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1.
Am J Epidemiol ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32003778

RESUMO

Over the past century, the field of epidemiology has evolved and adapted to the changing public health needs. Challenges include newly emerging public health concerns across broad and diverse content areas, new methods, and vast data sources. We recognize the need to engage and educate the next generation of epidemiologists and prepare them to tackle these issues of the 21st century. In this commentary, we suggest a skeleton framework upon which departments of epidemiology should build their curriculum. We propose domains thatinclude: applied epidemiology, biological and social determinants of health, communication, creativity and ability to collaborate and lead, statistical methods, and study design. We believe that all students should gain skills across these domains to tackle the challenges posed to us. The aim is to train smart thinkers, not technicians, to embrace challenges and move the expanding field of epidemiology forward.

2.
Emerg Infect Dis ; 26(2): 311-314, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31961288

RESUMO

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.

5.
Philos Trans R Soc Lond B Biol Sci ; 374(1782): 20190367, 2019 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-31401957

RESUMO

Leptospirosis is a widespread and potentially life-threatening zoonotic disease caused by spirochaetes of the genus Leptospira. Humans become infected primarily via contact with environmental reservoirs contaminated by the urine of shedding mammalian hosts. Populations in high transmission settings, such as urban slums and subsistence farming communities, are exposed to low doses of Leptospira on a daily basis. Under these conditions, numerous factors determine whether infection occurs, including the route of exposure and inoculum dose. Skin wounds and abrasions are risk factors for leptospirosis, but it is not known whether broken skin is necessary for spillover, or if low-dose exposures to intact skin and mucous membranes can also cause infection. To establish a quantitative relationship between dose, route and probability of infection, we performed challenge experiments in hamsters and rats, developed mechanistic dose-response models representing the spatial dynamics of within-host infection and persistence, and fitted models to experimental data. Results show intact skin is a strong barrier against infection, and that broken skin is the predominant route by which low-dose environmental exposures cause infection. These results identify skin integrity as a bottleneck to spillover of Leptospira and underscore the importance of barrier interventions in the prevention of leptospirosis. This article is part of the theme issue 'Dynamic and integrative approaches to understanding pathogen spillover'.

6.
J Infect Dis ; 220(9): 1489-1497, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31342075

RESUMO

BACKGROUND: The burden of leptospirosis in Puerto Rico remains unclear due to underreporting. METHODS: A cross-sectional survey and rodent trapping was performed in a community within San Juan, Puerto Rico to determine the seroprevalence and risk factors for Leptospira infection. The microscopic agglutination test was used to detect anti-Leptospira antibodies as a marker of previous infection. We evaluated Leptospira carriage by quantitative polymerase chain reaction among rodents trapped at the community site. RESULTS: Of 202 study participants, 55 (27.2%) had Leptospira agglutinating antibodies. Among the 55 seropositive individuals, antibodies were directed most frequently against serogroups Icterohaemorrhagiae (22.0%) and Autumnalis (10.6%). Of 18 captured rodents, 11 (61.1%) carried pathogenic Leptospira (Leptospira borgpetersenii, 7 and Leptospira interrogans, 2). Four participants showed their highest titer against an isolate obtained from a rodent (serogroup Ballum). Increasing household distance to the canal that runs through the community was associated with decreased risk of infection (odds ratio = 0.934 per 10-meter increase; 95% confidence interval, .952-.992). CONCLUSIONS: There are high levels of Leptospira exposure in an urban setting in Puerto Rico, for which rodents may be an important reservoir for transmission. Our findings indicate that prevention should focus on mitigating risk posed by infrastructure deficiencies such as the canal.

7.
Am J Trop Med Hyg ; 101(3): 585-589, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31333152

RESUMO

Leptospirosis is the leading cause of zoonotic morbidity and mortality globally, yet little is known about the immune mechanisms that may contribute to pathogenesis and severe disease. Although neutrophils are a key component of early immune responses to infection, they have been associated with tissue damage and inflammation in some febrile infections. To assess whether neutrophils contribute to the pathogenesis observed in severe leptospirosis, we quantitated levels of neutrophil activation markers in patients with varying disease severities. Hospitalized leptospirosis patients had significantly higher levels of toll-like receptors 2 and 4 (TLR2 and TLR4, respectively) on peripheral neutrophils than healthy controls, with the highest levels detected in patients with organ dysfunction. We observed no significant differences in other neutrophil baseline activation markers (CD62L and CD11b) or activation capacity (CD62L and CD11b levels following stimulation), regardless of disease severity. Our results provide preliminary evidence supporting the hypothesis that higher initial bacterial loads or inadequate or delayed neutrophil responses, rather than TLR-driven inflammation, may drive severe disease outcomes.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31184568

RESUMO

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.

10.
Trends Microbiol ; 27(5): 381-383, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30826180

RESUMO

After the discovery that Zika virus (ZIKV) could cause microcephaly and other birth defects, we have scrambled to understand how. Now, spreading along with the virus is misinformation that a ZIKV mutation is responsible for microcephaly. Putting too much onus on a single mutation could enhance a crisis in India.

12.
Science ; 363(6427): 607-610, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30733412

RESUMO

The clinical outcomes associated with Zika virus (ZIKV) in the Americas have been well documented, but other aspects of the pandemic, such as attack rates and risk factors, are poorly understood. We prospectively followed a cohort of 1453 urban residents in Salvador, Brazil, and, using an assay that measured immunoglobulin G3 (IgG3) responses against ZIKV NS1 antigen, we estimated that 73% of individuals were infected during the 2015 outbreak. Attack rates were spatially heterogeneous, varying by a factor of 3 within a community spanning 0.17 square kilometers. Preexisting high antibody titers to dengue virus were associated with reduced risk of ZIKV infection and symptoms. The landscape of ZIKV immunity that now exists may affect the risk for future transmission.


Assuntos
Anticorpos Antivirais/sangue , Reações Cruzadas , Dengue/imunologia , Proteínas não Estruturais Virais/imunologia , Infecção por Zika virus/imunologia , Adolescente , Adulto , Número Básico de Reprodução , Brasil , Criança , Surtos de Doenças , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Estudos Prospectivos , Estudos Soroepidemiológicos , População Urbana , Adulto Jovem , Zika virus
13.
PLoS Med ; 16(1): e1002737, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30677013

RESUMO

BACKGROUND: It has been hypothesized that prisons serve as amplifiers of general tuberculosis (TB) epidemics, but there is a paucity of data on this phenomenon and the potential population-level effects of prison-focused interventions. This study (1) quantifies the TB risk for prisoners as they traverse incarceration and release, (2) mathematically models the impact of prison-based interventions on TB burden in the general population, and (3) generalizes this model to a wide range of epidemiological contexts. METHODS AND FINDINGS: We obtained individual-level incarceration data for all inmates (n = 42,925) and all reported TB cases (n = 5,643) in the Brazilian state of Mato Grosso do Sul from 2007 through 2013. We matched individuals between prisoner and TB databases and estimated the incidence of TB from the time of incarceration and the time of prison release using Cox proportional hazards models. We identified 130 new TB cases diagnosed during incarceration and 170 among individuals released from prison. During imprisonment, TB rates increased from 111 cases per 100,000 person-years at entry to a maximum of 1,303 per 100,000 person-years at 5.2 years. At release, TB incidence was 229 per 100,000 person-years, which declined to 42 per 100,000 person-years (the average TB incidence in Brazil) after 7 years. We used these data to populate a compartmental model of TB transmission and incarceration to evaluate the effects of various prison-based interventions on the incidence of TB among prisoners and the general population. Annual mass TB screening within Brazilian prisons would reduce TB incidence in prisons by 47.4% (95% Bayesian credible interval [BCI], 44.4%-52.5%) and in the general population by 19.4% (95% BCI 17.9%-24.2%). A generalized model demonstrates that prison-based interventions would have maximum effectiveness in reducing community incidence in populations with a high concentration of TB in prisons and greater degrees of mixing between ex-prisoners and community members. Study limitations include our focus on a single Brazilian state and our retrospective use of administrative databases. CONCLUSIONS: Our findings suggest that the prison environment, more so than the prison population itself, drives TB incidence, and targeted interventions within prisons could have a substantial effect on the broader TB epidemic.


Assuntos
Prisões , Tuberculose Pulmonar/prevenção & controle , Brasil/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/prevenção & controle , Infecções Comunitárias Adquiridas/transmissão , Feminino , Humanos , Incidência , Tuberculose Latente/epidemiologia , Tuberculose Latente/prevenção & controle , Tuberculose Latente/transmissão , Masculino , Modelos Estatísticos , Prisões/organização & administração , Prisões/estatística & dados numéricos , Modelos de Riscos Proporcionais , Características de Residência , Fatores de Tempo , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/transmissão
14.
Am J Trop Med Hyg ; 100(1_Suppl): 3-8, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30430982

RESUMO

Mentoring is a proven path to scientific progress, but it is not a common practice in low- and middle-income countries (LMICs). Existing mentoring approaches and guidelines are geared toward high-income country settings, without considering in detail the differences in resources, culture, and structure of research systems of LMICs. To address this gap, we conducted five Mentoring-the-Mentor workshops in Africa, South America, and Asia, which aimed at strengthening the capacity for evidence-based, LMIC-specific institutional mentoring programs globally. The outcomes of the workshops and two follow-up working meetings are presented in this special edition of the American Journal of Tropical Medicine and Hygiene. Seven articles offer recommendations on how to tailor mentoring to the context and culture of LMICs, and provide guidance on how to implement mentoring programs. This introductory article provides both a prelude and executive summary to the seven articles, describing the motivation, cultural context and relevant background, and presenting key findings, conclusions, and recommendations.


Assuntos
Pesquisa Biomédica/educação , Educação/organização & administração , Saúde Global/educação , Tutoria/métodos , Mentores , Ensino/organização & administração , África , Ásia , Comparação Transcultural , Países em Desenvolvimento/economia , Humanos , Renda/estatística & dados numéricos , Institucionalização , Tutoria/economia , América do Sul
15.
Clin Infect Dis ; 69(8): 1353-1359, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30561554

RESUMO

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.

16.
One Health ; 6: 37-40, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30386815

RESUMO

Brucellosis and Q fever impart high morbidity in humans and economic losses among livestock worldwide. However their prevalence is still not fully known in Thailand. We conducted a sero-survey of brucellosis and Q fever in beef, dairy cattle, goat, and sheep herds from Thai communities at the border with Cambodia, a cross-border trading center. Serum samples were tested for brucellosis and Q fever by antibody-based tests at the National Institute of Animal Health, Thailand. We surveyed a total of 520 individuals from 143 herds. Brucellosis herd-level seroprevalence for beef cattle and small ruminants (goats and sheep) was 2.6% (3/117) and 13.3% (2/15) respectively. Q fever herd-level seroprevalence for beef cattle, dairy cattle, and small ruminants was 4.3% (5/117), 27.3% (3/11) and 33.3% (5/15) respectively. This study identified a significant burden of brucellosis and Q fever among small ruminants and dairy cattle at the Thai-Cambodian border.

17.
PLoS Negl Trop Dis ; 12(8): e0006752, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30169513

RESUMO

BACKGROUND: Human movement is likely an important risk factor for environmentally-transmitted pathogens. While epidemiologic studies have traditionally focused on household risk factors, individual movement data could provide critical additional information about risk of exposure to such pathogens. We conducted global positioning system (GPS) tracking of urban slum residents to quantify their fine-scale movement patterns and evaluate their exposures to environmental sources of leptospirosis transmission. METHODOLOGY/PRINCIPAL FINDINGS: We recruited participants from an ongoing cohort study in an urban slum in Brazil and tracked them for 24 hours at 30-second intervals. Among 172 subjects asked to participate in this cross-sectional study, 130 agreed to participate and 109 had good quality data and were included in analyses. The majority of recorded locations were near participant residences (87.7% within 50 meters of the house), regardless of age or gender. Similarly, exposure to environmental sources of leptospirosis transmission did not vary by age or gender. However, males, who have higher infection rates, visited a significantly larger area during the 24-hour period than did females (34,549m2 versus 22,733m2, p = 0.005). Four male participants had serologic evidence of Leptospira infection during the study period. These individuals had significantly larger activity spaces than uninfected males (61,310m2 vs 31,575m2, p = 0.006) and elevated exposure to rodent activity (p = 0.046) and trash deposits (p = 0.031). CONCLUSIONS/SIGNIFICANCE: GPS tracking was an effective tool for quantifying individual mobility in the complex urban slum environment and identifying risk exposures associated with that movement. This study suggests that in addition to source reduction, barrier interventions that reduce contact with transmission sources as slum residents move within their communities may be a useful prevention strategy for leptospirosis.


Assuntos
Microbiologia Ambiental , Sistemas de Informação Geográfica , Leptospira , Áreas de Pobreza , Brasil , Cidades , Humanos
18.
Am J Trop Med Hyg ; 99(4): 849-851, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30141390

RESUMO

Severe flooding has been linked to outbreaks of leptospirosis. Two sequential extreme flood events in Western Fiji caused the largest outbreak of leptospirosis recorded in the South Pacific, with 1,217 total suspected cases, of which 314 were probable and confirmed. Most (83%) cases occurred within 6 weeks of the flood events, displaying a biphasic epidemic curve associated with the floods. Given the temporal proximity of cases to flooding events, most of the transmission appeared to occur during or immediately after the floods; therefore, prevention of exposure to contaminated environments is a priority in the immediate flood and post-flood period. In addition, genotyping studies suggest that multiple animal reservoirs were implicated in the outbreak, reaffirming the importance of integrated human and animal health strategies for leptospirosis control.


Assuntos
Anticorpos Antibacterianos/sangue , DNA Bacteriano/genética , Surtos de Doenças , Inundações , Leptospira/isolamento & purificação , Leptospirose/epidemiologia , Ensaio de Imunoadsorção Enzimática , Fiji/epidemiologia , Humanos , Incidência , Leptospira/genética , Leptospira/imunologia , Leptospirose/sangue , Leptospirose/microbiologia , Reação em Cadeia da Polimerase , Chuva , Estudos Retrospectivos , Estações do Ano
19.
Artigo em Inglês | MEDLINE | ID: mdl-29971217

RESUMO

Leptospirosis is a worldwide zoonosis, responsible for more than 1 million cases and 60,000 deaths every year. Among the 13 pathogenic species of the genus Leptospira, serovars belonging to L. interrogans serogroup Icterohaemorrhagiae are considered to be the most virulent strains, and responsible for majority of the reported severe cases. Serovars Copenhageni and Icterohaemorrhagiae are major representatives of this serogroup and despite their public health relevance, little is known regarding the genetic differences between these two serovars. In this study, we analyzed the genome sequences of 67 isolates belonging to L. interrogans serovars Copenhageni and Icterohaemorrhagiae to investigate the influence of spatial and temporal variations on DNA sequence diversity. Out of the 1072 SNPs identified, 276 were in non-coding regions and 796 in coding regions. Indel analyses identified 258 indels, out of which 191 were found in coding regions and 67 in non-coding regions. Our phylogenetic analyses based on SNP dataset revealed that both serovars are closely related but showed distinct spatial clustering. However, likelihood ratio test of the indel data statistically confirmed the presence of a frameshift mutation within a homopolymeric tract of lic12008 gene (related to LPS biosynthesis) in all the L. interrogans serovar Icterohaemorrhagiae strains but not in the Copenhageni strains. Therefore, this internal indel identified can genetically distinguish L. interrogans serovar Copenhageni from serovar Icterohaemorrhagiae with high discriminatory power. To our knowledge, this is the first study to identify global sequence variations (SNPs and Indels) in L. interrogans serovars Copenhageni and Icterohaemorrhagiae.


Assuntos
DNA Bacteriano/genética , Variação Genética , Leptospira interrogans/genética , Leptospirose/microbiologia , Sorogrupo , Animais , Genoma Bacteriano/genética , Estudo de Associação Genômica Ampla , Humanos , Leptospira interrogans/isolamento & purificação , Filogenia , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Virulência/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-29868490

RESUMO

The spirochete endoflagellum is a unique motility apparatus among bacteria. Despite its critical importance for pathogenesis, the full composition of the flagellum remains to be determined. We have recently reported that FcpA is a novel flagellar protein and a major component of the sheath of the filament of the spirochete Leptospira. By screening a library of random transposon mutants in the spirochete Leptospira biflexa, we found a motility-deficient mutant harboring a disruption in a hypothetical gene of unknown function. Here, we show that this gene encodes a surface component of the endoflagellar filament and is required for typical hook- and spiral-shaped ends of the cell body, coiled structure of the endoflagella, and high velocity phenotype. We therefore named the gene fcpB for flagellar-coiling protein B. fcpB is conserved in all members of the Leptospira genus, but not present in other organisms including other spirochetes. Complementation of the fcpB- mutant restored the wild-type morphology and motility phenotypes. Immunoblotting with anti-FcpA and anti-FcpB antisera and cryo-electron microscopy of the filament indicated that FcpB assembled onto the surface of the sheath of the filament and mostly located on the outer (convex) side of the coiled filament. We provide evidence that FcpB, together with FcpA, are Leptospira-specific novel components of the sheath of the filament, key determinants of the coiled and asymmetric structure of the endoflagella and are essential for high velocity. Defining the components of the endoflagella and their functions in these atypical bacteria should greatly enhance our understanding of the mechanisms by which these bacteria produce motility.


Assuntos
Movimento Celular/fisiologia , Flagelos/fisiologia , Flagelina/metabolismo , Leptospira/fisiologia , Sequência de Aminoácidos , Movimento Celular/genética , Microscopia Crioeletrônica , Elementos de DNA Transponíveis , Flagelos/ultraestrutura , Flagelina/genética , Leptospira/genética , Leptospira/ultraestrutura , Microscopia de Vídeo , Fenótipo , Alinhamento de Sequência , Deleção de Sequência
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