Early Events following Experimental Infection with Peste-Des-Petits Ruminants Virus Suggest Immune Cell Targeting

Peste-des-petits ruminants virus (PPRV) is a viral pathogen that causes a devastating plague of small ruminants. PPRV is an economically significant disease that continues to be a major obstacle to the development of sustainable agriculture across the developing world. The current understanding of PPRV pathogenesis has been heavily assumed from the closely related rinderpest virus (RPV) and other morbillivirus infections alongside data derived from field outbreaks. There have been few studies reported that have focused on the pathogenesis of PPRV and very little is known about the processes underlying the early stages of infection. In the present study, 15 goats were challenged by the intranasal route with a virulent PPRV isolate, Côte d'Ivoire '89 (CI/89) and sacrificed at strategically defined time-points post infection to enable pre- and post-mortem sampling. This approach enabled precise monitoring of the progress and distribution of virus throughout the infection from the time of challenge, through peak viraemia and into a period of convalescence. Observations were then related to findings of previous field studies and experimental models of PPRV to develop a clinical scoring system for PPRV. Importantly, histopathological investigations demonstrated that the initial site for virus replication is not within the epithelial cells of the respiratory mucosa, as has been previously reported, but is within the tonsillar tissue and lymph nodes draining the site of inoculation. We propose that virus is taken up by immune cells within the respiratory mucosa which then transport virus to lymphoid tissues where primary virus replication occurs, and from where virus enters circulation. Based on these findings we propose a novel clinical scoring methodology for PPRV pathogenesis and suggest a fundamental shift away from the conventional model of PPRV pathogenesis

Peste des Petits Ruminants

Heartwater (or cowdriosis) is a tick-borne disease caused by Ehrlichia ruminantium, an obligatory intracellular bacterium of the order Rickettsiales, transmitted by several ticks of the genus Amblyomma. The organism is genetically highly variable which prevented until now the development of efficient vaccines. The disease is enzootic in sub-Sahelian Africa and in some Caribbean islands. It affects domestic and wild ruminants, the susceptibility to cowdriosis varying greatly between breeds and species: African wildlife shows mainly asymptomatic infections; local cattle breeds are generally protected due to enzootic stability; and introduced cattle breeds and small ruminants, even in enzootic regions, are usually susceptible to heartwater and can suffer high mortality rates. Cowdriosis is characterized by a sudden and acute fever followed by nervous, respiratory, and gastrointestinal symptoms and by hydrothorax and hydropericardium during postmortem examination. In West Africa, the only vector is Amblyomma variegatum, present in areas where pluviometry is higher than 500 mm. Therefore, animals of a high proportion of the Sahelian region are usually not infested by the tick and not infected by the bacterium. They are thus susceptible when introduced in southern parts of the Sahel or in the subhumid neighboring areas of the West African countries, for example during transhumance. Tetracyclines are effective drugs to treat heartwater when administered before occurrence of the nervous symptoms. Various vaccines have been tested, and are still developed, but, up to now, none of them showed enough effectiveness against all the field strains of E. ruminantium to allow its marketing. Prevention is therefore mainly achieved by drastic vector control or, on the contrary, acquisition of enzootic stability following tick infestation combined with tetracycline treatment as soon as hyperthermia occurs