PUBLIC HEALTH

Polio: The last frontier?

R. RAMACHANDRAN

The resurgence of polio in 2002 and its spread to zero prevalence areas in 2003 has revived the long-standing debate on the choice of appropriate vaccine for its eradication.

AFTER the severe setback to the national polio eradication programme last year, which prompted the Director-General of the World Health Organisation (WHO), Dr. Gro Harlem Brundtland, to pronounce India as "No.1 Priority Country" in the global polio eradication effort, there may be some cheer as 2003 comes to a close. The total number of virologically confirmed cases of poliomyelitis as of November 29 was 194, the lowest ever recorded. Health authorities and medical experts believe that now is the time for the "last push" to break the transmission of the disease and achieve eradication.

KAMAL KISHORE/ REUTERS

During the pulse polio campaign, in New Delhi.

Prior to 2002, the number of polio cases had declined from 1,934 in 1998, to 1,126 in 1999, 265 in 2000 and 268 in 2001. Indeed, even at that time health authorities had declared that the time for the final assault on polio had arrived. But in a dramatic reversal of this trend, 2002 witnessed a sharp increase in the number of cases to 1,600. This figure accounted for over 83 per cent of worldwide incidence of 1,919 cases. Uttar Pradesh (U.P.) alone (with 1,242 cases) was responsible for 65 per cent. Given the prevalence of the disease, the target year for global eradication, originally set as 2000, was pushed to 2005. India is one of the seven countries where the infection persists; the others being Afghanistan, Egypt, Niger, Nigeria, Pakistan and Somalia. In fact, some experts even commented in 2002 that India could well be the last country to achieve eradication.

In the 2002 upsurge, it was also established that wild poliovirus Type 1 - the predominant causative wild virus - accounted for nearly 95 per cent of the cases in the country. This was an indication of a disease outbreak. More important, cases were recorded in six States that had zero incidence in 2001. The outbreak also re-established transmission in States such as Gujarat and West Bengal that were on the verge of achieving zero transmission. U.P. and Bihar, where prevalence rate and endemicity had been traditionally high, were again the main cause for the spread of polio within the States and to previously polio-free regions through importation of the virus through migration of carriers. Indeed, the cause of the first case in 10 years in Lebanon, discovered in January, was genetically determined to be an Indian strain of the virus.

The main reason for the resurgence in 2002 seems to be inadequate coverage of routine immunisation under the Universal Immunisation Programme (UIP) as well as laxity in the door-to-door Pulse Polio Immunisation (PPI) campaigns. As the incidence fell and remained constant during 2000 and 2001, the entire eradication programme might have been affected by some complacency. The transfer of responsibility for the UIP from the Centre to the States and the latter's shortage of funds and workforce also seemed to be a contributing factor. Pulse immunisation, a phrase coined in 1981 by Dr. T. Jacob John, the well-known virologist (formerly of the Christian Medical College hospital, Vellore), refers to discontinuous but repetitive vaccination to interrupt the transmission once routine immunisation ensured that all children had a base level of protection against infection. But it is generally acknowledged that owing to various factors the routine immunisation programme has suffered at the cost of the PPIs.

According to an analysis of the 2002 outbreak by Dr. Jacob John and associates, given that the disease occurs only in about 0.5 per cent of the infected children, the number of cases in Gujarat and West Bengal indicated that the circulation of the virus was quite large. Genetic investigations have shown that in both Gujarat and West Bengal the wild virus type was introduced from U.P. or Bihar that established local transmission. The virus type in Delhi too was an importation from U.P. Indeed, even in 2001, the virus type in the remaining nine States have been shown to belong to the type that circulates in U.P. and Bihar. "The setback in 2002," Dr. Jacob John's team points out, "can be pinpointed to inadequate (routine and pulse mode) immunisation in U.P. and Bihar not only in 2002 but also in the preceding years."

Jonas Salk.

Unsatisfactory routine immunisation (through the UIP) is evident from the fact that the two States have seen an increase in the incidence of whooping cough and diphtheria in recent years. The reported coverage in PPI too seems to have been false as cross-checking of records revealed that 10-15 per cent of houses marked `immunised' were not immunised at all. Also, according to the scientists, the already inadequate PPI coverage in U.P. and Bihar in 2001 further deteriorated the following year. Moreover, in 2002, 61 per cent of the polio-affected children in U.P. belonged to the Muslim community, suggesting that the immunisation coverage of the minority community was worse. According to Dr. Shoban Sarkar, Deputy Director of Child Health, the Union Ministry of Health and Family Welfare, there was misinformation among Muslims that polio vaccine caused impotency. Also, according to Dr. Jacob John, the neglect of other routine vaccines, particularly measles as compared to PPI campaigns, made the Muslim community suspect the safety of the polio vaccine as well as the real purpose behind the PPI drives.

Besides the lowest ever incidence of the disease, the spatial and temporal spread of cases in 2003 is, however, qualitatively different from that in 2002, points out Dr. Shoban Sarkar. According to him, by the end of the year, at best the number of cases would go up by 10-12 because, unlike 2002, the spread has been mostly to areas which are not traditionally endemic. And this is what gives the authorities the hope that the spread can be arrested and virus transmission effectively broken before end-2004 by aggressive and intensive PPI campaigns as well as by ensuring adequate coverage in routine immunisation.

While U.P. did have episodes of high transmission throughout the year and transmission is still active in the State, the total transmission is the lowest ever achieved. Similar is the case with Bihar. This is possible because of better coverage in the region and the sensitisation of communities that were apprehensive about pulse polio campaigns, says Dr. Sarkar. Unlike the spill over earlier from U.P.-Bihar across the borders into the neighbouring States, the resurgence this year has a different characteristic. For instance, in West Bengal, it has moved down from the north to the south Bengal - there is an extensive spread to 11 districts from Murshidabad.

Also significantly, in Karnataka and western Andhra Pradesh, the cases are not in the traditionally endemic areas. They are also not due to importation of the virus from outside. "These cases are in certain pockets where there is an accumulation of unprotected children over a period," points out Dr. Sarkar. "This is evidence to the fact that the routine immunisation programme did not have the optimal effect and these areas were not properly covered in the pulse campaigns as well. What has emerged is that we cannot miss out any area and there is a need now to reach every child in the country during next year's pulse rounds," he adds.

Albert Sabin.

According to Dr. Sarkar, two features of the current situation suggest that we now have an opportunity to achieve zero transmission - the significant cut in transmission in traditional areas and the temporal profile of incidence in the various States. A polio year starts in March, peaks in September-October and goes down by February. A large fraction of the cases (67) are in the earlier part of 2003, suggesting that they are spill over from last year's outbreak. This implies that, after taking into account this and Karnataka's 31 and Andhra Pradesh's 18 (caused by gaps in immunisation in non-traditional areas), only 78 cases are owing to spread during the current polio year.

"So there is an opportunity to clean up and we need to seize this. If we miss this it will be difficult even though it would mean an overload on the system," says Dr. Sarkar. Besides routine immunisation, there were six pulse rounds in 2003 - four sub-national pulse rounds in the 10 high-risk States and two national rounds or national immunisation days (NIDs). The recommended strategy for 2004 to break the transmission is five NIDs in January, February, April, September and October and, based on the epidemiological scenario, one sub-national round in the month of May in areas where transmission seems to be active.

THE resurgence of the disease in 2002, and its spread to zero prevalence areas in 2003, has revived the long-standing debate among medical scientists and policymakers on the choice of appropriate vaccine for the eradication of the disease. There are two kinds of vaccines: 1. oral polio vaccine (OPV), discovered by Albert Sabin in 1960, that uses live-attenuated (weakened) virus and the inactivated (killed); 2. injectable polio vaccine (IPV), discovered by Jonas Salk in the 1950s. Both confer immunity against infection through multiple doses, generally three. For mass vaccination, OPV is the preferred vaccine in India, as it has been in most countries of the world. This is the vaccine recommended by the WHO as well.

There are pros and cons for both the vaccines. From the perspective of a developing country like India, the main factors have been the cost and mode of delivery. OPV is cheaper than IPV. It costs Rs.3 a dose, which works out to Rs.15 a child for the recommended five-dose course in routine immunisation. (In pulse modes, the number of doses could go up to about 10.) IPV costs $10 a dose, which works out to about Rs.1,500 a child. In India, about 25 million babies are born every year, which, for the recommended dose regimen, would imply a huge consumption and expenditure for mass immunisation programmes. Also, delivery of OPV, which is administered as drops, is easy and safe as against IPV, which can lead to various other infections because of unsafe injection practices. According to the Health Ministry, 30-50 per cent of injections given in India are unsafe.

Another important factor in favour of OPV is the `mucosal immunity' that it confers. That is, mucosal surfaces like the gastrointestinal tract and pharynx develop immunity against infection when exposed to wild virus. IPV does not confer mucosal immunity. So an individual can get infected with the wild virus if exposed to it and become a carrier of this disease-producing virus and transmit it.

INFOGRAPHICS: V.S. WASSON

Being a live (but attenuated) vaccine, the oral vaccine virus can replicate in the host's gut; the viral particles are shed in the stool, which get into the environment. Being a killed vaccine, IPV does not result in the shedding of virus. Because of this, OPV is believed to lead to `herd immunity' or protection to the community or close contacts of the vaccinated as unvaccinated individuals also get exposed to the vaccine virus through the faeco-oral route. IPV, on the other hand, confers immunity only to the vaccinated individual and, therefore, requires 100 per cent coverage. However, in recent years it has been argued that the herd immunity conferred by OPV is low.

The flip side to the replication of the live oral vaccine virus in the gut is what is known as vaccine associated paralytic polio (VAPP). Repeated passage of the vaccine virus through the host is known to result in a mutant form of the virus. This back-mutated virus can become neuro-virulent and cause acute flaccid paralysis (AFP) of the limbs, the predominant manifestation of polio infection, to the vaccinated children. Vaccine virus transmission is normally very low and its infectivity dies out quickly. According to WHO's Technical Consultative Group, the risk of VAPP is one per million births. In the Indian context, this would amount to 25 probable cases and the global burden would be about 120 cases. (According to the United States Centre for Disease Control (CDC), the risk in terms of doses is one in 2.4 million.) The rationale of using OPV is that this is an acceptable risk as weighed against its obvious advantages.

However, those in favour of IPV would find even a low risk burden ethically unacceptable especially when there is a safer vaccine available that does not lead to VAPP. Indeed, it is this - with mounting suits in U.S. courts against the use of OPV - that led to the U.S. switching over to IPV in a sequential regimen in 1997 and completely in 1999. But, according to scientists, WHO has underestimated OPV's negative aspects and overestimated its positive aspects. Citing the 181 VAPP cases in India in 1999, the only year when the National Polio Surveillance Project (NPSP) carried out genetic analysis (known as Intra Typic Differentiation) of virus isolates from AFP cases, Dr. Jacob John says that the risk constitutes an unacceptably high burden, morally and ethically.

But vaccine-virus can also acquire efficient transmissibility. When this happens - that is, both neurovirulence and transmissibility are acquired by the vaccine-virus - then it is virtually wild-like and is called circulating Vaccine-Derived Polio Virus (cVDPV). Four instances of cVDPV causing small or large outbreaks of typical polio have so far been established around the world. A strain of cVDPV circulated in Egypt between 1988 and 1993 and caused 30 cases of polio. During 2000-2001, a number of AFP cases occurred in the island of Hispaniola in the Caribbean. The two nations in Hispaniola - Haiti and Dominican Republic - had eradicated the disease 10 years ago but cVDPV, which seems to have been circulating for two years, caused 22 cases. Similarly, certain strains of cVDPV are known to have caused a cluster of three cases in the Philippines in 2001 and a cluster of four cases in Madagascar in 2002.

A.M. FARUQUI

Children from the slums of Bhopal take out a rally as part of the pulse polio campaign.

While these facts indicate the inherent risk of OPV, as long as immunity levels in the population are maintained at high levels through high coverage, the risk of infection by vaccine-derived neuro-virulent mutants will remain low. However, once the coverage drops, cVDPV transmission may increase. In India, since the minimum coverage with OPV is as high as 80 per cent, no cVDPV strain has so far been seen in circulation, according to Dr. Sarkar.

Practically all developed countries have switched to IPV because of the unacceptable burden of VAPP incidence. Scientists have been arguing for years for the introduction of IPV in a phased manner in the Indian programme. "The ethical imperative of distributive justice demands introduction of IPV," says Dr. Jacob John. In fact, he believes that if the country had prepared itself for IPV in terms of production capacity and necessary infrastructure and had also evolved a strategy for its introduction in a planned manner 10 years ago, polio would have been eradicated. The proponents of IPV believe that if the right policy initiatives had been taken, even the prices would have come down, as in the case of the recombinant Hepatitis-B vaccine.

In fact, under an Indo-French agreement the French government-owned Institut Pasteur Merieux was to transfer technology for IPV and even a company had been formed complete with buildings, and so on. However, with the privatisation of the company and its takeover by a Canadian firm, the agreement was never honoured. Also, the government wanted to continue with OPV for the eradication programme. So steps to produce IPV in the country never really took off and Dr. Jacob John and others have been quite critical of the government on this count.

Now, with India on the apparent threshold of achieving zero transmission, the crucial question is whether IPV should be introduced at this stage. Years ago, WHO's stand was to stop OPV once zero transmission is achieved. Clearly, the incidence of VAPP and cVDPV emphasises the need to immunise even after achieving zero transmission with OPV. "Stopping OPV without IPV cover will be suicidal," says Dr. Jacob John. "In fact, eradication should be redefined to mean zero transmission of wild virus and zero instances of VAPP and cVDPV. Only then can all vaccination be stopped," he says.

INFOGRAPHICS: V.S. WASSON

But should India introduce IPV concurrently with OPV now? "No," says Dr. Jacob John. "We are winning a war with a certain ammunition. Shifting over to a different ammunition is not wise and can upset the entire eradication drive." According to him, the country should be ready to introduce IPV by about 2009 after sustaining zero transmission for three years and be certified as polio-free by WHO. He believes that the correct strategy is to withdraw OPV completely three years after the introduction of IPV. "For that we should begin planning from now. As for the basic raw material, the bulk Sabin vaccine itself can be used for inactivation and IPV production. Before that, the government should encourage manufacturers and ensure market for IPV," he says.

There are only a few IPV manufacturers in the West and, at present, the price is high because demand far outstrips supply, says Dr. N. K. Ganguly, Director-General of the Indian Council of Medical Research (ICMR). "In principle the decision to introduce IPV after achieving zero transmission with OPV is there. The experts group is still discussing when exactly. First we need to set a target date for zero transmission," he says. According to him, the technology for IPV is not difficult because it is not a live virus and its introduction will not be difficult.

Thus, it is no longer a question of whether or not IPV, but when. The draft of the Strategic Plan for 2004-2008 in the Global Initiative for Polio Eradication spearheaded by WHO, CDC, United Nations Children's Fund (UNICEF) and Rotary International has called for increased IPV to meet global demand, particularly from the developing countries. That there is tacit approval for IPV from the Indian government too is evident from the authority granted to a private manufacturer to conduct limited trials with IPV. Animal and toxicological studies apparently have already been completed. Based on the successful completion of these trials, production licence for indigenous production is likely to be given.

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