Rift Valley fever (RVF) is a mosquito-borne zoonotic disease caused by Rift Valley fever virus (RVFV) that affects humans and ruminants. This virus belongs to the family Bunyaviridae and genus Phlebovirus. RVF is endemic to sub-Saharan African countries and has caused major outbreaks in several countries – including Kenya, Somalia, Tanzania, Madagascar, South Africa, Egypt, Sudan, and other countries.
About the virus
Akin to other bunyaviruses, RVFV is an enveloped RNA virus characterized by a negative-stranded genome composed of three segments, named small (S), medium (M) and large (L) segment. The S-segment encodes N and NSs genes in an ambisense manner, the M-segment encodes 78 kD (NSm1), NSm (NSm2), Gc and Gn genes, whereas the L-segment encodes the RNA-dependent RNA polymerase gene.
The viral particles consist of a lipid envelope with two integral glycoproteins, Gc and Gn, surrounding a core of three ribonucleoproteins. These ribonucleoproteins represent complexes of nucleoprotein, viral genomic RNA and RNA-dependent RNA polymerase.
The virus binds to an unidentified cellular receptor and enters the cell in a pH-dependent manner via clathrin-mediated endocytic pathway. All the replication steps take place in the cytoplasm of infected cells, with virions maturing by budding in the Golgi compartment.
RVFV encodes several different virulence factors. The major virulence factor is NSs that plays a crucial role in evading host innate immune responses. The virus successfully interacts with chromatin DNA to induce cell cycle arrest and affect various host gene expressions.
RVF was initially reported in a farm near Lake Naivasha in Kenya in 1930, and has been endemic to sub-Saharan Africa for almost a century now. A large RVF outbreak occurred in Egypt in 1977, which resulted in approximately 100 thousand infected patients and 600 deaths.
RVFV is predominately maintained in floodwater Aedes mosquitoes, where this pathogen is transmitted transovarially. Other genera of mosquitoes (such as Culex) serve as amplifying vectors of the virus. Ruminants (such as cattle, sheep or goats) and humans can be infected via mosquito bite, with pregnant animals showing a high rate of abortion and fetal malformation.
The disease has been reported in four ecological systems: dambo areas (shallow depressions located near rivers), semi-arid areas (characterized by temporary water points), irrigated areas (where permanent water bodies favor the development of mosquito populations) and temperate mountainous areas.
Potential introduction of RVFV into countries outside Africa that are non-endemic could initiate vast RVF outbreaks and result in the long persistence of the virus, which may in turn negatively influence the economy of the affected country. Due to such potentially serious consequences, RVFV was classified as Category A Priority Pathogen.
Diagnosis and treatment
Early detection of RVFV or diagnosis of RVF is pivotal if our end-goal is to minimize the time required for prevention of further spread of RVFV. Diagnosis is usually based on the epidemiological factors (for example, abnormal heavy rains), clinical symptoms and signs, occurrence of storm abortions in small ruminants and serological screening.
In humans, infections with RVFV are most often inapparent or associated with a moderate to severe influenza-like illness. A small percentage of affected individuals may develop encephalitis and retinal lesions, albeit severe hepatic disease with hemorrhagic manifestations and fatal outcome can also ensue.
Rapid detection of viral material from viremic samples can be done by RT-PCR (either conventional or real-time modalities), recombinase polymerase amplification assay (RPA) or loop-mediated isothermal amplification (LAMP). Sandwich ELISA is also useful to detect RVFV antigens in the field studies where viral RNA cannot be stably preserved.
No established course of treatment is currently available for patients with this disease. The development of therapeutics targeting this virus is cumbersome due to our limited understanding of the RVFV replicative cycle. Certain animal studies have shown promise for ribavirin and interferon as potential future candidates for use in humans.
The sustained way of infection prevention in endemic areas is through vaccination of animals. A veterinary vaccine commonly used in Africa is called the Smithburn vaccine. Several new generation vaccines are now under development for safe use in humans, with TSI-GSD 200 and MP-12 vaccines leading the way.