The effect of M. tuberculosis lineage on clinical phenotype

Duc Hong Du, Ronald B. Geskus, Yanlin Zhao, Luigi Ruffo Codecasa, Daniela Maria Cirillo, Reinout van Crevel, Dyshelly Nurkartika Pascapurnama, Lidya Chaidir, Stefan Niemann, Roland Diel, Shaheed Vally Omar, Louis Grandjean, Sakib Rokadiya, Arturo Torres Ortitz, Nguyen Huu Lân, Dang Thi Minh Hà, E. Grace Smith, Esther Robinson, Martin Dedicoat, Le Thanh Hoang NhatGuy E. Thwaites, Le Hong Van, Nguyen Thuy Thuong Thuong, Timothy M. Walker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Six lineages of Mycobacterium tuberculosis sensu stricto (which excludes M. africanum) are described. Single-country or small observational data suggest differences in clinical phenotype between lineages. We present strain lineage and clinical phenotype data from 12,246 patients from 3 low-incidence and 5 high-incidence countries. We used multivariable logistic regression to explore the effect of lineage on site of disease and on cavities on chest radiography, given pulmonary TB; multivariable multinomial logistic regression to investigate types of extra-pulmonary TB, given lineage; and accelerated failure time and Cox proportional-hazards models to explore the effect of lineage on time to smear and culture-conversion. Mediation analyses quantified the direct effects of lineage on outcomes. Pulmonary disease was more likely among patients with lineage(L) 2, L3 or L4, than L1 (adjusted odds ratio (aOR) 1.79, (95% confidence interval 1.49–2.15), p<0.001; aOR = 1.40(1.09–1.79), p = 0.007; aOR = 2.04(1.65–2.53), p<0.001, respectively). Among patients with pulmonary TB, those with L1 had greater risk of cavities on chest radiography versus those with L2 (aOR = 0.69(0.57–0.83), p<0.001) and L4 strains (aOR = 0.73(0.59–0.90), p = 0.002). L1 strains were more likely to cause osteomyelitis among patients with extra-pulmonary TB, versus L2-4 (p = 0.033, p = 0.008 and p = 0.049 respectively). Patients with L1 strains showed shorter time-to-sputum smear conversion than for L2. Causal mediation analysis showed the effect of lineage in each case was largely direct. The pattern of clinical phenotypes seen with L1 strains differed from modern lineages (L2-4). This has implications for clinical management and could influence clinical trial selection strategies.

Original languageEnglish
Article numbere0001788
JournalPLOS Global Public Health
Issue number12
Publication statusPublished - Dec 2023

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© 2023 Du et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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