Zoonotic Infections

Rift Valley Fever: a health risk in Africa

Infectious Disease News, July 2009
Arnon Shimshony, DVM

One of the diseases that is considered a health hazard to travelers visiting certain African countries is the zoonotic, arthropod–borne viral disease Rift Valley Fever, also known as Infectious Enzootic Hepatitis of Sheep and Cattle. Although humans are infected, mostly, by their exposure to blood, tissues and aborted foeti of infected domestic ruminants, transmission from animal to human by arthropod vectors plays its role as well.

The Rift Valley Fever (RVF) virus, an RNA virus in the genus Phlebovirus (family Bunyaviridae), is found throughout most of Africa and is endemic in southern and eastern Africa, where outbreaks occur at irregular intervals. Epidemics have also been reported in Egypt, Saudi Arabia and Yemen. The most recent upsurge of RVF has been observed, since December 2008, in Madagascar and its island neighbor Mayotte, off the east coast of Africa. South Africa (Kwazulu-Natal) reported an outbreak as well. Earlier in 2008, outbreaks were reported in Kenya, Swaziland and Sudan. (A map of recent RVF outbreaks is available on the CDC’s website.)

Arnon Shimshony, DVM
Arnon Shimshony

RVF is important in domestic ruminants, characterized by high mortality rates in young animals and abortions in pregnant ruminants. RVF is endemic in sub-Saharan Africa, where epidemics tend to occur at intervals, when heavy rainfalls cause infected mosquito eggs to hatch and large numbers of susceptible animals are present. Outbreaks are characterized by mass abortions and high mortality in neonates. Epizootics are often accompanied by human disease. Many human cases are caused by occupational exposure to blood and tissues from infected animals, but mosquito-borne transmission can cause epidemics. The most common form of the disease is a self-limiting, influenza-like illness; however, ocular disease and rare cases of fatal hemorrhagic fever also occur.

History

The disease was described in sheep since the beginning of the 20th century in the Rift Valley area of Kenya. The identification of the causative agent and the recognition of its zoonotic nature came in 1931. At that time it was demonstrated that a virus, involved in the sheep disease that was initially called “enzootic hepatitis,” also caused a disease in humans resembling “true dengue” and yellow fever. The virus had characteristic destructive action on hepatic cells of susceptible animals, mainly newborn sheep and cattle, abortifacient activity and possibly mosquito transmission. Eventually the described disease was designated as “Rift Valley Fever.”

It took 19 years before RVF was diagnosed in another African country, South Africa (1950-1951), where the diagnosis was initially done in veterinarians engaged in the autopsy of a breeding bull; only then it became apparent that the disease had been circulating throughout large parts of the Union, causing losses in sheep, goat and cattle herds and infecting humans, for several months. Since then, RVF has spread throughout the continent, reaching Egypt in 1976 and penetrating into the Arab peninsula in the late 1980s.

Transmission

RVF is transmitted by mosquitoes and is usually amplified in ruminant hosts. In endemic regions, cases can occur sporadically or in epidemics. The virus appears to survive in the dried eggs of Aedes mosquitoes; epidemics are associated with the hatching of these mosquitoes during years of heavy rainfall and localized flooding. In Africa, outbreaks typically occur in savannah grasslands every five to 15 years and in semi-arid regions every 25 to 35 years. Once it has been amplified in animals, the RVF virus can also be transmitted by other vectors, including many mosquito species and possibly other biting insects such as ticks and midges. The virus can be transmitted in utero to the fetus.

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.

Both animals and humans theoretically have the potential to introduce RVF into new areas by infecting mosquitoes.

Infections in animals

RVF can affect many species of animals, particularly sheep, cattle, goats, buffalo, camels and monkeys. The primary amplifying hosts are sheep and cattle. Experimental infections have been described in many mammals, including adult cats, dogs, horses and some monkeys, with severe disease seen in newborn puppies and kittens.

The incubation period can be as long as three days in sheep, cattle, goats and dogs. In newborn lambs, it is 12 to 36 hours.

The clinical signs vary with the age, species and breed of the animal. In endemic regions, epidemics of Rift Valley fever can be recognized by high mortality rates (as high as 90% to 100%!) in newborn animals, and abortions in adults, which vary from 5% to almost 100% in ewes, while in cattle typically less than 10%. Mortality rates in calves are 10% to 70%.

Other symptoms that may occur in adult sheep include fever, weakness, a mucopurulent nasal discharge, melena, hemorrhagic diarrhea, and vomiting. Icterus may also be seen, particularly in cattle. Similar but milder infections occur in goats.

No specific treatment, other than supportive care, is available.

The most consistent post-mortem lesion is hepatic necrosis, which is more extensive and severe in younger animals. The liver lesions are usually less severe in adult animals. Additional lesions may include jaundice, widespread cutaneous, gastric and intestinal hemorrhages, and fluid in the body cavities. Petechial and ecchymotic hemorrhages may be seen on the surface of other internal organs. Microscopically, hepatic necrosis is the most prominent lesion.

Diagnostic tests

RVF can be diagnosed by isolation of the virus from the blood of febrile animals and from the tissues of dead animals and aborted fetuses; the liver, spleen and brain are generally used. This virus can be grown in numerous cell lines. Hamsters, adult or suckling mice, embryonated chicken eggs or two-day-old lambs can also be used.

Viral titers in tissues are often high, and a rapid diagnosis can sometimes be made with CFT, neutralization or agar gel diffusion tests on tissue suspensions. Viral antigens can also be detected by immunofluorescent staining of impression smears from the liver, spleen or brain. Enzyme immunoassays and immunodiffusion tests can identify virus in the blood. RT-PCR testing can detect viral RNA.

Commonly used serologic tests include virus neutralization, ELISA and hemagglutination inhibition tests. Immunofluorescence, CF, radioimmunoassay and immunodiffusion are used less frequently. Cross-reactions with other phleboviruses can occur in serologic tests other than virus neutralization.

Similar techniques are applied for the diagnosis of RVF in humans.

Prevention in animals

Vaccines are generally used to protect animals in endemic regions and prevent their infecting people. Attenuated and inactivated RVF vaccines are both available. Attenuated vaccines produce better immunity; however, abortions and birth defects can occur in pregnant animals. Subunit vaccines are in development.

The movement of animals from endemic areas to RVF-free regions can result in epidemics.

Infections in humans

Humans are highly susceptible to RVF. Most infections involve animal breeders, abattoir workers, veterinarians, and others who work closely with blood and tissue samples from animals. During outbreaks in animals, mosquitoes may spread the virus to humans and cause epidemics.

Infection with the RVF virus usually results in an asymptomatic infection or a mild to moderate, nonfatal, influenza-like illness with fever and liver abnormalities. The symptoms of uncomplicated infections may include fever, headache, generalized weakness, dizziness, weight loss, myalgia and back pain. Some patients also have stiffness of the neck, photophobia and vomiting. Most people recover spontaneously within two days to a week. The incubation period is two to six days.

Complications, including hemorrhagic fever, meningoencephalitis or ocular disease, occur in a small percentage of patients. Hemorrhagic fever usually develops two to four days after the initial symptoms. The symptoms may include jaundice, hematemesis, melena, a purpuric rash, petechiae and bleeding from the gums. Hemorrhagic fever frequently progresses to frank hemorrhages, shock and death (case fatality rate of up to 50%).

Ocular disease and meningoencephalitis are usually seen one to three weeks after the initial symptoms. The ocular form, seen in approximately 0.5% to 2% of cases, is characterized by retinal lesions and may result in some degree of permanent visual impairment. Death rarely occurs. The overall case fatality rate for all patients with RVF is less than 1%.

Prevention in humans

Conventional arthropod control measures should be used to prevent transmission by mosquitoes and other potential insect vectors. During epidemics, vaccination of susceptible animals can prevent amplification of the virus and protect people as well as animals. Exposure to aerosols produced during the slaughter of animals should be avoided. A human vaccine has been developed, but it has limited availability. Additional vaccines are under investigation.

Arnon Shimshony, DVM, is Associate Professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail Animal Diseases Zoonoses Moderator. Dr. Shimshony was Chief Veterinary Officer, State of Israel, from 1974 to 1999.

One of the diseases that is considered a health hazard to travelers visiting certain African countries is the zoonotic, arthropod–borne viral disease Rift Valley Fever, also known as Infectious Enzootic Hepatitis of Sheep and Cattle. Although humans are infected, mostly, by their exposure to blood, tissues and aborted foeti of infected domestic ruminants, transmission from animal to human by arthropod vectors plays its role as well.

The Rift Valley Fever (RVF) virus, an RNA virus in the genus Phlebovirus (family Bunyaviridae), is found throughout most of Africa and is endemic in southern and eastern Africa, where outbreaks occur at irregular intervals. Epidemics have also been reported in Egypt, Saudi Arabia and Yemen. The most recent upsurge of RVF has been observed, since December 2008, in Madagascar and its island neighbor Mayotte, off the east coast of Africa. South Africa (Kwazulu-Natal) reported an outbreak as well. Earlier in 2008, outbreaks were reported in Kenya, Swaziland and Sudan. (A map of recent RVF outbreaks is available on the CDC’s website.)

Arnon Shimshony, DVM
Arnon Shimshony

RVF is important in domestic ruminants, characterized by high mortality rates in young animals and abortions in pregnant ruminants. RVF is endemic in sub-Saharan Africa, where epidemics tend to occur at intervals, when heavy rainfalls cause infected mosquito eggs to hatch and large numbers of susceptible animals are present. Outbreaks are characterized by mass abortions and high mortality in neonates. Epizootics are often accompanied by human disease. Many human cases are caused by occupational exposure to blood and tissues from infected animals, but mosquito-borne transmission can cause epidemics. The most common form of the disease is a self-limiting, influenza-like illness; however, ocular disease and rare cases of fatal hemorrhagic fever also occur.

History

The disease was described in sheep since the beginning of the 20th century in the Rift Valley area of Kenya. The identification of the causative agent and the recognition of its zoonotic nature came in 1931. At that time it was demonstrated that a virus, involved in the sheep disease that was initially called “enzootic hepatitis,” also caused a disease in humans resembling “true dengue” and yellow fever. The virus had characteristic destructive action on hepatic cells of susceptible animals, mainly newborn sheep and cattle, abortifacient activity and possibly mosquito transmission. Eventually the described disease was designated as “Rift Valley Fever.”

It took 19 years before RVF was diagnosed in another African country, South Africa (1950-1951), where the diagnosis was initially done in veterinarians engaged in the autopsy of a breeding bull; only then it became apparent that the disease had been circulating throughout large parts of the Union, causing losses in sheep, goat and cattle herds and infecting humans, for several months. Since then, RVF has spread throughout the continent, reaching Egypt in 1976 and penetrating into the Arab peninsula in the late 1980s.

Transmission

RVF is transmitted by mosquitoes and is usually amplified in ruminant hosts. In endemic regions, cases can occur sporadically or in epidemics. The virus appears to survive in the dried eggs of Aedes mosquitoes; epidemics are associated with the hatching of these mosquitoes during years of heavy rainfall and localized flooding. In Africa, outbreaks typically occur in savannah grasslands every five to 15 years and in semi-arid regions every 25 to 35 years. Once it has been amplified in animals, the RVF virus can also be transmitted by other vectors, including many mosquito species and possibly other biting insects such as ticks and midges. The virus can be transmitted in utero to the fetus.

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.

Both animals and humans theoretically have the potential to introduce RVF into new areas by infecting mosquitoes.

Infections in animals

RVF can affect many species of animals, particularly sheep, cattle, goats, buffalo, camels and monkeys. The primary amplifying hosts are sheep and cattle. Experimental infections have been described in many mammals, including adult cats, dogs, horses and some monkeys, with severe disease seen in newborn puppies and kittens.

The incubation period can be as long as three days in sheep, cattle, goats and dogs. In newborn lambs, it is 12 to 36 hours.

The clinical signs vary with the age, species and breed of the animal. In endemic regions, epidemics of Rift Valley fever can be recognized by high mortality rates (as high as 90% to 100%!) in newborn animals, and abortions in adults, which vary from 5% to almost 100% in ewes, while in cattle typically less than 10%. Mortality rates in calves are 10% to 70%.

Other symptoms that may occur in adult sheep include fever, weakness, a mucopurulent nasal discharge, melena, hemorrhagic diarrhea, and vomiting. Icterus may also be seen, particularly in cattle. Similar but milder infections occur in goats.

No specific treatment, other than supportive care, is available.

The most consistent post-mortem lesion is hepatic necrosis, which is more extensive and severe in younger animals. The liver lesions are usually less severe in adult animals. Additional lesions may include jaundice, widespread cutaneous, gastric and intestinal hemorrhages, and fluid in the body cavities. Petechial and ecchymotic hemorrhages may be seen on the surface of other internal organs. Microscopically, hepatic necrosis is the most prominent lesion.

Diagnostic tests

RVF can be diagnosed by isolation of the virus from the blood of febrile animals and from the tissues of dead animals and aborted fetuses; the liver, spleen and brain are generally used. This virus can be grown in numerous cell lines. Hamsters, adult or suckling mice, embryonated chicken eggs or two-day-old lambs can also be used.

Viral titers in tissues are often high, and a rapid diagnosis can sometimes be made with CFT, neutralization or agar gel diffusion tests on tissue suspensions. Viral antigens can also be detected by immunofluorescent staining of impression smears from the liver, spleen or brain. Enzyme immunoassays and immunodiffusion tests can identify virus in the blood. RT-PCR testing can detect viral RNA.

Commonly used serologic tests include virus neutralization, ELISA and hemagglutination inhibition tests. Immunofluorescence, CF, radioimmunoassay and immunodiffusion are used less frequently. Cross-reactions with other phleboviruses can occur in serologic tests other than virus neutralization.

Similar techniques are applied for the diagnosis of RVF in humans.

Prevention in animals

Vaccines are generally used to protect animals in endemic regions and prevent their infecting people. Attenuated and inactivated RVF vaccines are both available. Attenuated vaccines produce better immunity; however, abortions and birth defects can occur in pregnant animals. Subunit vaccines are in development.

The movement of animals from endemic areas to RVF-free regions can result in epidemics.

Infections in humans

Humans are highly susceptible to RVF. Most infections involve animal breeders, abattoir workers, veterinarians, and others who work closely with blood and tissue samples from animals. During outbreaks in animals, mosquitoes may spread the virus to humans and cause epidemics.

Infection with the RVF virus usually results in an asymptomatic infection or a mild to moderate, nonfatal, influenza-like illness with fever and liver abnormalities. The symptoms of uncomplicated infections may include fever, headache, generalized weakness, dizziness, weight loss, myalgia and back pain. Some patients also have stiffness of the neck, photophobia and vomiting. Most people recover spontaneously within two days to a week. The incubation period is two to six days.

Complications, including hemorrhagic fever, meningoencephalitis or ocular disease, occur in a small percentage of patients. Hemorrhagic fever usually develops two to four days after the initial symptoms. The symptoms may include jaundice, hematemesis, melena, a purpuric rash, petechiae and bleeding from the gums. Hemorrhagic fever frequently progresses to frank hemorrhages, shock and death (case fatality rate of up to 50%).

Ocular disease and meningoencephalitis are usually seen one to three weeks after the initial symptoms. The ocular form, seen in approximately 0.5% to 2% of cases, is characterized by retinal lesions and may result in some degree of permanent visual impairment. Death rarely occurs. The overall case fatality rate for all patients with RVF is less than 1%.

Prevention in humans

Conventional arthropod control measures should be used to prevent transmission by mosquitoes and other potential insect vectors. During epidemics, vaccination of susceptible animals can prevent amplification of the virus and protect people as well as animals. Exposure to aerosols produced during the slaughter of animals should be avoided. A human vaccine has been developed, but it has limited availability. Additional vaccines are under investigation.

Arnon Shimshony, DVM, is Associate Professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail Animal Diseases Zoonoses Moderator. Dr. Shimshony was Chief Veterinary Officer, State of Israel, from 1974 to 1999.