Browsing by Author "Heller, Rasmus"

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    Diversity and transboundary mobility of serotype O foot-and-mouth disease virus in East Africa: Implications for vaccination policies
    (Infection, Genetics and Evolution, 2010) Balinda, Sheila N.; Sangula, Abraham K.; Heller, Rasmus; Muwanika, Vincent B.; Belsham, Graham J.; Masembe, Charles; Siegismund, Hans R.
    Foot-and-mouth disease (FMD) virus serotype O has been responsible for most reported outbreaks of the disease in East Africa. A sustained campaign for the past 40 years to control FMD mainly by vaccination, combined with quarantine and zoosanitary measures has been undertaken with limited success. We investigated the genetic relationships among serotype O strains in eastern Africa using complete VP1 coding region sequences obtained from 46 FMD virus isolates collected in Kenya in the years 1964–2008 and 8 Ugandan isolates collected between 1999 and 2006. In addition, 21 selected FMDV sequences from Genbank representing reference strains from eastern Africa and elsewhere were included in the Bayesian inference analyses and the detection of selection forces. The results confirmed previous observations that eastern Africa harbours four distinct topotypes (clades with >15% sequence divergence). All but one strain isolated post-2000 belonged to topotypes EA-2, EA-3 and EA-4, while all three vaccines have been based on strains in the EA-1 topotype. The estimated dN/dS ratios across the individual codons of the entire VP1 coding region revealed that purifying (negative) selection constituted the dominant evolutionary force. Cross-border disease transmission within the region has been suggested with probable incursions of topotypes EA-3 and EA-4 into Kenya and Uganda from neighboring Ethiopia and Sudan. Weconclude that the vaccines have probably been effective in controlling EA-1, but less so for the other topotypes and propose a more comprehensive representation of topotypes in the development of new vaccines in recognition of the considerable diversity and transboundary nature of serotype O.
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    Evolutionary analysis of foot-and-mouth disease virus serotype SAT 1 isolates from east Africa suggests two independent introductions from southern Africa
    (BMC evolutionary biology,, 2010) Sangula, Abraham K.; Belsham, Graham J.; Muwanika, Vincent B.; Heller, Rasmus; Balinda, Sheila N.; Masembe, Charles; Siegismund, Hans R.
    In East Africa, foot-and-mouth disease virus serotype SAT 1 is responsible for occasional severe outbreaks in livestock and is known to be maintained within the buffalo populations. Little is known about the evolutionary forces underlying its epidemiology in the region. To enhance our appreciation of the epidemiological status of serotype SAT 1 virus in the region, we inferred its evolutionary and phylogeographic history by means of genealogy-based coalescent methods using 53 VP1 coding sequences covering a sampling period from 1948-2007. Results: The VP1 coding sequence of 11 serotype SAT 1 FMD viruses from East Africa has been determined and compared with known sequences derived from other SAT 1 viruses from sub-Saharan Africa. Purifying (negative) selection and low substitution rates characterized the SAT 1 virus isolates in East Africa. Two virus groups with probable independent introductions from southern Africa were identified from a maximum clade credibility tree. One group was exclusive to Uganda while the other was present within Kenya and Tanzania. Conclusions: Our results provide a baseline characterization of the inter-regional spread of SAT 1 in sub-Saharan Africa and highlight the importance of a regional approach to trans-boundary animal disease control in order to monitor circulating strains and apply appropriate vaccines.
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    Time Clustered Sampling Can Inflate the Inferred Substitution Rate in Foot-And- Mouth Disease Virus Analyses
    (PLoS ONE, 2015) Pedersen, Casper-Emil T.; Frandsen, Peter; Wekesa, Sabenzia N.; Heller, Rasmus; Sangula, Abraham K.; Wadsworth, Jemma; Knowles, Nick J.; Muwanika, Vincent B.; Siegismund, Hans R.
    With the emergence of analytical software for the inference of viral evolution, a number of studies have focused on estimating important parameters such as the substitution rate and the time to the most recent common ancestor (tMRCA) for rapidly evolving viruses. Coupled with an increasing abundance of sequence data sampled under widely different schemes, an effort to keep results consistent and comparable is needed. This study emphasizes commonly disregarded problems in the inference of evolutionary rates in viral sequence data when sampling is unevenly distributed on a temporal scale through a study of the foot-andmouth (FMD) disease virus serotypes SAT 1 and SAT 2. Our study shows that clustered temporal sampling in phylogenetic analyses of FMD viruses will strongly bias the inferences of substitution rates and tMRCA because the inferred rates in such data sets reflect a rate closer to the mutation rate rather than the substitution rate. Estimating evolutionary parameters from viral sequences should be performed with due consideration of the differences in short-term and longer-term evolutionary processes occurring within sets of temporally sampled viruses, and studies should carefully consider how samples are combined.