Nontuberculous mycobacterial pulmonary disease and associated risk factors in China: A prospective surveillance study

Abstract

Background

We aimed to address the knowledge gap that exists regarding the epidemiological, demographic, and clinical characteristics of nontuberculous mycobacterial pulmonary diseases (NTM-PDs) among smear-positive patients with symptoms suggestive of pulmonary tuberculosis (PTB) in China.

Methods

Prospective and national surveillance of NTM-PD was performed from 17 hospitals within the China Nontuberculous Mycobacteria Surveillance Study (CNTMS). Patients were eligible for inclusion if they had positive smears during hospitalization. Sputum specimens were collected for molecular species identification.

Results

6,766 patients with valid results were included, consisting of 6,236 (92.2%) with PTB, 458 (6.8%) with NTM-PD, and 72 (1.0%) with colonization. The proportion of NTM-PD in PTB patients exhibited significant geographic diversity, ranging from 3.2% in the northwest to 9.2% in the south. The most prevalent species was Mycobacterium intracellulare, followed by Mycobacterium abscessus complex. Females, elderly people, and patients with bronchiectasis or COPD are at high risk for developing NTM-PD, while patients with diabetes have a lower risk of NTM-PD when compared with non-diabetic patients. Regarding clinical symptoms, lower rates of persistent cough and weight loss were noted in NTM-PD patients than in PTB patients.

Conclusions

Approximately one-fifteenth of PTB patients are afflicted with nontuberculous mycobacterial infections in China. The prevalence of NTM shows geographic diversity across the country, and it showed a gradual increase from north to south and from west to east. NTM-PD patients are prone to exhibit less severe clinical symptoms than PTB patients, highlighting the importance of raising awareness of NTM diseases to improve decision making on how to best screen, diagnose, and treat NTM in TB-endemic settings.

Introduction

Nontuberculous mycobacteria (NTM) are opportunistic bacterial pathogens, and the prevalence of NTM disease has dramatically increased over the years in both developed and developing countries 1, 2, 3. As a consequence, this disease has attracted attention as a great public health concern worldwide [1]. The lung is the most common organ affected by NTM, which results in clinical presentation mimicking pulmonary tuberculosis (PTB) [4]. The inadequate antimicrobial treatment of NTM pulmonary disease (NTM-PD) increases the risk of poor outcome in these patients, which emphasizes the need for a rapid and accurate diagnosis of NTM-PD before the initiation of treatment [3]. Unfortunately, this is extremely challenging considering that NTM-PD must be distinguished from PTB in patients with chronic lung disease using molecular diagnostic assays, which remain inadequate or inaccessible in developing countries [5]. In other words, a positive sputum smear for NTM is likely to be misdiagnosed as TB in countries with a high TB burden. Thus, the epidemiology of NTM-PD is of importance to help clinicians determine whether to initiate antituberculosis treatment.

China has the third highest tuberculosis burden in the world [6]. Whilst great progress has been achieved in TB control over past decades, population-based data suggests that the rate of NTM among all isolates from patients with symptoms suggestive of TB has remarkedly increased from 11.1% in 1990 to 22.9% in 2010 [7]. In addition, the distribution of NTM exhibits great geographic diversity, with high prevalence in southern regions versus low prevalence in northern regions of China [2]. Researchers believe that the regional disparity in NTM prevalence reflects the distribution of species in local environments [1]. We however found that the existing evidence from previous studies were generated from laboratory mycobacterial isolates, thus making it impossible to distinguish NTM-PD from colonization of the respiratory tract [8]. Moreover, the lack of representativeness due to the retrospective single-center design of these studies affected the extrapolations made to the whole country. Despite the scatted studies, the overall prevalence of NTM-PD in China has not been assessed in the literature thus far; and the vulnerable populations for NTM infections also remains unclear. More efforts are therefore needed to describe the disease burden, temporal and geographic distribution, and associated mortality of NTM-PD [9].

We aimed to address the knowledge gap that exists regarding the epidemiological, demographic, and clinical characteristics of NTM-PDs among smear-positive patients with symptoms suggestive of pulmonary TB in China. In particular, we aimed to determine the risk factors associated with NTM-PD in Chinese populations.