Instead, the landmark Indian study by researchers at the Bengaluru-based National Institute of Mental Health and Neuro Sciences (NIMHANS) has found that most such deaths are linked to missed or incorrect steps in post-exposure prophylaxis (PEP) or incomplete vaccination, rather than the vaccine itself failing.
Published in the journal Clinical Infectious Diseases two weeks ago, the study examined 89 laboratory-confirmed rabies deaths among patients who had sought medical care and received at least one dose of rabies vaccine after an animal bite.
Researchers found that only three patients appeared to have developed rabies despite receiving post-exposure prophylaxis correctly. In the remaining cases, investigators identified one or more deviations from the recommended treatment protocol that likely reduced protection.
The findings come at a time when India continues to bear the world’s highest rabies burden.
According to estimates published in 2024 by the Indian Council of Medical Research – National Institute of Epidemiology (ICMR-NIE), around 9.1 million animal bites occur in India every year, more than three-fourths of them caused by dogs, resulting in an estimated 5,726 human rabies deaths annually.
BEYOND THE VACCINE
Dr Reeta S Mani, Head of Neurovirology at NIMHANS and the study’s lead author, said the research was prompted by growing public anxiety over reports of rabies deaths despite vaccination.
“Every time such a case is reported, people – including medical professionals – ask whether the vaccine has failed or whether there is a problem with its quality. That was precisely why we undertook this study,” she told India Today.
The researchers retrospectively reviewed medical records of patients who had developed laboratory-confirmed rabies and later died. They deliberately included only those patients who had sought medical attention and received at least one dose of anti-rabies vaccine, in order to understand why protection had failed.
Their analysis showed that the overwhelming majority of deaths were not due to vaccine failure but because one or more essential components of post-exposure prophylaxis were either missed, delayed or administered incorrectly.
Rabies post-exposure prophylaxis is much more than taking a vaccine. It includes immediate and thorough wound washing, administration of anti-rabies vaccines according to the prescribed schedule and, for severe Category III bites, infiltration of rabies immunoglobulin (RIG) directly into and around the wound.
Each of these steps is critical because they work at different stages of infection.
CRITICAL MISSED STEPS
Among the most common lapses identified by researchers was inadequate wound washing – a step that is often overlooked by both patients and healthcare providers.
“The virus is present in the saliva of a rabid animal and gets deposited at the bite site. Simply washing the wound under running water for 10 to 15 minutes mechanically flushes out much of the virus and can reduce the risk of rabies by 50 to 70 per cent,” Dr Mani said.
She noted that many people rush immediately to hospitals after a bite, while many healthcare facilities do not routinely prioritise wound cleansing before administering vaccines.
The study also documented several other preventable deviations.
Rabies wounds, especially severe ones, should generally not be sutured immediately because stitching can traumatise tissues, expose nerve endings and potentially facilitate viral entry into peripheral nerves. Tight bandaging should also be avoided since wounds need to drain naturally.
Errors were also seen in vaccine administration. Rabies vaccines should never be injected into the buttocks because the higher fat content delays absorption and slows the immune response. If administered at that site, the vaccination schedule has to be restarted.
Researchers also found confusion between the intradermal and intramuscular vaccination regimens. While both are equally effective, the dosage and schedules differ, and mistakes in administration can compromise protection.
Another major deviation involved rabies immunoglobulin. In patients with severe Category III bites, RIG must be infiltrated into and around the wound to neutralise the virus before it enters the nerves.
However, investigators found instances where it was simply administered as an intramuscular injection elsewhere in the body, a practice that offers little protection against infection at the bite site.
“These are not true breakthrough infections,” Dr Mani said. “Most represent failures in how post-exposure prophylaxis was delivered rather than failure of the vaccine.”
RARE TRUE FAILURES
Of the 89 deaths analysed, only three appeared to represent genuine post-exposure prophylaxis failures.
According to Dr Mani, such cases are extremely uncommon and usually involve exceptionally severe bites.
“When bites are very deep, multiple or located over highly nerve-rich areas such as the face, head or neck – particularly in children – the virus may enter the nerves before vaccines or immunoglobulin can neutralise it,” she explained.
Rabies virus travels almost exclusively through peripheral nerves to reach the brain rather than through the bloodstream. Once it enters the nerve tissue, neither vaccines nor immunoglobulin can eliminate it.
These rare biological failures differ fundamentally from the far more common failures caused by incomplete or incorrect treatment.
The researchers stressed that their findings should reassure the public that properly administered post-exposure prophylaxis remains highly effective.
‘QUALITY NOT THE PROBLEM’
The study did not directly assess vaccine quality or cold-chain maintenance because it was retrospective. However, Dr Mani said available evidence suggests these are unlikely to be the primary reasons behind most reported failures.
She cited investigations carried out during a rise in rabies deaths in Kerala a few years ago, where vaccine batches were independently tested for potency and found to meet quality standards. Antibody testing among recipients of the same vaccine batches also showed strong immune responses, indicating that the vaccines were functioning effectively.
“For every one person who develops rabies despite vaccination, there are thousands whose lives are saved by the very same vaccine,” she said.
While isolated issues related to storage or cold chain cannot be ruled out, she said they do not explain the majority of reported cases.
CASE FOR PRE-EXPOSURE VACCINATION
The study also highlights an under-recognised preventive option – pre-exposure rabies vaccination.
Unlike post-exposure prophylaxis, which begins after an animal bite, pre-exposure vaccination consists of three doses given before any exposure.
Dr Mani said awareness about this option remains low, even among many parents.
“If someone has already received a pre-exposure vaccination, then after a future dog bite they need only two booster doses and do not require rabies immunoglobulin, which is both the most painful and the costliest part of treatment,” she said.
She pointed out that the vaccine is among the more affordable optional vaccines available in India and is considered safe because it is an inactivated vaccine.
Although it is not part of India’s Universal Immunisation Programme or routinely recommended for the general population under national guidelines, the Indian Academy of Paediatrics (IAP) considers it an optional vaccine. Experts also believe it may be particularly useful for children living in remote areas where immediate access to healthcare following animal bites may be difficult.
Dr Mani acknowledged that introducing pre-exposure vaccination universally would impose a substantial financial burden, but said greater awareness could help families who are able to opt for it privately.
She added that awareness campaigns led by NIMHANS and other organisations, particularly around World Rabies Day, already encourage families and schools to understand the importance of both prevention and prompt treatment.
For researchers, however, the central message from the study remains clear.
“The rare reports of rabies after vaccination should not undermine public confidence in anti-rabies vaccines. Instead, they should reinforce the need to ensure that every component of post-exposure prophylaxis – immediate wound washing, correct vaccination in four or five recommended doses and appropriate use of rabies immunoglobulin where indicated – is carried out exactly as suggested,” Dr Mani emphasised.
– Ends
