THE VALUE OF GENOTYPE MAPPING1

In the past, most of the emphasis on DR TB has been on resistance acquired through incomplete or inappropriate treatment, said Neel R. Gandhi, Associate Professor, Departments of Epidemiology, Global Health, and Medicine, Rollins School of Public Health, Emory University. As a result, TB programs have concentrated on understanding how best to keep individuals from developing resistance through multidrug therapy, directly observed therapy, and other adherence measures. However, individuals also can become infected with DR TB through transmission from another person. This primary, or transmitted, resistance can occur even in individuals who have never been on anti-TB therapy.

The interventions used to treat acquired and transmitted resistance are very different, Gandhi noted. With acquired resistance, the way to prevent additional DR TB is to strengthen the drug-susceptible TB treatment program. With transmitted resistance, transmission needs to be prevented through infection control programs.

In the past, it has commonly been believed that the same mutations that create resistance to medications will exert a fitness cost, making these strains less likely to propagate and generate clinical disease through transmission. According to this perspective, existing drug-resistant strains eventually will die out, and thus the focus should be on ensuring that new drug-resistant strains are not being generated. The advent of genotyping methods in the 1990s enabled a much better understanding of transmission. Genotyping allowed assessment of whether patients had very similar drug-resistant strains, and in those cases one could conclude that transmission likely occurred between them.

Also in the 1990s, high-profile outbreaks in the United States and in Western Europe, and somewhat later in other parts of the world, demonstrated that DR TB strains can be transmitted quite efficiently. These outbreaks of transmitted strains occurred most commonly in congregate settings, such as hospitals. Most TB control programs in hospitals at the time relied on smear microscopy, which cannot reveal drug susceptibility or resistance; the result was delays in diagnosing drug resistance. Delays in performing culture and DST added more time to the process. As a consequence, many patients were not diagnosed as having MDR TB until weeks or months after they had arrived at an institution, during which time many other patients and workers may have been exposed to the disease.

The hospitals where many of these outbreaks occurred had few, if any, infection control measures in place. They tended to have congregate wards

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1 This section is based on the presentation by Neel R. Gandhi, Associate Professor, Departments of Epidemiology, Global Health, and Medicine, Rollins School of Public Health, Emory University.



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