The incidence of lung disease from nontuberculous mycobacteria (NTM) has been increasing worldwide, in both immunocompromised and immunocompetent patients. Infection with NTM is clinically indistinguishable from infection with the mycobacteria species that cause tuberculosis, and the two can also coexist. This poses challenges for diagnosis and management, especially in parts of the world where tuberculosis is endemic.

Globally, NTM is often not routinely diagnosed, despite the fact that the most common type of NTM associated with pulmonary disease, Mycobacterium avium complex (MAC), can be successfully treated with antimicrobials. In countries where tuberculosis is endemic, patients who have NTM are often treated empirically for tuberculosis (using a drug regimen that is often ineffective against NTM). This contributes to overall patient toxicity, cost, and tuberculosis drug resistance.

Current Tuberculosis Testing

Sputum smear microscopy is a longstanding and widely used diagnostic test for tuberculosis. It is easy to perform, but it fails to detect up to half of tuberculosis cases. Moreover, it cannot distinguish between the mycobacterium species that cause tuberculosis and NTM.

The gold standard for tuberculosis diagnosis is the much more sensitive sputum culture. However, it is time consuming and impractical in many of the parts of the world where tuberculosis is endemic, and it is inconvenient even in more resourced regions.

A diagnostic option endorsed by the World Health Organization, the Xpert molecular assay, has the advantage of providing information about rifampin-resistant strains of tuberculosis. However, it is less sensitive than sputum culture, and it only detects tuberculosis, not infections of NTM.

Study and Impact

Sarro and colleagues developed a new multiplex PCR assay that could be used to diagnose infection from tuberculous mycobacteria but also infection from MAC and from other types of NTM. They undertook a pilot clinical feasibility study, recently published in EBioMedicine, to evaluate the early performance of the assay, using sputum samples from 190 patients in Mali with presumptive tuberculosis.

The new multiplex assay had a sensitivity and specificity of 83.3 percent and 96.6 percent, respectively, with a positive predictive value of 92.5 percent and a negative predictive value of 92.2 percent. In testing for tuberculosis, the new multiplex PCR assay had a greater specificity than Xpert, although Xpert had greater sensitivity.

The new multiplex assay is not meant to replace Xpert, but rather to provide an additional fast and effective option that might make sense in specific contexts. Although the multiplex assay was not automated in the study, the authors believe it could easily be adapted into an easy and quick (<30 minute) point-of-care automated system.

Formal clinical validation is still needed. But if multicenter trials confirm these results, the multiplex assay may be able to save time and resources by quickly testing for both tuberculous mycobacteria and NTM (including MAC), promoting accurate diagnosis and proper treatment of both. This could potentially benefit areas both with and without endemic tuberculosis.