Are We Getting Closer to the Treatment of Rabies?

Rodney E Willoughby Jr

Disclosures

Future Virology. 2009;4(6):563-570. 

In This Article

Abstract and Introduction

Abstract

Rabies is a top-ten infectious killer and is newly re-emergent worldwide. Focusing on the unique aspects of the pathophysiology and immunology of rabies, we improvised a strategy that led to the first survivor of rabies without rabies prophylaxis. Our data support the long-standing speculation that rabies is a disorder of neurotransmission. Improvements in human survival have better delineated the immune and metabolic responses to rabies. We anticipate a new generation of rabies biologicals in the very near future, as well as the more remote possibility of rescue monoclonal antibodies engineered from several recent survivors of human rabies. The general approach to rabies treatment serves as a model for a more complex, physiological approach to treating infectious neurological disorders.

Introduction

Rabies is a disease of antiquity and currently ranks in the top-ten infectious killers of humans. To great acclaim, rabies was one of the first vaccine-preventable diseases (Louis Pasteur's report of 350 cases in 1886[1]), and remains completely vaccine preventable today.[2] It is newly re-emergent in regions undergoing rapid change: from China (single-child policies and affluence leading to a surge in unvaccinated pets), to the former Soviet Republics (crumbling medical and veterinary infrastructure), to southern Africa (AIDS-related depletion of human populations leading to the emergence of feral dog packs), to South America (deforestation-related changes in vampire bat ecosystems).

The true burden of disease is unknown because rabies is neglected. It is a disease of the most poor, geographically isolated and pediatric populations. It is misdiagnosed, particularly because the diagnosis of rabies requires specialized laboratories.[3] The rapid progression in rabies to death of the host (within 5–7 days) prevents access to health centers in remote areas. By extrapolating data from rates of rabies endemics in dogs and dog-bite attack rates, approximately 50,000 people die annually from rabies in Africa and Asia. This burden is equivalent to the annual infection of 2.5–5 million people by a respiratory virus conferring 1–2% mortality and exceeds the annual mortality for the dengue virus or Japanese encephalitis.

The 'one health, one medicine' concept has not yet gained traction among competing government ministries, so rabies remains the world's most important zoonosis.[101] Rabies is best prevented by veterinary approaches, but the disease is not economically a major veterinary pathogen, so allocations by ministries of agriculture or the environment are of low priority. It is a major human pathogen – ranked in the top-three infectious killers in China for the past 5 years – but is largely rural and, therefore, neglected relative to AIDS and TB with regard to public health allocations.

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