Medicine for Africa - Medical Information Service

IFT   ALLEY   EVER

Definition:

Rift Valley Fever (RVF) is a so-called zoonosis, a disease that can be transmitted to humans from both wild and domestic animals, usually via a vector.  RVF is a viral disease that is transmitted to humans primarily from ruminant, thus domesticated animals such as cattle, sheep, goats, camels and even buffalos. Transmission usually occurs via a bite of infected mosquitoes, such as the Aedes (Ae.) vexans, Ae. cumminsii, and Ae. circumluteolus, among other Aedes species, as well as blood-sucking insects and sandflies (e.g. Phlebotomus duboscqui).

The causative virus is a member of the genus Phlebovirus of the Bunyaviridae family of viruses.  Most infections to humans are the result of direct or indirect contacts with blood or organs of infected animals.  In addition to the transmission by a bite of a mosquito, the disease can also be transmitted through handling of infected animal tissue during the slaughtering or butchering processes, when assisting animal births, conducting certain veterinary procedures, or even during the disposal of animal carcasses.  Thus, farmers, shepherds, veterinarians and slaughterhouse workers are at an increased risk of infection.

Additional paths of transmission include aerosol transmission by inhaling heavily infected air, often produced during slaughtering and in other exposed surroundings, and through transcutaneous transmission via skin abrasions or even by ingesting unpasteurized or uncooked milk, derived from infected animals.

To date, no human-to-human transmissions have been documented, and no health care workers have been infected while adhering to standard infection control precaution procedures.

Since mosquitoes can be carried along wide distances by wind, RVF can potentially spread to new countries and even new continents within a relatively short period of time.

First signs of the surfacing of the virus may be recognized when an increased number of abortions by pregnant sheep have been observed, as an extraordinary number of deaths in new-born sheep and goats is typical, and up to 90% of lambs can die without presenting much more than some fever, lack of appetite and general weakness. 

Primary areas of potential infections with RVF consist of eastern and southern Africa, including most countries of sub-Saharan Africa and Madagascar.

While the virus lies dormant during the dry season in drought-resistant mosquito eggs, the mosquito population starts to flourish in shallow, water-filled ground depressions, following heavy periods of rain.
Sleeping in the open air significantly increases the chances of contracting RVF in potentially infected regions.

RVF in (domesticated) animal hosts can cause severe disease in cattle, sheep, goats and camels.  Sheep seem to be the most susceptible hosts, followed by cattle and camels. Age appears to be significant, as up to 90% of lambs die of the disease, versus only about 10% of adult sheep.

            Historic Review

While the disease was first reported in livestock in 1915 in Kenya, the virus was only isolated in 1931 during an investigation of an epidemic among sheep in the Rift Valley of Kenya.

Subsequently, significant outbreaks have been reported in African countries such as Cameroon, the Central African Republic, Egypt, Kenya, Madagascar, Mali, Mauritania, Nigeria, Senegal, Somalia, South Africa, Tanzania, Zambia and Zimbabwe, as well as outside of Africa in Saudi Arabia and even Yemen in 2000, raising concerns for the potential of a worldwide spread of the disease within the foreseeable future.

Major outbreaks usually occur in cycles of five to 20 years, often associated with heavy rainfalls which are associated with a marked increase of mosquito populations.

Symptoms:

Rift Valley Fever is a cytopathic illness; it replicates to high titers, forms plaques and prefers to target liver tissue, creating focal hepatic necrosis, and can even cross the blood-brain barrier, infecting the brain, neurons and glia, and subsequently result in necrotic encephalitis.

After transmission by an infected vector, the virus enters the lymph nodes, where it replicates, followed by systemic spread throughout the body via the lymphatic system.

Following an incubation period of two to six days, the clinical picture can range from no symptoms at all to the sudden onset of a mild fever with a biphasic course, to severe symptoms of liver and kidney disorders.  The most common complications of the disease consist of retinitis with a central scotoma (focal area of visual impairment), paramacular retinal hemorrhage and local edema.  Some kind of permanent vision loss may occur in 1% to 10% of convalescents.

While patients usually recover from the disease more or less unharmed within two to seven days after the onset of symptoms, severe cases of the disease can result in prominent fever, myalgia (muscle pain), encephalitis, including headaches, seizures and coma, as well as back pain, extreme weight loss, and occasional dizziness. 

Severe cases of RVF are subdivided into three categories:

1. Liver necrosis with hemorrhage,
2. Retinitis with visual impairment, and
3. Meningoencephalitis,

all of which can result in severe hemorrhages, vascular collapse, shock and subsequent death.

The overall mortality rate in humans is about 1%, while rates in livestock are usually significantly higher, especially for fetuses of pregnant livestock which is 100%.
 
General disease symptoms include:

• Fever associated, flu-like symptoms, including muscle and joint pains and headaches;
• Neck stiffness and light sensitivity, and
• Loss of appetite and vomiting.

Symptoms in severe RVF cases may include one or all of the following:

• Ocular involvement (in up to 2% of patients) – blurred or decreased vision after one to three weeks post infection. While most patients recover within 12 weeks, if disease associated changes occurred in the macula, up to 50% of patients will suffer a permanent loss of vision.
• Meningoencephalitis (in less than 1% of patients) – may be associated with often intense headaches. Loss of memory, confusion and hallucinations, as well as disorientation, vertigo, lethargy, convulsions and ultimately coma are some of the clinical features.  Neurological symptoms may occur as late as 60+ days post infection and result in permanent, often severe, residual neurological deficits, and, in rare instances, result in death.
• Hemorrhagic form of the disease is the most severe form. Two to four days after the onset of the disease, evidence of severe liver impairment (jaundice) appears, with subsequent bleeding incidents, such as vomiting blood, bleeding from the nose and/or gums, grossly identifiable blood in the stool, as well as bleeding within the skin (ecchymosis), and much more.  The case-fatality rate in this group approaches 50%, usually within three to six days after the onset of those symptoms.

 
Diagnosis:

Diagnosis of the RVF virus depends on a variety of mechanisms of identification:

• Indirectly – by serological tests such as enzyme-linked immunoassays (ELISA) may confirm the presence of IgM (immunoglobulin M – the ‘early antibody’) antibodies;
• Directly – by using cell cultures or reverse transcriptase polymerase chain reaction (RT-PCR) techniques, the virus can be identified during the early phase of the illness, or in post-mortem autopsy tissues.

 
Treatment:

For severe cases of RVF, the most favored treatment at this time is ribaverin, which has also shown to be effective against Lassa fever.  Obviously, general supportive therapy is adamant, in order to control the fever-related systemic symptoms.  Mild cases of the disease may not require any treatment at all.

Other, more or less promising treatment schedules include the application of interferon, immune modulators, and even convalescent-phase blood plasma.

Overall, there is currently no specific treatment available for Rift valley fever.

 
Prevention:

At this point in time, there is only an experimental inactivated vaccine available for human use, but only for the protection of veterinary and laboratory personnel in high risk areas.  This vaccine is not yet licensed or FDA approved for the general public.

Other vaccine trials are under investigation.

There are some vaccines available for animals – killed RVF virus vaccines, as well as live-attenuated RVF vaccines.  These vaccines are only approved for veterinary use, and still provide only very limited protection to cattle, while they can cause birth defects and abortions in sheep. 

Thus, the prediction of a potential RVF epidemic is still the best form of prevention:

• Effective containment of the disease and preparation towards a potential outbreak prior to anticipated weather conditions, such as heavy rains, the rain season, expected cyclones, etc., is difficult to achieve, if not impossible.  Sustained programs of prophylactic vaccination of livestock may provide some protection; however, in view of the often long intervals between epidemics (often five to ten years and more in certain areas), and the costs, this would not be a realistic way of prevention in most developing countries where the disease occurs most frequently). 

• Public health education regarding potential ways on how to prevent contamination during an outbreak can be effective, if applied effectively.  Thus, exposure to any kind of body fluids from animals, either directly or via aerosols, should be avoided.  In addition, general preventive measurements to protect against mosquito bites (nets, light colored clothing with long sleeved shirts, trousers, etc.) should be observed.

• Animal derived blood products, tissues (meat) and milk should be avoided or thoroughly cooked prior to consumption.

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