Aedes mosquito-borne viruses (ABVs) place a substantial strain on public health resources in the Americas. Vector control of Aedes mosquitoes is an important public health strategy to decrease or prevent spread of ABVs. The ongoing Targeted Indoor Residual Spraying (TIRS) trial is an NIH-sponsored clinical trial to study the efficacy of a novel, proactive vector control technique to prevent dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) infections in the endemic city of Merida, Yucatan, Mexico. The primary outcome of the trial is laboratory-confirmed ABV infections in neighborhood clusters. Despite the difficulties caused by the COVID-19 pandemic, by early 2021 the TIRS trial completed enrollment of 4,792 children aged 2-15 years in 50 neighborhood clusters which were allocated to control or intervention arms via a covariate-constrained randomization algorithm. Here, we describe the makeup and ABV seroprevalence of participants and mosquito population characteristics in both arms before TIRS administration. Baseline surveys showed similar distribution of age, sex, and socio-economic factors between the arms. Serum samples from 1,399 children were tested by commercially available ELISAs for presence of anti-ABV antibodies. We found that 45.1% of children were seropositive for one or more flaviviruses and 24.0% were seropositive for CHIKV. Of the flavivirus-positive participants, most were positive for ZIKV-neutralizing antibodies by focus reduction neutralization testing which indicated a higher proportion of participants with previous ZIKV than DENV infections within the cohort. Both study arms had statistically similar seroprevalence for all viruses tested, similar socio-demographic compositions, similar levels of Ae. aegypti infestation, and similar observed mosquito susceptibility to insecticides. These findings describe a population with a high rate of previous exposure to ZIKV and lower titers of neutralizing antibodies against DENV serotypes, suggesting susceptibility to future outbreaks of flaviviruses is possible, but proactive vector control may mitigate these risks.

Invasive fungal infections are associated with high mortality, which is exacerbated by the limited antifungal drug armamentarium and increasing antifungal drug resistance. Echinocandins are a frontline antifungal drug class targeting β-glucan synthase (GS), a fungal cell wall biosynthetic enzyme. Echinocandin resistance is generally low but increasing in species like Candida glabrata, an opportunistic yeast pathogen colonizing human mucosal surfaces. Mutations in GS-encoding genes (FKS1 and FKS2 in C. glabrata) are strongly associated with clinical echinocandin failure, but epidemiological studies show that other, as yet unidentified factors also influence echinocandin susceptibility. Furthermore, although the gut is known to be an important reservoir for emergence of drug-resistant strains, the evolution of resistance is not well understood. Here, we studied the evolutionary dynamics of C. glabrata colonizing the gut of immunocompetent mice during treatment with caspofungin, a widely-used echinocandin. Whole genome and amplicon sequencing revealed rapid genetic diversification of this C. glabrata population during treatment and the emergence of both drug target (FKS2) and non-drug target mutations, the latter predominantly in the FEN1 gene encoding a fatty acid elongase functioning in sphingolipid biosynthesis. The fen1 mutants displayed high fitness in the gut specifically during caspofungin treatment and contained high levels of phytosphingosine, whereas genetic depletion of phytosphingosine by deletion of YPC1 gene hypersensitized the wild type strain to caspofungin and was epistatic to fen1Δ. Furthermore, high resolution imaging and mass spectrometry showed that reduced caspofungin susceptibility in fen1Δ cells was associated with reduced caspofungin binding to the plasma membrane. Finally, we identified several different fen1 mutations in clinical C. glabrata isolates, which phenocopied the fen1Δ mutant, causing reduced caspofungin susceptibility. These studies reveal new genetic and molecular determinants of clinical caspofungin susceptibility and illuminate the dynamic evolution of drug target and non-drug target mutations reducing echinocandin efficacy in patients colonized with C. glabrata.

INTRODUCTION: The Vaccines for Children (VFC) program was established in 1994 to provide recommended vaccines at no cost to eligible children and help ensure that all U.S. children are protected from life-threatening vaccine-preventable diseases. METHODS: CDC analyzed data from the 2012-2022 National Immunization Survey-Child (NIS-Child) to assess trends in vaccination coverage with ≥1 dose of measles, mumps, and rubella vaccine (MMR), 2-3 doses of rotavirus vaccine, and a combined 7-vaccine series, by VFC program eligibility status, and to examine differences in coverage among VFC-eligible children by sociodemographic characteristics. VFC eligibility was defined as meeting at least one of the following criteria: 1) American Indian or Alaska Native; 2) insured by Medicaid, Indian Health Service (IHS), or uninsured; or 3) ever received at least one vaccination at an IHS-operated center, Tribal health center, or urban Indian health care facility. RESULTS: Overall, approximately 52.2% of U.S. children were VFC eligible. Among VFC-eligible children born during 2011-2020, coverage by age 24 months was stable for ≥1 MMR dose (88.0%-89.9%) and the combined 7-vaccine series (61.4%-65.3%). Rotavirus vaccination coverage by age 8 months was 64.8%-71.1%, increasing by an average of 0.7 percentage points annually. Among all children born in 2020, coverage was 3.8 (≥1 MMR dose), 11.5 (2-3 doses of rotavirus vaccine), and 13.8 (combined 7-vaccine series) percentage points lower among VFC-eligible than among non-VFC-eligible children. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Although the VFC program has played a vital role in increasing and maintaining high levels of childhood vaccination coverage for 30 years, gaps remain. Enhanced efforts must ensure that parents and guardians of VFC-eligible children are aware of, have confidence in, and are able to obtain all recommended vaccines for their children.

The second international meeting on endemic mycoses of the Americas (IMEMA) and the first international symposium on implantation mycoses (ISIM) took place in Santiago del Estero, Argentina, on September 25-27, 2023. The conference provided a platform for researchers, clinicians, and experts to discuss the latest developments in the field of endemic and implantation mycoses. Topics included epidemiology, diagnostic advances, treatment strategies, and the impact of environmental factors on the spread of these fungal diseases. IMEMA and ISIM contributed to the regional discourse on the mycoses, emphasizing the importance of international cooperation in addressing these public health challenges. | IMEMA/ISIM, held in Santiago del Estero, Argentina, convened experts to discuss endemic and implantation mycoses, covering topics such as epidemiology, diagnostics, treatment, and advocacy. The event highlighted ongoing efforts in combating these diseases. | eng

Background: Nearly one in six children lived in war zones in 2023. Evidence-based psychosocial and parenting support has potential to mitigate negative impacts for parents and children co-exposed to war and displacement, especially in relation to mental health and harsh parenting reactions. In the current war in Ukraine, local mental health experts co-created and evaluated, with global experts, the effectiveness of psychosocial and parenting support groups, called 'Hope Groups' on improvements in mental health, positive parenting, and violence against children. This paper aimed to assess the effectiveness of psychosocial and parenting support groups, called 'Hope Groups,' on improvements in caregiver mental health, positive parenting, and prevention of violence against children, for families affected by the war in Ukraine, using a pre/post study design. Method(s): Participants (n = 577) included Ukrainian caregivers, 66% (381) of whom were parents and co-residing caregivers of children ages 0-17, while the remaining 34% were non-resident informal caregivers. Internally displaced, externally displaced, and those living at-home in war-torn regions were invited to groups by trained Ukrainian peer facilitators. Using a pre-post design, we compared individual level frequency measures at three time-points - baseline, midline, and endline, to assess changes in 4 mental health, and 9 parenting and child health outcomes. We analyzed these outcomes using paired t-tests to compare outcomes at baseline-to-midline (after 4-sessions) and baseline-to-endline (after 10-sessions), which estimated the mean changes in days per week and associated percent change, during the respective periods; we quantified uncertainties using bias-corrected and accelerated (BCa) bootstrapping with 95% uncertainty ranges for baseline-midline and baseline-endline estimates. We used this same approach for stratified analyses to assess potential effect modification by displacement status and facilitator type. We further used linear models to adjust for age and sex. Finding(s): Compared to baseline, every mental health, parenting, and child health outcome improved significantly at midline and endline. Mental health ratings showed endline reductions in depressive symptoms of 56.8% (95% CI: -59.0,-54.3; -1.8 days/week), and increases in hopefulness, coping with grief, and self-care, ranging from 62.0% (95% CI: 53.6,71.3; 2.2 days/week) to 77.0% (95% CI: 66.3,88.3; 2.2 days/week). Significant improvements in parenting and child health outcomes included monitoring children, reinforcing positive behavior, supporting child development, protecting child, nonviolent discipline, and child verbalizing emotions. By endline, emotional violence, physical violence, and child despondency had dropped by 57.7% (95% CI: -63.0%,-51.9; -1.3 days/week), 64.0% (95% CI: -79.0,-39.5; -0.22 days/week), and 51.9% (95% CI: -45.1,-57.9; -1.2 days/week), respectively. Outcomes stratified by displacement status remained significant across all groups, as did those according to facilitator type (lay versus professional). Interpretation(s): This study demonstrates preliminary evidence, using a brief survey and pre-post design as is appropriate for acute and early protracted emergency settings, of the feasibility and effectiveness of Hope Groups for war-affected Ukrainian caregivers, on improved mental health, positive parenting, and reduced violence against children. Copyright © 2024

Trypanosoma cruzi, the causative agent of Chagas disease, is primarily transmitted to humans by hematophagous bugs of the Triatominae subfamily. In the Colombian Caribbean region, particularly on Margarita Island, T. cruzi transmission is highly endemic and associated with vectors such as Triatoma maculata and Rhodnius pallescens. Additionally, T. cruzi-infected Didelphis marsupialis are commonly found in close proximity to human dwellings. Given the complex transmission dynamics involving various domestic and non-domestic hosts, this study aimed to analyze 145 T. cruzi clones from twelve strains isolated from T. maculata, R. pallescens, and D. marsupialis using spliced leader intergenic region (SL-IR) sequences and nine polymorphic microsatellite loci. The results indicate the presence of a single polymorphic T. cruzi population, suggesting sustained local transmission dynamics between triatomines adapted to A. butyracea forests and peridomestic areas inhabited by synanthropic mammal reservoir such as D. marsupialis. Notably, this population appears to lack substructure, highlighting the importance of adopting an alternative eco-health approach to complement traditional chemical vector control methods for more effective and sustainable interruption of transmission. © 2024

BACKGROUND: Mexico has experienced a significant reduction in malaria cases over the past two decades. Certification of localities as malaria-free areas (MFAs) has been proposed as a steppingstone before elimination is achieved throughout the country. The Mexican state of Quintana Roo is a candidate for MFA certification. Monitoring the status of insecticide susceptibility of major vectors is crucial for MFA certification. This study describes the susceptibility status of Anopheles albimanus, main malaria vector, from historically important malaria foci in Quintana Roo, using both phenotypic and genotypic approaches. METHODS: Adult mosquito collections were carried out at three localities: Palmar (Municipality of Othon P. Blanco), Buenavista (Bacalar) and Puerto Morelos (Puerto Morelos). Outdoor human-landing catches were performed by pairs of trained staff from 18:00 to 22:00 during 3-night periods at each locality during the rainy season of 2022. Wild-caught female mosquitoes were exposed to diagnostic doses of deltamethrin, permethrin, malathion, pirimiphos-methyl or bendiocarb using CDC bottle bioassays. Mortality was registered at the diagnostic time and recovery was assessed 24 h after exposure. Molecular analyses targeting the Voltage-Gated Sodium Channel (vgsc) gene and acetylcholinesterase (ace-1) gene were used to screen for target site polymorphisms. An SNP analysis was carried out to identify mutations at position 995 in the vgsc gene and at position 280 in the ace-1 gene. RESULTS: A total of 2828 anophelines were collected. The main species identified were Anopheles albimanus (82%) and Anopheles vestitipennis (16%). Mortalities in the CDC bottle bioassay ranged from 99% to 100% for all the insecticides and mosquito species. Sequence analysis was performed on 35 An. albimanus across the three localities; of those, 25 were analysed for vgsc and 10 for ace-1 mutations. All individuals showed wild type alleles. CONCLUSION: The results demonstrated that An. albimanus populations from historical malaria foci in Quintana Roo are susceptible to the main insecticides used by the Ministry of Health.

Farmworkers, a group of essential workers, experience a disproportionately high burden of COVID-19 due to their living and working conditions. This project characterized farmworker mobility in and around Yuma County, Arizona, to identify opportunities to improve farmworker access to COVID-19 vaccination. We collected qualitative and geospatial data through a series of in-person and virtual focus group discussions, key informant interviews, and intercept interviews with participatory mapping. Participants included farmworkers, employers, and representatives of local institutions who serve or interact with farmworkers. We identified participants through purposive and referential sampling and grouped people by sociodemographic characteristics for interviews. We used qualitative and geospatial analyses to identify common themes and mobility patterns. The team interviewed 136 people from February 26 to April 2, 2021. Common themes emerged about how farmworkers have little or no access to COVID-19 vaccination unless offered at their workplaces or at locations where they congregate at convenient times. Further, farmworkers described how their demanding work schedules, long commute times, and caretaker commitments make it challenging to access vaccination services. Geospatial analyses identified three geographic areas in Yuma County where farmworkers reported living and working that did not have a COVID-19 vaccine clinic within walking distance. Coordination between local public health authorities and key partners, including employers and trusted representatives from local community-based organizations or the Mexican consulate, to offer vaccination at worksites or other locations where farmworkers congregate can help improve access to COVID-19 vaccines and booster doses for this population.

PURPOSE: To describe an evaluation conducted by 39 state Early Hearing Detection and Intervention (EHDI) programs on the reporting process and system usability for audiologists when reporting the hearing test results to the EHDI program and the barriers encountered during reporting. METHOD: Each author independently extracted numbers, percentages, and texts from the evaluation reports into an Excel spreadsheet, which then became the dataset. Authors then compared and cross-checked the datasets before coding. Texts conveying similar concepts were coded with the same name and organized into categories. Finally, thematic identification and analysis were performed when a theme(s) or concept(s) that pertained to similar challenges encountered by audiologists was identified and organized under a higher-order domain. RESULTS: Some audiologists reported no barriers when reporting hearing test results to the state EHDI programs. Among those audiologists who reported barriers, the most recurrent barrier was a non-user-friendly data system design. The second most recurrent barrier was not having adequate administrative time to report data as a busy clinician. The third most recurrent barrier was an incomplete understanding of the state EHDI reporting requirements. Finally, the method audiologists were required to use when reporting results also posed some challenges, such as no internet connection in rural areas when required to report via an internet portal. CONCLUSION: Because of the wide variety of barriers faced by audiologists, multiple strategies to improve the reporting process would likely be beneficial.

BACKGROUND: Data on the characteristics of individuals with mild and asymptomatic infections with different SARS-CoV-2 variants are limited. We therefore compared the characteristics of individuals infected with ancestral, Beta and Delta SARS-CoV-2 variants in South Africa. METHODS: We conducted a prospective cohort study in a rural and an urban site during July 2020-August 2021. Mid-turbinate nasal swabs were collected twice-weekly from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time reverse transcription polymerase chain reaction (rRT-PCR). Differences in demographic and clinical characteristics, shedding and cycle threshold (Ct) value of infection episodes by variant were evaluated using multinomial regression. Overall and age-specific incidence rates of infection were compared by variant. RESULTS: We included 1200 individuals from 222 households and 648 rRT-PCR-confirmed infection episodes (66, 10% ancestral, 260, 40% Beta, 322, 50% Delta). Symptomatic proportion was similar for ancestral (7, 11%), Beta (44, 17%), and Delta (46, 14%) infections (p=0.4). After accounting for previous infection, peak incidence shifted to younger age groups in successive waves (40-59 years ancestral, 19-39 years Beta, 13-18 years Delta). On multivariable analysis, compared to ancestral, Beta infection was more common in individuals aged 5-12 years (vs 19-39)(adjusted odds ratio (aOR) 2.6, 95% confidence interval (CI)1.1-6.6) and PCR cycle threshold (Ct) value <30 (vs >35)(aOR 3.2, 95%CI 1.3-7.9), while Delta was more common in individuals aged <5 (aOR 6.7, 95%CI1.4-31.2) and 5-12 years (aOR 6.6 95%CI2.6-16.7)(vs 19-39) and Ct value <30 (aOR 4.5, 95%CI 1.3-15.5) and 30-35 (aOR 6.0, 95%CI 2.3-15.7)(vs >35). CONCLUSIONS: Consecutive SARS-CoV-2 waves with Beta and Delta variants were associated with a shift to younger individuals. Beta and Delta infections were associated with higher peak viral loads, potentially increasing infectiousness.

OBJECTIVE: To identify and summarise the evidence on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection and persistence in body fluids associated with sexual activity (saliva, semen, vaginal secretion, urine and faeces/rectal secretion). ELIGIBILITY: All studies that reported detection of SARS-CoV-2 in saliva, semen, vaginal secretion, urine and faeces/rectal swabs. INFORMATION SOURCES: The WHO COVID-19 database from inception to 20 April 2022. RISK OF BIAS ASSESSMENT: The National Institutes of Health tools. SYNTHESIS OF RESULTS: The proportion of patients with positive results for SARS-CoV-2 and the proportion of patients with a viral duration/persistence of at least 14 days in each fluid was calculated using fixed or random effects models. INCLUDED STUDIES: A total of 182 studies with 10 023 participants. RESULTS: The combined proportion of individuals with detection of SARS-CoV-2 was 82.6% (95% CI: 68.8% to 91.0%) in saliva, 1.6% (95% CI: 0.9% to 2.6%) in semen, 2.7% (95% CI: 1.8% to 4.0%) in vaginal secretion, 3.8% (95% CI: 1.9% to 7.6%) in urine and 31.8% (95% CI: 26.4% to 37.7%) in faeces/rectal swabs. The maximum viral persistence for faeces/rectal secretions was 210 days, followed by semen 121 days, saliva 112 days, urine 77 days and vaginal secretions 13 days. Culturable SARS-CoV-2 was positive for saliva and faeces. LIMITATIONS: Scarcity of longitudinal studies with follow-up until negative results. INTERPRETATION: SARS-CoV-2 RNA was detected in all fluids associated with sexual activity but was rare in semen and vaginal secretions. Ongoing droplet precautions and awareness of the potential risk of contact with faecal matter/rectal mucosa are needed. PROSPERO REGISTRATION NUMBER: CRD42020204741.

Delays in illness recognition, healthcare seeking, and in the provision of appropriate clinical care are common in resource-limited settings. Our objective was to determine the frequency of delays in the "Three Delays-in-Healthcare", and factors associated with delays, among deceased infants and children in seven countries with high childhood mortality. We conducted a retrospective, descriptive study using data from verbal autopsies and medical records for infants and children aged 1-59 months who died between December 2016 and February 2022 in six sites in sub-Saharan Africa and one in South Asia (Bangladesh) and were enrolled in Child Health and Mortality Prevention Surveillance (CHAMPS). Delays in 1) illness recognition in the home/decision to seek care, 2) transportation to healthcare facilities, and 3) the receipt of clinical care in healthcare facilities were categorized according to the "Three Delays-in-Healthcare". Comparisons in factors associated with delays were made using Chi-square testing. Information was available for 1,326 deaths among infants and under 5 children. The majority had at least one identified delay (n = 854, 64%). Waiting >72 hours after illness recognition to seek health care (n = 422, 32%) was the most common delay. Challenges in obtaining transportation occurred infrequently when seeking care (n = 51, 4%). In healthcare facilities, prescribed medications were sometimes unavailable (n = 102, 8%). Deceased children aged 12-59 months experienced more delay than infants aged 1-11 months (68% vs. 61%, P = 0.018). Delays in seeking clinical care were common among deceased infants and children. Additional study to assess the frequency of delays in seeking clinical care and its provision among children who survive is warranted.

Trypanosoma cruzi, the etiologic agent of Chagas disease, is transmitted by hematophagous reduviid bugs within the subfamily Triatominae. These vectors take blood meals from a wide range of hosts, and their feeding behaviors have been used to investigate the ecology and epidemiology of T. cruzi. In this study we describe two PCR-based methodologies that amplify a fragment of the 16S mitochondrial rDNA, aimed to improve the identification of blood meal sources for Triatoma infestans: a.--Sequence analyses of two heminested PCRs that allow the identification of mammalian and avian species, and b.--restriction fragment length polymorphism (RFLP) analysis from the mammalian PCR to identify and differentiate multi-host blood meals. Findings from both methodologies indicate that host DNA could be detected and the host species identified in samples from laboratory reared and field collected triatomines. The implications of this study are two-fold. First, these methods can be used in areas where the fauna diversity and feeding behavior of the triatomines are unknown. Secondly, the RFLP method led to the identification of multi-host DNA from T. infestans gut contents, enhancing the information provided by this assay. These tools are important contributions for ecological and epidemiological studies of vector-borne diseases.

Data on respiratory syncytial virus (RSV) incidence and household transmission are limited. To describe RSV incidence and transmission, we conducted a prospective cohort study in rural and urban communities in South Africa over two seasons during 2017-2018. Nasopharyngeal swabs were collected twice-weekly for 10 months annually and tested for RSV using PCR. We tested 81,430 samples from 1,116 participants in 225 households (follow-up 90%). 32% (359/1116) of individuals had ≥1 RSV infection; 10% (37/359) had repeat infection during the same season, 33% (132/396) of infections were symptomatic, and 2% (9/396) sought medical care. Incidence was 47.2 infections/100 person-years and highest in children <5 years (78.3). Symptoms were commonest in individuals aged <12 and ≥65 years. Individuals 1-12 years accounted for 55% (134/242) of index cases. Household cumulative infection risk was 11%. On multivariable analysis, index cases with ≥2 symptoms and shedding duration >10 days were more likely to transmit; household contacts aged 1-4 years vs. ≥65 years were more likely to acquire infection. Within two South African communities, RSV attack rate was high, and most infections asymptomatic. Young children were more likely to introduce RSV into the home, and to be infected. Future studies should examine whether vaccines targeting children aged <12 years could reduce community transmission.

PURPOSE: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. METHODS: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. RESULTS: Between 29(th) February 2016 and 24(th) April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. CONCLUSION: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets.

Malaria in pregnancy (MiP) intervention coverage, especially intermittent preventive treatment in pregnancy (IPTp), lags behind other global malaria indicators. In 2020, across Africa, only 32% of eligible pregnant women received at least three IPTp doses, despite high antenatal care attendance. We conducted a secondary analysis of data collected during outreach, training, and supportive supervision visits from 2019 to 2020 to assess quality of care and explore factors contributing to providers' competence in providing IPTp, insecticide-treated nets, malaria case management, and respectful maternity care. Data were collected during observations of provider-patient interactions in six countries (Cameroon, Cote d'Ivoire, Ghana, Kenya, Mali, and Niger). Competency scores (i.e., composite scores of supervisory checklist observations) were calculated across three domains: MiP prevention, MiP treatment, and respectful maternity care. Scores are used to understand drivers of competency, rather than to assess individual health worker performance. Country-specific multilinear regressions were used to assess how competency score was influenced by commodity availability, training, provider gender and cadre, job aid availability, and facility type. Average competency scores varied across countries: prevention (44-90%), treatment (78-90%), and respectful maternity care (53-93%). The relative association of each factor with competency score varied. Commodity availability, training, and access to job aids correlated positively with competency in multiple countries. To improve MiP service quality, equitable access to training opportunities for different cadres, targeted training, and access to job aids and guidelines should be available for providers. Collection and analysis of routine supervision data can support tailored actions to improve quality MiP services.

Water, sanitation, and hygiene (WASH) services in schools are essential to reduce infectious disease transmission, including that of COVID-19. This study aimed to establish a baseline of WASH services in six public elementary schools in Guatemala, with a focus on hand hygiene. We used the WHO/UNICEF Joint Monitoring Programme (JMP) report indicators to assess the WASH infrastructure at each school. We collected water samples from easily accessible water points (pilas, or bathroom sinks) at each school to test for the presence of total coliforms and E. coli. In-depth interviews were carried out with teachers to understand hand hygiene practices and systems at school. Results indicate that all schools had water available at the time of the survey. All water samples at four schools tested positive for total coliforms and at one school, positive for E. coli. All schools had sanitation facilities, but services were limited. Only 43% of handwashing stations at schools had soap available. No school had disability-inclusive WASH services. Financial constraints and a lack of appropriate WASH infrastructure were the main barriers reported by teachers to meet hand hygiene needs at school. Appropriate access to WASH infrastructure and supplies could increase hand hygiene practices and improve learning conditions for students.

Leptospirosis, the most widespread zoonotic disease in the world, is broadly understudied in multi-host wildlife systems. Knowledge gaps regarding Leptospira circulation in wildlife, particularly in densely populated areas, contribute to frequent misdiagnoses in humans and domestic animals. We assessed Leptospira prevalence levels and risk factors in five target wildlife species across the greater Los Angeles region: striped skunks (Mephitis mephitis), raccoons (Procyon lotor), coyotes (Canis latrans), Virginia opossums (Didelphis virginiana), and fox squirrels (Sciurus niger). We sampled more than 960 individual animals, including over 700 from target species in the greater Los Angeles region, and an additional 266 sampled opportunistically from other California regions and species. In the five target species seroprevalences ranged from 5 to 60%, and infection prevalences ranged from 0.8 to 15.2% in all except fox squirrels (0%). Leptospira phylogenomics and patterns of serologic reactivity suggest that mainland terrestrial wildlife, particularly mesocarnivores, could be the source of repeated observed introductions of Leptospira into local marine and island ecosystems. Overall, we found evidence of widespread Leptospira exposure in wildlife across Los Angeles and surrounding regions. This indicates exposure risk for humans and domestic animals and highlights that this pathogen can circulate endemically in many wildlife species even in densely populated urban areas.

ABSTRACTDespite the human immunodeficiency virus (HIV) pandemic continuing worldwide for 40 years, no vaccine to combat the disease has been licensed for use in at risk populations. Here, we describe a novel recombinant vesicular stomatitis virus (rVSV) vector vaccine expressing modified HIV envelope glycoproteins and Ebola virus glycoprotein. Three heterologous immunizations successfully prevented infection by a different clade SHIV in 60% of nonhuman primates (NHPs). No trend was observed between resistance and antibody interactions. Resistance to infection was associated with high proportions of central memory T cell CD69 and CD154 marker upregulation, increased IL-2 production, and a reduced IFN-γ response, offering insight into correlates of protection.

Histoplasmosis is a fungal infection caused by the thermally dimorphic fungus Histoplasma capsulatum. This infection causes significant morbidity and mortality in people living with HIV/AIDS, especially in countries with limited resources. Currently used diagnostic tests rely on culture and serology but with some limitations. No molecular assays are commercially available and the results from different reports have been variable. We aimed to evaluate quantitative real-time PCR (qPCR) targeting three protein-coding genes of Histoplasma capsulatum (100-kDa, H and M antigens) for detection of this fungus in formalin-fixed paraffin-embedded (FFPE) samples from patients with proven histoplasmosis. The sensitivity of 100-kDa, H and M qPCR assays were 93.9%, 91% and 57%, respectively. The specificity of 100-kDa qPCR was 93% when compared against samples from patients with other mycoses and other infections, and 100% when samples from patients with non-infectious diseases were used as controls. Our findings demonstrate that real-time PCR assays targeting 100-kDa and H antigen showed the most reliable results and can be successfully used for diagnosing this mycosis when testing FFPE samples.

Background SARS-CoV-2 infections may be underestimated due to limited testing access, particularly in sub-Saharan Africa. South Africa experienced two SARS-CoV-2 waves, the second associated with emergence of variant 501Y.V2. In this study, we report longitudinal SARS-CoV-2 seroprevalence in cohorts in two communities in South Africa.Methods We measured SARS-CoV-2 seroprevalence two monthly in randomly selected household cohorts in a rural and an urban community (July 2020-March 2021). We compared seroprevalence to laboratory-confirmed infections, hospitalisations and deaths reported in the districts to calculate infection-case (ICR), infection-hospitalisation (IHR) and infection-fatality ratio (IFR) in the two waves of infection.Findings Seroprevalence after the second wave ranged from 18% (95%CrI 10-26%) and 28% (95%CrI 17-41%) in children &lt;5 years to 37% (95%CrI 28-47%) in adults aged 19-34 years and 59% (95%CrI 49-68%) in adults aged 35-59 years in the rural and urban community respectively. Individuals infected in the second wave were more likely to be from the rural site (aOR 4.7, 95%CI 2.9-7.6), and 5-12 years (aOR 2.1, 95%CI 1.1-4.2) or ≥60 years (aOR 2.8, 95%CI 1.1-7.0), compared to 35-59 years. The in-hospital IFR in the urban site was significantly increased in the second wave 0.36% (95%CI 0.28-0.57%) compared to the first wave 0.17% (95%CI 0.15-0.20%). ICR ranged from 3.69% (95%CI 2.59-6.40%) in second wave at urban community, to 5.55% (95%CI 3.40-11.23%) in first wave in rural community.Interpretation The second wave was associated with a shift in age distribution of cases from individuals aged to 35-59 to individuals at the extremes of age, higher attack rates in the rural community and a higher IFR in the urban community. Approximately 95% of SARS-CoV-2 infections in these two communities were not reported to the national surveillance system, which has implications for contact tracing and infection containment.Funding US Centers for Disease Control and PreventionEvidence before this study Seroprevalence studies provide better estimates of SARS-CoV-2 burden than laboratory-confirmed cases because many infections may be missed due to restricted access to care and testing, or differences in disease severity and health-care seeking behaviour. This underestimation may be amplified in African countries, where testing access may be limited. Seroprevalence data from sub-Saharan Africa are limited, and comparing seroprevalence estimates between countries can be challenging because populations studied and timing of the study relative to country-specific epidemics differs. During the first wave of infections in each country, seroprevalence was estimated at 4% in Kenya and 11% in Zambia. Seroprevalence estimates in South African blood donors is estimated to range between 32% to 63%. South Africa has experienced two waves of infection, with the emergence of the B.1.351/501Y.V2 variant of concern after the first wave. Reported SARS-CoV-2 cases may not be a true reflection of SARS-CoV-2 burden and specifically the differential impact of the first and second waves of infection.Added value of this study We collected longitudinal blood samples from prospectively followed rural and urban communities, randomly selected, household cohorts in South Africa between July 2020 and March 2021. From 668 and 598 individuals included from the rural and urban communities, respectively, seroprevalence was found to be 7% (95%CrI 5-9%) and 27% (95%CrI 23-31%), after the first wave of infection, and 26% (95%CrI 22-29%) and 41% (95%CrI 37-45%) after the second wave, in rural and urban study districts, respectively. After standardising for age, we estimated that only 5% of SARS-CoV-2 infections were laboratory-confirmed and reported. Infection-hospitalisation ratios in the urban community were higher in the first (2.01%, 95%CI 1.57-2.57%) and second (2.29%, 95%CI 1.63-3.94%) wave than the rural community where there was a 0.75% (95%CI 0.49-1.41%) and 0.66% (95%CI 0.50-0.98%) infection-hospitalisation ratio in the first and second wave respectively.When comparing the infection fatality ratios for the first and second SARS-CoV-2 waves, at the urban site, the ratios for both in-hospital and excess deaths to cases were significantly higher in the second wave (0.36%, 95%CI 0.28-0.57% in-hospital and 0.51%, 95%CI 0.34-0.93% excess deaths), compared to the first wave in-hospital (0.17%, 95%CI 0.15-0.20%) and excess (0.13%, 95%CI 0.10-0.17%) fatality ratios, p&lt;0.001 and p&lt;0.001, respectively). In the rural community, the point estimates for infection-fatality ratios also increased in the second wave compared to the first wave for in-hospital deaths, 0.13% (95%CI 0.10-0.23%) first wave vs 0.20% (95%CI 0.13%-0.28%) second wave, and excess deaths (0.51%, 95%CI 0.30-1.06% vs 0.70%, 95%CI 0.49-1.12%), although neither change was statistically significant.Implications of all the available evidence In South Africa, the overall prevalence of SARS-CoV-2 infections is substantially underestimated, resulting in many cases being undiagnosed and without the necessary public health action to isolate and trace contacts to prevent further transmission. There were more infections during the first wave in the urban community, and the second wave in the rural community. Although there were less infections during the second wave in the urban community, the infection-fatality ratios were significantly higher compared to the first wave. The lower infection-hospitalisation ratio and higher excess infection-fatality ratio in the rural community likely reflect differences in access to care or prevalence of risk factors for progression to severe disease in these two communities. In-hospital infection-fatality ratios for both communities during the first wave were comparable with what was experienced during the first wave in India (0.15%) for SARS-CoV-2 confirmed deaths. To our knowledge, these are the first longitudinal seroprevalence data from a sub-Saharan Africa cohort, and provide a more accurate understanding of the pandemic, allowing for serial comparisons of antibody responses in relation to reported laboratory-confirmed SARS-CoV-2 infections within diverse communities.Competing Interest StatementCheryl Cohen reports receiving grant funds from US-Centers for Disease Control and Prevention, Wellcome Trust and South African Medical Research Council.Funding StatementThis work was supported by the National Institute for Communicable Diseases of the National Health Laboratory Service and the US Centers for Disease Control and Prevention (cooperative agreement number 6U01IP001048-04-02).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:The study was approved by the University of the Witwatersrand Human Research Ethics Committee (Reference 150808) and the US Centers for Disease Control and Prevention relied on local clearance (IRB #6840).All 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.YesThe investigators welcome enquiries about possible collaborations and requests for access to the dataset. Data will be shared after approval of a proposal and with a signed data access agreement. Investigators interested in more details about this st dy, or in accessing these resources, should contact the corresponding author.

Purpose The PHIRST study (Prospective Household cohort study of Influenza, Respiratory Syncytial virus, and other respiratory pathogens community burden and Transmission dynamics in South Africa) aimed to estimate the community burden of influenza and respiratory syncytial virus (RSV) including the incidence of infection, symptomatic fraction, and disease severity, and to assess household transmission. We further aimed to estimate the impact of HIV infection and age on disease burden and transmission, and to assess the burden of Bordetella pertussis and Streptococcus pneumoniae.Participants We enrolled 1684 individuals in 327 randomly selected households in two sites (rural Agincourt subdistrict, Mpumalanga Province and urban Jouberton Township, North West Province) over 3 consecutive influenza and RSV seasons. A new cohort of households was enrolled each year. Eligible households included those with &gt;2 household members where ≥80% of household members provided consent (and assent for children aged 7-17 years). Enrolled household members were sampled with nasopharyngeal swabs twice weekly during the RSV and influenza seasons of the year of enrolment. Serology samples were collected at enrolment and before and after the influenza season annually.Findings to date There were 122,113 potential individual follow-up visits over the 3 years, and participants were interviewed for 105,783 (87%) of these. Out of 105,683 nasopharyngeal swabs from follow-up visits, 1,258 (1%), 1,026 (1%), 273 (&lt;1%), 38,829 (37%) tested positive on PCR for influenza viruses, respiratory syncytial virus, pertussis and pneumococcus respectively.Future plans Future planned analyses include analysis of influenza serology results and RSV burden and transmission. Households enrolled in the PHIRST study during 2016-2018 were eligible for inclusion in a study of SARS-CoV-2 transmission initiated in July 2020. This study uses similar testing frequency and household selection methods to assess the community burden of SARS-CoV-2 infection and the role of asymptomatic infection in virus transmission.Registration Clinical trials.gov NCT02519803Strengths and limitations of this studyPHIRST was conducted in urban and rural African settings with high HIV prevalence, allowing assessment of the effect of HIV on community burden and transmission dynamics of respiratory pathogens.Households were selected randomly to provide a representative sample of the community. Twice weekly sampling from each cohort of individuals for 6-10 months irrespective of symptoms allows estimation of community burden, household secondary infection risk, and serial interval including asymptomatic or paucisymptomatic episodes.Polymerase chain reaction testing of &gt;100,000 nasopharyngeal swab samples for multiple pathogens (influenza, respiratory syncytial virus, pertussis and Streptoccocus pneumonia) allows detailed examination of disease burden and transmission and pathogen interactionsPHIRST was not powered to assess severe outcomes (i.e. hospitalisation and death).We only examined four pathogens, but other micro-organisms may be important. Samples have been stored which could allow us to implement broader multi-pathogen testing in the future.Competing Interest StatementCheryl Cohen has received research grants awarded to her institution from Sanofi Pasteur, US Centers for Disease Control and Prevention. Cheryl Cohen has had costs for travel to a meeting supported by Parexel. Maimuna Carrim was awarded the Robert Austrian Research Award in Pneumococcal Vaccinology sponsored by Pfizer. Neil Martinson has a research grant awarded to his institution by Pfizer South Africa. Anne von Gottberg has received research grants awarded to her institution from Sanofi Pasteur, Pfizer and US Centers for Disease Control and Prevention.Clinical TrialNCT02519803Funding StatementThe study was funded through a cooperative agreement with the United States Centers for Disease Control and Prevention (CDC) (grant number 1U01IP001048). Testing for RSV and pneumococcus was supported by the Bill and Melin a Gates Foundation (Grant number: OPP1164778). Testing for B. pertussis was supported by Sanofi Pasteur (Grant number: PER00059). The Agincourt Health and Socio-Demographic Surveillance System is a node of the South African Population Research Infrastructure Network (SAPRIN) and is supported by the National Department of Science and Innovation, the Medical Research Council and the University of the Witwatersrand, South Africa, and the Wellcome Trust, UK (grants 058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z).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:University of the Witwatersrand Human Research Ethics CommitteeAll 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.YesPrimary study results for influenza as well as a description of the quality of housing at the two sites have been prepared and submitted to international peer-reviewed journals. Analysis of the data for other pathogens is planned to be completed by December 2021. Additional modelling and serologic studies will be concluded within 3 years and primary de-identified data should be publicly available no later than November 2023. The investigators welcome enquiries about possible collaborations and access to the data set. Investigators interested in more details about this study, or in accessing these resources, should contact the principle investigator, Prof Cheryl Cohen, at NICD (cherylc{at}nicd.ac.za).

Aedes aegypti is the main vector of dengue, chikungunya, and Zika viruses, which are of great public health importance in Colombia. Aedes control strategies in Colombia rely heavily on the use of organophosphate and pyrethroid insecticides, providing constant selection pressure and the emergence of resistant populations. In recent years, insecticide use has increased due to the increased incidence of dengue and recent introductions of chikungunya and Zika. In the present study, pyrethroid resistance was studied across six populations of A. aegypti from the Caribbean coast of Colombia. Susceptibility to λ-cyhalothrin, deltamethrin, and permethrin was assessed, and resistance intensity was determined. Activity levels of enzymes associated with resistance were measured, and the frequencies of three kdr alleles (V1016I, F1534C, V410L) were calculated. Results showed variations in pyrethroid susceptibility across A. aegypti populations and altered enzyme activity levels were detected. The kdr alleles were detected in all populations, with high variations in frequencies: V1016I (frequency ranging from 0.15–0.70), F1534C (range 0.94–1.00), and V410L (range 0.05–0.72). In assays of phenotyped individuals, associations were observed between the presence of V1016I, F1534C, and V410L alleles and resistance to the evaluated pyrethroids, as well as between the VI1016/CC1534/VL410 tri-locus genotype and λ-cyhalothrin and permethrin resistance. The results of the present study contribute to the knowledge of the mechanisms underlying the resistance to key pyrethroids used to control A. aegypti along the Caribbean coast of Colombia.

Confronted with the challenge of understanding population-level processes, disease ecologists and epidemiologists often simplify quantitative data into distinct physiological states (e.g. susceptible, exposed, infected, recovered). However, data defining these states often fall along a spectrum rather than into clear categories. Hence, the host-pathogen relationship is more accurately defined using quantitative data, often integrating multiple diagnostic measures, just as clinicians do to assess their patients. We use quantitative data on a bacterial infection (Leptospira interrogans) in California sea lions (Zalophus californianus) to improve both our individual-level and population-level understanding of this host-pathogen system. We create a “host-pathogen space” by mapping multiple biomarkers of infection (e.g. serum antibodies, pathogen DNA) and disease state (e.g. serum chemistry values) from 13 longitudinally sampled, severely ill individuals to visualize and characterize changes in these values through time. We describe a clear, unidirectional trajectory of disease and recovery within this host-pathogen space. Remarkably, this trajectory also captures the broad patterns in larger cross-sectional datasets of 1456 wild sea lions in all states of health. This mapping framework enables us to determine an individual’s location in their time-course since initial infection, and to visualize the full range of clinical states and antibody responses induced by pathogen exposure, including severe acute disease, chronic subclinical infection, and recovery. We identify predictive relationships between biomarkers and outcomes such as survival and pathogen shedding, and in certain cases we can impute values for missing data, thus increasing the size of the useable dataset. Mapping the host-pathogen space and using quantitative biomarker data provides more nuanced approaches for understanding and modeling disease dynamics in a system, yielding benefits for the clinician who needs to triage patients and prevent transmission, and for the disease ecologist or epidemiologist wishing to develop appropriate risk management strategies and assess health impacts on a population scale.Author Summary A pathogen can cause a range of disease severity across different host individuals, and these presentations change over the time-course from infection to recovery. These facts complicate the work of epidemiologists and disease ecologists seeking to understand the factors governing disease spread, often working with cross-sectional data. Recognizing these facts also highlights the shortcomings of classical approaches to modeling infectious disease, which typically rely on discrete and well-defined disease states. Here we show that by analyzing multiple biomarkers of health and infection simultaneously, treating these values as quantitative rather than binary indicators, and including a modest amount of longitudinal sampling of hosts, we can create a map of the host-pathogen interaction that shows the full spectrum of disease presentations and opens doors for new insights and predictions. By accounting for individual variation and capturing changes through time since infection, this mapping framework enables more robust interpretation of cross-sectional data; e.g., to detect predictive relationships between biomarkers and key outcomes such as survival, or to assess whether observed disease is associated with the pathogen of interest. This approach can help epidemiologists, ecologists and clinicians to better study and manage the many infectious diseases that exhibit complex relationships with their hosts.

Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we compare the genomes of 81 nematode and platyhelminth species, including those of 76 parasites. From 1.4 million genes, we identify gene family births and hundreds of large expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We use a wide-ranging in silico screen to identify and prioritise new potential drug targets and compounds for testing. We also uncover lineage-specific differences in core metabolism and in protein families historically targeted for drug development. This is the broadest comparative study to date of the genomes of parasitic and non-parasitic worms. It provides a transformative new resource for the research community to understand and combat the diseases that parasitic worms cause.

Leptospirosis is the most widespread zoonotic disease in the world, yet it is broadly understudied in multi-host wildlife systems. Knowledge gaps regarding Leptospira circulation in wildlife, particularly in densely populated areas, contribute to frequent misdiagnoses in humans and domestic animals. We assessed Leptospira prevalence levels and risk factors in five target wildlife species across the greater Los Angeles region: striped skunks (Mephitis mephitis), Northern raccoons (Procyon lotor), coyotes (Canis latrans), Virginia opossums (Didelphis virginiana), and fox squirrels (Sciurus niger). We sampled more than 960 individual animals, including over 700 from target species in the greater Los Angeles region, and an additional 260 sampled opportunistically from other regions and species. In the five target species, seroprevalences ranged from 5-60% and active infection prevalences ranged from 0.8-15.2% in all except fox squirrels (0%). Patterns of serologic reactivity suggest that mainland terrestrial wildlife, particularly mesocarnivores, could be the source of repeated observed introductions of Leptospira into local marine and island ecosystems. Overall, we found evidence of widespread Leptospira exposure in wildlife across Los Angeles and surrounding regions. This indicates exposure risk for humans and domestic animals and highlights that this pathogen can circulate endemically in many wildlife species even in densely populated urban areas. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

By November 2021, after the third SARS-CoV-2 wave in South Africa, seroprevalence was 60% (95%CrI 56%-64%) in a rural and 70% (95%CrI 56%-64%) in an urban community; highest in individuals aged 13-18 years. High seroprevalence prior to Omicron emergence may have contributed to reduced severity observed in the 4th wave. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Understanding the build-up of immunity with successive SARS-CoV-2 variants and the epidemiological conditions that favor rapidly expanding epidemics will facilitate future pandemic control. High-resolution infection and serology data from longitudinal household cohorts in South Africa reveal high cumulative infection rates and durable cross-protective immunity conferred by prior infection in the pre-Omicron era. Building on the cohort's history of past exposures to different SARS-CoV-2 variants and vaccination, we use mathematical models to explore the fitness advantage of the Omicron variant and its epidemic trajectory. Modelling suggests the Omicron wave infected a large fraction of the population, leaving a complex landscape of population immunity primed and boosted with antigenically distinct variants. Future SARS-CoV-2 resurgences are likely under a range of scenarios of viral characteristics, population contacts, and residual cross-protection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

BACKGROUND: Antimicrobial resistance has worsened in Latin America. There is an urgent need to understand the development of antimicrobial stewardship programs (ASPs) and the barriers to implementing effective ASPs in light of limited national action plans or policies to promote ASPs in the region. METHODS: We performed a descriptive mixed-methods study of ASPs in 5 Latin American countries in March-July 2022. An electronic questionnaire with an associated scoring system (hospital ASP self-assessment) was used, and ASP development was classified based on the scores (inadequate, 0-25; basic, 26-50; intermediate, 51-75; or advanced, 76-100). Interviews among healthcare workers (HCWs) involved in antimicrobial stewardship (AS) inquired about behavioral and organizational factors that influence AS activities. Interview data were coded into themes. Results from the ASP self-assessment and interviews were integrated to create an explanatory framework. RESULTS: Twenty hospitals completed the self-assessment, and 46 AS stakeholders from these hospitals were interviewed. ASP development was inadequate/basic in 35% of hospitals, intermediate in 50%, and advanced in 15%. For-profit hospitals had higher scores than not-for-profit hospitals. Interview data validated the self-assessment findings and provided further insight into ASP implementation challenges, which included limited formal hospital leadership support, inadequate staffing and tools to perform AS work more efficiently, limited awareness of AS principles by HCWs, and limited training opportunities. CONCLUSIONS: We identified several barriers to ASP development in Latin America, suggesting the need to create accurate business cases for ASPs to obtain the necessary funding for their effective implementation and sustainability.

BACKGROUND: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. METHODS: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. RESULTS: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. CONCLUSIONS: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.