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Unlocking mysteries of Rift Valley fever in southern Africa through integrated spatial and molecular analyses. Peter Thompson Department of Production Animal Studies, University of Pretoria, Onderstepoort, South Africa Peter Durr Australian Animal Health Laboratory, CSIRO,
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Unlocking mysteries of Rift Valley feverin southern Africathrough integrated spatial and molecular analyses Peter Thompson Department of Production Animal Studies, University of Pretoria, Onderstepoort, South Africa Peter Durr Australian Animal Health Laboratory, CSIRO, Geelong, Australia
Rift Valley fever • RNA arbovirus – Bunyaviridae, Phlebovirus • First described in 1930s in Rift Valley of W Kenya • Main vectors are Aedes and Culex spp. mosquitoes • Main hosts are sheep, goats and cattle • Important zoonosis
RVF outbreaks • Large outbreaks at long, irregular intervals • Abortion storms and mortality in livestock • Sheep most severely affected • Human disease • contact with diseased animal tissues • mosquito bites • severe complications in 1-2% • Role of wildlife uncertain • clinical disease / abortion • subclinical infection
Likely origin of Rift Valley fever virus Weaver & Reisen (2010) Antiviral Res. 85:328-345
RVF in South Africa • First recognised in South Africa in 1950/51 • ±100,000 sheep died and 500,000 aborted • Central plateau of South Africa • Largest outbreak occurred in 1973/74 • Extended across most of the central plateau • Next large series of outbreaks in 2008-10 • First in eastern part of SA, followed by large outbreak across central plateau • ±15,000 animal cases • Smaller outbreaks in some intervening years • Both in eastern areas and central plateau
Some unanswered questions • Mechanism(s) of RVFV persistence during the IEP? • Transovarial transmission in Aedes spp. with long-term survival of eggs • Low-level endemic circulation in livestock and/or wildlife • Overwintering of adult Culex spp. during mild winters • Mechanism(s) of disease emergence after IEP? • Emergence of infected Aedes eggs • Movement of infected hosts • ? Long-distance vector dispersal • ? Introduction of infected Aedes eggs by migratory waterfowl • Mechanism(s) of spread during outbreaks? • Vector dispersal • Movement of viraemic hosts • ? Multiple introductions or emergences • Can prediction models for Southern Africa be improved? • NDVI, ENSO, …
Jan-May 2008 • Mpumalanga and Gauteng provinces • Clinical disease in African buffalo near Mozambique border • Livestock: mainly cattle affected
Feb-Jun 2009 • Kwa-Zulu Natal, high rainfall area • One farm in Mpumalanga (May 2009) • Mainly cattle affected
Oct-Nov 2009 • Near Namibian border • Localised to a small area along the Orange River • Not associated with above-average rainfall • Flood irrigation
Jan-Aug 2010 • Across entire central plateau • Associated with high rainfall and flooding • 484 reported outbreaks • 14,342 animal cases, of which >90% sheep • Many wild antelope species affected
Jan-Jul 2011 • Mainly Eastern and Western Cape Provinces • 135 outbreaks reported
RVF in South Africa, 2008-2011: questions… • Where did the virus come from? • What was/is the reservoir? • How was the virus introduced? • What were the mechanisms of spread of the epidemic?
Origin and spread of the 2008-2011 outbreaks • Data of RVF outbreaks from OIE WAHID website • Space-time permutation scan statistic (Kulldorfet al. 2005) using SatScan 9.1.1 (www.satscan.org) • Detection of space-time clusters • Partial (490-nt) Gn glycoprotein gene sequences (M-segment) from 2008-2010 isolates (mainly human) (Grobbelaaret al. 2011) • Construction of Bayesian phylogeny of southern African RVFV isolates using MrBayes(mrbayes.sourceforge.net) • Investigation of genetic relationships between clusters
Time aggregation: 1 month Spatial window: 20% of cases Temporal window: 20% of study period 1 4 5 7 6 3 8 2 9 10
Time aggregation: 1 month Spatial window: 30% of cases Temporal window: 30% of study period 1 4 6 5 3 2 8 7
Time aggregation: 1 month Spatial window: 40% of cases Temporal window: 40% of study period 1 4 6 5 3 2 8 7
Time aggregation: 1 month Spatial window: 50% of cases Temporal window: 50% of study period 1 4 6 5 3 2 8 7
Indications from cluster analysis • 2008, 2009 (KZN) and 2009 (N Cape) outbreaks form three distinct clusters • 2010 epidemic consisted of several clusters, possibly resulting from a combination of: • short distance spread (vector dispersal) • long-distance spread (animal movement) • multiple introductions? • 2011 epidemic consisted of two simultaneous clusters: • at least two separate instances of overwintering
RVF in South Africa, 2008-2010 partial M-segment sequence available
1 2008 2 2009 2009 3 2010 4, 5, 6, … Bayesian phylogeny of southern African RVFV isolates
Indications from phylogenetic analysis • 2008 and 2009 (KZN) outbreaks were caused by very similar viruses • likely originated from livestock or wildlife reservoir in north-east – Mozambique/Zimbabwe? • mechanism of introduction and spread between clusters still unknown • 2009 (N Cape) and 2010 outbreaks were caused by very similar viruses • likely originated from N Namibia or N Botswana, mechanism of spread unknown • N Cape outbreak was a likely source of virus for 2010 outbreak in Free State, possibly via movement of infected animals
RVF lineages in South Africa, 2008-2010 (Grobbelaaret al. 2011) C H
1999 South African RVF isolates 2008-9 2009-10 1974-5 1951 Grobbelaaret al. (2011) Emerg.Infect.Dis. 17:2270-2276
A L C C N G N N G D E G C K B C M K L C RVF virus lineages E C A A C E H C J G K L K C M I O F H L Data from Grobbelaaret al. (2011) Emerg.Infect.Dis. 17:2270-2276
1995 L L 1963-4 RVF virus L-lineage L 1969-70 L 1971-4 Data from Grobbelaaret al. (2011) Emerg.Infect.Dis. 17:2270-2276
C 2000 C 2003 C 1998 1977-2007 C 1998 C RVF virus C-lineage 1985 C C 1976-98 1991, 2008 C C 1999, 2008-9 Data from Grobbelaaret al. (2011) Emerg.Infect.Dis. 17:2270-2276
RVF virus H-lineage H 2004 2009-11 H Data from Grobbelaaret al. (2011) Emerg.Infect.Dis. 17:2270-2276
RVF lineages in Africa, 1951-2010 2008-10 2009-11 1973-4 Data from Grobbelaaret al. (2011) Emerg.Infect.Dis. 17:2270-2276
Directions for further work • Further development of “conventional” spatial analyses • Cluster detection, multivariable models, spread models, etc. • Development of predictive models suited to southern Africa • Longitudinal serological monitoring to detect viral circulation during IEP • Vector population dynamics, host preference and dispersion • Phylogeography / phylodynamics • Reconstruction of timed viral dispersal patterns using time-scaled phylogenies to accommodate phylogenetic uncertainty (Lemeyet al. (2009) PLoS Comp. Biol. 5:e1000520) • Reconstruction of most likely transmission patterns and infection dates by combining spatio-temporal and genetic data (Morelliet al. (2012) PLoS Comp. Biol. 8:e1002768)
Acknowledgements • Bob Swanepoel, University of Pretoria • JanuszPaweska, National Institute for Communicable Diseases • RaphaelleMétras, Royal Veterinary College • Kerryne Graham, Australian Animal Health Laboratory