Alternative regulatory pathways for vaccine licensure without traditional Phase III efficacy trials are of increasing priority for epidemic pathogens. Using IXCHIQ, a chikungunya virus vaccine licensed through an accelerated pathway, we demonstrate that prior understanding of disease risk from infection can inform risk–benefit assessments for new vaccines. The mass deployment of IXCHIQ during an outbreak in La Réunion was suspended in those aged over 65 years following three deaths in vaccine recipients, although two appear unlikely to have been vaccine-linked. For individuals aged 18–64 years, we find the vaccine benefits outweigh risks across epidemiological settings. In those aged over 65 years, we estimate a net benefit in large outbreaks, including the La Réunion outbreak, and endemic settings over ten years. There is insufficient evidence of a net benefit in smaller outbreaks or in travellers. We also identify the level of vaccine-associated severe adverse events that would nevertheless still result in a net benefit for a set of endemic and epidemic pathogens. Our generalizable approach can help guide trial recruitment, inform vaccine implementation, and provide a foundation for weighing potential benefits against vaccine-associated risks. Using a statistical model that incorporates transmission intensity and stratum-specific rates of severe outcomes, either associated with disease or vaccination, a framework is proposed to compare the risks and benefits of deploying new vaccines, using early epidemiological data.

IntroductionMore than 15% of Brazil's urban population lives in slums characterized by limited access to essential urban services, heightened vulnerability to infectious pathogens and environmental hazards, and deprivation of citizenship rights. These conditions exacerbate social inequality, perpetuate cycles of poverty, and fuel violence, underscoring the urgent need for sustainable interventions.MethodsFollowing a social justice framework, we developed a community development program rooted in participatory research methods and popular health education to foster collaboration between university researchers and communities. The aim was to identify priorities and co-create locally driven, cost-effective, and sustainable solutions. This article describes our ongoing project in three prominent urban slums of Salvador, Brazil (Alto do Cabrito, Pau da Lima and Marechal Rondon), detailing the methodologies employed, activities initiated, and interventions developed.ResultsWe conducted ethnographic, eco-epidemiological, and collaborative mapping surveys to contextualize diverse health and well-being challenges. Furthermore, we organized consultative and socialization events with dynamic community groups and identified local priorities, leading to the design of thirteen interventions targeting citizenship rights, social cohesion, environmental restoration, waste management, and unemployment.DiscussionHere, we described how our interdisciplinary approach leveraged social capital and fostered inter-sectoral partnerships to empower marginalized urban communities towards addressing their health and environmental challenges through sustainable, locally tailored solutions. While the program has strengthened community trust, facilitated partnerships, and achieved notable environmental improvements, further evaluation is needed to assess the long-term impacts of these interventions on broader social health determinants.

Host condition is key in understanding disease dynamics. In this study, we investigated the relationship between infection with Leptospira interrogans and helminths, and the hematological and hormone-biochemical stress-related profiles of urban Rattus norvegicus. Rat kidney imprints and urine were used to identify and quantify L. interrogans, while fecal samples were analyzed for helminth eggs and corticosterone metabolites. Blood samples were taken for complete blood counts and specific biochemicals in rats' sera. Principal Component Analyses were conducted to group rats according to health profiles. A total of 120 rats were captured, and hematological and hormone-biochemical data were obtained from 95 and 61 rats, respectively. Hematological PCA revealed distinct rat groups: typical (T), eosinophil-deficient (Eos-D), eosinophil- and monocyte-deficient (EM-D) and monocyte deficient with high immature neutrophils (Mon-D). No significant association was found between L. interrogans or helminth infections and health profiles, except for Trichiuridae helminths, which had significantly higher mean intensity in the pooled deficient groups compared to the T-group. The poorest condition group was found in areas with fewer rat burrows than the T-group, indicating EM-D had a reduced ability to occupy higher-quality habitats. These findings suggest that hematological profiles may reflect host's overall condition, instead of responses to specific infections.

The 2015-16 Zika virus epidemic emerged in the Americas and rapidly spread throughout the region and beyond, showing the epidemic potential of this mosquito-borne Orthoflavivirus and its capacity to cause severe congenital malformations and neurological sequelae. WHO declared the Zika virus epidemic a public health emergency of international concern in 2016. Despite this declaration, there are no licensed Zika virus vaccines, therapeutics, or diagnostic tests appropriate for routine antenatal screening. To address this absence of essential tools to detect and mitigate the threat of future Zika virus outbreaks, a group of global experts developed a priority agenda for Zika virus research and development. This Series paper summarises crucial challenges and knowledge gaps and outlines a comprehensive strategy to advance research, surveillance, global capacity, policy, and investment for Zika virus preparedness and response. Lancet 25: Published February https://doi.org/10.1016/ S1473-3099(24)00794-1 This of to with All

PURPOSE:To describe an international response to the COVID-19 pandemic by estimating the prevalence of medication use for COVID-19 treatment in pregnancy, stratified by hospitalization, trimester of pregnancy, and country. METHODS:We conducted a two-stage individual participant data meta-analysis of proportions from primary data on medications used to treat COVID-19 during pregnancy. A common data model was developed to pool the data from single-country and international registries. Data from pregnant individuals with COVID-19 between February 2020 and October 2022 were included in study platforms across 9 data sources. Patient information was abstracted from medical records. RESULTS:Among 24 937 pregnant individuals, the pooled prevalences of individuals receiving medications to treat COVID-19 were: 34.7% heparin, 9.8% antibiotics, 4.9% corticosteroids, 2.2% antivirals, 0.8% antimalarials, 0.3% convalescent plasma, 0.2% immunosuppressants, and 0.02% monoclonal antibodies. Prevalence of medication use was higher in hospitalized individuals than in non-hospitalized individuals: 58.4% versus 17.9% for heparin, 26.9% versus 5.7% for antibiotics, 17.5% versus 1.3% for corticosteroids, 10.3% versus 0.3% for antivirals, and 4.5% versus 0.1% for antimalarials. The prevalence of corticosteroid use was lower in the first trimester (0.1%) compared with the second (7.2%) and third (4.9%) trimesters of pregnancy. The prevalence of medications differed widely across countries. CONCLUSION:Medication to treat COVID-19 was more frequently used in pregnant individuals hospitalized for COVID-19. Corticosteroids were used less in the first trimester of pregnancy. The differences in use between countries could reflect differences in the clinical management and access to medications for this population at risk of severe disease.

Test-negative designs are increasingly used to evaluate vaccine effectiveness because of desirable properties like reduced confounding due to healthcare-seeking behaviors and lower cost compared to other study designs. An individual's decision to seek care often depends on their disease severity, with severe disease more likely to be captured than mild disease. As many vaccines likely attenuate disease severity, this phenomenon generally results in an upward-biased estimate of vaccine effectiveness against symptomatic disease. To address the resulting bias, analytic solutions like adjusting for or matching on severity have been suggested. In this paper, we examine the performance of the test-negative design under different vaccine effects on disease severity and the utility of adjusting or matching on severity. We further consider the implications of studies that focus only on milder disease by restricting recruitment to outpatient settings. Through an analytic framework and simulations accompanied by a real-world example, we demonstrate that, when vaccination attenuates disease severity, the magnitude of bias is influenced by the degree of under-ascertainment of mild disease relative to severe disease. When vaccination does not attenuate disease severity, bias is not present. We further show that analytic fixes negligibly impact bias and that outpatient-only studies frequently produce downward-biased estimates.

Vulnerability to climate hazards and infectious diseases is not gender-neutral, meaning that men, women, and other gender identities experience different risks. Leptospirosis is a zoonotic climate-sensitive infectious disease caused by the bacteria Leptospira and is transmitted to humans through contact with infected animals or contaminated environments, particularly soil and floodwater. Globally, studies report a higher risk of leptospiral infection among men than women, a trend also observed in Salvador, Brazil; however, the factors driving this difference are poorly understood. This study aimed to investigate how Leptospira exposure differs between men and women living in urban informal settlements in Salvador. We conducted a cross-sectional serosurvey among 761 adults (280 men and 481 women) in four communities previously identified as high-risk by surveillance data. Using a causal inference approach and a two-part sex-disaggregated analysis, we applied logistic regression models to examine: (1) the association between perceived severity and high-risk behaviours with Leptospira seropositivity, and (2) the association between perceived severity with high-risk behaviours. Seroprevalence was 14.6% (95% CI: 10.5%-18.8%) in men and 9.4% (95% CI: 6.7%-12.0%) in women. Men who perceived leptospirosis as extremely serious had lower odds of being seropositive (OR: 0.38, 95% CI: 0.15-0.99), walking through sewage (OR: 0.41, 95% CI: 0.17-1.00), and walking barefoot outside (OR: 0.24, 95% CI: 0.08-0.76) compared with men who perceived leptospirosis as less serious. These associations were not observed in women and differed across age groups in men. Behaviours were not associated with seropositivity in either gender. Our results identify perceived severity as a potential driver of high-risk behaviours and exposure in men, indicating perceptions as targets for health promotion programs, while also highlighting evidence gaps in understanding exposure risks among women. As the first sex-disaggregated study investigating Leptospira exposure risks, we advocate for a gendered lens in future studies to understand gender-specific risks.

BACKGROUND:Chikungunya virus (CHIKV) is an arbovirus with a significant global public health burden. Delineating the specific contributions of individual behaviour, household, natural and built environment to CHIKV transmission is important for reducing risk in urban informal settlements but challenging due to their heterogeneous environments. The aim of this study was to quantify variation in CHIKV seroprevalence between and within four urban communities in a large Brazilian city, and identify the respective contributions of individual, household, and environmental factors for seropositivity. METHODOLOGY/PRINCIPAL FINDINGS:A cross-sectional serological survey was conducted in four low-income communities in Salvador, Brazil in 2018 to collect individual, household and CHIKV IgG serology data for 1318 participants. Fine-scale community mapping of high-risk environmental features and remotely sensed environmental data were used to improve characterisation of the microenvironment close to the household. We categorised risk factors into three domains - individual, household, and environmental and used binomial mixed-effect models to identify associations with CHIKV seropositivity. CHIKV seroprevalence was 4.8%, 6.1% and 4.3% in three communities and 22.6% in one community which had a distinct topographical profile. The only individual domain variable associated with seropositivity was male sex (OR 1.67, 95% CI 1.11 - 2.36), but several environmental variables, including living in a house on a steep hillside, at medium to high elevations, and with surface water nearby, were associated with higher seropositivity. CONCLUSIONS/SIGNIFICANCE:Our findings indicate that CHIKV exposure risk can vary significantly between nearby communities and at fine spatial scales within communities and is likely to be driven more strongly by the availability of mosquito breeding sites rather than individual exposure patterns. They suggest that environmental deficiencies and topography, a proxy for several environmental processes including the degree of urbanisation and flooding risk, may play an important role in driving risk at both of these scales.

Abstract Background We lack understanding of how health care workers’ (HCWs) contacts change over time or in response to pandemics. This study describes the social contact patterns of HCWs in a large United States health care system via standardized social contact diaries. Mean number of total contacts over time (Jan 2021-May 2022): The mean contacts noted with dark-blue line with 95% confidence intervals (95%CI) in dark gray. The dashed black line shows the linear regression of contacts over time. The-axis is interrupted as the study was closed in June and July 2021. Methods Inpatient and outpatient HCWs enrolled from October 2020 to June 2022. Participants completed a monthly survey of all contacts during a single representative working day selected by the participant. Direct contact was defined as being within 2 meters of another person. Indirect contact was defined as being in the same room but more than 2 meters. In June 2022, participants completed a 2-day individual-level contact diary. We generated age-stratified contact matrices. Contacts were described by contact type, duration and contact relationship. Number and duration of contacts by job were compared by chi-squared test and number of contacts over time by linear regression. Average contacts of health care worker with all individuals The individual tiles color and numeric fill denote the average number of contacts per HCW of that age range with a contact of that age range. A horizontal marginal histogram shows the age break down of HCW participants and a vertical marginal histogram shows the resulting distribution of contact’s ages. Results 360 HCWs enrolled, 95 completed 1 or more monthly contact diary and 88 completed the intensive 2-day diary. The total number of contacts was stable over time (β0.14, p 0.20, Fig.1). HCWs reported direct contacts with less than 5 patients, 5-9 patients, 10-19 patients or 20 more patients, 50%, 29%,15% or 6% of the time respectively. HCWs reported direct contact with less than 5 other HCWs, 6-10 HCWs, 11-20 or 21 or more 19%, 39%, 27 % or 15% of the time respectively. In the June 2022, a total of 2,550 contacts were reported, 1,592 (62%) were with HCWs, and 570 (22%) with patients. Social workers, rehab/transport and doctors were more likely to have contact with 20 or more patients vs. other professions. Nurses, imaging technologists and rehab/transport were more likely to spend 20 minutes or more with patients vs. other professions. Contact matrices were not age assortative with HCWs having similar contacts across all working ages (Fig. 2). HCWs’ physical contacts focused on extremes of age (Fig. 3). Contact type varied by job with nearly all groups having more contacts with colleagues than patients (Fig, 4). Average physical contacts of HCWs per day: The The individual tiles color and numeric fill denote the average number of physical contacts per HCW of that age range with a contact of that age range. A horizontal marginal histogram shows the age break down of HCW participants and a vertical marginal histogram plot the resulting distribution of contact’s ages. Conclusion HCW contacts concentrated in their work environment and most contacts were focused in the working-age population. These contacts were stable over time even in the COVID-19 pandemic response. HCWs were 2.8 time more likely to contact HCWs than patients. Number of contacts of 2 days by participant job and contact individual Grouped box plots show the number of contacts over the 2-day intensive diary by HCW job (x-axis) and the HCWs relationship with the contact (e.g. colleague, patient or other). Disclosures Lauren Pischel, MD, Auxa Health: Advisor/Consultant Amyn Malik, MBBS, MPH, PhD, Analysis Group, Inc: Former Employee. We consulted with Pharma and Biotech on different research studies Ben Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Albert I. Ko, MD, Merck: Grant/Research Support|Regeneron: Grant/Research Support Saad Omer, MBBS MPH PhD, Meta: Advisor/Consultant|Meta: Grant/Research Support

Before Zika virus (ZIKV) infections were observed in the Americas, an association between ZIKV and microcephaly or other congenital malformations was not well documented. Initial reports suggested strong associations between ZIKV and congenital malformations, but plausible estimates of causal effects from prospective studies with adequate sample size and covariate data were few. From 2016–2018, the Zika in Infants and Pregnancy (ZIP) study enrolled pregnant people before 18 weeks gestation or with confirmed symptomatic ZIKV in a prospective cohort across 10 sites in South and Central America, and in Puerto Rico. Pregnancies were followed monthly through delivery and 6 weeks postpartum. Infants were followed quarterly to age 12 months. Prespecified co-primary analyses evaluated the associations between a composite endpoint of adverse fetal, neonatal, and infant outcomes with intrauterine ZIKV exposure overall and with symptomatic intrauterine ZIKV exposure. Secondary analyses separately evaluated the association of intrauterine ZIKV exposure with individual components of the primary endpoint. Six thousand one hundred pregnant participants were included in the primary analysis, including 61 with ZIKV infection during pregnancy confirmed by a ZIKV-specific RNA test. For the primary analyses, the relative risk (RR) for the composite endpoint associated with any ZIKV exposure was 1.64 (95

Background Disadvantaged populations, especially those living in rural and informal settlements, constitute the most affected during the COVID-19 pandemic. However, there is limited information on the health-related quality of life (HRQOL) and indirect consequences of non-pharmaceutical interventions implemented during the pandemic.Methods We leveraged on an ongoing prospective open-cohort survey and performed a cross-sectional analysis of data collected between November 2021 and July 2022 among 793 residents above age 5 in a large slum community in the city of Salvador, Brazil. We describe the HRQOL of residents, explored participants’ perception about the pandemic, and the relationship between sociodemographic, economic and employment data on physical and mental health scores using both χ2 statistics and separate mixed-effects regression models.Results Most participants were female (58.9%), aged 18–45 years (45%), with nearly half (49.7%) employed before pandemic, of whom 38.8% lost jobs during the pandemic. Food insecurity was 69.6%, and only 27.1% received government aid. Those retaining employment during the pandemic had better physical (β: 4.02, 95% CI 1.34 to 6.69, p<0.001) and mental (β: 3.08, 95% CI 0.60 to 5.56, p<0.001) health. Females had lower physical health scores than males (β: −2.44, 95% CI −3.94 to −0.94, p=0.002). Older participants had lower physical health scores (β: −9.11, 95% CI −12.14 to −6.07, p<0.001), but higher schooling improved physical health (p<0.001). Females and older adults faced more COVID-impacted challenges (p<0.001) related to health, education, family, social relationships, work, finances and employment.Conclusion We found lower HRQOL among adults, females, the unemployed and those with lower school attainment. In addition, women and individuals in older age groups reported experiencing COVID-impacted mental challenges more frequently than others. These findings highlight the need to prioritise creation of economic opportunities and expansion of existing assistance programmes for marginalised populations residing in these slums.

OBJECTIVES:The SARS-CoV-2 BQ.1* variant rapidly spread globally in late 2022, posing a challenge due to its increased immune evasion.METHODS:We conducted a prevalence survey in Brazil from November 16 to December 22, 2022, as part of a cohort study. We conducted interviews and collected nasal samples for reverse transcription-polymerase chain reaction (RT-PCR) testing and whole-genome sequencing. Cumulative incidence was estimated using RT-PCR positivity, cycle threshold values, and external data on the dynamics of RT-PCR positivity following infection.RESULTS:Among 535 participants, 54% had documented SARS-CoV-2 exposure before this outbreak and 74% had received COVID-19 vaccination. In this study, 14.8% tested positive for SARS-CoV-2, with BQ.1* identified in 90.7% of cases. Using case data and cycle threshold values, cumulative incidence was estimated at 56% (95% confidence interval, 36-88%). Of the 79 positive participants, 48.1% had a symptomatic illness, with a lower proportion fulfilling the World Health Organization COVID-19 case definition compared to prior Omicron waves. No participants required medical attention.CONCLUSIONS:Despite high population-level hybrid immunity, the BQ.1* variant attacked 56% of our population. Lower disease severity was associated with BQ.1* compared to prior Omicron variants. Hybrid immunity may provide protection against future SARS-CoV-2 variants but in this case was not able to prevent widespread transmission.

Background. Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins like SG6 have been used as biomarkers of exposure to Anopheles mosquito bites. Here, we investigate 4 mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected with Plasmodium falciparum: mosGILT, SAMSP1, AgSAP, and AgTRIO. Methods. We tested population-level human immune responses in longitudinal and cross-sectional plasma from individuals with known P falciparum infection from low- and moderate-transmission areas in Senegal using a multiplexed magnetic bead- based assay. Results. AgSAP and AgTRIO were the best indicators of recent exposure to infected mosquitoes. Antibody responses to AgSAP, in a moderate-endemicity area, and to AgTRIO in both low- and moderate-endemicity areas, were significantly higher than nonendemic controls. No antibody responses significantly differed between low- and moderate-transmission areas, or between equivalent groups during and outside the malaria transmission seasons. AgSAP and AgTRIO reactivity peaked 2-4 weeks after clinical P falciparum infection and declined 3 months after infection. Conclusions. Reactivity to AgSAP and AgTRIO reflects exposure to infectious mosquitoes or recent bites rather than general mosquito exposure, highlighting their promise for incorporation into multiplexed assays for serosurveillance of population-level changes in P falciparum -infected mosquito exposure.

Background:Vulnerability to climate hazards and infectious diseases are not gender-neutral, meaning that men, women, boys, girls, and other gender identities experience different health risks. Leptospirosis, a zoonotic climate sensitive infectious disease, is commonly transmitted to humans via contact with animals and the environment, particularly soil and flood water. Gender differences in leptospiral infection risk are reported globally, with men consistently found to be at higher risk than women. However, the drivers of this difference in risk are poorly understood. Previous studies suggest that the interplay of knowledge, perceptions, and behaviours may shape differential infection risk among genders. Methodology/Principal Findings:To examine gender differences in Leptospira exposure risk we conducted a cross-sectional serosurvey among adult participants (n = 761) in four urban, marginalised, informal settlements in the city of Salvador, Brazil. We found that seroprevalence was 14.6% and 9.4% across men and women respectively. We then applied causal inference methodology to a two-part sex-disaggregated analysis to investigate: 1) the association of perceptions and behaviours with Leptospira seropositivity and 2) the association of perceptions with behaviours. We found that men who perceived leptospirosis as extremely serious had lower odds of seropositivity, walking through sewage water, or walking barefoot, suggesting an important link between perceptions, behaviours, and exposure risk. These associations were not found in women, and these behaviours were not associated with seropositivity in men or women. Conclusions:Our results highlight perceived severity of disease as a potential driver of behaviour in men, and perceptions of disease may be an important target for health education programs. Furthermore, our study identifies evidence gaps in the understanding of infection risks in women. As the first sex-disaggregated study investigating Leptospira infection risks, we advocate for a gendered lens in future studies to further understand risks specific to different gender identities.

Rickettsioses and leptospirosis are infectious diseases that are often underdiagnosed due to a lack of knowledge about their epidemiology, pathophysiology, diagnosis, management, among others. Objetive:to characterize the seroprevalence and seroincidence of both Rickettsia and Leptospira agents and determine the risk factors for these outcomes in rural areas of Urabá, Antioquia. Methods:a secondary data analysis using information on Rickettsia and Leptospira exposure from a prior prospective study that explored sociocultural and ecological aspects of Rickettsia infection in rural Urabá, Colombia. A multinomial mixed logistic regression model was employed to analyze factors linked to seroprevalent cases of Rickettsia, Leptospira and both, along with descriptive analyses of seroincident cases. Results:the concomitant seroprevalence against Rickettsiaand Leptospira was 9.38% [95%CI 6.08%-13.37%] (56/597). The factors associated with this seroprevalence were age (ORa= 1.02 [95%CI 1.007-1.03]), male gender (ORa= 3.06 [95%CI 1.75-5.37]), fever history (ORa= 1.71 [95%CI 1.06-2.77]) the presence of breeding pigs (ORa= 2.29 [95%CI 1.36-3.88]), peridomicile yucca crops(ORa= 2.5 [95%CI 1.1-5.62]), and deforestation practices(ORa= 1.74 [95%CI 1.06-2.87]). The concomitant seroincidence against Rickettsia and Leptospira was 1.09% (3/274) [95%CI 0.29%-4.05%], three cases were female, with a median age of 31.83 years-old (IQR 8.69-56.99). At the household level, all the seroincident cases had households built partially or totally with soil floors, wooden walls, and zinc roofs. Two seroincident cases described the presence of equines, canines, and domestic chickens in intra or peri-domicile. Finally, two cases were exposed to synanthropic rodents, and one case to tick infestation. Conclusion:there is evidence of seroprevalent and seroincident cases of seropositivity against both Rickettsia and Leptospira in rural areas of Urabá, Colombia. These findings can help improve public health surveillance systems in preventing, detecting, and attending to the different clinical cases caused by these pathogens.

Rats are major reservoirs for pathogenic Leptospira, the bacteria causing leptospirosis, particularly in urban informal settlements. However, the impact of variation in rat abundance and pathogen shedding rates on spillover transmission to humans remains unclear. This study aimed to investigate how spatial variation in reservoir abundance and pathogen pressure affect Leptospira spillover transmission to humans in a Brazilian urban informal settlement. A longitudinal eco-epidemiological study was conducted from 2013 to 2014 to characterize the spatial distribution of rat abundance and Leptospira shedding rates in rats and determine the association with human infection risk in a cohort of 2,206 community residents. Tracking plates and live-trapping were used to measure rat abundance and quantify rat shedding status and load. In parallel, four sequential biannual serosurveys were used to identify human Leptospira infections. To evaluate the role of shedding on human risk, we built three statistical models for: (1) the relative abundance of rats, (2) the shedding rate by individual rats, and (3) human Leptospira infection, in which “total shedding”, obtained by multiplying the predictions from those two models, was used as a risk factor. We found that Leptospira shedding was associated with older and sexually mature rats and varied spatially and temporally—higher at valley bottoms and with seasonal rainfall (December to March). The point estimate for “total shedding” by rat populations was positive, i.e., Leptospira infection risk increased with total shedding, but the association was not significant [odds ratio (OR) = 1.1; 95% confidence interval (CI): 0.9, 1.4]. This positive trend was mainly driven by rat abundance, rather than individual rat shedding (OR = 1.8; 95% CI: 0.6, 5.4 vs. OR = 1.0; 95% CI: 0.7, 1.4]. Infection risk was higher in areas with more vegetative land cover (OR = 2.4; 95% CI: 1.2, 4.8), and when floodwater entered the house (OR = 2.4; 95% CI: 1.6, 3.4). Our findings indicate that environmental and hydrological factors play a more significant role in Leptospira spillover than rat associated factors. Furthermore, we developed a novel approach combining several models to elucidate complex links between animal reservoir abundance, pathogen shedding and environmental factors on zoonotic spillover in humans that can be extended to other environmentally transmitted diseases.

Background The emergence of COVID-19 variants with immune scape and the waning of primary vaccine schemes effectiveness have prompted many countries to indicate fi rst and second booster COVID-19 vaccine doses to prevent severe COVID-19. However, current available evidence on second booster dose effectiveness are mostly limited to high-income countries, older adults, and mRNA-based vaccination schemes scenarios. We aimed to investigate the relative vaccine effectiveness (rVE) of the fourth dose compared to three doses for severe COVID-19 outcomes in Brazil; and compare the rVE of a fourth dose with an mRNA vaccine compared to adenovirus-based product in the same settings. Methods We performed a target emulated trial using a population-based cohort of individuals aged 40 years or older who have received a homologous primary scheme of CoronaVac, ChAdOx1, or BNT162b2, and any third dose product and were eligible for the fourth dose in Brazil. The primary outcome was COVID-19 associated hospitalization or death. We built Cohort A matching individuals vaccinated with a fourth dose to individuals who received three doses to estimate the rVE of the fourth dose. We built Cohort B, a subset of Cohort A, matching mRNA-based (mRNA) to adenovirus-based fourth dose vaccinated individuals to compare their relative hazards for severe COVID-19. Findings 46,693,484 individuals were included in Cohort A and 6,763,016 in Cohort B. 45% of them were aged between 40 and 60 years old, and 48% between 60 and 79 years old. In Cohort A, the most common previous series was a ChAdOx1 two-dose followed by BNT162b2 (44%), and a CoronaVac two-dose followed by a BNT162b2 (36%). Among those fourth dose vaccinated, 36.9% received ChAdOx1, 32.7% Ad26.COV2.S, 25.8% BNT162b2, and 4.7% CoronaVac. In Cohort B, among those who received an adenovirus fourth dose, 53.7% received ChAdOx1 and 46.3% received Ad26.COV2.S. The estimated rVE for the primary outcome of four doses compared to three doses was 44.1% (95% CI 42.3 - 46.0), with some waning during follow-up (rVE 7 - 60 days 46.8% [95% CI 44.4 - 49.1], rVE after 120 days 33.8% [95% CI 18.0 - 46.6]). Among fourth dose vaccinated individuals, mRNA-based vaccinated individuals had lower hazards for hospitalization or death compared to adenovirus-vaccinated individuals

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread globally. However, the contribution of community versus household transmission to the overall risk of infection remains unclear.Methods Between November 2021 and March 2022, we conducted an active case-finding study in an urban informal settlement with biweekly visits across 1174 households with 3364 residents. Individuals displaying coronavirus disease 2019 (COVID-19)-related symptoms were identified, interviewed along with household contacts, and defined as index and secondary cases based on reverse-transcription polymerase chain reaction (RT-PCR) and symptom onset.Results In 61 households, we detected a total of 94 RT-PCR-positive cases. Of 69 sequenced samples, 67 cases (97.1%) were attributed to the Omicron BA.1* variant. Among 35 of their households, the secondary attack rate was 50.0% (95% confidence interval [CI], 37.0%-63.0%). Women (relative risk [RR], 1.6 [95% CI, .9-2.7]), older individuals (median difference, 15 [95% CI, 2-21] years), and those reporting symptoms (RR, 1.73 [95% CI, 1.0-3.0]) had a significantly increased risk for SARS-CoV-2 secondary infection. Genomic analysis revealed substantial acquisition of viruses from the community even among households with other SARS-CoV-2 infections. After excluding community acquisition, we estimated a household secondary attack rate of 24.2% (95% CI, 11.9%-40.9%).Conclusions These findings underscore the ongoing risk of community acquisition of SARS-CoV-2 among households with current infections. The observed high attack rate necessitates swift booster vaccination, rapid testing availability, and therapeutic options to mitigate the severe outcomes of COVID-19. We found a high level of transmissibility of the SARS-CoV-2 BA.1* Omicron variant both within the community and households. Phylogenetic analysis suggests a diverse set of viruses were transmitted within the community and households, consistent with multiple introductions and high rates of incidence.