Rift Valley Fever Summary

Introduction and Epidemiology

Rift Valley Fever (RVF) is an acute, febrile, mosquito-borne and aerosol transmitted viral disease which affects both livestock and humans, primarily in Africa and on the Arabian Peninsula. The current range of the virus includes Eastern and Southern Africa and Madagascar, sub-Saharan Africa, Saudi Arabia and Yemen. Animals affected include cattle, sheep, goats, buffalo, monkeys, and camels. The virus, a three-stranded RNA virus in the Phlebovirus genus of the family Bunyaviridae, was first identified in the great Rift Valley of East Africa in 1931 during cattle and sheep epizootics. Outbreaks in humans are usually associated with animal disease occurrence. Most follow a period of heavy rains, which fill shallow grassland depressions known as "dambos". RVF virus may be present in dormant mosquito eggs in these pools, which then hatch and provide a source and vector for RVF outbreaks. Infected ruminant animals amplify the virus and then transmit it via further generations of mosquitoes to other animals or humans. People may also be infected in animal husbandry occupational settings by aerosols during slaughtering, handling aborted fetuses or products of conception, performing necropsies, or conducting laboratory procedures. Explosive outbreaks across Africa tend to occur every five to fifteen years, depending on weather patterns. Numerous outbreaks have occurred since 1950, the most recent being in Saudi Arabia and Yemen in 2000. Severe outbreaks have occurred in urban and suburban settings. In Egypt's 1977 outbreak, human infection rates in some areas were as high as 35%, 200,000 people fell ill, 18,000 cases were laboratory confirmed, and 598 deaths from hemorrhagic fever occurred.

Rift Valley Fever is considered both a significant biological warfare threat and a severe natural emerging disease threat to the United States, as the afore-mentioned case numbers illustrate. It may be spread by aerosols of the virus as well as being vector borne. In the age of rapid airplane travel around the world, it would not be surprising to have an infected mosquito or an infected person travel to the U.S. and become a source for further spread of the virus in this country. There are numerous competent mosquito vectors for RVF in the U.S. Aedes, Culex, and other species of mosquitoes may spread the virus, as may biting flies such as sandflies. Although there exist two vaccines for RVF, they are both investigational and are available in extremely limited quantities. The clinical severity of RVF is much greater than that of West Nile fever, and the implications of importation would potentially be much more drastic than has been seen with West Nile.

Clinical Features

Unlike West Nile fever, in which 80% of human infections are clinically inapparent, 90% of those infected by the RVF virus are demonstrably ill, and RVF victims are ten times more likely to die. The incubation period is 2 to 6 days, and the illness lasts from 2 to 7 days in most patients.

Most patients will experience sudden onset of a mild, biphasic febrile illness, which lasts for a few days and then they recover. Subclinical cases may occur. Signs and symptoms in ill patients may include weakness, malaise, back pain, dizziness, and weight loss in addition to fever. The most common complication is inflammation of the retina (15% of cases), causing retinitis with central scotoma and paramacular hemorrhages and swelling. As many as 1 to 10 percent of convalescent patients may have some degree of vision loss.

Severe cases may exhibit higher fever, myalgias, back pain, headache, coma, and seizures. As RVF is cytopathic and targets the liver and brain, liver necrosis with jaundice and hemorrhage (approximately 1% of cases), and meningoencephalitis (1% of cases) can occur. Death occurs in about one percent of patients and is usually due to hemorrhagic shock or severe meningoencephalitis. Higher mortality rates have been observed in some outbreaks (about 20% in the 2000 Saudi Arabia-Yemen outbreak). Neurological sequellae in patients who recover from encephalitis may be severe. Abortions can occur in a very high percentage of infected pregnant women.

Clinical and Laboratory Diagnosis

Diagnosis of RVF is usually clinical in the setting of a known outbreak with typical features in humans and animals in a known endemic area. Outbreaks may follow periods of heavy rains and high insect activity. Nonspecific laboratory abnormalities may include threefold elevations in liver enzymes such as AST, ALT, and GGT, hemoglobin less than 8 gm/dl, platelets less than 100,000 mm 3, increased LDH and CPK, and elevated BUN and creatinine. Specific diagnosis may be made serologically with acute and convalescent sera collected 30 days apart, by ELISA (antigen-capture and IgM), PCR, immunohistochemistry, and by virus isolation. Specimens for virus isolation must be collected and shipped with extra care due to the infectiousness of the virus; laboratory safety conditions for virus isolation must be at a minimum of bio-containment level 3.

Presenting Signs and Symptoms (Clinical Diagnosis)

• Fever
• Malaise
• Headache
• Back Pain
• Myalgias
• Vision Loss
• Nausea and Vomiting
• Hemorrhagic Manifestations
• Neurological Signs and Symptoms

Differential Diagnosis: Other febrile viral and arboviral illnesses, many other causes of impaired liver function, inflammatory causes of vision loss, bacterial and aseptic meningitis and encephalitis. Probably most important is ruling out treatable bacterial, fungal, or mycobacterial meningitis in cases with neurological involvement. Some other viral etiologies with liver involvement and/or neurological or hemorrhagic manifestations may include dengue, yellow fever, equine encephalitis viruses, Japanese encephalitis, West Nile, CCHF, Ebola, and Marburg, among others.

Prevention: Prevention of Rift Valley Fever may involve a number of measures, including measures designed to control outbreaks. Such measures may include intensive mosquito-control efforts in limited areas where people may be exposed, vaccination of susceptible animals, restrictions on animal movement and avoidance of slaughtering and butchering of animals possibly infected, use of insect repellents and bednets in endemic areas, comprehensive educational campaigns, and increased animal, human, and vector surveillance. An IND inactivated cell culture RVF vaccine is available in extremely limited quantities from USAMRIID, and this vaccine was used to help control the outbreak of RVF which occurred in Saudi Arabia and Yemen in 2000. Even the Army stocks of this vaccine may not all be available for human use, as most lots of vaccine have not been through phase I human lot- release safety studies - the Army's RVF vaccine research program has been dormant for some time. A live mutagen-attenuated human vaccine, MP-12, was also developed at USAMRIID in the early 1990's and is in further clinical testing at the University of Texas - Galveston, but it is not currently available. In occupational settings where animal handlers or laboratory workers may be susceptible to aerosols of RVF, those persons should be vaccinated routinely if vaccine is available. Both live and inactivated vaccines are available for livestock in endemic areas.

Infection Control Measures: Patients should be kept in a screened or insecticide treated room for at least 5 days after onset or until afebrile; viremia occurs early in the course of clinical symptoms. Blood and body fluid precautions should be observed. Acute phase blood specimens must be handled carefully.

Treatment: Treatment of Rift Valley Fever is generally supportive. Unpublished experience with ribavirin in the 2000 Saudi Arabia RVF outbreak indicated that mortality from meningoencephalitis may be higher in ribavirin treated patients. Thus routine treatment with this drug cannot be recommended at this time.