Rabies in a postpandemic world: resilient reservoirs, redoubtable riposte, recurrent roadblocks, and resolute recidivism

Abstract

Rabies is an ancient disease. Two centuries since Pasteur, fundamental progress occurred in virology, vaccinology, and diagnostics-and an understanding of pathobiology and epizootiology of rabies in testament to One Health-before common terminological coinage. Prevention, control, selective elimination, and even the unthinkable-occasional treatment-of this zoonosis dawned by the twenty-first century. However, in contrast to smallpox and rinderpest, eradication is a wishful misnomer applied to rabies, particularly post-COVID-19 pandemic. Reasons are minion. Polyhostality encompasses bats and mesocarnivores, but other mammals represent a diverse spectrum of potential hosts. While rabies virus is the classical member of the genus, other species of lyssaviruses also cause the disease. Some reservoirs remain cryptic. Although global, this viral encephalitis is untreatable and often ignored. As with other neglected diseases, laboratory-based surveillance falls short of the notifiable ideal, especially in lower- and middle-income countries. Calculation of actual burden defaults to a flux within broad health economic models. Competing priorities, lack of defined, long-term international donors, and shrinking local champions challenge human prophylaxis and mass dog vaccination toward targets of 2030 for even canine rabies impacts. For prevention, all licensed vaccines are delivered to the individual, whether parenteral or oral-essentially 'one and done'. Exploiting mammalian social behaviors, future 'spreadable vaccines' might increase the proportion of immunized hosts per unit effort. However, the release of replication-competent, genetically modified organisms selectively engineered to spread intentionally throughout a population raises significant biological, ethical, and regulatory issues in need of broader, transdisciplinary discourse. How this rather curious idea will evolve toward actual unconventional prevention, control, or elimination in the near term remains debatable. In the interim, more precise terminology and realistic expectations serve as the norm for diverse, collective constituents to maintain progress in the field.

Keywords: Diagnosis; Epidemiology; Lyssavirus; Neglected Tropical Diseases; Pathogenesis; Prophylaxis; Rabies; Surveillance; Vaccination; Zoonosis.

Fig. 1

Phylogenetic placement of lyssaviruses within the subfamily Alpharhabdovirinae, family Rhabdoviridae. The evolutionary history was inferred from an alignment of the complete L protein sequences of animal rhabdoviruses, using the Maximum Likelihood method. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Joining and BioNJ algorithms to a matrix of pairwise distances estimated using a JTT model. Statistical significance was assessed via 100 bootstrap replicates (values > 70 are shown for key nodes)

Fig. 2

Phylogenetic structure of the Lyssavirus genus based on the complete N gene sequences of representatives from each currently recognized species. The topology was inferred using the Maximum Likelihood method. Initial trees for the heuristic search were obtained automatically by applying Neighbor-Joining and BioNJ algorithms to a matrix of pairwise distances estimated using a JTT model. Statistical significance was assessed via 100 bootstrap replicates (values > 70 are shown for key nodes)

Fig. 3

Phylogenetic lineages of rabies viruses (RABV) circulating in wild carnivores that are related to canine rabies viruses. The tree was generated from full-length nucleoprotein (N) gene sequences by the neighbor-joining method supported by 1,000 bootstrap replicates. GenBank accession numbers are shown at tree tips, host species and geographic region are indicated after brackets, and conventional names for RABV lineages are shown on the right

Fig. 4

New World bat rabies virus (RABV) diversity (black) in association with infections in carnivores (red). Asterisks indicate viruses recovered during known outbreaks with sustained cross-species transmission of bat RABV among carnivores. Bat species and genera that serve as lineage hosts are indicated on the right. The neighbor-joining tree is based on RABV nucleoprotein (N) gene sequences with 1000 bootstrap replicates (shown as % for key nodes) and rooted with Mexican skunk, South-Central skunk, and raccoon RABV lineages (also related to American bat viruses within the "Indigenous American" RABV lineage)

Fig. 5

Hundefängerin (dog chasers), Ernst Barlach, woodcut, ca. ~ 1919. From: Die Kunst. Monatshefte für freie und angewandte Kunst, vol. 4 https://commons.wikimedia.org/wiki/File:Hundef%C3%A4nger,_Ernst_Barlach.jpg3, 1921, p143

Fig. 6

‘Aguador mata-perros ‘ (waterseller dog-killer), watercolor painting by Francisco ‘Pancho’ Fierro Palas (Lima, 1850). https://commons.wikimedia.org/wiki/File:Aguador_mata-perros_(1850).jpg

Fig. 7

Dog catchers, 1924. Library of Congress, Prints and Photographs Division, Washington, D.C. 20,540 USA http://hdl.loc.gov/loc.pnp/pp.print

Fig. 8

Street poster, emulating responsible dog ownership, downtown Ranchi, India