Project description:BackgroundA yellow fever epidemic occurred in Angola in 2016 with 884 laboratory confirmed cases and 373 deaths. Eleven unvaccinated Chinese nationals working in Angola were also infected and imported the disease to China, thereby presenting the first importation of yellow fever into Asia. In Angola, there are about 259,000 Chinese foreign workers. The fact that 11 unvaccinated Chinese workers acquired yellow fever suggests that many more Chinese workers in Angola were not vaccinated.MethodsWe applied a previously developed model to back-calculate the number of unvaccinated Chinese workers in Angola in order to determine the extent of lack of vaccine coverage.ResultsOur models suggest that none of the 259,000 Chinese had been vaccinated, although yellow fever vaccination is mandated by the International Health Regulations.ConclusionGovernments around the world including China need to ensure that their citizens obtain YF vaccination when traveling to countries where such vaccines are required in order to prevent the international spread of yellow fever.
Project description:Aedes aegypti mosquitoes infect hundreds of millions of people each year with dangerous viral pathogens including dengue, yellow fever, Zika, and chikungunya. Progress in understanding the biology of this insect, and developing tools to fight it, depends on the availablity of a high-quality genome assembly. Here we use DNA proximity ligaton (Hi-C) and Pacific Biosciences long reads to create AaegL5 - a highly contiguous A. aegypti reference.
Project description:BackgroundYellow fever is endemic in Africa and the Americas, occurring in urban or sylvatic environments. The infection presents varying symptoms, with high case-fatality among severe cases. In 2016, Brazil had sylvatic yellow fever outbreaks with more than 11 thousand cases, predominantly affecting the country's Southeast region. The state of Minas Gerais accounted for 30% of cases, even after the vaccine had been included in the immunization calendar for at least 30 years.Methodology and principal findingsWe applied parameters described in the literature from yellow fever disease into a compartmental model of vector-borne diseases, using namely generation time intervals, vital host and vector parameters, and force of infection, using macroregions as the spatial unit and epidemiological weeks as the time interval. The model permits obtaining the reproduction number, which we analyzed from reported cases of yellow fever from 2016 to 2018 in residents of the state of Minas Gerais, Brazil. Minas Gerais recorded two outbreak periods, starting in EW 51/2016 and EW 51/2017. Of all the reported cases (3,304), 57% were men 30 to 59 years of age. Approximately 27% of cases (905) were confirmed, and 22% (202) of these individuals died. The estimated effective reproduction number varied from 2.7 (95% CI: 2.0-3.6) to 7.2 (95% CI: 4.4-10.9], found in the Oeste and Nordeste regions, respectively. Vaccination coverage in children under one year of age showed heterogeneity among the municipalities comprising the macroregions.ConclusionThe outbreaks in multiple parts of the state and the estimated Re values raise concern since the state population was partially vaccinated. Heterogeneity in vaccination coverage may have been associated with the occurrence of outbreaks in the first period, while the subsequent intense vaccination campaign may have determined lower Re values in the second period.
Project description:BackgroundLike many infectious agents, yellow fever (YF) virus only causes disease in a proportion of individuals it infects and severe illness only represents the tip of the iceberg relative to the total number of infections, the more critical factor for virus transmission.MethodsWe compiled data on asymptomatic infections, mild disease, severe disease (fever with jaundice or hemorrhagic symptoms) and fatalities from 11 studies in Africa and South America between 1969 and 2011. We used a Bayesian model to estimate the probability of each infection outcome.ResultsFor YF virus infections, the probability of being asymptomatic was 0.55 (95% credible interval [CI] 0.37-0.74), mild disease 0.33 (95% CI 0.13-0.52) and severe disease 0.12 (95% CI 0.05-0.26). The probability of death for people experiencing severe disease was 0.47 (95% CI 0.31-0.62).ConclusionsIn outbreak situations where only severe cases may initially be detected, we estimated that there may be between one and seventy infections that are either asymptomatic or cause mild disease for every severe case identified. As it is generally only the most severe cases that are recognized and reported, these estimates will help improve the understanding of the burden of disease and the estimation of the potential risk of spread during YF outbreaks.
Project description:The yellow fever (YF) vaccine consists of an attenuated virus, and despite its relative safety, some adverse events following YF vaccination have been described. At the end of 2016, Brazil experienced the most massive sylvatic yellow fever outbreak over the last 70 years and an intense campaign of YF vaccination occurred in Minas Gerais state in Southeast Brazil from 2016 to 2018. The present study aimed to develop a genotyping tool and investigate 21 cases of suspected adverse events following YF vaccination. Initial in silico analyses were performed using partial NS5 nucleotide sequences to verify the discriminatory potential between wild-type and vaccine viruses. Samples from patients were screened for the presence of the YFV RNA, using 5'UTR as the target, and then used for amplification of partial NS5 gene amplification, sequencing, and phylogenetic analysis. Genotyping indicated that 17 suspected cases were infected by the wild-type yellow fever virus, but four cases remained inconclusive. The genotyping tool was efficient in distinguishing the vaccine from wild-type virus, and it has the potential to be used for the differentiation of all yellow fever virus genotypes.
Project description:Correlates of immune mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of forty volunteers followed for up to one year after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity including complement, the inflammasome and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (Modular IMmune In vitro Construct (MIMIC) system), by the coordinated up-regulation of transcripts for specific transcription factors including STAT1, IRF7 and ETS2 that are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of masters transcription factors, that lead to the development of a broad, polyfunctional and persistent immune response that integrates all effector cells of the immune system.