I have just returned from Kampala, Uganda, where I attended a Keystone Symposia conference on "Drug Resistance and Persistence in Tuberculosis." This thought-provoking meeting focused on the major challenges of tuberculosis in the developing world and attracted scientists from 40 different countries, including a strong contingent of Ugandan scientists and medics. While much complex science was presented and discussed, the one simple fact that hit me like a brick was that Uganda has suffered from a critical shortage of drugs necessary to fight the disease for the last six months. This means the country's tuberculosis patients are being left untreated - a huge problem for this wonderful land. But this is not just a Ugandan or African problem; the biology of this disease means it will soon be our problem.Tuberculosis is primarily a disease of the lungs, in which uncontrolled growth of the bacteria results in severe lung damage and ultimately death (in 2010, 8.8 million people fell ill with tuberculosis; 1.4 million died). The bacteria are readily transmitted through the air by infected individuals prone to severe bouts of coughing. The standard treatment for tuberculosis is a six- to 12-month course of powerful antibiotics. Fortunately, the treatment is relatively cheap - approximately $30 per person, a figure that includes the requisite monitoring. However, there is a growing problem of drug resistance, and many Ugandans are now infected with multi-drug-resistant strains of the tuberculosis bacterium (MDR-TB) that do not respond to the standard treatment. These strains can develop when the course of treatment is interrupted, either because the patients feel better and stop taking their medication, they forget to take them, stop because of side effects, or the drugs become scarce. The disease in these patients can then only be controlled by more powerful drugs that tend to have severe side effects and are much more expensive - approximately $3,000 per person.The challenges are many. The diagnosis of MDR-TB, as opposed to regular tuberculosis, is a major issue since the tests are expensive and require sophisticated equipment. Once a patient is diagnosed, the necessary drugs can have severe side effects, leading to poor patient compliance. In this regard, clinical monitoring of patients is also a challenge, given the limited medical facilities in many developing countries such as Uganda. Another challenge is that MDR-TB patients should be isolated to avoid the further spread of this more intractable form of the disease. But this is difficult to achieve in practice, especially when the patient is the family's only bread-winner. Finally, the drugs to treat tuberculosis need to be readily available to all who need them. The shortage of drugs in Uganda is simply not acceptable, and we in the developed world need to address this problem with all due urgency. It is estimated that about two billion people are currently infected with the tuberculosis bacterium - about one-third of the world's entire population. This incredible fact must be understood in the context of the biology of the infection. In general, only approximately 5-10 percent of individuals who become infected with the bacteria actually develop the severe and fatal form of the disease. In the other 90-95 percent, the immune system is able to contain the bacteria by walling them off in structures called granulomas. This process does not destroy the bacteria, which remain alive in the granulomas, but it does prevent them from spreading and doing any further damage to the lungs. Individuals who have controlled the infection in this manner may suffer no overt ill effects nor even know they were infected (they also cannot transmit the disease). This is usually the end of the story for these individuals. However, if extraneous factors subsequently weaken their immune systems, the bacteria can escape from the granulomas and mediate full-blown tuberculosis. The case rate for active tuberculosis is growing alarmingly in Uganda and many other countries. The primary reason is that the disease is exacerbated by the Human Immunodeficiency Virus (HIV) epidemic. As discussed in April's (Petri) Dish column, HIV suppresses the immune system and renders people perilously susceptible to other infections, such as tuberculosis. HIV can also cause the reactivation of disease in individuals that had previously controlled the bacteria in granulomas. In fact, in much of the developing world, tuberculosis and HIV go hand-in-hand as a dual infection in many individuals.At the beginning of the article, I hinted that tuberculosis will soon be a problem here in the United States. The problem is that new strains of tuberculosis are emerging that do not respond to almost all the currently available drugs. These extremely drug-resistant strains of tuberculosis (XDR-TB) are virtually uncontrollable and are likely to spread across the globe at some point in the future. This frightening fact underscores the importance of the Keystone Symposia conference in Kampala. The scientists and doctors at the meeting discussed a range of problems and solutions including promising candidates for new drugs. But it was also very apparent from Uganda's plight that far more attention needs to be directed at improving the delivery of primary health care in developing counties. Vigilant control of tuberculosis in high-burden countries will considerably delay the emergence of XDR-TB. Indeed this is a primary focus of the Bill & Melinda Gates Foundation, the leading sponsor of the Keystone Symposia meeting in Kampala. We all have a stake in resolving this global health crisis.David L. "Woody" Woodland, Ph.D. is the chief scientific officer of Silverthorne-based Keystone Symposia on Molecular and Cellular Biology, a nonprofit dedicated to accelerating life science discovery by convening internationally renowned research conferences in Summit County and worldwide. Woody can be reached at (970) 262-1230 ext. 131 or firstname.lastname@example.org.
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