What Does the Future Hold for Yellow Fever Virus? (I)

Abstract

The recent resurgence of yellow fever virus (YFV) activity in the tropical regions of Africa and South America has sparked renewed interest in this infamous arboviral disease. Yellow fever virus had been a human plague for centuries prior to the identification of its urban transmission vector, the Aedes (Stegomyia) aegypti (Linnaeus) mosquito species, and the development of an efficient live-attenuated vaccine, the YF-17D strain. The combination of vector-control measures and vaccination campaigns drastically reduced YFV incidence in humans on many occasions, but the virus never ceased to circulate in the forest, through its sylvatic invertebrate vector(s) and vertebrate host(s). Outbreaks recently reported in Central Africa (2015–2016) and Brazil (since late 2016), reached considerable proportions in terms of spatial distribution and total numbers of cases, with multiple exports, including to China. In turn, questions about the likeliness of occurrence of large urban YFV outbreaks in the Americas or of a successful import of YFV to Asia are currently resurfacing. This two-part review describes the current state of knowledge and gaps regarding the molecular biology and transmission dynamics of YFV, along with an overview of the tools that can be used to manage the disease at individual, local and global levels.

What Does the Future Hold for Yellow Fever Virus? (II)

“…They suggest that a preponderant role of transovarial transmission (TOT) within mosquitoes in the maintenance of the virus could be implicated as such a mechanism, where the virus may remain quiescent in mosquito eggs for many months, would decrease the replication rate of the virus [ 108 ]. As detailed in the first part of this review, several elements indicate that the TOT mechanism is not likely to play a significant role in YFV maintenance, neither in Africa nor in South America [ 112 ]. Notably, the rates of infection of the progeny observed under laboratory conditions are too low to enable the long-term survival of the virus through a TOT mechanism [ 113 ].…”

“…Hence, a TOT mode of survival is not likely to be preponderant in YF maintenance and would thus have a minor impact on the evolutionary rate of the virus. Finally, YFV and DENV differ importantly in terms of epidemiology, as DENV can establish sustained chains of transmission in humans while YFV does not (see first part of this review [ 112 ]). These distinct epidemiological trends could be the source of differences in evolutionary dynamics as these can be modulated according to the dynamics of transmission and between intra and inter-epidemic periods (e.g., [ 114 ]).…”

“…However, the NS5 coding sequence and the 3′UTR are still used on some occasions [ 137 , 141 ]. As detailed in the first section of this review, there is a strong association between the phylogenetic and the geographic clustering of YFV strains so genotypes correspond to specific geographic areas that rarely overlap [ 112 ]. This is suggestive of a predominant role of in situ evolution in shaping YFV diversity, consistent with the maintenance of YFV in a primarily “sylvatic” mode of transmission [ 142 ].…”

Survey on Non-Human Primates and Mosquitoes Does not Provide Evidences of Spillover/Spillback between the Urban and Sylvatic Cycles of Yellow Fever and Zika Viruses Following Severe Outbreaks in Southeast Brazil

“…In the last decade, several arboviruses of medical importance have caused outbreaks of global or national dimensions, among which are Zika (ZIKV) and Yellow Fever (YFV) viruses [1][2][3]. Both are Flavivirus originating from Africa, where they exhibit at least two ecologically distinct transmission cycles: a sylvatic cycle, in which arboreal mosquito species transmit them among non-human primates (NHPs), with humans accidentally infected; and an interhuman cycle, where the virus is transmitted among humans by Aedes mosquitoes, including the anthropophilic mosquito Aedes aegypti in the domicile or peridomicile [4][5][6][7]. The worldwide spread of the competent vector Ae.…”

“…Urban Yellow Fever has been identified in the Americas since the 17th century, causing great outbreaks, especially in port cities [8,9]. Until 1930, only the YFV urban transmission cycle was described [7,9] The establishment of a sylvatic cycle in the New World was documented after confirmation of human cases occurred in an Ae. aegypti-free rural area in southeast Brazil in 1932 [10].…”