Molecular laboratory testing for tuberculosis: innovators, early adopters, or laggards?

Despite the recent progress toward meeting the Millennium Development Goal target to halt and to reverse the tuberculosis epidemic by 2015, the global burden of tuberculosis remains significant. In 2012, there were an estimated 8.6 million new cases of tuberculosis and 1.3 million died from the disease—5 deaths every 2 minutes! Among these deaths, an estimated 170 000 were caused by multidrug-resistant (MDR) tuberculosis, a relatively high total compared with 450 000 incident MDR tuberculosis cases. Worldwide and in most countries with a high burden of MDR tuberculosis, less than one-third of the tuberculosis patients estimated to have MDR tuberculosis were actually detected in 2012 [1]. In 2012, a total of 9945 new tuberculosis cases were reported in the United States, representing a 5.4% decrease from 2011 and 62.7% decrease from 1992 when the tuberculosis resurgence peaked at 26 673 cases. While this is indeed an accomplishment, the fact that 17 states reported increased case counts from 2011 to 2012 is concerning. Primary MDR tuberculosis is reported in 1.1% of tuberculosis cases and fluctuated between 0.9% and 1.3%— stable but no progress. Thirty-one states reported ≥50% of tuberculosis cases in foreign-born persons and 11 states even reported≥70%. The top 5 countries of origin of foreign-born persons with tuberculosis during 2007–2012 were Mexico, the Philippines, India, Viet Nam, and China [2]. According to the World Health Organization (WHO), more than half of the global MDR tuberculosis cases are from India, China, and the Russian Federation [1]. Today, laboratory testing in the mycobacteriology field is experiencing more changes than ever before. Determining what assay will be most useful to the healthcare provider is a challenge, and rapid acceptance of the new technology by the medical community an even greater one. In August 2013, the US Food and Drug Administration permitted marketing of the Xpert MTB/RIF (Xpert) assay (Cepheid, Sunnyvale, California) to detect DNA of the Mycobacterium tuberculosis complex and genetic mutations associated with resistance to rifampin (RIF) in unprocessed sputum and concentrated sputum sediments. In this issue of Clinical Infectious Diseases, Sohn and colleagues [3] from the Montreal Chest Institute, Canada, evaluated the Xpert assay in a low-incidence, high-resource ambulatory setting, specifically, in a university hospital tuberculosis clinic for the detection of pulmonary tuberculosis on induced sputum samples, using mycobacterial cultures as the reference standard. During the duration of the study, 924 patients were evaluated for tuberculosis and 502 consecutive patients were enrolled in the study (most with abnormal chest radiographs; only 18% symptomatic). Reasons for not enrolling included language barrier and refusal of the patient. Four induced sputum samples were collected. The second sample was subjected to the Xpert assay and the other 3 samples were sent to the clinical microbiology laboratory for acid-fast bacilli (AFB) smear microscopy and culture using one liquid medium (Mycobacterium Growth Indicator Tube, BD). If the AFB smear was positive, a reflex nucleic acid amplification test (NAAT) was performed.ANAATwasperformedonAFB smear-negative sputum samples by request only. Xpert results were not made available for clinical decision making. Twenty-four subjects were identified with active tuberculosis by culture. Xpert had an overall sensitivity of 46% and a specificity of 100%. The sensitivity was 86% in the 7 AFB smear-positive subjects and 29% in the 18 AFB smear-negative, culture-positive subjects. Most participants with culture-positive tuberculosis had minimal disease: only 7 of 25 (28%) culture-positive subjects were AFB smearpositive, only 12 (44%) had symptoms at Received 29 December 2013; accepted 07 January 2014; electronically published 14 January 2014. Correspondence: Max Salfinger, MD, Mycobacteriology Laboratory, K 420, National Jewish Health, 1400 Jackson St, Denver, CO 80206 ([email protected]). Clinical Infectious Diseases 2014;58(7):977–9 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/ciu024