BACKGROUND: To demonstrate the application and utility of geostatistical modelling to provide comprehensive high-resolution understanding of the population's protective immunity during a pandemic and identify pockets with sub-optimal protection. METHODS: Using data from a national cross-sectional household survey of 6620 individuals in the Dominican Republic (DR) from June to October 2021, we developed and applied geostatistical regression models to estimate and predict Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike (anti-S) antibodies (Ab) seroprevalence at high resolution (1 km) across heterogeneous areas. RESULTS: Spatial patterns in population immunity to SARS-CoV-2 varied across the DR. In urban areas, a one-unit increase in the number of primary healthcare units per population and 1% increase in the proportion of the population aged under 20 years were associated with higher odds ratios of being anti-S Ab positive of 1.38 (95% confidence interval [CI]: 1.35-1.39) and 1.35 (95% CI: 1.32-1.33), respectively. In rural areas, higher odds of anti-S Ab positivity, 1.45 (95% CI: 1.39-1.51), were observed with increasing temperature in the hottest month (per°C), and 1.51 (95% CI: 1.43-1.60) with increasing precipitation in the wettest month (per mm). CONCLUSIONS: A geostatistical model that integrates contextually important socioeconomic and environmental factors can be used to create robust and reliable predictive maps of immune protection during a pandemic at high spatial resolution and will assist in the identification of highly vulnerable areas.

Little is known about the epidemiology of leptospirosis in the Dominican Republic, the second most populous country in the Caribbean. We report on findings from a multi-stage household survey across two regions in the country that reveals a previously under-estimated burden of human Leptospira infection. Our findings, based on the reference-standard microscopic agglutination test, indicate a complex picture of serogroup diversity, spatial heterogeneity in infection and risk, and a marked discrepancy between reported cases and serologically estimated infections. Given an overall seroprevalence of 11.3% (95% CI: 10.8-13.0%) and a lower estimated force of infection (0.30% per year [0.27%-0.35%]) the number of infections may exceed national reported case data by 145-fold or more. Icterohaemorrhagiae, associated with severe Weil's disease, was the most commonly identified serogroup with a serogroup-specific prevalence of 4.4%. Consistent with other settings, risk factors including age, male sex, and rat exposure were associated with higher seroprevalence. Our study highlights the need for targeted public health interventions informed by serogroup-specific dynamics, detailed spatial analyses, knowledge of local animal reservoirs, and strengthened laboratory surveillance to effectively control this pathogen.

The 2014 chikungunya outbreak in the Dominican Republic resulted in intense local transmission, with high postoutbreak seroprevalence. The resulting population immunity will likely minimize risk for another large outbreak through 2035, but changes in population behavior or environmental conditions or emergence of different virus strains could lead to increased transmission.

BACKGROUND: Individual immune responses to SARS-CoV-2 are well-studied, while the combined effect of these responses on population-level immune dynamics remains poorly understood. Given the key role of population immunity on pathogen transmission, delineation of the factors that drive population immune evolution has critical public health implications. METHODS: We enrolled individuals 5 years and older selected using a multistage cluster survey approach in the Northwest and Southeast of the Dominican Republic. Paired blood samples were collected mid-pandemic (Aug 2021) and late pandemic (Nov 2022). We measured serum pan-immunoglobulin antibodies against the SARS-CoV-2 spike protein. Generalized Additive Models (GAMs) and random forest models were used to analyze the relationship between changes in antibody levels and various predictor variables. Principal component analysis and partial dependence plots further explored the relationships between predictors and antibody changes. FINDINGS: We found a transformation in the distribution of antibody levels from an irregular to a normalized single peak Gaussian distribution that was driven by titre-dependent boosting. This led to the convergence of antibody levels around a common immune setpoint, irrespective of baseline titres and vaccination profile. INTERPRETATION: Our results suggest that titre-dependent kinetics driven by widespread transmission direct the evolution of population immunity in a consistent manner. These findings have implications for targeted vaccination strategies and improved modeling of future transmission, providing a preliminary blueprint for understanding population immune dynamics that could guide public health and vaccine policy for SARS-CoV-2 and potentially other pathogens. FUNDING: The study was primarily funded by the Centers for Disease Control and Prevention grant U01GH002238 (EN). Salary support was provided by Wellcome Trust grant 206250/Z/17/Z (AK) and the Australian National Health and Medical Research Council Investigator grant APP1158469 (CLL).

BACKGROUND: To monitor the progress of lymphatic filariasis (LF) elimination programmes, field surveys to assess filarial antigen (Ag) prevalence require access to reliable, user-friendly rapid diagnostic tests. We aimed to evaluate the performance of the new Q Filariasis Antigen Test (QFAT) with the currently recommended Filariasis Test Strip (FTS) for detecting the Ag of Wuchereria bancrofti, the causative agent of LF, under field laboratory conditions. METHODOLOGY/PRINCIPAL FINDINGS: During an LF survey in Samoa, 344 finger-prick blood samples were tested using FTS and QFAT. Microfilariae (Mf) status was determined from blood slides prepared from any sample that reported Ag-positive by either Ag-test. Each test was re-read at 1 hour and the next day to determine the stability of results over time. Overall Ag-positivity by FTS was 29.0% and 30.2% by QFAT. Concordance between the two tests was 93.6% (kappa = 0.85). Of the 101 Mf slides available, 39.6% were Mf-positive, and all were Ag-positive by both tests. Darker test line intensities from Ag-positive FTS were found to predict Mf-positivity (compared to same/lighter line intensities). QFAT had significantly higher reported test result changes than FTS, mostly reported the next day, but fewer changes were reported between 10 minutes to 1-hour. The field laboratory team preferred QFAT over FTS due to the smaller blood volume required, better usability, and easier readability. CONCLUSION/SIGNIFICANCE: QFAT could be a suitable and user-friendly diagnostic alternative for use in the monitoring and surveillance of LF in field surveys based on its similar performance to FTS under field laboratory conditions.

OBJECTIVES: Circulating filarial antigen (Ag) is used by elimination programs to monitor lymphatic filariasis (LF) transmission; however, antifilarial antibodies (Ab) may be more sensitive than Ag for detecting LF. Our objectives were to describe Ab seroprevalence, identify risk factors for Ab seropositivity, investigate age-specific associations between Ag and Ab, and evaluate geographic clustering of seropositivity. METHODS: Community-based serosurveys of participants aged ≥5 years were conducted in 35 primary sampling units (PSUs). Ag-positivity was detected using Alere™ Filariasis Test Strips and Ab-seropositivity using multiplex bead assays. Seroprevalence was adjusted for study design. RESULTS: Of 3795 participants (range:5-90 years), adjusted prevalence for Ag, Bm14 Ab, Wb123 Ab, and Bm33 Ab were 3.7% (n=117), 20.3% (n=583), 32.2% (n=987), and 51.0% (n=1659), respectively. Male sex, older age, and residents of suspected hotspots had higher odds of seropositivity to all seromarkers. Seroprevalence was lower in 5-9-year-olds vs ≥10-year-olds (p<0.001). Clustering was significantly higher in households (intra-cluster correlation for Ag:0.45; Bm14 Ab:0.32; Bm33 Ab:0.31; Wb123 Ab:0.29) compared to PSUs or region. CONCLUSIONS: Abs enabled identification of risk factors for seropositivity and geographical clustering to inform targeted interventions for LF programmes. Further research is needed to define Ab thresholds for active versus past infection and elimination targets.

OBJECTIVE: This study investigates the role of trust in shaping COVID-19 vaccine acceptance in the Dominican Republic (DR) during the COVID-19 pandemic. DESIGN: Cross-sectional household survey. SETTING: Randomly selected households across 134 clusters in the DR, from 30 June 2021 to 12 October 2021. PARTICIPANTS: 5999 participants ≥16 years of age were enrolled. OUTCOME MEASURES: COVID-19 vaccine hesitancy (CVH) data were collected from participants ≥16 years of age and analysed as both an ordinal and binary variable. RESULTS: Overall, CVH was low (5.2% (95% CI 4.6% to 5.8%)), but more common among younger individuals, women and individuals of Mestizo ethnicity. Higher trust in local government, national government, scientists and local doctors (considered official sources) was associated with lower odds of CVH (OR 0.89 (95% CI 0.72 to 0.88), 0.89 (95% CI 0.81 to 0.98), 0.87 (95% CI 0.80 to 0.94) and 0.70 (95% CI 0.62 to 0.80), respectively). Higher trust in religious leaders, social media and traditional media (considered unofficial sources) was associated with higher odds of CVH, with respective ORs of 1.32 (95% CI 1.18 to 1.47), 1.30 (95% CI 1.19 to 1.41) and 1.08 (95% CI 0.97 to 1.22). CONCLUSION: We report findings on CVH from a national household survey in the DR and identify overall low rates of CVH but marked heterogeneity by age, gender and ethnicity. Trust in unofficial versus official sources of information is associated with increased CVH. These findings highlight and quantify the importance of trust as a key parameter when considering public health communication strategies.

Viral pathogenesis and therapeutic screening studies that utilize small mammalian models rely on the accurate quantification and interpretation of morbidity measurements, such as weight and body temperature, which can vary depending on the model, agent and/or experimental design used. As a result, morbidity-related data are frequently normalized within and across screening studies to aid with their interpretation. However, such data normalization can be performed in a variety of ways, leading to differences in conclusions drawn and making comparisons between studies challenging. Here, we discuss variability in the normalization, interpretation, and presentation of morbidity measurements for four model species frequently used to study a diverse range of human viral pathogens - mice, hamsters, guinea pigs and ferrets. We also analyze findings aggregated from influenza A virus-infected ferrets to contextualize this discussion. We focus on serially collected weight and temperature data to illustrate how the conclusions drawn from this information can vary depending on how raw data are collected, normalized and measured. Taken together, this work supports continued efforts in understanding how normalization affects the interpretation of morbidity data and highlights best practices to improve the interpretation and utility of these findings for extrapolation to public health contexts.

Incidence of COVID-19 has been associated with sociodemographic factors. We investigated variations in SARS-CoV-2 seroprevalence at sub-national levels in the Dominican Republic and assessed potential factors influencing variation in regional-level seroprevalence. Data were collected in a three-stage cross-sectional national serosurvey from June to October 2021. Seroprevalence of antibodies against the SARS-CoV-2 spike protein (anti-S) was estimated and adjusted for selection probability, age, and sex. Multilevel logistic regression was used to estimate the effect of covariates on seropositivity for anti-S and correlates of 80% protection (PT(80)) against symptomatic infection for the ancestral and Delta strains. A total of 6683 participants from 134 clusters in all 10 regions were enrolled. Anti-S, PT80 for the ancestral and Delta strains odds ratio varied across regions, Enriquillo presented significant higher odds for all outcomes compared with Yuma. Compared to being unvaccinated, receiving ≥2 doses of COVID-19 vaccine was associated with a significantly higher odds of anti-S positivity (OR 85.94, [10.95-674.33]) and PT(80) for the ancestral (OR 4.78, [2.15-10.62]) and Delta strains (OR 3.08, [1.57-9.65]) nationally and also for each region. Our results can help inform regional-level public health response, such as strategies to increase vaccination coverage in areas with low population immunity against currently circulating strains.

BACKGROUND: Population-level SARS-CoV-2 immunological protection is poorly understood but can guide vaccination and non-pharmaceutical intervention priorities. Our objective was to characterise cumulative infections and immunological protection in the Dominican Republic. METHODS: Household members ≥5 years were enrolled in a three-stage national household cluster serosurvey in the Dominican Republic. We measured pan-immunoglobulin antibodies against the SARS-CoV-2 spike (anti-S) and nucleocapsid glycoproteins, and pseudovirus neutralising activity against the ancestral and B.1.617.2 (Delta) strains. Seroprevalence and cumulative prior infections were weighted and adjusted for assay performance and seroreversion. Binary classification machine learning methods and pseudovirus neutralising correlates of protection were used to estimate 50% and 80% protection against symptomatic infection. FINDINGS: Between 30 Jun and 12 Oct 2021 we enrolled 6683 individuals from 3832 households. We estimate that 85.0% (CI 82.1-88.0) of the ≥5 years population had been immunologically exposed and 77.5% (CI 71.3-83) had been previously infected. Protective immunity sufficient to provide at least 50% protection against symptomatic SARS-CoV-2 infection was estimated in 78.1% (CI 74.3-82) and 66.3% (CI 62.8-70) of the population for the ancestral and Delta strains respectively. Younger (5-14 years, OR 0.47 [CI 0.36-0.61]) and older (≥75-years, 0.40 [CI 0.28-0.56]) age, working outdoors (0.53 [0.39-0.73]), smoking (0.66 [0.52-0.84]), urban setting (1.30 [1.14-1.49]), and three vs no vaccine doses (18.41 [10.69-35.04]) were associated with 50% protection against the ancestral strain. INTERPRETATION: Cumulative infections substantially exceeded prior estimates and overall immunological exposure was high. After controlling for confounders, markedly lower immunological protection was observed to the ancestral and Delta strains across certain subgroups, findings that can guide public health interventions and may be generalisable to other settings and viral strains. FUNDING: This study was funded by the US CDC.

OBJECTIVE: To develop, implement, and assess implementation outcomes for a developmental monitoring and referral program for children in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). METHODS: Based on Centers for Disease Control and Prevention's Learn the Signs. Act Early. campaign, the program was developed and replicated in two phases at 20 demographically diverse WIC clinics in eastern Missouri. Parents were asked to complete developmental milestone checklists for their children, ages 2months to 4years, during WIC eligibility recertification visits; WIC staff referred children with potential concerns to their healthcare providers for developmental screening. WIC staff surveys and focus groups were used to assess initial implementation outcomes. RESULTS: In both phases, all surveyed staff (n=46) agreed the program was easy to use. Most (80%) agreed that checklists fit easily into clinic workflow and required5min to complete. Staff (55%) indicated using checklists with75% of their clients. 92% or more reported referring one or more children with potential developmental concerns. According to 80% of staff, parents indicated checklists helped them learn about development and planned to share them with healthcare providers. During thesecond phase, 18 of 20 staff surveyed indicated the program helped them learn when to refer children and how to support parents, and 19 felt the program promoted healthy development. Focus groups supported survey findings, and all clinics planned to sustain the program. CONCLUSIONS: Initial implementation outcomes supported this approach to developmental monitoring and referral in WIC. The program has potential to help low-income parents identify possible concerns and access support.

A 3 dose (0, 1, 6 months) intramuscular (3-IM) priming series of a human dose (HuAVA) and dilutions up to 1:10 of anthrax vaccine adsorbed (AVA) provided statistically significant levels of protection (60-100%) against inhalation anthrax for up to 4 years in rhesus macaques.Serum anti-protective antigen (PA) IgG and lethal toxin neutralization activity (TNA) were detectable following a single injection of HuAVA or 1:5 AVA, or two injections of diluted vaccine (1:10, 1:20, 1:40 AVA). Anti-PA and TNA were highly correlated (overall r(2) = 0.89 for log(10) transformed data). Peak responses were at 6.5 months (mo). In general, with the exception of animals receiving 1:40 AVA, serum anti-PA and TNA responses remained significantly above control levels at 28.5mo (last time point measured for 1:20 AVA) and through 50.5mo in HuAVA, 1:5 and 1:10 AVA groups (p <0.05).PA-specific IFN-gamma and IL-4 CD4(+) cell frequencies and T cell stimulation indices were sustained to 50.5mo (last time point measured). PA-specific memory B cell frequencies were highly variable, but in general were detectable in PBMC by 2mo, significantly above controls by 7mo, and remained detectable in the HuAVA, 1:5 and 1:20 AVA groups to 42mo (last time point measured).HuAVA and diluted AVA elicited a combined Th1/Th2 response and robust immunological priming with sustained production of high avidity PA-specific functional antibody, long term immune cell competence and immunological memory (30mo for 1:20 AVA; 52mo for 1:10 AVA). Vaccinated animals surviving inhalation anthrax developed high magnitude anamnestic anti-PA IgG and TNA responses.

Anthrax toxin (ATx) is comprised of binary exotoxins lethal toxin (LTx) and edema toxin (ETx). They have separate effector proteins (edema factor (EF) or lethal factor (LF)) and share the common binding protein Protective Antigen (PA). PA is the primary immunogen in current licensed vaccine "Anthrax Vaccine Adsorbed" (AVA, Biothrax(R)). AVA confers protective immunity by stimulating production of ATx neutralizing antibodies, which could block the intoxication process at several steps (binding of PA to target cells surface, furin cleavage, toxin complex formation, and binding/translocation of ATx into the cell. To evaluate ATx neutralization by anti-AVA antibodies, we developed two low-temperature LTx neutralization activity (TNA) assays that distinguish antibody blocking before and after binding of PA to target cells (non-complexed (NC) and receptor-bound (RB) TNAs). These assays were used to investigate anti-PA antibody responses in AVA-vaccinated Rhesus macaques (Macaca mulatta) that survived aerosol challenge with Bacillus anthracis Ames spores. Results showed that macaque anti-AVA sera neutralized LTx in vitro, even when PA was pre-bound to cells. Neutralization titers in surviving versus non-surviving animals and between pre-challenge versus post-challenge activity were highly correlated. These data demonstrate that AVA stimulates a myriad of antibodies that recognize multiple neutralizing epitopes, and confirm that change, loss, or occlusion of epitopes after PA is processed from PA83 to PA63 at the cell surface does not significantly affect in vitro neutralizing efficacy. Furthermore, these data support that full length PA83 monomer is an appropriate immunogen for inclusion in next-generation anthrax vaccines.