Rift Valley Fever

Last updated March 31, 2004

Agent
Hosts
Epidemiology
Rift Valley Fever As a Biological Weapon
Clinical Features
Laboratory Diagnosis
Differential Diagnosis
Treatment
Prevention
Outbreak Control
Public Health Issues
References

Agent

Rift Valley fever (RVF) is caused by a hemorrhagic fever virus (RVF virus) that causes disease in both humans and animals. This document deals only with disease in animals. For more information on RVF in humans, see Viral Hemorrhagic Fever.

Key features of the viral agent are as follows:

Family: Bunyaviridae
Genus: Phlebovirus
Virions enveloped, slightly pleomorphic, and 80 to 120 nm in diameter
Genome contains single-stranded negative-sense RNA with three segments

Segments are named S (small), M (medium), and L (large).
Each segment is enclosed in a separate nucleocapsid within the virion.

Major sites of viral replication: liver and spleen; the brain also a common site, especially in fetuses and neonates
Inactivated by disinfectants (eg, sodium or calcium hypochlorite [residual chlorine should exceed 5,000 ppm]) and solutions having a pH of less than 6.2 (eg, acetic acid) (see References: OIE: Rift Valley fever)
Viability: can be maintained for 4 months at 4°C when stored in neutral or alkaline solutions in the presence of proteins (such as those found in serum), or for 8 years when stored below 0°C

Hosts

RVF virus can affect a variety of livestock species as well as wild animals. Predominant animal hosts include:

Cattle
Sheep
Goats
Camels
African buffalo
Dromedaries
White rhinoceroses
Waterbucks
Bats and several rodent species, such as the Namaqua rock mouse
Wild ruminants
Dogs
Humans

Epidemiology

Transmission

RVF is a mosquito-borne disease. Aedes mosquitoes serve as the major reservoir and vector.
Transovarial transmission occurs within Aedes mosquitoes; infected eggs lie dormant for years until flooding occurs, allowing them to hatch and spread the virus to the livestock on which they feed (see References: LeDuc 1989).
Other mosquito species, 10 of which are native to North America, and other biting insects, such as sandflies, also can serve as vectors. They become infected after feeding on infected animals, further contributing to spread of the virus.
In Nigeria, livestock workers and wildlife rangers have been found to have significantly higher levels of RVF antibodies than other members of the population, suggesting that the virus may circulate at low levels in domestic livestock and possibly wild ruminants between epizootic periods.

Occurrence

RVF is found primarily in sub-Saharan Africa and North Africa. It was first recognized as a disease of livestock in the 1930s.
A major epidemic involving thousands of livestock cases and 18,000 human cases with approximately 600 deaths occurred in Egypt in 1977 (see References: Meegan 1979). Additional outbreaks in Egypt have been reported, probably representing repeated introductions of the virus.
Another large outbreak involving thousands of cases occurred in Somalia and Kenya in 1997-1998 (see References: Woods 2002).
In the fall of 2000, outbreaks occurred simultaneously in Yemen and Saudi Arabia, the virus was thought to have been introduced from Africa through the sheep trade (see References: CDC: Outbreak of Rift Valley fever—Yemen; CDC: Outbreak of Rift Valley fever—Saudi Arabia; Shoemaker 2002).
Epizootics often are multifocal and occur irregularly at 5- to 15-year intervals.

Communicability

RVF virus has not been shown to be directly communicable between animals in the absence of a mosquito vector.

Rift Valley Fever As a Biological Weapon

RVF is considered suitable as a biological weapon for the following reasons:

Several genera of mosquitoes found in the United States can serve as vectors for RVF virus (eg, Aedes, Anopheles, Culex); therefore, the disease could become endemic following an intentional release. This pattern recently has been illustrated following the natural introduction of West Nile virus (which also is a mosquito-borne disease) into North America.
RVF virus infects both humans and livestock and could, therefore, cause both economic damage to the livestock industry and human morbidity and mortality.
The disease has been demonstrated to cause severe socioeconomic damage, largely due to the high abortion rate in sheep.
Once introduced into a new area, the disease would be difficult to eradicate.

Clinical Features

The major clinical features of RVF in animals are outlined in the following table. Signs in all affected animals range from peracute to inapparent, and susceptibility is dependent on breed, genotype, and age.

Clinical Features of Rift Valley Fever in Animals
*Feature*	*Characteristics*
CATTLE
Incubation period	1-6 days
Clinical signs	Calves: —Fever of 40°-42°C (104°-106°F) —Depression —Icterus —Anorexia and weakness —Listlessness —Evident abdominal pain Adults: —Fever of 40°-42°C (104°-106°F) —Excessive salivation —Anorexia —Weakness —Fetid diarrhea —Fall in milk yield —Nasal discharge
Complications	—Abortion rates as high as 85% (aborted fetus often autolysed) —Hepatitis —Cerebral infections —Ocular infections
Case-fatality rate	—Calves: 10%-70% —Adults: <10%
SHEEP AND GOATS
Incubation period	Lambs: 12-36 hr Adults: 1-6 days
Clinical signs	Lambs: —Fever of 40°-42°C (104°-107°F) —Anorexia and weakness —Listlessness —Evident abdominal pain Adults: —Fever of 40°-41°C (104°-106°F) —Mucopurulent nasal discharge —Vomiting —Anorexia —Listlessness —Diarrhea —Icterus
Complications	—Abortion rates can reach 100% (aborted fetus often autolysed) —Peracute hepatic disease in lambs and kids <1 wk of age —Hepatitis —Cerebral infections —Ocular infections
Case-fatality rate	Lambs —<1 wk of age: as high as 100% —>1 wk of age: as high as 20% Adults: 20%-30%

Pathology

Aborted fetuses and neonates

Characteristic features include severe hepatic lesions and an enlarged liver that is friable, soft, and reddish to yellowish-brown in color with petechial hemorrhages. Areas of patchy congestion and small grayish foci may be scattered throughout the liver parenchyma (see Gray Book figure 91 [References: Mebus 1998])

Necrosis is severe and is characterized by dense aggregates of cellular and nuclear debris and also by the presence of fibrin and inflammatory cells.
Necropsies also show eosinophilic, rod-shaped intranuclear inclusion bodies in approximately half of hepatic samples examined.

The contents of the abomasum and small intestine of newborn lambs are chocolate brown.

Adult sheep

Hepatic lesions are less severe than those seen in lambs and fetuses, but icterus is more common.

Calves and adult cattle

Hepatic lesions are less severe than those in sheep and more localized, with visible necrotic foci and more distinct lobulation.

Most animals

Edema and hemorrhages in wall of the gallbladder
Enlarged peripheral and visceral lymph nodes
Extensive subcutaneous and serosal hemorrhages ranging from petechial to ecchymotic
Accumulation of blood-stained fluids in body cavities
Hemorrhagic enteritis and widespread cutaneous hemorrhages

Laboratory Diagnosis

RVF can be identified in the field on the basis of the characteristic histopathologic liver lesions, but infection should be confirmed by virus isolation or detection of viral antigen, viral antibody, or viral RNA.

Suitable specimens for antibody testing from live animals include heparinized blood and serum; a second blood sample should be drawn 30 days after the initial one.
Suitable pathology specimens include liver, spleen, kidney, lymph nodes, and heart blood; brain tissue from aborted fetuses also may be tested.
Samples must be securely packed on ice and appropriately labeled. When immediate transit is not possible, a duplicate set of samples should be sent: one in saline or glycerol and the other in formalin.
The virus can be cultured through inoculation of hamsters, mice, or cell cultures. Several types of cell cultures are acceptable; examples include:

African green monkey kidney (Vero)
Baby hamster kidney (BHK)
Chicken embryo reticulum (CER)

Viral antigens can be detected through several laboratory tests:

Immunofluorescence in cryostat sections and immunofluorescence on impression smears of infected tissues such as liver, spleen, or brain
Complement fixation and immunodiffusion on tissue suspensions
Immunodiffusion and enzyme immunoassay (EIA) for antigen detection in blood samples

Viral antibodies can be detected through several laboratory tests:

IgM or IgG antibody specific enzyme-linked immunoassay (ELISA)
Complement fixation
Indirect immunofluorescence
Virus neutralization
Immunodiffusion
Hemagglutination inhibition
Plaque reduction tests
Viral RNA can be detected via reverse transcriptase polymerase chain reaction (RT-PCR).

Differential Diagnosis

Conditions and agents to consider in differential diagnosis include:

Bacterial septicemias
Consumption of plant toxins
Rinderpest virus
Peste des petits ruminants
Nairobi sheep disease
Bluetongue
Wesselsbron disease
Bovine ephemeral fever
Enterotoxemia of sheep
Brucellosis
Vibriosis
Trichomoniasis
Heartwater disease
Ovine enzootic abortion

Treatment

There is no specific therapy for infected animals. Ribavirin may be efficacious in humans, although definitive clinical data are lacking (see References: Borio 2002).

Prevention

Animal Vaccination

Vaccination of animals against RVF has been used to prevent disease in endemic areas and to control epizootics.

Currently, the most commonly used vaccine is a live-virus vaccine derived from the Smithburn strain, which was attenuated through serial intracerebral inoculation of mice.

One inoculation confers immunity for 3 years and produces protection in 6 to 7 days.
The vaccine causes abortion in pregnant ewes.
The vaccine also is pathogenic for humans.

Inactivated vaccines also have been developed for use in both animals and humans.

The animal vaccine has been shown to be safe and effective but requires two inoculations, which has limited its utility in outbreak control.
The human vaccine is still under investigation, although initial studies suggest that it is safe and provides good long-term immunity (see References: Pittman).

Additional attenuated live-virus vaccines (such as the MV P12 vaccine) are also under development. The MV P12 vaccine appears to be safer in pregnant or lactating animals (see References: Baskerville 1992, Morrill 1997).

Other Preventive Approaches

Remote satellite sensing and monitoring of environmental conditions have been used to predict the occurrence of epizootics in endemic areas. These predictions allow implementation of measures aimed at reducing mosquito vectors before epizootics occur.

Outbreak Control

Rift Valley fever outbreaks in livestock populations can be difficult to control. Methods used in past outbreak settings include the following (see References: CDC: Outbreak of Rift Valley fever—Yemen):

Implement vector control of mosquito populations (eg, larviciding).
Restrict livestock movement, since animals can have high levels of viremia and serve to amplify transmission.
Prevent human exposure to infected animal tissues or abortuses through educational campaigns.
Prevent human exposure to mosquito vectors through use of protective clothing, application of insect repellents, and avoidance of outdoor activities during times of peak vector activity.

Public Health Issues

During epizootics in animal populations, infection can spread to humans and result in concurrent outbreaks of human disease. Humans can become infected through several different mechanisms:

Bites of infected mosquitoes
Direct contact with infected animal tissues (see References: Borio 2002) and aerosols generated during slaughter
Aerosols generated in the laboratory setting (see References: Smithburn 1949)

Subclinical infection in humans is common. In addition, there are four clinical patterns of RVF:

Undifferentiated fever lasting 2 to 7 days with or without nausea, vomiting, and abdominal pain (this form of illness occurs in >90% of clinical cases)
Hemorrhagic fever with marked hepatitis and bleeding manifestations (<1% of cases; occurs 2 to 4 days after onset of fever); common bleeding manifestations include gastrointestinal bleeding and epistaxis
Encephalitis (<1% of cases; occurs 2 to 3 weeks after onset of fever); neurologic symptoms include confusion, lethargy, tremors, ataxia, coma, seizures, meningismus, vertigo, and choreiform movements
Retinitis (up to 10% of cases; occurs 1 to 3 weeks after onset of fever); hemorrhages, exudates, and cotton wool spots may be visible on macula and blindness may result

The overall case-fatality rate is <1%; however, for cases complicated by hemorrhagic fever, the case-fatality rate may be as high as 50%. For more information on RFV in humans, see Viral Hemorrhagic Fever.

References

Baskerville A, Hubbard KA, Stephenson JR. Comparison of the pathogenicity for pregnant sheep of the Rift Valley fever virus and a live attenuated vaccine. Res Vet Sci 1992 May;52(3):307-11 [Abstract]

Borio L, Inglesby T, Peters CJ, et al. Hemorrhagic fever viruses as biological weapons: medical and public health management. JAMA 2002;287(18):2391-405 [Full text]

CDC. Outbreak of Rift Valley fever—Saudi Arabia, August-November 2000. MMWR 2000 Nov 3;49(43);982-5 [Full text]

CDC. Outbreak of Rift Valley fever—Yemen, August-October 2000. MMWR 2000 Dec 1;49(47):1065-6 [Full text]

LeDuc JW. Epidemiology of hemorrhagic fever viruses. Rev Infect Dis 1989;11(Suppl 4):S730-5

Mebus CA. Rift Valley fever. In: US Animal Health Association, Committee on Foreign Animal Disease. Foreign animal diseases: the gray book. Ed 6. Richmond, VA: US Animal Health Assoc, 1998 [Full text]

Meegan JM. Rift Valley fever epizootic in Egypt: description of the epizootic and virological studies. Trans R Soc Trop Med Hyg 1979;73:618-23

Morrill JC, Mebus CA, Peters CJ. Safety and efficacy of a mutagen-attenuated Rift Valley fever virus vaccine in cattle. Am J Vet Res 1997 Oct;58(10):1104-9 [Abstract]

OIE (Office International des Epizooties/World Organization for Animal Health). Rift Valley fever [Full text]

Pittman PR, Liu CT, Cannon TL, et al. Immunogenicity of an inactivated Rift Valley fever vaccine in humans: a 12-year experience. Vaccine 1999 Aug 20;18(1-2):181-9 [Abstract]

Shoemaker T, Boulianne C, Vincent MJ, et al. Genetic analysis of viruses associated with emergence of Rift Valley fever in Saudi Arabia and Yemen, 2000-01. Emerg Infect Dis 2002 Dec;8(12) [Full text]

Smithburn KC, Mahaffy AF, Haddow AJ, et al. Rift Valley fever: accidental infections among laboratory workers. J Immunol 1949;62:213-27

Woods CW, Karpati AM, Grein T, et al. An outbreak of Rift Valley fever in northeastern Kenya, 1997-98. Emerg Infect Dis 2002 Feb;8(2):138-44 [Full text]


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