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Investment in rabies PEP would prevent additional 489K deaths

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November 29, 2018

An investment aimed at expanding access to postexposure prophylaxis for rabies — and providing it for free — would prevent an additional 489,000 deaths globally between 2020 and 2035 and would be an “extremely cost-effective intervention” to substantially reduce the burden of the disease, the results of a modeling study conducted by the WHO Rabies Modelling Consortium showed.

Writing in The Lancet Infectious Diseases, the authors of the study noted that WHO and its partners have developed a plan to reach zero human deaths caused by dog-mediated rabies by 2030. The No. 1 objective of the WHO strategy is to “efficiently prevent and respond [to rabies] through effective use of vaccines, medicines, tools and technologies.”

The purpose of the modeling study was to estimate the impact of an investment in rabies post-exposure prophylaxis (PEP) by Gavi, the Vaccine Alliance, the authors explained. Gavi is currently considering the case for investment in rabies PEP.

“Enhancing access to rabies postexposure prophylaxis was considered by Gavi, the Vaccine Alliance, in their vaccine investment strategy in 2008 and 2013,” the authors wrote. “However, knowledge gaps were recognized, and observational studies were recommended to reduce uncertainties about implementation feasibility.”

The consortium developed epidemiological and economic models to investigate the impact of Gavi’s potential investment in rabies PEP in 46 countries that are currently eligible for investment and 67 countries that have ever been eligible. They compared several scenarios, including sticking with the status quo use of PEP and increasing access with free vaccination via WHO-recommended intradermal vaccination.

In 67 rabies-endemic countries, the researchers predicted more than 1 million deaths will occur between 2020 and 2035 under the status quo. If access to PEP is expanded and offered for free, an additional 489,000 deaths would be prevented between 2020 and 2035, on top of the approximately 56,000 deaths that are already prevented each year, the authors said. Moreover, they estimated that switching to intradermal PEP regimens — which spares doses — would allow for the vaccination of an additional 17.4 million people without needing more vaccine. The investment would save $635 per death averted and $33 per disability-adjusted life-years averted, according to the findings.

By also scaling up dog vaccination programs, dog-mediated rabies could be eliminated by 2035, the researchers estimated. Under this scenario, they said it would still be cost-effective to provide more people access to PEP, especially if unnecessary treatment was curbed.

“Improving access to PEP alongside a switch to the newly recommended intradermal 1-week regimen is feasible because vaccine vial requirements do not increase,” the authors wrote. “Moreover, shifting costs from bite victims to donors and governments overcomes the primary barrier limiting access to lifesaving vaccines and enables more efficient dose-sparing practices. To reduce an indefinite and escalating requirement for postexposure prophylaxis, mass dog vaccination is essential to control and eliminate rabies in the reservoir population.”

The study was accompanied by a comment from Pasteur Institute researchers Simon Cauchemez, PhD, and Hervé Bourhy, PhD, who noted that the WHO plan to eliminate rabies hinges on effective One Health interventions.

“Through the analysis of a wide range of data collected in multiple countries and the use of multilayer mathematical models, the authors show that increased investment in postexposure prophylaxis by Gavi, the Vaccine Alliance, would be extremely cost-effective and could substantially reduce disease burden,” they wrote.

A Gavi spokesperson confirmed to Infectious Disease News that the alliance’s board is currently considering the provision of PEP for rabies. Gavi reviews available and expected vaccines every 5 years to determine suitable candidates for support.

“This is an important paper which includes some of the modelling used in Gavi’s investment case for the vaccine, which is feeding into [vaccine investment strategy] discussions, however, it’s important to note that Gavi’s final estimates reflect a more conservative uptake of rabies postexposure prophylaxis as the analysis took into consideration the pace and timing of other vaccine introductions,” the Gavi spokesperson said. “The full investment case will be made public on the Gavi website in December.” – by Marley Ghizzone

Disclosures: Bourhy reports grants from Santé Publique France during the conduct of the study and non-financial support from Humabs BioMed SA outside of the submitted work. He also reports having a US provisional patent application (62/404,435; Oct 5, 2016) for phtazolinone derivatives used in the treatment and prevention of rabies; patents for antibodies that potentially neutralize rabies virus and other lyssaviruses and uses thereof (PCT/EP2014/003076; Nov 18, 2014); and for antibodies and methods for treatment of lyssavirus infection (PCT/ EP2018/078751; Oct 19, 2018). Cuachemez reports no relevant financial disclosures. Please see the study for all author’s relevant financial disclosures.

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