Disentangling the influence of reservoir abundance and pathogen shedding on zoonotic spillover of the Leptospira agent in urban informal settlements.

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.

Factors associated with differential seropositivity to Leptospira interrogans and Leptospira kirschneri in a high transmission urban setting for leptospirosis in Brazil.

BACKGROUND: Leptospirosis is a zoonosis caused by pathogenic species of bacteria belonging to the genus Leptospira. Most studies infer the epidemiological patterns of a single serogroup or aggregate all serogroups to estimate overall seropositivity, thus not exploring the risks of exposure to distinct serogroups. The present study aims to delineate the demographic, socioeconomic and environmental factors associated with seropositivity of Leptospira serogroup Icterohaemorraghiae and serogroup Cynopteri in an urban high transmission setting for leptospirosis in Brazil. METHODS/PRINCIPAL FINDINGS: We performed a cross-sectional serological study in five informal urban communities in the city of Salvador, Brazil. During the years 2018, 2020 2021, we recruited 2.808 residents and collected blood samples for serological analysis using microagglutination assays. We used a fixed-effect multinomial logistic regression model to identify risk factors associated with seropositivity for each serogroup. Seropositivity to Cynopteri increased with each year of age (OR 1.03; 95% CI 1.01-1.06) and was higher in those living in houses with unplastered walls (exposed brick) (OR 1.68; 95% CI 1.09-2.59) and where cats were present near the household (OR 2.00; 95% CI 1.03-3.88). Seropositivity to Icterohaemorrhagiae also increased with each year of age (OR 1.02; 95% CI 1.01-1.03) and was higher in males (OR 1.51; 95% CI 1.09-2.10), in those with work-related exposures (OR 1.71; 95% CI 1.10-2.66) or who had contact with sewage (OR 1.42; 95% CI 1.00-2.03). Spatial analysis showed differences in distribution of seropositivity to serogroups Icterohaemorrhagiae and Cynopteri within the five districts where study communities were situated. CONCLUSIONS/SIGNIFICANCE: Our data suggest distinct epidemiological patterns associated with the Icterohaemorrhagiae and Cynopteri serogroups in the urban environment at high risk for leptospirosis and with differences in spatial niches. We emphasize the need for studies that accurately identify the different pathogenic serogroups that circulate and infect residents of low-income areas.

Gender differences in the perception of leptospirosis severity, behaviours, and Leptospira exposure risk in urban Brazil: a cross-sectional study.

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.

Dynamics of chikungunya virus transmission in the first year after its introduction in Brazil: A cohort study in an urban community.

BACKGROUND: The first chikungunya virus (CHIKV) outbreaks during the modern scientific era were identified in the Americas in 2013, reaching high attack rates in Caribbean countries. However, few cohort studies have been performed to characterize the initial dynamics of CHIKV transmission in the New World. METHODOLOGY/PRINCIPAL FINDINGS: To describe the dynamics of CHIKV transmission shortly after its introduction in Brazil, we performed semi-annual serosurveys in a long-term community-based cohort of 652 participants aged ≥5 years in Salvador, Brazil, between Feb-Apr/2014 and Nov/2016-Feb/2017. CHIKV infections were detected using an IgG ELISA. Cumulative seroprevalence and seroincidence were estimated and spatial aggregation of cases was investigated. The first CHIKV infections were identified between Feb-Apr/2015 and Aug-Nov/2015 (incidence: 10.7%) and continued to be detected at low incidence in subsequent surveys (1.7% from Aug-Nov/2015 to Mar-May/2016 and 1.2% from Mar-May/2016 to Nov/206-Feb/2017). The cumulative seroprevalence in the last survey reached 13.3%. It was higher among those aged 30-44 and 45-59 years (16.1% and 15.6%, respectively), compared to younger (12.4% and 11.7% in <15 and 15-29 years, respectively) or older (10.3% in ≥60 years) age groups, but the differences were not statistically significant. The cumulative seroprevalence was similar between men (14.7%) and women (12.5%). Yet, among those aged 15-29 years, men were more often infected than women (18.1% vs. 7.4%, respectively, P = 0.01), while for those aged 30-44, a non-significant opposite trend was observed (9.3% vs. 19.0%, respectively, P = 0.12). Three spatial clusters of cases were detected in the study site and an increased likelihood of CHIKV infection was detected among participants who resided with someone with CHIKV IgG antibodies. CONCLUSIONS/SIGNIFICANCE: Unlike observations in other settings, the initial spread of CHIKV in this large urban center was limited and focal in certain areas, leaving a high proportion of the population susceptible to further outbreaks. Additional investigations are needed to elucidate the factors driving CHIKV spread dynamics, including understanding differences with respect to dengue and Zika viruses, in order to guide prevention and control strategies for coping with future outbreaks.

Prevalence of human leptospirosis in the Americas: a systematic review and meta-analysis.

Objective: To describe the prevalence of leptospirosis in the Americas. Methods: A systematic review and meta-analysis, in the period 1930 to 2017, performed on a search of six platforms: PubMed, Web of Science, Scopus, Lilacs, Embase, and Cochrane. Results: The search found 77 publications of which 53 (68%) were from the period 2000-2017. Of the 77, 62 studies were included in the analysis, from North America (11, 17%), Central America (9, 14%), and South America (42, 67%), and 22 studies were from urban areas. Leptospirosis prevalence in the 62 studies analyzed corresponded to 28% (95% CI [23, 32]). Countries with higher prevalence were United States of America (41%), Colombia (29%), and Brazil (21%). The most frequent serovars found were Icterohaemorrhagiae (43 of 77 publications, 55%), Canicola (35, 45%), Pomona (28, 36%), and Grippotyphosa (26, 33%). Conclusions: There is variability of Leptospira species and serovars with heterogenous distribution throughout the Americas, with high prevalence in some countries, highlighting the need for action to control the disease.

Environmental Biofilms from an Urban Community in Salvador, Brazil, Shelter Previously Uncharacterized Saprophytic Leptospira.

Biofilms are complex microecosystems with valuable ecological roles that can shelter a variety of microorganisms. Spirochetes from the genus Leptospira have been observed to form biofilms in vitro, in rural environments, and in the kidneys of reservoir rats. The genus Leptospira is composed of pathogenic and non-pathogenic species, and the description of new species is ongoing due to the advent of whole genome sequencing. Leptospires have increasingly been isolated from water and soil samples. To investigate the presence of Leptospira in environmental biofilms, we collected three distinct samples of biofilms formed in an urban setting with poor sanitation: Pau da Lima, in Salvador, Bahia, Brazil. All biofilm samples were negative for the presence of pathogenic leptospires via conventional PCR, but cultures containing saprophytic Leptospira were identified. Whole genomes were generated and analyzed for twenty isolates obtained from these biofilms. For species identification, we used digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) analysis. The obtained isolates were classified into seven presumptive species from the saprophytic S1 clade. ANI and dDDH analysis suggest that three of those seven species were new. Classical phenotypic tests confirmed the novel isolated bacteria as saprophytic Leptospira. The isolates presented typical morphology and ultrastructure according to scanning electron microscopy and formed biofilms under in vitro conditions. Our data indicate that a diversity of saprophytic Leptospira species survive in the Brazilian poorly sanitized urban environment, in a biofilm lifestyle. We believe our results contribute to a better understanding of Leptospira biology and ecology, considering biofilms as natural environmental reservoirs for leptospires.

Simplified sewerage to prevent urban leptospirosis transmission: a cluster non-randomised controlled trial protocol in disadvantaged urban communities of Salvador, Brazil.

INTRODUCTION: Leptospirosis is a globally distributed zoonotic and environmentally mediated disease that has emerged as a major health problem in urban slums in developing countries. Its aetiological agent is bacteria of the genus Leptospira, which are mainly spread in the urine of infected rodents, especially in an environment where adequate sanitation facilities are lacking, and it is known that open sewers are key transmission sources of the disease. Therefore, we aim to evaluate the effectiveness of a simplified sewerage intervention in reducing the risk of exposure to contaminated environments and Leptospira infection and to characterise the transmission mechanisms involved. METHODS AND ANALYSIS: This matched quasi-experimental study design using non-randomised intervention and control clusters was designed to assess the effectiveness of an urban simplified sewerage intervention in the low-income communities of Salvador, Brazil. The intervention consists of household-level piped sewerage connections and community engagement and public involvement activities. A cohort of 1400 adult participants will be recruited and grouped into eight clusters consisting of four matched intervention-control pairs with approximately 175 individuals in each cluster in baseline. The primary outcome is the seroincidence of Leptospira infection assessed through five serological measurements: one preintervention (baseline) and four postintervention. As a secondary outcome, we will assess Leptospira load in soil, before and after the intervention. We will also assess Leptospira exposures before and after the intervention, through transmission modelling, accounting for residents' movement, contact with flooding, contaminated soil and water, and rat infestation, to examine whether and how routes of exposure for Leptospira change following the introduction of sanitation. ETHICS AND DISSEMINATION: This study protocol has been reviewed and approved by the ethics boards at the Federal University of Bahia and the Brazilian National Research Ethics Committee. Results will be disseminated through peer-reviewed publications and presentations to implementers, researchers and participating communities. TRIAL REGISTRATION NUMBER: Brazilian Clinical Trials Registry (RBR-8cjjpgm).

Factors associated with differential seropositivity to Leptospira interrogans and Leptospira kirschneri in a high transmission urban setting for leptospirosis in Brazil.

Background: Leptospirosis is a zoonosis caused by pathogenic species of bacteria belonging to the genus Leptospira. Most studies infer the epidemiological patterns of a single serogroup or aggregate all serogroups to estimate overall seropositivity, thus not exploring the risks of exposure to distinct serogroups. The present study aims to delineate the demographic, socioeconomic and environmental factors associated with seropositivity of Leptospira serogroup Icterohaemorraghiae and serogroup Cynopteri in an urban high transmission setting for leptospirosis in Brazil. Methods/Principal Findings: We performed a cross-sectional serological study in five urban informal communities in the city of Salvador, Brazil. During the years 2018, 2020 2021, we recruited 2.808 residents and collected blood samples for serological analysis using microagglutination assays. We used a mixed-effect multinomial logistic regression model to identify risk factors associated with seropositivity for each serogroup. Seropositivity to Cynopteri increased with age in years (OR 1.03; 95% CI 1.01-1.06) and was higher in those living in houses with unplaster walls (exposed brick) (OR 1.68; 95% CI 1.09-2.59) and where cats were present near the household (OR 2.00; 95% CI 1.03-3.88). Seropositivity to Icterohaemorrhagiae also increased with age in years (OR 1.02; 95% CI 1.01-1.03) but was higher in males (OR 1.51; 95% CI 1.09-2.10), in those with work-related exposures (OR 1.71; 95% CI 1.10-2.66) or who had contact with sewage (OR 1.42; 95% CI 1.00-2.03). Spatial analysis showed differences in distribution of seropositivity to serogroups Icterohaemorrhagiae and Cynopteri within the five districts where study communities were situated. Conclusions/Significance: Our data suggests distinct epidemiological patterns associated with serogroups Icterohaemorrhagiae and Cynopteri within the high-risk urban environment for leptospirosis and with differences of spatial niches. Future studies must identify the different pathogenic serogroups circulating in low-income areas, and further evaluate the potential role of cats in the transmission of the serogroup Cynopteri in urban settings.

Structural factors associated with SARS-CoV-2 infection risk in an urban slum setting in Salvador, Brazil: A cross-sectional survey.

BACKGROUND: The structural environment of urban slums, including physical, demographic, and socioeconomic attributes, renders inhabitants more vulnerable to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Yet, little is known about the specific determinants that contribute to high transmission within these communities. We therefore aimed to investigate SARS-CoV-2 seroprevalence in an urban slum in Brazil. METHODS AND FINDINGS: We performed a cross-sectional serosurvey of an established cohort of 2,041 urban slum residents from the city of Salvador, Brazil between November 2020 and February 2021, following the first Coronavirus Disease 2019 (COVID-19) pandemic wave in the country and during the onset of the second wave. The median age in this population was 29 years (interquartile range [IQR] 16 to 44); most participants reported their ethnicity as Black (51.5%) or Brown (41.7%), and 58.5% were female. The median size of participating households was 3 (IQR 2 to 4), with a median daily per capita income of 2.32 (IQR 0.33-5.15) US Dollars. The main outcome measure was presence of IgG against the SARS-CoV-2 spike protein. We implemented multilevel models with random intercepts for each household to estimate seroprevalence and associated risk factors, adjusting for the sensitivity and specificity of the assay, and the age and gender distribution of our study population. We identified high seroprevalence (47.9%, 95% confidence interval [CI] 44.2% to 52.1%), particularly among female residents (50.3% [95% CI 46.3% to 54.8%] versus 44.6% [95% CI 40.1% to 49.4%] among male residents, p < 0.01) and among children (54.4% [95% CI 49.6% to 59.3%] versus 45.4% [95% CI 41.5% to 49.7%] among adults, p < 0.01). Adults residing in households with children were more likely to be seropositive (48.6% [95% CI 44.8% to 52.3%] versus 40.7% [95% CI 37.2% to 44.3%], p < 0.01). Women who were unemployed and living below the poverty threshold (daily per capita household income <$1.25) were more likely to be seropositive compared to men with the same employment and income status (53.9% [95% CI 47.0% to 60.6%] versus 32.9% [95% CI 23.2% to 44.3%], p < 0.01). Participation in the study was voluntary, which may limit the generalizability of our findings. CONCLUSIONS: Prior to the peak of the second wave of the COVID-19 pandemic, cumulative incidence as assessed by serology approached 50% in a Brazilian urban slum population. In contrast to observations from industrialized countries, SARS-CoV-2 incidence was highest among children, as well as women living in extreme poverty. These findings emphasize the need for targeted interventions that provide safe environments for children and mitigate the structural risks posed by crowding and poverty for the most vulnerable residents of urban slum communities.

Linking rattiness, geography and environmental degradation to spillover Leptospira infections in marginalised urban settings: An eco-epidemiological community-based cohort study in Brazil.

Background: Zoonotic spillover from animal reservoirs is responsible for a significant global public health burden, but the processes that promote spillover events are poorly understood in complex urban settings. Endemic transmission of Leptospira, the agent of leptospirosis, in marginalised urban communities occurs through human exposure to an environment contaminated by bacteria shed in the urine of the rat reservoir. However, it is unclear to what extent transmission is driven by variation in the distribution of rats or by the dispersal of bacteria in rainwater runoff and overflow from open sewer systems. Methods: We conducted an eco-epidemiological study in a high-risk community in Salvador, Brazil, by prospectively following a cohort of 1401 residents to ascertain serological evidence for leptospiral infections. A concurrent rat ecology study was used to collect information on the fine-scale spatial distribution of 'rattiness', our proxy for rat abundance and exposure of interest. We developed and applied a novel geostatistical framework for joint spatial modelling of multiple indices of disease reservoir abundance and human infection risk. Results: The estimated infection rate was 51.4 (95%CI 40.4, 64.2) infections per 1000 follow-up events. Infection risk increased with age until 30 years of age and was associated with male gender. Rattiness was positively associated with infection risk for residents across the entire study area, but this effect was stronger in higher elevation areas (OR 3.27 95% CI 1.68, 19.07) than in lower elevation areas (OR 1.14 95% CI 1.05, 1.53). Conclusions: These findings suggest that, while frequent flooding events may disperse bacteria in regions of low elevation, environmental risk in higher elevation areas is more localised and directly driven by the distribution of local rat populations. The modelling framework developed may have broad applications in delineating complex animal-environment-human interactions during zoonotic spillover and identifying opportunities for public health intervention. Funding: This work was supported by the Oswaldo Cruz Foundation and Secretariat of Health Surveillance, Brazilian Ministry of Health, the National Institutes of Health of the United States (grant numbers F31 AI114245, R01 AI052473, U01 AI088752, R01 TW009504 and R25 TW009338); the Wellcome Trust (102330/Z/13/Z), and by the Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB/JCB0020/2016). MTE was supported by a Medical Research UK doctorate studentship. FBS participated in this study under a FAPESB doctorate scholarship.

Unequal burden of Zika-associated microcephaly among populations with public and private healthcare in Salvador, Brazil.

OBJECTIVES: To describe the differences in clinical presentation and relative disease burden of congenital Zika syndrome (CZS)-associated microcephaly at 2 large hospitals in Salvador, Brazil that serve patients of different socioeconomic status (SES). METHODS: Clinical and serologic data were collected prospectively from pregnant women and their infants, who delivered at 2 study centers during the 2015-2016 Zika virus (ZIKV) epidemic in Salvador, Brazil. RESULTS: Pregnant women from Salvador, Brazil delivering in a low SES hospital had 3 times higher ZIKV exposure rate than women at a high SES hospital. However, different SES hospitals had similar prevalence of infants with CZS-associated microcephaly (10% vs 6%, p = 0.16) after controlling for ZIKV exposure in their mothers. CONCLUSIONS: Our study supports the positive association between low SES, high maternal ZIKV exposure, and high rates of CZS-associated microcephaly.

Why is leptospirosis hard to avoid for the impoverished? Deconstructing leptospirosis transmission risk and the drivers of knowledge, attitudes, and practices in a disadvantaged community in Salvador, Brazil.

Several studies have identified socioeconomic and environmental risk factors for infectious disease, but the relationship between these and knowledge, attitudes, and practices (KAP), and more importantly their web of effects on individual infection risk, have not previously been evaluated. We conducted a cross-sectional KAP survey in an urban disadvantaged community in Salvador, Brazil, leveraging on simultaneously collected fine-scale environmental and epidemiological data on leptospirosis transmission. Residents' knowledge influenced their attitudes which influenced their practices. However, different KAP variables were driven by different socioeconomic and environmental factors; and while improved KAP variables reduced risk, there were additional effects of socioeconomic and environmental factors on risk. For example, males and those of lower socioeconomic status were at greater risk, but once we controlled for KAP, male gender and lower socioeconomic status themselves were not direct drivers of seropositivity. Employment was linked to better knowledge and a less contaminated environment, and hence lower risk, but being employed was independently associated with a higher, not lower risk of leptospirosis transmission, suggesting travel to work as a high risk activity. Our results show how such complex webs of influence can be disentangled. They indicate that public health messaging and interventions should take into account this complexity and prioritize factors that limit exposure and support appropriate prevention practices.

Genetic Evidence for a Potential Environmental Pathway to Spillover Infection of Rat-Borne Leptospirosis.

In this study, we genotyped samples from environmental reservoirs (surface water and soil), colonized rat specimens, and cases of human severe leptospirosis from an endemic urban slum in Brazil, to determine the molecular epidemiology of pathogenic Leptospira and identify pathways of leptospirosis infection. We identified a well-established population of Leptospira interrogans serovar Copenhageni common to human leptospirosis cases, and animal and environmental reservoirs. This finding provides genetic evidence for a potential environmental spillover pathway for rat-borne leptospirosis through the environment in this urban community and highlights the importance of environmental and social interventions to reduce spillover infections.

Effect of Sewerage on the Contamination of Soil with Pathogenic Leptospira in Urban Slums.

Leptospirosis is an environmentally transmitted zoonotic disease caused by pathogenic Leptospira spp. that affects poor communities worldwide. In urban slums, leptospirosis is associated with deficient sanitary infrastructure. Yet, the role of sewerage in the reduction of the environmental contamination with pathogenic Leptospira has not been explored. Here, we conducted a survey of the pathogen in soils surrounding open and closed sewer sections in six urban slums in Brazil. We found that soils surrounding conventionally closed sewers (governmental interventions) were 3 times less likely to contain pathogenic Leptospira (inverse OR 3.44, 95% CI = 1.66-8.33; p < 0.001) and contained a 6 times lower load of the pathogen (0.82 log10 units difference, p < 0.01) when compared to their open counterparts. However, no differences were observed in community-closed sewers (poor-quality closings performed by the slum dwellers). Human fecal markers (BacHum) were positively associated with pathogenic Leptospira even in closed sewers, and rat presence was not predictive of the presence of the pathogen in soils, suggesting that site-specific rodent control may not be sufficient to reduce the environmental contamination with Leptospira. Overall, our results indicate that sewerage expansion to urban slums may help reduce the environmental contamination with the pathogen and therefore reduce the risk of human leptospirosis.

Heterogeneous development of children with Congenital Zika Syndrome-associated microcephaly.

OBJECTIVE: To describe the neurological and neurodevelopmental outcomes of children with Congenital Zika Syndrome (CZS) associated microcephaly beyond 2 years of age. METHOD: We followed children with CZS-associated microcephaly in an outpatient clinic in Salvador, Brazil. Neurological and neurodevelopmental assessments were performed using the Hammersmith Infant Neurological Examination (HINE) and Bayley Scales of Infant and Toddler Neurodevelopment (Bayley-III) respectively. RESULTS: Of the 42 children included, 19 were male (45.2%); median (interquartile range) age at neurological evaluation was 28 (25-32) months, and 36 (85.7%) had severe microcephaly. HINE and Bayley-III results were completed for 35/42 (83.3%) and 33/42 (78.5%) children respectively. Bayley-III identified a severe developmental delay in 32/33 (97.0%) children while 1/33 (3.0%) had only a mild delay. In the multivariable analysis, we found that Bayley-III and HINE scores were correlated. Better HINE scores were associated with higher Bayley-III cognitive raw scores (ß = 0.29; CI 95% = 0.02-0.57) and motor raw scores (ß = 0.43; CI 95% = 0.04-0.82) after adjusting for head circumference, prematurity, and age at neurodevelopmental evaluation. Furthermore, we found that greater head circumference at follow up was associated with higher cognitive (ß = 1.27; CI 95% = 0.01-2.53) and motor raw scores (ß = 2.03; CI 95% = 0.25-3.81). CONCLUSION: Children with CZS-associated microcephaly demonstrate severe neurodevelopmental delays and slower growth rates than their peers over time. Still, they have remarkably heterogeneous neurodevelopmental profiles according to neurological exam scores which correlate with their long-term outcomes. We found that HINE scores effectively captured the heterogeneity of neurological capabilities among these children and could be predictive of cognitive and motor development progress.

Social determinants associated with Zika virus infection in pregnant women.

This study aims to describe the sociodemographic determinants associated with exposure to Zika Virus (ZIKV) in pregnant women during the 2015-2016 epidemic in Salvador, Brazil. METHODS: We recruited women who gave birth between October 2015 and January 2016 to a cross-sectional study at a referral maternity hospital in Salvador, Brazil. We collected information on their demographic, socioeconomic, and clinical characteristics, and evaluated their ZIKV exposure using a plaque reduction neutralization test. Logistic regression was then used to assess the relationship between these social determinants and ZIKV exposure status. RESULTS: We included 469 pregnant women, of whom 61% had a positive ZIKV result. Multivariate analysis found that lower education (adjusted Prevalence Rate [aPR] 1.21; 95%CI 1.04-1.35) and food insecurity (aPR 1.17; 95%CI 1.01-1.30) were positively associated with ZIKV exposure. Additionally, age was negatively associated with the infection risk (aPR 0.99; 95%CI 0.97-0.998). CONCLUSION: Eve after controlling for age, differences in key social determinants, as education and food security, were associated with the risk of ZIKV infection among pregnant women in Brazil. Our findings elucidate risk factors that can be targeted by future interventions to reduce the impact of ZIKV infection in this vulnerable population.

Poverty, sanitation, and Leptospira transmission pathways in residents from four Brazilian slums.

Residents of urban slums suffer from a high burden of zoonotic diseases due to individual, socioeconomic, and environmental factors. We conducted a cross-sectional sero-survey in four urban slums in Salvador, Brazil, to characterize how poverty and sanitation contribute to the transmission of rat-borne leptospirosis. Sero-prevalence in the 1,318 participants ranged between 10.0 and 13.3%. We found that contact with environmental sources of contamination, rather than presence of rat reservoirs, is what leads to higher risk for residents living in areas with inadequate sanitation. Further, poorer residents may be exposed away from the household, and ongoing governmental interventions were not associated with lower transmission risk. Residents at higher risk were aware of their vulnerability, and their efforts improved the physical environment near their household, but did not reduce their infection chances. This study highlights the importance of understanding the socioeconomic and environmental determinants of risk, which ought to guide intervention efforts.

Effects of Accounting for Interval-Censored Antibody Titer Decay on Seroincidence in a Longitudinal Cohort Study of Leptospirosis.

Accurate measurements of seroincidence are critical for infections undercounted by reported cases, such as influenza, arboviral diseases, and leptospirosis. However, conventional methods of interpreting paired serological samples do not account for antibody titer decay, resulting in underestimated seroincidence rates. To improve interpretation of paired sera, we modeled exponential decay of interval-censored microscopic agglutination test titers using a historical data set of leptospirosis cases traced to a point source exposure in Italy in 1984. We then applied that decay rate to a longitudinal cohort study conducted in a high-transmission setting in Salvador, Brazil (2013-2015). We estimated a decay constant of 0.926 (95% confidence interval: 0.918, 0.934) titer dilutions per month. Accounting for decay in the cohort increased the mean infection rate to 1.21 times the conventionally defined rate over 6-month intervals (range, 1.10-1.36) and 1.82 times that rate over 12-month intervals (range, 1.65-2.07). Improved estimates of infection in longitudinal data have broad epidemiologic implications, including comparing studies with different sampling intervals, improving sample size estimation, and determining risk factors for infection and the role of acquired immunity. Our method of estimating and accounting for titer decay is generalizable to other infections defined using interval-censored serological assays.

Relationship between Physicochemical Characteristics and Pathogenic Leptospira in Urban Slum Waters.

Leptospirosis, a zoonosis caused by pathogenic Leptospira, primarily affects tropical, developing regions, especially communities without adequate sanitation. Outbreaks of leptospirosis have been linked with the presence of pathogenic Leptospira in water. In this study, we measured the physicochemical characteristics (temperature, pH, salinity, turbidity, electrical conductivity, and total dissolved solids (TDS)) of surface waters from an urban slum in Salvador, Brazil, and analyzed their associations with the presence and concentration of pathogenic Leptospira reported previously. We built logistic and linear regression models to determine the strength of association between physicochemical parameters and the presence and concentration of Leptospira. We found that salinity, TDS, pH, and type of water were strongly associated with the presence of Leptospira. In contrast, only pH was associated with the concentration of the pathogen in water. The study of physico-chemical markers can contribute to a better understanding of the occurrence of Leptospira in water and to the identification of sources of risk in urban slum environments.

Influence of Rainfall on Leptospira Infection and Disease in a Tropical Urban Setting, Brazil.

The incidence of hospitalized leptospirosis patients was positively associated with increased precipitation in Salvador, Brazil. However, Leptospira infection risk among a cohort of city residents was inversely associated with rainfall. These findings indicate that, although heavy rainfall may increase severe illness, Leptospira exposures can occur year-round.