Polio vaccine breach: India is perched atop the edge of crisis

Around 1.5 lakh kids in UP, Maharashtra and Telangana have received polio vaccines (OPV) contaminated with poliovirus type 2. A strand that has been pronounced ‘eradicated’. The breach is serious. Poliomyelitis is a highly contagious viral disease that can maim, paralyze or even kill children. And now, poliovirus type 2 is back in the environment and there is a small possibility that the virus might cause polio—if not in a child who received the dose (a tiny but ever-present risk), then in the wider population of kids born after 2016 who have not been inoculated against polio type 2. The world, and India with it, stopped vaccinating children against type 2 in April 2016.

“Among non-immune children, there is the possibility of some getting infected from the vaccinated children,” said T Jacob John, a polio researcher with the Christian Medical College in Vellore. “Very low probability of that happening, but in case it happens, then the result will be a polio outbreak.”

Experts say this situation could’ve been entirely avoided if India’s Universal Immunisation Programme (UIP) predominantly administered an injectable polio vaccine to kids, rather than the oral one. India does not because there’s a worldwide shortage of injectable vaccines (the “inactivated polio vaccine” or IPV) that will ease only in 2023—the result of a lack of foresight on the part of global health authorities.

The global community has learned its lesson on polio,” said Raj Shankar Ghosh, deputy director of vaccine delivery at the Bill and Melinda Gates Foundation. “No one expected the supply shortage’.

Four strategies for polio immunisation

These were endorsed by WHO and followed by India:
National immunisation programme
Surveillance of any child who complains of sudden weakness/paralysis
Mop-up: stepping up inoculations if a case is reported
Pulse polio program

And so, India is mostly giving out oral vaccines and rationing its limited IPV supplies. Kids are getting fractional doses on a schedule that is relatively less effective, said Vipin Vashishtha, a paediatrician and polio expert at Mangla Hospital and Research Center in Bijnor, Uttar Pradesh. And coverage is low—only 47% of Indian kids got IPV last year, according to the World Health Organization.

“If there is a resurgence or appearance of, for example, vaccine-derived type 2 [polio], with this type of schedule, you may have compromised efficacy,” said Vashishtha. “Population immunity may not be that great.”

If polio type 2 manifests in the community, it would be a serious setback to the global and India’s polio eradication efforts. India’s last wild polio case was in 2011, and it was certified polio-free in March 2014. The last case of polio type 2 was seen in 2002.

The government and WHO are now rushing to inoculate kids in the affected areas with IPV from emergency stockpiles. Surveillance is ongoing for signs of an outbreak, said Oliver Rosenbauer, spokesman for the Global Polio Eradication Initiative (GPEI), which is part of WHO. That is not nearly enough. Everyone, including the Government of India, agree that they need IPV for each and every child, and soon. Unfortunately, only one company is now selling the injectable vaccine to the government and at a price above the government’s budget.  

How we got here

Polio is no joke. It afflicted 200,000 to 400,000 Indian kids every year until the 1990s. Once a person ingests the virus, usually through contaminated food, it multiplies rapidly in the intestines. In the worst case scenario, it enters the bloodstream, travels into the central nervous system where it hijacks nerve cells that control a person’s movement—her ability to swallow, eat, breathe, move. It makes millions of copies of itself and then kills the nerve cell, leaving the person paralyzed.

There are two types of vaccines against polio—an injectable one that contains killed viruses and is extremely safe; and an oral one that contains weakened, but not fully killed, viral particles. OPV is considered better for the developing world because the weakened virus can spread into the environment, conferring so-called “herd” immunity. Everyone around the child also gets protected. It is also cheaper, simpler to manufacture and easier to administer. OPV was the mainstay of the WHO’s polio eradication initiative, called the Global Polio Eradication Initiative, in 1988.

But as early as 1954, scientists including OPV’s inventor, the late Albert Sabin of the University of Cincinnati, realised that as the weakened virus goes through the human gut, it can sometimes increase virulence. And in rare cases, it can lead to vaccine-derived paralysis. The risk is low, causing polio in about one case out of 1.5 million children immunised, said Vincent Racaniello, a professor of immunology at Columbia University. But the only way to avoid this probability would be to use killed viruses rather than weakened viruses. That is, IPV rather than OPV.

Indian scientists have, for long, been arguing against OPV use in India. Their entreaties were based on studies in Vellore, Tamil Nadu that found that Indian kids do not respond as well to OPV administration, unlike kids in the developed world. Where, in theory, four doses of OPV ought to be enough to confer protection from polio; in India, it might take more than 20 doses, said John of CMC Vellore. And greater the number of doses, greater the risk of vaccine-derived paralysis.

“The belief of government experts was IPV would not interrupt virus transmission, but that was based on belief, not evidence,” he said. “No evidence of cost and benefit analysis by anyone before one vaccine was chosen to the exclusion of the other.”

The Indian government in the 1960s set up factories to make both OPV and IPV, but after pressure from WHO, it shut them down—a move that’s widely recognised as short-sighted. WHO was concerned whether India could safely handle the wild poliovirus while making vaccines—a reversal of its earlier policies. In the 1960s, WHO would engage in knowledge transfer and train experts in the developing world in vaccine production.

We can’t really blame the government for not investing in producing IPV and continuing to produce OPV from scratch in India. Health was not a priority. There was no vaccinations policy. There were just nudges from international organisations. OPV became popular. Every developing country took to OPV without exception.

Former scientist with Polio unit, Pasteur Institute, Coonoor

“For quite some time, WHO would give scholarships to developing countries to teach vaccine-making,” said senior executive with an OPV producing company. “They stopped. We have to now do in-house. It is a very hard process.”

Today, all OPV and IPV vaccines that are “made in India” are actually derived from raw material (weakened viral seeds) imported from WHO-approved master seed banks.

Scientists have been warning WHO about vaccine-derived polio outbreaks for more than half a century. But it took a vaccine-derived outbreak in the Dominican Republic in 2002 to make them sit up and take notice.

The Polio Endgame – Botched

In 2009, WHO belatedly recognised that they would need to phase out OPV and replace with IPV. The 2014 “polio endgame” strategy would have three steps: nations would first stop giving type 2 polio oral vaccines to kids in a concerted move in April 2016. They would begin administering at least one dose of IPV. Finally, all nations would transition entirely to IPV.

This wasn’t a problem in the developed world, where IPV is manufactured by multinational corporations GlaxoSmithKline and Sanofi Pasteur and sold with other childhood vaccines at $50 per dose. These nations are self-sufficient.

But few people could pay these rates in the developing world. WHO realised that about 428 million doses would need to be introduced in more than 120 nations between 2014 and 2018. In 2014, the Serum Institute of India and Sanofi Pasteur responded to UNICEF’s tender for supplies and agreed to supply IPV at $2 per dose in low-and-middle-income countries. It would be an immense ramp up on a scale rarely seen before.

There were a number of issues. Vaccine makers need Biosafety Level-3 facilities to make IPV, labs where the virus is highly contained and the safety protocol needed is high. These are typically located in high-income nations, so vaccines could not be made indigenously. Moreover, the vaccine-makers would need WHO prequalification for their facilities, a process that can take up to two years. In comparison, OPV can be cultured and mass produced safely in low-income countries, said Gitanjali Chaturvedi, senior social development specialist at The World Bank, who has worked with polio programmes in UNICEF and WHO in the past.

Manufacturers globally did not have a sufficient bulk of the virulent wild virus, which is maintained in carefully-controlled seed banks, to generate the killed virus. There were unplanned production stops and delays after maintenance. At the same time, some of the vaccines had to be diverted to Nigeria (which experienced a vaccine-derived polio outbreak), and Pakistan and Afghanistan (where OPV reach is low).

By 2018, the manufacturers had managed to supply less than half of the agreed-upon amount.

“The scale-up by manufacturers to produce the required IPV had encountered a series of challenges, resulting in a considerable reduction in supply at the time,” said Rosenbauer of GPEI. “The supply situation has significantly improved as at 2018, and prior to that, supply had been prioritised to highest-risk areas.”

Ramping up India’s IPV supplies

India was expected to self-procure IPV beginning the last quarter of 2016. At present, Shantha Biotechnics, a subsidiary of Sanofi Pasteur, is the only one supplying IPV to the Indian government using manufacturing facilities abroad. But there is a significant shortage. There’s an acute shortage in the raw material of virus needed by vaccine-makers.

Five months ago, the Indian government floated a tender for IPV. This time, Shantha Biotech agreed to supply at a cost 80% higher than it quoted in 2017, according to a senior official consulting the ministry of health on UIP. The government is still negotiating the terms of procurement.

As a result, the government is vaccinating kids with IPV using fractional doses administered under the skin at six and 14 weeks of age. Studies have shown that this compromises the vaccine’s ability to confer protection. In the developed world, three doses are administered into the muscle at two, four, and between six to 18 months, and a booster dose at four to six years.

Other vaccine suppliers, such as Bharat Biotech, are now trying to make IPV using weakened poliovirus strains typically used in OPV production, according to senior executive with an OPV producing company quoted above. That’s widely considered the frontier of IPV production and China and Japan have already mastered the technique.

The probability of vaccine derived polio virus does not apply to India because our herd immunity is very high. But India faces the risk of wild virus being reintroduced from Pakistan and Afghanistan. Thus, immunity levels in India have to continue to be high, which is why the programme has to transition from OPV to IPV.

Gitanjali Chaturvedi, who worked with polio programme with UNICEF and WHO

“It’ll take time,” the person said. “It will take a number of years. We [the companies] need clinical studies and phase 1, 2 and 3, which takes time and money.”

Eyes firmly on the future, Panacea Biotec is planning to incorporate Serum’s IPV in a combination hexavalent vaccine called “EasySix” that includes five other childhood shots. The vaccine is now in the process of getting WHO’s pre-approval. But the health ministry is not planning to include it in the immunisation programme due to the exorbitant price it is expected to have.

The contamination scandal

In compliance with the WHO’s “polio endgame” strategy, the Indian government in 2016 asked vaccine-makers to remove the type 2 virus from their oral polio vaccine. So, all OPV in India should be “bivalent”, containing only polio type 1 and type 3, rather than “trivalent”. The kids would get bivalent OPV plus IPV, which contains all three types. The IPV would protect against any remnant type 2 poliovirus hanging around in the environment.

Except most Indian kids have not received IPV.  

WHO and the Indian government routinely surveil India’s sewage for polio outbreaks. They collect samples from 45 sites across eight states and test for the presence of poliovirus in five labs spread throughout the country, according to WHO. They also collect stools from patients who are afflicted with paralysis to see if they may have polio. Some 75,000 stool samples are collected every year, according to a WHO spokesperson.

In one such sample collected, they found the type 2 virus. When the investigators traced the virus back, it was found to have come from vials of OPV supplied by Ghaziabad-based Bio-Med. The authorities immediately withdrew all Bio-Med OPV vaccine from distribution and arrested the managing director of the company. At least three batches containing 1.5 lakh vials that have been administered to kids in UP, Telangana and Maharashtra were contaminated, according to news reports.

It’s not known how Bio-Med’s vaccine got contaminated. It is also not known how Bio-Med’s batches escaped the Indian government’s vaccine quality control system that checks for contamination.

“This incident boils down to the quality of vaccine,” said Chintesh Dwivedi, deputy general manager at Zydus Cadila who has worked at vaccine companies. “It puts a question on sourcing for universal immunisation program. If they can’t get oral right, which is very simple, what about the injectable ones?”

The government’s and WHO’s response to the breach have been muted. On 4 October, four days after news broke, the health ministry issued a press release. “A section of print media” has spoken about “quality issues” from a “particular manufacturer”, it stated. “The risk of any child getting vaccine-derived polio is practically nil,” it said. The mildness is with good reason. Seeds of doubt could flower into a full-blown anti-vaccine crisis. In the aughts, some Muslim clerics in UP issued fatwas against the polio vaccine, impeding vaccination efforts. To this day, people in northwest Pakistan distrust polio vaccinators and the region remains the last major polio reservoir in the world.

The government is giving IPV shots to kids in Bio-Med supplied areas to ensure they are protected from any type 2 virus that hangs around in the environment. But given the IPV shortage, the government is possibly pulling supplies away from inoculation programs elsewhere.

And the next time there is a crisis, India will again find itself racing to protect.

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