In 1987, the US Centers for Disease Control and Prevention (CDC) estimated a population NTM disease rate of 1.8/100,000 between 1981 and 1983 in North America [9]. However, the overall average annual age-adjusted prevalence rate rose from 8.7 to 13.9 per 100,000 persons between the 2008 and 2013 within five states of the United States [10]. The need for updated data was later recognized because of the increasing numbers of published case series, and the widespread belief among clinicians that NTM lung disease was becoming more prevalent. Investigators at a reference hospital in Korea noted an increase in the number of NTM patients from 2002 (n = 82) to 2008 (n = 133) [1]. Based on the Korean data from NHI, the prevalence of NTM infection per 100,000 population increased from 9.4 in 2009 to 36.1 in 2016 compared to the decreased prevalence of Tb from 106.5 in 2009 to 74.4 in 2016. Possible explanations for the perceived increase in NTM disease include an aging population, increase in the prevalence of immune-modulating co-morbidities (i.e., diabetes mellitus and obstructive pulmonary disease), oesophageal motility disorders, immunosuppressive medication use, and the development of sensitive diagnostic technology [11, 12]. One study showed that localized immunosuppression increased the risk of pulmonary NTM disease in a cohort of 464 patients receiving inhaled corticosteroids for asthma treatment [13]. In a recent systemic review, an increase in the proportion of mycobacterial disease caused by NTM was reported in several settings that had a decrease in Tb prevalence rates [14], as was similar to the findings in our study.
Notification of Tb but not of NTM, is mandatory in Taiwan. Partly due to the strict regulation of Tb notification, several patients infected with NTM were notified as Tb cases (9 per 100,000 patients), imposing additional burdens on the public health system [15]. NTM patients are subjected to mandatory public health reporting in Queensland, Australia, where pulmonary isolates increased from 5.5 to 10.2/100,000 population over a 6-year period [16]. However, NTM reporting is not mandatory in Japan.
The most often isolated cases in the USA are MAC cases, followed by M. kansasii and M. abscessus [12]. In Japan, MAC accounts for the majority of infections [17]. In this study, the proportion of SGM and RGM cases was 51.6% and 48.4%, respectively. MAC and M. abscessus were the most common SGM and RGM infections, respectively. These findings were similar to those from the study by Koh et al. in which M. abscessus was found to be the second most common pathogen responsible for lung diseases caused by NTM, after MAC in the Republic of Korea [18, 19]. The identification of bacterial species is clinically important because treatment and response rates differ depending on the bacterial species, and some are refractory disease [20].
Pulmonary presentation of NTM was characterized by the presence of bronchiectasis, cavitation, pneumoconiosis, fibrosis, and nodules. We also observed these radiographic findings, such as bronchiectasis (44.6%), cavities (43.1%), destroyed lung (18.5%), nodules (52.3%), infiltration (78.5%), and fibrosis (70.8%). The cardinal symptoms of fever, chest pain, and unintentional weight loss were prevalent in the survey participants with NTM. We also observed cough (93.8%), sputum (93.8%), chronic fatigue (75.4%), dyspnoea on exertion (30.8%), hemoptysis (27.7%), weight loss (26.2%), chest pain (10.8%), and fever (9.2%) among patients enrolled in this study.
Misdiagnosis or delayed diagnosis of NTM, due to similarity in clinical presentation to Tb, can result in inappropriate isolation with psychosocial stress [15] and serious morbidity and mortality [3]. Traditional culture methods, which take up to 6 weeks, may be required in order to differentiate the Tb and NTM [21]. It will be helpful to introduce nucleic acid amplification (NAA) tests as an additional assay for patients with acid fast bacilli (AFB) smear-positive sputum [22]. NAA tests performed in a timely manner will be helpful in differentiating between Tb and NTM in smear-positive specimens [15]. As our centre is specialized in Tb treatment, many patients initiated anti-Tb medications prior to obtaining their Tb results. Approximately 40% of patients had initiated anti-Tb medications during the study period within a mean duration of 68 days. If the NAA test was conducted when AFB was positive, the rate of misdiagnosis and mistreatment will decrease, further leading to decreased medical expenses, decreased side effects of anti-Tb medication, increased NTM diagnosis, and improvements to the quality of life in patients. National laboratories still need to standardize NTM protocols for improved diagnostic methods and management.
To the best of our knowledge, this was the first study conducted using epidemiologic NTM data from a specialized Tb treatment centre in Korea, a country that is endemic to Tb. As Tb and NTM show similar clinical manifestations, and relatively lower incidence of NTM, NTM has been neglected until now limiting the available epidemiologic data on NTM. Our study highlights the negative impact of NTM on Tb surveillance and control system. Understanding the epidemiology of NTM lung diseases remains crucial to addressing this burgeoning public health challenge [1]. It is essential to ensure that the de-notification of patients infected with NTM occurs as early as possible to reduce the burden on the public health system and ensure the quality of the Tb surveillance system [15]. Finally, a comprehensive multi-country evaluation of NTM is needed to better understand the extent of the NTM burden on the globe and to design strategic action plans.
