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Asymptomatic Rabies

By Amesh A. Adalja, MD, FACP, August 10, 2012

The rabies virus has a case fatality rate close to 100%, the highest of all pathogens known to infect humans. Before survival was demonstrated in a few patients treated with the Milwaukee protocol1 regimen of sedatives and antivirals, clinical disease caused by rabies was invariably fatal. However, susceptibility to the virus varies among mammalian species—foxes are highly susceptible while bats have seroprevalence rates that can reach 50%. In humans, abortive infections do not generally occur. For the most part, unvaccinated people do not have antibody titers. Rare exceptions are found among just a few groups that have a low seroprevalence rate (hunters, trappers, and residents of a Peruvian community affected by an outbreak in 1990).2 The results of a recently published study that quantified and characterized rabies seroprevalence rates in an endemic region of Peru provide important new insights into the pathophysiology of rabies and point to new directions in research.2

Seropositive Individuals Identified

In 2010, the researchers interviewed 92 residents of Truenococha and Santa Marta, 2 Peruvian communities in which rabies-carrying vampire bats are highly prevalent. They performed serological testing on 63 subjects. Of those surveyed, 54% reported being bitten by a bat. Risk factors for bat exposure included younger age, larger household size, and ownership of pets and/or livestock.2

Of the 63 sera samples tested, 9 had rabies-neutralizing antibody titers. All 9 of those subjects reported bat exposure, and one had been vaccinated. Positive titers were associated with older age but did not vary by gender.2

New Directions for Research

The authors suggest several possible explanations for the seroprevalence rate they observed: 1) genetic basis for resistance to productive infection; 2) virus exposure without replication; 3) small infectious dose; and 4) salivary cofactors that may induce immune response following bites. Cross reaction with similar viruses was not thought to be a factor.2

The discovery of asymptomatic rabies that provokes antibody formation advances our understanding of this disease, and further characterization of the seropositive will provide greater understanding of rabies pathophysiology. Future studies might aim to uncover the degree of protection the antibodies confer, their durability, and the mechanism of induction in the absence of clinical disease. Further along, identification of the genetics of immunity could lead to new treatment modalities.

References

  1. Willoughby RE Jr, Tieves KS, Hoffman GM, et al. Survival after treatment of rabies with induction of coma. N Engl J Med 2005;352:2508-2514.

  2. Gilbert AT, Petersen BW, Recuenco S, et al. Evidence of rabies exposure among humans in the Peruvian Amazon. Am J Trop Med Hyg 2012;87:206-215.