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1.
Acta Trop ; 225: 106199, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34740635

RESUMO

Yellow fever (YF) is a major public-health problem in Africa. Yellow fever virus (YFV), the etiological agent responsible for the disease, exhibits clear delineation of phylogeography between East/Central Africa and West Africa. In order to decipher the genetic nature of the YFV epidemic between these areas, we performed a genome-wide study on its African isolates using the McDonald-Kreitman (MK) test in combination with the type II functional divergence analysis. The results showed that adaptive genetic diversifications have occurred on viral nonstructural protein 1 (NS1) and NS5, which are essential for viral genome replication and immune antagonism, with the East/Central African-West African epidemic split. On both proteins, a number of amino acid replacements have been favored by functional divergence. These findings could help to bridge the gap between the phylogeographic delineation and niche adaptation underlying the YFV-epidemic across Africa and shed light on viral determinants of this process.


Assuntos
Febre Amarela , Vírus da Febre Amarela , África Central/epidemiologia , Estudo de Associação Genômica Ampla , Humanos , Epidemiologia Molecular , Filogeografia , Febre Amarela/epidemiologia , Vírus da Febre Amarela/genética
2.
Brasília, D.F.; OPAS; 2021-11-12.
em Português | PAHO-IRIS | ID: phr-55180

RESUMO

Em 2021, três países da Região das Américas (Brasil, Peru e Venezuela) notificaram casos confirmados de febre amarela. Em 2020, dois países da Região das Américas notificaram casos confirmados de febre amarela: Bolívia e Peru. A reemergência do vírus da febre amarela tem sido relatada na região extra-amazônica do Brasil desde 2014. A expansão da área histórica de transmissão da febre amarela para áreas anteriormente consideradas sem risco resultou em duas ondas de transmissão durante o período sazonal de 2016-2017, com 778 casos humanos confirmados incluindo 262 mortes, e outra durante o período sazonal de 2017-2018, com 1.376 casos humanos confirmados, incluindo 483 mortes. Consequentemente, o Brasil mudou suas áreas recomendadas de vacinação contra a febre amarela de modo a incluir todo o País.


Assuntos
Febre Amarela , Vigilância em Saúde Pública , Epidemiologia , Regulamento Sanitário Internacional , América , Brasil
3.
Cad Saude Publica ; 37(9): e00127620, 2021.
Artigo em Português | MEDLINE | ID: mdl-34669767

RESUMO

The objective was to analyze the diffusion of cases of yellow fever in time and space in the epidemic of 2017 in the state of Espírito Santo, Brazil. An ecological observational study was performed with spatial analysis of yellow fever cases. Georeferencing of information and spatial analysis used the digital grid for the state of Espírito Santo, divided into 78 municipalities (counties), using the Arcgis software, 10.3. Geostatistical analysis was performed using the ordinary kriging function. The study found an incidence of 4.85/100,000 inhabitants of sylvatic yellow fever in Espírito Santo in 2017, with 29.74% case-fatality. Sylvatic yellow fever cases were distributed across 34 of the state's 78 municipalities, representing 43% of its territory. The temporal distribution of reported yellow fever cases in the current study occurred from the 1st to the 19th Epidemiological Weeks (EW). The geostatistical spatial analysis via ordinary kriging demonstrated spatial diffusion by yellow fever contagion among the municipalities in the state of Espírito Santo, with spatial continuity. The disease emerged in the state in the EW 1 through municipalities bordering on the state of Minas Gerais. Geoprocessing showed that yellow fever reached the state of Espírito Santo through the municipalities bordering on the state of Minas Gerais, moving eastward in the state and reaching the Atlantic coastline. There was a higher concentration of cases and persistence in the state's Central and Metropolitan regions, which have areas of Atlantic Forest, showing a pattern of diffusion continuity by contagion.


Assuntos
Epidemias , Febre Amarela , Brasil/epidemiologia , Cidades , Humanos , Incidência , Febre Amarela/epidemiologia
4.
Front Public Health ; 9: 715759, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34676194

RESUMO

Vector-borne emerging and re-emerging diseases pose considerable public health problem worldwide. Some of these diseases are emerging and/or re-emerging at increasing rates and appeared in new regions in the past two decades. Studies emphasized that the interactions among pathogens, hosts, and the environment play a key role for the emergence or re-emergence of these diseases. Furthermore, social and demographic factors such as human population growth, urbanization, globalization, trade exchange and travel and close interactions with livestock have significantly been linked with the emergence and/or re-emergence of vector-borne diseases. Other studies emphasize the ongoing evolution of pathogens, proliferation of reservoir populations, and antimicrobial drug use to be the principal exacerbating forces for emergence and re-emergence of vector-borne infectious diseases. Still other studies equivocally claim that climate change has been associated with appearance and resurgence of vector-borne infectious diseases. Despite the fact that many important emerging and re-emerging vector-borne infectious diseases are becoming better controlled, our success in stopping the many new appearing and resurging vector-borne infectious diseases that may happen in the future seems to be uncertain. Hence, this paper reviews and synthesizes the existing literature to explore global patterns of emerging and re-emerging vector-borne infections and the challenges for their control. It also attempts to give insights to the epidemiological profile of major vector-borne diseases including Zika fever, dengue, West Nile fever, Crimean-Congo hemorrhagic fever, Chikungunya, Yellow fever, and Rift Valley fever.


Assuntos
Febre de Chikungunya , Doenças Transmissíveis Emergentes , Doenças Transmitidas por Vetores , Febre Amarela , Infecção por Zika virus , Zika virus , Animais , Doenças Transmissíveis Emergentes/epidemiologia , Vetores de Doenças , Humanos , Infecção por Zika virus/epidemiologia
5.
BMC Infect Dis ; 21(1): 1089, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34688249

RESUMO

BACKGROUND: Understanding the occurrence of yellow fever epidemics is critical for targeted interventions and control efforts to reduce the burden of disease. We assessed data on the yellow fever incidence and mortality rates in Africa. METHODS: We searched the Cochrane Library, SCOPUS, MEDLINE, CINAHL, PubMed, Embase, Africa-wide and Web of science databases from 1 January 1975 to 30th October 2020. Two authors extracted data from included studies independently and conducted a meta-analysis. RESULTS: Of 840 studies identified, 12 studies were deemed eligible for inclusion. The incidence of yellow fever per 100,000 population ranged from < 1 case in Nigeria, < 3 cases in Uganda, 13 cases in Democratic Republic of the Congo, 27 cases in Kenya, 40 cases in Ethiopia, 46 cases in Gambia, 1267 cases in Senegal, and 10,350 cases in Ghana. Case fatality rate associated with yellow fever outbreaks ranged from 10% in Ghana to 86% in Nigeria. The mortality rate ranged from 0.1/100,000 in Nigeria to 2200/100,000 in Ghana. CONCLUSION: The yellow fever incidence rate is quite constant; in contrast, the fatality rates vary widely across African countries over the study period. Standardized demographic health surveys and surveillance as well as accurate diagnostic measures are essential for early recognition, treatment and control.


Assuntos
Febre Amarela , Bases de Dados Factuais , Surtos de Doenças , Humanos , Incidência , Nigéria , Febre Amarela/epidemiologia
6.
BMC Infect Dis ; 21(1): 1054, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635069

RESUMO

BACKGROUND: Yellow fever outbreaks are documented to have a considerable impact not only on the individuals but on the health system with significant economic implications. Efforts to eliminate yellow fever outbreaks globally through the EYE strategy remains important following outbreaks in Africa, Nigeria included. The outbreaks reported in Nigeria, since 2017 and the response efforts provide an opportunity to document and guide interventions for improving future outbreaks in Nigeria and other countries in Africa. METHODS: We reviewed the available yellow fever surveillance and vaccination response data between September 2017 and September 2019 across the 36 states across Nigeria. We described the epidemiology of the difference outbreaks and the periods for all interventions. We also documented the emergency vaccination responses as well as preventive mass vaccinations implemented towards improving population immunity and limiting epidemic potentials in Nigeria. RESULTS: A total of 7894 suspected cases with 287 laboratory-confirmed cases were reported in Nigeria between September 2017 and September 2019 with a mean age of 19 years and a case fatality of 2.7% amongst all reported cases. Outbreaks were confirmed in 55 LGAs with most of the outbreaks across four major epicentres in Kwara/Kogi, Edo, Ebonyi and Bauchi states. In response to these outbreaks, eight reactive vaccination campaigns, supported through ICG applications, were implemented. The duration for responding to the outbreaks ranged from 15 to 132 days (average 68 days) and a total of 45,648,243 persons aged < 45 years vaccinated through reactive and preventive mass campaigns between September 2017 and September 2019. CONCLUSIONS: Nigeria experienced intermediate outbreaks of yellow fever between September 2017 and 2019 with vaccination responses conducted to control these outbreaks. However, there are delays in the timeliness of responses and more efforts required in improving reporting, response times and preparedness to further prevent morbidity and mortality from the yellow fever disease outbreaks. These efforts, including improving routine yellow fever coverage, contribute towards improving population immunity and other activities related to achieving the goals of the EYE strategy.


Assuntos
Surtos de Doenças , Febre Amarela , Adulto , Humanos , Vacinação em Massa , Nigéria/epidemiologia , Vacinação , Febre Amarela/epidemiologia , Febre Amarela/prevenção & controle , Adulto Jovem
7.
Washington, D.C.; OPS; 2021-10-14.
em Inglês, Espanhol | PAHO-IRIS | ID: phr-54999

RESUMO

In 2021, three countries in the Region of the Americas (Brazil, Peru, and Venezuela) have reported confirmed yellow fever cases. In 2020, two countries in the Region of the Americas reported confirmed cases of yellow fever: Bolivia and Peru. A situation summary of the countries that reported confirmed yellow fever cases in 2021 is provided here.


En 2021, tres países de la Región (Brasil, Perú y Venezuela) notificaron casos confirmados de fiebre amarilla. En 2020 fueron dos los países de la región de las Américas que notificaron casos confirmados de fiebre amarilla: Brasil y Perú. Aquí se presenta un resumen de la situación los países que notificaron casos confirmados de fiebre amarilla en 2021.


Assuntos
Febre Amarela , Vacina contra Febre Amarela , Regulamento Sanitário Internacional , Emergências , Brasil , Peru , Febre Amarela , Vacina contra Febre Amarela , Regulamento Sanitário Internacional , Emergências , Brasil , Peru
8.
BMJ Glob Health ; 6(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34535490

RESUMO

INTRODUCTION: COVID-19 vaccines are now being distributed to low- and middle-income countries (LMICs), with global urgency surrounding national vaccination plans. LMICs have significant experience implementing vaccination campaigns to respond to epidemic threats but are often hindered by chronic health system challenges. We sought to identify transferable lessons for COVID-19 vaccination from the rollout of three vaccines that targeted adult groups in Africa and South America: MenAfriVac (meningitis A); 17D (yellow fever) and rVSV-ZEBOV (Ebola virus disease). METHODS: We conducted a rapid literature review and 24 semi-structured interviews with technical experts who had direct implementation experience with the selected vaccines in Africa and South America. We identified barriers, enablers, and key lessons from the literature and from participants' experiences. Interview data were analysed thematically according to seven implementation domains. RESULTS: Participants highlighted multiple components of vaccination campaigns that are instrumental for achieving high coverage. Community engagement is an essential and effective tool, requiring dedicated time, funding and workforce. Involving local health workers is a key enabler, as is collaborating with community leaders to map social groups and tailor vaccination strategies to their needs. Vaccination team recruitment and training strategies need to be enhanced to support vaccination campaigns. Although recognised as challenging, integrating vaccination campaigns with other routine health services can be highly beneficial if well planned and coordinated across health programmes and with communities. CONCLUSION: As supplies of COVID-19 vaccines become available to LMICs, countries need to prepare to efficiently roll out the vaccine, encourage uptake among eligible groups and respond to potential community concerns. Lessons from the implementation of these three vaccines that targeted adults in LMICs can be used to inform best practice for COVID-19 and other epidemic vaccination campaigns.


Assuntos
COVID-19 , Vacinas contra Ebola , Doença pelo Vírus Ebola , Meningite , Febre Amarela , Adulto , Vacinas contra COVID-19 , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/prevenção & controle , Humanos , Programas de Imunização , SARS-CoV-2 , Febre Amarela/epidemiologia , Febre Amarela/prevenção & controle
9.
Acta Biomed ; 92(4): e2021098, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34487067

RESUMO

BACKGROUND AND AIM: Current demographic changes and improvement of quality of life of elderly population have direct consequences on international travelling. The older traveller demands for specific care and precautions to be observed, as for the yellow fever (YF) vaccination, due to the increased incidence rate of adverse events following immunization (AEFI) in people aged 60 years or over. The aim of our study was to determine the adherence to YF vaccine and travel behaviours in a sample of elderly travellers moving to YF endemic areas. METHODS: Participants in this cohort study were offered YF vaccine, and informed about the increased risk of AEFIs and the unavoidable risk of acquiring YF at the destination. The research was planned on survey-based design, using pre- and post-travel questionnaires. RESULTS: In 2018, 239 travellers aged 60 years or older attended our travel clinic, of whom 36.8% (n = 88) planned to travel to YF endemic areas and 23.0% (n = 55) for the first time. Of these, 63.6% accepted and 36.4% rejected the vaccination, with 15 travellers moving to endemic areas without immunization, including one patient who presented contraindications to YF vaccine. CONCLUSIONS: The presence of more than a third of elderly travellers who travelled without vaccination is a substantial public health problem and, since the number of older travellers continues to increase, it becomes necessary to implement robust actions to improve YF vaccine advocacy and adherence.


Assuntos
Vacina contra Febre Amarela , Febre Amarela , Idoso , Estudos de Coortes , Humanos , Qualidade de Vida , Viagem , Febre Amarela/prevenção & controle , Vacina contra Febre Amarela/efeitos adversos
10.
Nat Commun ; 12(1): 5374, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508072

RESUMO

The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and Zika virus, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic control system termed precision-guided sterile insect technique (pgSIT) in Aedes aegypti. PgSIT uses a simple CRISPR-based approach to generate flightless females and sterile males that are deployable at any life stage. Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, suppress, and even eliminate mosquito populations. This platform technology could be used in the field, and adapted to many vectors, for controlling wild populations to curtail disease in a safe, confinable, and reversible manner.


Assuntos
Aedes/virologia , Infertilidade Masculina/veterinária , Controle de Mosquitos/métodos , Mosquitos Vetores/virologia , Aedes/genética , Animais , Animais Geneticamente Modificados , Arbovírus , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/transmissão , Febre de Chikungunya/virologia , Dengue/prevenção & controle , Dengue/transmissão , Dengue/virologia , Feminino , Humanos , Infertilidade Masculina/genética , Masculino , Modelos Biológicos , Mosquitos Vetores/genética , Febre Amarela/prevenção & controle , Febre Amarela/transmissão , Febre Amarela/virologia , Zika virus , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
11.
Medicina (Kaunas) ; 57(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34577794

RESUMO

In the battle to quickly identify potential yellow fever arbovirus outbreaks in the Democratic Republic of the Congo, active syndromic surveillance of acute febrile jaundice patients across the country is a powerful tool. However, patients who test negative for yellow fever virus infection are too often left without a diagnosis. By retroactively screening samples for other potential viral infections, we can both try to find sources of patient disease and gain information on how commonly they may occur and co-occur. Several human arboviruses have previously been identified, but there remain many other viral families that could be responsible for acute febrile jaundice. Here, we assessed the prevalence of human herpes viruses (HHVs) in these acute febrile jaundice disease samples. Total viral DNA was extracted from serum of 451 patients with acute febrile jaundice. We used real-time quantitative PCR to test all specimens for cytomegalovirus (CMV), herpes simplex virus (HSV), human herpes virus type 6 (HHV-6) and varicella-zoster virus (VZV). We found 21.3% had active HHV replication (13.1%, 2.4%, 6.2% and 2.4% were positive for CMV, HSV, HHV-6 and VZV, respectively), and that nearly half (45.8%) of these infections were characterized by co-infection either among HHVs or between HHVs and other viral infection, sometimes associated with acute febrile jaundice previously identified. Our results show that the role of HHV primary infection or reactivation in contributing to acute febrile jaundice disease identified through the yellow fever surveillance program should be routinely considered in diagnosing these patients.


Assuntos
Infecções por Herpesviridae , Febre Amarela , Citomegalovirus , DNA Viral , República Democrática do Congo/epidemiologia , Herpesvirus Humano 3 , Humanos , Febre Amarela/diagnóstico , Febre Amarela/epidemiologia
12.
Einstein (Sao Paulo) ; 19: eAO5969, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34346987

RESUMO

OBJECTIVE: To assess Google Trends accuracy for epidemiological surveillance of dengue and yellow fever, and to compare the incidence of these diseases with the popularity of its terms in the state of São Paulo. METHODS: Retrospective cohort. Google Trends survey results were compared to the actual incidence of diseases, obtained from Centro de Vigilância Epidemiológica "Prof. Alexandre Vranjac", in São Paulo, Brazil, in periods between 2017 and 2019. The correlation was calculated by Pearson's coefficient and cross-correlation function. The accuracy was analyzed by sensitivity and specificity values. RESULTS: There was a statistically significant correlation between the variables studied for both diseases, Pearson coefficient of 0.91 for dengue and 0.86 for yellow fever. Correlation with up to 4 weeks of anticipation for time series was identified. Sensitivity was 87% and 90%, and specificity 69% and 78% for dengue and yellow fever, respectively. CONCLUSION: The incidence of dengue and yellow fever in the State of São Paulo showed a strong correlation with the popularity of its terms measured by Google Trends in weekly periods. Google Trends tool provided early warning, with high sensitivity, for the detection of outbreaks of these diseases.


Assuntos
Dengue , Febre Amarela , Brasil/epidemiologia , Dengue/epidemiologia , Surtos de Doenças , Humanos , Estudos Retrospectivos , Ferramenta de Busca , Febre Amarela/epidemiologia
13.
BMC Infect Dis ; 21(1): 819, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399718

RESUMO

BACKGROUND: Case fatality risk (CFR), commonly referred to as a case fatality ratio or rate, represents the probability of a disease case being fatal. It is often estimated for various diseases through analysis of surveillance data, case reports, or record examinations. Reported CFR values for Yellow Fever vary, offering wide ranges. Estimates have not been found through systematic literature review, which has been used to estimate CFR of other diseases. This study aims to estimate the case fatality risk of severe Yellow Fever cases through a systematic literature review and meta-analysis. METHODS: A search strategy was implemented in PubMed and Ovid Medline in June 2019 and updated in March 2021, seeking reported severe case counts, defined by fever and either jaundice or hemorrhaging, and the number of those that were fatal. The searches yielded 1,133 studies, and title/abstract review followed by full text review produced 14 articles reporting 32 proportions of fatal cases, 26 of which were suitable for meta-analysis. Four studies with one proportion each were added to include clinical case data from the recent outbreak in Brazil. Data were analyzed through an intercept-only logistic meta-regression with random effects for study. Values of the I2 statistic measured heterogeneity across studies. RESULTS: The estimated CFR was 39 % (95 % CI: 31 %, 47 %). Stratifying by continent showed that South America observed a higher CFR than Africa, though fewer studies reported estimates for South America. No difference was seen between studies reporting surveillance data and studies investigating outbreaks, and no difference was seen among different symptom definitions. High heterogeneity was observed across studies. CONCLUSIONS: Approximately 39 % of severe Yellow Fever cases are estimated to be fatal. This study provides the first systematic literature review to estimate the CFR of Yellow Fever, which can provide insight into outbreak preparedness and estimating underreporting.


Assuntos
Mortalidade , Febre Amarela/diagnóstico , Surtos de Doenças , Humanos , Febre Amarela/mortalidade
14.
Pan Afr Med J ; 38: 402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381546

RESUMO

Introduction: accurate and timely laboratory diagnosis of yellow fever (YF) is critical to the Eliminate Yellow Fever Epidemics (EYE) strategy. Gavi, the Vaccine Alliance recognized the need to support and build capacity in the national and regional laboratories in the Global YF Laboratory Network (GYFLN) as part of this strategy. Methods: to better understand current capacity, gaps and needs of the GYFLN laboratories in Africa, assessments were carried out in national and regional reference laboratories in the 25 African countries at high risk for YF outbreaks that were eligible for new financial support from Gavi. Results: the assessments found that the GYFLN in Africa has high capacity but 21% of specimens were not tested due to lack of testing kits or reagents and approximately 50% of presumptive YF cases were not confirmed at the regional reference laboratory due to problems with shipping. Conclusion: the laboratory assessments helped to document the baseline capacities of these laboratories prior to Gavi funding to support strengthening YF laboratories.


Assuntos
Surtos de Doenças , Laboratórios/estatística & dados numéricos , Febre Amarela/diagnóstico , África/epidemiologia , Fortalecimento Institucional , Epidemias , Humanos , Febre Amarela/epidemiologia
15.
Sci Rep ; 11(1): 16277, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381111

RESUMO

We investigated the sylvatic yellow fever (SYF) diffusion process in São Paulo (SP) between 2016 and 2019. We developed an ecological study of SYF through autochthonous human cases and epizootics of non-human primates (NHPs) that were spatiotemporally evaluated. We used kriging to obtain maps with isochrones representative of the evolution of the outbreak and characterized its diffusion pattern. We confirmed 648 human cases of SYF in SP, with 230 deaths and 843 NHP epizootics. Two outbreak waves were identified: one from West to East (2016 and 2017), and another from the Campinas region to the municipalities bordering Rio de Janeiro, Minas Gerais, and Paraná and those of the SP coast (2017-2019). The SYF outbreak diffusion process was by contagion. The disease did not exhibit jumps between municipalities, indicating that the mosquitoes and NHPs were responsible for transmitting the virus. There were not enough vaccines to meet the population at risk; hence, health authorities used information about the epizootic occurrence in NHPs in forest fragments to identify priority populations for vaccination.


Assuntos
Febre Amarela/epidemiologia , Animais , Brasil/epidemiologia , Surtos de Doenças/prevenção & controle , Humanos , Primatas/virologia , Vacinação/métodos , Febre Amarela/imunologia , Febre Amarela/virologia , Vírus da Febre Amarela/imunologia , Zoonoses/epidemiologia , Zoonoses/imunologia , Zoonoses/virologia
16.
J Environ Public Health ; 2021: 8230789, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34341668

RESUMO

Yellow Fever Virus (YFV) reemergence in Brazil was followed by human suffering and the loss of biodiversity of neotropical simians on the Atlantic coast. The underlying mechanisms were investigated with special focus on distinct landscape fragmentation thresholds in the affected municipalities. An ecological study in epidemiology is employed to assess the statistical relationship between events of YFV and forest fragmentation in municipal landscapes. Negative binomial regression model showed that highly fragmented forest cover was associated with an 85% increase of events of YFV in humans and simians (RR = 1.85, CI 95% = 1.24-2.75, p=0.003) adjusted by vaccine coverage, population size, and municipality area. Intermediate levels of forest cover combined with higher levels of forest edge densities contribute to the YFV dispersion and the exponential growth of YF cases. Strategies for forest conservation are necessary for the control and prevention of YF and other zoonotic diseases that can spillover from the fragmented forest remains to populated cities of the Brazilian Atlantic coast.


Assuntos
Febre Amarela , Animais , Brasil/epidemiologia , Humanos , Febre Amarela/epidemiologia , Vírus da Febre Amarela , Zoonoses
17.
PLoS Negl Trop Dis ; 15(8): e0009670, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34403427

RESUMO

BACKGROUND: Fever with jaundice is a common symptom of some infectious diseases. In public health surveillance within the Democratic Republic of the Congo (DRC), yellow fever is the only recognized cause of fever with jaundice. However, only 5% of the surveillance cases are positive for yellow fever and thus indicate the involvement of other pathogens. Leptospira spp. are the causative agents of leptospirosis, a widespread bacterial zoonosis, a known cause of fever with jaundice. This study aimed to determine the seropositivity of anti-Leptospira antibodies among suspected yellow fever cases and map the geographical distribution of possible leptospirosis in the DRC. METHODS: We conducted a retrospective study using 1,300 samples from yellow fever surveillance in the DRC from January 2017 to December 2018. Serum samples were screened for the presence of IgM against Leptospira spp. by a whole cell-based IgM ELISA (Patoc-IgM ELISA) at the Institut National de Recherche Biomedicale in Kinshasa (INRB) according to World Health Organization (WHO) guidance. Exploratory univariable and multivariable logistic regression analyses were undertaken to assess associations between socio-demographic factors and the presence of Leptospira IgM. RESULTS: Of the 1,300 serum samples screened, 88 (7%) showed evidence of IgM against Leptospira spp. Most positive cases (34%) were young adult males in the 20-29-year group. There were statistically significant associations between having Leptospira IgM antibodies, age, sex, and living area. Observed positive cases were mostly located in urban settings, and the majority lived in the province of Kinshasa. There was a statistically significant association between seasonality and IgM Leptospira spp. positivity amongst those living in Kinshasa, where most of the positive cases occurred during the rainy season. CONCLUSIONS: This study showed that leptospirosis is likely an overlooked cause of unexplained cases of fever with jaundice in the DRC and highlights the need to consider leptospirosis in the differential diagnosis of fever with jaundice, particularly in young adult males. Further studies are needed to identify animal reservoirs, associated risk factors, and the burden of human leptospirosis in the DRC.


Assuntos
Febre/diagnóstico , Febre/epidemiologia , Febre/microbiologia , Leptospirose/diagnóstico , Leptospirose/epidemiologia , Adolescente , Adulto , Animais , Anticorpos Antibacterianos/sangue , Criança , Pré-Escolar , República Democrática do Congo/epidemiologia , Humanos , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Icterícia/diagnóstico , Icterícia/epidemiologia , Icterícia/microbiologia , Leptospira/imunologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Febre Amarela/diagnóstico , Febre Amarela/epidemiologia , Febre Amarela/microbiologia , Adulto Jovem
18.
J Immunol ; 207(4): 1033-1043, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34321231

RESUMO

A single dose of the replication-competent, live-attenuated yellow fever virus (YFV) 17D vaccine provides lifelong immunity against human YFV infection. The magnitude, kinetics, and specificity of B cell responses to YFV 17D are relatively less understood than T cell responses. In this clinical study, we focused on early immune events critical for the development of humoral immunity to YFV 17D vaccination in 24 study subjects. More specifically, we studied the dynamics of several immune cell populations over time and the development of neutralizing Abs. At 7 d following vaccination, YFV RNA in serum as well as several antiviral proteins were detected as a sign of YFV 17D replication. Activation of Th1-polarized circulating T follicular helper cells followed germinal center activity, the latter assessed by the surrogate marker CXCL13 in serum. This coincided with a plasmablast expansion peaking at day 14 before returning to baseline levels at day 28. FluoroSpot-based analysis confirmed that plasmablasts were specific to the YFV-E protein. The frequencies of plasmablasts correlated with the magnitude of neutralizing Ab titers measured at day 90, suggesting that this transient B cell subset could be used as an early marker of induction of protective immunity. Additionally, YFV-specific memory B cells were readily detectable at 28 and 90 d following vaccination, and all study subjects tested developed protective neutralizing Ab titers. Taken together, these studies provide insights into key immune events leading to human B cell immunity following vaccination with the YFV 17D vaccine.


Assuntos
Anticorpos Neutralizantes/imunologia , Células T Auxiliares Foliculares/imunologia , Vacina contra Febre Amarela/imunologia , Febre Amarela/imunologia , Vírus da Febre Amarela/imunologia , Adolescente , Adulto , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Linfócitos B/imunologia , Citocinas/imunologia , Feminino , Humanos , Imunidade Humoral/imunologia , Cinética , Masculino , Pessoa de Meia-Idade , Vacinação/métodos , Vacinas Atenuadas/imunologia , Adulto Jovem
19.
J Chem Inf Model ; 61(8): 3804-3813, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34286575

RESUMO

Yellow fever (YF) is an acute viral hemorrhagic disease transmitted by infected mosquitoes. Large epidemics of YF occur when the virus is introduced into heavily populated areas with high mosquito density and low vaccination coverage. The lack of a specific small molecule drug treatment against YF as well as for homologous infections, such as zika and dengue, highlights the importance of these flaviviruses as a public health concern. With the advancement in computer hardware and bioactivity data availability, new tools based on machine learning methods have been introduced into drug discovery, as a means to utilize the growing high throughput screening (HTS) data generated to reduce costs and increase the speed of drug development. The use of predictive machine learning models using previously published data from HTS campaigns or data available in public databases, can enable the selection of compounds with desirable bioactivity and absorption, distribution, metabolism, and excretion profiles. In this study, we have collated cell-based assay data for yellow fever virus from the literature and public databases. The data were used to build predictive models with several machine learning methods that could prioritize compounds for in vitro testing. Five molecules were prioritized and tested in vitro from which we have identified a new pyrazolesulfonamide derivative with EC50 3.2 µM and CC50 24 µM, which represents a new scaffold suitable for hit-to-lead optimization that can expand the available drug discovery candidates for YF.


Assuntos
Febre Amarela , Infecção por Zika virus , Zika virus , Animais , Antivirais/farmacologia , Descoberta de Drogas , Aprendizado de Máquina , Vírus da Febre Amarela
20.
PLoS Negl Trop Dis ; 15(7): e0009594, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34283826

RESUMO

BACKGROUND: Yellow fever (YF) is a hemorrhagic disease caused by an arbovirus endemic in South America, with recent outbreaks in the last years. Severe cases exhibit fulminant hepatitis, but there are no studies regarding its late-term effects on liver parenchyma. Thus, the aim of this study was to determine the frequency and grade of liver fibrosis in patients who recovered from severe YF and to point out potential predictors of this outcome. METHODOLOGY/PRINCIPAL FINDINGS: We followed-up 18 patients who survived severe YF during a recent outbreak (January-April 2018) in Brazil using ultrasound (US) with shear-wave elastography (SWE) at 6 months after symptoms onset. No patient had previous history of liver disease. Median liver stiffness (LS) was 5.3 (4.6-6.4) kPa. 2 (11.1%) patients were classified as Metavir F2, 1 (8.3%) as F3 and 1 (8.3%) as F4; these two last patients had features of cardiogenic liver congestion on Doppler analysis. Age and cardiac failure were associated with increased LS (p = 0.036 and p = 0.024, respectively). SAPS-3 at ICU admission showed a tendency of association with significant fibrosis (≥ F2; p = 0.053). 7 patients used sofosbuvir in a research protocol, of which none showed liver fibrosis (p = 0.119). CONCLUSIONS/SIGNIFICANCE: We found a low frequency of liver fibrosis in severe YF survivors. US with SWE may have a role in the follow up of patients of age and / or with comorbidities after hospital discharge in severe YF, a rare but reemergent disease.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/etiologia , Ultrassonografia/métodos , Febre Amarela/complicações , Adulto , Idoso , Feminino , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Febre Amarela/patologia , Adulto Jovem
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