Genexpert

Perspective

GeneXpert—A Game-Changer for Tuberculosis Control?
Carlton A. Evans1,2,3*
1 Universidad Peruana Cayetano Heredia, Lima, Peru, 2 Imperial College London Hammersmith Hospital Campus, London, United Kingdom, 3 IFHAD: Innovation For Health And Development, London, United Kingdom

Tuberculosis (TB) kills more people than any other single infection, the global burden of TB cases anddrug resistance are increasing [1], and most patients still only have access to an inadequate diagnostic test developed more than a century ago. Recent evaluations of a desktop machine called the GeneXpert MTB/ RIF that in less than two hours simultaneously detects Mycobacterium tuberculosis and tests for drug resistance have stimulated tremendous enthusiasm [2,3]. Is this the breakthrough that TBcontrol has been waiting for?

Linked Articles
This Perspective discusses the following new articles published in PLoS Medicine: 1. Scott LE, McCarthy K, Gous N, Nduna M, Van Rie A, et al. (2011) Comparison of Xpert MTB/RIF with Other Nucleic Acid Technologies for Diagnosing Pulmonary Tuberculosis in a High HIV Prevalence Setting: A Prospective Study. PLoS Med 8(7): e1001061.doi:10.1371/journal.pmed.1001061 In this prospective, real world cohort study nested within a national screening program for tuberculosis, Lesley Scott and colleagues compare the performance of Xpert MTB/RIF on a single sputum sample with different TB sputum detection technologies. 2. Lawn SD, Brooks SV, Kranzer K, Nicol M, Whitelaw A, et al. (2011) Screening for HIV-Associated Tuberculosis and RifampicinResistance before Antiretroviral Therapy Using the Xpert MTB/RIF Assay: A Prospective Study. PLoS Med 8(7): e1001067. doi:10.1371/journal.pmed.1001067 In a prospective study, Stephen Lawn and colleagues find that pre-ART screening with Xpert MTB/RIF increased tuberculosis case detection by 45% compared to smear microscopy in HIV-positive patients at high risk of TB risk. 3. Dowdy DW, Cattamanchi A,Steingart KR, Pai M (2011) Is Scale-Up Worth It? Challenges in Economic Analysis of Diagnostic Tests for Tuberculosis. PLoS Med 8(7): e1001063. doi:10.1371/journal.pmed.1001063 David Dowdy and colleagues discuss the complexities of costing new TB diagnostic tests, including GeneXpert, and argue that flexible analytic tools are needed for decision-makers to adapt large-sample cost-effectiveness data tolocal conditions.

The Backstory
TB has non-specific clinical features, so diagnosis usually requires laboratory testing. Traditional sputum smear microscopy is the only laboratory test for TB that is accessible to most of the world’s population. Smear microscopy is inexpensive, appropriate for basic laboratories, rapidly diagnoses the most infectious patients, and has high specificity, sopositive results almost always prompt treatment. However, smear microscopy has two key inadequacies: (1) it is insensitive, prone to false-negative ‘‘smear-negative TB’’ results; and (2) it cannot test for drug resistance, which is important because patients with drugresistant TB require prompt second-line treatment to prevent morbidity, mortality, and dissemination of increasingly resistantmulti-drug-resistant tuberculosis (MDRTB) and extensively drug-resistant tuberculosis (XDRTB) [4,5]. Traditional TB culture for diagnosing smear-negative TB and testing for drug resistance takes weeks, too slow to adequately address these inadequacies. Newer rapid tests for TB and drug resistance such as MODS, Griess, MGIT, thin-layer agar, colorimetric assays, and some molecular tests [6,7] are potentialsolutions but require specialised laboratories and skills that are often unavailable in the regions where most cases of TB and MDRTB occur [1].

MTB/RIF test is feasible for use in peripheral labs and clinics by unskilled personnel [9]. In two multi-centre studies, a single MTB/RIF test detected almost all smear-positive TB patients and about three-quarters of the smear-negative TB patients...