Association between mycobacterial genotypes and disease progression in Mycobacterium avium pulmonary infection
- T Kikuchi1,
- A Watanabe1,2,
- K Gomi1,
- T Sakakibara1,
- K Nishimori3,
- H Daito4,
- S Fujimura2,
- R Tazawa5,
- A Inoue1,
- M Ebina1,4,
- Y Tokue6,
- M Kaku7,
- T Nukiwa1,4
- 1Department of Pulmonary Medicine, Tohoku University Hospital, Sendai, Japan
- 2Research Division for Development of Anti-Infective Agents, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
- 3Research Team for Paratuberculosis, National Institute of Animal Health, Tsukuba, Japan
- 4Department of Pulmonary Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
- 5Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan
- 6Infection Control and Prevention Center, Gunma University Hospital, Maebashi, Japan
- 7Department of Infection Control and Laboratory Diagnostics, Tohoku University Graduate School of Medicine, Sendai, Japan
- Correspondence to Dr T Kikuchi, Department of Pulmonary Medicine, Tohoku University Hospital, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan; kikuchi{at}idac.tohoku.ac.jp
- Received 29 January 2009
- Accepted 5 June 2009
- Published Online First 23 June 2009
Abstract
Background: Non-tuberculous mycobacterial lung disease, most commonly caused by Mycobacterium avium infection, tends to show variable disease progression, and significant disease predictors have not been adequately established.
Methods: Variable numbers of tandem repeats (VNTR) were evaluated in 16 mycobacterial interspersed repetitive unit (MIRU) loci from M avium isolates cultured from respiratory specimens obtained from 2005 to 2007. Specifically, the association between VNTR profiles and disease progression was assessed.
Results: Among the 37 subjects who provided positive respiratory cultures for M avium during the 2005–6 period, 15 subjects were treated within 10 months following a microbiological diagnosis of progressive M avium lung disease. Nine subjects underwent long-term follow-up (>24 months) without treatment for stable M avium lung disease. Based on a neighbour-joining cluster analysis used to classify M avium-positive subjects according to the VNTR profile, subjects with progressive versus stable lung disease were found to be grouped together in distinct clusters. Further analysis using logistic regression modelling showed that disease progression was significantly associated with the genetic distance of the M avium isolate from an appropriately selected reference (age-adjusted odds ratio 1.95; 95% confidence interval 1.16 to 3.30; p = 0.01 for the most significant model). A best-fit model could be used to predict the progression of M avium lung disease when subjects from the 2005–6 period were combined with those from 2007 (p = 0.003).
Conclusion: Progressive lung disease due to M avium infection is associated with specific VNTR genotypes of M avium.
Footnotes
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Funding These studies were supported in part by the Ministry of Education, Culture, Sports, Science and Technology (Tokyo, Japan) and the Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency (Tokyo, Japan).
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Competing interests None.
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Provenance and Peer review Not commissioned; externally peer reviewed.
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