Origin of Rift Valley fever

History

Rift Valley fever (RVF) is an arboviral infection.¹ It was first isolated in 1931 during an epizootic outbreak among sheep in Kenya’s Rift Valley.² The first major human epidemic occurred in Egypt in 1977, when between 18,000 and 200,000 cases were reported, resulting in approximately 600 deaths.¹

Endemic in sub-Saharan Africa and the Middle East, RVF outbreaks typically occur following periods of exceptionally heavy rainfall that promote mosquito proliferation.¹˒² In France, Mayotte recorded ten confirmed human cases of RVF in 2007, mainly associated with contact with ruminants.³ In 2018–2019, the archipelago reported 142 confirmed cases, 73% of which were linked to animal exposure.⁴ The outbreak was successfully controlled through veterinary investigations, vector control measures and targeted prevention efforts.

The RVF virus

The RVF virus is an arbovirus, meaning a virus transmitted through the bite of blood-feeding arthropod vectors. This single-stranded RNA virus belongs to the genus Phlebovirus, within the family Phenuiviridae and the order Bunyavirales.¹˒⁵˒⁶

Diagnosis

RVF can be clinically difficult to distinguish from other infectious diseases such as malaria, dengue, yellow fever or other viral haemorrhagic fevers.⁷ Symptoms including fever, headache, muscle pain and, in some cases, haemorrhagic or neurological manifestations may resemble those of other systemic infections.

RVF diagnosis can be confirmed using several laboratory methods:⁶˒⁷

• RT-PCR, used to detect viral RNA in blood or other body fluids, particularly during the acute phase of infection.
• ELISA tests, used to detect viral antigens or RVF-specific antibodies (IgM and IgG), helping to confirm recent or past infection.
• Virus isolation through cell culture, although this method is mainly restricted to specialised high-containment laboratories.
• Serum neutralisation tests, used to identify neutralising antibodies and commonly employed in retrospective or epidemiological studies.

Symptoms and treatment of Rift Valley fever

Symptoms

In animals, RVF causes widespread abortions and high mortality rates.²˒⁷

In humans, most infections are asymptomatic. Among symptomatic cases, the most frequently reported clinical manifestations are fever (81%), renal failure (41%), nausea (38%) and encephalitis (21%). Death occurs in 21% of cases; most patients who died had been hospitalised.⁸

The incubation period ranges from two to six days.⁷

Treatment

There is currently no specific treatment available for RVF virus infection. In most human cases, where the disease is relatively mild and self-limiting, no specific treatment is required. Management is based on supportive and symptomatic care aimed at relieving fever and pain and preventing hepatic or ocular complications.⁷˒⁹

For more severe cases, treatment relies primarily on early intensive supportive care, including rehydration and symptom management.⁷

• Research directions

Research is underway to identify antiviral compounds active against RVF virus, including molecules already approved for other viral diseases. Certain antivirals, such as ribavirin, favipiravir and viral replication inhibitors, have shown partial efficacy in vitro or in animal models, although none has yet demonstrated sufficient clinical efficacy in humans.¹⁰

The results obtained with two monoclonal antibodies capable of providing post-exposure protection in mouse models offer promising prospects for future targeted immunotherapy in humans.¹¹

Vaccines

To date, only one vaccine has been used in humans. This is the inactivated vaccine TSI-GSD-200, developed by the United States Army. However, it is not commercially available and remains experimental, being reserved for the protection of veterinarians and laboratory personnel at high risk of exposure.²˒¹²

• Research directions

Several vaccine candidates are currently under development, including the inactivated vaccine TSI-GSD-200 and the live-attenuated vaccine MP-12, both of which have demonstrated good immunogenicity. Both are currently being evaluated in Phase II clinical trials.¹³

The University of Oxford, through a project supported by the Coalition for Epidemic Preparedness Innovations (CEPI), has developed the ChAdOx1 RVF vaccine. This candidate uses an adenoviral vector platform similar to that employed in the development of certain Covid-19 vaccines. Preclinical and Phase I studies have demonstrated a favourable safety profile, strong immunogenicity and promising thermostability. The vaccine is currently being evaluated in Kenya in a Phase II clinical trial conducted by the KEMRI-Wellcome Trust Research Programme, making it one of the most advanced candidates for human use in endemic regions.

The vaccination approach for RVF has evolved considerably. It now incorporates strategies allowing vaccinated individuals to be distinguished from naturally infected individuals through serological testing (DIVA – Differentiating Infected from Vaccinated Animals). Several next-generation vaccine candidates currently under development, including RVFV-4s, DDVax, ChAdOx1-RVF and MP12, are vector-based vaccines intended for both human and veterinary use. Among these, RVFV-4s, a four-segmented virus, and DDVax, a virus containing two genetic deletions, have been specifically designed to maximise safety. Because they are incapable of further propagation, they reduce vaccination-related risks while enabling accurate serological monitoring.

Promising results suggest that these vaccines could provide effective protection in humans, reduce transmission risks and facilitate outbreak management, which would be crucial for improving prevention of this zoonotic disease in regions at risk.¹³

Regular scientific monitoring updates were shared with members of the agency’s network, and a research meeting was held on 7 November 2025, bringing together experts from Senegal and Mauritania. The objectives of this meeting were to review the epidemiological situation in both countries, identify major challenges to the response, define priority research areas and foster collaborative initiatives. Several research priorities emerged from these discussions:

• Animal health and vaccination, including the need to develop safer and traceable vaccines (DIVA-compatible vaccines), improve understanding of viral persistence in livestock populations and analyse animal trade flows.
• Early warning systems based on climate models and satellite data, enabling anticipation of conditions favourable to outbreaks and implementation of targeted preventive measures before the first human cases occur.
• Modelling studies of livestock and human vaccination strategies.
• Social sciences research, essential for understanding community perceptions, trust in health authorities, meat and milk consumption practices, and the acceptability of preventive measures.