The probability of a polio outbreak from use of a discontinued vaccine is small but if such an outbreak occurs, it can have a big impact, said Jacob T John, a paediatrician and one of India’s leading polio researchers.
The risk has emerged after health officials found a weakened form of the type 2 polio virus, which is used to manufacture a polio vaccine, in the stool samples of two children with acute flaccid paralysis, which is a sudden onset of paralysis in the limbs. All acute flaccid paralysis cases are not caused by the polio virus but every case is checked for polio. Although the type 2 polio virus was present in the stool samples, health officials have said the paralysis is not connected to the virus.
The virus in the samples has been traced to some batches of the oral polio vaccine or OPV manufactured by a company in Ghaziabad, Uttar Pradesh, and the Health Ministry has ordered an investigation into the matter. The presence of the type 2 vaccine virus has been confirmed in one batch of 50,000 vials, and it is suspected in two more batches of 1 lakh vials, a ministry official told PTI. Officials confirmed on Monday that some vials of the contaminated vaccine were given to children in Maharashtra and Telangana as well.
The weakened virus in the vaccine itself does not pose a threat to the children who have received doses from these vials, since it is designed to trigger an immune response.
“The [weakened virus in the vaccine] is not going to harm recipients,” said SG Kasi, a paediatrician in Bengaluru and former member of Indian Academy of Paediatrics committee on immunisation.
Prabir Chatterjee, a doctor from West Bengal, who has been associated with the national immunisation programme, said, “If something had to go wrong among the children who have received the vaccine, it would have happened within the first 30 days to 40 days of them getting the vaccine, which should be over by now. It is unlikely that anything is going to happen because of the first dose of the vaccine.”
But the presence of this type 2 virus in the the vials and stool samples raises the possibility of the virus once again circulating in the population.
The type 2 virus used in the vaccine, also called Sabin type 2 after the creator of the oral vaccine Albert Sabin, can spread among children. Since April 2016, this live, weakened type 2 virus was discontinued in immunisations. Since 2016, the only protection against the type 2 virus is through the inactivated polio vaccine or IPV that is administered by injection. The real risk of the live vaccine virus re-entering the environment lies in the possibility of it undergoing mutation and regaining virulence with the ability to once again cause paralytic polio.
“Among non-immune children, Sabin type 2 can spread and the real risk is transmission leading to [the virus] regaining neurovirulence and transmission efficiency, when you have vaccine-derived poliovirus type 2, which can cause polio paralysis,” said John in an email to Scroll.in. “If transmission efficiency is regained, then it can become circulating VDPV or cVDPV that can cause polio outbreak. So, we have a low probability but high impact risk.”
Vaccine-associated paralytic polio manifests in the same way as polio caused by wild polio virus.
The low probability of a VDPV outbreak stems from the long time it takes for virus shed from the vaccine to become VDPV. According to the World Health Organisation, “It takes a long time for a cVDPV to occur. Generally, the strain will have been allowed to circulate in an un- or under-immunised population for a period of at least 12 months.”
The WHO also says that although 90% of cVDPV cases until 2015 have been caused by the type 2 virus, since 2000, more than 10 billion doses of OPV have been administered to nearly three billion children worldwide, with fewer than 760 VDPV cases.
However, in India, containing the risk depends on widespread use of IPV, which the national immunisation programme has only recently started using.
“IPV has not picked up much,” cautioned John.
Polio’s mechanism and the vaccines’ counteraction
There are three strains of the polio virus – type 1, type 2 and type 3 – all of which were originally wild, naturally occurring viruses that cause infections and, in some cases, paralysis in children. Rare cases of paralytic polio have also been seen in adults. In the 1950s and 1960s, researchers in the United States developed two vaccines against polio. One was Jonas Salk’s vaccine that was made from killed or inactivated polio virus and administered through injection. The other was Albert Sabin’s vaccine that used a weakened or attenuated live polio virus to trigger an immune response. This was administered orally.
The IPV is effective in protecting an individual from infection by polio but does not stop transmission of the virus between people. The OPV, on the other hand, has been used in global polio programmes for its ability to wipe out wild polio in the environment by replacing it with weakened, non-pathogenic forms of the virus. Until recently, OPV contained attenuated type 1, type 2 and type 3 polio viruses. These weakened viruses trigger immune responses in children, safeguarding them against the disease. But the vaccine virus is also passed through the excreta of immunised children into the environment. Under conditions of poor hygiene and sanitation, the vaccine virus can even enter the systems of children who have not been vaccinated, through the faecal-oral route, transferring immunity to the larger population. This is one of the underlying principles of the Pulse Polio campaign.
India’s mass polio immunisation programme is part of the global eradication programme and the Pulse Polio strategy has worked well, making the country one of the big polio immunisation successes in the world. The wild type 2 polio virus was last seen in India in 1999. Since then, health officials have continued to use the OPV with the goal of eradicating the type 3 and type 1 wild polio viruses as well. The last wild polio virus infection occurred in 2011. In 2012, a year after the last wild polio infection, the WHO removed India from the list of countries with active endemic wild polio transmission and declared India polio-free in 2014.
The switch
The global strategy for all areas that have eradicated wild polio viruses is to switch from using OPV with live attenuated polio virus to IPV. This is because of the risk the oral polio vaccine carries. Sometimes, the vaccine virus shed in human excreta can undergo a reversion as it multiplies in the environment to regain its virulence and become VDPV. This VDPV can cause polio in children who have not been immunised. India has recorded cases of VDPV infections.
According to John, the rate of paralysis varies, depending on the strain of virus causing infection. For instance, the type 1 virus may cause one case of paralysis for every 160 to 200 infections. Type 2 and type 3 may cause one case of infection in every 1,000 to 2,000 cases. Both John and Kasi said that the paralysis rate is likely to be much lower in case of infection from VDPV.
“The burden of the disease has changed,” said Kasi, explaining the rationale of the global switch to IPV. “There was time when we were losing about 350,000 children every year to polio. At that time, OPV came into the picture because [use of] a live virus is always better than inactivated virus but there is a reversion to neurovirulence, which was known from the time that OPV was manufactured but was taken as an acceptable risk.”
The OPV was also perceived to be better because it was one-tenth the cost of IPV, easy to administer, and because most Western countries had eliminated polio using OPV.
“Today the scenario has changed,” said Kasi. “The risk benefit ratio is changing. But, India cannot just stop OPV and change to IPV because of two reasons – cost and availability.”
As a first step to switching entirely to IPV, India, along with the rest of the world, adopted a new polio immunisation mechanism on April 26, 2016, when all trivalent oral polio stocks were destroyed to prevent any form of the live type 2 vaccine circulating again. Only a bivalent oral polio vaccine containing the live weakened type 1 and type 3 viruses has been used since then along with the trivalent injectable vaccine containing killed strains of all three types of viruses. However, health officials were prepared to find the live type 2 virus in the environment till 2017 because it can survive outside human hosts in tropical countries for between six months and a year after.
In fact, in June 2016, shortly after the switch, health authorities in Telangana announced a polio vaccination drive because a strain of polio had been found in Amberpet Nala in Hyderabad. The announcement triggered alarm that polio had resurfaced in India but this was actually an expected outcome of the immunisation strategy.
As India has slowly tried to phase out the oral polio vaccine and replace it with the injectable polio vaccine since 2016, there have, however, been global shortages of the injectable vaccine that have affected India as well.
Kasi said that standalone IPV is not available in the private sector and paediatricians are using combination vaccines like the hexavalent vaccine, which is the polio vaccine, along with the vaccines for diphtheria, pertussis, typhoid, hepatitis and influenza.
The breach
As opposed to what happened in Telangana, the new cases of live type 2 viruses being found in stool samples and vials in Uttar Pradesh indicate a serious breach in polio immunisation protocol. Since the live type 2 virus is known to survive in the environment for up to a year, and it has been more than two years since the global coordinated switch from trivalent OPV to the bivalent OPV without type 2, the only reason for the presence of the virus is contamination.
Kasi also said that the fact that health workers discovered the breach in stool samples and in sewage points to the strong polio surveillance system in India. “All this has happened because of the very strong surveillance that has been going on against polio,” he said.
Chatterjee agreed that the incident pointed to a robust surveillance system but also to a lax regulatory system. “This shows there is no proper regulation by the government or WHO of vaccine manufacturers and the only reason this has come to light is because it was picked up in regular surveillance,” Chatterjee said.
Both John and Chatterjee said there need not be a mop-up round of immunisations but continued vigilant surveillance. India will also have to make sure that it has adequate stock of IPV in the coming months and years that can continue to provide immunity against the type 2 virus.
According to John, even though the risk of an outbreak of vaccine-derived polio virus is low, that risk still has to be mitigated. He pointed out that this was the whole point of the global synchronous switch from trivalent OPV to bivalent OPV in April 2016. “Now we have to watch for type 2 spread beyond vaccinated children,” he said. “Sewage surveillance is the best method, in addition to acute flaccid paralysis surveillance. In all probability, type 2 virus will die out soon.”
However, public health researcher Sylvia Karpagam is seeking stronger action and better communication from the government. “The key to successful outbreak response is high level of government engagement and declaration of a public health emergency,” she told Scroll.in via email. “The Indian government should declare the crisis, notify all global partners, take the necessary precautions and release vaccine recommendations for tourists and visitors to the country, particularly children. They should also up the surveillance and most importantly keep communities involved with regular updates and guidelines. This would certainly be more useful than denying the problem and pretending that everything is under control.”
