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1.
Sci. rep ; 9(1): 20418, Dec. 2019. ilus
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IIERPROD, Sec. Est. Saúde SP | ID: biblio-1047632

RESUMO

The largest outbreak of yellow fever of the 21st century in the Americas began in 2016, with intense circulation in the southeastern states of Brazil, particularly in sylvatic environments near densely populated areas including the metropolitan region of São Paulo city (MRSP) during 2017­2018. Herein, we describe the origin and molecular epidemiology of yellow fever virus (YFV) during this outbreak inferred from 36 full genome sequences taken from individuals who died following infection with zoonotic YFV. Our analysis revealed that these deaths were due to three genetic variants of sylvatic YFV that belong the South American I genotype and that were related to viruses previously isolated in 2017 from other locations in Brazil (Minas Gerais, Espírito Santo, Bahia and Rio de Janeiro states). Each variant represented an independent virus introduction into the MRSP. Phylogeographic and geopositioning analyses suggested that the virus moved around the peri-urban area without detectable human-to-human transmission, and towards the Atlantic rain forest causing human spill-over in nearby cities, yet in the absence of sustained viral transmission in the urban environment.


Assuntos
Febre Amarela/epidemiologia , Brasil/epidemiologia
2.
PLoS Comput Biol ; 15(9): e1007355, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31545790

RESUMO

Yellow fever is a vector-borne disease endemic in tropical regions of Africa, where 90% of the global burden occurs, and Latin America. It is notoriously under-reported with uncertainty arising from a complex transmission cycle including a sylvatic reservoir and non-specific symptom set. Resulting estimates of burden, particularly in Africa, are highly uncertain. We examine two established models of yellow fever transmission within a Bayesian model averaging framework in order to assess the relative evidence for each model's assumptions and to highlight possible data gaps. Our models assume contrasting scenarios of the yellow fever transmission cycle in Africa. The first takes the force of infection in each province to be static across the observation period; this is synonymous with a constant infection pressure from the sylvatic reservoir. The second model assumes the majority of transmission results from the urban cycle; in this case, the force of infection is dynamic and defined through a fixed value of R0 in each province. Both models are coupled to a generalised linear model of yellow fever occurrence which uses environmental covariates to allow us to estimate transmission intensity in areas where data is sparse. We compare these contrasting descriptions of transmission through a Bayesian framework and trans-dimensional Markov chain Monte Carlo sampling in order to assess each model's evidence given the range of uncertainty in parameter values. The resulting estimates allow us to produce Bayesian model averaged predictions of yellow fever burden across the African endemic region. We find strong support for the static force of infection model which suggests a higher proportion of yellow fever transmission occurs as a result of infection from an external source such as the sylvatic reservoir. However, the model comparison highlights key data gaps in serological surveys across the African endemic region. As such, conclusions concerning the most prevalent transmission routes for yellow fever will be limited by the sparsity of data which is particularly evident in the areas with highest predicted transmission intensity. Our model and estimation approach provides a robust framework for model comparison and predicting yellow fever burden in Africa. However, key data gaps increase uncertainty surrounding estimates of model parameters and evidence. As more mathematical models are developed to address new research questions, it is increasingly important to compare them with established modelling approaches to highlight uncertainty in structures and data.


Assuntos
Modelos Biológicos , Febre Amarela/transmissão , Aedes/virologia , África , Animais , Teorema de Bayes , Biologia Computacional , Humanos , Modelos Estatísticos , Febre Amarela/epidemiologia , Vírus da Febre Amarela
3.
PLoS Negl Trop Dis ; 13(8): e0007661, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31425507

RESUMO

BACKGROUND: French Guiana, a French overseas department located in South America between Brazil and Surinam, is the only European territory geographically located in the Amazonian forest complex and is considered endemic for yellow fever (YF). In the context of the emergent threat of YF in Latin America, we conducted a large household cross-sectional survey from June to October 2017 to estimate vaccination coverage in the population and to determine associations with sociodemographic and geographical characteristics. METHODOLOGY/PRINCIPAL FINDINGS: In total, 1,415 households and 2,697 individuals were included from the 22 municipalities of French Guiana. YF vaccination coverage was estimated at 95.0% (95% CI: 93.4-96.2) in the entire territory but was spatially heterogeneous, with the lowest levels estimated in the western part of the territory along the Surinamese cross-border region, particularly in children under 16 years who were not enrolled in school, immigrant adults and disadvantaged populations with low socioeconomic indexes. CONCLUSIONS/SIGNIFICANCE: Despite the good vaccination coverage against YF in the general population of French Guiana resulting from the compulsory nature of YF vaccination for residents and travelers, there is an urgent need to improve vaccination coverage in vulnerable populations living in the northwestern part of the territory to limit the risk of transmission in the context of the emerging YF threat in South America. Despite the relative rarity of YF and the significant number of infectious and tropical diseases in French Guiana, clinicians should adopt a high index of suspicion for YF, particularly in vulnerable and at-risk populations.


Assuntos
Transmissão de Doença Infecciosa/prevenção & controle , Cobertura Vacinal/estatística & dados numéricos , Vacina contra Febre Amarela/administração & dosagem , Febre Amarela/epidemiologia , Febre Amarela/prevenção & controle , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , Demografia , Características da Família , Feminino , Guiana Francesa/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Adulto Jovem
4.
Int J Infect Dis ; 87: 143-150, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31382047

RESUMO

OBJECTIVES: Yellow fever virus historically was a frequent threat to American and European coasts. Medical milestones such as the discovery of mosquitoes as vectors and subsequently an effective vaccine significantly reduced its incidence, in spite of which, thousands of cases of this deathly disease still occur regularly in Sub-Saharan Africa and the Amazonian basin in South America, which are usually not reported. An urban outbreak in Angola, consecutive years of increasing incidence near major Brazilian cities, and imported cases in China, South America and Europe, have brought this virus back to the global spotlight. The aim of this article is to underline that the preventive YFV measures, such as vaccination, need to be carefully revised in order to minimize the risks of new YFV outbreaks, especially in urban or immunologically vulnerable places. Furthermore, this article highlights the diverse factors that have favored the spread of other Aedes spp.-associated arboviral diseases like Dengue, Chikungunya and Zika, to northern latitudes causing epidemics in the United States and Europe, emphasizing the possibility that YFV might follow the path of these viruses unless enhanced surveillance and efficient control systems are urgently initiated.


Assuntos
Febre Amarela/epidemiologia , Vírus da Febre Amarela/isolamento & purificação , Animais , Humanos , Mosquitos Vetores/fisiologia , Mosquitos Vetores/virologia , América do Norte/epidemiologia , Febre Amarela/transmissão , Febre Amarela/virologia , Vírus da Febre Amarela/classificação , Vírus da Febre Amarela/genética
5.
PLoS Negl Trop Dis ; 13(7): e0007625, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31329590

RESUMO

BACKGROUND: New strategies for collecting post-mortem tissue are necessary, particularly in areas with emerging infections. Minimally invasive autopsy (MIA) has been proposed as an alternative to conventional autopsy (CA), with promising results. Previous studies using MIA addressed the cause of death in adults and children in developing countries. However, none of these studies was conducted in areas with an undergoing infectious disease epidemic. We have recently experienced an epidemic of yellow fever (YF) in Brazil. Aiming to provide new information on low-cost post-mortem techniques that could be applied in regions at risk for infectious outbreaks, we tested the efficacy of ultrasound-guided MIA (MIA-US) in the diagnosis of patients who died during the epidemic. METHODOLOGY/PRINCIPAL FINDINGS: In this observational study, we performed MIA-US in 20 patients with suspected or confirmed YF and compared the results with those obtained in subsequent CAs. Ultrasound-guided biopsies were used for tissue sampling of liver, kidneys, lungs, spleen, and heart. Liver samples from MIA-US and CA were submitted for RT-PCR and immunohistochemistry for detection of YF virus antigen. Of the 20 patients, 17 had YF diagnosis confirmed after autopsy by histopathological and molecular analysis. There was 100% agreement between MIA-US and CA in determining the cause of death (panlobular hepatitis with hepatic failure) and main disease (yellow fever). Further, MIA-US obtained samples with good quality for molecular studies and for the assessment of the systemic involvement of the disease. Main extrahepatic findings were pulmonary hemorrhage, pneumonia, acute tubular necrosis, and glomerulonephritis. One patient was a 24-year-old, 27-week pregnant woman; MIA-US assessed the placenta and provided adequate placental tissue for analysis. CONCLUSIONS: MIA-US is a reliable tool for rapid post-mortem diagnosis of yellow fever and can be used as an alternative to conventional autopsy in regions at risk for hemorrhagic fever outbreaks with limited resources to perform complete diagnostic autopsy.


Assuntos
Autopsia/métodos , Epidemias , Ultrassonografia de Intervenção/métodos , Febre Amarela/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Estudos Prospectivos , Febre Amarela/epidemiologia , Adulto Jovem
6.
Am. j. trop. med. hyg ; 101(1): 180-188, July 2019. ilus, tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IIERPROD, Sec. Est. Saúde SP | ID: biblio-1016853

RESUMO

Faced with the reemergence of yellow fever (YF) in the metropolitan region of São Paulo, Brazil, we developed a retrospective study to describe the cases of YF attended at the Institute of Infectology Emilio Ribas from January to March 2018 and analyze the factors associated with death, from the information obtained in the hospital epidemiological investigation. A total of 72 cases of sylvatic YF were confirmed, with 21 deaths (29.2% lethality rate). Cases were concentrated in males (80.6%) and in the age group of 30 to 59 years (56.9%). Two logistic regression models were performed, with continuous variables adjusted for the time between onset of symptoms and hospitalization. The first model indicated age (odds ratiosadjusted [ORadj]: 1.038; CI 95%: 1.008-1.212), aspartate aminotransferase (AST) (ORadj: 1.038; CI 95%: 1.005-1.072), and creatinine (ORadj: 2.343; CI 95%: 1.205-4.553) were independent factors associated with mortality. The second model indicated age (ORadj: 1.136; CI 95%: 1.013-1.275), alanine aminotransferase (ALT) (ORadj: 1.118; CI 95%: 1.018-1.228), and creatinine (ORadj: 2.835; CI 95%: 1.352-5,941). The risk of death in the model with continuous variables was calculated from the increase of 1 year (age), 1 mg/dL (creatinine), and 100 U/L for AST and ALT. Another logistic regression analysis with dichotomous variables indicated AST > 1,841 IU/L (ORadj: 12.92; CI 95%: 1.50-111.37) and creatinine > 1.2 mg/dL (ORadj: 81.47; CI 95%: 11.33-585.71) as independent factors associated with death. These results may contribute to the appropriate clinical management of patients with YF in health-care services and improve the response to outbreaks and public health emergencies


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Febre Amarela/epidemiologia , Brasil/epidemiologia
7.
Mem Inst Oswaldo Cruz ; 114: e190076, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038550

RESUMO

BACKGROUND: In Brazil, the Yellow Fever virus (YFV) is endemic in the Amazon, from where it eventually expands into epidemic waves. Coastal south-eastern (SE) Brazil, which has been a YFV-free region for eight decades, has reported a severe sylvatic outbreak since 2016. The virus spread from the north toward the south of the Rio de Janeiro (RJ) state, causing 307 human cases with 105 deaths during the 2016-2017 and 2017-2018 transmission seasons. It is unclear, however, whether the YFV would persist in the coastal Atlantic Forest of RJ during subsequent transmission seasons. OBJECTIVES: To conduct a real-time surveillance and assess the potential persistence of YFV in the coastal Atlantic Forest of RJ during the 2018-2019 transmission season. METHODS: We combined epizootic surveillance with fast diagnostic and molecular, phylogenetic, and evolutionary analyses. FINDINGS: Using this integrative strategy, we detected the first evidence of YFV re-emergence in the third transmission season (2018-2019) in a dying howler monkey from the central region of the RJ state. The YFV detected in 2019 has the molecular signature associated with the current SE YFV outbreak and exhibited a close phylogenetic relationship with the YFV lineage that circulated in the same Atlantic Forest fragment during the past seasons. This lineage circulated along the coastal side of the Serra do Mar mountain chain, and its evolution seems to be mainly driven by genetic drift. The potential bridge vector Aedes albopictus was found probing on the recently dead howler monkey in the forest edge, very close to urban areas. MAIN CONCLUSIONS: Collectively, our data revealed that YFV transmission persisted at the same Atlantic Forest area for at least three consecutive transmission seasons without the need of new introductions. Our real-time surveillance strategy permitted health authorities to take preventive actions within 48 h after the detection of the sick non-human primate. The local virus persistence and the proximity of the epizootic forest to urban areas reinforces the concern with regards to the risk of re-urbanisation and seasonal re-emergence of YFV, stressing the need for continuous effective surveillance and high vaccination coverage in the SE region, particularly in RJ, an important tourist location.


Assuntos
Aedes/virologia , Febre Amarela/epidemiologia , Febre Amarela/virologia , Vírus da Febre Amarela/genética , Alouatta , Animais , Brasil/epidemiologia , Surtos de Doenças , Humanos , Filogeografia , Estações do Ano , População Urbana , Febre Amarela/transmissão
8.
Mem Inst Oswaldo Cruz ; 114: e180509, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31066755

RESUMO

BACKGROUND: The outbreak of sylvatic Yellow Fever (SYF) in humans during 2016-2017 in Brazil is one of the greatest in the history of the disease. The occurrence of the disease in areas with low vaccination coverage favoured the dissemination of the disease; therefore, it is necessary to identify the areas vulnerability to the YF virus (YFV) to assist in the adoption of preventive measures. OBJECTIVE: To correlate the physical-environmental elements associated with the occurrence of SYF in humans via a multicriteria analysis. METHODS: For the multicriteria analysis, preponderant elements related to SYF occurrences, including soil usage and coverage, temperature, precipitation, altitude, mosquito transmitters, and non-human primate occurrence areas, were considered. The results were validated by assessing the correlation between the incidence of SYF and the vulnerable areas identified in the multicriteria analysis. RESULTS: Two regions with different vulnerability to the occurrence of the disease were identified in the multicriteria analysis, with emphasis on the southern areas of the state of São Paulo northeast areas of Minas Gerais, and the entire states of Rio de Janeiro and Espírito Santo. The map of SYF vulnerability obtained in the multicriteria analysis coincides with the areas in which cases of the disease have been recorded. The regions that presented the greatest suitability were in fact the municipalities with the highest incidence. MAIN CONCLUSIONS: The multicriteria analysis revealed that the elements that were used are suited for and consistent in the prediction of the areas that are vulnerable to SYF. The results obtained indicate the proximity of the areas that are most vulnerable to the disease to densely populated areas where an Aedes aegypti infestation was observed, which confers a high risk of re-urbanisation of YF.


Assuntos
Aedes/virologia , Febre Amarela/transmissão , Animais , Brasil/epidemiologia , Doenças Endêmicas/prevenção & controle , Sistemas de Informação Geográfica , Humanos , Densidade Demográfica , Vigilância da População , Medição de Risco , Urbanização , Febre Amarela/epidemiologia , Febre Amarela/prevenção & controle , Vacina contra Febre Amarela
9.
Am J Trop Med Hyg ; 101(1): 180-188, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31134884

RESUMO

Faced with the reemergence of yellow fever (YF) in the metropolitan region of São Paulo, Brazil, we developed a retrospective study to describe the cases of YF attended at the Institute of Infectology Emilio Ribas from January to March 2018 and analyze the factors associated with death, from the information obtained in the hospital epidemiological investigation. A total of 72 cases of sylvatic YF were confirmed, with 21 deaths (29.2% lethality rate). Cases were concentrated in males (80.6%) and in the age group of 30 to 59 years (56.9%). Two logistic regression models were performed, with continuous variables adjusted for the time between onset of symptoms and hospitalization. The first model indicated age (odds ratiosadjusted [ORadj]: 1.038; CI 95%: 1.008-1.212), aspartate aminotransferase (AST) (ORadj: 1.038; CI 95%: 1.005-1.072), and creatinine (ORadj: 2.343; CI 95%: 1.205-4.553) were independent factors associated with mortality. The second model indicated age (ORadj: 1.136; CI 95%: 1.013-1.275), alanine aminotransferase (ALT) (ORadj: 1.118; CI 95%: 1.018-1.228), and creatinine (ORadj: 2.835; CI 95%: 1.352-5,941). The risk of death in the model with continuous variables was calculated from the increase of 1 year (age), 1 mg/dL (creatinine), and 100 U/L for AST and ALT. Another logistic regression analysis with dichotomous variables indicated AST > 1,841 IU/L (ORadj: 12.92; CI 95%: 1.50-111.37) and creatinine > 1.2 mg/dL (ORadj: 81.47; CI 95%: 11.33-585.71) as independent factors associated with death. These results may contribute to the appropriate clinical management of patients with YF in health-care services and improve the response to outbreaks and public health emergencies.


Assuntos
Febre Amarela/diagnóstico , Febre Amarela/mortalidade , Adolescente , Adulto , Brasil/epidemiologia , Criança , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Febre Amarela/epidemiologia , Adulto Jovem
10.
Emerg Infect Dis ; 25(6): 1248-1249, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30870138

RESUMO

In 2018, yellow fever with hepatitis was diagnosed for 2 unvaccinated travelers returning to France from Brazil. Hepatitis persisted for >6 months; liver enzyme levels again increased 2 months after disease onset with no detection of yellow fever virus RNA or other pathogens. Persistent hepatitis with hepatic cytolysis rebound probably resulted from immune response.


Assuntos
Hepatite/epidemiologia , Febre Amarela/epidemiologia , Vírus da Febre Amarela , Biópsia , Brasil/epidemiologia , Comorbidade , Hepatite/diagnóstico , Hepatite/etiologia , Humanos , Testes de Função Hepática , Vigilância em Saúde Pública , Febre Amarela/diagnóstico , Febre Amarela/virologia
11.
Emerg Microbes Infect ; 8(1): 218-231, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30866775

RESUMO

The yellow fever virus (YFV) caused a severe outbreak in Brazil in 2016-2018 that rapidly spread across the Atlantic Forest in its most populated region without viral circulation for almost 80 years. A comprehensive entomological survey combining analysis of distribution, abundance and YFV natural infection in mosquitoes captured before and during the outbreak was conducted in 44 municipalities of five Brazilian states. In total, 17,662 mosquitoes of 89 species were collected. Before evidence of virus circulation, mosquitoes were tested negative but traditional vectors were alarmingly detected in 82% of municipalities, revealing high receptivity to sylvatic transmission. During the outbreak, five species were found positive in 42% of municipalities. Haemagogus janthinomys and Hg. leucocelaenus are considered the primary vectors due to their large distribution combined with high abundance and natural infection rates, concurring together for the rapid spread and severity of this outbreak. Aedes taeniorhynchus was found infected for the first time, but like Sabethes chloropterus and Aedes scapularis, it appears to have a potential local or secondary role because of their low abundance, distribution and infection rates. There was no evidence of YFV transmission by Aedes albopictus and Aedes aegypti, although the former was the most widespread species across affected municipalities, presenting an important overlap between the niches of the sylvatic vectors and the anthropic ones. The definition of receptive areas, expansion of vaccination in the most affected age group and exposed populations and the adoption of universal vaccination to the entire Brazilian population need to be urgently implemented.


Assuntos
Surtos de Doenças , Mosquitos Vetores/classificação , Febre Amarela/epidemiologia , Febre Amarela/transmissão , Animais , Brasil/epidemiologia , Cidades , Feminino , Masculino , Mosquitos Vetores/virologia , Filogeografia , Dinâmica Populacional , Vírus da Febre Amarela
13.
Travel Med Infect Dis ; 28: 46-51, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30583006

RESUMO

BACKGROUND: Yellow Fever (YF) is a high fatality rate disease (30-50%) caused by Flavivirus, present in some African and South American countries. In order to determine the magnitude and epidemiological distribution of YF cases, vaccination coverage and most affected regions in Brazil, a descriptive epidemiological study monitoring the last outbreak was undertaken in Portugal. METHOD: The Brazilian database "Portal da Saude" was used to collect data on cases of YF. We used Microsoft Excel on a weekly basis to update the suspected, confirmed and mortality cases as well as the case fatality rate and epizootics in non-human primates. RESULTS: Case Fatality Rate was 33.6%. A total and 82% of confirmed cases were males. The outbreak predominantly affected two south-eastern states, Minas Gerais and Espírito Santo, both with a very low vaccination coverage. CONCLUSIONS: The last outbreak of YF was by far the largest observed over the last few decades! Until the emergence of this outbreak, Espírito Santo, Bahia and Rio de Janeiro were states of low risk for YF and the vaccine not previously recommended. The World Health Organization's "Global Strategy to Eliminate Yellow Fever Epidemic" (EYE) should be on the way, to prevent YF outbreaks in Brazil and other countries in Africa and South America.


Assuntos
Febre Amarela/epidemiologia , Animais , Brasil/epidemiologia , Surtos de Doenças , Monitoramento Epidemiológico , Humanos , Portugal , Febre Amarela/mortalidade , Febre Amarela/prevenção & controle , Zoonoses/epidemiologia
14.
Am J Cardiol ; 123(5): 833-838, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30545483

RESUMO

Incidence of Yellow Fever (YF) has increased in Brazil, and cardiac findings such as bradyarrhythmias and conduction abnormalities have been described. We aimed to perform a comprehensive cardiac evaluation of patients with YF, and to assess the association between cardiac involvement and disease severity. Patients hospitalized with YF from February to March 2018 underwent clinical and laboratory evaluation, focused bedside echocardiography (GE Vivid IQ), electrocardiogram and, in case of alterations, 24-hours Holter. Patients were divided into 2 groups according to YF severity. Five patients underwent magnetic resonance imaging and 3 had necropsy. Seventy patients had confirmed YF, 69% with severe form. Mean age was 48 ± 14 years, 63 (90%) were males and 5 (7%) died. Significant electrocardiogram abnormalities were present in 52% of patients with mild/moderate form of YF (G1) and 77% of those with severe form (G2), p = 0.046. Sinus bradycardia was observed in 24% (N = 17): G1 23% versus G2 25%, p = 0.67. Among 32 patients who underwent Holter, 14 (44%) had mean HR <60 beats per minute, being 8 from G2. Echocardiogram revealed left ventricular dysfunction in 4 (6%) patients, from G2. Left ventricular wall thickening with a hyper-refringent myocardial texture suggesting infiltration was observed in 17 patients (G1 18% vs G2 27%, p = 0.55). One magnetic resonance (G2) was suggestive of myocarditis, and one necropsy revealed areas of myocardial necrosis and acute myocarditis. In conclusion, cardiac involvement was observed in patients with YF, most commonly bradycardia and myocardial hyper-refringent texture suggestive of infiltration.


Assuntos
Bradicardia/etiologia , Eletrocardiografia , Imagem Cinética por Ressonância Magnética/métodos , Miocardite/etiologia , Miocárdio/patologia , Febre Amarela/complicações , Bradicardia/epidemiologia , Brasil/epidemiologia , Ecocardiografia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Miocardite/epidemiologia , Estudos Retrospectivos , Febre Amarela/epidemiologia
15.
Acta Trop ; 190: 395-402, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30552880

RESUMO

Arboviruses have become a major public health concern in Brazil, especially after Zika virus (ZIKV) and Chikungunya virus (CHIKV) introduction, leading to massive epidemics. We conducted an investigation of arboviruses in patients with acute febrile illness for less than five days in Mato Grosso state (MT) during the period of ZIKV and CHIKV dissemination in Brazil. To achieve that, 453 human serum samples of patients suspected of Dengue (DENV), Yellow Fever (YFV), ZIKV or CHIKV collected in health units of 31 cities of MT were subjected to RT-PCR protocols for 10 flaviviruses, 5 alphaviruses and orthobunyaviruses from Simbu serogroup, nucleotide sequencing and viral isolation. Regarding flaviviruses, five (1.1%) patients were infected with DENV-1 genotype V, 22 (4.4%) with DENV-4 genotype II, 3 (0.7%) with YFV South American genotype II and five (1.1%) with ZIKV Asian genotype. The first human case of ZIKV in MT was detected in this study during August, 2015 in Tapurah. Alphaviruses were detected in 2 (0.4%) patients infected with CHIKV genotype ECSA, 1 (0.2%) with Madariaga (EEEV) lineage III and 34 (7.5%) with Mayaro (MAYV) genotype L. Four (11.4%) patients presented dual infections with DENV-1/ZIKV, DENV-1/DENV4, DENV-4/MAYV and ZIKV/MAYV. The majority - 13/34 positive for MAYV, one for Madariaga virus - are residents in Várzea Grande (VG), metropolitan region of Cuiabá, capital of MT. The first CHIKV infection in MT was detected in this study in Mirassol D'Oeste, during July, 2015. In addition, 20 (4.4%) patients were positive for OROV Segment S genotype IA. These results reinforce the variation in arboviruses frequency and distribution during outbreaks, highlinghing the importance of differential diagnosis to identify agents silently co-circulating with major health problem arboviruses.


Assuntos
Arbovirus/genética , Arbovirus/isolamento & purificação , Febre de Chikungunya/epidemiologia , Dengue/epidemiologia , Febre/virologia , Infecção por Zika virus/epidemiologia , Adolescente , Adulto , Brasil/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Criança , Pré-Escolar , Coinfecção/epidemiologia , Coinfecção/virologia , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Febre Amarela/epidemiologia , Febre Amarela/virologia , Vírus da Febre Amarela/genética , Vírus da Febre Amarela/isolamento & purificação , Adulto Jovem , Zika virus/genética , Zika virus/isolamento & purificação , Infecção por Zika virus/virologia
16.
N Engl J Med ; 381(5): 444-454, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29443626

RESUMO

BACKGROUND: In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign. METHODS: We recruited participants in four age strata at six vaccination sites. We assessed neutralizing antibody titers against yellow fever virus in blood samples obtained before vaccination and at 1 month and 1 year after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT50). Participants with a PRNT50 titer of 10 or higher were considered to be seropositive. Those with a baseline titer of less than 10 who became seropositive at follow-up were classified as having undergone seroconversion. Participants who were seropositive at baseline and who had an increase in the titer by a factor of 4 or more at follow-up were classified as having an immune response. RESULTS: Among 716 participants who completed the 1-month follow-up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after vaccination. Among 493 participants who were seronegative at baseline, 482 (98%; 95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response. Lower baseline titers were associated with a higher probability of having an immune response (P<0.001). Among 684 participants who completed the 1-year follow-up, 666 (97%; 95% CI, 96 to 98) were seropositive for yellow fever antibody. The distribution of titers among the participants who were seronegative for yellow fever antibody at baseline varied significantly among age groups at 1 month and at 1 year (P<0.001 for both comparisons). CONCLUSIONS: A fractional dose of the 17DD yellow fever vaccine was effective at inducing seroconversion in participants who were seronegative at baseline. Titers remained above the threshold for seropositivity at 1 year after vaccination in nearly all participants who were seropositive at 1 month after vaccination. These findings support the use of fractional-dose vaccination for outbreak control. (Funded by the U.S. Agency for International Development and the Centers for Disease Control and Prevention.).


Assuntos
Vacina contra Febre Amarela/imunologia , Febre Amarela/prevenção & controle , Vírus da Febre Amarela/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , República Democrática do Congo/epidemiologia , Surtos de Doenças , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Soroconversão , Febre Amarela/epidemiologia , Febre Amarela/imunologia , Vacina contra Febre Amarela/administração & dosagem , Vírus da Febre Amarela/isolamento & purificação , Adulto Jovem
20.
PLoS Negl Trop Dis ; 12(12): e0007029, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30532188

RESUMO

BACKGROUND: Between December 2015 and July 2016, a yellow fever (YF) outbreak affected urban areas of Angola and the Democratic Republic of the Congo (DRC). We described the outbreak in DRC and assessed the accuracy of the YF case definition, to facilitate early diagnosis of cases in future urban outbreaks. METHODOLOGY/PRINCIPAL FINDINGS: In DRC, suspected YF infection was defined as jaundice within 2 weeks after acute fever onset and was confirmed by either IgM serology or PCR for YF viral RNA. We used case investigation and hospital admission forms. Comparing clinical signs between confirmed and discarded suspected YF cases, we calculated the predictive values of each sign for confirmed YF and the diagnostic accuracy of several suspected YF case definitions. Fifty seven of 78 (73%) confirmed cases had travelled from Angola: 88% (50/57) men; median age 31 years (IQR 25-37). 15 (19%) confirmed cases were infected locally in urban settings in DRC. Median time from symptom onset to healthcare consultation was 7 days (IQR 6-9), to appearance of jaundice 8 days (IQR 7-11), to sample collection 9 days (IQR 7-14), and to hospitalization 17 days (IQR 11-26). A case definition including fever or jaundice, combined with myalgia or a negative malaria test, yielded an improved sensitivity (100%) and specificity (57%). CONCLUSIONS/SIGNIFICANCE: As jaundice appeared late, the majority of cases were diagnosed too late for supportive care and prompt vector control. In areas with known local YF transmission, a suspected case definition without jaundice as essential criterion could facilitate earlier YF diagnosis, care and control.


Assuntos
Febre Amarela/epidemiologia , Adulto , Angola , República Democrática do Congo/epidemiologia , Surtos de Doenças , Feminino , Humanos , Masculino , Viagem , População Urbana , Febre Amarela/diagnóstico , Febre Amarela/virologia , Vírus da Febre Amarela/genética , Vírus da Febre Amarela/isolamento & purificação , Vírus da Febre Amarela/fisiologia
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