Despite oral polio vaccine causing vaccine-derived poliovirus (VDPV) and vaccine-associated paralytic poliomyelitis (VAPP) cases, India did not switch over from OPV to inactivated polio vaccine (IPV). While circulating VDPV strains are tracked, and outbreaks and cases recorded, little is known about VAPP cases. The justification that VAPP cases are “sporadic and pose little or no threat to others” so can be ignored is ethically flawed.
With polio caused by wild polio virus strains reduced by 99.9% since 1988, the world is quite close to eradicating polio from the face of the Earth. Unfortunately, more children are today affected by live, weakened virus contained in oral polio vaccine (OPV) that is meant to protect them. The weakened virus in the vaccine can circulate in the environment, occasionally turn neurovirulent and attack the central nervous system in unprotected children causing vaccine-derived poliovirus (VDPV). While the wild type virus caused 22 and 25 polio cases in 2017 and 2018 (as on October 30, 2018) respectively in just two countries (Pakistan and Afghanistan), VDPV was responsible for 96 and 75 polio cases in more countries during the same period. “Paradoxically, vaccination [using OPV] has become the main source of polio paralysis in the world,” notes an August 2018 paper in The Lancet.
VDVP counted but VAPP cases ignored
While circulating VDPV strains are tracked, and outbreaks and cases recorded and shared faithfully, little is known about the vaccine-associated paralytic poliomyelitis (VAPP) cases, particularly in India. VAPP occurs when the virus turns virulent within the body of the recently vaccinated child and causes polio. The frequency of VAPP cases varies from country to country. With high-income countries switching to inactivated polio vaccine (IPV) that uses dead virus to immunise children, VAPP burden is concentrated in low-income countries which continued to use the OPV.
In spite of the World Health Organisation asking all countries using the OPV to include a “continuous and effective system of surveillance” to monitor the frequency of VAPP way back in 1982, India did not comply. Data on VAPP became available only years after active polio surveillance was initiated in 1997, say Dr. Jacob John and Dhanya Dharmapalan in a paper published on September 21 in the Indian Journal of Medical Ethics.
Ironically, even after initiating the active polio surveillance in 1997, India did not count VAPP cases. “We don’t measure VAPP cases in India as it does not add value to the polio elimination programme,” said Dr. Pradeep Haldar, Deputy Commissioner — Immunisation, Ministry of Health and Family Welfare, Government of India. “VAPP is not diagnosed in labs; we must make special efforts to identify VAPP cases.”
The justification that VAPP cases are “sporadic and pose little or no threat to others” so can be ignored is ethically flawed. The stand that VAPP cases are epidemiologically irrelevant is ethically problematic, note Dr. John and Vipin M Vashihtha in a 2012 perspective piece in the Indian Pediatrics.
VAPP cases in 1999-2001
While many member countries autonomously chose the IPV over the OPV mainly to avoid any risk of VAPP, the only way to avoid VAPP cases in India is to wait for the government to completely stop using the OPV to immunise children. “India ignored the problem of VAPP until their numbers were counted,” writes Dr. John, a virologist and formerly with the Christian Medical College (CMC), Vellore and a polio expert. A paper and a letter published in 2002 in the Bulletin of the World Health Organisation said the number of VAPP cases in India in 1999, 2000 and 2001 were 181, 129 and 109 respectively.
According to WHO’s estimation in 2002, the annual global burden of VAPP was estimated to be just 120 cases on the basis of one VAPP case per million initial doses of the OPV administered. This would have meant that India had merely 25 VAPP cases per year, while the observed number was 181 cases in 1999. “This indicates that the actual risk is seven times the expected number… It is reasonable to assume that there would be 400-800 annual cases of VAPP globally,” Dr. John wrote in a 2002 letter in the Bulletin of the World Health Organisation. And that would have meant there were 100-200 VAPP cases in India each year. The global estimated incidence of VAPP was thereafter revised to 200-400 cases.
Continued usage of OPV
Despite knowing the higher burden of polio (both VAPP and VDVP) caused by oral vaccines, India continued to use the OPV. “The decision to use only the OPV was faulty. The risk of the OPV is on two fronts. Yet, parents were denied to choose the best vaccine and were obliged to accept the OPV and face the consequences of VAPP as well as VDVP,” Dr. John said.
“India’s goal was to eradicate polio and the OPV was crucial for that. The IPV produces humoral immunity [involving antibodies in body fluids] so the immunised child does not get paralysis but it can’t stop the circulation of wild polio viruses,” said Dr. Haldar. “For instance, no polio cases were seen in Israel but wild polio viruses were detected in the environment. The viruses will continue to circulate in the community.”
“The primary objective of polio vaccination is to prevent the disease, which the OPV failed to fully achieve. The OPV was used for eradicating purposes but without fully protecting the children,” Dr. John said disagreeing with Dr. Haldar. “When you give vaccine you must ensure that the child doesn’t get polio. That only the IPV can do. A child has to be given several doses of the OPV and still it doesn’t fully protect. There was no reason for not using both the IPV and the OPV.”
Of course, it was easier to administer the OPV than the IPV and this becomes particularly important considering the challenges in covering nearly every child across India. Also, the cost per dose of the OPV was lower than the IPV but the OPV fared poorly on two important counts — safety and efficacy. “Yes, administering the OPV was easier than the IPV but no cost-benefit analysis was ever done before choosing the OPV,” said Dr. John. “Three doses protected only two-thirds of Indian children and many developed polio before they turned one year. So we had to give more doses per child.”
Since 1984, the new-generation the IPV made without thimerosal, a mercury-containing preservative, was 100% efficacious. And the cost of production was substantially lower than the old IPV. Since fewer doses of IPV would have fully protected children unlike the OPV, the cost for protecting a child would have been lesser with the IPV.
So while the high-income countries preferred the IPV, India and other low-income countries continued to rely on the OPV. India licensed the IPV only in 2006 but still did not switch to the IPV.
While high-income countries preferred the IPV, India and other low-income countries continued to rely on the OPV. India licensed IPV only in 2006 but still did not introduce it in routine immunisation.
“The reason for not switching over to the IPV is because global production was far less to meet India’s demand. India is the largest cohort and needs 48 million doses per year to immunise all children,” Dr. Haldar said. This excuse is at best lame. As Dr. Pushpa Bhargava noted in his June 2008 article in The Hindu, a decision to manufacture tbe IPV in India was taken in 1988 and a company was eventually set up with technology transfer from France. “Indigenous production of the IPV before 1991 shall be aimed at… As new IPV programme ramps up, the OPV will ramp down,” the minutes of the meeting reads. But the project was eventually shelved heeding to WHO’s advice that developing countries continue to use the OPV, says Dr. Bhargava.
The road ahead
The IPV is essential for post wild-type polio virus eradication to get rid of VDPV and VAPP. The globally synchronised switch from trivalent (which contains type-1, type-2 and type-3 strains) to bivalent (type-1 and type-3 strains) OPV in mid 2016 has been accompanied by a single dose of IPV given prior to administering the OPV. “A single dose of IPV given before the OPV totally prevents VAPP cases,” Dr. John said. A single dose of IPV primes the immune system and the antibodies against polio virus are seen in more than 90% of immunised infants, notes the paper in The Lancet.
Ironically, with no surveillance in place to monitor VAPP cases in India, there is no way of knowing if the use of a single dose of the IPV followed by immunisation using the bivalent OPV has led to a reduction in the number of VAPP cases.