Genomic Diversity and Evolution of the Lyssaviruses

Lyssaviruses are RNA viruses with single-strand, negative-sense genomes responsible for rabies-like diseases in mammals. To date, genomic and evolutionary studies have most often utilized partial genome sequences, particularly of the nucleoprotein and glycoprotein genes, with little consideration of genome-scale evolution. Herein, we report the first genomic and evolutionary analysis using complete genome sequences of all recognised lyssavirus genotypes, including 14 new complete genomes of field isolates from 6 genotypes and one genotype that is completely sequenced for the first time. In doing so we significantly increase the extent of genome sequence data available for these important viruses. Our analysis of these genome sequence data reveals that all lyssaviruses have the same genomic organization. A phylogenetic analysis reveals strong geographical structuring, with the greatest genetic diversity in Africa, and an independent origin for the two known genotypes that infect European bats. We also suggest that multiple genotypes may exist within the diversity of viruses currently classified as ‘Lagos Bat’. In sum, we show that rigorous phylogenetic techniques based on full length genome sequence provide the best discriminatory power for genotype classification within the lyssaviruses

Renewed global partnerships and redesigned roadmaps for rabies prevention and control

Canine rabies, responsible for most human rabies deaths, is a serious global public health concern. This zoonosis is entirely preventable, but by focusing solely upon rabies prevention in humans, this "incurable wound" persists at high costs. Although preventing human deaths through canine rabies elimination is feasible, dog rabies control is often neglected, because dogs are not considered typical economic commodities by the animal health sector. Here, we demonstrate that the responsibility of managing rabies falls upon multiple sectors, that a truly integrated approach is the key to rabies elimination, and that considerable progress has been made to this effect. Achievements include the construction of global rabies networks and organizational partnerships; development of road maps, operational toolkits, and a blueprint for rabies prevention and control; and opportunities for scaling up and replication of successful programs. Progress must continue towards overcoming the remaining challenges preventing the ultimate goal of rabies elimination

Rabies, Still Neglected after 125 Years of Vaccination

International audienceno abstrac

Taxonomy and evolutionary studies on Lyssaviruses with special reference to Africa

Currently, the Lyssavirus genus is composed of four serotypes and the ungrouped European bat lyssaviruses (EBL). Using previously described PCR amplification and direct sequencing methods, the N genes of 70 representative lyssaviruses collected from 40 different countries were examined. From the results, a phylogenetic tree with six branches (genotypes) was constructed: genotypes 1-4 correlated with the classification of serotypes 1-4 and in addition EBL 1 and EBL 2 were identified as two further genotypes (5 and 6). Analysis of the 51 rabies (genotype 1) viruses in the study identified nine distinct groups which could be correlated with their geographical origins. A comparison of the six genotypes with four principal Vesiculovirus serotypes showed that their relationship was closer than that of even the two most closely related Vesiculovirus serotypes. Antigenic site sequences of isolates from vaccine/treatment failures were similar to vaccine and field strains, suggesting that failures were not due to genetic variation at the N protein level.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.mn201

Temporal Dynamics of European Bat Lyssavirus Type 1 and Survival of Myotis myotis Bats in Natural Colonies

Many emerging RNA viruses of public health concern have recently been detected in bats. However, the dynamics of these viruses in natural bat colonies is presently unknown. Consequently, prediction of the spread of these viruses and the establishment of appropriate control measures are hindered by a lack of information. To this aim, we collected epidemiological, virological and ecological data during a twelve-year longitudinal study in two colonies of insectivorous bats (Myotis myotis) located in Spain and infected by the most common bat lyssavirus found in Europe, the European bat lyssavirus subtype 1 (EBLV-1). This active survey demonstrates that cyclic lyssavirus infections occurred with periodic oscillations in the number of susceptible, immune and infected bats. Persistence of immunity for more than one year was detected in some individuals. These data were further used to feed models to analyze the temporal dynamics of EBLV-1 and the survival rate of bats. According to these models, the infection is characterized by a predicted low basic reproductive rate (R0 = 1.706) and a short infectious period (D = 5.1 days). In contrast to observations in most non-flying animals infected with rabies, the survival model shows no variation in mortality after EBLV-1 infection of M. myotis. These findings have considerable public health implications in terms of management of colonies where lyssavirus-positive bats have been recorded and confirm the potential risk of rabies transmission to humans. A greater understanding of the dynamics of lyssavirus in bat colonies also provides a model to study how bats contribute to the maintenance and transmission of other viruses of public health concern

From reverse innovation to global innovation in animal health: a review

Reverse innovation refers to learning from or diffusion of innovations developed in low income settings and further translated to industrialized countries. There is lack of consensus regarding terminology, but the idea that innovations in low-income countries are promising for adoption in high-income contexts is not new. However, in healthcare literature globally, the vast majority of publications referring to 'disruptive innovation' were published in the last ten years. To assess the potential of innovative developments and technologies for improving animal health, we initiated a literature review in 2020. We used a combined approach, incorporating targeted searching in PubMed using a key word algorithm with a snowball technique, to identify 120 relevant publications and extract data for qualitative coding. Heterogeneity of articles precluded meta-analysis, quality scoring and risk of bias analysis. We can distinguish technical innovations like new digital devices, diagnostic tests and procedures, and social innovations of intersectoral cooperation. We profile two case studies to describe potential global innovations: an integrated surveillance and response system in Somali Regional State, Ethiopia and a blockchain secured One Health intervention to optimally provide post-exposure prophylaxis for rabies exposed people in West Africa. Innovation follows no borders and can also occur in low-income settings, under constraints of cost, lack of services and infrastructure. Lower administrative and legal barriers may contribute to produce innovations that would not be possible under conditions of high density of regulation. We recommend using the term global innovation, which highlights those emanating from international partnership to solve problems of global implications

Rabies molecular virology, diagnosis, prevention and treatment

Rabies is an avertable viral disease caused by the rabid animal to the warm blooded animals (zoonotic) especially human. Rabies occurs in more than 150 countries and territories. According to an estimation by WHO, almost 55,000 people die because of rabies every year. The Dogs are the major reason behind this, approximately 99% human deaths caused by dog's bites. Developing and under developing countries, both are the victims of rabies. With the post-exposure preventive regimes, 327,000 people can prevent this disease annually

More Accurate Insight into the Incidence of Human Rabies in Developing Countries through Validated Laboratory Techniques

International audienceNo abstract availabl

Rabies Situation in Cambodia

In Cambodia, rabies still elicits fear in the communities. Since 1998 the Institut Pasteur in Cambodia (IPC), Phnom Penh has been the only source of free post-exposure prophylaxis (PEP) and post mortem diagnosis. During 1998–2007, on average ∼12,400 patients received PEP annually at IPC (range 8,907–14,475) and 63 fatal human cases presenting with encephalitis following a dog bite were reported including 73% who tested positive by fluorescent-antibody test on brain samples or/and by reverse-transcriptase polymerase chain reaction on skin, cerebrospinal fluid, or urine. In 2007, 14,475 patients received PEP (100 PEP/100,000 people in Cambodia) including 95% who resided in Phnom Penh city (615 PEP/100,000) or five neighboring provinces. Using a step-by-step probability model, we estimated that 810 human rabies deaths would occur in 2007 (95% confidence interval [CI] 394–1,607); an incidence of 5.8/100,000 (95%CI 2.8–11.5). As a result, despite high attendance at the IPC's PEP center most Cambodians living in peripheral provinces in Cambodia may not have adequate access to PEP. Finally, the model generated one of the highest incidences of rabies worldwide. A national rabies control program is needed to improve surveillance and access to PEP, and to initiate vaccination campaigns in dogs