Re-emergence of yellow fever in the neotropics - quo vadis?

Abstract

Yellow fever virus (YFV) is the etiological agent of yellow fever (YF), an acute hemorrhagic vector-borne disease with a significant impact on public health, is endemic across tropical regions in Africa and South America. The virus is maintained in two ecologically and evolutionary distinct transmission cycles: an enzootic, sylvatic cycle, where the virus circulates between arboreal Aedes species mosquitoes and non-human primates, and a human or urban cycle, between humans and anthropophilic Aedes aegypti mosquitoes. While the urban transmission cycle has been eradicated by a highly efficacious licensed vaccine, the enzootic transmission cycle is not amenable to control interventions, leading to recurrent epizootics and spillover outbreaks into human populations. The nature of YF transmission dynamics is multifactorial and encompasses a complex system of biotic, abiotic, and anthropogenic factors rendering predictions of emergence highly speculative. The recent outbreaks in Africa and Brazil clearly remind us of the significant impact YF emergence events pose on human and animal health. The magnitude of the Brazilian outbreak and spillover in densely populated areas outside the recommended vaccination coverage areas raised the specter of human - to - human transmission and re-establishment of enzootic cycles outside the Amazon basin. Herein, we review the factors that influence the re-emergence potential of YFV in the neotropics and offer insights for a constellation of coordinated approaches to better predict and control future YF emergence events.

Keywords: arbovirus; epizootics; outbreak; re-emergence; transmission cycles; yellow fever virus.

Figure 1.. Global distribution of yellow fever virus and recommended vaccination coverage areas.

Figure 2.. Global disease burden of YFV.

(A) Human cases reported yearly by the World Health Organization (WHO), from 1980 to 2018. The numbers of cases by year for Africa (blue line) and the Americas (green line). Black line denotes the global disease burden of YFV. Data obtained from [76]. (B) Confirmed human yellow fever cases (green line) and mortality rate (black line) in Brazil, from 1980 to present day as reported by the Ministry of Health.

Figure 3.. Phylogeny of yellow fever virus.

Phylogeny of YFV virus inferred using the maximum likelihood method. The tree was obtained from a sequence dataset of 112 isolates using the General Time Reversible (GTR) substitution model. Branches are labeled with bootstrap values representing the percentage of 1000 replicates in which the members of a given clade were predicted to relate in the same topography. The scale shows a genetic distance of 0.05 or a 5% nucleotide sequence divergence. Evolutionary analyses were conducted in MEGA7 [77]. Abbreviations: VE, Venezuela; BR, Brazil; PE, Peru; TT, Trinidad and Tobago; US, USA; SU, Suriname; EC, Ecuador; BO, Bolivia; SG, Singapore; ES, Spain; GH, Ghana; SN, Senegal; GW, Guinea-Bissau; CI, Côte d'Ivoire; GM, The Gambia; NG, Nigeria; UG, Uganda; CN, China; AO, Angola.

Figure 4.. Transmission cycles of yellow fever virus.

Abbreviation: TOT, transovarial transmission.