ON GUARD AGAINST THE ACUTE—BLINDSIDED BY THE CHRONIC: THE WAYS WE HAVE FOUGHT
Why has the war metaphor so dominated our approach to infectious disease? One reason is that the metaphor has been successful in some arenas. We humans rally to the defense against a common enemy, and this support led to the control of many damaging infectious diseases during the first half of the twentieth century. Still, the only case of complete victory—eradication of the enemy—has been the smallpox campaign, and that vaccine was no high-tech wonder. William Jenner took pus from a sore on a cow and used it to inoculate those whom he hoped to protect from smallpox. The primary technological advance for vaccine development involved growing the still mysterious vaccinia virus in cows to amplify the virus, and then scraping the infected cow tissue to get the material for the vaccine. If we allow the definition of war to include organized attacks on populations of other species, the eradication of smallpox during the 1970s was literally a war, the most cost-effective antimicrobial war that has ever been fought. It was accomplished in just over a decade with a modest price tag of $300 million. The army comprised a few hundred officers (physicians and epidemiologists) and a few thousand foot soldiers (assistants working in the lab and outside community). In 1977 they rooted out the smallpox virus from its last refugia: Bangladesh and Somalia. Their efforts were heroic but their enemy was vulnerable. As microbial targets go, the smallpox virus was a clay pigeon. Its ability to change form was so limited that vaccination with a different virus of the same evolutionary group, the vaccinia virus, could trigger an immunity that would knock out the entire spectrum of smallpox viruses. To win wars, social values must be compromised. One of the first to be diminished is the value of human life, because war involves the killing of people. Freedom is another casualty. Imagine what would have happened if each soldier in the trenches of the Somme or Galipoli had been given a free choice to go back to his family without penalty or to die in a fruitless rush against the enemy trenches. How many would have stayed? The actions taken in microbial wars need not be as severe, but it is wishful thinking to expect that we can win these wars while adhering to all our peacetime values. Administrative agencies such as the World Health Organization set up guidelines to help preserve such values. Yet even in the war against smallpox—the most lopsidedly winnable of our microbe wars and the most illustrious victory of the World Health Organization—these guidelines had to be violated. One of the commanders in this war, Isao Arita, later confided, “If we hadn’t broken every single WHO rule many times over, we would never have defeated smallpox. Never.” Part of the problem is that the need to break these rules increases the closer one gets to eradication. Some people are willing to receive a vaccine, others are obstinately opposed. The early positive effects of vaccination provide an inflated sense of success because the success is enhanced by those who choose to cooperate. The completion of the campaigns often requires that the last holdouts are persuaded to cooperate or forced to submit. All eradication campaigns suffer from this Achilles’ heel. Some people want to have their houses fumigated, others resist. Some prefer to have their contagious illness treated, others refuse. If we are to win some of the more winnable wars—those against measles and polio, for example—we may need to violate more rules than have been violated to date. Vaccines were the first great strategic success in the war against infectious disease, but the return on the investment has steadily declined as increasing amounts of money have been invested in this option. The most successful vaccination campaign, the eradication of smallpox, is attributable to an eighteenth-century innovation, the vaccinia vaccine. It cost almost nothing and swept aside one of humankind’s worst infectious adversaries. The great vaccination efforts of the first half of the twentieth century were cheap and marvelously successful. Vaccines against diphtheria and tetanus were developed with less money than is now sometimes awarded in one grant from the National Institutes of Health. Vaccines against pertussis and polio were developed during the 1950s; they were successful but came with greater financial cost and more collateral damage than the smallpox program. Some of the viruses in live polio vaccines reverted to neurovirulence, causing paralysis in a small number of those vaccinated. Moreover, vaccine viruses proved infectious for those in contact with the vaccine recipients. This secondary transmission of vaccine virus increased the protection of the population and was therefore considered a bonus so long as the viruses did not revert to neurovirulence. But polioviruses are particularly prone to mutations. The live viruses in the polio vaccines were like unseasoned soldiers who could not be trusted to protect without shooting innocent civilians. The threat of reversion to neurovirulence has been recognized since it was encountered in Philadelphia in 1935 when an experimental polio vaccine was administered to several thousand children. Viruses from an attenuated live vaccine reverted to neurovirulence, killing five of the nine children who contracted polio from it. Reversions to neurovirulence have occurred sporadically since then and have made vaccine researchers apprehensive; they are hoping that the vaccine viruses left as a legacy of the live poliovirus vaccination programs will not develop similar reversions to virulence, generating new polio outbreaks where wild polio has been eradicated. A more sinister problem was recognized by Michele Carbone in the early 1990s. Some polio vaccine batches were contaminated with a monkey virus, SV40, which now appears to be causing cancers of the brain and lungs in a small percentage of those who were vaccinated in the 1950s and early 1960s. Live vaccines against measles and mumps were developed in the 1960s, and a few more vaccines were added during the last three decades of the twentieth century: vaccines against hepatitis viruses A and B, Haemophilus influenzae, and the perennial ones against influenza. The effectiveness of these vaccines has varied from the magnificent suppression of encephalitis by the Haemophilus vaccine to the erratic performance of the influenza vaccines. But the important point is that these successes came from increasing expenditures in vaccine research. The cost-effectiveness of vaccine development has eroded because of the many failures, such as the efforts to develop vaccines against malaria and AIDS. Vaccine development certainly has a place in our future, but their use as weapons to destroy infectious adversaries is becoming more costly and generally less effective. We will need to develop and use vaccines more cleverly to improve their performance.
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