In an ideal world, whenever a new vaccine was developed, it would instantly be made available to those who need it most. But in reality, many vaccines are made available in industrialized countries for years or decades without reaching developing countries, where infectious disease rates are usually higher. The pneumococcal conjugate vaccine, for instance, has been given to every infant in the United States for the last five years. Of the one million children under the age of five who die every year from pneumococcal infection, 90 percent live in developing countries that large-scale vaccination programs have not reached.
A cost-effectiveness analysis by researchers at HMS, the University of Medicine & Dentistry of New Jersey, and Johns Hopkins Bloomberg School of Public Health offers evidence that vaccinating infants in developing countries against pneumococcal infection would be highly cost-effective and could prevent hundreds of thousands of deaths per year. The study, published in the Feb. 3 Lancet, found that vaccination was cost-effective in nearly all of the 72 countries in the analysis.
Tracy Lieu, senior author of the paper and professor of ambulatory care and prevention at HMS, said that the goal of this type of study is to help people imagine the potential outcomes of investing in health care. First author Anushua Sinha, assistant professor of preventive medicine and community health at the University of Medicine & Dentistry of New Jersey, led the development of a computer model that can estimate how vaccination would affect each of 72 developing countries eligible for funding from the GAVI Alliance, a multilateral organization involved in bringing vaccines to the developing world. Previous studies of pneumococcal conjugate vaccination had relied on data from industrialized countries; this study was able to make use of a large trial in the Gambia, which provided a scenario closer to the countries that the study examined. That trial not only measured how well the vaccine prevented death by pneumococcal infection, but also provided an estimate of the vaccine’s total impact on child mortality. It found that vaccinating children against pneumococcal infection had an impact on preventing death from pneumonia and reduced total childhood mortality by 16 percent.
While the Gambian trial provided a reference point in the developing world, each country in the study is very different. “The challenging part of the analysis is that for the 72 countries we had to make some estimate of how effective the vaccine would be at preventing death,” Lieu said. “For each one, we made a set of assumptions tailored to that country.” One of the key pieces of information available was infant mortality rates. In countries where infant mortality is very low, the vaccine would probably have less impact than in countries in which mortality is high. The researchers were also able to get data on existing vaccination rates for other routine infant vaccines, allowing them to estimate how many children the vaccine would likely reach. In addition, they estimated costs of delivering the vaccine in each country.
Their first analysis found that in the study countries, pneumococcal vaccination could prevent 262,000 deaths per year in children aged three to 29 months. That would avert more than eight million disability-adjusted life years (DALYs), a measure that accounts for time lost from premature death and disability. At a cost of $5 per dose, the vaccination program would cost $838 million dollars, or $100 per DALY averted. When the team also factored in hospital visits for nonfatal pneumonia that would be offset by the vaccine, the cost-effectiveness ratio was $80 per DALY.
“The standard of what’s considered cost-effective in developing nations is still being debated,” Lieu said. One of the most widely used standards is that a health service is cost-effective if the cost per DALY is less than three times the country’s per capita gross national product (GNP), and is very cost-effective if it is less than the per capita GNP. The results for each country varied widely, largely based on infant mortality rates. But overall, the researchers concluded that vaccination was cost-effective for all but one of the countries.
Though the vaccine looks like a good investment in this analysis, Lieu believes that the estimate was rather conservative, and the team is planning on publishing a further analysis that will include other potential benefits of vaccination. “In this particular analysis, we assumed the vaccine would be effective until 29 months of age, and then it wouldn’t help you at all,” she said. In reality, studies suggest the vaccine would remain effective until at least five years of age. Another potential benefit not included in this analysis is herd immunity—the ability of vaccination to help even those people who do not receive the vaccine. In the United States, pneumonia rates in adults have declined following vaccination of children, which has been attributed to a herd immunity effect.
Orin Levine, study co-author, directs the Pneumococcal Vaccines Accelerated Development and Introduction Plan (PneumoADIP) at Johns Hopkins, a project to build an evidence base for pneumococcal vaccination in developing countries. Because his work was directly involved with GAVI, the team members were able to get feedback on their data as they developed it. Lieu said that researchers doing analyses like these can often feel removed from the real world, but this project was particularly satisfying because the team worked in collaboration with their end user. “There was a lot more interaction between us as investigators and the real-world people who make the decision based on our analysis,” she said.
The report helped GAVI reach a decision to invest $200 million dollars in vaccination for rotavirus and pneumococcal infection. And this month, a group of five European countries and the Bill & Melinda Gates Foundation committed a total of $1.5 billion to a program that provides financial incentives for pharmaceutical companies to deliver pneumococcal vaccines to poor countries. The funding will create an artificial market for the development of new vaccines that can be manufactured on a large scale and tailored to the needs of the developing world.
