RIFT VALLEY FEVER : A DISEASE UPDATE. Dr Pamela Oberem BVSc (Hons) P.O. Box Onderstepoort

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1 RIFT VALLEY FEVER : A DISEASE UPDATE Dr Pamela Oberem BVSc (Hons) P.O. Box Onderstepoort pete.pam@iafrica.com Introduction Rift Valley fever is a mosquito-borne viral zoonosis endemic to the African continent but it has made incursions into the Middle Eastern countries and Madagascar. In domestic ruminants the disease is characterised by abortions and high mortalities in young animals. Humans in direct contact with infected animals contract an influenza-like disease, which can be complicated in a small percentage of cases by ocular problems, liver damage and cerebral infections. Epizootics have a severe economic impact on farming and present a health hazard for humans in the agricultural sector. The RVF virus is thought to be maintained in the mosquito vector by a low level cycle interaction of hosts during the inter-epizootic periods. Epizootics are preceded by the occurrence of exceptionally heavy rainfall which causes an explosive increase in floodwater-breeding mosquitoes. Major epizootics occurred in South Africa in the 1950s and the 1970s when flooding occurred across wide areas in the country including the OFS, NW and Limpopo. Huge loses of livestock were experienced in the 1950s due to the unavailability of a vaccine. After the 1970s the disease appeared to become quiescent, but sporadic isolations of virus were made for example from a RVF induced abortion in buffalo in the Kruger National Park in 1996, indicating that the virus was still present in the mosquito population. Recent localised outbreaks in game and livestock in Mpumalanga and Limpopo warn of the potential for an epidemic, if wet weather cycles continue into subsequent years. Sustained vaccination of all ruminant livestock with the live RVF vaccine is recommended. Aetiology The Rift Valley fever virus is a Phlebovirus of the Bunyaviridae family. There is no antigenic difference between the various isolates involved in the outbreaks in different African countries, although there is some evidence that there may be differences in the virulence of these isolates. The virus is fairly stable under conditions of moderate temperate and high humidity, but is susceptible to a ph below 6.8. Citric acid solution (4%) is a useful disinfectant but its efficacy is reduced in the presence of organic matter. The virus is effectively inactivated with low concentrations of formalin.

2 Epidemiology The RVF virus is transmitted by aedine mosquitoes which feed on livestock and wild vertebrates. Outbreaks in southern Africa are usually associated with abnormally heavy rains resulting in an accumulation of surface water in dams and vleis, ideal conditions for the hatching of the mosquito eggs which can survive in dried mud for a number of seasons. The RVF virus is transmitted transovarially in the mosquitoes which provides for a reservoir of infection during epizootics, the disease becoming manifest when weather conditions allow for sufficient numbers of mosquitoes to breed. However the precise epidemiological conditions necessary for epidemics remain to be elucidated. During RVF outbreaks mosquitoes feed on livestock such as cattle, sheep and goats causing abortion storms and the deaths of newborn and young animals. While mosquito transmission is the main method of infection in livestock, humans contract the infection by direct contact with infected animals and their tissues. This most commonly occurs during the handling of aborted foetuses, cutting up carcases or performing post-mortems, and also the handling of blood, serum and tissues from infected animals. Humans generally do not contract the disease from mosquito bites since the species involved prefer livestock and wild animals, and avoid entering houses. Pathogenesis After a limited replication of the virus at the site of infection it reaches the spleen, brain, liver where secondary replication takes place with a resulting viraemia. Extremely high virus titres in the order of MLD50 per ml is seen in the most susceptible animals, permitting vector and mechanical transmission for example by inoculation needles. The lytic effect of the virus causes extensive necrotic hepatitis. The virus sis also thought to cause impairment of coagulation resulting in a haemorrhagic syndrome, with widespread haemorrhages seen throughout the body. Young calves, lambs and kids are most susceptible to the virus animal, newborns being the most severely affected and adult animals being the least severely affected. Abortion is an almost invariable outcome mainly as a result of the fatal necrotic hepatitis in the foetus. Foetuses of all ages are affected, so abortion can occur at any stage or pregnancy. Clinical signs Abortions storms occur in cattle, sheep and goats at any stage of pregnancy. Sheep are particularly susceptible with abortion rates of % while cattle are somewhat less affected with rates of 15-40% reported. The disease has a very short incubation period in young lambs and kids less than 2 weeks old (12-36 hr). They show a high fever, listlessness and are unwilling to move. Signs of abdominal pain and rapid respiration may be seen. These animals die within high hours and are often just found dead without any symptoms being noticed. There is a 90% mortality in this age group. Animals over 2 weeks of age and adults show high fever, listlessness, anorexia and weakness. Diarrhoea or meleana may be seen. The mortality rate of these age groups is 5-30%. In calves there is fever, inappetence, weakness, icterus and bloody diarrhoea are sometimes seen.

3 Adults may have inapparent infections with abortions being the only sign of the infection, but some animals show fever, malaise and bloody diarrhoea. The mortality rates are lower than in sheep, with calves showing 20% and adults 10% mortalities. Pathology Hepatic necrosis is a feature of all animals of all ages. In newborns and foetuses this is sever and widespread. In adults there is hepatic congestion with focal haemorrhages. Haemorrhages occur extensively the gastrointestinal tract of many animals, with partly digested blood found in the lumen of the abomasums and intestines. Petechiae and ecchymoses can be seen on mucosal or serosal surfaces. Sub-cutaneous haemorrhages and blood tinged effusions into body cavities may be seen. Other features are oedematous lymph nodes with petechiae, as well as nephrosis of the kidney. Diagnosis RVF should always be considered as a possible cause of abortions during wet summers. Deaths in young animals with hepatic necrosis as a main post-mortal feature, and reports of flu-like illness in humans on the affected farm will be additional supportive evidence. Organs such as the liver, spleen, kidney and lymph nodes should be taken for histopathology in 10% buffered formalin, since particularly the liver lesions are considered pathognomonic. Foetal tissues often show advanced autolysis so the brain should also be sampled. Virus isolation or detection can be performed on tissue samples and heparinised blood kept at 4 o C until reaching the laboratory. Packages containing these samples must be securely packed to prevent leakages and clearly marked as suspicious for RVF. Virus isolation can be on tissue culture or by inoculation into laboratory animals. Viral antigen can be detected by ELIZA or PCR techniques. Sera can be submitted from recovering animals for antibody detection. All efforts should be made to confirm the diagnosis and eliminate other causes of abortion. RVF in humans Humans become infected by handling aborting animals, aborted foetuses, processing animals for post-mortem examination, or handling blood, serum or infected tissues for laboratory techniques. The incubation period of RVF in humans is roughly 4 days and has a sudden onset. Most people develop either inapparent infections or moderate to severe, non-fatal flu like symptoms characterised by fever, headache, light- sensitivity, muscle and joint pains. Complete recovery usually occurs within two weeks. A smaller percentage of those affected will develop ocular lesions resulting in blurred vision which may resolve with time, but detachment of the retina may occur in a few cases causing permanent blindness. Less than 1% of people affected develop a severe haemorrhagic syndrome or encephalitis which may be fatal.

4 It is essential that veterinarians and their assistants performing post mortems or laboratory investigations during suspected RVF outbreaks wear protective clothing in the form of overalls, gloves, and goggles. The generation of aerosols must be minimised. Citric acid solutions can be used as a cheap and general disinfectant. Treatment There is no economic treatment for the disease in animals. Humans contracting RVF can be treated by medical practitioners with the antiviral agent ribavirin. Control The only effective control measure for RVF in livestock is sustained vaccination, especially during wet seasonal cycles. On farms where animals are unvaccinated vector control can be used as emergency measure until 3-4 weeks after vaccination (see discussion below). RVF vaccination Live vaccines The Smithburn vaccine currently produced by Onderstepoort Biological Products was initially developed by K.C. Smithburn and fellow researchers in 1944 in the course of yellow fever investigations in Uganda. The strain was isolated from mosquitoes, then attenuated by sequential intracerebral passage in suckling mice which reduced the hepatotropism of the virus. Smithburn demonstrated that this strain could protect lambs from challenge with virulent RVF virus. Further work demonstrated that the vaccine protected animals 19 months after a single inoculation. It was erroneously reported that the Smithburn strain does not protect cattle because it induces low antibody titres, but protection against clinical disease has subsequently been demonstrated in challenge experiments. The Smithburn vaccine induces a low percentage of abortion and teratology in sheep vaccinated between days of pregnancy when the neural development of the foetus is occurring. The strain s affinity for the neural tissue of the lamb causes hydranencephaly and arthrogryposis with subsequent abortion or stillbirth. However no such teratogenic effects have been reported for cattle despite its widespread use in pregnant cows in East Africa. In addition after 50 years of use of the Smithburn vaccine in the field in southern and east Africa even in inter-epizootic periods there have been no incidents of reversion to virulence or reassortment with wild virus. It remains the most useful RVF vaccine currently available in South Africa, because it is cheap and easy to produce, and confers good protection 3-4 weeks after a single inoculation. A single administration is said to confer life-long protection. Inoculation during outbreaks is usually too late to confer adequate immunity and is fraught with problems such as possible needle transmission of the disease from infected animal. Farmers should therefore be encouraged to vaccinate on a sustained basis since

5 after the initial vaccination of all animals, only the young or newly introduced stock will have to be vaccinated. Livestock can be vaccinated at any age except of calves, lambs and kids of vaccinated dams, because of the interference of colostral immunity. These animals can be vaccinated at 6 months. The use of the vaccine should be avoided during pregnancy in sheep since a small percentage of ewes will experience abortion or teratology. Cattle, sheep and goats should be vaccinated in spring since the disease occurs in summer to autumn when outbreaks are likely to occur. An attenuated isolate designated Clone 13 has been investigated for safety and efficacy in sheep. It ahs been shown to have no teratogenic effects, and to protect ewes from abortion on virulent challenge. It is therefore a suitable alternative for the Smithburn vaccine. Killed vaccines A killed vaccine was developed for use in pregnant sheep and cattle since the latter were perceived erroneously to develop poor immunity on vaccination with the Smithburn strain. It was shown that killed vaccines did not give adequate protection against abortion experimentally unless vaccination was repeated. Killed vaccines have been reported to perform poorly in controlling epizootics. In addition the production of this vaccine is cumbersome, expensive, and hazardous to human health. Vector control Farms where animals are unvaccinated at the time of RVF outbreaks can attempt treatment of animals to prevent mosquito attacks, in conjunction with vaccination. Treatment should be aimed at the most vulnerable animals, namely pregnant and young stock. The insecticide of choice is the pyrethroid deltamethrin which has a knock down effect on mosquitoes. Dipping should be done at weekly intervals until vaccine immunity has had time to develop (3-4 weeks). Adult cattle can be dipped or sprayed weekly with deltamethrin containing dips (e.g. Decatix 3). Sprays must be applied at not less than 3 litres per animal. Alternately deltamethrin containing pour-ons (e. g. Clout or Decaspot in dairy cattle ) can be applied, ensuring that application starts on the poll and is continued along the backline. Young calves can be dipped or sprayed as for adult cattle. Deltamethrin pour-ons are less safe and effective in this age group. Wooled sheep breeds can be treated with water based pour-ons (e.g. Wipe out) which must be applied to the head and along the backline. Ideally they should also be belly bathed with deltamethrin containing dips (e.g. Decatix 3) to protect the legs and underline, since pour-on formulations tend to run off these areas. Non-wooled sheep and goats can be dipped with deltamethrin-containing dips (e.g. Decatix 3). Alternately oil-based pour-ons ( e.g. Clout) can be applied from the poll along the back, as well as in the axilla and the groin. Lambs should be carefully hand dipped with a deltamethrin dip.

6 Acknowledgements My thanks to Dr Truske Gerdes of Onderstepoort Veterinary Institute s Virology section for information on recent RVF virus isolations. Technical advice on vector control was provided by Afrivet Business Management. Photos courtesy of Department of Tropical diseases, Faculty of Veterinary science. References 1. Gerdes T Personal communication. 2. Swanepoel R 2004 Rift Valley fever in Livestock diseases of southern Africa Eds. JAW Coetzer and RC Tustin. Oxford University Press 3. Barnard BJH and Botha MJ An inactivated Rift Valley fever vaccine. Journal of South African Veterinary Association, 48: Barnard BJH Rift Valley fever vaccine- antibody and immune response in cattle to a live and inactivated vaccine. Journal of South African Veterinary association 50: Coackley W, Pini A, and Gosden D, The immunity induced in cattle and sheep by inoculation of neurotropic or pantropic RVF viruses. Research in Veterinary Science 8: Coetzer JAW and Barnard BJH Hydrops amni with hydraencephaly and arthrogryposis with Wesselsbron disease and RVF viruses as aetiological agents. Onderstepoort Journal of Veterinary Research 44: Hunter P and Bouloy M, Investigation of Clone 13 RVF mutant as a vaccine strain. Proceedings of 5 th International Veterinary Sheep congress, Stellenbosch, South Africa. 8. Abd el-rahim IH, Abd el-hakim, and Hussein M An epizootic of RVF in Egypt in Revue Scientifique et Technique de OIE 18: