Despite an active vaccination program to stop polio, India still accounts for half the world's cases of the crippling childhood disease. And now scientists may finally have determined why. After comparing records of Indian children who were paralyzed by polio with those who staved off the disease, researchers inferred that the key causes of ongoing polio transmission are high population density and poor sanitation. And those are surmountable problems, the group says.

"If we maintain wide coverage we should be able to eliminate polio from India," says infectious disease epidemiologist Nicholas Grassly of Imperial College London, a member of the research team. Some researchers had begun to give up on the possibility of eliminating the disease from the world's second most populous country.

Since 1988 the global health community has worked to eradicate polio from the world and has nearly succeeded: in the Americas, Europe and the western Pacific, the disease is gone. Of the handful of remaining countries in which it still crops up, India accounts for about half of all new cases. "India was particularly puzzling and challenging because there's a supplementary vaccine program in place that has vaccinated many children many times," Grassly says. It wasn't clear whether the problem was the vaccine itself, pockets of kids who weren't receiving treatment or poor living conditions.

To pin down the answer, Grassly and his colleagues at the World Health Organization had to see how effective vaccinations were in different locations. They gathered detailed data on 96,421 children paralyzed in India from 1997 to 2005. To make sure the paralyzed kids were not simply exposed to more of the virus than other children, the group matched each record to that of a child who did not contract the disease but was similar in age, number of reported vaccinations, neighborhood of residence and other characteristics. After controlling for these influences they found that vaccinations were only 9 percent effective per dose in the northern provinces of Uttar Pradesh and Bihar, where polio transmission is high. In the rest of India, health officials estimate that vaccine efficacy is 21 percent.

High population density and poor sanitation are the most likely explanations for this disparity, the group reports in the November 17 Science. The vaccine itself shouldn't be the problem because of procedures for monitoring the temperature at which it is stored, Grassly says. Crowded, dirty conditions may be more likely to blame, because they favor the spread of polio and other infections, such as diarrheal illnesses, which can prevent the immune system from responding properly to a vaccine. Despite the ongoing problem, "it gives you confidence that the vaccine program has attained its goals outside of Uttar Pradesh and Bihar," Grassly says. Careful deployment of a more specific form of the vaccine in the problem regions might help reduce transmission, he adds.

Not all experts are convinced by the new analysis. Distributing the existing vaccine might still be more of problem than crowding and poor sanitation, which also exist in other places that don't have polio, says epidemiologist Donald Henderson of the University of Pittsburgh. "This is a large population and it's quite a large area. There has to be a very high order of management and quality control." The number of polio cases in India has jumped 10-fold from last year, he points out, suggesting that such management might be lacking.