Extensively Drug-resistant Tuberculosis: Epidemiology and Management Challenges

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Insights from clinical epidemiology

Results from the fourth round of the Global Project on Anti-Tuberculosis Drug Resistance Surveillance,3 based on data from more than 90,000 patients from 83 countries, indicate that the median prevalence of resistance to any drug in newly identified TB cases is currently about 11%. The prevalence of MDR-TB is increasing most strongly in South Korea and certain areas of the former Soviet Union. Almost 40 countries (ie, approximately 50% of those countries contributing representative data

Insights from molecular epidemiology

Classic epidemiology continues to provide valuable insights into the epidemiology of TB. However, these analytical methods have assumed that the phenotype of the causative agent (M tuberculosis) does not directly influence the epidemiology of disease. This notion has been challenged with the discovery of polymorphic genetic elements, which allow for the classification of M tuberculosis strains and their spatial and temporal analysis in different epidemiologic settings.

Numerous genotyping

Diagnosis of MDR and XDR-TB

A definitive diagnosis of MDR-TB and XDR-TB depends on identification of the presence of M tuberculosis and the DST thereof. Thus, the accuracy of the laboratory-based DST is crucial for diagnosis of MDR-TB or XDR-TB, with profound implications for the individual patient. This diagnosis can be achieved only if laboratory quality-assurance programs are implemented. The gold standard for DST is the indirect proportion method on agar medium.69, 70 This method requires obtaining a pure culture of M

Management challenges

The first step is to make the correct diagnosis. In settings of appreciable drug resistance, a laboratory result may reflect sample contamination or administrative error. As outlined earlier, because of several reasons, second-line DST information from different laboratories may yield different results. It is also possible that one may be sampling a subpopulation of pulmonary bacilli that are of a different strain and have a different DST profile. In a patient failing a first-line drug regimen

Ethical dilemmas

In high-burden settings, given the extent of the TB pandemic and poor treatment outcomes, increasing numbers of patients with MDR and particularly XDR-TB fail medical therapy. These patients may have limited or extensive bilateral disease, are not suitable candidates for surgery, have high-grade bacillary resistance with no option for additional agents, have had other copathologies ruled out, and have failed to culture convert after 12 months of intensive inpatient therapy, after which the

Summary

The prevalence of MDR-TB has increased globally in the past decade and likely will continue to increase in many areas within resource-poor settings like India, China, territories within the former Soviet Union, and Africa. This increase has the capacity to destabilize TB control, and additional prevalence data on MDR-TB and XDR-TB are urgently needed from these regions. Molecular epidemiologic studies suggest MDR-TB and XDR-TB are predominantly acquired with subsequent horizontal spread within

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    This work and KD were supported by a TBsusgent grant from the European Commission (EU-FP7), the European and Developing Countries Clinical Trials Partnership, a South African Medical Research Council Career Development Award, and a National Research Foundation/South African Research Chairs Initiative award.

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