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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 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"/>

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"/>  

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" />

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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 FAO Signs of Rift Valley Fever] accessed June 23, 2013</ref>

==Treatment==

==Treatment==

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 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 name="fao"/>

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 name="stability"> ''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 name="fao"/>

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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 name="stability"/>It is safe to use in pregnant ewes. Biosecurity is also a consideration when using this vaccine as reversion to virulence is a possibility.

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Vaccines should be administered prior to outbreak to prevent an epizootic. Vaccination during an outbreak may worsen the situation, especially if multi dose vials are used, due to the possibility of viraemic animals being vaccinated and then the same vial being used on a healthy animal, thus spreading the virus.<ref name="who"/> The use of the Smithburn vaccine is restricted in non endemic areas and during outbreaks due to the possibility of reassortment and a return to virulence.  

Vaccines should be administered prior to outbreak to prevent an epizootic. Vaccination during an outbreak may worsen the situation, especially if multi dose vials are used, due to the possibility of viraemic animals being vaccinated and then the same vial being used on a healthy animal, thus spreading the virus.<ref name="who"/> The use of the Smithburn vaccine is restricted in non endemic areas and during outbreaks due to the possibility of reassortment and a return to virulence.  

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More recently a naturally attenuated virus vaccine has been developed (Clone 13) that is marketed in South Africa and Namibia.<ref>''Kortekaas J, Zingeser J, de Leeuw P, de La Rocque S, Unger H, Moormann RJ.'',2011 Rift Valley Fever Vaccine Development, Progress and Constraints. Emerg Infect Dis. 2011 Sep;17(9)</ref><ref>http://www.rr-africa.oie.int/docspdf/en/2012/RVF/MBAO01.pdf</ref> Testing in pregnant ewes and lambs demonstrated safety and it has been shown to be as effective as the Smithburn vaccine in conferring immunity.<ref>''Dungu B, Louw I, Lubisi A, Hunter P, von Teichman BF, Bouloy M'' (2010). Evaluation of the efficacy and safety of the Rift Valley Fever Clone 13 vaccine in sheep.,  Vaccine. 2010 Jun 23;28(29):4581-7</ref> <ref>''von Teichman B, Engelbrecht A, Zulu G, Dungu B, Pardini A, Bouloy M'' (2011). Safety and efficacy of Rift Valley fever Smithburn and Clone 13 vaccines in calves. . Vaccine. 2011 Aug 5;29(34):5771-7</ref> The vaccine has however shown to cause neurological disease and paralysis in some vaccinated mice.<ref>''Vialat P., Billecocq A., Kohl A., and Bouloy M.'' (2000). The S segment of Rift Valley fever phlebovirus (Bunyaviridae) carries determinants for attenuation and virulence in mice. J Virol 74:1538‐1543.</ref>

More recently a naturally attenuated virus vaccine has been developed (Clone 13) that is marketed in South Africa and Namibia.<ref>''Kortekaas J, Zingeser J, de Leeuw P, de La Rocque S, Unger H, Moormann RJ.'',2011 Rift Valley Fever Vaccine Development, Progress and Constraints. Emerg Infect Dis. 2011 Sep;17(9)</ref><ref>[http://www.rr-africa.oie.int/docspdf/en/2012/RVF/MBAO01.pdf GALVmed Rift Valley Fever vaccination strategy] accessed June 23, 2013</ref> Testing in pregnant ewes and lambs demonstrated safety and it has been shown to be as effective as the Smithburn vaccine in conferring immunity.<ref>''Dungu B, Louw I, Lubisi A, Hunter P, von Teichman BF, Bouloy M'' (2010). Evaluation of the efficacy and safety of the Rift Valley Fever Clone 13 vaccine in sheep.,  Vaccine. 2010 Jun 23;28(29):4581-7</ref> <ref>''von Teichman B, Engelbrecht A, Zulu G, Dungu B, Pardini A, Bouloy M'' (2011). Safety and efficacy of Rift Valley fever Smithburn and Clone 13 vaccines in calves. . Vaccine. 2011 Aug 5;29(34):5771-7</ref> The vaccine has however shown to cause neurological disease and paralysis in some vaccinated mice.<ref>''Vialat P., Billecocq A., Kohl A., and Bouloy M.'' (2000). The S segment of Rift Valley fever phlebovirus (Bunyaviridae) carries determinants for attenuation and virulence in mice. J Virol 74:1538‐1543.</ref>

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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 name="vaccine"/> Colostrum from vaccinated ewes gives temporary immunity to lambs.<ref name="fao"/>  

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 name="vaccine"/> Colostrum from vaccinated ewes gives temporary immunity to lambs.<ref name="fao"/>  

DNA and virus particle based vaccines are currently being developed and have demonstrated some level of protection against RVF virus. Plant derived subunit vaccines are also being researched.<ref>''Kortekaas J, Zingeser J, de Leeuw P, de La Rocque S, Unger H, Moormann RJ''  Rift Valley Fever Vaccine Development, Progress and Constraints. Emerg Infect Dis. 2011 Sep;17(9)</ref>

DNA and virus particle based vaccines are currently being developed and have demonstrated some level of protection against RVF virus. Plant derived subunit vaccines are also being researched.<ref>''Kortekaas J, Zingeser J, de Leeuw P, de La Rocque S, Unger H, Moormann RJ''  Rift Valley Fever Vaccine Development, Progress and Constraints. Emerg Infect Dis. 2011 Sep;17(9)</ref>

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Vaccine storage and transport is an issue within developing countries; breaking of the cold chain may result in ineffective vaccines being administered. However, a study has shown that the use of a formalin inactivated vaccine transported 200km at ambient temperatures had no adverse effect on antibody responses.<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>

Vaccine storage and transport is an issue within developing countries; breaking of the cold chain may result in ineffective vaccines being administered. However, a study has shown that the use of a formalin inactivated vaccine transported 200km at ambient temperatures had no adverse effect on antibody responses.<ref name="stability"/>