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The Path of Least Resistance

Billions are being spent on disease-fighting drugs in poor countries, but millions are still dying. Why? Because what doesn't kill a virus only makes it stronger.

Never before has there been such a generous and concerted global effort to fight the diseases that afflict poor countries as there is today. More money is being spent, more research is being conducted, and more governments and organizations have pledged to eradicate the illnesses that kill millions in the developing world each year. Between 2001 and 2006, annual assistance for health programs in developing countries more than doubled, from about $6 billion to $14 billion. Roughly half of that total is dedicated to reducing infectious diseases, with several billion spent each year on drug treatments. The vast sums of money are coming from governments in both developed and developing countries, as well as from well-funded private groups and charities such as the Bill & Melinda Gates Foundation.

Despite these colossal efforts, the battle against infectious diseases is not yet being won. Cases of both malaria and tuberculosis (TB), two diseases that have been singled out for donor attention, are on the rise. Together, these diseases kill more than 3 million people each year, and many millions more suffer bouts. About 402 million cases of malaria occurred worldwide in 2004, up 47 percent from 1998. Meanwhile, new TB cases rose nearly 30 percent between 1996 and 2006, from 7 million to 9 million. Other infectious diseases, such as cholera, shigellosis, and Streptococcus pneumoniae infections, most of which are largely eradicated in the rich world, remain common killers. What’s worse, these diseases are becoming increasingly difficult to treat.

How can we be working harder than ever against these ailments but making so little headway? Because the microbes we are fighting are adapting faster than we are. The drugs used to treat many diseases in the developing world are becoming less effective at killing the viruses, bacteria, and parasites that cause illness. Microbes are constantly evolving organisms, and many are proving to be impervious to the drugs designed to combat them. Hardy viruses, capable of mutating faster than we can kill them, can wipe out years of research and millions of dollars spent on drug development. And as resistant strains of disease are born, new drugs must be developed that can successfully attack the mutated form of the disease, creating a vicious cycle of infection-treatment-mutation. Too often, the labors of drug companies and the international health community lag far behind the speed with which diseases evolve. Add to the problem weak and unresponsive health systems, drug makers uninterested in products for poor customers, and dangerous fake drugs, and our well-intended billions in health aid don’t stand a chance against the next generation of mutating microbes.

Time and again in recent years, drugs that once successfully treated infectious diseases have had to be abandoned because of a bug’s ability to fight back. In the 20th century, eight different drugs were developed for treating malaria. Today, only one remains widely effective, and it is so expensive that it is often rejected in favor of cheaper, less potent options. Quinoline-based drugs have been the bulwark of malaria treatment for decades, but an estimated 50 to 60 percent of cases in East and Central Africa, where roughly 110 million people are exposed to the disease, are resistant to the drugs. In extreme cases, such as Burundi, the one-time standard treatment, chloroquine, is ineffective in 69 percent of cases, and its newer replacement fails 31 percent of the time. In South America, resistance is as high as 80 percent. In Peru, for instance, chloroquine cannot cure 86 percent of patients. Fortunately, quinoline-based drugs are not the only tool in the antimalarial arsenal. A breakthrough successor was introduced in 1967, but within a few years, malaria parasites managed to become largely resistant to the new treatment. Parasites developed a resistance to two drugs developed earlier this decade within 12 months.

Tuberculosis is another disease prone to drug resistance. Run-of-the-mill TB is complicated to treat, requiring six to nine months of drug therapy and many different antibiotics in specific combinations. Both the long treatment period and the difficulty patients have in adhering to the regimen give the TB microbe good conditions for mutating before the drugs can cure. And because the same drugs have been used to treat the disease for more than five decades, they are becoming less powerful. Health workers are encountering a sharp rise in drug-resistant TB, including incurable cases. Today, about 20 percent of new TB cases each year are resistant to at least one of the drugs available, and almost a half a million cases (about 5 percent of the world’s total) are classified as multidrug resistant based on their resistance to the two most powerful first-line drugs. In Tashkent, Uzbekistan, for example, approximately 60 percent of cases where the patient has previously been treated for TB are multidrug resistant; more than 85 percent of repeat patients are resistant to at least one drug. Of newly infected patients, the highest rate of resistance is found in Baku, Azerbaijan, where nearly 1 of every 4 new patients is infected with an already multidrug resistant strain. The costs of treating these resistant patients can be as much as 300 times more expensive than for regular cases of TB, and fewer than 10 percent of them currently receive treatment. TB is also spread easily from person to person, so the remaining untreated cases create a substantial public-health threat.

The reality is that we are in a battle with the microbial world that we cannot ultimately win. Diseases move around with people, and so does resistance. But that doesn’t mean we shouldn’t try to level the playing field. The international health community must act quickly to preserve the efficacy of our existing drugs, while we keep at the arduous and expensive task of replacing those that no longer work. Key to improving our chances is to learn where microbes are mounting a comeback. Better information sharing about which drugs have lost their effectiveness, how fast people build up resistance, and how resistant strains spread is critical for improving our odds against swiftly mutating diseases. At a minimum, more timely information about resistance will reduce the all-too-frequent mistake of people taking drugs that can no longer help them. It will also divert those drugs to places where they can still make a difference. Having in place an internationally linked resistance-surveillance system will give us a fighting chance against fast-moving parasites. Until then, we will never be confident that we are getting the right drugs to the right people at the right time.

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