Study measures the annual prevalence of nontuberculous mycobacterial lung disease in Ontario, Canada

By Neha MathurJun 1 2023Reviewed by Lily Ramsey, LLM

In a recent article published in Emerging Infectious Diseases journal, researchers performed a retrospective cross-sectional study in Ontario, Canada, to determine the prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) in 2020 based on screening/testing of pulmonary NTM isolates.

Study: Pulmonary Nontuberculous Mycobacteria, Ontario, Canada, 2020. Image Credit: KaterynaKon/Shutterstock.com

Background

There is a scarcity of radiological and clinical data needed to study the epidemiology of NTM-PD because this disease remains unreported in most jurisdictions of Ontario. Thus, investigators solely use microbiological data as a proxy definition for NTM-PD.

Between 1998 and 2010, researchers observed a surge in Mycobacterium avium complex (MAC) isolation in Ontario. It is a lung disease caused by several Mycobacterium species, including M. avium, M. intracellulare, M .abscessus, and M. xenopi.

About the study

In the present study, researchers used BACTEC MGIT 960 instrument to culture NTM isolates collected by Ontario's public health laboratories. To identify NTM at the subspecies level, they used the following methods:

i) LASER desorption or ionization time-of-flight mass spectrometry (MS);

ii) line-probe assays;

iii) a lab-engineered MAC real-time polymerase chain reaction (PCR); or

iv) 16S ribosomal deoxyribonucleic acid (rDNA) sequencing.

Next, they categorized NTM-PD isolates into uncertain, standard, and strict based on microbiological criteria. The 'standard' NTM-PD isolates had a 70 to 100% positive predictive value.

Yet, the researchers created the 'strict' category because they did not know how the diagnostic test changed environmental NTM exposure levels, which affected sample contamination.

Further, the researchers reviewed 24-month sample histories of patients whose NTM isolates were collected in 2020 to ascertain if they attained disease thresholds.

Furthermore, they used Canadian population data to compute prevalence and age- and gender-based standardization.

Results

In 2020, 8,412 of 41,471 (20.3%) pulmonary samples tested for mycobacteriology grew NTM. The NTM-PD prevalence of the standard category in 2020 was almost double the reported cases in 2010 (19 vs. 9.8 cases/100,000 persons).

Based on strict microbiological criteria, the total NTM-PD prevalence remained comparable to that reported in 2010, i.e., 10.9 cases per 100,000 persons.

The results attributed most cases of microbiologically defined NTM-PD in Ontario to M. avium, followed by M. intracellulare, M. abscessus, and M. xenopi. Specifically, M. avium caused 69.2% and 73.1% of standard and strict microbiological diseases, whereas M. xenopi caused only 4.4% and 3.9% of cases, respectively.

It implied that M. avium pulmonary disease, meeting the standard microbiological definition, surged 2.5-fold between 2010 and 2020.

Even M. intracellulare and M .abscessus caused much lesser standard and strict (73.1%) microbiological disease cases than M. avium, i.e., only 6.4%, 6.3%, and 5.8%, 7.1%, respectively.

The authors noted marked discrepancies in gender-based classification, with more female than male patients classified under the 'standard' category (1,507 vs. 1,285). Except for M. xenopi, all three mycobacterial strains favored female patients for causing NTM-PD.

Age-standardized prevalence ratio was higher in the oldest age group (4.46) for patients meeting standard criteria. Likewise, it was higher (4.56) for patients meeting strict criteria.

Furthermore, the researchers noted high regional heterogeneity, with the prevalence of NTM-PD being highest in Toronto, i.e., 49.8 and 28.8 cases per 100,000 persons among patients meeting standard and strict criteria, respectively.

Previously, many population-based studies conducted in the United States, Denmark, Croatia, and Spain have demonstrated increases in NTM-PD. Eight such studies even fetched species-level data.

However, none of these studies generated convincing results. For instance, a population-based survey conducted in Croatia showed M. fortuitum prevalence increased between 2006 and 2010.

According to the authors, the Ontario experience was similar. Notably, in this study, they did not change laboratory methods to explain the observed increase in M. avium-caused NTM-PD cases.

Though there was not much testing bias, the percentage of culture-positive pulmonary samples increased between 2010 and 2020, from 10% to 20.3%.

Conclusions

Taken together, the study results pointed to vast increases in the prevalence of M. avium-caused lung disease in Ontario. Clinicians must remain aware of the causes of these increases and the extent to which these increases reflect actual disease burden.

The authors could not find a convincing explanation for why M. xenopi cases decreased in this study. Though increased use of computed tomography (CT) scanning contributes to more significant detection of actual disease burden, it could not explain the reduction in M. xenopi.

Most likely, it was related to M. avium outcompeting M. xenopi when sharing a common environmental niche.