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Emerging Diseases : Biological Terrorism : Biological Warfare

Drug Resistance, MDR

Microorganisms are a wonderful laboratory in which to witness evolution in action. Given their numbers and lifespan, they can react quite quickly to new environmental influences. Thus one can see them change with extreme rapidity. Using a variety of genetic techniques, they have the capability to very quickly acquire biochemical traits to take advantage of new situations or to defend against new threats.

In evolutionary terms, these new situations constitute selection pressures. That is, they are environmental pressures on the organisms which select certain individual organisms as being better suited to this new environment than others. These selected organisms then pass on their beneficial traits to their offspring. In this manner, beneficial traits accrue in the population while loss which are less-beneficial disappear. Given enough such changes and given other criteria (such as geographic isolation) these changes can add up to the point where a population can no longer interbreed with its ancestor population. Because of different selection pressures over time, these populations are now so different that they are genetically isolated in the reproductive sense. They can no longer mate and produce viable offspring. In this manner new species are created.

From the perspective of a microbe, anti-bacterial and anti-viral drugs are selection pressures. They present the pathogen with a range of hostile environments. Given this, those microorganisms that have through chance mutation or recombination acquired traits that resist these selection pressures have a great advantage. While all their fellow organisms might be destroyed, they survive. Thus it is more likely that their genes for resisting these hostile environments will be passed on to the next generation.

This is exactly what has happened over the past few decades. Pathogens have rapidly evolved resistance to the modern technology of antibiotics. As antibiotics have become more widespread - and abused - microorganisms have increasingly developed resistance. In addition, new drugs have become rare and increasingly expensive. Therefore a host of diseases once easily treatable are now potentially fatal.

Consider malaria. Human malaria first arose in West Africa in prehistoric times. In a sign of how ancient the disease is, west African populations have evolved significant genetic resistance to the parasite. This resistance takes the form of the Sickle Cell gene. One copy of this gene alters red blood cells in a way which discourages parasitization by the malarial organism. (Whereas two copies of this gene induce Sickle Cell Anemia, an often-fatal result.)

In historic times malaria has spread to all parts of the globe. Once considered a tractable disease, it has recently evolved resistance to many antibiotics. As a result, malaria is a growing affliction. For example, chloroquine - once the first-line treatment for malaria- is no longer effective in over 80 countries. But evolution doesn't stop there. In addition, many malaria strains have evolved Multiple Drug Resistance (MDR). That is, they are resistant to not just a single medication but to a broad array of such treatments. Thus there now exists in this world untreatable malaria, a situation which has not existed for centuries. For malaria, modern technology is in retreat in its fight against evolution and microbes.

MDR is now a pervasive problem throughout the world. For example, dysentery is now 90% immune to the two first-line drugs. Typhoid epidemics are increasingly immune to treatment. Tuberculosis is now often untreatable. Epidemics of MDR-TB (Multi-Drug Resistance) are now being reported all over the world, from the poorest shanty-towns of Brazil to the plushest suburbs of Chicago.

Drug-resistance is pervasive amongst viral diseases as well. Here HIV is a textbook example of evolution in action. HIV is genetically unstable and has an extremely high mutation rate. Because of this, even small HIV populations rapidly evolve resistance to anti-viral drugs. This is the reason why anti-viral "cocktails" (a mixture of multiple drugs) are the only effective treatment for AIDS: the virus evolves so rapidly that it quickly finds ways to defeat a single anti-viral agent. Therefore only by administering multiple drugs is the virus held in check.

This rapid evolution is also the reason, by the way, why there are more HIV strains (technically known as clades) in Africa than in the rest of the world. Since HIV originated in Africa it has had more time to evolve greater diversity relative to the rest of the world, where just a few viral strains predominate. Because of this, HIV is much more difficult to treat in Africa than in Europe or America. The higher innate diversity of the wild African HIV strains makes them more likely to resist a given treatment or vaccine.

The implications of MDR are most immediate for non-developed world. Here cost is a more important factor and so options are limited. But don't think the problem stops there. In 1999, 14,000 patients in the US died from drug-resistant bacteria. The fear of MDR haunts the finest hospitals in the developed world. Illnesses that just a few years ago were easily treated now can cause panics, as physicians race to determine which - if any - drugs can still deal with the problem. Indeed, MDR organisms are increasingly dragging the world back to the terrors of pre-modern days.

Link: Revenge Of The Bugs: Why Old Drugs No Longer Work
Link: The Epidemic Of Multi-Drug Resistant Tuberculosis (MDR TB)
Link: The Evolutionary Arms Race
Link: WHO 1999 Infectious Disease Report
Link: Fighting Mutant Super Bugs
Link: MDR TB Epidemics Spreading In Russia
Link: Outstanding site on Malarial Ecology, Disease, Symptoms and Treatment
Link: Sickle Cell Anemia and Malaria
Link: Bill Gates Foundation - Eliminating Malaria
Link: Malaria, AIDS and Evolution