Volume 22, Number 6—June 2016
Epidemiology of Pulmonary Nontuberculous Mycobacterial Disease, Japan1
To the Editor: Incidence of pulmonary nontuberculous mycobacterial disease (PNTMD) is reportedly increasing globally (1,2). Although such an increase is expected in Japan (3,4), the epidemiologic situation is unclear. The most recent survey, which used the 1997 American Thoracic Society diagnostic criteria, reported that the incidence rate for PNTMD in 2007 was 5.7 cases per 100,000 person-years (5). To update the data, we performed a nationwide hospital-based survey in Japan.
After a preliminary survey of 20 hospitals, we developed and disseminated questionnaires to all 884 hospitals in Japan that were certified by the Japanese Respiratory Society. The surveys asked about the number of newly diagnosed cases, from January through March 2014, of PNTMD, pulmonary Mycobacterium avium disease, M. intracellulare disease, or M. avium complex (MAC; the combination of the first 2 species listed); pulmonary M. kansasii disease; pulmonary M. abscessus disease; and tuberculosis (TB) for inpatients and outpatients. Hospital respondents returned the completed questionnaires by mail, fax, or Internet. To avoid potential reporting bias and misclassification, we counted only cases that met the 2007 American Thoracic Society/Infectious Diseases Society of America statements (6) and excluded cases diagnosed at other hospitals. Because the source population can be ascertained by using the epidemiologic data for TB as a reportable disease, to estimate the incidence rate of PNTMD, we used the ratio of TB to PNTMD cases. The PNTMD incidence rate was calculated as the national incidence rate of TB multiplied by the ratio of new PNTMD to TB cases reported by the responding hospitals (online Technical Appendix Figure 1, http://wwwnc.cdc.gov/EID/article/22/6/15-1086-Techapp1.pdf).
To clarify the chronologic changes in incidence, we followed the same method for comparing TB and PNTMD used in a prior epidemiologic study in Japan (5). We established methods for maximizing survey response rates and facilitating ease of completion by offering extensive support to survey recipients (Technical Appendix Table 1).
We achieved a high response rate of 62.3% (551 hospitals), and in all regions the response rate exceeded 50% (Technical Appendix Table 2). The numbers of newly diagnosed cases were 2,327 for TB and 2,652 for PNTMD. Because the incidence rate for TB was reported to be 12.9 cases per 100,000 person-years, that of PNTMD was estimated to be 14.7 cases per 100,000 person-years, which is ≈2.6 times the incidence rate reported in 2007 (Figure). By using the same method, we found the incidence of pulmonary MAC, M. kansasii, and M. abscessus disease to be 13.1, 0.6, and 0.5 cases per 100,000 person-years, respectively (Technical Appendix Table 2). The ratio of pulmonary M. avium disease to MAC was higher in the northern and eastern parts of Japan, whereas the ratio of pulmonary M. intracellulare disease to MAC was higher in the southern and western parts of Japan (Technical Appendix Figure 1).
From this survey, we observed that the incidence rate of PNTMD may exceed that of TB and that incidence rates of PNTMD in Japan may be among the highest worldwide (Figure). This finding implies that the prevalence of PNTMD as a chronic infection is estimated to be much higher than that of TB.
We assume that the high rates of PNTMD in Japan are consistent with data suggesting that Asians are particularly susceptible to PNTMD (1,7,8). Other factors contributing to the increase might be the simplified diagnosis according to the 2007 American Thoracic Society/Infectious Diseases Society of America statements, increased awareness by medical staff, population aging, and increased frequency of medical checkups with computed tomography of the chest.
Another finding was the characteristic gradient clustering of the ratios of M. avium and M. intracellulare (Technical Appendix Figure 2). This finding supports the widely accepted belief that environmental factors strongly affect the epidemiology of PNTMD; therefore, the role of factors such as soil, humidity, temperature, and saturated vapor pressure should be seriously considered (9).
We also found dramatic increases in incidence of pulmonary M. abscessus disease and pulmonary MAC disease, whereas incidence of pulmonary M. kansasii disease was stable. Although we did not distinguish M. massiliense from M. abscessus, the incidence rate for pulmonary M. abscessus disease increased from 0.1 cases in 2001 to 0.5 cases per 100,000 person-years in 2014. This epidemiologic tendency should be monitored (10).
This study has several limitations. First, differing characteristics between the responding and nonresponding hospitals could cause bias. Second, we did not collect data outside of hospitals. Third, incomplete reporting could undermine the accuracy of our estimates (Technical Appendix Tables 3, 4). Therefore, the epidemiologic data should be verified by using other approaches (Technical Appendix Table 1).
The dramatic increase in incidence rates for PNTMD warrants its recognition as a major public health concern. Because the prevalence rates of this currently incurable lifelong chronic disease are estimated to be high, the effect on the community could be enormous. Further investigations are needed.
This research was supported by the Research Program on Emerging and Re-emerging Infectious Disease from the Japan Agency for Medical Research and Development. The nationwide survey was also supported by the Japanese Respiratory Society; the Japanese Society for Tuberculosis; and the Ministry of Health, Labour and Welfare.
- Adjemian J, Olivier KN, Seitz AE, Holland SM, Prevots DR. Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries. Am J Respir Crit Care Med. 2012;185:881–6 .
- Thomson RM. Changing epidemiology of pulmonary nontuberculous mycobacteria infections. Emerg Infect Dis. 2010;16:1576–83.
- Morimoto K, Iwai K, Uchimura K, Okumura M, Yoshiyama T, Yoshimori K, A steady increase in nontuberculous mycobacteriosis mortality and estimated prevalence in Japan. Ann Am Thorac Soc. 2014;11:1–8.
- Ide S, Nakamura S, Yamamoto Y, Kohno Y, Fukuda Y, Ikeda H, Epidemiology and clinical features of pulmonary nontuberculous mycobacteriosis in Nagasaki, Japan. PLoS ONE. 2015;10:e0128304.
- Kajiki A. Non-tuberculous mycobacteriosis. What has been coming out [in Japanese]. Kekkaku. 2011;86:113–25 .
- Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007;175:367–416.
- Koh WJ, Kwon OJ, Jeon K, Kim TS, Lee KS, Park YK, Clinical significance of nontuberculous mycobacteria isolated from respiratory specimens in Korea. Chest. 2006;129:341–8.
- Lai CC, Tan CK, Chou CH, Hsu HL, Liao CH, Huang YT, Increasing incidence of nontuberculous mycobacteria, Taiwan, 2000–2008. Emerg Infect Dis. 2010;16:294–6.
- Chou MP, Clements AC, Thomson RM. A spatial epidemiological analysis of nontuberculous mycobacterial infections in Queensland, Australia. BMC Infect Dis. 2014;14:279.
- Prevots DR, Marras TK. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin Chest Med. 2015;36:13–34.
FigureCite This Article
1Preliminary results from this study were presented at the American Thoracic Society 2015 International Conference; 2015 May 15–20; Denver, Colorado, USA (http://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2015.191.1_MeetingAbstracts.A5268).