version 2022.1.

Wearing a facemask can help to decrease the transmission of COVID-19. We investigated self-reported mask use among subjects aged 18 years and older participating in the COVID-19 Community Research Partnership (CRP), a prospective longitudinal COVID-19 surveillance study in the mid-Atlantic and southeastern United States. We included those participants who completed >=5 daily surveys each month from December 1, 2020 through August 31, 2021. Mask use was defined as self-reported use of a face mask or face covering on every interaction with others outside the household within a distance of less than 6 feet. Participants were considered vaccinated if they reported receiving >=1 COVID-19 vaccine dose. Participants (n=17,522) were 91% non-Hispanic White, 68% female, median age 57 years, 26% healthcare workers, with 95% self-reported receiving >=1 COVID-19 vaccine dose through August; mean daily survey response was 85%. Mask use was higher among vaccinated than unvaccinated participants across the study period, regardless of the month of the first dose. Mask use remained relatively stable from December 2020 through April (range 71-80% unvaccinated; 86-93% vaccinated) and declined in both groups beginning in mid-May 2021 to 34% and 42% respectively in June 2021; mask use has increased again since July 2021. Mask use by all was lower during weekends and on Christmas and Easter, regardless of vaccination status. Independent predictors of higher mask use were vaccination, age >=65 years, female sex, racial or ethnic minority group, and healthcare worker occupation, whereas a history of self-reported prior COVID-19 illness was associated with lower use. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Targeting malaria interventions in elimination settings where transmission is heterogeneous is essential to ensure the efficient use of resources. Identifying the most important risk factors among persons experiencing a range of exposure can facilitate such targeting. A cross-sectional household survey was conducted in Artibonite, Haiti, to identify and characterize spatial clustering of malaria infections. Household members (N = 21,813) from 6,962 households were surveyed and tested for malaria. An infection was defined as testing positive for Plasmodium falciparum by either a conventional or novel highly sensitive rapid diagnostic test. Seropositivity to the early transcribed membrane protein 5 antigen 1 represented recent exposure to P. falciparum. Clusters were identified using SaTScan. Associations among individual, household, and environmental risk factors for malaria, recent exposure, and living in spatial clusters of these outcomes were evaluated. Malaria infection was detected in 161 individuals (median age: 15 years). Weighted malaria prevalence was low (0.56%; 95% CI: 0.45-0.70%). Serological evidence of recent exposure was detected in 1,134 individuals. Bed net use, household wealth, and elevation were protective, whereas being febrile, over age 5 years, and living in either households with rudimentary wall material or farther from the road increased the odds of malaria. Two predominant overlapping spatial clusters of infection and recent exposure were identified. Individual, household, and environmental risk factors are associated with the odds of individual risk and recent exposure in Artibonite; spatial clusters are primarily associated with household-level risk factors. Findings from serology testing can further strengthen the targeting of interventions.

We describe a strain of Lassa virus representing a putative new lineage that was isolated from a cluster of human infections with an epidemiologic link to Togo. This finding extends the known range of Lassa virus to Togo.

INTRODUCTION: We developed a standardized method, "Possible poor treatment response" (PPTR), to help ascertain efficacy endpoints in Study S31/A5349 (NCT02410772), an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regimen for the treatment of pulmonary TB. We describe the use of the PPTR process and evaluate whether the goals of minimizing bias in efficacy endpoint assessment and attainment of relevant data to determine outcome for all participants were achieved. METHODS/DESIGN: A PPTR event was defined as the occurrence of one or more pre-specified triggers. Each PPTR required initiation of a standardized evaluation process that included obtaining multiple sputum samples for microbiology. RESULTS: Among 2,343 participants with culture-confirmed drug-susceptible TB, 454 individuals (19.4%) had a total of 534 individual PPTR events, of which 76.6% were microbiological (positive smear or culture at or after 17 weeks). At least one PPTR event was experienced by 92.4% (133 of 144) of participants with TB-related unfavorable outcome, and between 13.8 and 14.7% of participants with favorable and not assessable outcomes. 75% of participants with TB-related unfavorable outcomes had microbiological confirmation of failure to achieve disease-free cure. DISCUSSION: Standardized methodologies, such as our PPTR approach, could facilitate unbiased efficacy outcome determinations, improve discrimination between outcomes that are related and unrelated to regimen efficacy, and enhance the ability to conduct pooled analyses of contemporary trials. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT02410772.

On September 30, 2022, after >3 years with no confirmed cholera cases (1), the Directorate of Epidemiology, Laboratories and Research (DELR) of the Haitian Ministry of Public Health and Population (Ministère de la Santé Publique et de la Population [MSPP]) was notified of two patients with acute, watery diarrhea in the metropolitan area of Port-au-Prince. Within 2 days, Haiti's National Public Health Laboratory confirmed the bacterium Vibrio cholerae O1 in specimens from the two patients with suspected cholera infection, and an outbreak investigation began immediately. As of January 3, 2023, >20,000 suspected cholera cases had been reported throughout the country, and 79% of patients have been hospitalized. The moving 14-day case fatality ratio (CFR) was 3.0%. Cholera, which is transmitted through ingestion of water or food contaminated with fecal matter, can cause acute, severe, watery diarrhea that can rapidly lead to dehydration, shock, and death if not treated promptly (2). Haiti is currently facing ongoing worsening of gang violence, population displacement, social unrest, and insecurity, particularly in the metropolitan area of Port-au-Prince, including Belair, Bas-Delmas, Centre-Ville, Martissant, Cité Soleil, Croix-des Bouquets, and Tabarre, creating an environment that has facilitated the current resurgence of cholera (3). This report describes the initial investigation, ongoing outbreak, and public health response to cholera in Haiti. Cholera outbreak responses require a multipronged, multisectoral approach including surveillance; case management; access to safe water, sanitation, and hygiene (WASH) services; targeted oral cholera vaccine (OCV) campaigns; risk communication; and community engagement. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.

Gulf War Illness (GWI) is a chronic illness that affects upward of 32% of deployed Veterans to the 1991 Gulf War (GW). The symptoms are medically unexplained, ranging across cognitive deficits, fatigue, gastrointestinal problems, and musculoskeletal pain. Research indicates that chemical warfare agents play a key role in the onset and progression of GWI. The Khamisiyah ammunition storage that housed chemical warfare agents such as sarin, an acetylcholinesterase (AChE) inhibitor, was demolished during the GW, releasing toxicants into the atmosphere affecting deployed troops. Exposure to other chemical agents such as pyridostigmine bromide, N,N-diethyl-m-toluamide, permethrin and chlorpyrifos, were also prevalent during the war. These additional chemical agents have also been shown to inhibit AChE. AChE inhibition induces an acetylcholine build-up, disrupting signals between nerves and muscles, which in high doses leads to asphyxiation. Little is known about low dose exposure. As bioactive compounds tend to interact with multiple proteins with various physiological effect, we aimed to identify other potential shared targets to understand the extent in which these chemicals could lead to GWI. We followed a reverse screening approach where each chemical is computationally docked to a library of protein targets. The programs PharmMapper and TargetNet were used for this purpose, and further analyses were conducted to mark significant changes in participants with GWI. Previously published work on DNA methylation status in GWI was reanalyzed focusing specifically on the predicted shared targets indicating significant changes in DNA methylation of the associated genes. Our findings thus suggest that exposure to GWI-related agents may converge on similar targets with roles in inflammation, neurotransmitter and lipid metabolism, and detoxification which may have impacts on neurodegenerative-like disease and oxidative stress in Veterans with GWI.

The Centers for Disease Control and Prevention's (CDC) Division of Adolescent and School Health (DASH) works with local decision makers, schools, youth-serving organizations, and parents across the nation to equip youth with knowledge, skills, and resources needed for healthy adolescence and adulthood. Aligned with this effort, DASH maintains high-quality surveillance systems to understand youth health behaviors and assess school health programs and policies. The Youth Risk Behavior Surveillance System (YRBSS) is a system of surveys administered every other year to high school students. In addition to the national Youth Risk Behavior Survey conducted by CDC, YRBSS features Youth Risk Behavior Surveys (YRBS) conducted by state, territorial, and local education and health agencies and tribal governments across the nation.1 Local decision makers collaborate with partners to develop questionnaires for their respective YRBS, then coordinate data dissemination and utilization. Since its inception in 1991, YRBSS has collected data from more than 5 million high school students in approximately 2200 separate surveys across the United States.1 The School Health Profiles (Profiles) is a system of surveys conducted by state, territorial, and local education and health agencies and tribal governments. These surveys collect data every other year from principals and lead health education teachers to assess school-implemented health programs and policies.2 Since 1994, Profiles data have helped evaluate health programs and informed professional development needs for educators in middle and high schools.2 Together, YRBSS and Profiles offer metrics to inform public health needs, which are then translated into evidence-based programs to protect youth.

BACKGROUND: Haiti's first COVID-19 cases were confirmed on March 18, 2020, and subsequently spread throughout the country. The objective of this study was to describe clinical manifestations of COVID-19 in Haitian outpatients and to identify risk factors for severity of clinical manifestations. METHODS: We conducted a retrospective study of COVID-19 outpatients diagnosed from March 18-August 4, 2020, using demographic, epidemiological, and clinical data reported to the Ministry of Health (MoH). We used univariate and multivariate analysis, including multivariable logistic regression, to explore the risk factors and specific symptoms related to persons with symptomatic COVID-19 and the severity of symptomatic COVID-19 disease. RESULTS: Of 5,389 cases reported to MOH during the study period, 1,754 (32.5%) were asymptomatic. Amongst symptomatic persons 2,747 (75.6%) had mild COVID-19 and 888 (24.4%) had moderate-to-severe disease; the most common symptoms were fever (69.6%), cough (51.9%), and myalgia (45.8%). The odds of having moderate-to-severe disease were highest among persons with hypertension (aOR = 1.72, 95% Confidence Interval [CI] (1.34, 2.20), chronic pulmonary disease (aOR = 3.93, 95% CI (1.93, 8.17)) and tuberculosis (aOR = 3.44, 95% CI (1.35, 9.14)) compared to persons without those conditions. The odds of having moderate-to-severe disease increased with age but was also seen among children aged 0-4 years (OR: 1.73, 95% CI (0.93, 3.08)), when using 30-39 years old as the reference group. All of the older age groups, 50-64 years, 65-74 years, 75-84 years, and 85+ years, had significantly higher odds of having moderate-to-severe COVID-19 compared with ages 30-39 years. Diabetes was associated with elevated odds of moderate-to-severe disease in bivariate analysis (OR = 2.17, 95% CI (1.58,2.98) but, this association did not hold in multivariable analyses (aOR = 1.22,95%CI (0.86,1.72)). CONCLUSION: These findings from a resource-constrained country highlight the importance of surveillance systems to track emerging infections and their risk factors. In addition to co-morbidities described elsewhere, tuberculosis was a risk factor for moderate-to-severe COVID-19 disease.

BACKGROUND: Haiti introduced a monovalent human group A rotavirus (RVA) vaccine (Rotarix) into its routine infant immunization program in April 2014. The goal of the surveillance program was to characterize RVA strains circulating in Haiti before and after RVA vaccine introduction. METHODS: Stool samples were collected from children <5 years old presenting with acute gastroenteritis at 16 hospitals in Haiti. RVA antigen enzyme immunoassay (EIA) testing was performed, and G and P genotypes were determined for positive specimens. In this study, genotype data for samples collected from May 2012 through April 2014 (the pre-vaccine introduction era) and May 2014 through July 2019 (post-vaccine introduction era) were analyzed. RESULTS: A total of 809 specimens were tested by the Centers for Disease Control and Prevention. During the pre-vaccine introduction era (May 2012 through April 2014), G12P[8] was the predominant genotype, detected in 88-94% of specimens. There was a high prevalence of the equine-like G3P[8] genotype among Haitian children with RVA after vaccine introduction. CONCLUSIONS: The predominance of equine-like G3P[8] in three of five RVA seasons post-vaccine introduction suggests possible vaccine-specific selection pressure in Haiti. These temporal variations in RVA genotype predominance will require continued monitoring in Haiti as the vaccination program continues.

Maternal mortality is increasingly recognized as a public health crisis in the United States, with growing attention on the 3 major systems of national surveillance. National maternal mortality statistics are reported by the Centers for Disease Control and Prevention’s (CDC’s) National Vital Statistics System (NVSS)1 within the National Center for Health Statistics (NCHS) and the Pregnancy Mortality Surveillance System (PMSS)2 within the Division of Reproductive Health (DRH). Comprehensive surveillance data at the state and local level are also available from maternal mortality review committees (MMRCs) via the Maternal Mortality Review Information Application (MMRIA).3 Each surveillance system has inherent strengths and limitations, but all rely on valid, accurate, and timely case identification via vital statistics data. We outline recent innovations to improve identification and ensure robust and accurate surveillance of maternal mortality in the United States.

The social setting of animal subjects in the research environment has known effects on a variety of dependent measures used in biomedical research. Proper evaluation of the robustness of published research is dependent upon transparent, detailed, and accurate reporting of research methods, including the animals' social housing conditions. However, to date, most research articles utilizing nonhuman primates (NHPs) provide only partial data on this topic, hampering transparency, and reproducibility. Therefore, we call for the inclusion of information pertaining to the social aspects of the animals' housing conditions in publications involving NHPs to improve transparency. We argue that including this information in scientific publications is crucial for the interpretation of research findings in the appropriate context and for understanding unexplained variability in study findings. Finally, the inclusion of this information in publications will additionally familiarize scientists with how other researchers conducting similar studies are housing their animals and will encourage them to consider the implications of various housing conditions on their research outcomes.

Little is known about respiratory viruses infection in Guinea. Influenza surveillance has not been implemented in Guinea mainly because of the paucity of laboratory infrastructure and capacity. This paper presents the first influenza surveillance data in Guinea.Swabs were obtained from August 2018 through December 2019 at influenza sentinel sites and transported to the Institut National de Sante Publique for testing. Ribonucleic acid was extracted and tested for the presence of influenza A and B by real-time reverse transcription-polymerase chain reaction (RT-PCR). Positive samples were further characterised to determine the subtypes and lineages of influenza viruses.A total of 862 swabs were collected and tested. Twenty-three per cent of samples tested positive for influenza A and B viruses. Characterisation of positive specimens identified influenza A/H1N1pmd09 (2.5%), influenza A/H3N2 (57.3%), influenza B/Victoria lineage (36.7%) and 7 (3.5%) influenza B with undetermined lineage. Influenza B virus activity clustered in August through November while influenza A/H3N2 displayed two clusters of activities that appeared in May through August and November through December.For the first time in Guinea, the epidemiology, diversity and period of circulation of influenza viruses were studied. The results indicate the predominance and the periods of activities of influenza B Victoria lineage and influenza A/H3N2 which are important information for preventive strategies. It is warranted to extend the influenza surveillance to other parts of Guinea to better understand the epidemiology of the viruses and monitor the emergence of influenza strains with pandemic potential.

Multisectoral investments over the past decade have accelerated the growth of Maternal Mortality Review Committee (MMRC) programs across the United States. The U.S. Centers for Disease Control and Prevention (CDC) launched the Enhancing Reviews and Surveillance to Eliminate Maternal Mortality (ERASE MM) Initiative in 2019. Under ERASE MM, CDC directly funds 24 U.S. jurisdictions supporting MMRCs in 25 states. With increased investment in programs nationally, the CDC has designed a performance management framework to identify areas for improvement or sustained achievement and standardize measurement of key process benchmarks across programs. This article presents a report on the baseline measures collected through this performance management approach and suggests key partnerships required to continue to accelerate progress toward the elimination of preventable maternal mortality in the United States.

Rotavirus is responsible for 26% of diarrheal deaths in Latin America and the Caribbean. Haiti introduced the monovalent rotavirus vaccine in April 2014. The objective of this analysis is to describe the impact of the rotavirus vaccine on hospitalizations among Haitian children younger than 5 years old during the first 5 years after introduction. This analysis includes all children with diarrhea who were enrolled as part of a sentinel surveillance system at two hospitals from May 2013 to April 2019. We compare the proportion of rotavirus-positive specimens in each post-vaccine introduction year to the pre-vaccine period. To account for the potential dilution of the proportion of rotavirus-positive specimens from a waning cholera outbreak, we also analyzed annual trends in the absolute number of positive stools, fit a two-component finite-mixture model to the negative specimens, and fit a negative binomial time series model to the pre-vaccine rotavirus-positive specimens to predict the number of rotavirus diarrhea hospital admissions in the absence of rotavirus vaccination. The overall percentage of rotavirus-positive specimens declined by 22% the first year after introduction, increased by 17% the second year, and declined by 33% to 50% the subsequent 3 years. All sensitivity analyses confirmed an overall decline. We observed a clear annual rotavirus seasonality before and after vaccine introduction, with the greatest activity in December through April, and a biennial pattern, with high sharp peaks and flatter longer periods of increased rotavirus activity in alternating years, consistent with suboptimal vaccination coverage. Overall, our study shows evidence that the introduction of the rotavirus vaccine reduced the burden of severe rotavirus diarrhea.

BACKGROUND: Rotavirus vaccine (RV) coverage levels for U.S. infants are <80%. METHODS: We surveyed nationally representative networks of pediatricians by internet/mail from April-June, 2019. Multivariable regression assessed factors associated with difficulty administering the first RV dose (RV#1) by the maximum age. RESULTS: Response rate was 68% (303/448). 99% of providers reported strongly recommending RV. The most common barriers to RV delivery overall (definite/somewhat of a barrier) were: parental concerns about vaccine safety overall (27%), parents wanting to defer (25%), parents not thinking RV was necessary (12%) and parent concerns about RV safety (6%). The most commonly reported reasons for non-receipt of RV#1 by 4-5 months (often/always) were parental vaccine refusal (9%), hospitals not giving RV at discharge from nursery (7%), infants past the maximum age when discharged from NICU/nursery (6%), and infant not seen before maximum age for well care visit (3%) or seen but no vaccine given (4%). Among respondents 4% strongly agreed and 25% somewhat agreed that they sometimes have difficulty giving RV#1 before the maximum age. Higher percentage of State Child Health Insurance Program/Medicaid-insured children in the practice and reporting that recommendations for timing of RV doses are too complicated were associated with reporting difficulty delivering the RV#1 by the maximum age. CONCLUSIONS: U.S. pediatricians identified multiple, actionable issues that may contribute to suboptimal RV immunization rates including lack of vaccination prior to leaving nurseries after prolonged stays, infants not being seen for well care visits by the maximum age, missed opportunities at visits and parents refusing/deferring.

BACKGROUND: Rotavirus vaccines are effective in preventing severe rotavirus. Haiti introduced 2-dose monovalent (G1P[8]) rotavirus vaccine recommended for infants at 6 and 10 weeks of age in 2014. We calculated the effectiveness of rotavirus vaccine against hospitalization for acute gastroenteritis in Haiti. METHODS: We enrolled children 6-59 months old admitted May 2014-September 2019 for acute watery diarrhea at any sentinel surveillance hospital. Stool was tested for rotavirus using enzyme immunoassay (EIA) and genotyped with multiplex one-step RT-PCR assay and Sanger sequencing for stratification by genotype. We used a case-negative design where cases were children positive for rotavirus and controls were negative for rotavirus. Only children eligible for vaccination were included and a child was considered vaccinated if vaccine was given ≥ 14 days before enrollment. We used unconditional logistic regression to calculate odds ratios and calculated 2-dose and 1-dose vaccine effectiveness (VE) as (1 - odds ratio) * 100. RESULTS: We included 129 (19%) positive cases and 543 (81%) negative controls. Among cases, 77 (60%) were positive for equine-like G3P[8]. Two doses of rotavirus vaccine were 66% (95% CI: 44, 80) effective against hospitalizations due to any strain of rotavirus and 64% (95% CI: 33, 81) effective against hospitalizations due to the equine-like G3P[8] genotype. CONCLUSIONS: These findings are comparable to other countries in the Americas region. To the best of our knowledge, this is the first VE estimate both against the equine-like G3P[8] genotype and from a Caribbean country. Overall, these results support rotavirus vaccine use and demonstrate the importance of complete vaccination.

BACKGROUND: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. METHODS: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months. RESULTS: Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group. CONCLUSIONS: The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.).

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.

BACKGROUND: Two novel type 2 oral poliovirus vaccine (OPV2) candidates, novel OPV2-c1 and novel OPV2-c2, designed to be more genetically stable than the licensed Sabin monovalent OPV2, have been developed to respond to ongoing polio outbreaks due to circulating vaccine-derived type 2 polioviruses. METHODS: We did two randomised studies at two centres in Belgium. The first was a phase 4 historical control study of monovalent OPV2 in Antwerp, done before global withdrawal of OPV2, and the second was a phase 2 study in Antwerp and Ghent with novel OPV2-c1 and novel OPV2-c2. Eligible participants were healthy adults aged 18-50 years with documented history of at least three polio vaccinations, including OPV in the phase 4 study and either OPV or inactivated poliovirus vaccine (IPV) in the novel OPV2 phase 2 study, with no dose within 12 months of study start. In the historical control trial, participants were randomly assigned to either one dose or two doses of monovalent OPV2. In the novel OPV2 trial, participants with previous OPV vaccinations were randomly assigned to either one or two doses of novel OPV2-c1 or to one or two doses of novel OPV2-c2. IPV-vaccinated participants were randomly assigned to receive two doses of either novel OPV2-c1, novel OPV2-c2, or placebo. Vaccine administrators were unmasked to treatment; medical staff performing safety and reactogenicity assessments or blood draws for immunogenicity assessments were masked. Participants received the first vaccine dose on day 0, and a second dose on day 28 if assigned to receive a second dose. Primary objectives were assessments and comparisons of safety up to 28 days after each dose, including solicited adverse events and serious adverse events, and immunogenicity (seroprotection rates on day 28 after the first vaccine dose) between monovalent OPV2 and the two novel OPV2 candidates. Primary immunogenicity analyses were done in the per-protocol population. Safety was assessed in the total vaccinated population-ie, all participants who received at least one dose of their assigned vaccine. The phase 4 control study is registered with EudraCT (2015-003325-33) and the phase 2 novel OPV2 study is registered with EudraCT (2018-001684-22) and ClinicalTrials.gov (NCT04544787). FINDINGS: In the historical control study, between Jan 25 and March 18, 2016, 100 volunteers were enrolled and randomly assigned to receive one or two doses of monovalent OPV2 (n=50 in each group). In the novel OPV2 study, between Oct 15, 2018, and Feb 27, 2019, 200 previously OPV-vaccinated volunteers were assigned to the four groups to receive one or two doses of novel OPV2-c1 or novel OPV2-c2 (n=50 per group); a further 50 participants, previously vaccinated with IPV, were assigned to novel OPV2-c1 (n=17), novel OPV2-c2 (n=16), or placebo (n=17). All participants received the first dose of assigned vaccine or placebo and were included in the total vaccinated population. All vaccines appeared safe; no definitely vaccine-related withdrawals or serious adverse events were reported. After first doses in previously OPV-vaccinated participants, 62 (62%) of 100 monovalent OPV2 recipients, 71 (71%) of 100 recipients of novel OPV2-c1, and 74 (74%) of 100 recipients of novel OPV2-c2 reported solicited systemic adverse events, four (monovalent OPV2), three (novel OPV2-c1), and two (novel OPV2-c2) of which were considered severe. In IPV-vaccinated participants, solicited adverse events occurred in 16 (94%) of 17 who received novel OPV2-c1 (including one severe) and 13 (81%) of 16 who received novel OPV2-c2 (including one severe), compared with 15 (88%) of 17 placebo recipients (including two severe). In previously OPV-vaccinated participants, 286 (97%) of 296 were seropositive at baseline; after one dose, 100% of novel OPV2 vaccinees and 97 (97%) of monovalent OPV2 vaccinees were seropositive. INTERPRETATION: Novel OPV2 candidates were as safe, well tolerated, and immunogenic as monovalent OPV2 in previously OPV-vaccinated and IPV-vaccinated adults. These data supported the further assessment of the vaccine candidates in children and infants. FUNDING: University of Antwerp and Bill & Melinda Gates Foundation.

BACKGROUND: With increasing interest in eliminating malaria from the Caribbean region, Haiti is one of the two countries on the island of Hispaniola with continued malaria transmission. While the Haitian population remains at risk for malaria, there are a limited number of cases annually, making conventional epidemiological measures such as case incidence and prevalence of potentially limited value for fine-scale resolution of transmission patterns and trends. In this context, genetic signatures may be useful for the identification and characterization of the Plasmodium falciparum parasite population in order to identify foci of transmission, detect outbreaks, and track parasite movement to potentially inform malaria control and elimination strategies. METHODS: This study evaluated the genetic signals based on analysis of 21 single-nucleotide polymorphisms (SNPs) from 462 monogenomic (single-genome) P. falciparum DNA samples extracted from dried blood spots collected from malaria-positive patients reporting to health facilities in three southwestern Haitian departments (Nippes, Grand'Anse, and Sud) in 2016. RESULTS: Assessment of the parasite genetic relatedness revealed evidence of clonal expansion within Nippes and the exchange of parasite lineages between Nippes, Sud, and Grand'Anse. Furthermore, 437 of the 462 samples shared high levels of genetic similarity-at least 20 of 21 SNPS-with at least one other sample in the dataset. CONCLUSIONS: These results revealed patterns of relatedness suggestive of the repeated recombination of a limited number of founding parasite types without significant outcrossing. These genetic signals offer clues to the underlying relatedness of parasite populations and may be useful for the identification of the foci of transmission and tracking of parasite movement in Haiti for malaria elimination.

Chloroquine remains the first-line treatment for uncomplicated malaria in Haiti, and until recently, sulfadoxine-pyrimethamine was the second-line treatment. A few studies have reported the presence of molecular markers for resistance in Plasmodium falciparum parasites, and in vivo therapeutic efficacy studies (TESs) have been limited. Recognizing the history of antimalarial resistance around the globe and the challenges of implementing TESs in low-endemic areas, the Ministry of Health established a surveillance program to detect molecular markers of antimalarial resistance in Haiti. Sentinel sites were purposefully selected in each of Haiti's 10 administrative departments; an 11th site was selected in Grand'Anse, the department with the highest number of reported cases. Factors considered for site selection included the number of malaria cases identified, observed skills of laboratory technicians conducting rapid diagnostic tests (RDTs), stock and storage conditions of RDTs, accuracy of data reporting to the national surveillance system, and motivation to participate. Epidemiologic data from 2,437 patients who tested positive for malaria from March 2016 to December 2018 and consented to provide samples for molecular sequencing are presented here. Of these, 936 (38.4%) patients reported self-treatment with any medication since the onset of their illness before diagnosis; overall, 69 (2.8%) patients reported taking an antimalarial. Ten patients (0.4%) reported travel away from their home for at least one night in the month before diagnosis. Establishing a molecular surveillance program for antimalarial drug resistance proved practical and feasible in a resource-limited setting and will provide the evidence needed to make informed treatment policy decisions at the national level.

In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.