Current status of rabies and prospects for elimination

Abstract

Rabies is one of the most deadly infectious diseases, with a case-fatality rate approaching 100%. The disease is established on all continents apart from Antarctica; most cases are reported in Africa and Asia, with thousands of deaths recorded annually. However, the estimated annual figure of almost 60,000 human rabies fatalities is probably an underestimate. Almost all cases of human rabies result from bites from infected dogs. Therefore, the most cost-effective approach to elimination of the global burden of human rabies is to control canine rabies rather than expansion of the availability of human prophylaxis. Mass vaccination campaigns with parenteral vaccines, and advances in oral vaccines for wildlife, have allowed the elimination of rabies in terrestrial carnivores in several countries worldwide. The subsequent reduction in cases of human rabies in such regions advocates the multidisciplinary One Health approach to rabies control through the mass vaccination of dogs and control of canine populations.

Figure 1

WHO rabies risk map Data from WHO. Most of the cases of human rabies occur in Africa and Asia. Attempts to accurately map the distribution of rabies risk or incidence show the absence of quantitative data and the irrelevance of political boundaries in the control of a disease with animal reservoirs. In low-risk areas, pre-exposure immunisation is recommended for individuals who will come into contacts with bats. In medium risk areas, pre-exposure immunisation is recommended for individuals who will come into contact with bats and other wildlife. In high-risk areas, pre-exposure immunisation is recommended for individuals who will come into contact with domestic animals such as dogs, and other rabies vectors.

Figure 2

Phylogenetic tree of the lyssavirus phylogroups and their respective species Nucleoprotein sequences (405 nucleotides) were aligned with ClustalW and the phylogenetic tree was visualised using TreeView version 3.2. Bootstrap values at relevant nodes are shown. According to the proposed antigenicity of each group of isolates, the viruses are divided into different phylogroups. Where available, accession numbers for sequences are rabies virus (RABV AY102999, AY062068, AY103008, AY062069, AY102993,AY352514, AY330735, AY062090, AY062070, AY062047), Lagos bat virus (LBV EF547459, EF547449, EF547447, GU170202), West Caucasian bat virus (WCBV EF614258), Shimoni bat virus (SHIBV GU170201), Mokola virus (MOKV AY062074,AY062077), Duvenhage virus (DUVV AY062079), European bat lyssavirus type 1 (EBLV-1 AY062088, EF157976), Irkut virus (IRKV EF614260), Australian bat lyssavirus (ABLV AF418014), European bat lyssavirus type 2 (EBLV-2AY062091, AY062089), Bokeloh bat lyssavirus (BBLV JF311903), Khujand virus (KHUV EF614261), Aravan virus (ARAV EF614259), and Ikoma lyssavirus (IKOV JX193798). Several sequences within the phylogeny are unpublished and as such do not have accession numbers. The scale bar represents 0·1 substitutions per nucleotide site. The number of human cases are shown next to silhouettes where reported.

Figure 3

Pathogenesis of rabies virus Reproduced from Singh and Ruzek, by permission of Taylor & Francis. 1) Virus enters muscle tissue of host through bite wound, then 2) enters the peripheral nervous system (PNS) via neuromuscular junction, and then 3) travels from PNS to spinal cord and brain. 4) Virus enters brain and undergoes extensive replication leading to neuronal dysfunction (slide shows virus in Purkinje cells of cerebellum 40x magnification). 5a) The virus replicates in salivary glands and is excreted in saliva, 5b) enters peripheral nerves of skin and Purkinje cells, and 5c) spreads from the brain to infect many tissues and organs in the host.

Figure 4

Immunohistochemical detection of rabies virus nucleoprotein and chemokines in infected tissue Immunohistochemical detection of rabies virus nucleoprotein (brown staining) in human neurons (A). Section prepared from a brain sample from a human case of rabies in the UK. Magnification, ×200. Immunohistochemical staining for chemokines within the brain of mice infected with rabies virus (B–D). Specific staining for CCL2 (B), CCL5 (C), and CXCL10 (D) are shown. Magnification ×200.