Genetic Evidence for Rift Valley Fever Outbreaks in Madagascar Resulting from Virus Introductions from the East African Mainland rather than Enzootic Maintenance

Carroll, Serena A.; Reynes, Jean-Marc; Khristova, Marina L.; Andriamandimby, Soa Fy; Rollin, Pierre E.; Nichol, Stuart T.

doi:10.1128/jvi.00335-11

Cited by 61 publications

(57 citation statements)

References 23 publications

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“…RVF has been endemic in sub-Saharan African countries for more than 80 years and has spread to Egypt, Madagascar, Saudi Arabia, and Yemen (6,7,12,68,71). RVFV causes a high rate of abortion and acute lethal infection in newborn ruminants, such as sheep, goats, and cattle, and febrile illness in humans (13,68,71).…”

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confidence: 99%

The Dominant-Negative Inhibition of Double-Stranded RNA-Dependent Protein Kinase PKR Increases the Efficacy of Rift Valley Fever Virus MP-12 Vaccine

Lihoradova

Kalveram

Indran

et al. 2012

J Virol

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f Rift Valley fever virus (RVFV), belonging to the genus Phlebovirus, family Bunyaviridae, is endemic to sub-Saharan Africa and causes a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. MP-12 is the only RVFV strain excluded from the select-agent rule and handled at a biosafety level 2 (BSL2) laboratory. MP-12 encodes a functional major virulence factor, the NSs protein, which contributes to its residual virulence in pregnant ewes. We found that 100% of mice subcutaneously vaccinated with recombinant MP-12 (rMP12)-murine PKRN167 (mPKRN167), which encodes a dominant-negative form of mouse double-stranded RNA (dsRNA)-dependent protein kinase (PKR) in place of NSs, were protected from wild-type (wt) RVFV challenge, while 72% of mice vaccinated with MP-12 were protected after challenge. rMP12-mPKRN167 induced alpha interferon (IFN-␣) in sera, accumulated RVFV antigens in dendritic cells at the local draining lymph nodes, and developed high levels of neutralizing antibodies, while parental MP-12 induced neither IFN-␣ nor viral-antigen accumulation at the draining lymph node yet induced a high level of neutralizing antibodies. The present study suggests that the expression of a dominant-negative PKR increases the immunogenicity and efficacy of live-attenuated RVFV vaccine, which will lead to rational design of safe and highly immunogenic RVFV vaccines for livestock and humans.

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confidence: 99%

The Dominant-Negative Inhibition of Double-Stranded RNA-Dependent Protein Kinase PKR Increases the Efficacy of Rift Valley Fever Virus MP-12 Vaccine

Lihoradova

Kalveram

Indran

et al. 2012

J Virol

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“…Reassortment of genome RNA segments by members of the family Bunyaviridae during coinfection has been reported in laboratory-derived and field-isolated viruses (2,8,12,30). Importantly, the absence of p.v.…”

Section: Discussionmentioning

confidence: 99%

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

Bird

Maartens

Campbell

et al. 2011

J Virol

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111

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Rift Valley fever virus (RVFV) is a mosquito-borne human and veterinary pathogen causing large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Safe and effective vaccines are critically needed, especially those that can be used in a targeted one-health approach to prevent both livestock and human disease. We report here on the safety, immunogenicity, and efficacy of the ⌬NSs-⌬NSm recombinant RVFV (rRVFV) vaccine (which lacks the NSs and NSm virulence factors) in a total of 41 sheep, including 29 timed-pregnant ewes. This vaccine was proven safe and immunogenic for adult animals at doses ranging from Rift Valley fever virus (RVFV) (family Bunyaviridae, genus Phlebovirus) is a mosquito-borne human and veterinary pathogen associated with large outbreaks of severe disease throughout Africa and the Arabian Peninsula. The virus was first identified following the sudden death of approximately 4,700 lambs and ewes on a single farm along the shores of Lake Naivasha in the Great Rift Valley of Kenya over a 4-week period in 1931 (15). Since then, RVFV has caused numerous economically devastating epizootics often characterized by sweeping "abortion storms," neonatal animal mortality approaching 100%, and significant mortality (ϳ10 to 20%) among adult ruminant livestock, especially sheep and cattle (7,13,14,28,32). Human infections are typically self-limiting febrile illnesses that, in 1 to 2% of affected individuals, can progress to more severe disease that includes fulminant hepatitis, encephalitis, retinitis, blindness, or a hemorrhagic syndrome. Fatality ratios in hospitalized patients are 10 to 20% (22,24).RVFV is uniquely suitable for a one-health approach to prevent both livestock and human disease through animal vaccination. Livestock provide two key ecological links between the transovarially infected Aedes sp. floodwater mosquito and the human population. First, infected livestock rapidly develop high viremias, allowing the spillover of RVFV into secondary vectors (Culex and Anopheles sp. mosquitoes) that are more likely to feed on humans. Second, the high virus loads found in livestock are also a significant risk factor for human infection by direct contact with contaminated blood, tissues, and aborted fetal materials (1). A vaccination strategy targeted at preventing the virus amplification step in livestock could provide a window of opportunity to interrupt nascent RVFV outbreaks by both reducing the potential for secondary vector spillover and eliminating the threat posed by infected livestock tissues.Currently, no RVFV vaccine has been approved for veterinary use outside areas of endemicity, although a variety of vaccines for either human or livestock use have been developed since RVFV was first isolated (9, 29). Problems with prior RVFV vaccines include poor immunogenicity, requiring multiple vaccination doses; difficulties with manufacturing; and

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“…3 A recent RVF outbreak that occurred in Madagascar was probably associated with infected domestic animals imported from east Africa. 4,5 Another study suggested that this outbreak most likely originated from an endemic cycle localized in southern Madagascar, where virus circulation may occur annually. 6 Although not quantified, it is possible that these two mechanisms co-occur in Madagascar, with a recurrent introduction that helps RVFV maintenance and recirculation in the endemic cycle.…”

Section: Introductionmentioning

confidence: 99%

A Review of Mosquitoes Associated with Rift Valley Fever Virus in Madagascar

Tantely¹,

Boyer²,

Fontenille³

2015

The American Society of Tropical Medicine and Hygiene

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Abstract. Rift Valley fever (RVF) is a viral zoonotic disease occurring throughout Africa, the Arabian Peninsula, and Madagascar. The disease is caused by a Phlebovirus (RVF virus [RVFV]) transmitted to vertebrate hosts through the bite of infected mosquitoes. In Madagascar, the first RVFV circulation was reported in 1979 based on detection in mosquitoes but without epidemic episode. Subsequently, two outbreaks occurred: the first along the east coast and in the central highlands in 1990 and 1991 and the most recent along the northern and eastern coasts and in the central highlands in 2008 and 2009. Despite the presence of 24 mosquitoes species potentially associated with RVFV transmission in Madagascar, little associated entomological information is available. In this review, we list the RVFV vector, Culex antennatus, as well as other taxa as candidate vector species. We discuss risk factors from an entomological perspective for the re-emergence of RVF in Madagascar.

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Genetic Evidence for Rift Valley Fever Outbreaks in Madagascar Resulting from Virus Introductions from the East African Mainland rather than Enzootic Maintenance

Abstract: Rift Valley fever virus (RVFV),

Cited by 61 publications

References 23 publications

The Dominant-Negative Inhibition of Double-Stranded RNA-Dependent Protein Kinase PKR Increases the Efficacy of Rift Valley Fever Virus MP-12 Vaccine

The Dominant-Negative Inhibition of Double-Stranded RNA-Dependent Protein Kinase PKR Increases the Efficacy of Rift Valley Fever Virus MP-12 Vaccine

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

A Review of Mosquitoes Associated with Rift Valley Fever Virus in Madagascar

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