Recurrent Potent Human Neutralizing Antibodies to Zika Virus in Brazil and Mexico.

Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with pre-existing reactivity to DENV1 in humans.

Rickettsial Infections Causing Acute Febrile Illness in Urban Slums, Brazil.

We conducted enhanced acute febrile illness surveillance in an urban slum community in Salvador, Brazil. We found that rickettsial infection accounted for 3.5% of urgent care visits for acute fever. Our results suggest that rickettsiae might be an underrecognized, treatable cause of acute febrile illness in impoverished urban populations in Brazil.

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.

Risk of Sexually Transmitted Zika Virus in a Cohort of Economically Disadvantaged Urban Residents.

To understand the disease burden of sexually transmitted Zika virus (ZIKV), we prospectively followed a cohort of 359 adult and adolescent residents of an urban community in Salvador, Brazil, through the 2015 ZIKV epidemic. Later, in 2017, we used a retrospective survey to associate sexual behavior during the epidemic with ZIKV infection as defined by immunoglobulin G3 NS1 enzyme-linked immunosorbent assay. We found that males who engaged in casual sexual encounters during the epidemic were more likely (adjusted odds ratio, 6.2 [95% confidence interval, 1.2-64.1]) to be ZIKV positive, suggesting that specific groups may be at increased risk of sexually transmitted infections.

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.

Transmission of Chikungunya Virus in an Urban Slum, Brazil.

After a chikungunya outbreak in Salvador, Brazil, we performed a cross-sectional, community-based study of 1,776 inhabitants to determine chikungunya virus (CHIKV) seroprevalence, identify factors associated with exposure, and estimate the symptomatic infection rate. From November 2016 through February 2017, we collected sociodemographic and clinical data by interview and tested serum samples for CHIKV IgG. CHIKV seroprevalence was 11.8% (95% CI 9.8%-13.7%), and 15.3% of seropositive persons reported an episode of fever and arthralgia. Infections were independently and positively associated with residences served by unpaved streets, a presumptive clinical diagnosis of chikungunya, and recall of an episode of fever with arthralgia in 2015-2016. Our findings indicate that the chikungunya outbreak in Salvador may not have conferred sufficient herd immunity to preclude epidemics in the near future. The unusually low frequency of symptomatic disease points to a need for further longitudinal studies to better investigate these findings.

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.

Correction: Cathelicidin Insufficiency in Patients with Fatal Leptospirosis.

[This corrects the article DOI: 10.1371/journal.ppat.1005943.].

Cathelicidin Insufficiency in Patients with Fatal Leptospirosis.

Leptospirosis causes significant morbidity and mortality worldwide; however, the role of the host immune response in disease progression and high case fatality (>10-50%) is poorly understood. We conducted a multi-parameter investigation of patients with acute leptospirosis to identify mechanisms associated with case fatality. Whole blood transcriptional profiling of 16 hospitalized Brazilian patients with acute leptospirosis (13 survivors, 3 deceased) revealed fatal cases had lower expression of the antimicrobial peptide, cathelicidin, and chemokines, but more abundant pro-inflammatory cytokine receptors. In contrast, survivors generated strong adaptive immune signatures, including transcripts relevant to antigen presentation and immunoglobulin production. In an independent cohort (23 survivors, 22 deceased), fatal cases had higher bacterial loads (P = 0.0004) and lower anti-Leptospira antibody titers (P = 0.02) at the time of hospitalization, independent of the duration of illness. Low serum cathelicidin and RANTES levels during acute illness were independent risk factors for higher bacterial loads (P = 0.005) and death (P = 0.04), respectively. To investigate the mechanism of cathelicidin in patients surviving acute disease, we administered LL-37, the active peptide of cathelicidin, in a hamster model of lethal leptospirosis and found it significantly decreased bacterial loads and increased survival. Our findings indicate that the host immune response plays a central role in severe leptospirosis disease progression. While drawn from a limited study size, significant conclusions include that poor clinical outcomes are associated with high systemic bacterial loads, and a decreased antibody response. Furthermore, our data identified a key role for the antimicrobial peptide, cathelicidin, in mounting an effective bactericidal response against the pathogen, which represents a valuable new therapeutic approach for leptospirosis.

Overestimation of Severe Acute Respiratory Syndrome Coronavirus 2 Household Transmission in Settings of High Community Transmission: Insights From an Informal Settlement Community in Salvador, Brazil.

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.

Extensive transmission of SARS-CoV-2 BQ.1* variant in a population with high levels of hybrid immunity: A prevalence survey.

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.

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.

Social determinants of adult COVID-19 vaccine acceptance and uptake in a Brazilian urban informal community: a longitudinal time-to-event study.

Residents of informal urban settlements have a high risk of COVID-19 exposure and have less access to medical care, making vaccine-driven prevention critical in this vulnerable population. Despite robust vaccination campaigns in Brazil, vaccine uptake and timing continue to be influenced by social factors and contribute to health disparities. To address this, we conducted a sequential survey in a cohort of 717 adults in an urban favela in Salvador, Brazil where participants were interviewed in 2020, before vaccines were rolled out, and in 2022, after primary and booster dose distribution. We collected data on demographics, social characteristics, and COVID-19 vaccination status and intent. Primary series uptake was high (91.10% for 1 st dose and 94.74% for 2 nd dose among eligible); however, booster uptake was lower (63.51% of eligible population) at the time of the second interview, suggesting a decreasing interest in vaccination. To account for both vaccine refusal and delays, we conducted a Cox time-to-event analysis of dose uptake using sequential independent outcomes. Exposure times were determined by dose eligibility date to account for age and comorbidities. Intent to vaccinate in 2020 (hazard ratio [HR]: 1.54, CI: [1.05, 1.98]) and age (HR: 1.27, CI: [1.01, 2.08]) were associated with higher vaccination rates for the 1 st dose. Males were less likely to receive the 1 st dose (HR: 0.61, CI: [0.35, 0.83]), and, compared to catholics, 2 nd dose uptake was lower for those identifying with Pentecostalism (HR: 0.49, CI: [0.37, 0.66]) and without a religion (HR: 0.49, CI: [0.37, 0.66]), with the latter association disappearing after controlling by age. Risk perception was associated with 2 nd dose uptake (HR: 1.15, CI: [1.08, 1.26]). The role of sex and religion in vaccination behavior highlights the need for targeted outreach and interfacing with local organizations. The data offers lessons to build a long-term COVID-19 vaccination strategy beyond availability.

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.

Predictors of Neurodevelopment in Microcephaly Associated with Congenital Zika Syndrome: A Prospective Study.

The municipality of Salvador, situated in Brazil, distinguished itself as the epicenter of the emergence of microcephaly related to congenital manifestations of Zika syndrome. Despite the anticipated significant developmental setbacks in these children, research has indicated a varied range of outcomes, with certain instances even reflecting minimal developmental delay. Our objective was to pinpoint determinants that could forecast developmental anomalies in children diagnosed with microcephaly associated with congenital Zika syndrome (CZS). METHODOLOGY: A forward-looking clinical and neurodevelopmental examination was conducted focusing on neonates diagnosed with microcephaly with CZS, birthed between September 2015 and April 2016 at the Hospital Geral Roberto Santos, in Salvador city. That infants were monitored up to their third year by a multiprofessional team. Child development was assessed using the composite Bayley III score. Undertaken by two blinded experts, cranial CT scan analysis was performed during the neonate period for the detection of brain abnormalities and to quantify ventricle enlargement, measured by Evans' index (EI). RESULTS: Fifty newborns were evaluated with a median head circumference of 28 cm (interquartile range 27-31 cm). EI was associated with neurodevelopmental delay at three years and remained significant after adjustment for head circumference. A 0.1-point increase in EI was associated with a delay of 3.2 months in the receptive language (p = 0.016), 3.4 months in the expressive language (p = 0.016), 3.4 months in the cognitive (p = 0.016), 2.37 months in the gross motor (p = 0.026), and 3.1 months in the fine motor (p = 0.021) domains. CONCLUSIONS: EI predicted neurodevelopmental delay in all Bayley domains in children with microcephaly associated with CZS.

Biannual and Quarterly Comparison Analysis of Agglutinating Antibody Kinetics on a Subcohort of Individuals Exposed to Leptospira interrogans in Salvador, Brazil.

Introduction: Leptospirosis is a zoonosis with a worldwide spread that leads to clinical manifestations ranging from asymptomatic infection to a life-threatening disease. The immune response is predominantly humoral mediated limited to the infecting serovar. Individuals living in an area endemic for leptospirosis are often exposed to an environment contaminated with leptospires and there is a paucity of information on naturally acquired immunity. In the present study, we evaluated the kinetics of agglutinating antibodies in individuals from an endemic area for leptospirosis in Salvador, Brazil comparing two different intersample collection times. Methods: Between 2017-2018, we carried out a biannual prospective cohort with 2,086 individuals living in an endemic area for leptospirosis in Salvador, Brazil. To compare agglutinating antibody kinetics using microscopic agglutination test (MAT) with different collection times, a subcohort of 72 individuals with quarterly follow-up was carried out in parallel. Results: The results revealed that using a shorter time for intersample collection led to the detection of a higher number of infections and reinfection events. Furthermore, we observed a higher rate of titer decay indicating partial and short protection. However, there was no indication of major changes in risk factors for the disease. Conclusions: We evaluated antibody kinetics among residents of an endemic area for leptospirosis comparing two sample collection times. The constant exposure to the contaminated environment increases the risk for leptospirosis infection with reinfection events being more common than expected. This indicates that the burden of leptospirosis might be underestimated by serological surveys, and further studies are necessary to better characterize the humoral response after infection.

Reliable estimation of SARS-CoV-2 anti-spike protein IgG titers from single dilution optical density values in serologic surveys.

Reliable and scalable seroepidemiology methods are needed to estimate SARS-CoV-2 incidence and monitor the dynamics of population-level immunity as the pandemic evolves. We aimed to evaluate the reliability of SARS-CoV-2 normalized ELISA optical density (nOD) at a single dilution compared to titers derived from serial dilutions. We conducted serial serosurveys within a community-based cohort in Salvador, Brazil. Anti-S IgG ELISA (Euroimmun AG) was performed with 5 serial 3-fold dilutions of paired sera from 54 participants. Changes in nOD reliably predicted increases and decreases in titers (98.1% agreement, κ = 95.8%). Fitting the relationship between nOD and interpolated titers to a log-log curve yields highly accurate predictions of titers (r2 = 0.995) and changes in titers (r2 = 0.975), using only 1 to 2 dilutions. This approach can significantly reduce the time, labor and resources needed for large-scale serosurveys to ascertain population-level changes in exposure and immunity.

Rainfall and other meteorological factors as drivers of urban transmission of leptospirosis.

BACKGROUND: Leptospirosis is an important public health problem affecting vulnerable urban slum populations in developing country settings. However, the complex interaction of meteorological factors driving the temporal trends of leptospirosis remain incompletely understood. METHODS AND FINDINGS: From March 1996-March 2010, we investigated the association between the weekly incidence of leptospirosis and meteorological anomalies in the city of Salvador, Brazil by using a dynamic generalized linear model that accounted for time lags, overall trend, and seasonal variation. Our model showed an increase of leptospirosis cases associated with higher than expected rainfall, lower than expected temperature and higher than expected humidity. There was a lag of one-to-two weeks between weekly values for significant meteorological variables and leptospirosis incidence. Independent of the season, a weekly cumulative rainfall anomaly of 20 mm increased the risk of leptospirosis by 12% compared to a week following the expected seasonal pattern. Finally, over the 14-year study period, the annual incidence of leptospirosis decreased significantly by a factor of 2.7 (8.3 versus 3.0 per 100,000 people), independently of variations in climate. CONCLUSIONS: Strategies to control leptospirosis should focus on avoiding contact with contaminated sources of Leptospira as well as on increasing awareness in the population and health professionals within the short time window after low-level or extreme high-level rainfall events. Increased leptospirosis incidence was restricted to one-to-two weeks after those events suggesting that infectious Leptospira survival may be limited to short time intervals.

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.