Rabies—what is necessary to achieve ‘zero by 30’?

Against a backdrop of decades of neglect, the adoption of a firm goal to achieve zero human deaths due to canine rabies by 2030, which was initially set in 2013 and reaffirmed by all 180 World Organization for Animal Health member countries in 2016, provides the impetus for making a real global public health difference.1 With the effective tools at our disposal it is almost unconscionable that 59 000 people, many of whom are young children, are dying unnecessarily due to canine rabies each year.2 The constellation of veterinary and public health programme failures that characterize rabies control and response in too many endemic countries must now be addressed as a matter of urgency—the goal will remain elusive unless effective dog control, dog vaccination, and effective pre- and post-exposure management of humans, including increasing awareness of risk, is guaranteed everywhere that canine rabies continues to exact a heavy toll. Strengthened veterinary and public health systems will be paramount to achieving the elimination of human deaths due to canine rabies. In most settings, 70% of dogs will need to be vaccinated for this goal to be achieved.3 This requires a reliable and adequate supply of vaccine locally, a well-trained and enthusiastic workforce, and a well-informed community. As dog ownership is ubiquitous, establishing reliable information and service delivery portals between veterinary services and local communities could deliver exceptional and very valuable complementary benefits for other important stock and domestic animal diseases, and their prevention. Useful tools have been developed to allow local services to monitor their progress against pivotal system strengthening requirements.4 There is a real possibility that current dog rabies vaccine production capacity will be unable to meet demand. It has been estimated that should production continue at 2015 levels, there will be a cumulative shortage of about 7.5 billion doses to meet expected demand to achieve dog rabies elimination by 2030.5 This comes with a sizeable price-tag estimated to present a US$3900 million gap when compared with current spending. Clearly, without political statement being translated into a hard cash commitment, the goal will remain illusionary. The opportunity to administer lower doses of vaccine by the intradermal route, which has provided comparative immunity at reduced expense, should be fully embraced. The requirement to ensure a reliable supply of potent human rabies vaccine and rabies immunoglobulin administered timeously following a high-risk exposure is a definitive litmus test of the logistics, supply and cold chain, motivation and training of frontline health staff, and their relationships with the communities they serve. While routine system strengthening should remain the principal focus, where a local veterinary programme in a rabies hyper-endemic area perpetually fails to achieve 70% coverage in the dog population, or tardy access to rabies vaccine and/or immunoglobulin post-exposure results in ongoing childhood rabies deaths, health services may need to carefully consider complementing traditional control strategies with pre-exposure vaccination if justified by the local epidemiology of rabies.6 A clear understanding of the epidemiology, however, depends on accurate surveillance. This is a major shortfall currently, with ‘best guesses’ and modelling forming the basis of local and global burden estimates. There is an urgent need to ensure that human rabies cases are notified.7 Misdiagnosis of rabies in humans commonly occurs and laboratory confirmation is constrained by limited availability of laboratories performing rabies diagnostic tests on humans, particularly in Africa, and securing access to post-mortem brain tissue samples.8 Although there are some reassuring examples from rabies–endemic countries that application of an effective One Health approach to canine rabies elimination is possible,9 it is likely that full global application will prove elusive without major innovations in surveillance, diagnosis, and vaccine administration. For increasing the reach of surveillance, notification using cellular phones has shown some promise and should be further explored.10 Simpler diagnostic tools are under development, including direct rapid immunohistochemical tests, which could greatly enhance rapid diagnosis and thus expand the reach of surveillance.11 There is some optimism that new technologies currently under evaluation by WHO, including more thermostable rabies vaccines and monoclonal antibodies, as an alternative to human and equine RIG, could enable cost-effective delivery of post-exposure prophylaxis. Simpler regimens using reduced vaccine volumes and the number of vaccine doses to humans post-exposure and ways of optimizing available RIG usage are under consideration. In addition, microarray patches, which are being trialled for influenza and measles vaccine delivery, may prove to be a thermostable, biodegradable, minimal storage game changer for administering rabies vaccine following high-risk exposures in remote areas.12 The gap between wealthy and poor nations could be no more conspicuous than the differential rabies burden—where the need is greatest ‘most often’ the systems are the weakest.13 Thus, as we commemorate the Anniversary of Louis Pasteur’s death on World Rabies Day (28 September), let us not lose sight of the deep appreciation for the sanctity of children’s lives that exercised Pasteur—‘When I approach a child he inspires in me two sentiments; tenderness for what he is and respect for what he may become’—and strive towards the 2030 target as an investment in global equity. Disclaimer: No disclaimer. Authors’ contributions: DND and LB prepared and approved the final version. DND is the guarantor of the paper. Funding: None. Competing interests: None declared. Ethical approval: Not required.