Control Tools

• Diagnostics availability

• Commercial diagnostic kits available worldwide

  Antigen/virus detection: Various PCR based kits are commercially available to test for the presence of RVFV genome in different matrixes such as serum, blood and tissue samples. Furthermore, there are also rapid diagnostic kits (Lateral Flow Devices (LFD) available for antigen detection that have been tested and validated during RVF outbreaks [1] Antibody detection: In addition to RVFV molecular detection kits (PCR kits), several commercialised ELISA kits for the detection of RVFV-specific IgG and/or IgM antibodies are available on the market. Some kits use a competitive format to allow multispecies detection. Prototypes of LFDs for antibody detection have also been developed. These are very easy to use, but their sensitivity is generally lower than that of ELISA or virus neutralisation tests (VNTs), which therefore remain the gold standard. List of commercially available diagnostics (Diagnostics for Animals).

  GAPS

  There are no official diagnostic standards within the veterinary field. These would be a valuable resource for validating diagnostic performance. It would support endemic countries in collecting and maintaining diagnostic resources (e.g. serum and organ samples). Of note, a WHO International antibody standard was established in 2023 for the human field on neutralisation assays here.

• Diagnostic kits validated by International, European or National Standards

  None officially validated.

  GAP

  Reference laboratories to provide standardized tools for official diagnostic kit validation.

• Diagnostic method(s) described by International, European or National standards

  Details of standardised diagnostic tests are described in the WOAH Manual of Diagnostic Tests and Vaccines, 2024 edition Chapter 3.1.20.

• Commercial potential for diagnostic kits worldwide

  High in at risk, disease-free countries for surveillance purposes.

• DIVA tests required and/or available

  None available, but would be important in non-endemic-at risk countries performing routine RVF surveillance. These would be useful for epidemiological studies and vaccine field studies, but not essential for trade in Africa for several reasons. First, RVFV is not a contagious disease and infection does not result in persistence of the virus. Animals that are infected with RVFV, whether vaccinated or not, will develop antibodies that are protective (strong correlation of neutralizing antibodies with protection). Therefore, a seropositive animal can safely be transported. Specifically, use of a DIVA vaccine is not needed if animals are kept in quarantine for 3 weeks before export to free countries. Preferably, the animals are vaccinated before going into quarantine. Recommending DIVA vaccines could prevent transport of animals with protective antibodies and thereby not improve, but reduce free trade. Finally, it should be noted that DIVA diagnostics, when done properly, is very costly (much more costly than vaccination and almost certainly too costly for most African countries). However, in the event of an introduction of RVF in Europe these tests would be desirable if vaccination campaigns or emergency vaccination are implemented.

  GAPS

  Development of cheap diagnostic tests that identify unequivocally whether animals have been vaccinated or infected. Development of accompanying DIVA tests appropriate for each type of vaccine Potential development of DIVA LFD tests Look for either unique infection signatures or unique vaccination signatures.

• Vaccines availability

• Commercial vaccines availability (globally)

  No RVF vaccine is available worldwide.

  Inactivated and live-attenuated vaccines (Clone 13 and Smithburn) are available in some African countries. Other live attenuated vaccine, the well-known MP12 strain, not yet commercialized.

  GAPS

  Support clinical evaluation for promising vaccine candidates. Many experimental vaccines showed efficacy in preclinical trials.

• Marker vaccines available worldwide

  None available at this moment though various potentially DIVA compliant vaccines are being developed at this moment.

  GAPS

  Develop marker vaccines in combination with DIVA tests.

• Effectiveness of vaccines / Main shortcomings of current vaccines

  Both the live-attenuated and the inactivated vaccines have had extensive field use. Lifelong immunity against clinical disease is likely obtained with the live vaccines, however some of the current commercially available live-attenuated vaccines can provoke abortions or malformations when used in pregnant animals. The inactivated vaccines fail to protect animals with a single dose and a second dose as well as (yearly) booster doses are required.

  GAPS

  Lack of data on efficacy of these vaccines or vaccination campaigns in African countries. Inactivated vaccines are used in areas where RVF is not endemic and, therefore, the knowledge of their efficacy is limited, as natural field challenge does not occur. Developing safer alternative vaccines that are highly efficacious and safe in all animals including gestating animals.

• Commercial potential for vaccines

  The current market is limited to African countries due to the unpredictability of RVF outbreaks. There could be a significant impact if a single RVF case is reported in Europe or other non-endemic region.

  GAPS

  Rigorous studies on the commercial viability and potential for profit of RVF vaccines for livestock are needed.

• Regulatory and/or policy challenges to approval

  None, apart from the process of obtaining a marketing authorisation.

• Commercial feasibility (e.g manufacturing)

  Manufacturing both attenuated and other platform-based vaccines is not a technological problem. However, in certain areas, maintaining the cold chain would be difficult.

  GAPS

  One potential avenue for exploration is the development of thermostable vaccines.

• Opportunity for barrier protection

  Live-attenuated or vectored vaccines may provide life-long immunity, therefore effectively contributing to herd immunity.

  GAPS

  Testing duration of immunity of next-generation vaccines. Studies of prime boost combination vaccines.

• Pharmaceutical availability

• Current therapy (curative and preventive)

  None for livestock. For humans, prevention of close contact with infected cattle or meat as well as prevention of mosquito bites is key in endemic areas.

  GAP

  Exploring efficacy of antiviral drugs approved for human use.

• Future therapy

  None anticipated at present. For humans, Ig -based therapies could be a promising treatment for post viral exposure

  GAP

  Passive transfer studies to inform on antibody treatments (for human use) are needed.

• Commercial potential for pharmaceuticals

  Low for livestock use but high for human use.

• Regulatory and/or policy challenges to approval

  None, apart from the process of obtaining a marketing authorisation.

• Commercial feasibility (e.g manufacturing)

  May depend on cost benefit.

  GAP

  As for vaccines studies on the commercial viability and potential for profit of RVF, therapies are lacking.

• New developments for diagnostic tests

• Requirements for diagnostics development

  Rapid RVF test prototypes already developed (or being developed) by some companies and labs.

  GAP

  Look for improvements over current diagnostic tests. May need sensitivity improvements particularly for antigen detection. Interest for DIVA strategy in Antigen detection. Investigate on RVFV specific biomarker discovery.

• Time to develop new or improved diagnostics

  Unknown. Depends on the type of diagnostic method.

• Cost of developing new or improved diagnostics and their validation

  Unknown. Depends on the type of diagnostic method.

• Research requirements for new or improved diagnostics

  Current commercial diagnostic kits cannot differentiate animals vaccinated with attenuated or inactivated RVFV vaccines.

  GAP

  Develop accompanying diva tests for next generation live-attenuated vaccines

• Technology to determine virus freedom in animals

  Conventional technologies (virus isolation, molecular detection) available.

  GAP

  Proteomic approaches need to be investigated and next-generation sequencing techniques to be further optimized.

• New developments for vaccines

• Requirements for vaccines development / main characteristics for improved vaccines

  In case of introduction of the disease into Europe or the US, vaccination would be probably recommended. Novel and safer candidate vaccines have been developed and tested but these are not yet available commercially. Since the erratic cycle of RVF outbreaks means that annual vaccination is unlikely to be adopted routinely in Africa, development of combined vaccines may ease to include RVF in annual vaccination of livestock.

  GAP

  If RVF outbreaks occur in Europe, no vaccine will be available for a quick intervention against disease spread. Investigate the need for vaccine stockpiling in Europe based on current epidemiology knowledge.

• Time to develop new or improved vaccines

  Currently available candidate vaccines could be licensed within 3 years if funds are available.

• Cost of developing new or improved vaccines and their validation

  ~10m€ for a new vaccine. Probably not needed since highly promising candidates are available.

• Research requirements for new or improved vaccines

  GAP

  For next generation vaccines elaborate safety studies in pregnant ruminants are a main cost driver as well as duration of immunity studies.

• New developments for pharmaceuticals

• Requirements for pharmaceuticals development

  Not obvious for production animals. Yes for humans. Some authorised drugs (such as favipiravir) have shown efficacy against RVFV.

  GAP

  Testing authorised antivirals against RVFV

• Time to develop new or improved pharmaceuticals

  Unknown.

• Cost of developing new or improved pharmaceuticals and their validation

  Unknown

• Research requirements for new or improved pharmaceuticals

  Tools for high throughput screening of novel molecules have been developed.

  GAP

  Comparative testing of current antivirals. Assessing effectiveness of novel and repurposed compounds.

Disease details

• Description and characteristics

• Pathogen

  RVFV is a member of the family Phenuiviridae, genus Phlebovirus. The virus comprises a three-segmented negative-strand RNA genome. Great progress in the molecular biology of RVFV has been made during the last decades. Like other bunyaviruses, RVFV encodes non-structural proteins: NSs, NSm and P78 (Gn-NSm). NSs is a major virulence factor that suppresses host general transcription counteracting both the antiviral interferon (IFN)-β response and the double-stranded RNA (dsRNA)-dependent protein kinase (PKR) activity.

  NSm was related with apoptosis inhibition in mammalian host cell [6] and it may play a role for dissemination in both vertebrate and invertebrate tissues.

  GAP

  As for Bunyamwera virus investigate the role of NSm for virus dissemination in mosquitoes in more details.

• Variability of the disease

  All isolates belong to a single serotype. Isolates were firstly classified into 7 [9] and, more recently, 15 genetic lineages [10]. A re-assortant strain has been described in the last 2010 South African outbreak. Host range includes:
  • Cattle, sheep, goats, camels
  • Wild ruminants, buffaloes, antelopes, wildebeest, etc.
  • Humans

  GAP

  Get more insight into variability of genes involved in RVF strains virulence, particularly in countries where the presence of inter-epizootic periods has been clearly defined without causing any major clinical outbreaks.

• Stability of the agent/pathogen in the environment

  RVF is able to infect many species of animals causing severe disease in domesticated animals including cattle, sheep, camels and goats. Sheep (particularly newborn lambs and pregnant ewes) are most susceptible to disease. An important role for camels in the RVF epidemiological cycle has been described. Camelids can now be fully considered as a susceptible host with fatal cases and abortions.

  GAP

  Since camels are a susceptible host for the virus, vaccine efficacy studies in these animals are advisable.

• Species involved

• Animal infected/carrier/disease

  RVF is able to infect many species of animals causing severe disease in domesticated animals including cattle, sheep, camels and goats. Sheep (particularly newborn lambs and pregnant ewes) are most susceptible to disease. An important role for camels in the RVF epidemiological cycle has been described[5]. Camelids can now be fully considered as a susceptible host with fatal cases and abortions.

  GAP

  Since camels are a susceptible host for the virus, vaccine efficacy studies in these animals may be needed.

• Human infected/disease

  Humans are susceptible with flu-like symptoms prevailing.

  GAP

  The pathogenesis of the variable disease progression observed in RVFV-infected humans is still poorly understood. Why do most infected patients exhibit low-grade fever, while others suffer fatal haemorrhagic fever and/or encephalitis?

• Vector cyclical/non-cyclical

  The virus has been isolated from more than 30 different species of mosquito (Aedes, Anopheles, Culex, Eretmapodites, Mansonia etc.). The biological cycle of mosquito vectors conditions the enzootic/epizootic virus cycle.

  GAP

  There is still insufficient knowledge about the vector competence of European mosquito species. Particularly Aedes vexans is relevant to study. Identification of the minimum viral load for a vector to play its role of competent vector (amplification/spread) and impact on the environmental factors on the vector competence. Furthermore, the vector to host density to allow transmission is not well understood.

• Reservoir (animal, environment)

  In specific species of Aedes mosquitoes, the virus can transmit to the eggs, according to previous field evidences. Most recent evidence has confirmed vertical transmission in laboratory setting using Culex tarsalis mosquitoes [15]. These mosquitoes can therefore be considered as reservoir hosts, although a role for other wild small mammal reservoirs cannot be ruled out. Serological and virological analyses in Madagascar indicated seroconversions in animals that did not move from their village, suggesting RVFV local circulation when mosquitoes are rare or inactive. Three hypothesis were formulated to explain these seroconversions: 1) Direct transmission mechanisms, 2) virus overwintering in vectors (residual active mosquito population during the dry and cold season and ticks), or 3) the existence of a wild reservoir other than wild terrestrial small mammals.

  GAP

  Identify wild reservoirs other than small mammals.

  Transovarian transmission was only demonstrated once and should be confirmed, at least with Aedes mcintoshi mosquitoes.

• Description of infection & disease in natural hosts

• Transmissibility

  RVF is transmitted among ruminants via bites from infected mosquitoes and possibly other biting insects that have virus-contaminated mouthparts. Although humans can also be infected via mosquito bite, most human infections are attributed to contact with contaminated animal products during the slaughtering of diseased animals. RVFV can be infectious and virulent when inhaled by humans or experimental animals (rats). RVFV remains stable for up to 96 hours in refrigerated milk and up to two days in milk stored in warm ambient conditions. Commonly performed pasteurization techniques and boiling of milk fully inactivates RVFV in milk.

  GAPS

  Horizontal transmission of RVFV was previously reported however, more recently it was also found that co-housing of RVFV-infected lambs with immunocompetent or immunosuppressed lambs does not result in virus transmission. This discrepancy warrants further investigations. The risk of unpasteurised milk consumption is still unclear. In many countries, drinking raw milk is a basic, and needs to be considered in terms of pathogens transmission risk. Up to now, there are no specific studies. The risk of RVF semen transmission needs to be further analysed.

• Pathogenic life cycle stages

  Female mosquitoes which feed on infected animals can become infected with RVFV. Transovarian transmission can occur in at least one Aedes species (Aedes mcintoshi). The eggs of these mosquitoes can survive for several years in dry conditions. During periods of heavy rainfall, flooding will often occur which enables the eggs to hatch with the consequent rapid increase in the mosquito population. After floodwater Aedes mosquitoes have infected the first ruminants, also other mosquito species may contribute to further spread.

  GAPS

  Transovarian transmission was only demonstrated once and should be confirmed, at least with Aedes mcintoshi mosquitoes. The survival of eggs containing the virus could also be investigated in other European-range mosquito species.

• Signs/Morbidity

  The disease is characterised by high mortality among young animals and high rate of abortion in ruminants. Among pregnant infected ewes abortion rates may reach almost 100%. The start of an epidemic may be indicated by a wave of unexplained abortions among livestock. Sheep are the most severely affected. The course of the disease in different animal species including humans and domesticated ruminant was reviewed by Easterday [12]. Cattle Calves: fever (40-41°C), depression. Adults: fever (40-41°C), excessive salivation, anorexia, weakness, fetid diarrhoea, fall in milk yield. Abortion may reach 85% in the herd. Mortality rate is usually less than 10% Sheep, goats Lambs: fever (40-42°C), anorexia, weakness, death within 36 hours after inoculation. Adults: fever (40-41°C), mucopurulent nasal discharge, vomiting; in pregnant ewes, abortion may reach 100%. Camels: Adults : conjunctivitis and ocular discharge, hemorrhages of the gums, and edema of the trough; hemorrhages of gums and tongue; foot lesions (cracks in the sole) with secondary myasis; oedema at the base of the neck; abortion, convulsions, and arching of the neck.

  GAP

  The mechanisms of late onset neurological disease often observed in rodent models are not fully understood.

• Incubation period

  The incubation period varies from 1 to 3 days in sheep, cattle, goats. In newborn lambs, it is 12 to 36 hours. Experimental infections usually become evident after 12 hours in newborn lambs, calves and kids.

• Mortality

  Cattle: Mortality rate: 10%, mortality can be up to 70% in young calves.

  Lamb: Mortality rate: for animals under 1 week of age - up to 90%; for animals over 1 week of age - up to 70%.

  Adult sheep, goats: mortality may reach 20-30%.

• Shedding kinetic patterns

  Viraemic animals pose a risk as mosquitoes feeding on these animals can become infected.

  GAP

  The infectious period of sheep and cattle should be investigated (the period of viremia sufficiently high to result in infection of mosquitoes). Such data can be used to improve epidemiological models.

• Mechanism of pathogenicity

  Related to liver and brain tropism of the virus as well as immunopathogenic effects. Although there has been great advances in characterizing clinical, pathological, and virological features of RVFV infection (reviewed in and the exact mechanisms of pathogenicity are unknown and may vary between species.

  GAPS

  Mechanism that triggers haemorrhagic fever, entry to the brain, or retinal complication are unknown.

  Despite efforts to characterize the immune response in natural hosts including humans, or experimental animals little is known about how the host immune response influences clinical outcome during the primary RVFV infection.

• Zoonotic potential

• Reported incidence in humans

  Humans are highly susceptible to RVF. During outbreaks in animals, mosquitoes may spread the virus to humans and cause epidemics. However, most human infections are attributed to contact with animal products during the slaughtering of diseased animals. The role of mosquitoes in epidemics obviously depends on the presence of mosquitoes that feed on both humans and ruminants. The major source of human infection is aerosols transported from sick infected animals to healthy humans, not mosquitoes.

  GAP

  The real involvement of mosquitoes in humans infection needs to be studied as well as the risk of human to human RVFV transmission.

• Risk of occurence in humans, populations at risk, specific risk factors

  Most cases develop in veterinarians, abattoir workers and others who come into contact with blood and tissue samples from animals.

  Genetic host factors have been established as a key element in RVF disease in rodent models [28-30]. Association between immune related genes and severe symptoms suspected in humans [31].

  GAP

  Genes associated with RVF clinical disease in high-risk populations remain to be identified in experimental animals, livestock, and humans.

• Symptoms described in humans

  Most people with RVF recover spontaneously within a week. Ocular disease is seen in approximately 0.5% to 2% of cases, and encephalitis or hemorrhagic fever in less than 1%. Recent evidence using the Zebra fish model suggests that RVFV-induced blindness likely occurs due to direct damage to the eye and peripheral neurons, rather than the brain. The case fatality rate for hemorrhagic fever is approximately 50%. Deaths rarely occurs in people with eye disease or meningoencephalitis, but 1% to 10% of patients with ocular disease have some permanent visual impairment. Level of underreporting in humans is unknown but probably high in non-developed countries. In many cases patients suffering from hyperthermia, headache, dengue like syndromes are not initially diagnosed of RVF since the clinical signs fall under “dengue-like syndromes” but further laboratory testing identified these patients as RVF cases.

  GAPS

  The symptoms are well described in humans. However, the physiopathological mechanisms are poorly understood, as for examples:

  - The mechanism of entry of the virus in the central nervous system.

  - The physiopathology of the encephalitis.

  - The mechanisms of clearance of the virus.

• Likelihood of spread in humans

  No human to human spread has been reported. Nasal discharge, blood, vaginal secretions after abortion in animals, mosquitoes, contaminated fresh meat and raw milk are potential sources.

  Nosocomial transmission risks evaluated as low.

  GAP

  The risk of consumption of raw milk and transmission through semen (as Zika virus) should be assessed.

• Impact on animal welfare and biodiversity

• Both disease and prevention/control measures related

  Quarantine.

• Endangered wild species affected or not (estimation for Europe / worldwide)

  Wild ruminants (buffalo, antelope and wildebeest) are susceptible.

  GAP

  Incidence of abortions in these species not known.

• Slaughter necessity according to EU rules or other regions

  No.

• Geographical distribution and spread

• Current occurence/distribution

  RVF has been recognised exclusively in African countries with some incursions into the Middle East. RVF usually occurs in epizootics in Africa, which may involve several countries at the same time. The first reported occurrence of disease outside Africa occurred in 2000 when cases were confirmed in Saudi Arabia and Yemen. There remains a concern that RVF could spread to other regions, particularly Europe and Asia. Serological evidence of exposure suggests active circulation of RVFV in Tunisia in 2014. Absence of RVFV in domestic and wild ruminants from southern Spain has been reported. Recent outbreaks of RVF occurred in the South West of the Indian Ocean (SWIO), specifically Madagascar.

  GAP

  In the Northern part of Africa and particularly in Tunisia, RVF has been reported to be present. No definitive data are available for Morocco and Algeria which are countries closely linked together and to Europe other than serological evidence of Rift Valley fever viral infection among camels imported into Southern Algeria.

• Epizootic/endemic- if epidemic frequency of outbreaks

  Epizootics follow the periodic cycles of exceptionally heavy rain, which may occur very rarely in semi-arid zones (25–35-year cycles), or more frequently (5–15-year cycles) in higher rainfall savannah grasslands. During the inter epizootic period low level RVFV activity may occur.

  Outbreaks are generally associated with above normal rainfall and explosions of mosquito populations.

• Seasonality

  The periodic RVF outbreaks have been associated with variability in rainfall patterns in most of Eastern Africa. RVF is most commonly associated with mosquito-borne epidemics during years of unusually heavy rainfall.

• Speed of spatial spread during an outbreak

  Unknown

• Transboundary potential of the disease

  Yes. The movement of clinically viraemic animals into unaffected areas where vectors are present has the potential to cause epidemics and epizootics. This could explain some outbreaks in the Horn of Africa and Indian Ocean islands

  GAP

  Perform risk analysis studies linked to animal mobility in order to develop adequate surveillance plans based on risk of introduction and settlement of the infection.

• Route of Transmission

• Usual mode of transmission (introduction, means of spread)

  The virus is transmitted by mosquitoes. Transovarial transmission can occur in at least one Aedes species (Aedes mcintoshi), which may, at least partially, explain the survival of the virus during inter-epidemic periods.

  GAPS

  -Competence of mosquitoes from Southern Europe (Greece, Spain, Italy) should be assessed including transovarial transmission.

  -Competence of ticks, phlebotomus, and culicoides from Southern Europe should be evaluated.

• Occasional mode of transmission

  Transmission of RVF virus by mechanical means via biting flies is also possible.

  During parturition, necropsy or slaughter, viruses in the tissues can become aerosolized or enter the skin through abrasions (direct contact). The RVF virus has also been found in raw milk and may be present in semen.Tick infection (Hyalomma) could be experimentally induced but the role of ticks in transmission is unknown.

  GAPS

  The biology of the virus in mosquitoes is poorly documented.

  The role of biting insects and perhaps even ticks should be investigated. This does not seem to play a major role in Africa, but this may be different in Europe.

  The presence of RVFV genomic RNA in semen raises the possibility of sporadic sexual transmission.

• Conditions that favour spread

  Heavy rainfall and movement of infected animals into free areas.

• Detection and Immune response to infection

• Mechanism of host response

  Natural infection results in a high neutralizing antibody response which correlates with protection.

  GAP

  Late onset neurologic disease may be related with inappropriate/uncontrolled immune responses. The exact mechanisms are unknown and should be the matter for future research.

• Immunological basis of diagnosis

  Detection of antibodies (neutralizing or anti nucleoprotein antibodies)

  GAP

  Identification of the host immune response (humoral and cellular) elicited during a natural RVF infection.

• Main means of prevention, detection and control

• Sanitary measures

  Vector control may be beneficial.

• Mechanical and biological control

  Interference with the mosquito life-cycle may be beneficial.

  GAP

  Identification of the risk areas based on environmental factors (rainfalls, wind, waterpoints) favouring the abundance and distribution of the competent mosquito species.

• Diagnostic tools

  Conventional virological as well as both molecular and serological tests are developed (listed in OIE’s Manual). Commercial antibody detection test fully available. Virus neutralization remains a gold-standard.

  GAP

  Development of sensitive specific rapid bench tests. Perform RVF diagnostic ring trials among European and northern African countries. Implement international standards.

• Vaccines

  Both live-attenuated virus and inactivated virus vaccines have been developed for veterinary use. Only one dose of the live vaccine is required to provide long-term immunity but the vaccine that is currently in use may result in spontaneous abortion if given to pregnant animals. The inactivated virus vaccine does not have this side effect, but multiple doses are required in order to provide protection. The Clone 13 vaccine was marketed by Onderstepoort Biological Products in 2010 and later on by MCI and was extensively used in the field. This vaccine provides solid protection after a single vaccination and is safe for young lambs. However, a recent safety study that was performed according to the regulations and guidelines from the OIE and European Pharmacopeia demonstrated that the Clone 13 virus can transmit to the ovine fetus, which was associated with stillbirths and fetal malformation when administered during the first trimester of gestation. MP12 is another alternative vaccine with extensive data on field and clinical trials. An adenovirus-based vaccine has shown full protection against viremia in several livestock species. Protein Subunit and DNA vaccines based on recombinant RVFV glycoproteins are able to elicit protective immune responses, but not after a single immunization. Novel Live attenuated vaccines have been developed as well, and some have shown promise candidates. The Coalition for Epidemic Preparedness Innovations (CEPI), currently funds four human RVF candidates for use in humans.

  GAPS

  Several candidate vaccines were developed that have shown great promise in target animals (sterile immunity after a single vaccination). The safety and efficacy of these vaccines should be evaluated in sheep and cattle (at least) according to the guidelines and regulations of the OIE and European Pharmacopeia so that these vaccines can be used in Europe in emergency situations. It is strongly preferred that these vaccines are evaluated in close collaboration with pharmaceutical companies. Developments towards human vaccines must be addressed, particularly those based on approaches already proved safe for human use (subunit/ DNA/adenovirus and/or MVA platforms) Efficacy of adenovirus vaccine against RVFV should be tested in pregnant animals. Develop methods ensuring protective efficacy of subunit vaccines after a single dose. Develop methods to enhance the efficacy of DNA vaccines.

• Therapeutics

  No specific treatment. Supportive treatment in severe human cases. However several molecules with anti-RVFV activity have been demonstrated in laboratory animal models: - Combined administration of Ribavirin and Favipiravir reported to be beneficial post infection in Golden Hamsters. Not tested in human patients. - Screenings for compounds with antiviral activities are currently performed in cell cultures.

  GAPS

  Antiviral products for human patients (should be discussed with the experts). Vaccine manufacturers have little incentive to develop vaccines against human RVF owing to a perceived non-credit worthy market in Africa Protection of human populations, will rather depend on the development of specific anti-viral compounds to control the infection and/or its clinical corollaries. The success of this strategy is critically dependent on the identification of new antiviral targets. The use of drugs tested in humans against other infectious diseases could be an alternative for RVFV (Favipiravir against flu, ebola etc).

• Biosecurity measures effective as a preventive measure

  1. Restrict or stop all animal movement to prevent introduction into unaffected areas.

  2. Observe, detect and report any disease or unusual signs as quickly as possible.

  3. Removal of mosquito breeding sites (stock tanks, ponds, old tires etc.) helps to prevent spread of the disease.

  4. Protect humans against mosquito bites and use personal protective equipment (respirator, gloves, eye protection etc.) when handling tissues from animals that have aborted and during slaughter of diseased animals (which should be prevented when possible).

• Border/trade/movement control sufficient for control

  Restricting or banning the movement of livestock may be effective in slowing the expansion of the virus from infected to uninfected areas. However, after found seropositive and a quarantine period animals could be transported safely to free countries. Of note, DIVA is only useful for epidemiological studies. It would greatly facilitate trade if seropositive animals are deemed safe for transport.

  GAP

  To support the notion that seropositive animals can indeed be transported safely, the duration of immunity after infection or vaccination with a given vaccine should be carefully determined. This would include demonstration that organs from these animals do not pose a risk for risk groups (slaughterhouse workers) after a given period.

• Prevention tools

  Vaccines. Additional, less commonly used, preventative measures include vector control, movement of stock to mosquito-free areas (e.g. higher altitudes), and the confinement of stock in insect-proof stables. All these control methods are often impractical, or are ineffective because they are instituted too late. The movement of animals from endemic areas to RVF-free regions might result in epidemics. Alternatively, animals can be kept in quarantine for a period of 2-3 weeks and subsequently transported to free areas. Preferably, these animals are vaccinated before being placed in quarantine. Other methods for vector control with modest success have been tested in laboratory, such as the use of endosymbiotic bacterium (Wolbachia spp) to suppress virus replication when introduced to naive mosquito species.

  GAP

  European countries should be able to show their contingency plans.

  All trade animals from endemic to free areas should be vaccinated before movement. In this case a DIVA vaccine is advantageous.

  Estimate the minimum time needed for effective quarantine.

• Surveillance

  Animal health surveillance is critical to detect new cases and to identify the initial stages of an epidemic. This act as an early warning system for both the veterinary and public health authorities. RVF should be suspected when abortions and deaths among newborns occur following unusually heavy rains along with reports of influenza-like illness among humans.

  GAP

  Develop control strategies in non-endemic areas (routine monitoring of sentinel animals, monitoring virus circulation in mosquito species in wetland areas in Southern Europe.

• Past experiences on success (and failures) of prevention, control, eradication in regions outside Europe

  Although there is very little doubt that vaccination has contributed significantly to control RVF outbreaks, there is no quantitative data about the effect of vaccination campaigns. The difficulty with RVF outbreaks is that they tend to occur after many years of apparent absence of the disease. As risk perception dismisses farmers have no incentive to vaccinate their livestock. When outbreaks suddenly occur, vaccine manufacturers do not have sufficient time to produce the vaccine and even if they have, it is extremely challenging to deploy the vaccine in the field in a timely manner. Therefore, either emergency stockpiles have to be prepared or combination vaccines should become available that protect not only against RVF but also against another, preferably endemic disease that affects the same species. As it is unclear who will pay for the maintenance of a vaccine stockpile, the second option is probably the most realistic.

  GAPS

  Vaccines protecting against RVF and another disease, preferably an endemic disease that affects the same animal species should be developed. Examples: RVF/Lumpy skin disease for cattle and RVF/PPR for sheep and goats. Plans for stockpiling novel multivalent temperature resistant vaccines (no cold chain need to be maintained) Of note, the development of a combinational vaccine is more expensive.

• Costs of above measures

  Not publicly known but probably high.

• Disease information from the WOAH

• Disease notifiable to the WOAH

  Yes.

• WOAH disease card available

  Direct links to the WOAH

• WOAH Terrestrial Animal Health Code

  Direct links to the WOAH

• WOAH Terrestrial Manual

  Direct links to the WOAH

• Socio-economic impact

• Zoonosis: impact on affected individuals and/or aggregated DALY figures

  No details but the overall case fatality rate for all patients with RVF fever is less than 1%. In humans, the incubation period is 2 to 6 days. However in more recent outbreaks the case/fatality rates increased considerably.

  GAP

  Understand the nature of the increased CF ratio observed in some recent RVF outbreaks.

• Zoonosis: cost of treatment and control of the disease in humans

  There is no treatment (apart from supportive therapy) for humans. Control of human disease depends of quality of public health systems.

  GAP

  It would be extremely valuable to assess the economic damage of a future RVF epidemic as accurately as possible.

• Direct impact (a) on production

  Major impact in Africa with mortality and morbidity.

  GAP

  It would be valuable to assess the impact of RVF outbreaks on political instability in (the horn of) Africa.

• Direct impact (b) cost of private and public control measures

  Unknown .

• Indirect impact

  Major economic impact in nomadic areas with loss of food animals and restrictions on movements especially exports from Africa to the Middle East, in particular the Arabian Peninsula.

• Trade implications

• Impact on international trade/exports from the EU

  No impact as the disease is not reported in the EU but can have a serious trade impact on those countries where the disease is endemic. Detailed standards for trade are described in the WOAH Terrestrial Animal Health code.

• Impact on EU intra-community trade

  No impact as disease not currently reported in the EU.

• Impact on national trade

  No impact as disease not reported in the EU.

• Links to climate

  Seasonal cycle linked to climate

  Related to mosquito populations and breeding cycles.

• Distribution of disease or vector linked to climate

  Closely related.

• Outbreaks linked to extreme weather

  Sustained heavy rain. Studies on climate variability and RVF activity have focused on precipitation and epizootics. Periods of excessive rainfall are believed to increase the egg hatching and larval survival of certain African Aedes floodwater mosquito species.

  GAP

  Impact on the climate change of the RVF spread. The role of soil composition and ground water levels is understudied. This may explain why predictions of outbreaks are still poor.

• Sensitivity of disease or vectors to the effects of global climate change (climate/environment/land use)

  Vectors may have the potential to extend their geographical distribution to Europe. Also, native mosquito species may be capable of spreading the virus, such as demonstrated for several European mosquito species already.

  GAPS

  Competence of mosquitoes from Southern Europe (Greece, Spain, Italy) should be assessed

  Competence of ticks, phlebotomus, and culicoides from Southern Europe should be evaluated.

  More knowledge on the RVF vector competence of European and Asian-breed mosquitoes for RVFV is needed as well as about the different mosquito species present in Europe.

  Environmental factors (including vector microbiota) that may influence vector competence.

• Main perceived obstacles for effective prevention and control

  Unpredictability of outbreaks in animals Affecting mainly low-income countries precludes more investment and developments for control

• Main perceived facilitators for effective prevention and control

  One-health approach for integrated prevention and control is key to reduce disease burden and spread. Set up of sentinel herds based on very high risk areas of RVF occurrence.

  GAP

  Reason for the disease inter-epizootic periods is still unknown.

Main critical gaps

• main critical gaps

  Entomology

  RVFV competence of mosquitoes, ticks, phlebotomus, and culicoides from Southern Europe (Greece, Spain, Italy, France). Enhance our knowledge of the biology of the virus in mosquitoes to find novel strategies to block transmission and anti-vector vaccine developments.

  Physiopathology

  Understand increased CF ratios in humans in recent outbreaks We lack an integrated view of the host immune response to RVFV. Why are most infected patients exhibiting low-grade fever while other patients suffer fatal hemorrhagic fever and/or encephalitis? Identification of genes associated with high risk to develop severe forms of RVF disease in livestock and humans. Mechanisms of clearance of the virus and prevention of RVFV-induced disease unknown. Physio-pathological mechanisms poorly understood in humans: entry in the central nervous system, encephalitis, retinal complications.

  Epidemiology

  Estimate the potential spread of the disease in the next decade Estimate the probability of RVF to become endemic/enzootic out of Africa Identify wild reservoir(s) other than small mammals. Horizontal transmission in livestock should be assessed. Assess the possibility of sporadic sexual transmission through semen of infected patients. The risk of consumption of raw milk should be assessed in more details

  New developments

  Licensing candidate vaccines in Europe should be encouraged as well as plans for vaccine stockpiling Additional commercial diagnostic kits should be developed for humans, and livestock. DIVA diagnostic tests. Combined (multivalent) vaccines Antiviral products for human patients treatment are needed Novel diagnostic approaches (proteomics, whole genome sequencing)

Conclusion

• Conclusion summary (s)

  Anticipation of the incursion of RVF in Europe by studying epidemiology and preparing vaccine and diagnostic solutions is recommended. Contingency planning required to ensure availability of appropriate vaccines and diagnostics should there be incursions of RVF into Europe.

Sources of information

• Expert group composition

  Names of expert group members are included where permission has been given.

  Alejandro Brun, CSIC, Spain – [Leader]

  Paul Wichgers-Schreur, WUR, The Netherlands

  Catherine Cetre, CIRAD, France

• Reviewed by

  Project Management Board

• Date of submission by expert group

  30 September 2025

• References

  This analysis is based on expert insights and, in some instances, supported by selected references. However, some information may reflect expert opinions, which could influence interpretations. Readers are encouraged to seek additional sources if they require specific details.

  Recommended Citation:

  “ Brun A., Schreur PW., Cetre C., 2025. DISCONTOOLS chapter on Rift Valley Fever. https://www.discontools.eu/database/47-rift-valley-fever.html.”

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