ON THE MARCH TO ERADICATE CHILD ILLNESS

Dr. Bruce Aylward is yielding no ground. As coordinator of the World Health Organization's $4 billion Global Polio Eradication Initiative, Aylward runs a worldwide immunization program that is supposed to eliminate the virus forever by the end of this year. He's still not ready to push back the schedule, even though cases of the devastating childhood illness have been popping up in countries like Indonesia and Yemen, where it was wiped out long ago. "The virus has never been in this much trouble," he insists. When the global campaign began in 1988, the disease was paralyzing

350,000 or more victims a year on five continents--mostly children. So far this year, the number of confirmed cases hasn't passed the low hundreds. Now, says Aylward, the essential thing is to finish wiping out the disease. "If we blink," he says, "it will be not hundreds, but hundreds of thousands."

People forget too quickly the horrors of sicknesses like polio. In 1954, the year before Jonas Salk introduced his vaccine, the virus killed more than 3,000 Americans and crippled roughly 20,000 others. Today the United States has been effectively polio- free for more than a quarter century. That success story is hardly unique. A century ago, before childhood immunization became routine in America, the upper-respiratory infection known as diphtheria was a worse killer than cancer. Now the United States gets an average of three cases a year. Whooping cough, measles, mumps and rubella have become rarities in America. Wider vaccine coverage could further reduce the burden of other important illnesses already in decline, like hepatitis A, hepatitis B, chickenpox and invasive disease from Haemophilus influenzae type b (Hib for short), a bacterial meningitis that can cause deafness or mental retardation in children when it doesn't kill them outright.

But the economics of vaccines can be as cruel as any disease. A third of the world gets none of the childhood immunizations that are routine in the West. More than 2 million children a year die as a result, according to Dr. Julian Lob-Levyt, executive secretary of the Global Alliance for Vaccines and Immunization. For drugmakers, the profitability of developing and distributing vaccines tends to be marginal at best, and medical aid to the Third World is chronically underfunded. And yet for humanity as a whole, immunization programs pay huge dividends, not only in lives saved but in reduced medical and social burdens. "The cost benefit of vaccines is overwhelmingly the best investment yield in biomedicine and health," says Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. "It is much more economical to prevent a disease than to treat a disease." "[Immunization] is the most cost-effective technology in public health, bar any," says Lob-Levyt.

That fact is a powerful motivation for scientists, relief groups, philanthropists and others in the fight against communicable diseases. Earlier this year the Bill & Melinda Gates Foundation teamed up with the Norwegian government to make a joint pledge of $1 billion for standard childhood immunizations in the Third World. Meanwhile, immunologists are working to expand their arsenal. A few of the most promising targets:

Dengue Health workers have spent decades in a losing fight to stop the mosquito that transmits dengue. Every year the hot-climate viral illness infects as many as 100 million people, many of them children. Roughly 500,000 end up hospitalized for intravenous feedings, oxygen and sometimes transfusions. Up to 5 percent die anyway. "Parents go through hell," says Scott Halstead, research director for the Pediatric Dengue Vaccine Initiative. One form of the disease, dengue hemorrhagic fever, mimics the Ebola virus: victims bleed from their bodily orifices as they die. Now scientists at Aventis and GlaxoSmithKline are closing in on vaccines to ward off the disease. Studies are underway in Vietnam, Thailand and Nicaragua, and Halstead says the result could be available by 2010--for under $2 a dose, he hopes. The best thing about dengue is that it needs human hosts to survive. If a population is immunized, the disease will be gone, no matter how bad the mosquitoes get.

Pneumococcus Streptococcus pneumoniae, also known as pneumococcus, kills more than 1 million children a year around the world. In the five years since Wyeth Pharmaceuticals won FDA approval for the pneumococcus vaccine Prevnar, the incidence of pneumococcal disease and related cases of meningitis among U.S. children under 2 has plunged by 80 percent, according to Peter Paradiso, a Wyeth vice president. Now the company is developing special formulations of the vaccine for the international market. Bacterial strains of pneumococcus vary from region to region around the globe. In April company researchers reported favorable results in Gambia. The U.S. price per dose is $50--more than a week's pay in Gambia--but Paradiso says the company is looking for ways to make the vaccine available to the world's poorest countries.

Malaria Of the more than 1 million people a year who die of malaria, 90 percent are under 5. "By the time kids are about 5, they've mostly built up their immunities," says Melinda Moree, director of the Malaria Vaccine Initiative. "They have malaria parasites in their bloodstream, but they're not sick." Last year researchers tested a GlaxoSmithKline vaccine on 1,000 children between 1 and 4 in Mozambique. It seemed to protect most recipients from severe illness, and it worked better in kids 2 and under than in the others. This summer, researchers will test it on infants. Moree thinks a working vaccine might be available in five years, but no sooner.

HPV Scientists at Merck Research Laboratories have almost finished testing a vaccine against human papilloma virus (HPV), which causes more than 99 percent of all cervical cancer. Up to 70 percent of all women are likely to catch the virus sooner or later without realizing it: although it's the world's most prevalent sexually transmitted disease, HPV has few symptoms aside from being a slow carcinogen. "Guys don't know they've got it. Girls don't know they've got it," says Dr. Eliav Barr, senior director of clinical research at Merck Labs. Because of the virus, one woman in four is likely to develop precancerous cells in the cervix at some point in her life. "If caught early, it's treatable," says Barr. And if not? Cervical cancer kills more than 200,000 women a year worldwide. Merck says its vaccine, in human trials since 1997, prevents 100 percent of the cervical precancers and occasional genital warts caused by the four most common HPV types. Merck is also testing the vaccine in men and evaluating whether it helps infected patients to fight the virus. The company expects to submit its findings to the Food and Drug Administration later this year; if the FDA approves, young people may be routinely immunized before they become sexually active.

TB Approximately one third of the entire human race is infected with tuberculosis, a disease that kills 2 million people a year, mostly in the Third World. It's a gruesome death: the disease slowly eats away the victim's lungs. Antibiotics can fight the pathogen, but resistant strains have sprung up. The first vaccine for TB, introduced in 1921, was never very effective. With backing from the Aeras Global TB Vaccine Foundation, researchers are working on a more effective vaccine, which might be available by 2013. It doesn't have to be perfect. Nine out of 10 carriers of the infection never develop the actual illness or the contagion that goes with it. Even a small improvement in the odds would be a big step toward eliminating the disease in much of the world.

Other challenges will be far tougher. The search for an AIDS vaccine has attracted far more public support than other major killers like TB and malaria, but medical researchers say it's still no more than a distant dream. "I'll be delighted if I see an effective HIV vaccine in my lifetime," says Lob-Levyt. "It's going to require the kind of scientific breakthrough where we're not even sure in which area that breakthrough would occur. It's probably one of the biggest challenges to science we have faced." Still, medical researchers have performed miracles before. A quarter century ago, they achieved the once unthinkable feat of completely eradicating smallpox. Within the next year or two, the polio virus should be similarly extinct. The important thing is to try.