Rift Valley fever (RVF) is present in Africa, Madagascar, some Indian Ocean islands, and the Arabian Peninsula. The disease is due to infection with a Phlebovirus in the family Phenuiviridae. Sporadic, sometimes very large, outbreaks of disease in ruminants are usually associated with heavy rainfall and localized flooding. The virus is maintained between epidemics by silent circulation between mosquito vectors and susceptible domestic or wild ruminants and/or by vertical transmission by certain Aedes spp mosquitoes.
During epidemics, abortions in production animals and deaths among young animals, particularly lambs, together with an influenza-like disease in humans, are characteristic. However, infections in both animals and humans are frequently subclinical or mild. Diagnosis is based on identification of characteristic histopathological lesions in the liver and demonstration of the presence of the virus by immunohistochemical staining, PCR assay, and/or increasing antibody titer. Tissues and fluids from infected animals carry a high risk of infection for human handlers. Treatment is supportive, and effective prevention can be achieved by vaccination.
Etiology and Epidemiology of Rift Valley Fever in Animals
Rift Valley fever virus (RVFV) belongs to the order Bunyavirales, family Phenuiviridae, and genus Phlebovirus. An enveloped spherical particle of 80–100 nm in diameter, it has a three-segmented, single-stranded, negative-sense RNA genome with a total length of ~11.9 kilobases (kb). Each of the segments, L (large: 6.4 kb), M (medium: 3.9 kb), and S (small: 1.7 kb), is contained in a separate nucleocapsid within the virion. Remarkably little genetic diversity has been found among RVFV isolates from many countries, and no noteworthy antigenic differences have been demonstrated. However, some differences in pathogenicity occur.
The disease is endemic in many tropical and subtropical regions of sub-Saharan Africa, Madagascar, Comoros, Mayotte, and the Arabian Peninsula. Thought to have been originally confined to the Rift Valley region of eastern and southern Africa, since the 1970s the virus has spread, with major outbreaks having occurred in Egypt since 1977, West Africa since 1987, Madagascar since 1990, and the Arabian Peninsula in 2000. There has also been unconfirmed serologic evidence of RVFV infection in other parts of the Middle East. Particularly large epidemics including large numbers of human cases occurred in Egypt in 1977–1978 and in Kenya in 2006–2007. Between 2016 and 2018, 10 outbreaks of RVF occurred in Uganda, the first in almost 50 years. In 2020, two outbreaks were reported in Libya.
Sporadic large epidemics have occurred at 5–10 year intervals in drier areas of eastern Africa and less frequently in southern Africa. Outbreaks are usually associated with periods of abnormally heavy rainfall or, in some cases, with localized flooding due to dam building or flood irrigation. Smaller outbreaks are likely to occur more often and may frequently be overlooked due to suboptimal veterinary surveillance and confusion with other causes of abortion and neonatal mortality. RVF is considered a threat in other regions of the world, including Europe and North America, where competent mosquito vectors are present, and the potential exists for the virus to become endemic if introduced.
During interepidemic periods, the virus is thought to remain dormant in transovarially infected eggs of floodwater-breeding Aedes spp mosquitoes (subgenera Neomelaniconion and Aedimorphus) in the dry soil of small, ephemeral wetlands (dambos or pans). In some areas, this transovarial transmission is believed to be the most important interepidemic survival strategy of the virus; however, this has seldom been demonstrated, and it is unknown for how long RVFV can survive in this manner. Inapparent cycling of the virus between vectors and wild or domestic mammalian hosts has been reported to occur, and this may be the most important survival strategy for the virus in many areas. Serologic evidence of exposure to RVFV has been found in many wildlife species, either associated with outbreaks in animals or in the absence of reported outbreaks.
RVFV may also be transmitted and emerge or re-emerge by movement of viremic animals, (eg, via the production animal trade and possibly by wind-borne mosquitoes). When either the emergence of infected Aedes spp mosquitoes or the introduction of virus to an area coincides with abnormally wet conditions and the presence of a highly susceptible host population, a large epidemic may ensue. The virus is then amplified in ruminants and transmitted locally by many species of mosquitoes, particularly Culex spp, mechanically by other insects such as biting flies, or iatrogenically such as by reuse of needles between infected animals.
The incidence of RVF peaks during the late rainy season. In areas with cold winters, both the disease and vectors may disappear after the first frost. In warmer climates where insect vectors are present continuously, seasonality is less pronounced and outbreaks are likely to be smaller due to the maintenance of some level of herd immunity.
Humans are readily infected with RVFV via exposure to:
tissues or fluids from infected animals and aborted fetuses
aerosolized blood from infected animals during slaughter
mosquito bites (considered less likely)
Therefore, farmers, farm workers, slaughterhouse workers, and veterinarians are particularly at risk.
Clinical Findings of Rift Valley Fever in Animals
Clinical signs of Rift Valley fever tend to be nonspecific, rendering it difficult to recognize individual cases. The incubation period is 12–36 hours in lambs, and a biphasic fever of up to 108°F (42°C) may develop. Affected animals are listless and reluctant to move or eat and may also show signs of abdominal pain. Mortality in young lambs is high (90%–100%), and animals usually die within 2–3 days. Adult sheep are less susceptible, with 10%–30% mortality; the incubation period is 24–72 hours, and animals show a generalized febrile response, lethargy, hematemesis, hematochezia, and nasal discharge, although infection may also be inapparent.
Calves are less susceptible than lambs; however, mortality may still be as high as 70%. Clinical signs are similar to those in sheep, but icterus is more common. Disease in adult cattle is often inapparent; however, they may show anorexia, lacrimation, salivation, nasal discharge, dysgalactia, and bloody or fetid diarrhea, with a mortality of 5%–10%. Camelids, equids, pigs, dogs, and cats may be infected by RVFV but appear largely resistant to disease, whereas birds, reptiles, and amphibians appear to be refractory to infection.
Sometimes, abortion may be the only sign of infection; the aborted fetus is usually autolyzed. In pregnant ewes, abortion rates vary from 5% to almost 100% in different outbreaks and on different farms; abortion rates in cattle are usually <10%. Vaccination of ewes with live Smithburn strain vaccine may result in early embryonic death, congenital CNS anomalies and arthrogryposis Inherited Defects Embryonic and fetal development are the result of a complex series of well orchestrated events. When properly accomplished, the outcome is a healthy neonate. Errors in the sequential steps of... read more , abortion, or stillbirth. Clinical signs and abortions have also been reported in goats, and occasionally in camels, water buffalo, and some wild ungulate species, including African buffalo (Syncerus caffer), springbok (Antidorcas marsupialis), blesbok (Damaliscus dorcas), kudu (Tragelaphus strepsiceros), nyala (T angasii), sable (Hippotragus niger), and roan (H equinus).
In humans, RVF is usually inapparent or associated with a self-limiting febrile illness characterized by abrupt onset of malaise, myalgia, and arthralgia. Rarely, the condition progresses to ocular disorders, meningoencephalitis, or a hemorrhagic form (which has a 50% case fatality rate).
The hepatic lesions are similar in all species and vary mainly with the age of the affected individual. The most severe lesions, present in aborted fetuses and newborn lambs, are moderately to greatly enlarged, soft, friable livers with irregular congested patches. Numerous grayish-white necrotic foci are invariably present but may not be clearly visible. Hemorrhage and edema of the wall of the gallbladder and mucosa of the abomasum are common. Intestinal contents are dark chocolate-brown.
In all animals, the spleen and peripheral lymph nodes are enlarged and edematous and may show petechiae. Histopathologically, the liver lesions are severe and extensive, with hepatic necrosis being the most striking histologic lesion of RVF in affected animals.
Diagnosis of Rift Valley Fever in Animals
Abortions and death associated with heavy rainfall and flooding
Characteristic histological lesions in liver specimens (necrotic hepatitis)
Immunohistochemistry, PCR assay, or viral isolation
Demonstration of seroconversion
Rift Valley fever should be suspected when abnormally heavy rains and flooding are followed by abortions and neonatal mortality in domestic ruminants, particularly sheep, with necrotic hepatitis. Concurrent influenza-like disease in humans handling animals or their products should increase the index of suspicion for RVF.
The necropsy of infected animals poses considerable risk to the operator and should be performed only by trained personnel using appropriate personal protective equipment. The virus can readily be isolated from tissues of aborted fetuses and the blood of infected animals.
The viral titer in these tissues is often high enough to use organ suspensions as antigen for a rapid diagnosis in neutralization, complement fixation, ELISA, agar gel diffusion tests, or staining of organ impression smears. These tests can be supplemented by isolation in suckling mice or hamsters injected intracerebrally or in cell cultures such as baby hamster kidney (BHK21), monkey kidney (Vero), chicken embryo–related (CER) and mosquito cells, or primary kidney and testis cell cultures of lambs. However, definitive diagnosis of RVFV infection is now routinely performed via detection of viral nucleic acid by conventional reverse transcriptase-PCR assay or by real-time (quantitative) PCR assay. Virus can be demonstrated in organ sections using immunohistochemical stains.
A variety of serologic tests can detect antibody against RVFV; they are helpful in epidemiologic studies and in showing seroconversion during active infection. Commercial ELISA test kits are available for detection of either total immunoglobulin (IgG and IgM) or IgM only. An IgM ELISA can demonstrate recent infection using a single serum sample, with IgM detectable for up to 2–3 months after infection.
Serologic surveys may be complicated by lack of specificity, possibly due to cross-reactivity between RVFV and other phleboviruses. Positive reactions, particularly when the seroprevalence is low, should ideally be confirmed with a virus neutralization test (VNT), which is highly specific and generally regarded as the gold standard assay. A disadvantage of most VNTs is the requirement for high levels of biosafety due to the use of virulent virus; however, recently, safe VNTs with lower biosafety requirements have been developed by using laboratory-produced avirulent RVFV strains.
Wesselsbron disease Overview of Wesselsbron Disease Wesselsbron disease is an acute, arthropod-borne flavivirus infection of mainly sheep, cattle, and goats in sub-Saharan Africa. Infection is common, but clinical disease is infrequent although... read more and other insect-borne viral diseases tend to occur under the same climatic conditions that favor explosive proliferation of arthropod vectors. RVF mortality associated with hepatic lesions should also be distinguished from hepatotoxic plant and algal intoxications; bacterial septicemias such as pasteurellosis Pasteurellosis of Sheep and Goats Pasteurellosis commonly refers to mixed, often secondary, bacterial infection of the lower respiratory tract due to Pasteurella multocida, Mannheimia haemolytica (formerly Pasteurella... read more , salmonellosis Salmonellosis in Animals Salmonellosis is infection with Salmonella spp bacteria. It affects most animal species as well as humans and is a major public health concern. The clinical presentation can range from... read more , and anthrax Anthrax in Animals Anthrax is a noncontagious zoonotic disease caused by the spore-forming bacterium Bacillus anthracis. Anthrax primarily affects domestic and wild herbivores. Clinical features, characterized... read more ; and other viral infections such as Nairobi sheep disease Nairobi Sheep Disease Nairobi sheep disease is a serious tickborne viral disease of small ruminants in Africa. It is characterized by peracute deaths and acute illness with severe hemorrhagic gastroenteritis. Ganjam... read more and peste des petits ruminants Overview of Peste des Petits Ruminants Peste des petits ruminants (PPR) is an acute or subacute viral disease of goats and sheep characterized by fever, necrotic stomatitis, gastroenteritis, pneumonia, and sometimes death. It was... read more . When abortion is the only finding, other important diseases such as brucellosis Overview of Brucellosis in Large Animals Brucellosis is caused by bacteria of the genus Brucella and is characterized by abortion, retained placenta, and to a lesser extent, orchitis and infection of the accessory sex glands... read more , leptospirosis Leptospirosis in Animals - Overview Leptospirosis is a zoonotic disease with a worldwide distribution caused by infection with any of several pathogenic serovars of Leptospira. The disease affects virtually all mammals... read more , chlamydiosis Overview of Chlamydiosis Bacteria of the order Chlamydiales are ubiquitous, obligate intracellular gram-negative bacteria. Within the host cell, they replicate via a unique developmental cycle competing with the host... read more , campylobacteriosis Overview of Enteric Campylobacteriosis Campylobacter spp are spiral, microaerobic, gram-negative bacteria that cause gastroenteritis in people and animals. Several Campylobacter spp are zoonotic. Many domestic animals... read more , toxoplasmosis Toxoplasmosis in Animals Toxoplasmosis is an important zoonotic protozoal infection worldwide. All homoeothermic animal species may be infected. Infection is generally asymptomatic and chronic in immunocompetent individuals... read more , Coxiella burnetii infection, and salmonellosis should be eliminated.
Control and Prevention of Rift Valley Fever in Animals
Prediction may provide early warning
Vaccination of susceptible animals
Once an outbreak of Rift Valley fever has started, any efforts to mitigate its course are usually futile. Control of vectors, movement of stock to high-lying areas, and confinement of stock in insect-proof stables are usually impractical, instituted too late, and of little value. Treatment of individual clinically affected animals should be symptomatic, and the high risk of zoonotic transmission to humans via tissues or fluids should be considered.
Immunization remains the only effective way to protect production animals from RVF. The mouse neuro-adapted Smithburn strain of RVFV can be readily produced in large quantities, is inexpensive, and induces a durable immunity 6–7 days after inoculation in sheep. However, it produces a relatively poor antibody response in cattle. It should typically not be administered for protection of pregnant animals, because it may cause abortion, congenital defects, and hydrops amnii in the ewe; however, its use may be contemplated during an outbreak when possible adverse effects may be outweighed by the dangers of natural infection. Although not proved, it is theoretically possible for the attenuated virus to revert to virulence, and therefore it is not advisable to use live attenuated vaccines in nonendemic countries or regions.
A formalin-inactivated vaccine is safe to use in pregnant animals; however, it induces short-lived immunity and requires booster doses. Subsequently, a naturally attenuated avirulent isolate of RVFV, clone 13, has been used in a commercially available vaccine and is reportedly safer to administer to pregnant animals. Possible future recombinant DNA vaccines and viral strains with deletions of the major virulence genes should offer improved options.
Because large RVF outbreaks occur only very occasionally in any particular area, and areas at risk are often in under-resourced countries, it is difficult to motivate farmers or authorities to vaccinate animals regularly to prevent outbreaks. As a result, vaccination is often employed as an emergency measure in the face of an outbreak, resulting in vaccine shortages, apparent vaccine failure, and iatrogenic transmission within herds/flocks due to reuse of needles on already-viremic animals. The development of multivalent recombinant capripox-vectored vaccines combining RVF with lumpy skin disease Lumpy Skin Disease in Cattle Lumpy skin disease is a viral infection of cattle. Originally found in Africa, it has also spread to countries in the Middle East, Asia, and eastern Europe. Clinical signs include fever, lacrimation... read more and/or peste des petits ruminants Overview of Peste des Petits Ruminants Peste des petits ruminants (PPR) is an acute or subacute viral disease of goats and sheep characterized by fever, necrotic stomatitis, gastroenteritis, pneumonia, and sometimes death. It was... read more may improve vaccine uptake in many areas of Africa affected by these diseases.
Much effort has been directed toward means to predict RVF outbreaks. This includes use of meteorologic and remote-sensing data to identify high-risk areas and time periods. This analysis has been somewhat successful in predicting outbreaks in eastern Africa but less so in southern Africa, and work on predictive models is ongoing. However, outbreaks cannot yet reliably be predicted and are usually of sudden onset. Therefore, routinely immunizing lambs at 6 months old, which should afford lifelong protection, is advisable. The offspring of susceptible ewes can be immunized at any age. Pregnant ewes and cattle can be vaccinated with a formalin-inactivated vaccine, which elicits a better immunity in cattle and is safe in pregnancy. Revaccination after 3 months is advisable to induce an immunity that will last >1 year and to confer colostral immunity to the offspring.
Zoonotic Risk of Rift Valley Fever in Animals
Because RVFV can cause severe and potentially fatal disease in humans, those involved in the food-producing animal industry should be made aware of the potential dangers of exposure to RVFV-infected animals and tissues. Appropriate protective measures should be taken when investigating cases of abortion, handling potentially infected animals, and collecting diagnostic samples.
Rift Valley fever is a vector-borne zoonotic disease with potential for global transmission.
Abortions and death in domestic ruminants associated with heavy rainfall and flooding should suggest the possibility of RVF, particularly if influenza-like symptoms occur concurrently in humans.
The only effective prevention or control method is vaccination, which should be applied in cattle and sheep in areas at risk, particularly if high rainfall is expected.
Strict precautions should be taken to prevent zoonotic transmission via close contact with tissues or fluids from diseased animals or aborted fetuses.
For More Information
Coetzer JAW, Paweska JT, Bird B, Swanepoel R, Odendaal L, Fafetine J. Rift Valley fever. Anipedia. Published online May 31, 2021. https://anipedia.org/resources/rift-valley-fever/1167
Linthicum KJ, Britch SC, Anyamba A. Rift Valley fever: An emerging mosquito-borne disease. Annu Rev Entomol. 2016;61:395-415. doi:10.1146/annurev-ento-010715-023819
CDC: Notes from the Field: Rift Valley Fever Response — Kabale District, Uganda, March 2016.
Kwasnik M, Rozek W, Rola J. Rift Valley Fever – a Growing Threat To Humans and Animals. J Vet Res. 2021 Mar; 65(1): 7–14. doi: 10.2478/jvetres-2021-0009
Shoemaker TR, Nyakarahuka L, Balinandi S, et al. First Laboratory-Confirmed Outbreak of Human and Animal Rift Valley Fever Virus in Uganda in 48 Years. Am J Trop Med Hyg. 2019 Mar; 100(3): 659–671. Published online 2019 Jan 21. doi: 10.4269/ajtmh.18-0732
Faburay B, LaBeaud AD, McVey DS, Wilson WC, and Richt JA. Current Status of Rift Valley Fever Vaccine Development. Vaccines (Basel). 2017 Sep; 5(3): 29. Published online 2017 Sep 19. doi: 10.3390/vaccines5030029