National Agricultural Biosecurity Center

Synopsis of Rift Valley Fever

Rift Valley Fever (RVF) is an arthropod-borne (primarily mosquito), acute, fever-causing disease that affects primarily domestic animals, such as cattle, sheep, and goats. Since the primary vector is the mosquito, epidemics of RVF mainly occur following heavy rainfall combined with localized flooding. Mosquito eggs are naturally infected with the RVF virus, and the resulting mosquitoes transfer the virus to the livestock on which they feed. Researchers found RVF to be present in dormant eggs of the mosquito. During periods of heavy rainfall, these eggs hatch and infected mosquitoes develop. The infected mosquitoes infect amplifying hosts, which, in turn, serve as a source of infection for many other genera of mosquitoes that rapidly spread the disease. RVF, thus far, appears to be restricted to Africa and the Arabian Peninsula. The virions have a selective affinity for parenchymal cells of the liver and outbreaks of RVF may initially manifest as a wave of unexplained abortions amongst livestock. RVF is highly contagious to humans. Humans develop a sufficient viremia to be a source of infection for mosquitoes and, thus, could introduce the disease into uninfected areas. Herdsmen, abattoir workers, veterinarians, and slaughterhouse workers are at higher risk than the general population for contracting RVF because they have contact with potentially infected animals. International travelers are at higher risk when traveling to countries where RVF is endemic and carried by mosquitoes and other biting insects.

• RVF is zoonotic (a disease that primarily affects animals, but occasionally causes human disease) and is listed as one of the 15 pathogens on the Office International des Epizooties (OIE) "List A" (disease with a high potential for rapid spread, serious economic or public health consequences, and significant impact on the international trade of animals and animal products).
• RVF is transmitted by mosquitoes and is usually amplified in ruminant hosts. Mosquitoes, ticks, and other biting insects can transmit infections from amplifying hosts.
• Humans are accidental hosts and become infected during epizootics either by being bitten by infected mosquitoes, or through contact with infected animal tissues during parturition, necropsy, slaughter, laboratory procedures, or meat preparation. The virus may also infect humans through inoculation (e.g., if the skin is broken) or through inhalation as an aerosol.
• RVF virus can also be found in raw milk.

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Clinical Signs and Symptoms

RVF host range and disease severity.³

Mortality ~ 100%	Severe illness: Abortion, mortality	Severe illness: Viremia, abortion	Infection: Viremia	Refractive to infection
Lambs Calves Kids Puppies Kittens White mice Hamsters Field mice Door mice Field voles	Sheep Cattle Goats Water buffalo Humans	Monkeys Camels Rats Gray squirrels	Horses Cats Dogs Monkeys	Guinea pigs Rabbits Pigs Hedgehogs Tortoises Frogs Chickens Canaries Pigeons parakeets

Animals:

• Incubation period: Up to three days in sheep, cattle, and dogs; 12 to 36 hours in newborn lambs.
• Clinical signs vary with the age, species, and breed of animal and is usually most severe in young animals.
• Clinical signs and symptoms (lambs):
  • Biphasic fever
  • Anorexia
  • Lymphadenopathy
  • Weakness
  • Death within 36 hours (mortality rate: 90 to 100%)
• Clinical signs and symptoms (adult sheep):
  • Fever
  • Mucopurulent nasal discharge
  • Hemorrhagic or foul-smelling diarrhea
  • Vomiting
  • Jaundice
  • Abortion (abortion rate is almost 100%)
  • Unsteady gait
• Clinical signs and symptoms (calves):
  • Fever
  • Anorexia
  • Depression
  • Mortality rate: 10 to 70%
• Clinical signs and symptoms (adult cattle):
  • Fever
  • Anorexia
  • Weakness
  • Excessive salivation
  • Fetid diarrhea
  • Abortion
  • Decreased milk production
• RVF can affect many species, including cattle, sheep, goats, buffalo, camels, monkeys, gray squirrels, and other rodents.
• Cattle and sheep are the primary amplifying hosts.
• Viremia without severe disease can be seen in adult cats, dogs, horses, and some monkeys; however, severe disease can occur in newborn puppies and kittens.
• Rabbits, pigs, guinea pigs, chickens and hedgehogs are relatively resistant.
• Post-mortem lesions:
  • Hepatic necrosis is the most common post-mortem lesion and is more extensive and severe in younger animals,
  • Jaundice,
  • Widespread cutaneous hemorrhages and fluid in body cavities,
  • Peripheral lymph nodes and spleen may be enlarged and edematous, and
  • Inflammation or hemorrhagic enteritis in the intestines.

Humans:

• Incubation period: two to six days.
• Overall case-fatality rate is less than 1 percent.
• Asymptomatic infection or a relatively mild illness with fever and liver abnormalities is common.
• Clinical signs and symptoms (uncomplicated infection):
  • Fever
  • Headache
  • Generalized weakness
  • Dizziness
  • Weight loss
  • Myalgia
  • Back pain
  • Possibly stiffness of the neck, photophobia, and vomiting
  • Most people recover spontaneously within two days to a week
• Complications:
  • Hemorrhagic fever is seen in less than 1 percent of cases (develops two to four days after initial symptoms). The case-fatality rate is about 50 percent,
  • Meningoencephalitis is seen is less than 1 percent of cases (develops one to three weeks after initial symptoms). The case-fatality rate is extremely low, and
  • Ocular disease is seen in approximately 0.5 to 2 percent of cases (develops one to three weeks after initial symptoms). The case-fatality rate is extremely low; however, 1 to 10 percent of patients with ocular disease have some permanent visual impairment.
• Click here for more human-related information on RVF posted on the UAB Website for Bioterrorism and Emerging Infectious Education.⁵

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Diagnosis and Treatment

Diagnostic Samples:

• Samples for diagnostic purposes for animals include blood, tissues from dead animals (usually the brain, spleen, and liver), and aborted fetuses.
• Samples for diagnostic purposes for humans include blood, brain, liver, or other tissues.
• In living hosts, viremia is usually seen only during the first three days of fever.

Differential Diagnosis:

• In animals, the differential diagnoses include bluetongue, Wesselsbron, ephemeral fever, enterotoxemia of sheep, brucellosis, vibriosis, trichomoniasis, Nairobi sheep disease, heartwater, or ovine enzootic abortion.
• In humans, the differential diagnoses include other febrile viral and arboviral illnesses, many other causes of impaired liver function, inflammatory causes of vision loss, bacterial and aseptic meningitis, and encephalitis.

Clinical Diagnosis:

• RVF should be considered in the differential diagnosis whenever the following observations are made in a disease outbreak:
  • High abortion rates (possibly approaching 100%) in ewes, cows, and bitches but lower rates in goats and other ruminants,
  • High mortality (possibly approaching 100%) in lambs and calves less than seven days of age and lower rates of disease and mortality in older animals,
  • Extensive liver lesions in aborted fetuses and neonatal animals,
  • An influenza-like disease in man - particularly in individuals associated with livestock,
  • Occurrence of the disease during a period of high insect activity, and
  • Rapid spread.

Laboratory Tests:

• The virus can be grown in numerous cell lines, including baby hamster kidney cells, monkey kidney cells, chicken embryo reticulum, and primary cultures from cattle or sheep.
• The appropriate test depends on the phase of infection.
• Viral antigens can be detected in blood and tissue samples by the following techniques:
  • For diagnosis in the acute phase:
    • Reverse transcription polymerase chain reaction (RT-PCR)
    • Enzyme-linked immunoassay (ELISA)
    • Immunohistochemistry
  • For diagnosis during the viremic phase:
    • Identification of the antigen
  • Other diagnostic technologies:
    • Non-nested PCR (works well due to the amplitude of viremia)
    • Nested amplimers (yield sequence data that can be used for phylogenetic analyses)
    • Molecular diagnosis
• Key Issue: Plum Island Animal Disease Center is the only agricultural BSL-3 laboratory in the U.S. with RVFV diagnostic capability. Click here for more information relating to key issues and recommendations from the Rift Valley Fever Virus Working Group, 2004.¹¹

Treatment:

• In animals:
  • No specific treatment other than supportive care
  • Vaccines are available in some countries
    • The live vaccine requires only one dose and produces long-lived immunity (may cause abortion if given to pregnant animals)
    • The killed vaccine requires multiple doses to produce protective immunity, which may prove problematic in endemic areas
• In humans:
  • No specific treatment other than supportive care
  • Animal studies has shown ribavirin to be promising
  • Interferon, immune modulators, and convalescent-phase plasma have also been shown to be helpful
  • Human vaccines are in the early stages of investigation
    • An inactivated vaccine has been developed for human use but is not licensed or commercially available. It has been used experimentally to protect veterinary and laboratory personnel at high risk of exposure to RVF
    • Other candidate vaccines are also under investigation

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Economic Consequences and Disease Eradication

Economic Consequences:

• Loss of livestock,
• Costs associated with eradication efforts,
• Costs associated with human illness,
• International trade embargoes and costs associated with production of the necessary documents to reopen trade once a disease-free status is obtained, and
• Increased costs to consumers.

Disease Eradication:

• Immediate notification of state and federal health officials.
• RVF can be prevented by a sustained program of animal vaccination.
• Gloves and other protective clothing should be worn when handling sick animals and their tissues.
• Universal precautions should be taken when handling and processing specimens from animals or patients with suspected or confirmed RVF.
• Protection from and control of the mosquito vectors.
• Wear protective clothing when outdoors (e.g., long shirts and trousers, bednets, insect repellent, etc.).
• Avoid outdoor activity during peak biting times of the vector species.
• Viability:
  • Under optimal conditions, RVF virus can remain viable in aerosols for more than one hour at 25°C.
  • In a neutral or alkaline pH, mixed with serum or other proteins, the virus can survive for as long as four months at 4°C and eight years below 0°C.
• RVF is highly susceptible to low pH, lipid solvents and detergents, ether, chloroform, and solutions of sodium or calcium hypochlorite with residual chlorine content greater than 5,000 ppm.
  • The change in acidity of meat shortly after slaughter is sufficient to kill the virus
  • Pasteurization of milk kills the virus

RVF and Bioterrorism:

• Under optimal conditions, RVF virus can remain viable in aerosols for more than one hour (optimal conditions: 25°C, neutral or alkaline pH, mixed with serum or other proteins).
• Regardless of how RVF may be introduced, the nature of its vector-borne epidemiology means that, if it is not rapidly contained, it would spread as rapidly as West Nile Fever virus, but with far more serious consequences - the most likely tip-off event would be an "animal abortion storm".¹¹
• Considered to be potentially suitable as a biological weapon for the following reasons:¹¹
  • RVF can be disseminated through aerosols (RVF virus in aerosols has a half-life in excess of 75 minutes at 25°C and 30 percent relative humidity),
  • RVF has a low infectious dose,
  • RVF can cause high morbidity and mortality (human mortality rate of patients presented may exceed 10% for a non-endemic population),
  • RVF has the potential to cause fear and panic in the general public,
  • Effective vaccines for RVF are not yet available to the general public, and
  • RVF pathogens are available and/or can be readily produced in large quantities.
• For more information on RVF and bioterrorism, click here, (Emerging Infectious Diseases, 2003).¹³

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Outbreaks

• No reported outbreaks have occurred outside of the African Continent and the Arabian Peninsula thus far.
• RVF was first isolated in 1930 in the Rift Valley of Kenya. Since that time, the disease has reached epidemic proportions, emerging irregularly in Kenya every 3 to 10 years.
• Extensive human disease associated with RVF was not reported until 1951; an estimated 20,000 persons were infected during an epizootic of cattle and sheep in South Africa.
• 1977-78: The first RVF event occurring outside of the sub-Saharan Africa occurred in Egypt, with an estimated 18,000 persons infected and 598 deaths.
• 1997-98: A severe epizootic occurred in East Africa that resulted in hug losses among the domestic goats, as well as 89,000 human cases and more that 500 human deaths. Click here for more information on this outbreak published in the MMWR by the CDC⁷ or here for more information published in the Emerging Infectious Disease journal by the CDC.¹⁶
• 2000: RVF events were reported in Saudi Arabia and Yemen, representing the first cases reported outside of Africa. These outbreaks demonstrated that the human mortality rate of patients presented may exceed 10% for a non-endemic population. For more information on these outbreaks, click on the following links: 1 (MMWR, 2000), 2 (JAMA, 2000), and 3 (MMWR, 2000).^{8, 9, 10}
• 2004: RVF outbreaks were reported in Saudi Arabia and in Senegal. According to OIE officials, five seropositive cases were detected in four sheep flocks in Saudi Arabia; however, there was no clinical evidence either on the positive cases or on the contact animals. Furthermore, no clinical cases have been presented and results of tests to detect the virus in mosquitoes were negative. Cases reported in Senegal were based on clinical diagnosis. According to this report, there were a total of 35 susceptible animals (sheep) and five abortions. For more information on these outbreaks, click on one of the following links: 1 (OIE, 2005),¹⁴ 2 (Center for Emerging Issues, 2004),¹⁵ and 3 (CDC, 2005).¹²

• Source: Rift Valley Fever Distribution Map published on the Centers for Disease Control and Prevention (CDC) Website. Available at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/rvfmap.htm.

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Sources and Related Articles

Sources:

1. Centers for Disease Control and Prevention. Rift Valley Fever Fact Sheet. Available at http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Fact_Sheets/Rift_Valley_Fever_Fact_Sheet.pdf.
2. Center for Infectious Disease Research and Policy at the University of Minnesota. Rift Valley Fever. Available at http://www.cidrap.umn.edu/cidrap/content/biosecurity/ag-biosec/anim-disease/rvf.html.
3. Mebus, C. A., 1998. Rift Valley Fever (Infectious enzootic hepatitis of sheep and cattle). In Foreign Animal Diseases. "The Gray Book" (6th ed., pp. 324-331). Richmond, Pat Campbell & Associates and Carter Printing Company. Available at http://www.vet.uga.edu/vpp/gray_book/fad.pdf.←
4. Office International des Epizooties Institute for International Cooperation in Animal Biologics and Iowa State University's Center for Food Security and Public Health, January 2004. Rift Valley Fever: Infectious Enzootic Hepatitis of Sheep and Cattle. Available at http://www.cfsph.iastate.edu/Factsheets/pdfs/rift_valley_fever.pdf.
5. University of Alabama at Birmingham's Bioterrorism and Emerging Infections Education Website. Rift Valley Fever Summary: Introduction and Epidemiology. Available at http://www.bioterrorism.uab.edu/EI/riftValley/summary.asp.←
6. World Health Organization. September 2000. Rift Valley Fever. Fact Sheet N°207. Available at http://www.who.int/mediacentre/factsheets/fs207/en/print.html.

Related Articles:

7. Anonymous, April 10, 1998. Rift Valley Fever - East Africa, 1997-1998. MMWR. 47(13):261-264. Available at http://www.cdc.gov/mmwr/PDF/wk/mm4713.pdf.←
8. Anonymous, October 13, 2000. Outbreak of Rift Valley Fever - Saudi Arabia, August-October, 2000. MMWR. 49(40):905-908. Available at http://www.cdc.gov/mmwr/PDF/wk/mm4940.pdf.←
9. Anonymous, November 8, 2000. Rift Valley Fever Strikes the Middle East. JAMA. 284(18):2309. Available at http://jama.ama-assn.org/cgi/reprint/284/18/2309.pdf.←
10. Anonymous, December 1, 2000. Outbreak of Rift Valley Fever - Yemen, August-October 2000. MMWR. 49(47):1065-1066. Available at http://www.cdc.gov/mmwr/PDF/wk/mm4947.pdf.←
11. ANSER, August 2004. Rift Valley Fever Virus Working Group: Summary Report and Recommendations. Arlington, VA. Click here to access this document.←
12. Chavalier, V., R. Lancelot, Y. Thiongane, B. Sall, A. Diaité, and B. Mondet, November 2005. Rift Valley Fever in Small Ruminants, Senegal, 2003. Emerging Infectious Diseases. 11(11):1693-1700. Available at http://www.cdc.gov/ncidod/EID/vol11no11/pdfs/05-0193.pdf.←
13. DiGiovanni, C., B. Reynolds, R. Harwell, E. B. Stonecipher, and F. M. Burkle, June 2003. Community Reaction to Bioterrorism: Prospective Study of Simulated Outbreak. Emerging Infectious Diseases. 9(6):708-712. Available at http://www.cdc.gov/ncidod/EID/vol9no6/pdfs/02-0769.pdf.←
14. Office International des Epizooties. Most recent outbreak information worldwide. Available at http://www.oie.int/eng/info/hebdo/A_DSUM.htm.←
15. Orloski, K. and W. Weber, September 27, 2004. Suspected Rift Valley Fever, Saudi Arabia, September 27, 2004: Impact Worksheet. Published on the Center for Emerging Issues Website by Veterinary Services. Available at http://www.aphis.usda.gov/vs/ceah/cei/IW_2004_files/RVF_SaudiArabia_092004_files/.←
16. Woods, C. W., A. M. Karpati, T. Grein, N. McCarthy, P. Gaturuk, et.al., February 2002. An Outbreak of Rift Valley Fever in Northeastern Kenya, 1997-98. Emerging Infectious Disease. 8(2):138-144. Available at http://www.cdc.gov/ncidod/EID/vol8no2/pdf/01-0023.pdf.←

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