Overview of Rift Valley Fever
Rift Valley fever (RVF) is a peracute or acute, mosquito-borne, zoonotic disease of domestic and wild ruminants in Africa, Madagascar, and the Arabian Peninsula. Large outbreaks of clinical disease are usually associated with heavy rainfall and localized flooding. During epidemics, the occurrence of abortions in livestock and deaths among young animals, particularly lambs, together with an influenza-like disease in people, is characteristic. However, infections are frequently subclinical or mild.
RVF virus belongs to the genus Phlebovirus and is a typical Bunyavirus. 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 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 between RVF virus isolates from many countries, and no significant antigenic differences have been demonstrated, but differences in pathogenicity are seen. The disease is endemic in many tropical and subtropical regions of Africa, Madagascar, and the Arabian Peninsula. Thought to have been originally confined to the Rift Valley region of eastern and southern Africa, the virus has recently expanded its range, with major outbreaks having occurred in Egypt since 1977, West Africa since 1987, Madagascar since 1990, and the Arabian Peninsula in 2000. Particularly large epidemics with large numbers of human cases occurred in Egypt in 1977–1978 and in Kenya in 2006–2007. It is considered a threat to regions further afield, where competent mosquito vectors are present. Sporadic, large epidemics have occurred at 5–10 yr 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. During interepidemic periods, the virus may remain dormant in eggs of floodwater-breeding aedine mosquitoes 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, inapparent cycling of the virus between vectors and wild or domestic mammalian hosts has been shown to occur in many areas. RVF virus may also spread by movement of viremic animals and possibly by wind-borne mosquitoes. When emergence of infected mosquitoes, or 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 when the virus is amplified in ruminants and spread locally by many species of mosquitoes or mechanically by other insects. 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 not seen.
People are readily infected through blood aerosols from infected animals during slaughter, or by exposure to infected animal tissues, aborted fetuses, mosquito bites, and laboratory procedures. Therefore, veterinarians, farm laborers, and abattoir workers are particularly at risk. People can also act as amplifying hosts and introduce the disease (via mosquitoes) to animals in uninfected areas.
Clinical signs of RVF tend to be nonspecific, rendering it difficult to recognize individual cases. The incubation period is 12–36 hr in lambs, and a biphasic fever of up to 108°F (42°C) may develop. Affected animals are listless and reluctant to move or feed and may 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 hr, 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, but 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, but they may show anorexia, lacrimation, salivation, nasal discharge, dysgalactia, and a bloody or fetid diarrhea, with a mortality of 5%–10%. 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, or abortion or stillbirth. Clinical signs and abortions have also been reported in goats, and occasionally in camels, water buffalo, and some wild ungulate species. In people, RVF is usually inapparent or associated with a self-limiting febrile illness characterized by abrupt onset of malaise, myalgia, and arthralgia. A minority (1%–2%) may develop severe disease with ocular lesions, encephalitis, or severe hepatic lesions with hemorrhages; in such cases, the fatality rate may be 10%–20%.
The hepatic lesions are similar in all species and vary mainly with the age of the affected individual. The most severe lesions, seen 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 microscopic lesion of RVF in all domestic animals and people.
RVF should be suspected when abnormally heavy rains and flooding are followed by widespread occurrence of abortions and mortality among newborn animals characterized by necrotic hepatitis, concurrent with influenza-like disease in people handling animals or their products.
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; however, these tests should 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. Detection of viral nucleic acid by PCR is possible, and reverse transcriptase-PCR tests have been described. Virus can be demonstrated in organ sections using immunohistochemical stains.
All conventional serologic tests can be used to detect antibody against RVF virus and are helpful in epidemiologic studies. In some areas, however, serologic surveys may be complicated by cross-reactivity between RVF virus and other phleboviruses; virus neutralization tests are the most specific in this situation. An IgM ELISA can demonstrate recent infection using a single serum sample.
Wesselsbron disease (see Wesselsbron Disease) and other insect-borne viral diseases tend to occur under the same climactic conditions. RVF mortality associated with hepatic lesions should be distinguished from hepatotoxic plant and algal intoxications; bacterial septicemias such as pasteurellosis, salmonellosis, and anthrax; and other viral infections such as Nairobi sheep disease and peste des petits ruminants. When abortion is the only finding, other important diseases such as brucellosis, leptospirosis, chlamydiosis, campylobacteriosis, Coxiella burnetii infection, and salmonellosis should be eliminated.
Immunization remains the only effective way to protect livestock from RVF. The mouse neuro-adapted Smithburn strain of RVF virus can readily be produced in large quantities, is inexpensive, and induces a durable immunity 6–7 days after inoculation. It should normally not be used 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. A small-plaque variant and a mutagen-induced strain have been investigated as potential vaccine candidates but have not been accepted as replacements for the Smithburn strain. More recently, a naturally attenuated avirulent isolate of Rift Valley fever, clone 13, has been used in a commercially available vaccine. It is not advisable to use live attenuated vaccines in nonendemic countries. Possible future recombinant DNA vaccines and viral strains with deletions of the major virulence genes should offer a better alternative. 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.
Much work has gone into attempts to predict RVF outbreaks using meteorologic and remote-sensing data to identify high-risk areas and time periods; this has been somewhat successful in predicting outbreaks in eastern Africa but less so in southern Africa. However, outbreaks cannot yet reliably be predicted and are usually of sudden onset. Therefore, routinely immunizing lambs at 6 mo of age, 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 mo is advisable to induce an immunity that will last >1 yr and to confer colostral immunity to the offspring.
Because RVF virus can cause a severe and potentially fatal disease in people, those involved in the livestock industry should be made aware of the potential dangers of exposure to RVF-infected animals and tissues. Appropriate protective measures should be taken when investigating cases of abortion, handling potentially infected animals, and collecting diagnostic samples.