Review of oral rabies vaccination of dogs and its application in India

Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and need for the use of ORVs in free-roaming dogs to control dog-transmitted rabies in India. Iterative work to improve ORVs over the past four decades has resulted in vaccines that have high safety profiles whilst generating a consistent protective immune response to the rabies virus. The available evidence for safety and efficacy of modern ORVs in dogs and the broad and outspoken support from prominent global public health institutions for their use provides confidence to national authorities considering their use in rabies-endemic regions. India is estimated to have the largest rabies burden of any country and, whilst considerable progress has been made to increase access to human rabies prophylaxis, examples of high-output mass dog vaccination campaigns to eliminate the virus at the source remain limited. Efficiently accessing a large proportion of the dog population through parenteral methods is a considerable challenge due to the large, evasive stray dog population in many settings. Existing parenteral approaches require large skilled dog-catching teams to reach these dogs, which present financial, operational and logistical limitations to achieve 70% dog vaccination coverage in urban settings in a short duration. ORV presents the potential to accelerate the development of approaches to eliminate rabies across large areas of the South Asia region. Here we review the use of ORVs in wildlife and dogs, with specific consideration of the India setting. We also present the results of a risk analysis for a hypothetical campaign using ORV for the vaccination of dogs in an Indian state

The epidemiology of foot-and-mouth disease in the kingdom of Bhutan

Foot-and-mouth disease (FMD) is a highly infectious viral disease of all cloven-hoofed animals. It can have a significant impact on the livelihood of livestock owners, especially in developing nations such as Bhutan. Prior to the study reported in this thesis, there was limited understanding of the epidemiology of FMD in Bhutan in terms of its spatiotemporal distribution, risk factors, role of animal movement, and disease surveillance. Retrospective and prospective studies were conducted to unravel the epidemiology of FMD in Bhutan in order to support and refine the current control programme. The study demonstrated that FMD is endemic and periodically epidemic in Bhutan with the districts and sub-districts bordering India being at higher risk of disease than the interior districts. The districts and sub-districts bordering India appear to behave like primary endemic areas for the introduction and persistence of FMD virus through frequent unofficial movements of cattle across the porous border. The interior districts and subdistricts appear to behave like secondary endemic areas where virus propagation occurs due to limited vaccination coverage and unrestricted movement of animals. The study showed that O was the principal serotype in Bhutan, consistent with the disease epidemiology in the neighbouring countries. Cattle are the most susceptible animal while small ruminants and pigs seem to have minor roles in the disease’s epidemiology. However, unvaccinated small ruminants can be used as tracers for disease surveillance in areas where cattle are routinely vaccinated. Waves of outbreaks of FMD, in cyclical patterns, have occurred in Bhutan due to the incursion of the PanAsia strain of the O serotype, possibly through transboundary movement of livestock from neighbouring countries. The devastating capacity of the PanAsia strain of the O serotype, especially in a FMD-naïve population, was shown through the large scale morbidity and mortality of cattle and pigs during the 2007 epidemic in Bhutan. The disease produced significantly higher morbidities and mortalities in Zhemgang district (36.5% vaccination coverage) as compared with Sarpang district (87.6% vaccination coverage). Husbandry practices, such as mixing of cattle within and between villages at grazing and watering areas, and feeding kitchen wastes to cattle significantly increased the risk of transmission of FMD in FMD-endemic herds. The seroprevalence of FMD in the migratory herds (24.8%, 95% CI: 20.6, 29.5) was significantly higher than in the sedentary herds (17.5%, 95% CI: 15.6, 19.5) thus underlining the significance of this livestock production system for the disease’s epidemiology. Animal movements occurred in several forms including the daily movement of animals within and between villages for grazing and watering purposes; livestock trading within and between villages, sub-districts, and districts; and the traditional migratory practices. All these movements pose significant risks for disease transmission given the ineffective regulatory and quarantine services. The animal movement patterns were more complex in an FMD-endemic district (Sarpang) compared with an FMD-free district (Tsirang). There were more inward than outward movements for all species in the endemic district as compared with the FMD-free district. The presence of numerous unofficial trading routes along the Indo-Bhutan border in Sarpang district could be an important determinant for the frequent incursion and persistence of FMD in this district. Active serological and questionnaire-based surveys have validated the usefulness of the country’s passive surveillance system. Although the current findings have increased the level of confidence in the passive surveillance system of Bhutan, there is a need to complement this with active serological and clinical surveys from time to time. Several factors, such as extensive livestock husbandry practices, rugged terrain, inadequate vaccination coverage, ineffective regulation of movement control, porous borders, a lack of awareness of the disease by the farming community, and budgetary constraints, pose significant challenges to the prevention and control of FMD in Bhutan. Given the disease’s endemicity, controlling FMD for the whole country is currently both difficult and costly. Therefore alternative approaches using the concepts of zoning are proposed. Longitudinal studies, using active serological and clinical surveillance, indicated the absence of FMD infection in the district of Tsirang at the time of this study. This has now paved the way for initiation of progressive zoning approaches as an alternative control method in line with the global framework for the control of transboundary diseases. It is concluded that a regional approach is needed in order to successfully control this transboundary disease in Bhutan and neighbouring countries

Detection of Echinococcus granulosus and Echinococcus ortleppi in Bhutan

In this pilot study, fecal samples were collected from community dogs around slaughterhouses and from the city of Thimphu (n = 138) as well as from carnivores in the forest area around a farm in Bhutan (n = 28). Samples were analyzed microscopically for the presence of taeniid eggs by the floatation and sieving method. Further molecular analyses of 20 samples of community dogs positive for taeniid eggs confirmed 10 Echinococcus granulosus sensu lato and one Taenia hydatigena case. From 14 environmental fecal samples from the forest area positive for taeniid eggs, one contained E. granulosus s.l., six T. hydatigena and one Taenia taeniaeformis DNA. In the remaining samples considered positive for taeniid eggs, no molecular confirmation could be achieved. Additionally, Echinococcus cysts were collected from locally slaughtered cattle and imported cattle organs. Seven Echinococcus cysts (one fertile) from the local animals and 35 (four fertile) from imported cattle organs were confirmed as E. granulosus (G1–3) by PCR/sequencing. One Echinococcus cyst each from a local animal and from an imported cattle organ (both fertile) were confirmed to be Echinococcus ortleppi (G5). Sterile Echinococcus cysts were also collected from local yaks (n = 10), and all revealed to be E. granulosus (G1–G3). Hospital records of cystic echinococcosis in humans and the presence of Echinococcus spp. in dogs and ungulates indicate the existence of local transmission for both E. ortleppi and E. granulosus in Bhutan

Occurrence of Echinococcusgranulosussensulato and other Taeniids in Bhutan

The present research shows the results of a national study documenting the occurrence and genetic diversity of Echinococcus and Taenia species across Bhutan. Environmental dog faecal samples (n = 953) were collected from 2016 to 2018 in all 20 Bhutanese districts, mainly in urbanised areas. Cystic echinococcosis cysts were isolated from 13 humans and one mithun (Bos frontalis). Isolation of taeniid eggs from faeces was performed by sieving/flotation technique, followed by DNA isolation, PCR and sequence analyses for species identification (gene target: small subunit of ribosomal RNA). Genetic diversity of E. granulosuss.s. was based on the sequence (1609 bp) of the cox1 gene. A total of 67 out of 953 (7%) dog faecal samples were positive for at least one taeniid species. From the 670 free-roaming dog faecal samples, 40 (5.9%) were positive for taeniid DNA, 22 (3.2%) of them were identified as E. granulosuss.s. and four (0.5%) as E. ortleppi (G5). From the 283 faecal samples originating from yak-grazing areas, 27 (9.5%) were taeniid positive, including eight (2.8%) infected with E. granulosuss.s. and four (1.4%) with E. ortleppi. E. granulosuss.s. was identified in all isolates from human and the cyst from mithun. A haplotype network (cox1 gene) from E. granulosuss.s, including isolates from 12 dogs, two human and one mithun, revealed eight different haplotypes. The most common cox1 haplotype was the globally distributed Eg01, followed by Eg40 and Eg37 (previously described in China). Five new cox1 haplotypes (EgBhu1–5) originated from human, dogs, and a mithun were identified. The study indicated the contamination of urban areas and pastures with Echinococcus eggs in seven districts in Bhutan. The molecular characterisation of E. granulosuss.l. revealed different E. granulosuss.s. haplotypes as well as E. ortleppi. The transmission of T. multiceps was documented only in the western part of the country. Considering the zoonotic feature of E. granulosus s.s. and E. ortleppi and the economic impact of coenurosis caused by T. multiceps (also known as gid) in Bhutan, the findings of this study represent a significant contribution towards an epidemiological baseline for the establishment of a national control programme

Reconstructing the evolutionary history of pandemic foot-and- mouth disease viruses: the impact of recombination within the emerging O/ME-SA/Ind-2001 lineage

Foot-and-mouth disease (FMD) is a highly contagious disease of livestock affecting animal production and trade throughout Asia and Africa. Understanding FMD virus (FMDV) global movements and evolution can help to reconstruct the disease spread between endemic regions and predict the risks of incursion into FMD-free countries. Global expansion of a single FMDV lineage is rare but can result in severe economic consequences. Using extensive sequence data we have reconstructed the global space-time transmission history of the O/ME-SA/Ind-2001 lineage (which normally circulates in the Indian sub-continent) providing evidence of at least 15 independent escapes during 2013-2017 that have led to outbreaks in North Africa, the Middle East, Southeast Asia, the Far East and the FMD-free islands of Mauritius. We demonstrated that sequence heterogeneity of this emerging FMDV lineage is accommodated within two co-evolving divergent sublineages and that recombination by exchange of capsid-coding sequences can impact upon the reconstructed evolutionary histories. Thus, we recommend that only sequences encoding the outer capsid proteins should be used for broad-scale phylogeographical reconstruction. These data emphasise the importance of the Indian subcontinent as a source of FMDV that can spread across large distances and illustrates the impact of FMDV genome recombination on FMDV molecular epidemiology