Rift Valley fever

In humans, the virus can cause several syndromes. Usually, they have either no symptoms or only a mild illness with fever, headache, muscle pains, and liver abnormalities. In a small percentage of cases (< 2%), the illness can progress to hemorrhagic fever syndrome, meningoencephalitis (inflammation of the brain and tissues lining the brain), or affect the eye. Patients who become ill usually experience fever, generalised weakness, back pain, dizziness, and weight loss at the onset of the illness. Typically, people recover within two to seven days after onset. About 1% of people with the disease die of it. In livestock, the fatality level is significantly higher. Pregnant livestock infected with RVF abort virtually 100% of foetuses. In livestock, outbreaks of RVF are often first recognized by a wave of unexplained abortions. Other signs in livestock include vomiting and diarrhea, respiratory disease, fever, lethargy, anorexia, and sudden death in young animals. ==Cause==

Virology The virus belongs to the Bunyaviricetes class. This is a class of enveloped negative single-stranded RNA viruses. All bunyaviruses have an outer lipid envelope with two glycoproteins—G(N) and G(C)—required for cell entry. They deliver their genome into the host-cell cytoplasm via endocytosis of prepackaged virions . The virus' G(C) protein has a class II membrane fusion protein architecture similar to that found in flaviviruses and alphaviruses. This structural similarity suggests that there may be a common origin for these viral families. The virus' 11.5 kb tripartite genome is composed of single-stranded RNA. As a Phlebovirus, it has an ambisense genome. Its L and M segments are negative-sense, but its S segment is ambisense. These three genome segments code for six major proteins: L protein (viral polymerase), the two glycoproteins G(N) and G(C), the nucleocapsid N protein, and the nonstructural NSs and NSm proteins. Transmission The virus is transmitted through mosquito vectors, as well as through contact with the tissue of infected animals. Two species—Culex tritaeniorhynchus and Aedes vexans—are known to transmit the virus. Other potential vectors include Aedes caspius, Aedes mcintosh, Aedes ochraceus, Culex pipiens, Culex antennatus, Culex perexiguus, Culex zombaensis and Culex quinquefasciatus. Contact with infected tissue is considered to be the main source of human infections. The virus has been isolated from two bat species: the Peter's epauletted fruit bat (Micropteropus pusillus) and the aba roundleaf bat (Hipposideros abae), which are believed to be reservoirs for the virus. == Pathogenesis ==

Although many components encoded by RVFV's RNA play an important role in the virus' pathology, the nonstructural protein encoded on the S segment (NSs) is the only component that has been found to directly affect the host. NSs is hostile and combative against the host interferon (IFNs) antiviral response. IFNs are essential for the immune system to fight off viral infections in a host. This inhibitory mechanism is believed to be due to several reasons, the first being, competitive inhibition of the formation of the transcription factor. This interaction cause competitive inhibition with another transcription factor component and prevents the assembly process of the transcription factor complex, which results in the suppression of the host antiviral response. Transcription suppression is believed to be another mechanism of this inhibitory process. This occurs when an area of NSs interacts with and binds to the host's protein, SAP30 and forms a complex. This complex causes histone acetylation to regress, which is needed for transcriptional activation of the IFN promoter. This causes IFN expression to be obstructed. Lastly, NSs has also been known to affect regular activity of double-stranded RNA-dependent protein kinase R. This protein is involved in cellular antiviral responses in the host. When RVFV can enter the host's DNA, NSs forms a filamentous structure in the nucleus. This allows the virus to interact with specific areas of the host's DNA that relates to segregation defects and induction of chromosome continuity. This increases host infectivity and decreases the host's antiviral response. ==Diagnosis==

Diagnosis relies on viral isolation from tissues, or serological testing with an ELISA. As of September 2016, the Kenya Medical Research Institute (KEMRI) has developed a product called Immunoline, designed to diagnose the disease in humans much faster than in previous methods. ==Prevention==

A person's chances of becoming infected can be reduced by taking measures to decrease contact with bodily fluids or tissues of infected animals and protect against mosquitoes and other bloodsucking insects. The use of mosquito repellents and bed nets are two effective methods. For persons working with animals in RVF-endemic areas, wearing protective equipment to avoid any exposure to blood or tissues of animals that may potentially be infected is an important protective measure. Potentially, establishing environmental monitoring and case surveillance systems may aid in the prediction and control of future RVF outbreaks. Different types of vaccines for veterinary use are available. The killed vaccines are impractical in routine animal field vaccination because of the need for multiple injections. Live vaccines require a single injection but are known to cause birth defects and abortions in sheep and induce only low-level protection in cattle. The live-attenuated vaccine, MP-12, has demonstrated promising results in laboratory trials in domesticated animals, but more research is needed before the vaccine can be used in the field. The live-attenuated clone 13 vaccine was recently registered and used in South Africa. Alternative vaccines using molecular recombinant constructs are in development and show promising results. It has been shown that knockout of the NSs and NSm nonstructural proteins of this virus produces an effective vaccine in sheep as well. ==Epidemiology==

RVF outbreaks occur across sub-Saharan Africa, with outbreaks occurring elsewhere infrequently. Outbreaks of this disease usually correspond with the warm phases of the EI Niño/Southern Oscillation. During this time there is an increase in rainfall, flooding, and greenness of vegetation index, which leads to an increase in mosquito vectors. RVFV can be transmitted vertically in mosquitos, meaning that the virus can be passed from the mother to her offspring. During dry conditions, the virus can remain viable for many years in the egg. Mosquitos lay their eggs in water, where they eventually hatch. As water is essential for mosquito eggs to hatch, rainfall and flooding cause an increase in the mosquito population and an increased potential for the virus. As with other infectious diseases, climate change is expected the increase the prevalence of Rift Valley fever. In domestic animals, climate-induced heat stress can directly animals' immunity against all diseases, and climate change also impacts the distribution of many livestock pathogens themselves. Due to these factors, Rift Valley Fever outbreaks in East African livestock are expected to increase. The first documented outbreak was identified in Kenya in 1931, in sheep, cattle, and humans; another severe outbreak in the country in 1950–1951 involved 100,000 deaths in livestock and an unrecorded number of humans with fever. An outbreak occurred in South Africa in 1974–1976, with more than 500,000 infected animals and the first deaths in humans. In Egypt in 1977–78, an estimated 200,000 people were infected and there were at least 594 deaths. In Kenya in 1998, the virus killed more than 400 people. Since then, there have been outbreaks in Saudi Arabia and Yemen (2000), East Africa (2006–2007), Sudan (2007), South Africa (2010), Uganda (2016), Kenya (2018), Mayotte (2018–2019), Kenya (2020–2021) and Burundi (2022). ==Biological weapon==

Rift Valley fever was one of more than a dozen agents that the United States researched as potential biological weapons before the nation suspended its biological weapons program in 1969. ==Research==

The disease is one of several identified by WHO as a likely cause of a future epidemic in a new plan developed after the Ebola epidemic for urgent research and development toward new diagnostic tests, vaccines and medicines. ==See also==