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 greater than a decade of remaining polio-free, the U.S., the U.Okay, Israel and Canada reported kind 2 vaccine-derived poliovirus in environmental samples. The U.S. (Rockland County in New York) additionally reported one case of polio in a younger grownup brought on by kind 2 vaccine-derived poliovirus (VDPV) in July 2022.

What brought on the kind 2 VDPV case to emerge within the U.S.?

Vaccine protection

Vaccine protection with three routine doses of inactivated polio vaccine (IPV) within the U.S. was 92% in 2021. However, vaccine protection in Rockland County in New York, the place the younger grownup was contaminated by poliovirus and developed flaccid decrease limb weak point, was very low —  60.3% in August 2022, and the zip code-specific protection was as little as 37.3% — in keeping with an August 2022 report within the Morbidity and Mortality Weekly Report (MMWR). Most importantly, the younger grownup who acquired polio was unvaccinated.

In March 2022, a three-year-old baby in Jerusalem metropolis, Israel developed polio attributable to kind 3 VDPV. Like the younger grownup in New York, the kid in Jerusalem metropolis was not vaccinated. The kind 3 VDPV virus was detected in six extra kids who have been asymptomatic. “Of these seven children, one had incomplete polio immunisation while the other six were unvaccinated,” says a WHO report.

No matter the polio standing of a rustic and which vaccine is getting used, so long as wild poliovirus is current and any nation continues to make use of the oral polio vaccine (OPV), the chance of polio emergence, together with in polio-free nations, is actual in a globalised village particularly when vaccine protection is low. While growing vaccination protection nationally and at a group degree will assist forestall kids from getting polio illness, full eradication from the world will turn out to be attainable solely when wild polioviruses are worn out and the usage of OPV is stopped.

Type 2 poliovirus has been accountable for over 95% of VDPV instances, and since 1999, when wild poliovirus kind 2 was eradicated, all polio instances brought on by kind 2 virus have been both attributable to VDPV or vaccine-associated paralytic poliomyelitis (VAPP). Since the worldwide change from trivalent (containing varieties 1, 2, and three) to bivalent (containing varieties 1 and three) OPV in 2016, no baby in India has been vaccine-protected with OPV towards kind 2 virus. All the safety has come solely from IPV, which accommodates varieties 1, 2 and three. Yet not a single kind 2 VDPV case in India has been reported since 2016. This additional demonstrates why India can safely change to exclusive-IPV immunisation on the earliest.

Since wild and VDPV instances are nonetheless reported in Pakistan and Afghanistan, the compulsion to take care of a really excessive polio vaccine protection in India can’t be overemphasised. Also, India has remained polio-free since January 2011 whilst wild poliovirus and VDPV instances have been reported in Pakistan and Afghanistan, because of excessive polio vaccine protection right here. Any particular person travelling to India from a polio-endemic nation is required to get immunised with a dose of OPV previous to journey, to cut back the chance of spreading the virus right here.

The want to take care of excessive polio vaccine protection in India arises even with out contemplating the chance of imported instances, as continued use of bivalent OPV in India carries the chance of kind 1 and sort 3 VDPV and VAPP instances rising. VDPV instances can emerge solely when sufficient persons are not vaccinated towards polio.

Decreasing VAPP incidence

Despite wild kind 2 poliovirus being non-existent and never utilized in oral vaccines, kind 2 VDPV has brought on many instances every year even after the worldwide change to bivalent OPV in 2016. Nearly 40% of vaccine-associated paralytic poliomyelitis (VAPP) are brought on by kind 2 oral polio vaccine. Almost all VDPV and VAPP instances have been reported within the final 20 years are from nations that proceed utilizing oral polio vaccine. In distinction, nations that switched to inactivated polio vaccine have remained polio-free (each VDPV and VAPP), besides in 2022.

Many developed nations discontinued OPV use and converted to IPV just a few a long time in the past. The U.S., for instance, moved to IPV in a sequential method in 1997 the place each IPV and OPV vaccines have been 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 danger related to VAPP if OPV was used was estimated to be 30-40 cases throughout 1997-2000 (a median of 8-10 VAPP instances per yr) within the U.S., whereas the sequential vaccination schedule was anticipated to cut back VAPP instances by at the very least half.

In addition to the chance of inflicting VDPV and VAPP, the OPV in India, opposite to well-liked notion, was discovered to have low seroconversion rates for varieties 1 and three — about 65% — and 96% for kind 2. Low vaccine efficacy resulted in “increasing numbers of vaccine-failure polio as trivalent OPV coverage increased in India”.

Seroconversion after every extra dose was on the similar frequency as after the primary dose, notes a 2016 paper printed in Indian Pediatrics. Children in India, even after receiving half-a-dozen doses, have been nonetheless vulnerable to getting contaminated by poliovirus. As many as 10 doses of OPV vaccine have been required to realize a three-dose vaccine efficacy seen in different nations. Wild poliovirus transmission was interrupted in most elements of India solely when a median of eight-nine OPV doses got to a toddler.

Seroconversion

Compared with poliovirus-naïve kids, these contaminated with wild poliovirus shed the least quantity of virus and for a shorter period when challenged with OPV. Children vaccinated with OPV after which challenged with OPV shed a lesser quantity of virus and for a shorter period than these given IPV and challenged with OPV.

According to virologist Dr. Jacob John, virus shedding goes on past 24 hours and continues for just a few weeks even in kids initially given OPV after which 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 usually cited as a cause for persevering with the usage of OPV. But attributable to scarcity of IPV, nations have been inspired to go for a fractional dose of IPV vaccine administered intradermally previous to the worldwide change. India has been utilizing a fractional dose (0.1 ml) of IPV vaccine administered intradermally at 6 and 14 weeks since 2016. Administering an intradermal vaccine is more difficult than an intramuscular dose. Yet India has been efficiently immunising hundreds of thousands of youngsters every year with fractional IPV doses. Since January 2023, a 3rd fractional dose of IPV at 9-12 months has been included within the nationwide immunisation programme.

A trial conducted in India discovered that two fractional doses of IPV administered intradermally at six and 14 weeks adopted by bivalent OPV at delivery, and age six, 10, and 14 weeks is efficient and supplies over 95% seroconversion towards poliovirus varieties 1 and three and over 85% seroconversion towards kind 2 poliovirus.

Manufacturing OPV is certainly simple and such vaccines are additionally low-cost. Traditionally, IPV was manufactured utilizing wild polioviruses. But IPV could be manufactured utilizing the attenuated viruses (Sabin IPV). Bharat Biotech, which has a BSL-3 manufacturing facility, was at an early stage of producing Sabin IPV vaccines in 2020 when the pandemic struck and the manufacturing facility was as an alternative used to supply Covaxin. When Bharat Biotech is licensed to fabricate Sabin IPV, India will now not have to depend on different nations for vaccine provide.

Ground to change

The addition of a third fractional dose of IPV at 9-12 months within the nationwide immunisation programme will additional enhance the safety towards all three kinds of polioviruses, each wild and VDPV. Considering that India has not reported any case of untamed poliovirus or VDPV because it was licensed polio-free and even when different nations reported VDPV instances through the pandemic, India can plan to make a change from OPV to IPV as soon as the vaccine protection reaches over 85% throughout the nation with the revised immunisation schedule of IPV at 9 months.

In an April 2020 report, WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) wished nations planning to maneuver from bivalent OPV to IPV-only immunisation schedule to train warning and really helpful that these nations ought to as an alternative 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 kids was already 95% towards poliovirus kind 1 and sort 3 and over 85% towards kind 2 poliovirus. The extra fractional dose of IPV given intradermally at 9-12 months is anticipated to spice up the seroconversion, notably for kind 2, which is presently solely over 85%.

Like the U.S. in 1997, India has made floor to change over to unique IPV in a sequential method since 2016 with the introduction of two fractional doses of IPV. The addition of a 3rd fractional dose at 9-12 months is in keeping with this sequential change and the advice by SAGE. The transfer to unique use of IPV for polio immunisation in India can start as soon as we now have the proof for very excessive seroconversion for all three kinds of polioviruses.

All nations which have made a change from OPV to IPV have solely thought-about the final occasion of untamed poliovirus and VDPV instances inside their borders. India too ought to undertake such an method and after proof of very excessive seroconversion after three fractional doses of IPV and as soon as excessive vaccine protection has been achieved utilizing three fractional IPV doses.