Non-tuberculous mycobacteria: a disease beyond TB and preparedness in India

ABSTRACT

Background and Methods

Fifty-six Indian studies on NTM diseases were selected between 1981 and 2020 from various electronic databases (PubMed, EMBASE, Medline, BIOSIS preview, and Scopus) for systematic review.

Results

NTM isolation rates increased from 0.9% between 2001 and 2010 to 1.6% between 2011 and 2020. Prevalence of NTM-pulmonary disease (NTM-PD) among presumptive-TB patients in India was 1.1% (395/34,829). M. avium complex (MAC) (19%) was most commonly isolated from pulmonary specimens followed by M. chelonae (10%), M. fortuitum (9.8%), and M. abscessus (8.8%). M. fortuitum (35.5%), M. chelonae (23.6%) and M. abscessus (15%) were frequently reported from extra-pulmonary specimens. Patients with NTM-PD were mostly treated with a macrolide-based three-drug regimen. Clarithromycin-based-drug regimen in combination with amikacin, ciprofloxacin and several other drugs (rifampicin, imipenem, ofloxacin, linezolid, azithromycin) was used for treatment of EP-NTM. Median duration of the treatment in NTM-PD was 12 months, (6–18 months) whereas it was 6 months (3.1–8.7 months) in EP-NTM. Treatment was successful in 45% (19/42) of NTM-PD patients and 75% (93/124) of EP-NTM patients.

Conclusion

It is concluded from this review that most Indian studies have published laboratory data on NTM isolation and speciation and lacked information on clinical, microbiological and radiological correlation and treatment outcome details. Future studies should address these issues while publishing on NTM diseases.

KEYWORDS:

• Nontuberculous mycobacteria
• ntm
• NTM pulmonary disease
• NTM extrapulmonary disease
• NTM diagnosis
• NTM treatment

Article highlights

• In India, nontuberculous mycobacterial diseases are usually neglected, patients are often misdiagnosed and treated as drug-sensitive and drug-resistant TB. Exact incidence and prevalence of NTM disease in India is not known.

• Most published studies from India have reported NTM species that were isolated in laboratories without establishing their clinical relevance.

• Indian studies lack information on the characterization of subspecies of M. avium complex (MAC) and M. abscessus.

• Only a few Indian studies on NTM disease have published information on risk factors, clinical and radiological features of patients.

• A very few Indian studies have published treatment details including drug-regimens, duration, description of adverse events and treatment outcomes.

• None of the studies from India has reported follow-up details regarding relapse and re-infection.

• Increased awareness among clinicians and laboratory staff about NTM disease is required. It is suggested to establish a network between clinicians and laboratory personnel to determine the clinical relevance of isolated NTM species.

• Laboratories under National TB Elimination Programme (NTEP) should be well equipped with newer methods such as line probe assays (LPA), matrix assisted laser desorption ionization-time of flight mass spectrometry(MALDI-ToF MS), targeted gene and whole genome sequencing for the diagnosis of NTM species.

• Future studies on NTM diseases should focus on reporting true disease prevalence, adequate description of underlying risk factors and clinico-radiological features, characterization of NTM species and subspecies (in MAC and M. abscessus).

• Treatment for NTM- pulmonary disease should be initiated immediately rather than watchful waiting, especially in patients with positive acid-fast bacilli smear results and/or cavitary lung disease.

• DST should be done for MAC (clarithromycin and amikacin); M. kansasii (rifampicin and clarithromycin); and M. abscessus (at least clarithromycin, amikacin and cefoxitin); and preferably tigecycline, imipenem, minocycline, doxycycline, moxifloxacin, linezolid, co-trimoxazole and clofazimine). Along with DST, Minimum inhibitory concentration should also be estimated where facilities exist. Phenotypic (on day 3rd and 14th) and genotypic (for erm41 gene) DST for clarithromycin is recommended in M. abscessus disease.

• Future publications from India should describe treatment details, including outcomes, along with long-term follow-up of patients with NTM disease should be systematically reported

• Efforts should be made to formulate consensus-based guidelines on diagnosis and treatment of NTM diseases in India.

Declaration of interest

The author(s) have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

SKS conceived the idea and formulated the structure of the review. SKS drafted the manuscript and performed the final editing. VU led data acquisition from relevant publications and analysis and assisted in drafting of the manuscript.

Declaration of interest

None.

Additional information

Funding

This paper was not funded.