Phylodynamics of vampire bat-transmitted rabies in Argentina.

Common vampire bat populations distributed from Mexico to Argentina are important rabies reservoir hosts in Latin America. The aim of this work was to analyse the population structure of the rabies virus (RABV) variants associated with vampire bats in the Americas and to study their phylodynamic pattern within Argentina. The phylogenetic analysis based on all available vampire bat-related N gene sequences showed both a geographical and a temporal structure. The two largest groups of RABV variants from Argentina were isolated from northwestern Argentina and from the central western zone of northeastern Argentina, corresponding to livestock areas with different climatic, topographic and biogeographical conditions, which determined their dissemination and evolutionary patterns. In addition, multiple introductions of the infection into Argentina, possibly from Brazil, were detected. The phylodynamic analysis suggests that RABV transmission dynamics is characterized by initial epizootic waves followed by local enzootic cycles with variable persistence. Anthropogenic interventions in the ecosystem should be assessed taking into account not only the environmental impact but also the potential risk of disease spreading through dissemination of current RABV lineages or the emergence of novel ones associated with vampire bats.

Teste PCR em tempo real para diagnóstico antemortem em humanos e triagem de high throughtput do vírus da raiva / Real time PCR for antemortem diagnosis in humans and high throughput rabies virus screening

a raiva é uma das mais antigas e devastadoras doenças, tipicamente com um índice de mortalidade de 100% dos casos. O diagnóstico da raiva antemortem em humanos é importante para definir os procedimentos de controle da infecção e evitar maior exposição das equipes de saúde e de outras pessoas que podem ter tido contato com a saliva do paciente; para determinar epidemiologicamente seoutros indivíduos foram expostos à mesma fonte; para monitorar a progressão da doença, medianteintervenções terapêuticas experimentares; para evitar a infecção cruzada durante transplantes de órgãos e, caso negativa, para examinar outros diagnósticos diferenciais. A obtenção de quatro amostras é o recomendadopara testes antemortem de raiva em humanos (por meio da saliva, do soro, de biópsia de pele da nuca e do fluido cerebroespinhal), nos quais os anticorpos, os antígenos virais e os ácidos nucleicos são detectados empregando métodos de neutralização, imunofluorescência direta e indireta e transcrição reversa de PCR. O momento chave para obtenção de resultados conclusivos, nas quatro amostras analisadas por todas as técnicas, é aproximadamente de 24 a 48 horas. A PCR em tempo real parece ser umatécnica promissora para acelerar os resultados da detecção no ácido nucleico e quantificar, com maior precisão, as cargas virais nas amostras dos pacientes. Não existe, porém, primer ou probe universal que possa detectar a ampla diversidade dos lissavirus descrita até o momento, o que reduz drasticamente a sensibilidade do teste. O objetivo deste estudo foi traçar o desenho de um ensaio sensível e específico de PCR em tempo real capaz de detectar e quantificar uma ampla variedade dos vírus de raiva em amostras antemortem e postmortem em tecidos e fluidos corporais de humanos e animais. MÉTODOS: Mais de2.500 sequências completas de nucleoproteínas de RABV representativas de um espectro global devariantes obtidas das bases de dados do GenBank e do CDC foram analisadas para ...

Immune response after rabies vaccine in a kidney transplant recipient.

A 48-year-old male kidney-transplant recipient was bitten by a rabid dog. His immunosuppressive treatment consisted of cyclosporine 60 mg b.i.d., mycophenolate mofetil (MMF) 250 mg t.i.d., and prednisone 5 mg. After wound care, he received 5 doses of purified vero cell rabies vaccine on days 0, 3, 7, 14, and 28, and human rabies immunoglobulin, according to international guidelines. Adequate levels of rabies virus neutralizing antibodies were observed after the administration of the third vaccine dose. However, a decrease of antibody titer was detected by day 28. Immunosuppressive medication was minimized, withdrawing MMF and reducing the dose of cyclosporine. Booster doses of the same vaccine were administered on days 38, 41, 45, 52, and 66. Adequate neutralizing antibody response was recovered during the ensuing 12 months, under reduced immunosuppression. Nineteen months after the incident, the patient remains with good graft function and is asymptomatic for rabies. It remains to be determined whether the attained immune response was either the result of the booster vaccinations or the reduction of immunosuppression alone. Nevertheless, such an outcome would have been possible only with the combined management strategy implemented.

New rabies virus variant found during an epizootic in white-nosed coatis from the Yucatan Peninsula.

In February 2008, three white-nosed coatis (Nasua narica) were found dead in a recreational park in Cancun, Mexico. The diagnosis of rabies virus (RABV) infection was confirmed by direct immunofluorescence test. The phylogenetic analysis performed with the complete RABV nucleoprotein gene positioned this isolate close to a sequence of a human rabies case reported during 2008 from Oaxaca, Mexico, sharing 93% similarity. In turn, these two variants are related to another variant found in rabid Tadarida brasiliensis mexicana bats across North America. Anti-RABV neutralizing activity (1.3 IU/ml) was found in the serum of one white-nosed coati captured with another five that cohabited with the dead animals. Enhanced rabies surveillance and pathogenesis studies should be conducted in coatis and insectivorous bats of the region to clarify the role of these species as potential emergent or long-term unidentified RABV reservoirs.

Molecular epidemiology identifies only a single rabies virus variant circulating in complex carnivore communities of the Serengeti.

Understanding the transmission dynamics of generalist pathogens that infect multiple host species is essential for their effective control. Only by identifying those host populations that are critical to the permanent maintenance of the pathogen, as opposed to populations in which outbreaks are the result of 'spillover' infections, can control measures be appropriately directed. Rabies virus is capable of infecting a wide range of host species, but in many ecosystems, particular variants circulate among only a limited range of potential host populations. The Serengeti ecosystem (in northwestern Tanzania) supports a complex community of wild carnivores that are threatened by generalist pathogens that also circulate in domestic dog populations surrounding the park boundaries. While the combined assemblage of host species appears capable of permanently maintaining rabies in the ecosystem, little is known about the patterns of circulation within and between these host populations. Here we use molecular phylogenetics to test whether distinct virus-host associations occur in this species-rich carnivore community. Our analysis identifies a single major variant belonging to the group of southern Africa canid-associated viruses (Africa 1b) to be circulating within this ecosystem, and no evidence for species-specific grouping. A statistical parsimony analysis of nucleoprotein and glycoprotein gene sequence data is consistent with both within- and between-species transmission events. While likely differential sampling effort between host species precludes a definitive inference, the results are most consistent with dogs comprising the reservoir of rabies and emphasize the importance of applying control efforts in dog populations.