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.

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.

Bartonella in Norway rats (Rattus norvegicus) from the urban slum environment in Brazil.

Bartonella are rodent-borne bacteria that cause varied human etiologies. Studies on synanthropic rodents are rare, causing gaps in epidemiological knowledge. We tested bloodclot samples from 79 rats from an urban slum in Salvador, Brazil through PCR targeting gltA gene. Nine samples (11.4%) were positive: six had 100% identity with Bartonella sp. isolate JF429580 and 99.5% with B. queenslandensis strain AUST/NH8; three were 100% identical to isolate JF429532 and 99.7% to B. tribocorum. This is the second report on urban rat Bartonella indicating bacterial circulation at detectable rates. Its presence in rats from vulnerable human settlements demands public health attention.

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.

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.

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.

A Systematic Review of the geographic distribution of pathogenic Leptospira serovars in the Americas, 1930-2017.

Leptospirosis is an important public health problem caused by Leptospira. The objective is to characterize the geographic distribution of pathogenic leptospira serovars in the Americas through a systematic review of the literature between 1930-2017. Searches were conducted in six scientific databases (PubMed, Web of Science, Embase, Lilacs, Scopus and Cochrane). We included studies conducted unambiguously in the Americas, that investigated infection of Leptospira in humans and animals in their natural environments with serovar identification. 283 articles were included, of which 69 were studies in humans, 86 in wild animals, and 182 in domestic animals. Most of them conducted in Brazil (104, 36.7%) and in rural environments (158, 55.8%). Bovines, equines and dogs where the most frequently studied domestic species. However, a large diversity including 80 species of wild animals were studied. Icterohaemorrhgiae, Canicola, Pomona and Grippotyphosa were the most common serovars, described in 46 (16.2%), 38 (13.3%), 32 (11.3%) and 26 (9%) of the articles, respectively. The Results indicate a large concentration of studies in Latin America, with emphasis on Brazil, in wild mammals and three main domestic animal groups. Our results emphasize the need for studies that delve into the relationships of the epidemiological cycle, environment, and health.

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.

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.

Angiostrongylus cantonensis in urban populations of terrestrial gastropods and rats in an impoverished region of Brazil.

The nematode Angiostrongylus cantonensis is the most common cause of neuroangiostrongyliasis (manifested as eosinophilic meningitis) in humans. Gastropod molluscs are used as intermediate hosts and rats of various species are definitive hosts of this parasite. In this study, we identified several environmental factors associated with the presence and abundance of terrestrial gastropods in an impoverished urban region in Brazil. We also found that body condition, age and presence of co-infection with other parasite species in urban Rattus norvegicus, as well as environmental factors were associated with the probability and intensity of A. cantonensis infection. The study area was also found to have a moderate prevalence of the nematode in rodents (33% of 168 individuals). Eight species of molluscs (577 individuals) were identified, four of which were positive for A. cantonensis. Our study indicates that the environmental conditions of poor urban areas (presence of running and standing water, sewage, humidity and accumulated rain and accumulation of construction materials) influenced both the distribution and abundance of terrestrial gastropods, as well as infected rats, contributing to the maintenance of the A. cantonensis transmission cycle in the area. Besides neuroangiostrongyliasis, the presence of these hosts may also contribute to susceptibility to other zoonoses.

Effectiveness of a dance-physiotherapy combined intervention in Parkinson's disease: a randomized controlled pilot trial.

BACKGROUND: Physical therapies have been recommended as crucial components in Parkinson's disease (PD) rehabilitation. OBJECTIVE: The study aims to examine the effectiveness of a new dance-physiotherapy combined intervention, called DArT method, in mild PD patients. METHODS: A prospective, randomized, single-blind, controlled pilot trial was conducted on 38 mild PD patients under dopaminergic therapy. The intervention consisted in an add-on protocol: the control group received 1 h of conventional physiotherapy followed by 1 h of conventional physiotherapy each day, 3 times a week, for 5 weeks. The experimental group received 1 h of conventional physiotherapy followed by 1 h of dance class each day, 3 times a week, for 5 weeks. The week before and after the training period, patients were assessed for motor, cognitive, emotional, and sensory components of PD, with MDS-UPDRS-III as primary outcome measure. RESULTS: DArT method was associated with a 2.72-point reduction in the post-treatment MDS-UPDRS-III total score compared to control group (95% CI - 5.28, - 0.16, p = 0.038, d = 0.71), and with a 2.16-point reduction in the post-treatment MDS-UPDRS-III upper body subscore (95% CI - 3.56, - 0.76, p = 0.003, d = 1.02). Conversely, conventional physiotherapy program was associated with a 2.95-point reduction in the post-treatment trait anxiety compared to the experimental group (95% CI 0.19, 5.71, p = 0.037, d = 0.70). Withdrawal and fall rates were equal to 0% in both groups. CONCLUSION: DArT method showed to be safe, well accepted, and more effective than an intensive program of conventional physiotherapy in improving motor impairment in mild PD.

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.

Leptospira yasudae sp. nov. and Leptospira stimsonii sp. nov., two new species of the pathogenic group isolated from environmental sources.

Four spirochetes (F1T, B21, YaleT and AMB6-RJ) were isolated from environmental sources: F1T and B21 from soils of an urban slum community in Salvador (Brazil), YaleT from river water in New Haven, Connecticut (USA) and AMB6-RJ from a pond in a horse farm in Rio de Janeiro (Brazil). Isolates were helix-shaped, aerobic, highly motile and non-virulent in a hamster model of infection. Draft genomes of the strains were obtained and analysed to determine the relatedness to other species of the genus Leptospira. The analysis of 498 core genes showed that strains F1T/B21 and YaleT/AMB6-RJ formed two distinct phylogenetic clades within the 'Pathogens' group (group I). The average nucleotide identity (ANI) values of strains F1T/B21 and YaleT/AMB6-RJ to other previously described Leptospira species were below <84 % and <82 %, respectively, which confirmed that these isolates should be classified as representatives of two novel species. Therefore, we propose Leptospirayasudae sp. nov. and Leptospirastimsonii sp. nov. as new species in the genus Leptospira. The type strains are F1T (=ATCC-TSD-163=KIT0259=CLEP00287) and YaleT (=ATCC-TDS-162=KIT0258=CLEP00288), respectively.

COVID-19: urgent actions, critical reflections and future relevance of 'WaSH': lessons for the current and future pandemics.

The COVID-19 pandemic placed hygiene at the centre of disease prevention. Yet, access to the levels of water supply that support good hand hygiene and institutional cleaning, our understanding of hygiene behaviours, and access to soap are deficient in low-, middle- and high-income countries. This paper reviews the role of water, sanitation and hygiene (WaSH) in disease emergence, previous outbreaks, combatting COVID-19 and in preparing for future pandemics. We consider settings where these factors are particularly important and identify key preventive contributions to disease control and gaps in the evidence base. Urgent substantial action is required to remedy deficiencies in WaSH, particularly the provision of reliable, continuous piped water on-premises for all households and settings. Hygiene promotion programmes, underpinned by behavioural science, must be adapted to high-risk populations (such as the elderly and marginalised) and settings (such as healthcare facilities, transport hubs and workplaces). WaSH must be better integrated into preparation plans and with other sectors in prevention efforts. More finance and better use of financing instruments would extend and improve WaSH services. The lessons outlined justify no-regrets investment by government in response to and recovery from the current pandemic; to improve day-to-day lives and as preparedness for future pandemics.

Worldwide overview of human infections with Hymenolepis diminuta.

Hymenolepis diminuta is a zoonotic cestode parasitizing the small intestine of rodents (definitive hosts). Humans can accidentally enter into the life cycle of this tapeworm via the ingestion of infected insects (intermediate hosts) containing cestode cysticercoids in their body cavity. More than two centuries after the first record in humans, there are no accurate estimates of the number of human cases around the world. In order to have a more precise idea about the number of human cases with H. diminuta and the current status of the disease (hymenolepiasis) worldwide, we conducted a literature review of published records on human infection with H. diminuta. One thousand five hundred and sixty-one published records of infection with H. diminuta from 80 countries were identified. This review presents an estimate of the number of human cases with H. diminuta and a current overview of the prevalence, geographic distribution, symptoms, diagnosis, exposure to infective stages, and therapeutic approaches for this underestimated zoonotic tapeworm.

A systematic literature review of leptospirosis outbreaks worldwide, 1970-2012.

OBJECTIVE: This review describes the geographic and temporal distribution of, detection methods for, and other epidemiological features of published leptospirosis outbreaks, with the aim of informing efforts to standardize outbreak-reporting practices. METHODS: We conducted a systematic review of leptospirosis outbreaks reported in the scientific literature and ProMED during 1970-2012. Predefined criteria were used to identify and classify outbreaks and a standard form was used to extract information. RESULTS: During 1970-2012, we identified 318 outbreaks (average: 7 outbreaks/year; range: 1-19). Most outbreaks were reported in the Latin America and the Caribbean region (36%), followed by Southern Asia (13%), and North America (11%). Most outbreaks were located in tropical and subtropical ecoregions (55%). Quality classification showed that there was clear description of laboratory-confirmed cases in 40% of outbreaks. Among those, the average outbreak size was 82 cases overall (range: 2-2 259) but reached 253 cases in tropical/subtropical ecoregions. Common risk factors included outdoor work activities (25%), exposure to floodwaters (23%), and recreational exposure to water (22%). Epidemiologic investigation was conducted in 80% of outbreaks, mainly as case interviews. Case fatality was 5% overall (range: 0%-60%). CONCLUSIONS: Outbreak reporting increased over the study period with outbreaks covering tropical and non-tropical regions. Outbreaks varied by size, setting, and risk factors; however, data reviewed often had limited information regarding diagnosis and epidemiology. Guidelines are recommended to develop standardized procedures for diagnostic and epidemiological investigations during an outbreak and for reporting.

OBJETIVO: Describir la distribución geográfica y temporal, los métodos de detección y otras características epidemiológicas de los brotes de leptospirosis publicados con el fin de fundamentar los esfuerzos tendientes a estandarizar las prácticas empleadas en la notificación de brotes. MÉTODOS: Se llevó a cabo una revisión sistemática de los brotes de leptospirosis notificados en la bibliografía científica y en ProMED entre 1970 y 2012. Se utilizaron criterios predefinidos para identificar y clasificar los brotes y se empleó un formulario estándar para extraer la información. RESULTADOS: Entre 1970 y 2012 se identificaron 318 brotes (promedio: 7 brotes/año; rango: 1-19), la mayoría de ellos en América Latina y el Caribe (36%), región seguida por Asia meridional (13%) y América del Norte (11%). La mayoría de los brotes se localizaron en ecorregiones tropicales y subtropicales (55%). La clasificación cualitativa reveló que en el 40% de los brotes había una clara descripción de los casos confirmados por laboratorio. Entre ellos, el tamaño promedio del brote fue de 82 casos (rango: 2-2259 casos) pero alcanzó los 253 casos en ecorregiones tropicales o subtropicales. Entre los factores de riesgo frecuentes figuraban las actividades laborales al aire libre (25%), la exposición a agua proveniente de inundaciones (23%) y la exposición a agua con fines recreativos (22%). En el 80% de los brotes se realizaron investigaciones epidemiológicas, principalmente entrevistas de casos. La mortalidad específica de los casos fue del 5% (rango: 0%-60%). CONCLUSIONES: La notificación de brotes aumentó durante el período de estudio, y los brotes abarcaron regiones tropicales y no tropicales. Los brotes fueron diferentes en cuanto a su tamaño, el entorno y los factores de riesgo; sin embargo, los datos examinados con frecuencia incluían una información limitada respecto del diagnóstico y la epidemiología. Se recomiendan directrices para elaborar procedimientos estandarizados para las investigaciones diagnósticas y epidemiológicas durante un brote y para su notificación.

Urban rat races: spatial population genomics of brown rats (Rattus norvegicus) compared across multiple cities.

Urbanization often substantially influences animal movement and gene flow. However, few studies to date have examined gene flow of the same species across multiple cities. In this study, we examine brown rats (Rattus norvegicus) to test hypotheses about the repeatability of neutral evolution across four cities: Salvador, Brazil; New Orleans, USA; Vancouver, Canada; and New York City, USA. At least 150 rats were sampled from each city and genotyped for a minimum of 15 000 genome-wide single nucleotide polymorphisms. Levels of genome-wide diversity were similar across cities, but varied across neighbourhoods within cities. All four populations exhibited high spatial autocorrelation at the shortest distance classes (less than 500 m) owing to limited dispersal. Coancestry and evolutionary clustering analyses identified genetic discontinuities within each city that coincided with a resource desert in New York City, major waterways in New Orleans, and roads in Salvador and Vancouver. Such replicated studies are crucial to assessing the generality of predictions from urban evolution, and have practical applications for pest management and public health. Future studies should include a range of global cities in different biomes, incorporate multiple species, and examine the impact of specific characteristics of the built environment and human socioeconomics on gene flow.