RESUMEN
Despite the disease's long history, little progress has been made toward a treatment for rabies. The prognosis for patient recovery remains dire. For any prospect of survival, patients require aggressive critical care, which physicians in rabies endemic areas may be reluctant or unable to provide given the cost, clinical expertise required, and uncertain outcome. Systematic clinical research into combination therapies is further hampered by sporadic occurrence of cases. In this Perspective, we examine the case for a One Medicine approach to accelerate development of an effective therapy for rabies through the veterinary care and investigational treatment of naturally infected dogs in appropriate circumstances. We review the pathogenesis of rabies virus in humans and dogs, including recent advances in our understanding of the molecular basis for the severe neurological dysfunction. We propose that four categories of disease process need to be managed in patients: viral propagation, neuronal degeneration, inflammation and systemic compromise. Compassionate critical care and investigational treatment of naturally infected dogs receiving supportive therapy that mimics the human clinical scenario could increase opportunities to study combination therapies that address these processes, and to identify biomarkers for prognosis and therapeutic response. We discuss the safety and ethics of this approach, and introduce the Canine Rabies Treatment Initiative, a non-profit organization with the mission to apply a One Medicine approach to the investigation of diagnostic, prognostic, and therapeutic options for rabies in naturally infected dogs, to accelerate transformation of rabies into a treatable disease for all patients.
RESUMEN
To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by manufacturers in older dogs, ostensibly due to concerns over interference of maternally-acquired immunity with immune response to the vaccine. Adverse effects of vaccination in this age group of dogs have also not been adequately assessed under field conditions. In a single-site, owner-blinded, randomized, placebo-controlled trial in puppies born to mothers vaccinated within the previous 18 months in a high-mortality population of owned, free-roaming dogs in South Africa, we assessed immunogenicity and effect on survival to all causes of mortality of a single dose of rabies vaccine administered at 6 weeks of age. We found that puppies did not have appreciable levels of maternally-derived antibodies at 6 weeks of age (geometric mean titer 0.065 IU/mL, 95% CI 0.061-0.069; n = 346), and that 88% (95% CI 80.7-93.3) of puppies vaccinated at 6 weeks had titers ≥0.5 IU/mL 21 days later (n = 117). Although the average effect of vaccination on survival was not statistically significant (hazard ratio [HR] 1.35, 95% CI 0.83-2.18), this effect was modified by sex (p = 0.02), with the HR in females 3.09 (95% CI 1.24-7.69) and the HR in males 0.79 (95% CI 0.41-1.53). We speculate that this effect is related to the observed survival advantage that females had over males in the unvaccinated group (HR 0.27; 95% CI 0.11-0.70), with vaccination eroding this advantage through as-yet-unknown mechanisms.
RESUMEN
In the Caribbean region, Dirofilaria immitis (heartworm) has been detected on almost all of the islands. While it is assumed to be endemic throughout the region, there is a lack of baseline data from the Leeward Islands (north-east of the Caribbean region). The objective of this study was to estimate the prevalence and the spatial distribution of heartworm disease in dogs on St. Kitts, a small 174km2 island which is part of the Leeward Islands. A cross-sectional study was conducted in 2014 with 100 dogs tested using a commercial antigen test. Dogs were from all regions of the island except the southeastern region, which differs socio-economically from the rest of the island. Heartworm was not detected in these 100 dogs. To complete the survey, in 2015, fifteen dogs from the southeast region were tested, eight of which were positive for heartworm. Prevalence was estimated at 7.0% (95% confidence interval: 4.6-11.6). Data from two other sources were added to complete the report: data from dogs enrolled in a free spay and neuter program and tested against heartworm (164 dogs with 3 positive for heartworm), and the data from positive dogs diagnosed at the Ross University Veterinary Clinic in 2014 and 2015 (3 dogs). Most of the heartworm positive dogs (10/14) lived in a delimited area in the southeast of the island. These results indicate an overall low prevalence of Dirofilaria immitis in St. Kitts, lower than that observed in the other Caribbean islands. Heterogeneity in the spatial distribution of the parasite was observed, with the majority of cases residing in the southeast of the island. Previous spatial models focused on the spread of the parasite over large geographical areas and long distances, but not within a restricted area. Our results indicate the presence of local factors which may have limited spread of the disease over short distances. Further studies are needed to understand this markedly heterogeneous distribution.