Mumbai: India’s public hospitals and dispensaries may soon have a safer, more affordable option for preventing rabies after a suspected rabid dog bite: one already in use in private clinics since 2017 and by BMC since 2019. A post-marketing clinical trial involving more than 4,000 participants, conducted and funded by a pharmaceutical company and recently published in The Lancet, could now pave the way for its large-scale public use.
For decades, the life-saving protocol has been the same across public or private health set ups: wash the wound, inject a dose of rabies immunoglobulin if the bite is severe, and follow with multiple doses of anti-rabies vaccine. The possible shift lies in the kind of immunoglobulin used. The relatively new lab-made candidate could replace the animal and human derived versions in use since the 1970s.
An immunoglobulin is a concentrated solution of antibodies, injected directly into and around the bite, that offers immediate but short-term protection against the virus, effectively buying time until the vaccine takes full effect. The earliest ones in use have been derived either from rabies-vaccinated horses (Equine Rabies Immunoglobulin – ERIG) or human donated plasma (Human Rabies Immunoglobulin – HRIG). In 2016, Serum Institute of India (SII) received permission to make immunoglobulin which has monoclonal (lab-made,RmAb) antibodies.
“Most private facilities at least in Mumbai have phased out the use of the horse-derived one. While it has been proven safe at large, there are risks associated; it can cause mild allergic reactions or in rare cases a serious adverse event,” said Dr Trupti Gilada, city-based infectious disease specialist.
The private facilities have moved on to either the human derived or lab-made ones. “Both, human derived one and the lab-made one have high efficacy. The former has risk of infection transmission, though rare. The ones made in labs are safer and more easily available due to ease of large scale production,” said Dr Mandar Kubal, another infectious disease specialist.
A survey by ICMR published in July on the availability of anti-rabies vaccine and rabies immunoglobulin in health facilities found that, of the 534 facilities surveyed across 15 states and 60 districts — 467 in the public sector — 78% still used horse derived immunoglobulin. But even that was out of stock for most apart from a small 20.3% of those surveyed. While BMC uses the lab-made alternative, it is no stranger to shortages; at the moment it is short of rabies vaccine shots.
A senior doctor from one of the four BMC-run medical college hospitals, said, “Mumbai has a heavy burden of dog bite cases and early on BMC decided to move on from animal derived ones due to risks associated. We either use generic human derived immunoglobulin or largely lab-made alternatives.”
But this lab-made alternative is still to make its way into the National Guidelines for Rabies Prophylaxis. The ICMR survey states, “RmAb presents as a promising alternative to both HRIG and ERIG. Compared to ERIG, RmAb offers the potential scope for large-scale production with standardised quality, elimination of animal use in the manufacturing, and reduced risk of adverse events.
“It is cheaper compared to HRIG. Studies have shown that RmAbs are safe for human use, but… [there is] need for larger clinical trials and post-marketing surveillance to assess the safety and efficacy of RmAbs in the Indian setting.”
The Serum Institute–funded post marketing trial of its lab-made product compared with horse-derived immunoglobulin found to be equally effective in preventing rabies, with slightly higher average antibody levels on day 14. It was linked to fewer mild adverse events (11 vs. 17), and no serious reactions related to RmAb were reported, compared with one serious reaction related to ERIG. “Anti-rabies vaccines and immunoglobulins are severely in shortage across the country. Monoclonal antibodies is the answer [due to scalability] and it needs to be included in the national guidelines,” said one of the authors of the ICMR survey.
