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1.
Cell ; 169(4): 597-609.e11, 2017 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-28475892

RESUMEN

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.


Asunto(s)
Anticuerpos Neutralizantes/química , Anticuerpos Antivirales/química , Infección por el Virus Zika/inmunología , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Linfocitos B/inmunología , Brasil , Femenino , Humanos , Memoria Inmunológica , Leucocitos Mononucleares/inmunología , Masculino , México , Ratones , Infección por el Virus Zika/sangre
2.
An Acad Bras Cienc ; 95(suppl 2): e20220809, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37909607

RESUMEN

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.


Asunto(s)
Bartonella , Humanos , Ratas , Animales , Bartonella/genética , Reservorios de Enfermedades , Brasil , Áreas de Pobreza , Roedores/microbiología
3.
J Infect Dis ; 225(1): 130-134, 2022 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-34139761

RESUMEN

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.


Asunto(s)
Ambiente , Leptospira/aislamiento & purificación , Leptospirosis/epidemiología , Microbiología del Suelo , Microbiología del Agua , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Animales , Brasil/epidemiología , Humanos , Leptospira/genética , Leptospira interrogans/genética , Leptospirosis/diagnóstico , Epidemiología Molecular , Filogenia , Ratas , Análisis de Secuencia de ADN
4.
Emerg Infect Dis ; 28(10): 2132-2134, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36148970

RESUMEN

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.


Asunto(s)
Infecciones por Rickettsia , Rickettsia , Anticuerpos Antibacterianos , Brasil/epidemiología , Fiebre/epidemiología , Humanos , Áreas de Pobreza , Infecciones por Rickettsia/diagnóstico , Infecciones por Rickettsia/epidemiología
5.
PLoS Med ; 19(9): e1004093, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36074784

RESUMEN

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.


Asunto(s)
COVID-19 , Adulto , Brasil/epidemiología , COVID-19/epidemiología , Niño , Estudios Transversales , Femenino , Humanos , Inmunoglobulina G , Masculino , Pandemias , Áreas de Pobreza , SARS-CoV-2 , Estudios Seroepidemiológicos , Glicoproteína de la Espiga del Coronavirus
6.
J Infect Dis ; 224(5): 860-864, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-33395487

RESUMEN

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.


Asunto(s)
Áreas de Pobreza , Conducta Sexual , Enfermedades Virales de Transmisión Sexual/epidemiología , Infección por el Virus Zika/epidemiología , Virus Zika/aislamiento & purificación , Adolescente , Adulto , Femenino , Humanos , Masculino , Estudios Retrospectivos , Población Urbana
7.
Trop Med Int Health ; 26(3): 272-280, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33190402

RESUMEN

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.


Asunto(s)
Dengue/epidemiología , Infección por el Virus Zika/epidemiología , América Central/epidemiología , Virus Chikungunya/inmunología , Dengue/complicaciones , Virus del Dengue , Epidemias , Humanos , Incidencia , Modelos Lineales , América del Sur/epidemiología , Virus Zika , Infección por el Virus Zika/etiología
8.
Environ Sci Technol ; 55(23): 15882-15890, 2021 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-34767339

RESUMEN

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.


Asunto(s)
Leptospira , Leptospirosis , Animales , Brasil , Leptospirosis/epidemiología , Áreas de Pobreza , Ratas , Suelo
9.
Parasitology ; 148(8): 994-1002, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33843507

RESUMEN

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.


Asunto(s)
Angiostrongylus cantonensis/aislamiento & purificación , Gastrópodos/parasitología , Ratas/parasitología , Enfermedades de los Roedores/parasitología , Infecciones por Strongylida/veterinaria , Animales , Brasil/epidemiología , Heces/parasitología , Femenino , Gastrópodos/clasificación , Masculino , Moluscos/parasitología , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/parasitología , Enfermedades del Sistema Nervioso/veterinaria , Áreas de Pobreza , Prevalencia , Enfermedades de los Roedores/epidemiología , Enfermedades de los Roedores/transmisión , Infecciones por Strongylida/epidemiología , Infecciones por Strongylida/parasitología , Infecciones por Strongylida/transmisión , Población Urbana
10.
Molecules ; 26(13)2021 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-34202190

RESUMEN

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.


Asunto(s)
Donantes de Sangre , Hepacivirus/metabolismo , Hepatitis C/sangre , Hepatitis C/diagnóstico , Ácido Hialurónico/sangre , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C/genética , Humanos , Cirrosis Hepática/genética , Masculino , Persona de Mediana Edad
11.
J Clin Rheumatol ; 27(6S): S193-S197, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34525002

RESUMEN

INTRODUCTION: Jaccoud arthropathy (JA) is a nonerosive and deforming arthropathy experienced frequently by patients with systemic lupus erythematosus (SLE). Although genetic polymorphisms are associated with SLE development, the association between genetic polymorphisms and JA has not been studied to date. The main objective of this study was to evaluate an association between HLA, STAT4, IRF5, and BLK polymorphisms and the presence of JA in Brazilian individuals with SLE. METHODS: Patients were selected from a cohort of individuals with SLE followed at 2 rheumatology reference centers in Salvador, Bahia, Brazil. The JA diagnosis was based on clinical and radiological criteria. The participants were genotyped for rs9271100, rs7574865, rs10488631, and rs13277113 polymorphisms in the HLA, STAT4, IRF5, and BLK genes, respectively, using real-time polymerase chain reaction. The presence of JA was correlated with allele frequencies, and clinical and laboratory data. RESULTS: One hundred forty-four individuals with SLE (38 with JA and 106 with SLE without JA) were studied. The mean age of the patients was 45 ± 12 years; the majority were women and had brown skin. Patients with JA had a longer disease duration than patients without JA. Serositis and neuropsychiatric manifestations were more frequent in the JA population. The A allele of rs13277113 in the BLK gene was associated with the presence of JA. CONCLUSIONS: The rs13277113 polymorphism in the BLK gene was found to be a possible genetic risk for JA development. However, further studies in larger populations should be performed to confirm this finding.


Asunto(s)
Artropatías , Lupus Eritematoso Sistémico , Adulto , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Factores Reguladores del Interferón , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/genética , Masculino , Persona de Mediana Edad , Proyectos Piloto , Polimorfismo de Nucleótido Simple
12.
Emerg Infect Dis ; 26(9): 2190-2192, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32818405

RESUMEN

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.


Asunto(s)
Leptospirosis , Meningitis Aséptica , Meningitis , Brasil , Humanos , Leptospirosis/diagnóstico , Leptospirosis/epidemiología , Meningitis/diagnóstico , Meningitis/epidemiología
13.
Emerg Infect Dis ; 26(7): 1364-1373, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32568045

RESUMEN

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.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Anticuerpos Antivirales , Brasil/epidemiología , Fiebre Chikungunya/epidemiología , Estudios Transversales , Brotes de Enfermedades , Humanos , Áreas de Pobreza , Estudios Seroepidemiológicos
14.
Emerg Infect Dis ; 26(2): 311-314, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31961288

RESUMEN

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.


Asunto(s)
Hospitalización , Leptospirosis/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Preescolar , Femenino , Humanos , Incidencia , Leptospirosis/etiología , Masculino , Persona de Mediana Edad , Pobreza , Lluvia , Factores de Riesgo , Estaciones del Año , Adulto Joven
15.
Int J Syst Evol Microbiol ; 70(3): 1450-1456, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31184568

RESUMEN

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.


Asunto(s)
Leptospira/clasificación , Filogenia , Estanques/microbiología , Ríos/microbiología , Microbiología del Suelo , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , Brasil , Ciudades , Connecticut , ADN Bacteriano/genética , Granjas , Caballos , Leptospira/aislamiento & purificación , Hibridación de Ácido Nucleico , Áreas de Pobreza , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
16.
Int J Mol Sci ; 21(17)2020 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-32846867

RESUMEN

Due to its importance in the pathogenesis of oral squamous cell carcinoma (OSCC), the Hedgehog (HH) pathway is considered a potential therapeutic target. We investigated the effects of GANT61, a GLI inhibitor, on HH gene expression, as well as on metastatic OSCC cell proliferation and death. Following culture in DMEM medium, cytotoxicity of GANT61 against different tumor and non-tumor cell types was assessed by alamarBlue assays. Cytotoxicity analysis revealed that the metastatic HSC3 cell line was the most sensitive (IC50: 36 µM) to the tested compound. The compound's effects on the expression of HH pathways components were analyzed by qPCR and Western blot; cell viability was analyzed by trypan blue assay and flow cytometry were used to investigate cell cycle phase, morphology, and death patterns in HSC3 cells. A significant reduction in mRNA levels of the GLI1 transcription factor was found after 12 h of treatment withGANT61. Protein expression levels of other HH pathway components (PTCH1, SHH, and Gli1) and HSC3 cell viability also decreased after 24 h of treatment. Cell cycle analysis and death pattern evaluations revealed significantly increased nuclear fragmentation in sub-G1 phase, as well as cell death due to apoptosis. In conclusion, the significantly reduced GLI1 gene expression seen in response to the GLI inhibitor indicates diminished downstream activation in HH pathway components. GANT61 significantly reduced cell viability in the metastatic cell line of OSCC and promoted a significant increase in nuclear fragmentation and cell death by apoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/patología , Piridinas/farmacología , Pirimidinas/farmacología , Proteína con Dedos de Zinc GLI1/genética , Adulto , Apoptosis/genética , Carcinoma de Células Escamosas/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Células Cultivadas , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias de la Boca/genética , Metástasis de la Neoplasia , Proteína con Dedos de Zinc GLI1/metabolismo
17.
Clin Infect Dis ; 69(8): 1353-1359, 2019 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-30561554

RESUMEN

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.


Asunto(s)
Fiebre Chikungunya/transmisión , Virus Chikungunya/fisiología , Virus del Dengue/fisiología , Dengue/transmisión , Infección por el Virus Zika/transmisión , Virus Zika/fisiología , Adolescente , Adulto , Brasil/epidemiología , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/virología , Coinfección , Dengue/epidemiología , Dengue/virología , Monitoreo Epidemiológico , Femenino , Fiebre , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/virología
19.
BMC Infect Dis ; 19(1): 609, 2019 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-31296179

RESUMEN

BACKGROUND: Bloodstream infections (BSI) are associated with high morbidity and mortality. This scenario worsens with the emergence of drug-resistant pathogens, resulting in infections which are difficult to treat or even untreatable with conventional antimicrobials. The aim of this study is to describe the epidemiological aspects of BSI caused by multiresistant gram-negative bacilli (MDR-GNB). METHODS: We conducted a laboratory-based surveillance for gram-negative bacteremia over a 1-year period. The bacterial isolates were identified by MALDI-TOF/MS and the antimicrobial susceptibility testing was performed by VITEK®2. Resistance genes were identified through PCR assays. RESULTS: Of the 143 patients, 28.7% had infections caused by MDR-GNB. The risk factors for MDR bacteremia were male sex, age ≥ 60, previous antimicrobial use, liver disease and bacteremia caused by K. pneumoniae. K. pneumoniae was the most frequently observed causative agent and had the highest resistance level. Regarding the resistance determinants, SHV, TEM, OXA-1-like and CTX-M-gp1 were predominant enzymatic variants, whereas CTX-M-gp9, CTX-M-gp2, KPC, VIM, GES, OXA-48-like, NDM and OXA-23-like were considered emerging enzymes. CONCLUSIONS: Here we demonstrate that clinically relevant antibiotic resistance genes are prevalent in this setting. We hope our findings support the development of intervention measures by policy makers and healthcare professionals to face antibiotic resistance.


Asunto(s)
Bacteriemia/epidemiología , Bacteriemia/microbiología , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Adolescente , Adulto , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Brasil/epidemiología , Niño , Preescolar , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/genética , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Lactante , Recién Nacido , Infecciones por Klebsiella/microbiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Prevalencia
20.
Mem Inst Oswaldo Cruz ; 114: e180597, 2019 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-30843962

RESUMEN

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.


Asunto(s)
Fiebre Chikungunya/epidemiología , Virus Chikungunya , Brotes de Enfermedades/estadística & datos numéricos , Adulto , Brasil/epidemiología , Fiebre Chikungunya/diagnóstico , Fiebre Chikungunya/virología , Virus Chikungunya/genética , Virus Chikungunya/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Reacción en Cadena de la Polimerasa , Estaciones del Año , Adulto Joven
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