Rift Valley fever virus
The Rift Valley fever virus (RVFV), a three-segmented RNA virus, belongs to the Phlebovirus genus of the Bunyaviridae family. The Bunyaviridae family includes viruses that cause many other serious diseases in both animals and humans. RVF is an arthropod borne viral (arboviral) disease transmitted via mosquitoes. Aedes and Culex genera, the primary and secondary mosquito vectors, transmit the virus between animals or from viremic animals to humans.
RVFV infects and causes disease in humans as well as livestock (e.g., sheep, goat, cattle, and camel). Several studies have suggested that many wildlife species (e.g., the African buffalo, rodents, bats, and monkeys) are affected by RVFV, but it is unclear if these species act as reservoirs of RVFV during inter-epidemic seasons. The wildlife/livestock interface that occurs when animals are grazing is a potential risk for RVFV infection of livestock. Human behaviour, such as direct contact with infected animals or their fluids and particularly aborted animals, and being exposed to infected mosquitos increase the risk of being infected by RVFV.
History of the disease
Rift Valley fever was first recognized as a disease in sheep in Rift Valley, Kenya around 1900. The virus was not isolated until 1930. Since then there have been intermittent outbreaks throughout Kenya. A major epizootic occurred in 1950-51 which resulted in 500,000 sheep abortions and 100,000 sheep deaths. In 1977-78, an outbreak of RVF occurred along the Nile in Egypt. This was the first epidemic out of sub-Saharan Africa. This outbreak resulted in an estimated 18,000 human cases. There were 598 human deaths which occurred from encephalitis and hemorrhagic fever. Many abortions and deaths were reported in sheep, goats, cattle, water buffalo and camels.
In 1987, an outbreak of RVF occurred in the Senegal River basin (West Africa). This epizootic differed from prior outbreaks in that it was not associated with the typical heavy rainfall. Mosquito breeding occurred in large rivers and dams. The largest outbreak of RVF reported occurred in Kenya, Africa in 1997-1998. An estimated 89,000 humans were infected with 478 deaths. An RVF outbreak occurred in Saudi Arabia from August 2000 to September 2001; it was the first confirmed outbreak of RVF outside of Africa. This outbreak illustrated the potential for the spread of this disease to other regions of the world. An outbreak of Rift Valley fever occurred in Egypt in August of 2003. Forty-five cases of RFV were diagnosed with 17 deaths. The outbreak occurred in a rural region 150 kilometers north of Cairo and all cases were Egyptian farmers.
In 2006, an outbreak of Rift Valley fever began in Kenya. It soon spread to the surrounding countries of United Republic of Tanzania and Somalia. Over 1000 human case were reported with case-fatality varying between the countries from 23 to 45%. Animal movement and slaughter restrictions were implemented as has vaccination efforts for livestock in affected areas. In 2010, South Africa had over 14,000 cases of RVF; 489 separate outbreaks were observed. Abnormally high rainfall likely contributed to these outbreaks.
Rift Valley fever is transmitted by mosquitoes, particularly Aedes species. The virus is transovarially transmitted to the eggs of the mosquito. These eggs lay dormant for many years in the dry soil of grassland areas. Following heavy rainfalls, the pooling water gives the eggs a proper environment to hatch. These newly hatched infected mosquitoes then seek a feeding source (human or animal). Once a ruminant is infected, it serves as an amplifying host. Infected livestock can have be highly viremic and cause infection other mosquitoes. Humans also develop a high enough viremia to be a source of infection for mosquitoes
Secondary arthropod vectors can become infected from the ruminant and rapidly spread the disease. Culex and Anopheles mosquitoes can serve as secondary vectors. Biting flies such as midges, phlebotomids, stomoxids and simulids may serve as mechanical transmitters of the virus, however this is thought to be minimal route of infection. The virus can also be transmitted in utero to the fetus. It has also been found in semen and raw milk.
Humans do not seem to be infected by casual contact with live hosts, but can be infected by aerosols or direct contact with tissues during parturition, necropsy, slaughter, laboratory procedures or meat preparation for cooking
Disease in Humans
Signs and Symptoms RVF virus has an incubation period of 2-6 days following infection and can cause several different disease syndromes. Most commonly, people with RVF have either no symptoms or a mild illness associated with fever and liver abnormalities. Patients who become ill usually experience fever, generalized weakness, back pain, and dizziness at the onset of the illness. Typically, patients recover within two days to one week after onset of illness. However, a small percentage (less than 8%) of people infected with RVF develops much more severe symptoms, including:
• Ocular disease (diseases affecting the eye), which sometimes accompanies the mild symptoms described above. Lesions on the eyes may occur 1-3 weeks after onset of initial symptoms with patients reporting blurred and decreased vision. For many patients, lesions disappear after 10-12 weeks; however, for those with lesions occurring in the macula, approximately 50% of patients will have permanent vision loss.
• Encephalitis, or inflammation of the brain, which can lead to headaches, coma, or seizures. This occurs in less than 1% of patients and presents 1-4 weeks after first symptoms appear. Though death from this is rare, neurological deficits, sometimes severe, may persist.
• Hemorrhagic fever, which occurs in less than 1% of overall RVF patients, but fatality for those who do develop these symptoms, is around 50%. Symptoms of hemorrhaging may begin with jaundice and other signs of liver impairment, followed by vomiting blood, bloody stool, or bleeding from gums, skin, nose, and injection sites. These symptoms appear 2-4 days and death usually occurs 3-6 days after.
Risk of Exposure
Approximately 1% of humans infected with RVF die of the disease. Case-fatality proportions for infected animals, on the other hand, are significantly higher. The most severe impact is observed in pregnant livestock infected with RVF, which results in abortion of virtually 100% of fetuses.
For humans, studies have shown that spending time in rural areas and sleeping outdoors at night in regions where outbreaks occur could be a risk factor for exposure to mosquito and other insect vectors. Animal herdsmen, abattoir workers, veterinarians, and other individuals who work with potentially-infected animals in RVF-endemic areas (areas where the virus is present) have an increased risk for infection. International travelers increase their chances of getting the disease when they visit RVF-endemic locations during periods when sporadic cases or epidemics are occurring.
Diagnosis and treatment
During the early phase of illness in the blood and in postmortem tissue, the virus may be detected using virus isolation, antigendetection ELISA, and molecular techniques (PCR). Antibody testing using enzyme-linked immunoassay (ELISA) can be used to confirm presence of IgM antibodies, which appear as an early, transient response, and IgG antibodies, which persist for several years. Both IgM and IgG antibodies are specific to RVF virus.
Treatment is symptomatic and supportive therapy. With the hemorrhagic syndrome, blood transfusions may be needed to replace coagulation factors. The anti-viral medication, ribavirin, may prove helpful.
Disease in animals
RVF can affect many species of animals. Sheep and cattle are most severely affected and they are the primary amplifying hosts for the virus. Adult sheep and cattle may develop clinical disease and abortions can reach 100%. In kids and calves clinical disease is severe and mortalities are high. Other ruminants are also affected. Generally, the adults do not show clinical disease but abortion and disease of young animals can be severe. The same is true for dogs and cats. Some rodents are susceptible and others are resistant. Neutralizing antibody has been reported in a small percentage of horses and some monkeys in areas where the disease is endemic. Pigs, birds, rabbits, guinea pigs, and others appear to be resistant to the virus.
Abortion in adult sheep and goats is the most common sign of RVF. It can occur at any state of gestation. The fetus will have an autolysed appearance. Abortion rates are very high – in some cases as high as 100%. Remember parturient material can contain RVF virus. Adult sheep can have inapparent infection. Clinical signs most commonly seen include fever, mucopurulent nasal discharge and possibly vomiting. Mortality in adults, especially those that have aborted, can be 20 to 30%; however, abortion may be the only sign seen.
Lamb and kids
The incubation period in lambs and kids is 12 to 36 hours. As previously mentioned, aborted fetuses are the most common sign. Newborns are highly susceptible. Signs include high fever (105.8 oF), listlessness, and anorexia. Most lambs die within 2 days, but can occur in as short as 12 hours. Mortality can be over 90% for young less than 1 week old. Lambs and kids over 2 weeks old have a mortality rate over 20%.
Cattle are also affected by RVF. Adults usually have inapparent disease. Clinical signs seen include fever, weakness, anorexia, excessive salivation and fetid diarrhea. Icterus is also commonly seen. Death in adult cattle can be 10%. Abortions also occur in cattle and can be as high as 100%. Calves show similar signs as lambs and kids – fever, depression and acute death. Mortality in calves can be from 10 to 70%.
Other species can be infected by RVF, but such cases are less common. Dogs can have abortion rates as high as 100%. Puppies are severely affected and typically die. Kittens have also been reported to be highly susceptible to RVF virus. Horses have been experimentally shown to have a low grade viremia; however, to date there have been no equine cases. Pigs have been reported to either be very resistant to the virus or have inapparent infections. Birds have been found to be refractory to the virus.
Post Mortem Lesions
Post mortem lesions found in sheep, cattle and goats indicate hepatic necrosis. This can be quite extensive in younger animals and fetuses. The liver is greatly enlarged, yellow and friable. Petechial hemorrhages may be very prominent and found on cutaneous or serosal surfaces. [Photo shows a sheep liver that is pale, swollen and contains multiple foci of hemorrhage.
A person’s chances of becoming infected can be reduced by taking measures to decrease contact with blood, body fluids, or tissues of infected animals and protecting themselves against mosquitoes and other bloodsucking insects. Use of mosquito repellents and bed nets are two effective methods. For persons working with animals in RVF-endemic areas, wearing protective equipment to avoid any exposure to blood or tissues of animals that may potentially be infected is an important protective measure. A number of questions and challenges remain in the control and prevention of RVF.
Knowledge regarding virus maintenance and transmission within different mosquito species and the risk factors associated with severe cases of RVF in humans are still under investigation. Potentially, establishing environmental monitoring and case surveillance systems may aid in the prediction and control of future RVF outbreaks.
No vaccines are currently available for human vaccination. Different types of vaccines for veterinary use are available.
The killed vaccines are not practical in routine animal field vaccination because of the need of multiple injections. Live vaccines require a single injection but are known to cause birth defects and abortions in sheep and induce only low-level protection in cattle.
The live-attenuated vaccine, MP-12, has demonstrated promising results in laboratory trials in domesticated animals, but more research is needed before the vaccine can be used in the field.
The live-attenuated clone 13 vaccine was recently registered and used in South Africa. Alternative vaccines using molecular recombinant constructs are in development and show promising results.
• Center for Food Security and Public Health, Iowa State University, 2011: Rift Valley Fever; Infectious Enzootic Hepatitis of Sheep and Cattle
• Centers for Disease Control and Prevention. Update: Outbreak of Rift Valley fever—Saudi Arabia, August– November 2000. MMWR Morb. Mortal. Wkly. Rep. 2000, 49, 982–985.
• Centers for Disease Control and Prevention. Outbreak of Rift Valley fever—Saudi Arabia, August–October, 2000. MMWR Morb. Mortal. Wkly. Rep. 2000, 49, 905–908.
• Ratovonjato, J.; Olive, M.M.; Tantely, L.M.; Andrianaivolambo, L.; Tata, E.; Razainirina, J.; Jeanmaire, E.; Reynes, J.M.; Elissa, N. Detection, isolation, and genetic characterization of Rift Valley fever virus from Anopheles (Anopheles) coustani, Anopheles (Anopheles) squamosus, and Culex (Culex) antennatus of the Haute Matsiatra region, Madagascar. Vector Borne Zoonotic Dis. 2011, 11, 753–759.
• MMWR Rift Valley Fever Outbreak — Kenya, November 2006–January 2007: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5604a3.htm
• MMWR Rift Valley Fever — East Africa, 1997-1998: http://www.cdc.gov/mmwr/preview/mmwrhtml/00051976.htm
• Viral Special Pathogens Branch Outbreaks: http://www.cdc.gov/ncezid/dhcpp/vspb/outbreaks.html
• WHO disease outbreak news: http://www.who.int/csr/don/en/