Rift Valley fever: biology and epidemiology

Abstract

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that was first discovered in Kenya in 1930 and is now endemic throughout multiple African countries and the Arabian Peninsula. RVF virus primarily infects domestic livestock (sheep, goats, cattle) causing high rates of neonatal mortality and abortion, with human infection resulting in a wide variety of clinical outcomes, ranging from self-limiting febrile illness to life-threatening haemorrhagic diatheses, and miscarriage in pregnant women. Since its discovery, RVF has caused many outbreaks in Africa and the Arabian Peninsula with major impacts on human and animal health. However, options for the control of RVF outbreaks are limited by the lack of licensed human vaccines or therapeutics. For this reason, RVF is prioritized by the World Health Organization for urgent research and development of countermeasures for the prevention and control of future outbreaks. In this review, we highlight the current understanding of RVF, including its epidemiology, pathogenesis, clinical manifestations and status of vaccine development.

Keywords: Rift Valley fever; epidemiology; one health; pathogenesis; transmission; vaccine.

Fig. 1

RVFV cycle. Between epidemics RVFV may be maintained through transovarial transmission in Aedes (Neomelaniconion) mcintoshi eggs. Wild ungulates and livestock can also harbour low-level infection. During heavy rains, a surge in mosquito populations leads to increased infection of livestock and viral amplification between numerous vector species and ruminants occurs. As more livestock become infected, the chances of spillover into humans increases. Human infection can occur via mosquito bite, or more commonly, via contact with infected animal tissue and fluid.

Fig. 2

Case fatality rates among patients hospitalized with RVF disease. Data sourced from [35, 37, 49, 55].

Fig. 3

Schematic of the RVFV genome. The L segment encodes the RNA-dependent RNA polymerase (RdRp) gene. The M segment encodes the precursor protein, which is cleaved into NSm, Gn and Gc. By using different AUG initiation sites, the M segment also codes for a precursor protein containing the 78 kD protein (which includes Gn) together with Gc. The S segment encodes for the N and NSs proteins in an ambisense manner.

Fig. 4

Replication cycle of RVFV. (1) Viral attachment to host membrane. (2) GnGc-mediated endocytosis. (3) Uncoating by acidification of endocytic vesicles, fusion of viral and endosomal membranes. (4) Primary transcription of mRNA by viral RNA polymerase. (5) Translation of viral proteins, cleavage of M-segment polyprotein and dimerization of GnGc in the endoplasmic reticulum (ER). (6) Transportation of GnGc hetrerodimers to the Golgi, glycosylation of Gn and Gc and budding into the Golgi cisternae. (7) RNA replication into positive-sense complimentary RNA (cRNA), which serves as a template for negative-sense viral RNA (or in the case of the ambisense S segment, templates for sub-genomic mRNA). (8) Migration of Golgi vesicles containing viruses to cell surface, fusion of vesicular membranes with plasma membrane, release of infectious virions. Adapted from [87]. Permission was obtained to adapt the figure from the authors and the copyright holder.