RVF is an acute mosquito-borne viral disease mainly affecting ruminant animals and humans. It can cause abortions in pregnant animals and a high mortality in young animals. However, most indigenous livestock species in Africa demonstrate a high level of resistance to the disease. In humans RVF causes a severe influenza-like illness, with occasionally more serious haemorrhagic complications and death. Over its range, it causes major epidemics at irregular intervals of 5-35 years.
RVF was first identified in an outbreak of abortions and deaths in exotic wool sheep and illness in humans that occurred in the Rift Valley of Kenya after heavy rainfall in 1930-31. Outbreaks have since occurred in the highlands of Kenya at irregular intervals of 3-15 years. The most recent epizootic in the East African region was in 1997-98 in the drier areas of northeast Kenya and southwest Somalia after heavy El Niño-associated rains. This caused human deaths and some livestock losses, particularly of camels, but more significantly, disruption to livestock exports to the Middle East from the Horn of Africa.
The disease was first recorded in southern Africa in 1950, when a major epizootic in South Africa caused an estimated 100 000 deaths and 500 000 abortions in sheep. A second extensive epizootic occurred in Namibia and South Africa in 1974-75. Periodic severe outbreaks have also been experienced in Mozambique, Zambia and Zimbabwe.
In 1973, RVF outbreaks occurred in irrigation areas of the Sudan. In 1977 the disease was recognized in Egypt and caused an estimated 600 human deaths as well as heavy losses in sheep, goats, cattle, buffaloes and camels along the Nile Valley and Delta. RVF outbreaks again occurred in Egypt in 1993.
In 1987, a serious outbreak of RVF occurred in the Senegal River basin of southern Mauritania and northern Senegal. This outbreak first came to attention through severe illness and deaths of people in the area, but there was also a high abortion rate in sheep and goats. A further outbreak of the disease occurred there in 1998.
The RVF virus is probably present in all countries of sub-Saharan Africa. Many of these countries, outside eastern and southern Africa, do not have populations of the highly susceptible exotic livestock breeds that serve as disease hosts and act as indicators of RVF virus activity. Human disease may be the first indication that RVF virus amplification is occurring at high levels in these countries, where the indigenous ruminants may not show any clinical signs of disease other than insignificant low levels of abortion.
Until recently RVF was thought to be restricted to Africa. However, it was reported in the Tihama region of both Saudi Arabia and Yemen in September 2000. The Tihama plain - about 50 km wide - is in the west of these countries, between the mountains and the Red Sea, on the eastern side of the Great Rift Valley. It is a semi-arid zone with alluvial fanning from the mountains that form the scarp of the Rift. Its ecological characteristics are similar to those in the corresponding western side of the Rift Valley in Africa, where RVF occurs. RVF virus activity is highly associated with such limited riverine alluvium zones. There were extensive abortions in sheep and goats and some 855 severe human cases with 118 deaths. The virus was similar to that circulating in Kenya and Somalia in 1997-98.
RVF, however, has the potential for further international spread, particularly with the climatic changes that might be expected with global warming. High-risk receptive areas are, for example, the Tigris/Euphrates Delta zone to the northeast in Iraq and the Islamic Republic of Iran.
Typical swamp area susceptible to mosquito breeding
By Roger Paskin
The RVF virus is a member of the Phlebovirus genus of the Bunyaviridae. It is a single-stranded RNA virus with three segments. The Zinga and Lunya viruses first isolated, respectively, in the Central African Republic in 1969 and in Uganda in 1955, are identical.
The RVF virus is serologically related to other phleboviruses, but can be differentiated from these by virus-serum neutralization tests. There is only one serotype of RVF virus. The virus is inactivated by lipid solvents (e.g. ether) and by strong solutions of sodium or calcium hypochlorite (residual chlorine should exceed 5 000 ppm).
Although many mammalian species are susceptible to RVF infection, birds are not. Of the livestock species, sheep are the most susceptible, followed in order by goats, cattle, camels and water buffaloes. In Africa, exotic livestock breeds are far more susceptible to the clinical disease than indigenous breeds. Infection in the latter is usually subclinical. There is a high level of genetically determined resistance to RVF in indigenous breeds of sheep, goats and cattle, mainly Bos indicus, in Africa. Other susceptible animal species to RVF virus infection include antelopes, Cape buffaloes, monkeys, cats, dogs and rodents.
Human beings are susceptible to RVF. The disease manifests itself in a small percentage (2.5-5 percent) as one of the viral haemorrhagic fevers with a high fatality rate. Other clinical presentations are severe hepatitis or ocular lesions. There may also be meningo-encephalitis.
The virus circulates between vertebrate hosts and mosquitoes. It does not require continuous vector-host-vector feeding cycles for maintenance. Interepizootic maintenance exists by transovarial transmission of the virus in the eggs of Aedes spp. of the Neomelaniconium group. These are flood-breeding mosquito species whose eggs may remain dormant in floodplains or a grassland habitat for long periods. The virus is transmitted biologically in mosquitoes and many mosquito species are efficient vectors - notably species of the Culex, Aedes, Anopheles, Eretmapodites and Mansonia genera. Other biting insects may transmit the virus mechanically. Animals are infectious during their viraemic period, which may be brief (6-18 hours) or persist for up to six to eight days. There is no carrier state in animals. Non-vector-borne transmission is not significant in animals.
Infected mosquitoes may be transported for long distances in low-level wind or air currents, which may lead to the rapid spread of the virus from region to region or even internationally. This may have been a factor in the spread to and within Egypt in 1977 and 1993.
Humans can become infected from mosquito bites but the majority of human cases are thought to result from handling the blood, tissues, secretions or excretions of infected animals, notably after abortion. This may be through handling, milking, slaughtering, butchering or autopsying such animals. Laboratory-acquired infections also occur.
Theoretical cycle of RVF virus transmission
By Bernard Mondet (IRD)
In Africa, major epidemics occur at irregular intervals of 3-15 years or even longer in the forest edge, highland or coastal zones with high rainfall and humidity. In the semi-arid to arid areas, epidemic activity is much less frequent, possibly only once in every 25-50 years. The frequency depends upon the ecological characteristics of the country or parts of the country. The periodicity of RVF epizootics may be greatly changed by the increasing southern ocean temperatures, which influence precipitation in Africa and elsewhere to a major extent. There is evidence of greater amplitude of these oscillations in the recent past with dramatic effects upon flooding and drought conditions worldwide.
For epidemics to occur, three factors must be present:
During RVF epidemics, extremely high levels of virus amplification occur in the period when the vector populations are at their greatest. Most susceptible animals become infected at such times. These periods of intense virus activity usually persist for 6-12 weeks. The degree of morbidity and mortality experienced in livestock will depend upon whether the population is made up predominantly of exotic and improved breeds or relatively resistant indigenous animals. Quite high levels of virus activity can occur in Bos indicus zebu-type cattle, for example, with no clinical manifestation whatsoever. Likewise the number of human cases will depend upon the number of people exposed and their level of contact with infected animals or mosquitoes.
During the long interepidemic periods, low levels of virus activity may occur in certain foci within the epidemic and enzootic areas and these will remain undetected unless intensive surveillance activities are carried out. Virus activity may be revealed by random isolations from mosquitoes or by occasional human disease. Small local RVF outbreaks may occur, when and where the micro-environmental conditions are favourable and susceptible livestock are present. However, the incidence of infection is usually so low as to be undetectable. Clinical disease in humans or animals is generally missed in the absence of specific, well-focused, active surveillance.
Transovarial and sexual transmission of RVF virus occurs in some species of Aedes mosquitoes of the Neomelaniconium group. The eggs of these mosquitoes, and the virus that they carry, may remain viable for very long periods in the mud of dried-up surface pools or shallow depressions (locally known as dambos or pans), or in floodplains. Infected mosquitoes hatch from these when they are again flooded. This is the reason why the virus persists during prolonged interepidemic periods in the grasslands and semi-arid regions of eastern, western and southern Africa.
In Africa, the infection cycle among indigenous, domestic and wild vertebrate animals and mosquitoes is subclinical, both in livestock and people. In the rain forest and wetter wooded areas of the country, the virus circulates silently between wild and domestic species and insect vectors. This is referred to as cryptic or sylvatic RVF virus activity. Cryptic RVF is extremely difficult to identify and occurs in most of the countries of sub-Saharan Africa.
Clinical disease occurs in susceptible sheep (such as imported wool sheep) of all ages, but is most severe in young lambs. The morbidity rate in infected flocks approaches 100 percent. The mortality rate may be as high as 95 percent in lambs less than one week old, about 40-60 percent in weaner lambs, and 5-30 percent in adult sheep. The abortion rate may approach 100 percent.
In peracute cases, sheep are either found dead or suddenly weaken and collapse when driven. In acute cases, there is a very short incubation period - less than 24 hours - followed by fever, rapid pulse, weakness, unsteady gait, vomiting, mucopurulent nasal discharge and death in 24-72 hours. Other signs often observed are lymphadenitis, colic, haemorrhagic diarrhoea and petechial or ecchymotic haemorrhages in visible mucous membranes.
Subacute disease is more likely in adult sheep. Diphasic fever is accompanied by anorexia and weakness. There may be some vomiting and evidence of abdominal pain, with or without haemorrhagic gastroenteritis. Hepatitis with jaundice develops in most cases. Abortion is an almost inevitable consequence of infection of pregnant ewes, and may occur in either the acute or convalescent stages of the disease.
RVF in goats is similar to that in sheep but is usually not quite so severe. It is important to remember that the indigenous hair sheep and goats in Africa may show none of the above signs and no clinical signs other than some abortions. Flocks with or adjacent to exotic animals with severe RVF disease may show no signs at all.
In cattle, as in sheep, the most severe disease is seen in young animals. The mortality rate in exotic calves of Bos taurus breeds, such as Friesians, may be up to 30 percent, or even higher in neonates. Some animals up to 6 and even 12 months may be severely ill and debilitated with hepatitis and jaundice for some months. The acute disease is similar to that in sheep. In adult cattle the mortality rate is less than 2-5 percent. Cows abort. They may show fever, a sharp drop in milk production, with lymphadenitis, anorexia and malaise. Haemorrhage from the mouth and nares often occurs, with colic and haemorrhagic diarrhoea. In extensively ranched cattle, abortions may not be observed and a drop in calving rates may be the only sign recognized.
Although infection is generally subclinical in mature animals, pregnant camels may abort at any stage of pregnancy and neonatal deaths can occur. Abortion rates of 70 percent of those pregnant have occurred with many deaths in foals up to 3-4 months of age.
After an incubation period of two to six days, patients experience an influenza-like disease with a sudden onset of fever, debility, headache, backache and other muscle pains, and often photophobia and vomiting. The fever is diphasic. There is usually a degree of liver damage with jaundice. In uncomplicated cases, the illness generally resolves itself within a week. Many cases are mild. However, RVF in people who have pre-existing diseases such as shistosomiasis or malnutrition may be severe or even fatal.
Complications of RVF that occur in a small percentage of human infections include:
SAFETY PRECAUTIONS Many cases of Rift Valley fever have occurred in veterinarians, laboratory workers, farmers and others through handling infected blood or tissues or other virus-contaminated materials. Great care should be taken in carrying out autopsies on animals suspected of having died of the disease, and in handling aborted foetuses. Rubber gloves and face masks should be worn and personal disinfection should be thorough. Autopsied carcasses should be disposed of by burial, burning or incineration. A high level of biocontainment is also required in laboratories handling infectious materials associated with the RVF virus. People at high occupational risk of contracting RVF infection should consider being immunized. An experimental inactivated tissue culture vaccine for human use manufactured in the United States may be made available for this purpose. |
The most characteristic lesions are of various degrees of necrosis of the liver. There are also petechial and ecchymotic haemorrhages on all serous surfaces, lymph nodes, subcutis, the kidneys and in various tissues.
When severely affected - for example, in young lambs - the liver is swollen and the capsule tense, giving an external impression of firmness. However, on section the organ is quite friable, congested and contains many haemorrhages. When not masked by blood, the colour of the liver ranges from pale grey-brown to yellow-brown. Numerous grey-white foci, 1-2 mm in diameter, are scattered throughout the parenchyma. The gall bladder may be oedematous and contain petechial or ecchymotic haemorrhages. All the carcass lymph nodes are likely to be enlarged, oedematous and haemorrhagic.
The gastrointestinal tract exhibits varying degrees of inflammation, from catarrhal to haemorrhagic and necrotic. Petechial or ecchymotic haemorrhages are present in most internal organs. Ascites, hydropericardium, hydrothorax and pulmonary oedema may be present. The fluid in the body cavities is frequently bloodstained and the carcass jaundiced.
In the livers of young animals, there are well-defined primary foci of severe coagulative necrosis, which may be centrilobular. These are accompanied by diffuse and massive pan-necrosis involving most (or all) of the rest of the parenchyma. Some livers also show mineralization of scattered (or small groups of) necrotic hepatocytes. The primary necrotic foci are later infiltrated by histiocytes, lymphocytes and neutrophils, many with marked pyknosis and karyorrhexis. Intracytoplasmic Councilman-like bodies may be present in degenerate hepatocytes or free in sinusoids. Eosinophilic inclusion bodies are often found in the nuclei of cells that are still recognizable as hepatocytes.
In older animals, the hepatic necrosis may be less extensive and confined to focal areas of individual lobules.
IgM antibodies first appear three to five days after the onset of RVF infection, at which time viraemia ceases. They persist for one to two months, or even three to four months in some animals. IgG antibodies appear 10-14 days after the onset of infection and persist for at least one to two years or for life. Convalescent immunity after natural infection lasts for a long time. The offspring of immune mothers may have passively acquired maternal immunity for the first three to four months of their lives.
RVF epidemics should always be strongly suspected when there is a sudden onset of large numbers of abortions in sheep, goats, cattle or camels and deaths in lambs, kids or calves. This is specially the case if there is surface flooding in savannah or semi-arid areas following prolonged rains (or in irrigated areas); if the mosquito populations are high; and if there is concurrent illness in human populations. The disease in domestic animals may only be noticed after the illness in people has been identified as RVF.
There may also be sporadic cases or small outbreaks in non-epidemic circumstances, which are more difficult to diagnose in the field and may therefore be missed.
There are a number of diseases that may be confused clinically with RVF. It should also be remembered that conditions favourable for an RVF outbreak may also be favourable for other insect-borne diseases such as bluetongue, Nairobi sheep disease and Wesselsbron disease. Other livestock diseases and transboundary diseases such as peste des petits ruminants (PPR), rinderpest, contagious caprine and bovine pleuropneumonias and foot-and-mouth disease (FMD) may also occur through dislocation of farming communities and movement of animals as a result of flooding. The simultaneous occurrence of other diseases may compound diagnostic difficulties.
Together with all causes of abortion in ruminant animals, diseases to be taken into consideration in the differential diagnosis of RVF include:
Collection and transport of diagnostic specimens. Whole blood, liver, lymph nodes and spleen are the tissues of choice for isolation of the virus. Blood samples should be collected from febrile animals into ethylene-diamine-tetra-acetic acid (EDTA) or heparin to which antibiotics have been added as preservatives (penicillin 200 units and streptomycin 200 µg/ml, final concentration). Samples of liver and spleen should be collected aseptically both from freshly dead animals at autopsy and from aborted foetuses, if available, and placed in sterile containers. Duplicate tissue specimens should be collected in neutral buffered formalin for histopathology.
Blood samples, about 20 ml each, should be collected from animals in the acute and convalescent phases of the disease, for serum.
Histopathology. The finding of characteristic histological lesions with pan-necrosis (see section on Histopathology on p. 14) in the livers of young animals or foetuses is suggestive of RVF.
Virus isolation. The RVF virus can be isolated from whole blood or homogenates of fresh tissues by intracerebral injection of suckling mice or intraperitoneal injection of adult mice or hamsters. It can also be readily isolated in various primary cell cultures (e.g. primary lamb and calf kidney or testis) or cell lines (e.g. BHK-21 and Vero). The identity of the isolated virus is confirmed by polymerase chain reaction (PCR), enzyme linked immunosorbent assay (ELISA), fluorescent antibody staining or virus-serum neutralization tests.
Antigen detection. The RVF antigen may be detected by direct or indirect immunofluorescence tests on impressions smears or cryostat sections of liver, spleen and brain. A rapid diagnosis can sometimes be made by agar gel immunodiffusion (AGID) tests on fresh tissues. Immunocapture-ELISA and histochemical staining of cryostat sections or formalin fixed tissues and PCR are now much more widely used for RVF.
Antibody detection. The ELISA test has now replaced the older inhibition of haemagglutination (IHA), immunofluorescence assay (IFA) and serum neutralization tests as the test of choice. ELISA systems are available to test for the presence of IgM and IgG, which are extremely valuable in epidemiological investigations. The virus serum neutralization test in microtitre tissue culture systems is still the definitive test system. It is highly specific with little or no cross-neutralization with other phleboviruses. It can be used to detect antibodies in all animal species. However, as it requires the use of live virus, it is not recommended for use outside endemic countries unless a high level of biocontainment is available in laboratories.
Other serological tests are less specific, but still have a very useful role.
The indirect ELISA test is a reliable and sensitive test and can provide results within hours. There are tests for both IgM and IgG antibodies. In an index case in an outbreak situation the low-level serological cross-reactions with other members of the Phlebovirus genus may cause problems. Doubtful results should therefore be interpreted with caution and may need to be confirmed by serum neutralization (SN) tests at a reference laboratory.
Detection of viral genetic material. A reverse transcriptase PCR test is now available for detection of viral genetic material. Sequencing of the NS (S) protein-coding region of the genome may be used for phylogenetic analysis (genetic fingerprinting) of virus isolates.
