The enigma of yellow fever in East Africa.
TL;DR: This review describes historical findings, highlights a number of disease indicators, and provides clarification regarding the natural history, recent emergence and future risk of YF in East Africa.
Abstract: Despite a safe and effective vaccine there are approximately 200000 cases including 30000 deaths due to yellow fever virus (YFV) each year of which 90% are in Africa The natural history of YFV has been well described especially in West Africa but in East Africa yellow fever (YF) remains characterised by unpredictable focal periodicity and a precarious potential for large epidemics Recent outbreaks of YF in Kenya (1992-1993) and Sudan (2003 and 2005) are important because each of these outbreaks have involved the re-emergence of a YFV genotype (East Africa) that remained undetected for nearly 40 years and was previously unconfirmed in a clinically apparent outbreak In addition unlike West Africa and South America YF has yet to emerge in urban areas of East Africa and be vectored by Aedes (Stegomyia) aegypti This is a significant public health concern in a region where the majority of the population remains unvaccinated This review describes historical findings highlights a number of disease indicators and provides clarification regarding the natural history recent emergence and future risk of YF in East Africa
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TL;DR: Efforts to limit the effect of mosquito-borne diseases in endemic areas face the twin challenges of controlling mosquito populations and delivering effective public health interventions.
377 citations
TL;DR: Ivermectin, a broadly used anti-helminthic drug, proved to be a highly potent inhibitor of YFV replication and inhibited, although less efficiently, the replication of several other flaviviruses, i.e. dengue fever, Japanese encephalitis and tick-borne encephalopathy viruses.
Abstract: Objectives
Infection with yellow fever virus (YFV), the prototypic mosquito-borne flavivirus, causes severe febrile disease with haemorrhage, multi-organ failure and a high mortality. Moreover, in recent years the Flavivirus genus has gained further attention due to re-emergence and increasing incidence of West Nile, dengue and Japanese encephalitis viruses. Potent and safe antivirals are urgently needed.
327 citations
TL;DR: Structural and functional aspects emerging from the characterization of two main components (NS3 and NS5 proteins) of the flavivirus replication complex are reviewed to shed light on the design and development of antiviral drug leads.
296 citations
University of Oxford1, Institute for Health Metrics and Evaluation2, University of Melbourne3, Pasteur Institute4, Centre national de la recherche scientifique5, Centers for Disease Control and Prevention6, Harvard University7, Johns Hopkins University8, Robert Koch Institute9, Instituto Superior de Ciências da Saúde Egas Moniz10, University of Lisbon11, ETH Zurich12, University of California, San Francisco13, University Health Network14, St. Michael's Hospital15, University of Southampton16, University of KwaZulu-Natal17
TL;DR: The findings show the contributions of ecological and demographic factors to the ongoing spread of the yellow fever outbreak and provide estimates of the areas that could be prioritised for vaccination, although other constraints such as vaccine supply and delivery need to be accounted for before such insights can be translated into policy.
Abstract: Summary Background Since late 2015, an epidemic of yellow fever has caused more than 7334 suspected cases in Angola and the Democratic Republic of the Congo, including 393 deaths. We sought to understand the spatial spread of this outbreak to optimise the use of the limited available vaccine stock. Methods We jointly analysed datasets describing the epidemic of yellow fever, vector suitability, human demography, and mobility in central Africa to understand and predict the spread of yellow fever virus. We used a standard logistic model to infer the district-specific yellow fever virus infection risk during the course of the epidemic in the region. Findings The early spread of yellow fever virus was characterised by fast exponential growth (doubling time of 5–7 days) and fast spatial expansion (49 districts reported cases after only 3 months) from Luanda, the capital of Angola. Early invasion was positively correlated with high population density (Pearson's r 0·52, 95% CI 0·34–0·66). The further away locations were from Luanda, the later the date of invasion (Pearson's r 0·60, 95% CI 0·52–0·66). In a Cox model, we noted that districts with higher population densities also had higher risks of sustained transmission (the hazard ratio for cases ceasing was 0·74, 95% CI 0·13–0·92 per log-unit increase in the population size of a district). A model that captured human mobility and vector suitability successfully discriminated districts with high risk of invasion from others with a lower risk (area under the curve 0·94, 95% CI 0·92–0·97). If at the start of the epidemic, sufficient vaccines had been available to target 50 out of 313 districts in the area, our model would have correctly identified 27 (84%) of the 32 districts that were eventually affected. Interpretation Our findings show the contributions of ecological and demographic factors to the ongoing spread of the yellow fever outbreak and provide estimates of the areas that could be prioritised for vaccination, although other constraints such as vaccine supply and delivery need to be accounted for before such insights can be translated into policy. Funding Wellcome Trust.
188 citations
TL;DR: This review summarizes current understanding of sylvatic transmission cycles of YFV and DENV, considers possible explanations for their disjunct distributions, and speculates on the potential consequences of future establishment of a sylvatics cycle of DENV in the Americas.
147 citations
Cites background from "The enigma of yellow fever in East ..."
...…that have similar larval habitats and biting preferences are also involved in YFV transmission, including Ae. furcifer-taylori, Ae. vittatus, Ae. luteocephalus, Ae. opok, Ae. metallicus, and Ae. simpsoni sensu latu (including Ae. bromeliae) (Cordellier, 1991; Ellis and Barrett, 2008; Monath 1989)....
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References
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TL;DR: The observation that a single amino acid substitution can influence vector specificity provides a plausible explanation of how this mutant virus caused an epidemic in a region lacking the typical vector, and has important implications with respect to how viruses may establish a transmission cycle when introduced into a new area.
Abstract: Chikungunya virus (CHIKV) is an emerging arbovirus associated with several recent large-scale epidemics. The 2005–2006 epidemic on Reunion island that resulted in approximately 266,000 human cases was associated with a strain of CHIKV with a mutation in the envelope protein gene (E1-A226V). To test the hypothesis that this mutation in the epidemic CHIKV (strain LR2006 OPY1) might influence fitness for different vector species, viral infectivity, dissemination, and transmission of CHIKV were compared in Aedes albopictus, the species implicated in the epidemic, and the recognized vector Ae. aegypti. Using viral infectious clones of the Reunion strain and a West African strain of CHIKV, into which either the E1–226 A or V mutation was engineered, we demonstrated that the E1-A226V mutation was directly responsible for a significant increase in CHIKV infectivity for Ae. albopictus, and led to more efficient viral dissemination into mosquito secondary organs and transmission to suckling mice. This mutation caused a marginal decrease in CHIKV Ae. aegypti midgut infectivity, had no effect on viral dissemination, and was associated with a slight increase in transmission by Ae. aegypti to suckling mice in competition experiments. The effect of the E1-A226V mutation on cholesterol dependence of CHIKV was also analyzed, revealing an association between cholesterol dependence and increased fitness of CHIKV in Ae. albopictus. Our observation that a single amino acid substitution can influence vector specificity provides a plausible explanation of how this mutant virus caused an epidemic in a region lacking the typical vector. This has important implications with respect to how viruses may establish a transmission cycle when introduced into a new area. Due to the widespread distribution of Ae. albopictus, this mutation increases the potential for CHIKV to permanently extend its range into Europe and the Americas.
1,303 citations
TL;DR: The results indicate that the chikungunya virus outbreak was initiated by a strain related to East-African isolates, from which viral variants have evolved following a traceable microevolution history and may be due to adaptation to the mosquito vector.
Abstract: A chikungunya virus outbreak of unprecedented magnitude is currently ongoing in Indian Ocean territories. In Reunion Island, this alphavirus has already infected about one-third of the human population. The main clinical symptom of the disease is a painful and invalidating poly-arthralgia. Besides the arthralgic form, 123 patients with a confirmed chikungunya infection have developed severe clinical signs, i.e., neurological signs or fulminant hepatitis.
1,085 citations
TL;DR: The factors responsible for this resurgence of yellow fever in Africa, and of dengue worldwide, are discussed, as are current options for prevention and control.
Abstract: Yellow fever and dengue are old diseases, having caused major epidemics in centuries past. Both were effectively controlled in the mid 1900s, yellow fever in Francophone Africa by vaccination and yellow fever and dengue in the Americas by effective control of the principal urban vector of both viruses, Aedes aegypti. In the last 25 years of the 20th century, however, there was a resurgence of yellow fever in Africa, and of dengue worldwide. The factors responsible for this resurgence are discussed, as are current options for prevention and control.
433 citations
TL;DR: Molecular epidemiologic data suggest there are seven genotypes of YFV that are geographically separated, and outbreaks of disease are more associated with particular genotypes, which present serious potential public health problems to large population centers.
Abstract: Yellow fever virus (YFV) is the prototype member of the genus Flavivirus, a group of viruses that are transmitted between vertebrates by arthropod vectors. The virus is found in tropical regions of Africa and South America and is transmitted to primates by mosquitoes: Aedes spp. in Africa and Haemagogus and Sabethes spp. in South America. Despite the availability of an effective vaccine, yellow fever (YF) is considered a reemerging disease owing to its increased incidence in the past 25 years. Molecular epidemiologic data suggest there are seven genotypes of YFV that are geographically separated, and outbreaks of disease are more associated with particular genotypes. In addition, the risk of urban YF, owing to transmission of the virus by Aedes aegypti, is increasing in Africa, as is the potential of urban YF returning to South America. Both present serious potential public health problems to large population centers.
324 citations
TL;DR: Direct contact with animals, particularly contact with sheep body fluids, was the most important modifiable risk factor for RVFV infection and public education during epizootics may reduce human illness and deaths associated with future outbreaks.
Abstract: In December 1997, 170 hemorrhagic fever-associated deaths were reported in Carissa District, Kenya. Laboratory testing identified evidence of acute Rift Valley fever virus (RVFV). Of the 171 persons enrolled in a cross-sectional study, 31(18%) were anti-RVFV immunoglobulin (Ig) M positive. An age-adjusted IgM antibody prevalence of 14% was estimated for the district. We estimate approximately 27,500 infections occurred in Garissa District, making this the largest recorded outbreak of RVFV in East Africa. In multivariate analysis, contact with sheep body fluids and sheltering livestock in one’s home were significantly associated with infection. Direct contact with animals, particularly contact with sheep body fluids, was the most important modifiable risk factor for RVFV infection. Public education during epizootics may reduce human illness and deaths associated with future outbreaks.
306 citations