While lay critics blame vaccines for everything from AIDS to autism, among vaccinologists one of the biggest concerns is a phenomenon known as replacement disease. This is the worry that in eliminating one pathogen, vaccines may clear an ecological niche for a new one that is just as bad. It's why a recent study published in the Journal of the American Medical Association sent a ripple of anxiety through the community of doctors and scientists who fight the world's most deadly childhood pathogen: Streptococcus pneumoniae, the bacteria also known as pneumococcus.
In the JAMA article, scientists from the Centers for Disease Control's Arctic Investigations Program reported that serious pneumococcal infections (such as meningitis and pneumonia) were again on the rise among the Native Alaskans they studied—after an initial dramatic decline that followed the introduction of the first effective childhood vaccine against the bacteria. Before 2000, when the American Academy of Pediatrics began urging all parents to get their babies vaccinated with the shot, which has the trade name Prevnar, about 4 in every 1,000 Native Alaskan children contracted invasive pneumococcal disease each year. Within two years of the introduction of the vaccine, the rate had fallen to about 1.3 per 1,000, according to the study. But by last year the rate had crept back up to 2.4 per 1,000.
Vaccine producers and experts worry about replacement disease nearly every time a new vaccine is rolled out and given to millions of people. Usually, these fears don't pan out. But the JAMA paper seemed to indicate that, this time, they might be justified. This demonstration of replacement disease, the authors of the JAMA paper wrote, "may signify a limit to the usefulness of the currently available vaccine."
Chucking Prevnar is an alarming idea for vaccine proponents. Pediatricians hailed the arrival of the vaccine as a technical and humanitarian triumph, and have rewarded Wyeth with more than $1 billion a year in sales. While some have accused the company of price-gouging, its success with the sophisticated vaccine—which was made by fusing bacterial proteins onto a polysaccharide backbone—is a good thing for all of our health. But you don't want to spend years and hundreds of millions of dollars developing such a product unless you can be sure it will make you a lot of money by successfully diminishing disease. If the bug outwits the vaccine, it could have unpredictable consequences for disease, and discourage vaccine makers in general.
Pneumococcus, which kills about 1 million children around the world every year, has bedeviled infectious disease experts for a century because it contains 90 different strains. It is too cumbersome and expensive to include all or even most strains in a single vaccine, so Wyeth, the maker of Prevnar, included seven of the most invasive and antibiotic-resistant strains in its vaccine.
The good news is that in the Prevnar-using world, those strains of bacteria have nearly vanished. The bad news from the Alaska study is that strains not covered by the vaccine seem to be moving into the vacuum the vaccine created—making an end run around Prevnar. In particular, a highly virulent strain called 19A, minor in the pre-vaccine era, was now responsible for a third of the serious infections among native Alaskans.
The rise of 19A has stirred up some old fears. In the 1960s, for example, many public-health specialists were concerned that immunity would wane in toddlers getting the new measles and rubella vaccines, causing them to become infected later in life. This was of particular concern because rubella infection during pregnancy can cause severe birth defects, including autism. Similar fears followed the 1991 introduction of infant vaccines for haemophilus influenza type B, or HiB, disease. They've also been voiced about the new cervical cancer vaccine, which prevents infections by the two deadliest human papilloma viruses but which theoretically could allow other viral strains to move into the niche and cause just as much cancer.
In the end, however, replacement disease and related worries failed to materialize in the cases of rubella and measles. Widespread vaccination eliminated transmission of these viruses, with only rare cases reported in the United States every year. Nor have other strains of the HiB bacteria posed a serious threat. It may be too soon to make a judgement on the cervical-cancer vaccine, but there's no sign yet of new strains emerging. And so the Prevnar story marks the first time an organism has successfully managed to elude a marketed vaccine and raise the real threat of replacement disease.
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