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RIFT
VALLEY FEVER
Overview
Rift Valley Fever (RVF),
is a zoonosis (a disease which primarily affects animals, but occasionally
causes disease in humans). It may cause severe disease in both animals and
humans leading to high morbidity and mortality. The death of RVF-infected
livestock often leads to substantial economic losses.Since 1930, when the
virus was first isolated during an investigation into an epidemic amongst
sheep on a farm in the Rift Valley of Kenya, there have been outbreaks in
sub-Saharan and North Africa. In 1997-98, there was a major outbreak in
Kenya and Somalia. In September 2000, RVF was for the first time reported
outside of the African Continent. Cases were confirmed in Saudi Arabia and
Yemen. This virgin-soil epidemic in the Arabian Peninsula raises the
threat of expansion into other parts of Asia and Europe.
Many different
species of mosquitoes are vectors for the RVF virus. There is, therefore,
a potential for epizootics (epidemics amongst animals) and associated
human epidemics following the introduction of the virus into a new area
where these vectors are present. This has been demonstrated in the past
and remains a concern.
RVF Virus
The virus, which
causes RVF, is a member of the Phlebovirus genus, one of the five
genera in the family Bunyaviridae.
RVF Vectors
- RVF virus is primarily spread
amongst animals by the bite of infected mosquitoes.
- A wide variety of mosquito
species may act as the vector for transmission of the RVF virus; in
different regions a different species of mosquito may prove to be the
predominant vector. In addition, the various vector species play
differing roles in sustaining transmission of the virus.
- Aedes
mosquitoes, for example, may acquire the virus from feeding on infected
animals, and are capable of transovarial transmission (transmission of
the virus from infected female mosquitoes to offspring via eggs), so new
generations of infected mosquitoes may hatch from their eggs.
This provides a
durable mechanism for maintaining the virus in nature, as the eggs of
these mosquitoes may survive for periods of up to several years in dry
conditions. During periods of inundation of larval habitats by rainfall,
for example, in the rainy season, the eggs will hatch, and the mosquito
population will increase and spread the virus to the animals on which
they feed.
Previously
uninfected Aedes and other species of mosquitoes will feed on
infected, viraemic (virus circulating in the bloodstream) animals and
thus amplify and perpetuate the outbreak by transmitting the virus to
the animals on which they subsequently feed.
RVF Virus Non-human Hosts
- Many types of animals may be
infected with RVF, and disease may be severe in many domesticated
animals including cattle, sheep, camels and goats. Sheep appear to be
more susceptible than cattle and goats are less susceptible.
- Exotic breeds, which have been
recently introduced into an endemic area, fare worse than breeds long
adapted to local conditions.
- Animals of different ages also
differ in their susceptibility to severe illness: over 90% of lambs
infected with RVF die, whereas mortality amongst adult sheep can be as
low as 10%.
- The abortion rate amongst
pregnant, infected ewes is almost 100%. An epizootic (epidemic animal
disease) of RVF is usually first manifested as a wave of unexplained
abortions amongst livestock. This may signal the start of an epidemic.
Transmission to Humans
- During epizootics, people may
become infected with RVF either by being bitten by infected
mosquitoes, or through contact with the blood, other body fluids or
organs of infected animals.
- Such contact may occur during the
care or slaughtering of infected animals, or possibly from the
ingestion of raw milk.
- The virus may infect humans
through inoculation (e.g., if the skin is broken, or through a wound
from an infected knife), or through inhalation as an aerosol. The
aerosol mode of transmission has also led to infection in laboratory
workers.
Clinical Features
- The incubation period (interval
from infection to onset of symptoms) of RVF varies from two to six
days.
- There then follows an
influenza-like illness, with sudden onset of fever, headache, myalgia
(muscle pain) and backache. Some patients also develop neck stiffness,
photophobia (the patient finds exposure to light uncomfortable) and
vomiting; in these patients the disease, in the early stages, may be
mistaken for meningitis.
- The symptoms of RVF usually last
from four to seven days, after which time the immune response to
infection becomes detectable with the appearance of IgM and IgG
antibodies, and the disappearance of circulating virus from the
bloodstream.
Clinical Features of Severe Cases
- While most human cases are
relatively mild, a small proportion of patients develops a much more
severe disease. This generally appears as one of several recognizable
syndromes: eye disease, meningoencephalitis (inflammation of the brain
and surrounding tissue) or haemorrhagic fever. The proportion of
patients developing these three types of complications is about 0.5-2%
for eye disease, and less than 1% for meningoencephalitis and
haemorrhagic fever syndrome.
The fever and other symptoms
described in the preceding section, Clinical Features, may appear in
association with eye disease, which characteristically manifests itself
in retinal lesions. The onset of eye disease is usually one to three
weeks after the first symptoms appear. When the lesions are in the
macula, some degree of permanent visual loss will result. Death in
patients with only ocular disease is uncommon.
Another syndrome manifests itself
with acute neurological disease, meningo-encephalitis. The onset of this
syndrome is also usually one to three weeks after the first symptoms
appear. Death in patients with only meningoencephalitis is uncommon.
- RVF may also manifest itself as
haemorrhagic fever. Two to four days after the onset of illness, the
patient shows evidence of severe liver disease, with jaundice and
haemorrhagic phenomena, such as vomiting blood, passing blood in the
faeces, developing a purpuric rash (a rash caused by bleeding in the
skin), and bleeding from the gums. Patients with the RVF-haemorrhagic
fever syndrome may remain viraemic for up to 10 days. The
case-fatality rate for patients developing haemorrhagic disease is
high at approximately 50%.
- Most fatalities occur in patients
who have developed haemorrhagic fever. The total case fatality rate
has varied widely in the various documented epidemics, but, overall,
is less than 1%.
Diagnosis and Treatment
- Several approaches may be used in
diagnosing acute RVF. Serological tests such as enzyme-linked
immunoassay (the "ELISA" or "EIA" methods) may
demonstrate the presence of specific IgM antibodies to the virus. The
virus itself may be detected in blood during the viremia phase of
illness or post-mortem tissues by a variety of techniques including
virus propagation (in cell cultures or inoculated animals), antigen
detection tests, and PCR, a molecular method for detecting the viral
genome.
- The antiviral drug ribavirin has
been shown to inhibit viral growth in experimental systems, but has
not been evaluated in the clinical setting. Most human cases of RVF
are relatively mild and of short duration, so will not require any
specific treatment. For the more severe cases, the mainstay of
treatment is general supportive therapy.
Prevention and Control
- RVF can be prevented by a
sustained program of animal vaccination. Both live, attenuated, and
killed vaccines have been developed for veterinary use. The live
vaccine requires only one dose and produces long-lived immunity, but
the presently-available vaccine may cause abortion if given to
pregnant animals. The killed vaccines do not cause these unwanted
effects, but multiple doses must be given to produce protective
immunity. This may prove problematic in endemic areas.
- An inactivated vaccine has been
developed for human use. This vaccine is not licensed and is not
commercially available, but has been used experimentally to protect
veterinary and laboratory personnel at high risk of exposure to RVF.
Other candidate vaccines are under investigation.
The risk of transmission from
infected blood or tissues exists for people working with infected
animals or people during an outbreak. Gloves and other appropriate
protective clothing should be worn, and care taken when handling sick
animals or their tissues. Healthcare workers looking after patients with
suspected or confirmed RVF should employ universal precautions when
taking and processing specimens from patients. Hospitalized patients
should be nursed using barrier techniques. As noted above, laboratory
workers are at risk, so samples taken for diagnosis from suspected human
and animal cases of RVF should be handled by trained staff and processed
in suitably equipped laboratories.
Other approaches to the control of
disease involve protection from and control of the mosquito vectors.
Personal protection is important and effective. Where appropriate,
individuals should wear protective clothing, such as long shirts and
trousers, use bednets and insect repellent, and avoid outdoor activity
at peak biting times of the vector species. Measures to control
mosquitoes during outbreaks, e.g., use of insecticides, are effective if
conditions allow access to mosquito breeding sites.
New systems that
monitor variations in climatic conditions are being applied to give
advance warning of impending outbreaks by signalling events which may lead
to increases in mosquito numbers. Such warnings will allow authorities to
implement measures to avert an impending epidemic.
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