DevExplains: Vaccine-derived polio and the challenge of eradication

MANILA — The Global Commission for the Certification of the Eradication of Poliomyelitis is expected to announce a major milestone this week: the global eradication of wild poliovirus type 3. The announcement will mean there’s only one wild poliovirus still in circulation — type 1, in Afghanistan and Pakistan — considered the last frontiers of the fight against the disease. But several countries’ weak health systems and the scourge of vaccine skepticism worldwide are posing challenges to polio eradication efforts. What’s the current situation? Since January, there have been 95 cases of circulating vaccine-derived polio cases in 12 countries in Asia and Africa, exceeding the 88 cases of wild poliovirus in Pakistan and Afghanistan. As the name suggests, vaccine-derived polio are “rare strains of poliovirus that have genetically mutated from the strain contained in the oral polio vaccine” or OPV, which contains a weakened poliovirus meant to help an individual develop an immune response against it. But on very rare circumstances, especially in areas with low immunization coverage and weak surveillance coupled with poor sanitation and hygiene, that weakened virus may live longer and genetically change to a form that can cause paralysis and potentially an outbreak, said Tigran Avagyan, technical officer of the World Health Organization’s expanded program on immunization in Western Pacific. While OPV has been very effective in getting the world closer to eradication, the risks associated with it led the Global Polio Eradication Initiative to recommend the eventual withdrawal of OPV worldwide, starting with the removal of the type 2 poliovirus component in OPV. In 2016, stocks of trivalent OPV were destroyed and the world switched to bivalent OPV, which now only contains a weakened form of poliovirus type 1 and type 3. The switch also led to the introduction of the inactivated polio vaccine, or IPV, in routine immunization programs, although challenges in supply meant several countries experienced delays in incorporating it in their immunization programs. In Western Pacific, Vietnam was only able to introduce IPV on September 2018, while Mongolia was only able to do so last March-April 2019, Avagyan said. He said UNICEF was only able to contract two vaccine manufacturers to supply countries with IPV as several manufacturers stopped production. “The capacity of these two producers was not enough to ensure the global supply. This is why the shortage immediately affected several countries, and [only] started improving from 2017,” he added. While Avagyan said there are no shortages of one-dose IPV globally currently, some countries may experience stockouts due to procurement delays or logistical issues. The switch was meant to reduce the risks associated with the type 2 component in OPV. While the type 2 wild poliovirus was declared eradicated in 2015, the type 2 component in OPV has been a major source of circulating vaccine-derived polio cases globally. The environmental samples taken in Manila’s sewage system and Davao’s waterways were positive of the vaccine-derived type 2 component, as well as the positive human case in Lanao del Sur. Why do countries experience circulating vaccine-derived type 2 cases if the oral vaccine in routine immunization no longer carries it? There are a number of reasons, from individuals with immune deficiency shedding the virus to the limited effectivity of IPV to induce intestinal immunity in individuals, said Walter Orenstein, associate director of the Emory Vaccine Center, and director of Emory’s vaccine policy and development. Orenstein was the director of the U.S. immunization program 1988-2000 and served as deputy director on immunization programs at the Bill & Melinda Gates Foundation 2008-2011. Some vaccine-derived type 2 viruses were also still in circulation when the switch took place. “And then the effort to try and contain them [was] using the [monovalent] oral polio vaccine type 2. And there's a danger there that while we may control the outbreak we're trying to control, putting all that type 2 vaccine into the population can lead to a generation of more circulating vaccine-derived poliovirus type 2s, so that in a sense we're fighting fire with fire,” Orenstein told Devex. In the Philippines, the ongoing vaccination campaign in Davao and Lanao del Sur provinces uses monovalent OPV that specifically protects against the type 2 virus. At the recent meeting of the Strategic Advisory Group of Experts on Immunization, it recommended the use of one drop of monovalent OPV type 2 instead of two-drops to ensure continued sufficient supply of the vaccine for outbreak control. However, they also acknowledged the problem with using the vaccine in controlling vaccine-derived type 2 outbreaks, given its potential to circulate in populations with low immunization coverage. To prevent further vaccine-derived type 2 virus circulation and outbreak, experts called for accelerating the clinical development of a novel OPV type 2 vaccine. The novel OPV type 2 is targeted to replace monovalent OPV type 2 in controlling outbreaks caused by circulating vaccine-derived poliovirus type 2. “This would be more genetically stable and would prevent emergence of new circulating vaccine-derived poliovirus type 2. And we believe we should have access to that new vaccine around the middle of 2020,” Orenstein said. Can the world stop using oral polio vaccines entirely? That’s the plan. But until a type of poliovirus remains in circulation, OPV remains necessary, given the risk of exportation to other countries, said WHO’s Avagyan. “Oral polio vaccine is the only vaccine that can stop transmission of [the] virus in the population,” he said. But there are countries, like the U.S., that are only using inactivated polio vaccine. The issue is a matter of cost and complexity in administering the vaccine. IPV is five times more expensive than OPV, according to the Global Polio Eradication Initiative. This means only a few countries can afford to completely switch to IPV to protect their populations from the three types of poliovirus. It also requires trained health workers to administer the vaccine. But there’s also the issue of transmission. In places like the U.S., the major mode of transmission is often oral-oral, for which IPV works well to induce immunity. But in many other low- and middle-income countries, the predominant mode of transmission is fecal-oral, for which IPV has limited effectivity as it induces low intestinal immunity, whereas OPV can induce high levels of both oral and intestinal immunity, Orenstein said. “It's unclear how good IPV is in developing countries in protecting the community. We have conflicting evidence. For example, in Israel in 2005, they went to an all IPV schedule for the whole country. And in 2013 they had an introduction of a wild poliovirus type 1, and then had sustained transmission for over a year,” he said. “In contrast, in Yogyakarta, Indonesia, they switched to an all IPV schedule. And while they had evidence that vaccine viruses were introduced, they never saw the development of a circulating vaccine-derived poliovirus type 2, or any [circulating vaccine-derived poliovirus] type for that matter. And so it's unclear how much IPV helps in preventing the generation of new cases … But it clearly helps in protecting people against paralytic polio. It prevents the virus from invading the central nervous system,” he said. How to prevent circulating vaccine-derived polio cases? The best way is to ensure the highest possible coverage of routine vaccines, Avagyan said. But in some countries, achieving more than 90% coverage remains a struggle, he said. When a case of circulating vaccine-derived polio emerged in China, it was in a geographic location with low immunization coverage for years. In the Philippines, immunization rates have been declining in the past few years, and this was exacerbated by the controversy surrounding the dengue vaccine, Dengvaxia. “It's different from country to country. In some countries it is the whole country. In other countries it's some targeted population. But the reason, the main reason, is declined or chronically low coverage with routine vaccines,” Avagyan said. “We can get rid of the wild viruses ... and then we can stop generating new outbreaks by getting rid of the vaccines. So we need to finish the job. And this is emphasizing that until we do, we run the risk of outbreaks,” Orenstein said. How do you convince populations to vaccinate, when the cases are triggered by circulating vaccine-derived viruses? “This is [a] very valid and very difficult question actually. But the answer to this question is that by vaccinating the child, the parents, we ensure that we are giving protection [against] any poliovirus, even vaccine-derived poliovirus,” Avagyan said.