This article is a response to ‘The case for the oral polio vaccine in the world’s quest for eradication’, July 21, 2023, by Vipin M. Vashishtha and Puneet Kumar.
In 2022, after more than a decade of remaining polio-free, the U.S., the U.K, Israel and Canada reported type 2 vaccine-derived poliovirus in environmental samples. The U.S. (Rockland County in New York) also reported one case of polio in a young adult caused by type 2 vaccine-derived poliovirus (VDPV) in July 2022.
What caused the type 2 VDPV case to emerge in the U.S.?
Vaccine coverage
Vaccine coverage with three routine doses of inactivated polio vaccine (IPV) in the U.S. was 92% in 2021. However, vaccine coverage in Rockland County in New York, where the young adult was infected by poliovirus and developed flaccid lower limb weakness, was very low — 60.3% in August 2022, and the zip code-specific coverage was as low as 37.3% — according to an August 2022 report in the Morbidity and Mortality Weekly Report (MMWR). Most importantly, the young adult who got polio was unvaccinated.
In March 2022, a three-year-old child in Jerusalem city, Israel developed polio due to type 3 VDPV. Like the young adult in New York, the child in Jerusalem city was not vaccinated. The type 3 VDPV virus was detected in six more children who were asymptomatic. “Of these seven children, one had incomplete polio immunisation while the other six were unvaccinated,” says a WHO report.
No matter the polio status of a country and which vaccine is being used, as long as wild poliovirus is present and any country continues to use the oral polio vaccine (OPV), the risk of polio emergence, including in polio-free countries, is real in a globalised village especially when vaccine coverage is low. While increasing vaccination coverage nationally and at a community level will help prevent children from getting polio disease, complete eradication from the world will become possible only when wild polioviruses are wiped out and the use of OPV is stopped.
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Type 2 poliovirus has been responsible for over 95% of VDPV cases, and since 1999, when wild poliovirus type 2 was eradicated, all polio cases caused by type 2 virus have been either due to VDPV or vaccine-associated paralytic poliomyelitis (VAPP). Since the global switch from trivalent (containing types 1, 2, and 3) to bivalent (containing types 1 and 3) OPV in 2016, no child in India has been vaccine-protected with OPV against type 2 virus. All the protection has come only from IPV, which contains types 1, 2 and 3. Yet not a single type 2 VDPV case in India has been reported since 2016. This further demonstrates why India can safely switch to exclusive-IPV immunisation at the earliest.
Since wild and VDPV cases are still reported in Pakistan and Afghanistan, the compulsion to maintain a very high polio vaccine coverage in India cannot be overemphasised. Also, India has remained polio-free since January 2011 even as wild poliovirus and VDPV cases have been reported in Pakistan and Afghanistan, thanks to high polio vaccine coverage here. Any individual travelling to India from a polio-endemic country is required to get immunised with a dose of OPV prior to travel, to reduce the risk of spreading the virus here.
The need to maintain high polio vaccine coverage in India arises even without considering the risk of imported cases, as continued use of bivalent OPV in India carries the risk of type 1 and type 3 VDPV and VAPP cases emerging. VDPV cases can emerge only when enough people are not vaccinated against polio.
Decreasing VAPP incidence
Despite wild type 2 poliovirus being non-existent and not used in oral vaccines, type 2 VDPV has caused many cases each year even after the global switch to bivalent OPV in 2016. Nearly 40% of vaccine-associated paralytic poliomyelitis (VAPP) are caused by type 2 oral polio vaccine. Almost all VDPV and VAPP cases have been reported in the last two decades are from countries that continue using oral polio vaccine. In contrast, countries that switched to inactivated polio vaccine have remained polio-free (both VDPV and VAPP), except in 2022.
Many developed countries discontinued OPV use and switched over to IPV a few decades ago. The U.S., for example, moved to IPV in a sequential manner in 1997 where both IPV and OPV vaccines were used. The rationale: “This strategy was intended to decrease the incidence of VAPP while maintaining high levels of population immunity to polioviruses to prevent poliomyelitis outbreaks should wild poliovirus be reintroduced to the U.S.,” as per a January 1997 MMWR report. The risk associated with VAPP if OPV was used was estimated to be 30-40 cases during 1997-2000 (an average of 8-10 VAPP cases per year) in the U.S., while the sequential vaccination schedule was expected to reduce VAPP cases by at least half.
In addition to the risk of causing VDPV and VAPP, the OPV in India, contrary to popular notion, was found to have low seroconversion rates for types 1 and 3 — about 65% — and 96% for type 2. Low vaccine efficacy resulted in “increasing numbers of vaccine-failure polio as trivalent OPV coverage increased in India”.
Seroconversion after each additional dose was at the same frequency as after the first dose, notes a 2016 paper published in Indian Pediatrics. Children in India, even after receiving half-a-dozen doses, were still at risk of getting infected by poliovirus. As many as 10 doses of OPV vaccine were required to attain a three-dose vaccine efficacy seen in other countries. Wild poliovirus transmission was interrupted in most parts of India only when an average of eight-nine OPV doses were given to a child.
Seroconversion
Compared with poliovirus-naïve children, those infected with wild poliovirus shed the least amount of virus and for a shorter duration when challenged with OPV. Children vaccinated with OPV and then challenged with OPV shed a lesser amount of virus and for a shorter duration than those given IPV and challenged with OPV.
According to virologist Dr. Jacob John, virus shedding goes on beyond 24 hours and continues for a few weeks even in children initially given OPV and then challenged. “This clearly demonstrates that mucosal immunity is not absolute in the case of OPV,” he says. “Virus shedding in the stools does not automatically translate into transmission.”
The ease of administering OPV is often cited as a reason for continuing the use of OPV. But due to shortage of IPV, countries were encouraged to opt for a fractional dose of IPV vaccine administered intradermally prior to the global switch. India has been using a fractional dose (0.1 ml) of IPV vaccine administered intradermally at 6 and 14 weeks since 2016. Administering an intradermal vaccine is more challenging than an intramuscular dose. Yet India has been successfully immunising millions of children each year with fractional IPV doses. Since January 2023, a third fractional dose of IPV at 9-12 months has been included in the national immunisation programme.
A trial conducted in India found that two fractional doses of IPV administered intradermally at six and 14 weeks followed by bivalent OPV at birth, and age six, 10, and 14 weeks is effective and provides over 95% seroconversion against poliovirus types 1 and 3 and over 85% seroconversion against type 2 poliovirus.
Manufacturing OPV is indeed easy and such vaccines are also cheap. Traditionally, IPV was manufactured using wild polioviruses. But IPV can be manufactured using the attenuated viruses (Sabin IPV). Bharat Biotech, which has a BSL-3 manufacturing facility, was at an early stage of manufacturing Sabin IPV vaccines in 2020 when the pandemic struck and the manufacturing facility was instead used to produce Covaxin. When Bharat Biotech is licensed to manufacture Sabin IPV, India will no longer need to rely on other countries for vaccine supply.
Ground to switch
The addition of a third fractional dose of IPV at 9-12 months in the national immunisation programme will further boost the protection against all three types of polioviruses, both wild and VDPV. Considering that India has not reported any case of wild poliovirus or VDPV since it was certified polio-free and even when other countries reported VDPV cases during the pandemic, India can plan to make a switch from OPV to IPV once the vaccine coverage reaches over 85% across the country with the revised immunisation schedule of IPV at nine months.
In an April 2020 report, WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) wanted countries planning to move from bivalent OPV to IPV-only immunisation schedule to exercise caution and recommended that these countries should instead take a “gradual approach, first introducing a second dose of IPV into routine immunisation”. Seroconversion after two fractional doses of IPV given at six and 14 weeks in Indian children was already 95% against poliovirus type 1 and type 3 and over 85% against type 2 poliovirus. The additional fractional dose of IPV given intradermally at 9-12 months is expected to boost the seroconversion, particularly for type 2, which is currently only over 85%.
Like the U.S. in 1997, India has made ground to switch over to exclusive IPV in a sequential manner since 2016 with the introduction of two fractional doses of IPV. The addition of a third fractional dose at 9-12 months is in line with this sequential switch and the recommendation by SAGE. The move to exclusive use of IPV for polio immunisation in India can begin once we have the evidence for very high seroconversion for all three types of polioviruses.
All countries that have made a switch from OPV to IPV have only considered the last instance of wild poliovirus and VDPV cases within their borders. India too should adopt such an approach and after evidence of very high seroconversion after three fractional doses of IPV and once high vaccine coverage has been achieved using three fractional IPV doses.
