Polio eradication nears the end game
Authors: James Butcher
Journal: The Lancet Neurology (2008)

The Global Polio Eradication Initiative has achieved a great deal since its launch in 1988, with 1303 polio cases reported last year compared with 350 000 cases 20 years ago. But eradicating all three types of poliovirus once and for all is proving hard to do. James Butcher investigates. When Margaret Chan became Director General of WHO at the beginning of 2007 she immediately ordered an assessment of the Global Polio Eradication Initiative (GPEI) to find out whether there was the collective will and resources in place to finish off the task that was first started, at least in the richer regions of the world, in 1988. Chan convened a meeting in Geneva on Feb 28, 2007, that included representatives from the governments of the four countries where poliovirus remains endemic (Pakistan, Afghanistan, India, and Nigeria). “That meeting signalled a real change in the programme”, says Bruce Aylward, Director of the GPEI. “Everything was in place technically but it wasn't going to happen unless the stakes were high enough politically”, he says. After the meeting, the fight against polio intensified, and a set of milestones to measure progress were published. A year on, there are signs that the campaign is close to achieving its goal. But there have been considerable set-backs since the original GPEI deadline passed in 2000, most notably international outbreaks in 2003 that saw 27 countries that had previously been polio-free become reinfected over the subsequent 3 years. So what is the likelihood that wild polioviruses really will now be eradicated from the face of the planet, once and for all? When the GPEI was launched in 1988, more than 350 000 children in 125 countries were permanently paralysed by polioviruses each year, even though a cheap and effective oral polio vaccine (OPV) was readily available. By 1999, the GPEI had reduced the number of annual cases of polio by 99%, and type 2 polioviruses now seem to have been eradicated worldwide, proving that the concept of eradication could work. Many observers pointed the finger of blame for the 2003–06 resurgence at Nigeria, particularly the northern state of Kano where vaccination was stopped because of local concerns about safety. “A myth of the polio programme is that the outbreak was caused solely by Nigeria stopping vaccination”, says Aylward. “But when you look at it, what really happened was that a number of countries got reinfected before Nigeria even stopped vaccinating, and India also exported virus during that period.” Aylward says that in many countries the quality of the campaigns dropped because the local health workers had been lured into a false sense of security by their previous successes and had begun to vaccinate less thoroughly. “The international outbreaks were exacerbated by what happened in northern Nigeria without a doubt”, says Aylward, “but they may well have happened anyway.” Afghanistan, Pakistan, and Nigeria are struggling to eradicate the disease because of logistical and political difficulties. For example, many of the polio-infected regions in Afghanistan are war zones, which makes running vaccination campaigns difficult; however, in the middle of 2007 the Taliban issued a directive that vaccinators should be given access to children in southern Afghanistan. The problems facing India have been technical; some children have developed symptoms even though they received more than 10 doses of OPV. According to Nick Grassly, a researcher from Imperial College London, “The programme appeared to be getting good coverage with the trivalent vaccine and yet the poliovirus was persisting in Uttar Pradesh and Bihar, and so the question was why was that?” Although no one knows for sure, it seems probable that the poor sanitation and high population densities in these regions were to blame. “It's a live attenuated vaccine, so if you give it to children who have got diarrhoea or other enteroviral infections then it doesn't take in the gut and they don't become immune”, explains Grassly. In addition, says Aylward, the health workers faced a race against time to vaccinate the children quickly enough. “Another problem was the huge number of kids being born. About a million children were being born in Uttar Pradesh between each campaign—the campaigns were about 8 weeks apart; we just couldn't get ahead of the susceptibles and that, combined with the sanitation and other problems, was killing us.” The GPEI went back to the drawing board and reassessed the technical tools that they had at their disposal and what could realistically be achieved. “In 2005/2006 we entered into a period of unprecedented innovation as we tried to figure out how to optimise our tools and our tactics”, says Aylward. An important step forward was the development of a monovalent vaccine for type 1 polio that was designed to help combat the disease in India and in Egypt, where, at that time, only type 1 poliovirus remained. Grassly and Aylward were authors on a case–control study, published in The Lancet in April 2007, that showed that the monovalent type 1 vaccine was three times more efficacious than trivalent OPV in these regions of India. As a result, the vaccinators there have switched to the monovalent vaccine. “We haven't seen wild-type poliovirus type 1 in western Uttar Pradesh, the only part of India that never stopped endemic polio, for 12 months”, enthuses Aylward. “If it sticks, that is the single most important development in the programme in the last couple of years because it means that the tools and tactics are good enough to stop transmission everywhere.” But the task that faces the immunisation teams is immense, and the logistical challenges require considerable political will to implement properly. “People often question Indian commitment, but this is a country that went out and decided to immunise 70 million kids every month and committed US$290 million of their own resources for the purpose. I think people have lost perspective when they think about what these countries are doing”, says Aylward. The other big development in the past year is that in Nigeria the number of children that miss vaccination has halved. “Pakistan continues to be a big challenge. The good news is that the big, populated areas of the Punjab are now polio-free, but the tribal areas right along the border still need to be worked on”, says Aylward. Indeed, Aylward hopes that the GPEI will be able to stop transmission of wild-type poliovirus type 1 in 2008, and to do the same for type 3 poliovirus by the end of 2009. But he admits that this might not be possible, particularly if access to the remaining regions becomes difficult because of war, deteriorating political situations, or some other, unforeseen, circumstances. “The key thing to get done this year is to get type 1 finished in India because, with that, the international risk of spread from India drops dramatically”, says Aylward. In addition, because of the scale of the vaccination campaign there, India takes up around a third of the GPEI's budget; therefore, eradicating type 1 is essential for economic reasons too. “The other thing is to get parts of Nigeria polio-free, like Borno, which keeps reinfecting Chad”, says Aylward. With the end nearly in sight, many observers are switching their attention towards the post-eradication era, when the main problem will be polioviruses that spontaneously arise from the OPV and display neurovirulence. This is why richer countries, with well developed health systems, use inactivated polio vaccine (IPV), which is given by intramuscular injection and currently costs ten times the price of OPV. The WHO expert advisory groups on polio have recommended that the world stops vaccinating with the OPV once eradication is complete. Ellie Ehrenfeld, who works at the National Institute of Allergy and Infectious Diseases in the USA, is concerned that this is the wrong thing to do. “In 1988, when that policy was designed, it made perfectly good sense”, says Ehrenfeld, “but what we've learned in the past 20 years is that the virus can circulate undetected for very long periods of time; for example, there are immunodeficient people who never clear the virus and continue to excrete it.” Ehrenfeld convened a meeting at the National Institutes of Health, Bethesda, USA, in September, 2007, that brought together interested parties to discuss the post-eradication problem. “The major message that came out of the meeting was that everything that we've learned about the biological behaviour of this virus tells us that we're not going to be able to do this with OPV alone.” Aylward agrees with this conclusion and says that completely stopping vaccination worldwide or just using OPV is “a non-starter”, particularly given the threat of terrorism in the western world. “The question then becomes, should everyone use IPV or just some people? Having eradicated the disease and having a risk right across sub-Saharan Africa of maybe 30% of seeing a vaccine-derived poliovirus there somewhere, should they use IPV at ten times the cost? That's a real hard sell for low-income countries.” As a result, Aylward argues that the challenge now is to remove cost from the decision making by looking for affordable strategies for IPV in low-income countries. These include the investigation of whether two doses can be used instead of four, whether giving an adjuvant with the vaccine could increase its effectiveness—and therefore reduce the required dose—and whether low-income countries could safely produce IPV themselves, with, for example, the Sabin virus rather than a wild-type virus. Over the years, the GPEI has come under intense criticism, but most observers believe that it is on track to complete its mission. “Personally, I think they are doing a very difficult job in the best possible way: being driven by data and opening themselves up to scrutiny”, says Grassly, who was granted access by WHO to epidemiological data that enabled him to show that the type 1 monovalent vaccine is more effective than the trivalent one. “Initially, having a message saying that the [trivalent] vaccine had low efficacy was not necessarily what they wanted”, explains Grassly. “But, to their credit, they were open to us publishing our results and putting them in the public domain.”