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1.
Cell ; 169(4): 597-609.e11, 2017 May 04.
Article in English | MEDLINE | ID: mdl-28475892

ABSTRACT

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.


Subject(s)
Antibodies, Neutralizing/chemistry , Antibodies, Viral/chemistry , Zika Virus Infection/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , B-Lymphocytes/immunology , Brazil , Female , Humans , Immunologic Memory , Leukocytes, Mononuclear/immunology , Male , Mexico , Mice , Zika Virus Infection/blood
2.
An Acad Bras Cienc ; 95(suppl 2): e20220809, 2023.
Article in English | MEDLINE | ID: mdl-37909607

ABSTRACT

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.


Subject(s)
Bartonella , Humans , Rats , Animals , Bartonella/genetics , Disease Reservoirs , Brazil , Poverty Areas , Rodentia/microbiology
3.
J Infect Dis ; 225(1): 130-134, 2022 01 05.
Article in English | MEDLINE | ID: mdl-34139761

ABSTRACT

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.


Subject(s)
Environment , Leptospira/isolation & purification , Leptospirosis/epidemiology , Soil Microbiology , Water Microbiology , Amplified Fragment Length Polymorphism Analysis , Animals , Brazil/epidemiology , Humans , Leptospira/genetics , Leptospira interrogans/genetics , Leptospirosis/diagnosis , Molecular Epidemiology , Phylogeny , Rats , Sequence Analysis, DNA
4.
Emerg Infect Dis ; 28(10): 2132-2134, 2022 10.
Article in English | MEDLINE | ID: mdl-36148970

ABSTRACT

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.


Subject(s)
Rickettsia Infections , Rickettsia , Antibodies, Bacterial , Brazil/epidemiology , Fever/epidemiology , Humans , Poverty Areas , Rickettsia Infections/diagnosis , Rickettsia Infections/epidemiology
5.
PLoS Med ; 19(9): e1004093, 2022 09.
Article in English | MEDLINE | ID: mdl-36074784

ABSTRACT

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.


Subject(s)
COVID-19 , Adult , Brazil/epidemiology , COVID-19/epidemiology , Child , Cross-Sectional Studies , Female , Humans , Immunoglobulin G , Male , Pandemics , Poverty Areas , SARS-CoV-2 , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus
6.
J Infect Dis ; 224(5): 860-864, 2021 09 01.
Article in English | MEDLINE | ID: mdl-33395487

ABSTRACT

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.


Subject(s)
Poverty Areas , Sexual Behavior , Sexually Transmitted Diseases, Viral/epidemiology , Zika Virus Infection/epidemiology , Zika Virus/isolation & purification , Adolescent , Adult , Female , Humans , Male , Retrospective Studies , Urban Population
7.
Trop Med Int Health ; 26(3): 272-280, 2021 03.
Article in English | MEDLINE | ID: mdl-33190402

ABSTRACT

OBJECTIVE: We tested the hypothesis that Zika virus (ZIKV) immunity may protect against dengue virus (DENV) infection, disease severity or human amplification, based on analysis of epidemiological data from our long-term surveillance study (2009-2016) in the city of Salvador, Brazil, that indicated a substantial reduction in the frequency of laboratory-confirmed dengue cases following the Zika outbreak. To assess whether similar patterns were observed across the Americas, we did a broader explorative investigation of historical series (2004 to 2019) of suspected cases of dengue fever, covering 20 DENV-endemic South and Central American countries. METHODS: We used segmented linear regressions of single group interrupted time series (ITS) analysis to evaluate whether the Zika epidemic had a statistical effect on the trends of annual dengue incidence. RESULTS: We observed in our 16-year historical series that in all countries, the incidence of dengue exhibited periodic oscillations over time, with a general trend of statistically significant increase during the pre-Zika period overall and for 11 of the 20 countries. Following the peak of the first population exposure to ZIKV in the Americas, in 2016, the overall rate of reported dengue cases in 2017 and 2018 in the countries under study sharply dropped (P < 0.05) and was the lowest reported since 2005. Individually in each country, a statistically significant reduction in the annual dengue incidence beginning in 2016 or in 2017-2018 occurred in 13 of the 20 studied countries. However, in 2019, reports of suspected dengue cases increased across the Americas. In Brazil, Dominican Republic, Guatemala and Honduras, dengue incidence was >5 times higher in 2019 than in 2017 and 2018, and, in 2019, they had the greater dengue incidence than in all previous years throughout the historical series. CONCLUSIONS: The widespread decline in suspected dengue cases recorded in 2017 and 2018 lends further support to our previous epidemiological hypothesis of ZIKV-induced cross-species immunity to DENV. However, the cross-protection appears to be transient (around 2 years). Long-term, prospective follow-ups of dengue reports are needed to confirm (or refute) these findings, which could have significant public health implications, in particular regarding DENV vaccine development and application.


CONTEXTE: Nous avons émis l'hypothèse que l'immunité contre le virus Zika (ZIKV) pourrait protéger contre l'infection par le virus de la dengue (DENV), la sévérité de la maladie ou l'amplification humaine, sur la base de l'analyse des données épidémiologiques de notre étude de surveillance à long terme (2009-2016) dans la ville de Salvador, au Brésil, qui a indiqué une réduction substantielle de la fréquence des cas de dengue confirmés en laboratoire à la suite de l'épidémie de Zika. MÉTHODES: Pour évaluer si des tendances similaires ont été observées dans les Amériques, nous avons mené une enquête exploratoire plus large sur des séries historiques (2004 à 2019) de cas suspects de dengue, couvrant 20 pays d'Amérique du Sud et d'Amérique centrale endémiques pour DENV. Nous avons utilisé des régressions linéaires segmentées de l'analyse des séries chronologiques interrompues pour un seul groupe pour évaluer si l'épidémie de Zika avait un effet statistique sur les tendances de l'incidence annuelle de la dengue. RÉSULTATS: Nous avons observé dans notre série historique de 16 ans que dans tous les pays, l'incidence de la dengue présentait des oscillations périodiques au fil du temps, avec une tendance générale à une augmentation statistiquement significative pendant la période pré-Zika en général et pour 11 des 20 pays. Après le pic de la première exposition de la population au ZIKV dans les Amériques en 2016, le taux global des cas de dengue rapportés en 2017 et 2018 dans les pays étudiés a fortement diminué (p <0,05) et était le plus bas depuis 2005. Individuellement dans chaque pays, une réduction statistiquement significative de l'incidence annuelle de la dengue à partir de 2016 ou en 2017-2018 s'est produite dans 13 des 20 pays étudiés. Cependant, en 2019, les reports de cas suspects de dengue ont augmenté dans les Amériques. Dans des pays comme le Brésil, la République Dominicaine, le Guatemala et le Honduras, l'incidence de la dengue était >5 fois plus élevée en 2019 qu'en 2017 et 2018, et, en 2019, l'incidence de la dengue était plus élevée qu'au cours de toutes les années précédentes de la série historique. CONCLUSIONS: Le déclin généralisé des cas suspects de dengue enregistrés en 2017 et 2018 vient étayer notre hypothèse épidémiologique précédente de l'immunité inter-espèces induite par le ZIKV contre le DENV. Cependant, la protection croisée semble être transitoire (environ 2 ans). Des suivis prospectifs à long terme des reports sur la dengue sont nécessaires pour confirmer (ou réfuter) ces résultats, qui pourraient avoir des implications importantes pour la santé publique, en particulier en ce qui concerne le développement et l'application d'un vaccin DENV.


Subject(s)
Dengue/epidemiology , Zika Virus Infection/epidemiology , Central America/epidemiology , Chikungunya virus/immunology , Dengue/complications , Dengue Virus , Epidemics , Humans , Incidence , Linear Models , South America/epidemiology , Zika Virus , Zika Virus Infection/etiology
8.
Environ Sci Technol ; 55(23): 15882-15890, 2021 12 07.
Article in English | MEDLINE | ID: mdl-34767339

ABSTRACT

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.


Subject(s)
Leptospira , Leptospirosis , Animals , Brazil , Leptospirosis/epidemiology , Poverty Areas , Rats , Soil
9.
Parasitology ; 148(8): 994-1002, 2021 07.
Article in English | MEDLINE | ID: mdl-33843507

ABSTRACT

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.


Subject(s)
Angiostrongylus cantonensis/isolation & purification , Gastropoda/parasitology , Rats/parasitology , Rodent Diseases/parasitology , Strongylida Infections/veterinary , Animals , Brazil/epidemiology , Feces/parasitology , Female , Gastropoda/classification , Male , Mollusca/parasitology , Nervous System Diseases/epidemiology , Nervous System Diseases/parasitology , Nervous System Diseases/veterinary , Poverty Areas , Prevalence , Rodent Diseases/epidemiology , Rodent Diseases/transmission , Strongylida Infections/epidemiology , Strongylida Infections/parasitology , Strongylida Infections/transmission , Urban Population
10.
Molecules ; 26(13)2021 Jun 25.
Article in English | MEDLINE | ID: mdl-34202190

ABSTRACT

Background: The disease caused by hepatitis C virus (HCV) is asymptomatic, silent, and progressive liver disease. In HCV-infected patients the increase in serum HA is associated with the development of hepatic fibrosis and disease progression. Methods: HCV-RNA detection was performed in all serological samples of blood donors that tested positive using HCV Ultra ELISA. Determination of hyaluronan (HA) was performed in positive HCV samples using ELISA-like fluorometric method. The HA content was compared to HCV viral load, genotype of the virus, liver fibrosis as well as ALT and GGT liver biomarkers. Results: Persistently normal ALT (<40 U/L) and GGT (<50 U/L) serum levels were detected in 75% and 69% of the HCV-Infected blood donors, respectively. Based on ROC analysis, the HA value < 34.2 ng/mL is an optimal cut-off point to exclude HCV viremia (specificity = 91%, NPV = 99%). Applying HA value ≥34.2 ng/mL significant liver fibrosis (≥F2) can be estimated in 46% of the HCV-infected blood donors. HA serum level (≥34.2 ng/mL) associated with a high ALT level (>40 U/mL) can correctly identify HCV infection and probable liver fibrosis (sensitivity = 96% and specificity = 90%) in asymptomatic blood donors. Conclusions: A high level of HA (≥34.2 ng/mL) in association with ALT (≥40 U/L) in serum can provide a good clinical opportunity to detect HCV-infected asymptomatic persons that potentially require a liver biopsy confirmation and antiviral treatment to prevent the development of advanced liver fibrosis or cirrhosis.


Subject(s)
Blood Donors , Hepacivirus/metabolism , Hepatitis C/blood , Hepatitis C/diagnosis , Hyaluronic Acid/blood , Liver Cirrhosis/blood , Liver Cirrhosis/diagnosis , Adult , Enzyme-Linked Immunosorbent Assay , Female , Genotype , Hepacivirus/genetics , Hepatitis C/genetics , Humans , Liver Cirrhosis/genetics , Male , Middle Aged
11.
Emerg Infect Dis ; 26(9): 2190-2192, 2020 09.
Article in English | MEDLINE | ID: mdl-32818405

ABSTRACT

While studying aseptic meningitis in Salvador, Brazil, we diagnosed anicteric leptospirosis in 1.7% (5/295) of patients hospitalized for aseptic meningitis. Leptospirosis-associated meningitis patients had lower mean cerebrospinal fluid cell counts and protein than other-cause aseptic meningitis (p<0.05). Clinicians must consider leptospirosis-associated meningitis in appropriate clinical-epidemiologic contexts.


Subject(s)
Leptospirosis , Meningitis, Aseptic , Meningitis , Brazil , Humans , Leptospirosis/diagnosis , Leptospirosis/epidemiology , Meningitis/diagnosis , Meningitis/epidemiology
12.
Emerg Infect Dis ; 26(2): 311-314, 2020 02.
Article in English | MEDLINE | ID: mdl-31961288

ABSTRACT

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.


Subject(s)
Hospitalization , Leptospirosis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Brazil/epidemiology , Child , Child, Preschool , Female , Humans , Incidence , Leptospirosis/etiology , Male , Middle Aged , Poverty , Rain , Risk Factors , Seasons , Young Adult
13.
Emerg Infect Dis ; 26(7): 1364-1373, 2020 07.
Article in English | MEDLINE | ID: mdl-32568045

ABSTRACT

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.


Subject(s)
Chikungunya Fever , Chikungunya virus , Antibodies, Viral , Brazil/epidemiology , Chikungunya Fever/epidemiology , Cross-Sectional Studies , Disease Outbreaks , Humans , Poverty Areas , Seroepidemiologic Studies
14.
Int J Syst Evol Microbiol ; 70(3): 1450-1456, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31184568

ABSTRACT

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.


Subject(s)
Leptospira/classification , Phylogeny , Ponds/microbiology , Rivers/microbiology , Soil Microbiology , Animals , Bacterial Typing Techniques , Base Composition , Brazil , Cities , Connecticut , DNA, Bacterial/genetics , Farms , Horses , Leptospira/isolation & purification , Nucleic Acid Hybridization , Poverty Areas , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA
15.
Clin Infect Dis ; 69(8): 1353-1359, 2019 09 27.
Article in English | MEDLINE | ID: mdl-30561554

ABSTRACT

BACKGROUND: Since their emergence in the Americas, chikungunya (CHIKV) and Zika (ZIKV) viruses co-circulate with dengue virus (DENV), hampering clinical diagnosis. We investigated clinical and epidemiological characteristics of arboviral infections during the introduction and spread of CHIKV and ZIKV through northeastern Brazil. METHODS: Surveillance for arboviral diseases among febrile patients was performed at an emergency health unit of Salvador, Brazil, between September 2014 and July 2016. We interviewed patients to collect data on symptoms, reviewed medical records to obtain the presumptive diagnoses, and performed molecular and serological testing to confirm DENV, CHIKV, ZIKV, or nonspecific flavivirus (FLAV) diagnosis. RESULTS: Of 948 participants, 247 (26.1%) had an acute infection, of which 224 (23.6%) were single infections (DENV, 32 [3.4%]; CHIKV, 159 [16.7%]; ZIKV, 13 [1.4%]; and FLAV, 20 [2.1%]) and 23 (2.4%) coinfections (DENV/CHIKV, 13 [1.4%]; CHIKV/FLAV, 9 [0.9%]; and DENV/ZIKV, 1 [0.1%]). An additional 133 (14.0%) patients had serological evidence for a recent arboviral infection. Patients with ZIKV presented with rash and pruritus (69.2% each) more frequently than those with DENV (37.5% and 31.2%, respectively) and CHIKV (22.9% and 14.7%, respectively) (P < .001 for both comparisons). Conversely, arthralgia was more common in CHIKV (94.9%) and FLAV/CHIKV (100.0%) than in DENV (59.4%) and ZIKV (53.8%) (P < .001). A correct presumptive clinical diagnosis was made for 9%-23% of the confirmed patients. CONCLUSIONS: Arboviral infections are frequent causes of febrile illness. Coinfections are not rare events during periods of intense, concomitant arboviral transmission. Given the challenge to clinically distinguish these infections, there is an urgent need for rapid, point-of-care, multiplex diagnostics.


Subject(s)
Chikungunya Fever/transmission , Chikungunya virus/physiology , Dengue Virus/physiology , Dengue/transmission , Zika Virus Infection/transmission , Zika Virus/physiology , Adolescent , Adult , Brazil/epidemiology , Chikungunya Fever/epidemiology , Chikungunya Fever/virology , Coinfection , Dengue/epidemiology , Dengue/virology , Epidemiological Monitoring , Female , Fever , Humans , Male , Middle Aged , Young Adult , Zika Virus Infection/epidemiology , Zika Virus Infection/virology
17.
Mem Inst Oswaldo Cruz ; 114: e180597, 2019 Feb 28.
Article in English | MEDLINE | ID: mdl-30843962

ABSTRACT

A localized Chikungunya virus (CHIKV; East/Central/South African genotype) outbreak (50 cases, 70% laboratory-confirmed; attack rate: 5.3 confirmed cases/100 people) occurred in a Salvador, Brazil neighborhood, between Apr-Jun/2017. Highly clustered cases in space and time, mostly along a single street, highlight an increased risk of CHIKV transmission among pockets of susceptible populations. This finding underscores the need for ongoing local level surveillance for arboviral outbreaks.


Subject(s)
Chikungunya Fever/epidemiology , Chikungunya virus , Disease Outbreaks/statistics & numerical data , Adult , Brazil/epidemiology , Chikungunya Fever/diagnosis , Chikungunya Fever/virology , Chikungunya virus/genetics , Chikungunya virus/immunology , Enzyme-Linked Immunosorbent Assay , Female , Genotype , Humans , Male , Middle Aged , Phylogeny , Polymerase Chain Reaction , Seasons , Young Adult
18.
PLoS Pathog ; 12(11): e1005943, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27812211

ABSTRACT

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.


Subject(s)
Antimicrobial Cationic Peptides/immunology , Antimicrobial Cationic Peptides/metabolism , Leptospirosis/immunology , Animals , Brazil , Cluster Analysis , Cricetinae , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Mesocricetus , Oligonucleotide Array Sequence Analysis , Risk Factors , Cathelicidins
19.
Virol J ; 15(1): 108, 2018 07 13.
Article in English | MEDLINE | ID: mdl-30005683

ABSTRACT

BACKGROUND: Serologic detection of Zika virus (ZIKV) infections is challenging because of antigenic similarities among flaviviruses. OBJECTIVE: To evaluate the sensitivity and specificity of commercial ZIKV IgM and IgG enzyme-linked immunoassay (ELISA) kits. METHODS: We used sera from febrile patients with RT-PCR-confirmed ZIKV infection to determine sensitivity and sera from RT-PCR-confirmed dengue cases and blood donors, both of which were collected before ZIKV epidemics in Brazil (2009-2011 and 2013, respectively) to determine specificity. RESULTS: The ZIKV IgM-ELISA positivity among RT-PCR ZIKV confirmed cases was 0.0% (0/14) and 12.5% (1/8) for acute- and convalescent-phase sera, respectively, while its specificity was 100.0% (58/58) and 98.3% (58/59) for acute- and convalescent-phase sera of dengue patients, and 100.0% (23/23) for blood donors. The ZIKV IgG-ELISA sensitivity was 100.0% (6/6) on convalescent-phase sera from RT-PCR confirmed ZIKV patients, while its specificity was 27.3% (15/55) on convalescent-phase sera from dengue patients and 45.0% (9/20) on blood donors' sera. The ZIKV IgG-ELISA specificity among dengue confirmed cases was much greater among patients with primary dengue (92.3%; 12/13), compared to secondary dengue (7.1%; 3/42). CONCLUSIONS: In a setting of endemic dengue transmission, the ZIKV IgM-ELISA had high specificity, but poor sensitivity. In contrast, the ZIKV IgG-ELISA showed low specificity, particularly for patients previously exposed to dengue infections. This suggests that this ZIKV IgM-ELISA is not useful in confirming a diagnosis of ZIKV infection in suspected patients, whereas the IgG-ELISA is more suitable for ZIKV diagnosis among travelers, who reside in areas free of flavivirus transmission, rather than for serosurveys in dengue-endemic areas.


Subject(s)
Enzyme-Linked Immunosorbent Assay , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Zika Virus Infection/diagnosis , Zika Virus Infection/immunology , Zika Virus/immunology , Adolescent , Adult , Female , Humans , Male , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Young Adult , Zika Virus/genetics , Zika Virus Infection/virology
20.
Parasitology ; 145(6): 797-806, 2018 05.
Article in English | MEDLINE | ID: mdl-29113595

ABSTRACT

Urban slums provide suitable conditions for infestation by rats, which harbour and shed a wide diversity of zoonotic pathogens including helminths. We aimed to identify risk factors associated with the probability and intensity of infection of helminths of the digestive tract in an urban slum population of Rattus norvegicus. Among 299 rats, eleven species/groups of helminths were identified, of which Strongyloides sp., Nippostrongylus brasiliensis and, the human pathogen, Angiostrongylus cantonensis were the most frequent (97, 41 and 39%, respectively). Sex interactions highlighted behavioural differences between males and females, as eg males were more likely to be infected with N. brasiliensis where rat signs were present, and males presented more intense infections of Strongyloides sp. Moreover, rats in poor body condition had higher intensities of N. brasiliensis. We describe a high global richness of parasites in R. norvegicus, including five species known to cause disease in humans. Among these, A. cantonensis was found in high prevalence and it was ubiquitous in the study area - knowledge which is of public health importance. A variety of environmental, demographic and body condition variables were associated with helminth species infection of rats, suggesting a comparable variety of risk factors for humans.


Subject(s)
Helminthiasis, Animal/epidemiology , Poverty Areas , Rats/parasitology , Rodent Diseases/epidemiology , Zoonoses/epidemiology , Angiostrongylus cantonensis/isolation & purification , Animals , Brazil/epidemiology , Female , Helminthiasis, Animal/parasitology , Helminthiasis, Animal/transmission , Humans , Male , Public Health , Risk Factors , Rodent Diseases/parasitology , Rodent Diseases/transmission , Urban Renewal , Zoonoses/parasitology , Zoonoses/transmission
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