Rabies virus-neutralising antibodies in healthy, unvaccinated individuals: What do they mean for rabies epidemiology?

Abstract

Rabies has been a widely feared disease for thousands of years, with records of rabid dogs as early as ancient Egyptian and Mesopotamian texts. The reputation of rabies as being inevitably fatal, together with its ability to affect all mammalian species, contributes to the fear surrounding this disease. However, the widely held view that exposure to the rabies virus is always fatal has been repeatedly challenged. Although survival following clinical infection in humans has only been recorded on a handful of occasions, a number of studies have reported detection of rabies-specific antibodies in the sera of humans, domestic animals, and wildlife that are apparently healthy and unvaccinated. These 'seropositive' individuals provide possible evidence of exposure to the rabies virus that has not led to fatal disease. However, the variability in methods of detecting these antibodies and the difficulties of interpreting serology tests have contributed to an unclear picture of their importance. In this review, we consider the evidence for rabies-specific antibodies in healthy, unvaccinated individuals as indicators of nonlethal rabies exposure and the potential implications of this for rabies epidemiology. Our findings indicate that whilst there is substantial evidence that nonlethal rabies exposure does occur, serology studies that do not use appropriate controls and cutoffs are unlikely to provide an accurate estimate of the true prevalence of nonlethal rabies exposure.

Dried blood spot cards: A reliable sampling method to detect human antibodies against rabies virus

“…Whereas rabies is generally seen as an inevitable fatal disease, this idea is challenged by some studies that found rabies antibodies in serum of unvaccinated populations living in endemic areas [ 29 ]. The studies are limited—as populations with high exposure to possible rabies-infected wildlife are often hard to reach—and heterogeneous due to the variance in serological assays and used cut-offs [ 30 ]. DBS sampling provides solutions for both issues, and could therefore contribute to the understanding of the immunopathology of rabies in seropositive populations.…”

Neglected challenges in the control of animal rabies in China

“…In Taiwan, although rabies in FBs has been reported since 2012, no human cases have been documented [ 25 ]. The high percentage (69.6%) of rabies seroconversion in FBs suggests that the occasional exposure of FBs to RABV may cause peripheral abortive infection rather than rabies development in the central nervous system [ 10 , 26 ]. Therefore, rabies pathogenesis and the potential threat of asymptomatic infections in FBs must be further studied [ 26 ].…”

Defining New Pathways to Manage the Ongoing Emergence of Bat Rabies in Latin America

“…Bats have similar or longer lifespans (e.g., up to 15 years for wild common vampire bats [51]) than currently vaccinated carnivores (e.g., up to 12 years for wild red foxes [52]), but 3-to 6-fold slower reproduction, which would extend vaccine-induced population immunity to a point that effective herd immunity may prevent transmission definitively [53,54]. Moreover, naturally acquired VNAs from sublethal exposures potentially creates substantial baseline immunity not observed for carnivore reservoirs, which may also help reach effective herd immunity faster [55]. Existing recombinant viral vaccines using vaccinia [56,57] and raccoonpox [58,59] vectors are immunogenic and protective in bats.…”