Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution.DOI: http://dx.doi.org/10.7554/eLife.14552.001
Rabies has profound public health, social and economic impacts on developing countries, with an estimated 59,000 annual human rabies deaths globally. Mass dog vaccination is effective at eliminating the disease but remains challenging to achieve in India due to the high proportion of roaming dogs that cannot be readily handled for parenteral vaccination. Two methods for the vaccination of dogs that could not be handled for injection were compared in Goa, India; the oral bait handout (OBH) method, where teams of two travelled by scooter offering dogs an empty oral bait construct, and the catch-vaccinate-release (CVR) method, where teams of seven travel by supply vehicle and use nets to catch dogs for parenteral vaccination. Both groups parenterally vaccinated any dogs that could be held for vaccination. The OBH method was more efficient on human resources, accessing 35 dogs per person per day, compared to 9 dogs per person per day through CVR. OBH accessed 80% of sighted dogs, compared to 63% by CVR teams, with OBH accessing a significantly higher proportion of inaccessible dogs in all land types. All staff reported that they believed OBH would be more successful in accessing dogs for vaccination. Fixed operational team cost of CVR was four times higher than OBH, at 127 USD per day, compared to 34 USD per day. Mean per dog vaccination cost of CVR was 2.53 USD, whilst OBH was 2.29 USD. Extrapolation to a two week India national campaign estimated that 1.1 million staff would be required using CVR, but 293,000 staff would be needed for OBH. OBH was operationally feasible, economical and effective at accessing the free roaming dog population. This study provides evidence for the continued expansion of research into the use of OBH as a supplementary activity to parenteral mass dog vaccination activities in India.
Dog-mediated rabies kills tens of thousands of people each year in India, representing one third of the estimated global rabies burden. Whilst the World Health Organization (WHO), World Organization for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) have set a target for global dog-mediated human rabies elimination by 2030, examples of large-scale dog vaccination programs demonstrating elimination remain limited in Africa and Asia. We describe the development of a data-driven rabies elimination program from 2013 to 2019 in Goa State, India, culminating in human rabies elimination and a 92% reduction in monthly canine rabies cases. Smartphone technology enabled systematic spatial direction of remote teams to vaccinate over 95,000 dogs at 70% vaccination coverage, and rabies education teams to reach 150,000 children annually. An estimated 2249 disability-adjusted life years (DALYs) were averted over the program period at 526 USD per DALY, making the intervention ‘very cost-effective’ by WHO definitions. This One Health program demonstrates that human rabies elimination is achievable at the state level in India.
Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.
BackgroundPreventable wounds are a common welfare issue in working donkeys in many countries. In the Bukombe District of Tanzania, there are estimated to be 3000 working donkeys, used primarily to transport loads for direct income generation. For historical reasons, oxen-yoke carts are used; their design is inappropriate for donkeys and results in serious neck wounds. The project aim was to assess the prevalence and nature of wounds in working donkeys.MethodsIn November 2018, 148 donkeys owned by 48 owners were examined, and data were collected.ResultsThe study revealed that one or more wounds were present in 56.1% of the population and yoke-related, dorsal neck wounds comprised 79.5% of these. These wounds ranged in surface area from 1 cm2 to 300 cm2. Clinically, 96.6% of all wound types were superficial and the majority of these (51.1%) were granulating.ConclusionThese data will enable the future evaluation of targeted interventions aimed at reducing the prevalence of these specific wounds.
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