N. Gopal Raj

New research in the journalSciencecalls for a change in the immunisation strategy for polio eradication in India.

HIGH POPULATION density and poor sanitation, the very factors that help the poliovirus spread, are also responsible for greatly diminishing the efficacy of oral vaccine in Uttar Pradesh where the disease continues to be firmly entrenched, according to research being published this week in the journal Science.

India is one of only a handful of countries where polio is still endemic. But even in India, the polio eradication programme launched in December 1995 has had notable success. Before the programme began, an estimated 35,000 children were being paralysed by polio each year. Last year saw an all-time low of just 66 polio cases nationwide and by the end of the year the virus was circulating in only a few districts in western Uttar Pradesh and Bihar. This year, instead of the virus being eradicated, there has been an upsurge with over 520 polio cases reported so far, more than 80 per cent of them in Uttar Pradesh.

By the end of last year, children less than five years old in Uttar Pradesh and Bihar were reported to have received on average 15 doses of oral polio vaccine and only four per cent of the children (mostly babies less than six months old) had received less than three doses. Even under conditions highly favourable for transmission of the poliovirus, that level of vaccine coverage ought to have stopped children from becoming infected, pointed out researchers in their Science paper. The authors are Nicholas Grassly and Christophe Fraser of the Imperial College, London; Jay Wenger of the National Polio Surveillance Project in Delhi; Jagdish Deshpande of the Enterovirus Research Centre in Mumbai; and Ronald Sutter, David Heymann, and Bruce Aylward of the WHO's Global Polio Eradication Initiative.

Analysis showed that the districts in the country with a high density of children and where diarrhoea was prevalent and with low use of oral vaccine in routine infant immunisation were more likely to report polio cases during 2000 to 2005, according to the paper. The districts with these characteristics that supported persistent poliovirus transmission are located mainly in Uttar Pradesh and Bihar.

The oral vaccine used in India has been of the "trivalent" kind that seeks to create immunity against all three strains of the poliovirus. The researchers discovered, however, that this trivalent vaccine provided a protective efficacy per dose against the type 1 poliovirus, the most widely prevalent strain, of just 9 per cent in Uttar Pradesh, compared to 18 per cent in Bihar, 21 per cent in the rest of India, and about 65 per cent in industrialised nations.

In Uttar Pradesh, it appears that high population density and bad sanitation allowed other viral infections and diarrhoea to spread, which then interfered with the action of the oral polio vaccine, thereby lowering its efficacy, explained Dr. Grassly in an email.

Monovalent vaccine

In their paper, the scientists have argued for the "careful use" of `monovalent' oral vaccines that target only a single strain. The type 2 virus has been eradicated globally and separate monovalent oral polio vaccines are needed to eradicate the type 1 and type 3 strains.

Preliminary analyses showed that in Uttar Pradesh the monovalent oral vaccine was about three times more efficacious than the trivalent vaccine against the type 1 poliovirus, said Dr. Grassly. Increasing the vaccine's efficacy two-fold would be equivalent to almost doubling the average number of oral vaccine doses received by children in Uttar Pradesh and Bihar, according to the paper.

The use of monovalent oral vaccine type 1 began last year itself in high-risk districts of Uttar Pradesh and Bihar, and in Mumbai-Thane. As a result, transmission of the wild virus was interrupted in Mumbai, reduced by two-thirds in Bihar, and by 80 per cent in western Uttar Pradesh, observed Dr. Aylward, Coordinator of the Global Polio Eradication Initiative at WHO Headquarters in Geneva, in a journal paper published earlier this year. Monovalent oral vaccine type 3 was administered in western Uttar Pradesh last December, the very first time that this vaccine had been used in the global eradication programme, he added.

"The unfortunate increase in cases in 2006 appears to be explained by a drop in the number of children vaccinated in western Uttar Pradesh. However, across Uttar Pradesh, as the distribution of monovalent vaccine had proceeded, the fraction of children protected has shown dramatic improvements," said Dr. Grassly in his email.

If monovalent oral polio vaccine had not been introduced when it was, India would have had a worse epidemic this year, pointed Dr. Aylward in an email. "It has limited the epidemic and set the stage for eradication [but] like any vaccine it can only work, however, if you get it into all children."

The information that the trivalent oral polio vaccine was not efficacious enough had been known for the last three decades, observed T. Jacob John, formerly of the Christian Medical College at Vellore and a veteran of the Indian polio eradication effort. He had published papers in the mid-1970s showing that even when children in India were given three doses of the oral polio vaccine, their immune response was less than what would be expected from a single dose given to a child in the United States, he told The Hindu.

The Union Government had chosen the oral vaccine for the polio eradication programme for three reasons, said Dr. Jacob John. One was that just three doses of the oral vaccine would protect a child from polio. The second was that the live but weakened viral strain used in the oral vaccine would spread to other children who had not been immunised and protect them too. Lastly, it was said the oral vaccine would induce strong immunity in the intestines and protect children from becoming infected.

"What this paper shows is what I have been saying for 30 years that none of this is true," said Dr. Jacob John. Even with monovalent oral vaccines, it would be necessary to get five doses of the vaccine against type 1 virus and five doses of the vaccine against type 3 into every infant, he believed.

This would not be easy as routine immunisation of infants was totally neglected in Uttar Pradesh and mass immunisation campaigns generally caught older children.

Dr. Jacob John argues that it is necessary to introduce injectible polio vaccines while continuing to give oral vaccines. Just two doses of the injectible vaccine given to a baby at eight weeks and 16 weeks of age would provide 99 per cent protection against polio, he said. The India Expert Advisory Group, the official body in the country that monitors progress towards polio eradication and provides technical advice, at its meeting in July this year recommended that two rounds of injectible polio vaccines be administered to children in Moradabad and J.P. Nagar districts of Uttar Pradesh.

"A polio-free India will unlock the door to a polio-free world," wrote Dr. Heymann, Representative for Polio Eradication at WHO Headquarters, in a journal editorial last December. "If the job can be finished in India where the transmission of poliovirus is so efficient, there is a sense that it can also be finished in all other remaining polio-affected areas in the world."