Research ArticleTuberculosis

Community-Wide Isoniazid Preventive Therapy Drives Drug-Resistant Tuberculosis: A Model-Based Analysis

Science Translational Medicine  10 Apr 2013:
Vol. 5, Issue 180, pp. 180ra49
DOI: 10.1126/scitranslmed.3005260

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A Deeper Look at Drug Resistance

Although some things may seem obvious at first glance, looking in more depth may paint a different picture. In some complex situations, asking questions in different ways may lead to very different answers. One example is the use of isoniazid preventive therapy (IPT) for tuberculosis (TB) in HIV-prevalent communities. Because HIV-infected individuals are much more likely to develop TB than immunocompetent people, the World Health Organization has recommended the use of IPT in HIV-infected individuals that are symptom-free for TB co-infection. The use of IPT has raised the specter of drug resistance; however, to date, studies have not observed an increase in drug-resistant TB in individuals on IPT. Now, Mills et al. use mathematical modeling to show that even if IPT does not increase drug resistance in infected individuals, community-wide IPT can drive increases in drug resistance at the population level.

The authors developed mathematical models to identify the conditions under which community-wide IPT could increase the burden of drug-resistant TB. They found that community-wide IPT increases selective suppression of drug-sensitive infection, thus indirectly conferring an advantage to drug-resistant strains. These data should be considered when determining policy for preventive therapy.