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==Introduction==

==Introduction==

Rift Valley Fever (RVF) is a viral zoonotic disease belonging to the family [[:Category:Bunyaviridae|''Bunyaviridae'']] in the ''Phlebovirus'' genus, possessing a segmented negative sense RNA genome. The disease has an episodic occurrence reemerging ever 5-25 years and is seasonal in its occurrence <ref> http://www.hpa.org.uk/web/HPAweb&Page&HPAwebAutoListName/Page/1274087829165 </ref> . The occurrence of non immune animal populations every 5-25years combined with the introduction of RVF (due to rainfall) accounts for the explosive cyclical nature of the disease <ref> http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf </ref>. RVF primarily affects animals but can infect humans and has the capacity to cause severe disease in both.  

Rift Valley Fever (RVF) is a viral zoonotic disease belonging to the family [[:Category:Bunyaviridae|''Bunyaviridae'']] in the ''Phlebovirus'' genus, possessing a segmented negative sense RNA genome. The disease has an episodic occurrence reemerging ever 5-25 years and is seasonal in its occurrence <ref> http://www.hpa.org.uk/web/HPAweb&Page&HPAwebAutoListName/Page/1274087829165 </ref> . The occurrence of non immune animal populations every 5-25years combined with the introduction of RVF (due to rainfall) accounts for the explosive cyclical nature of the disease <ref name="oie"> http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf </ref>. RVF primarily affects animals but can infect humans and has the capacity to cause severe disease in both.  

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RVF has a wide economic impact due to livestock loss and trade restrictions as well as public health implications. It is a notifiable disease.

RVF has a wide economic impact due to livestock loss and trade restrictions as well as public health implications. It is a notifiable disease.

Virus particles are shed in milk but animals have not been infected via suckling or ingestion of milk <ref>''Lagerqvist, N'', Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013 </ref> .

Virus particles are shed in milk but animals have not been infected via suckling or ingestion of milk <ref>''Lagerqvist, N'', Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013 </ref> .

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It is currently unknown if there are animal reservoirs of RVF between outbreaks. The namaqua rock rat and bats have been implicated and have been shown to be capable of infection but the potential impact of this is unknown. <ref>''Oelofsen MJ, Van der Ryst E. (1999)'' Could bats act as reservoir hosts for Rift Valley fever virus? Onderstepoort J Vet Res. 1999 Mar;66(1):51-4.</ref> Low levels of circulation between livestock or wild ruminants and mosquitoes (sylvatic cycle) is also likely to occur.<ref> http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf</ref>

It is currently unknown if there are animal reservoirs of RVF between outbreaks. The namaqua rock rat and bats have been implicated and have been shown to be capable of infection but the potential impact of this is unknown. <ref>''Oelofsen MJ, Van der Ryst E. (1999)'' Could bats act as reservoir hosts for Rift Valley fever virus? Onderstepoort J Vet Res. 1999 Mar;66(1):51-4.</ref> Low levels of circulation between livestock or wild ruminants and mosquitoes (sylvatic cycle) is also likely to occur.<ref name="oie" />  

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Outbreaks occur after heavy rain and flooding due to favourable breeding conditions for mosquitoes.

Outbreaks occur after heavy rain and flooding due to favourable breeding conditions for mosquitoes.

During an outbreak in Egypt RVF virus was also isolated from horses as well as camels <ref>''Imam, Z. E., Karamany R. El., Darwish, M.A.'' (1979) An epidemic of Rift Valley fever in Egypt 2. Isolation of the virus from animals Bull World Health Organ. 1979; 57(3): 441–443.</ref>.

During an outbreak in Egypt RVF virus was also isolated from horses as well as camels <ref>''Imam, Z. E., Karamany R. El., Darwish, M.A.'' (1979) An epidemic of Rift Valley fever in Egypt 2. Isolation of the virus from animals Bull World Health Organ. 1979; 57(3): 441–443.</ref>.

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Other species (e.g. dogs and cats) have been infected experimentally and have become viraemic. The only species that are resistant are reptiles, birds and amphibians <ref> http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf </ref>.

Other species (e.g. dogs and cats) have been infected experimentally and have become viraemic. The only species that are resistant are reptiles, birds and amphibians <ref name="oie" />.

==Clinical Signs==

==Clinical Signs==

RVF has an incubation period of 1-6 days (12-36 hrs in lambs).<ref> http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf </ref> Once in the lymph nodes viral replication occurs which leads to viraemia and systemic infection. Spontaneous abortions are seen as the hallmark of RVF outbreaks.<ref>http://www.who.int/mediacentre/factsheets/fs207/en/</ref> Pregnant animals can abort at any stage often with 100% of stock aborting.<ref> ''Lagerqvist, N'', Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013 </ref>   

RVF has an incubation period of 1-6 days (12-36 hrs in lambs).<ref name="oie" /> Once in the lymph nodes viral replication occurs which leads to viraemia and systemic infection. Spontaneous abortions are seen as the hallmark of RVF outbreaks.<ref>http://www.who.int/mediacentre/factsheets/fs207/en/</ref> Pregnant animals can abort at any stage often with 100% of stock aborting.<ref> ''Lagerqvist, N'', Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013 </ref>   

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Newborn lambs and kids are highly susceptible to RVF, presenting with pyrexia and anorexia shortly followed by death 24-36hrs after infection.<ref>''Lagerqvist, N'', Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref> <ref> http://www.fao.org/docrep/006/y4611e/y4611e00.htm#Contents</ref>  In newborn lambs hepatocytes of the liver are the predominant target cell with hepatic necrosis being a significant post mortem finding. Other organs affected include the gall bladder (haemorrhage and oedema), gastrointestinal tract haemorrhage, lymph node haemorrhage, cutaneous haemorrhage and haemothorax.<ref>http://www.fao.org/docrep/006/y4611e/y4611e00.htm#Contents</ref> <ref>http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf </ref>  

Newborn lambs and kids are highly susceptible to RVF, presenting with pyrexia and anorexia shortly followed by death 24-36hrs after infection.<ref>''Lagerqvist, N'', Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref> <ref> http://www.fao.org/docrep/006/y4611e/y4611e00.htm#Contents</ref>  In newborn lambs hepatocytes of the liver are the predominant target cell with hepatic necrosis being a significant post mortem finding. Other organs affected include the gall bladder (haemorrhage and oedema), gastrointestinal tract haemorrhage, lymph node haemorrhage, cutaneous haemorrhage and haemothorax.<ref>http://www.fao.org/docrep/006/y4611e/y4611e00.htm#Contents</ref> <ref name="oie" />  

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Signs in older lambs, kids, calves and adults vary from acute to subclinical (20-70% mortality), Signs can include fever (lasts 24-96hrs), weakness, bloody diarrhoea, abdominal pain, photosensitivity, anorexia, excessive salivation and decreased milk production. Signs in adult cattle are most often subclinical with less than 10% mortality.<ref>http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf</ref> <ref>http://www.fao.org/docrep/006/y4611e/y4611e00.htm#Contents</ref> <ref>''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref>  

Signs in older lambs, kids, calves and adults vary from acute to subclinical (20-70% mortality), Signs can include fever (lasts 24-96hrs), weakness, bloody diarrhoea, abdominal pain, photosensitivity, anorexia, excessive salivation and decreased milk production. Signs in adult cattle are most often subclinical with less than 10% mortality.<ref name="oie" /> <ref>http://www.fao.org/docrep/006/y4611e/y4611e00.htm#Contents</ref> <ref>''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref>  

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Camels display signs similar to those seem with Pasteurellosis infection, though infection can also be subclinical or asymptomatic. Abortions can also occur. During the 2010 outbreak in Mauritania 2 forms of disease were observed in camels; a hyperacute form causing sudden death in <24hrs and an acute form causing fever, ataxia, respiratory signs, icterus, oedema, foot lesions and neurological signs. If haemorrhagic signs were observed death occurred in a few days.<ref> ''Ahmed B. Ould El Mamy, Mohamed Ould Baba, Yahya Barry, Katia Isselmou, Mamadou L. Dia,

Camels display signs similar to those seem with Pasteurellosis infection, though infection can also be subclinical or asymptomatic. Abortions can also occur. During the 2010 outbreak in Mauritania 2 forms of disease were observed in camels; a hyperacute form causing sudden death in <24hrs and an acute form causing fever, ataxia, respiratory signs, icterus, oedema, foot lesions and neurological signs. If haemorrhagic signs were observed death occurred in a few days.<ref> ''Ahmed B. Ould El Mamy, Mohamed Ould Baba, Yahya Barry, Katia Isselmou, Mamadou L. Dia,

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Differential diagnosis should include: bluetongue, Wesselbron disease, Enterotoxaemia of sheep, Ephemeral fever, Brucellosis, Vibrosis, Trichomonosis, Nairobi sheep disease, Heartwater, Ovine enzootic abortion, plant toxicity, bacterial septicaemias, Rinderpest, Anthrax.<ref>http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf</ref>

Differential diagnosis should include: bluetongue, Wesselbron disease, Enterotoxaemia of sheep, Ephemeral fever, Brucellosis, Vibrosis, Trichomonosis, Nairobi sheep disease, Heartwater, Ovine enzootic abortion, plant toxicity, bacterial septicaemias, Rinderpest, Anthrax.<ref name="oie" />

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Humans develop '''malarial-like''' disease. High risk individuals include farmers, veterinarians and abattoir staff. Mild disease is most common but severe hepatitis, encephalitis and ocular damage can develop. The usual presentation is of sudden onset fever, myalgia, biphasic behaviour and gastrointestinal disease.<ref>http://www.who.int/mediacentre/factsheets/fs207/en/</ref>

Humans develop '''malarial-like''' disease. High risk individuals include farmers, veterinarians and abattoir staff. Mild disease is most common but severe hepatitis, encephalitis and ocular damage can develop. The usual presentation is of sudden onset fever, myalgia, biphasic behaviour and gastrointestinal disease.<ref>http://www.who.int/mediacentre/factsheets/fs207/en/</ref>

During the acute stages ELISA or EIA can be used to confirm the presence of IgM antibody to the virus, which allows recent infections to be diagnosed. ELISA’s based on recombinant RVF virus proteins have been developed which negates the need for biosecure facilities and are used in a number of species.<ref>''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013  Cross reactions may occur with other ''phleboviruses''</ref>  

During the acute stages ELISA or EIA can be used to confirm the presence of IgM antibody to the virus, which allows recent infections to be diagnosed. ELISA’s based on recombinant RVF virus proteins have been developed which negates the need for biosecure facilities and are used in a number of species.<ref>''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013  Cross reactions may occur with other ''phleboviruses''</ref>  

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RT-PCR is the standard method used in most laboratories as it has a high sensitivity. This is useful for rapid diagnosis and can also be used to detect RVF virus in mosquito pools.<ref> http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf</ref>

RT-PCR is the standard method used in most laboratories as it has a high sensitivity. This is useful for rapid diagnosis and can also be used to detect RVF virus in mosquito pools.<ref name="oie" />

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Virus neutralisation tests (VNT) are very specific and sensitive and can be performed in a biosecure laboratory. They are also the prescribed test for international trade, though it cannot differentiate between vaccinated and infected animals.<ref>http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf</ref> It is the only method to detect functional antibodies though a low level of cross reaction to some other ''phleboviruses'' has been observed.<ref>Lagerqvist, N, Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref> Plaque reduction neutralisation assays are the most commonly used VNTs and involve incubating the virus and heat inactivated serum allowing the virus to infect. 4-6 days later the presence of cytopathic plaques is observed.

Virus neutralisation tests (VNT) are very specific and sensitive and can be performed in a biosecure laboratory. They are also the prescribed test for international trade, though it cannot differentiate between vaccinated and infected animals.<ref name="oie" /> It is the only method to detect functional antibodies though a low level of cross reaction to some other ''phleboviruses'' has been observed.<ref>Lagerqvist, N, Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref> Plaque reduction neutralisation assays are the most commonly used VNTs and involve incubating the virus and heat inactivated serum allowing the virus to infect. 4-6 days later the presence of cytopathic plaques is observed.

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Haemagglutination inhibition (HI) and complement fixation assays are available but show extensive cross reactivity with other ''phlebovirus'' species.<ref>''Lagerqvist, N'', Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref>  HI assays are used in non endemic areas but animals previously infected with other ''phleboviruses'' may show a positive result.<ref>http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf</ref> Immunofluorescence can also be used.

Haemagglutination inhibition (HI) and complement fixation assays are available but show extensive cross reactivity with other ''phlebovirus'' species.<ref>''Lagerqvist, N'', Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref>  HI assays are used in non endemic areas but animals previously infected with other ''phleboviruses'' may show a positive result.<ref name="oie" /> Immunofluorescence can also be used.

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Definitive confirmation can be carried out by virus isolation, however due to the zoonotic risk this can only be carried out in biosecure facilities.<ref> http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf</ref>

Definitive confirmation can be carried out by virus isolation, however due to the zoonotic risk this can only be carried out in biosecure facilities.<ref name="oie" />

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Histopathology on tissue samples will show cytopathology and immunostaining can be used to identify RVF antigen in cells. On post mortem during the viraemic stage, widespread petechiae and ecchymoses on serous surfaces and organs will be seen and  present in the body cavities. In older animals, the liver is enlarged and inflamed, with many foci of necrosis which are bronzed and jaundiced. The gall bladder may also be distended and haemorrhagic. Lymph nodes are enlarged and their germinal centres may be necrotic on closer examination. Extensive subcapsular haemorrhage in the spleen is usual. Renal changes include oedema and congestion. Epicardial and endocardial haemorrhages are often present on the heart.<ref>http://www.fao.org/docrep/006/Y4611E/y4611e05.htm</ref>

Histopathology on tissue samples will show cytopathology and immunostaining can be used to identify RVF antigen in cells. On post mortem during the viraemic stage, widespread petechiae and ecchymoses on serous surfaces and organs will be seen and  present in the body cavities. In older animals, the liver is enlarged and inflamed, with many foci of necrosis which are bronzed and jaundiced. The gall bladder may also be distended and haemorrhagic. Lymph nodes are enlarged and their germinal centres may be necrotic on closer examination. Extensive subcapsular haemorrhage in the spleen is usual. Renal changes include oedema and congestion. Epicardial and endocardial haemorrhages are often present on the heart.<ref>http://www.fao.org/docrep/006/Y4611E/y4611e05.htm</ref>

Mosquito breeding sites should be reduced through drainage and larvicidal measures. Methoprene spraying, larvicidal toxins and controlled burning can be used, though low level aerial spraying has been shown to have little effect.<ref>http://www.fao.org/docrep/006/y4611e/y4611e00.htm#Contents</ref>

Mosquito breeding sites should be reduced through drainage and larvicidal measures. Methoprene spraying, larvicidal toxins and controlled burning can be used, though low level aerial spraying has been shown to have little effect.<ref>http://www.fao.org/docrep/006/y4611e/y4611e00.htm#Contents</ref>

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Education of risk factors and mosquito bite prevention, appropriate clothing, use of insect repellent and mosquito nets should be undertaken.  Local populations should be educated as to the risks of eating raw meat and milk products (though a fall in pH destroys the virus so some uncooked meat may be safe).<ref>http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf,</ref>

Education of risk factors and mosquito bite prevention, appropriate clothing, use of insect repellent and mosquito nets should be undertaken.  Local populations should be educated as to the risks of eating raw meat and milk products (though a fall in pH destroys the virus so some uncooked meat may be safe).<ref name="oie" />

   

   

===Vaccination===  

===Vaccination===  

A live attenuated vaccine MP12 has been shown to be safe in newborns, lambs and pregnant cows and ewes. Malformation has occurred when the vaccine was administered to sheep during the first trimester (days 35-56)<ref>''Hunter P, Erasmus BJ, Vorster JH.'' (2002) Teratogenicity of a mutagenised Rift Valley fever virus (MVP 12) in sheep,. Onderstepoort J Vet Res. 2002 Mar;69(1):95-8.</ref> and viral shedding has been documented in macaques following MP12 vaccination.<ref> ''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref> Colostrum from vaccinated ewes gives temporary immunity to lambs.<ref>http://www.fao.org/docrep/006/y4611e/y4611e00.htm#Contents</ref>  

A live attenuated vaccine MP12 has been shown to be safe in newborns, lambs and pregnant cows and ewes. Malformation has occurred when the vaccine was administered to sheep during the first trimester (days 35-56)<ref>''Hunter P, Erasmus BJ, Vorster JH.'' (2002) Teratogenicity of a mutagenised Rift Valley fever virus (MVP 12) in sheep,. Onderstepoort J Vet Res. 2002 Mar;69(1):95-8.</ref> and viral shedding has been documented in macaques following MP12 vaccination.<ref> ''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref> Colostrum from vaccinated ewes gives temporary immunity to lambs.<ref>http://www.fao.org/docrep/006/y4611e/y4611e00.htm#Contents</ref>  

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An R566 strain has been developed from MP12 and Clone 13 and has shown to confer immunity in laboratory experiments. <ref>''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref><ref>http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/RIFT_VALLEY_FEVER_FINAL.pdf</ref>

An R566 strain has been developed from MP12 and Clone 13 and has shown to confer immunity in laboratory experiments. <ref>''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref><ref name="oie" />

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Viral vector vaccines using sheep pox and lumpy skin disease viruses have been shown to give protection, and have the advantage that the diseases exist in the same habitats and could potentially confer protection to two diseases with one vaccination but the use is restricted to countries with sheep pox and lumpy skin disease due to the use of the vectors.  A vaccine using Newcastle disease virus as a vector has also been developed.<ref>''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref>

Viral vector vaccines using sheep pox and lumpy skin disease viruses have been shown to give protection, and have the advantage that the diseases exist in the same habitats and could potentially confer protection to two diseases with one vaccination but the use is restricted to countries with sheep pox and lumpy skin disease due to the use of the vectors.  A vaccine using Newcastle disease virus as a vector has also been developed.<ref>''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref>