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Lives lost as vaccine programs face delays

Companies have developed two vaccines that theoretically could save the lives of several million children over the next decade, but efforts to get them to the poor countries that need them most are lagging.
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Companies have developed two vaccines that theoretically could save the lives of several million children over the next decade, but efforts to get them to the poor countries that need them most are lagging.

One vaccine, which protects against a life-threatening form of pneumonia, has been available to children in the United States for five years and has had a dramatic impact on disease here. The other, a vaccine that protects against a deadly form of diarrhea, is poised for a rollout soon among middle-income countries in Latin America.

The vaccines are the subject of special programs designed to speed them to poorer countries. With the Bill & Melinda Gates Foundation spending billions to improve global health and encouraging efforts to solve long-standing problems, excited doctors have been trying to create a system that would get such vaccines to rich and poor alike at the same time.

But the efforts have faltered amid a dizzying array of snafus, misjudgments and business difficulties. One company can't produce enough vaccine, and studies needed to support widespread use of another have been slowed by behind-the-scenes squabbling. The problems have proven so vexing that the vaccines are expected to take another three to five years to reach the poorest villages.

Historically, vaccine companies rarely focused on lower-income markets, and would not scale their manufacturing plants to produce excess vaccine for them. Life-saving shots would trickle down to poor countries after decades on the market, costing many lives.

To break that cycle, the Global Alliance for Vaccines and Immunization, a disease-fighting coalition in Geneva, selected the pneumonia and diarrhea vaccines for special emphasis three years ago. The alliance of governments and organizations, known as GAVI, is closely tied to the World Health Organization but receives much of its funding from the Gates Foundation in Seattle.

In establishing the program to accelerate a vaccine against rotavirus, a diarrhea-causing intestinal germ, organizers said in a statement that they aimed to ensure "that rotavirus vaccine is available to children in developing countries at the same time as those living in the developed world."

Bigger trouble to come?
That is now all but certain not to happen, nor has it happened with the pneumonia vaccine. Some experts see the problems as a harbinger of bigger trouble to come, as the Gates Foundation funds development of vaccines for malaria and tuberculosis that could save tens of millions of lives but may face similar deployment hurdles.

Prevnar, the pneumonia vaccine sold by Wyeth, a drug maker in Madison, N.J., has had a sharp impact in the United States. Though expensive, it has been a runaway success, with sales topping $1 billion a year -- a first in the history of vaccines.

The company initially underestimated demand even in rich countries, and has struggled to expand a complex manufacturing procedure. Wyeth says it is working on a version of the vaccine that it hopes to sell to poor countries at reduced prices, but many public-health experts believe the supply situation won't be solved until new manufacturers come into the market in several years.

Wyeth's critical supply decisions had already been made by the time GAVI funded a $30 million program at Johns Hopkins University nearly three years ago to accelerate introduction of Prevnar or a similar vaccine to poor countries.

The director of that project, Orin Levine, has worked with Wyeth to refine its long-term plans, but has mainly focused on laying the groundwork for a rollout in poor countries once competing vaccines are licensed. Levine's efforts have received high marks, even though doctors are disappointed to see lives lost to a vaccine-preventable disease. The germ in question, Streptococcus pneumoniae , kills an estimated 1.6 million people a year, about half of them children in poor countries.

The case of rotavirus vaccine is more troubling to many experts, for a plentiful vaccine that became available last year isn't being widely used.

Most people have never heard of rotavirus, but every child in the world contracts it early in life. In the United States, some children are hospitalized with rotavirus diarrhea, but they get good care and don't die. In countries with poor health systems, children often progress to catastrophic dehydration and an estimated 440,000 die of rotavirus every year.

Reading that statistic was one of the things that drew Bill Gates, the Microsoft Corp. founder, into global-health issues in the 1990s. "I thought, 'Rotavirus? -- I've never even heard of it,' " Gates recalled in a speech in May. " 'How could I never have heard of something that kills half a million children every year?' "

Further study convinced him that many millions of poor children die of preventable diseases. One of the Gates Foundation's first big moves was to grab underused vaccines, such as one against a serious liver virus, and make them more widely available, a strategy that is on track to save millions of lives.

Public-health doctors wanted to go further, proving that new vaccines can be made available worldwide as soon as they're ready. It seemed for a while that rotavirus vaccine would be the case in point.

Past experience suggested potential safety problems with a vaccine, so GlaxoSmithKline PLC of London, the drug company furthest ahead with a new product, launched huge trials in Latin America. Merck & Co. Inc. of Whitehouse Station, N.J., is also working on a vaccine.

Heartened by statements from GAVI about a quick rollout, Glaxo's biologicals division in Rixensart, Belgium, built a plant able to supply much of the world with its vaccine, Rotarix.

Even with a manufacturer willing to sell to poor countries, public-health doctors still have to accomplish a formidable list of tasks to introduce a vaccine. Many health ministers won't embrace a new vaccine until they see studies convincing them the disease in their country is severe and that the vaccine is cost-effective in combating it. Moreover, money must be identified to help poor countries pay for the vaccine.

The Rotavirus Vaccine Program, similar to the Hopkins program on pneumonia, was set up in 2003 to tackle those problems. People close to the situation said there has been considerable tension behind closed doors between the managers of this program and GlaxoSmithKline. Executives at the company's biologicals division said they had difficulty getting the program to commit to funding and a strategy for tests in Africa and Asia.

‘A bit frustrated’
"We're a bit frustrated," said Deborah E. Myers, director of external and government affairs at GlaxoSmithKline Biologicals. "We've asked about what we need to do to supply information to make the case. We could never get them to make a decision."

John Wecker, a former pharmaceutical executive who directs the Rotavirus Vaccine Program, acknowledged vigorous discussions. "I think it's fair to say that we've struggled sometimes with the manufacturers" about how to proceed, he said. But the main problem, he contended, was not any lethargy in his program, but the sheer difficulty of setting up complex research in poor countries. Key studies are finally underway, but aren't close to being finished.

Christopher J. Elias, president of the Program for Appropriate Technology in Health, a Seattle organization that houses and oversees the rotavirus program, said he felt it was making progress. "In terms of whether it's working, the only honest answer is that it's too soon to tell," he said.

All parties involved said it had become evident that two or three years of groundwork is not enough to accelerate a vaccine, and one lesson is that regional studies need to be planned far ahead. "Start earlier," Wecker declared. Charities funded by Gates that are developing vaccines for tuberculosis and malaria are already applying this finding.

It is clear that Glaxo created some delays itself: To hasten a rollout in poor countries, the company first licensed its vaccine in Mexico. But problems with that country's drug regulators slowed the World Health Organization in declaring the vaccine safe and effective for global use -- a crucial step.

Julian Lob-Levyt, executive secretary of GAVI, emphasized the experimental nature of the rotavirus and pneumococcal acceleration programs that his group created. "We need to be open and self-critical and see how we can move faster," he said.

Merck and Glaxo are expected to enter U.S. and European markets with rotavirus vaccines as early as next year. Merck recently cut a deal with the Rotavirus Vaccine Program to pursue research in poor countries, but the studies won't begin until late next year. People in the field estimated that it will be at least three to five years before the new vaccines begin to reach the children that need them most.

‘Still not fixed’
"It was the industry that was being chastised a decade ago," said Steven Drew, a vice president at Glaxo. "We've done our bit, and the problem is still not fixed."

Some public-health doctors, while regretting that the original goal won't be met, urged a sense of perspective, noting that the vaccine may reach poor children just a few years after it reaches those in rich countries. "If we can cut the lag time from 30 years to a decade or less, that's 20 years of lives saved," said Nils Daulaire, president of the Global Health Council, an advocacy group in White River Junction, Vt.

The sentiment, however valid, is a measure of the degree to which the public-health world has become accustomed to death on a mass scale.

If the rotavirus and pneumonia vaccines take another three years to reach poor countries, 3.7 million children will have died of the diseases by then. That is 3,397 children for every day's delay.