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A number of [[Culicidae |mosquito]] species (''Aedes'', ''Culex'', ''Mansonia'', ''Anopheles'') are implicated as vectors of RFV, the most important being ''Aedes'' and ''Culex'' ''spp''. They are responsible for both maintenance and amplification of RVF.

A number of [[Culicidae |mosquito]] species (''Aedes'', ''Culex'', ''Mansonia'', ''Anopheles'') are implicated as vectors of RFV, the most important being ''Aedes'' and ''Culex'' ''spp''. They are responsible for both maintenance and amplification of RVF.

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Mosquitoes can be infected via feeding on infected animals. Vertical transmission can also occur (particularly in ''Aedes spp''); female infected mosquitoes lay virus infected eggs leading to a new generation of infected mosquitoes. Vertical transmission is important in the survival of the virus as the eggs laid by the female can survive for many months in dry conditions, hatching after a period of rain and so increasing spread post rainfall leading to epizootics <ref> ''Lagerqvist, N'', Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013 </ref>. Once animal infection has occurred mosquitoes are then responsible for amplifying infection. ''Aedes'' mosquito numbers decrease following rain but ''Culex'' tend to breed in more permanent water sites, hence the continuation of virus spread. <ref> ''Lagerqvist, N'', Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013 </ref>

Mosquitoes can be infected via feeding on infected animals. Vertical transmission can also occur (particularly in ''Aedes spp''); female infected mosquitoes lay virus infected eggs leading to a new generation of infected mosquitoes. Vertical transmission is important in the survival of the virus as the eggs laid by the female can survive for many months in dry conditions, hatching after a period of rain and so increasing spread post rainfall leading to epizootics <ref name="vaccine"> [''Lagerqvist, N'', Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013] </ref>. Once animal infection has occurred mosquitoes are then responsible for amplifying infection. ''Aedes'' mosquito numbers decrease following rain but ''Culex'' tend to breed in more permanent water sites, hence the continuation of virus spread. <ref name="vaccine"/>

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RVF affects 4 areas: <ref name="efsa"/>  

RVF affects 4 areas: <ref name="efsa"/>  

No outbreaks have been reported in urban areas.   

No outbreaks have been reported in urban areas.   

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Zoonotic transmission occurs through direct or indirect contact with infective blood or organs through slaughter, assisting with births and carcass disposal amongst other means. Faecal shedding of virus also occurs, as does spread through nasal and ocular secretions. Aerosol infection has also occurred within laboratory workers <ref>''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013 </ref>. Consuming unpasteurised or uncooked milk has also been associated with infection and seropositivity <ref> ''LaBeaud AD, Muiruri S, Sutherland LJ, Dahir S, Gildengorin G, Morrill J, Muchiri EM, Peters CJ, King CH. (2011)'' Postepidemic analysis of Rift Valley fever virus transmission in northeastern kenya: a village cohort study, PLoS Negl Trop Dis. 2011 Aug;5(8).</ref> <ref>''Mohamed M, Mosha F, Mghamba J, Zaki SR, Shieh WJ, Paweska J, Omulo S, Gikundi S, Mmbuji P, Bloland P, Zeidner N, Kalinga R, Breiman RF, Njenga MK, (2010)'' Epidemiologic and clinical aspects of a Rift Valley fever outbreak in humans in Tanzania, 2007, Am J Trop Med Hyg. 2010 Aug;83(2 Suppl):22-7. doi: 10.4269/ajtmh.2010.09-0318.</ref> . Mosquito bites have resulted in infection, and blood feeding flies also have the potential to transmit infection. There is no evidence of human to human transmission.

Zoonotic transmission occurs through direct or indirect contact with infective blood or organs through slaughter, assisting with births and carcass disposal amongst other means. Faecal shedding of virus also occurs, as does spread through nasal and ocular secretions. Aerosol infection has also occurred within laboratory workers <ref name="vaccine"/>. Consuming unpasteurised or uncooked milk has also been associated with infection and seropositivity <ref> ''LaBeaud AD, Muiruri S, Sutherland LJ, Dahir S, Gildengorin G, Morrill J, Muchiri EM, Peters CJ, King CH. (2011)'' Postepidemic analysis of Rift Valley fever virus transmission in northeastern kenya: a village cohort study, PLoS Negl Trop Dis. 2011 Aug;5(8).</ref> <ref>''Mohamed M, Mosha F, Mghamba J, Zaki SR, Shieh WJ, Paweska J, Omulo S, Gikundi S, Mmbuji P, Bloland P, Zeidner N, Kalinga R, Breiman RF, Njenga MK, (2010)'' Epidemiologic and clinical aspects of a Rift Valley fever outbreak in humans in Tanzania, 2007, Am J Trop Med Hyg. 2010 Aug;83(2 Suppl):22-7. doi: 10.4269/ajtmh.2010.09-0318.</ref> . Mosquito bites have resulted in infection, and blood feeding flies also have the potential to transmit infection. There is no evidence of human to human transmission.

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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 name="vaccine"/> .

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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 name="oie" />  

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" />  

RVF causes severe disease in animals, mainly cattle, sheep, goats and camels, with sheep being more susceptible.  ''Bos Taurus'' cattle and other European breed imported into Africa appear highly susceptible to RVF.  

RVF causes severe disease in animals, mainly cattle, sheep, goats and camels, with sheep being more susceptible.  ''Bos Taurus'' cattle and other European breed imported into Africa appear highly susceptible to RVF.  

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Age is an important factor in determining the severity of the disease, young stock are more susceptible – 90% of infected lambs die whereas in adult sheep mortality can be as low as <10% <ref name="who"/>. Small ruminants are also more susceptible. Pigs are resistant to low doses of RVF but high doses can cause viraemia <ref>''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013 </ref> .  

Age is an important factor in determining the severity of the disease, young stock are more susceptible – 90% of infected lambs die whereas in adult sheep mortality can be as low as <10% <ref name="who"/>. Small ruminants are also more susceptible. Pigs are resistant to low doses of RVF but high doses can cause viraemia <ref name="vaccine"/> .  

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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==Clinical Signs==

==Clinical Signs==

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 name="who"/> 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 name="who"/> Pregnant animals can abort at any stage often with 100% of stock aborting.<ref name="vaccine"/>   

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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 name="oie" />  

Newborn lambs and kids are highly susceptible to RVF, presenting with pyrexia and anorexia shortly followed by death 24-36hrs after infection.<ref name="vaccine"/> <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 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>  

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 name="vaccine"/>

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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,

The nucleocapsid protein is used as the antigen of choice in serological assays. Blood samples can be used to detect the virus during the early phase using virus propagation, antigen detection and RT-PCR.  

The nucleocapsid protein is used as the antigen of choice in serological assays. Blood samples can be used to detect the virus during the early phase using virus propagation, antigen detection and RT-PCR.  

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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 name="vaccine"/>.Cross reactions may occur with other ''phleboviruses''<ref name="vaccine"/>  

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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 name="oie" />

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 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.

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 name="vaccine"/> 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 name="oie" /> Immunofluorescence can also be used.

Haemagglutination inhibition (HI) and complement fixation assays are available but show extensive cross reactivity with other ''phlebovirus'' species.<ref name="vaccine"/>  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 name="oie" />

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" />

Modified live attenuated and inactivated virus vaccines are available.  

Modified live attenuated and inactivated virus vaccines are available.  

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The live attenuated '''Smithburn''' vaccine only requires one dose but may cause spontaneous abortion in pregnant stock.  This vaccine has adverse effects in newborn kids and lambs and teratogenic effects or abortion in pregnant cows, ewes and goats.<ref> ''Lagerqvist N, Moiane B, Bucht G, Fafetine J, Paweska J.T., Lundkvist Å and Falk K.I. 2012''. Stability of a formalin‐inactivated Rift Valley fever vaccine: evaluation of a vaccination campaign for cattle in Mozambique. Vaccine 30(46):6534‐40.</ref><ref>''Botros B, Omar A, Elian K, Mohamed G, Soliman A, Salib A, Salman D, Saad M, Earhart K.'' (2006) Adverse response of non-indigenous cattle of European breeds to live attenuated Smithburn Rift Valley fever vaccine. J Med Virol. 2006 Jun;78(6):787-91.</ref><ref>''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref> Protection is conferred to offspring via suckling. Antibody titres post vaccination are higher in sheep than cattle.<ref>''Lagerqvist, N,'' Rift Valley fever virus vaccine strategies, Karolinska Institutet 2013</ref>  One dose will protect for three years.<ref>http://www.fao.org/docrep/006/y4611e/y4611e00.htm#Contents</ref>

The live attenuated '''Smithburn''' vaccine only requires one dose but may cause spontaneous abortion in pregnant stock.  This vaccine has adverse effects in newborn kids and lambs and teratogenic effects or abortion in pregnant cows, ewes and goats.<ref> ''Lagerqvist N, Moiane B, Bucht G, Fafetine J, Paweska J.T., Lundkvist Å and Falk K.I. 2012''. Stability of a formalin‐inactivated Rift Valley fever vaccine: evaluation of a vaccination campaign for cattle in Mozambique. Vaccine 30(46):6534‐40.</ref><ref>''Botros B, Omar A, Elian K, Mohamed G, Soliman A, Salib A, Salman D, Saad M, Earhart K.'' (2006) Adverse response of non-indigenous cattle of European breeds to live attenuated Smithburn Rift Valley fever vaccine. J Med Virol. 2006 Jun;78(6):787-91.</ref><ref name="vaccine"/> Protection is conferred to offspring via suckling. Antibody titres post vaccination are higher in sheep than cattle.<ref name="vaccine"/>  One dose will protect for three years.<ref>http://www.fao.org/docrep/006/y4611e/y4611e00.htm#Contents</ref>

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The formalin inactivated virus vaccine (with Aluminium Hydroxide adjuvant) requires multiple doses to achieve immunity, and annual boosters are needed as it is less immunogenic.<ref> ''Lagerqvist N, Moiane B, Bucht G, Fafetine J, Paweska J.T., Lundkvist Å and Falk K.I.'' 2012. Stability of a formalin‐inactivated Rift Valley fever vaccine: evaluation of a vaccination campaign for cattle in Mozambique. Vaccine 30(46):6534‐40.</ref>It is safe to use in pregnant ewes. Biosecurity is also a consideration when using this vaccine as reversion to virulence is a possibility.

The formalin inactivated virus vaccine (with Aluminium Hydroxide adjuvant) requires multiple doses to achieve immunity, and annual boosters are needed as it is less immunogenic.<ref> ''Lagerqvist N, Moiane B, Bucht G, Fafetine J, Paweska J.T., Lundkvist Å and Falk K.I.'' 2012. Stability of a formalin‐inactivated Rift Valley fever vaccine: evaluation of a vaccination campaign for cattle in Mozambique. Vaccine 30(46):6534‐40.</ref>It is safe to use in pregnant ewes. Biosecurity is also a consideration when using this vaccine as reversion to virulence is a possibility.

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 name="oie" />

An R566 strain has been developed from MP12 and Clone 13 and has shown to confer immunity in laboratory experiments. <ref name="vaccine"/>

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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 name="vaccine"/>

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A recombinant virus vaccine has been found to be safe and effective in pregnant and non pregnant ewes, even when challenged with the virus. This vaccine has the advantage that it would allow differentiation between vaccinated and previously infected animals using a DIVA ELISA test (as would vector vaccines).<ref> ''Bird BH, Maartens LH, Campbell S, Erasmus BJ, Erickson BR, Dodd KA, Spiropoulou CF, Cannon D, Drew CP, Knust B, McElroy AK, Khristova ML, Albariño CG, Nichol ST'' (2011) Rift Valley fever virus vaccine lacking the NSs and NSm genes is safe, nonteratogenic, and confers protection from viremia, pyrexia, and abortion following challenge in adult and pregnant sheep, J Virol. 2011 Dec;85(24):12901-9</ref>

A recombinant virus vaccine has been found to be safe and effective in pregnant and non pregnant ewes, even when challenged with the virus. This vaccine has the advantage that it would allow differentiation between vaccinated and previously infected animals using a DIVA ELISA test (as would vector vaccines).<ref> ''Bird BH, Maartens LH, Campbell S, Erasmus BJ, Erickson BR, Dodd KA, Spiropoulou CF, Cannon D, Drew CP, Knust B, McElroy AK, Khristova ML, Albariño CG, Nichol ST'' (2011) Rift Valley fever virus vaccine lacking the NSs and NSm genes is safe, nonteratogenic, and confers protection from viremia, pyrexia, and abortion following challenge in adult and pregnant sheep, J Virol. 2011 Dec;85(24):12901-9</ref>