Mycobacterium tuberculosis complex strain discordance among people with tuberculosis and a history of household contact: a systematic review and meta-analysis.

Authors

Tom A Yates, Martha Chipinduro, Robert W Aldridge, Baktash Khozoee, Joanne R Winter, Frank Tanser, Ibrahim Abubakar, Katharina Kranzer

Published in

The Lancet. Microbe. Pages 101511. Oct 26, 2026. Epub Oct 26, 2026.

Abstract

Tuberculosis disease clusters within households, but the proportion of disease among household contacts that results from recent within-household transmission remains unclear. We aimed to estimate the prevalence of Mycobacterium tuberculosis complex strain discordance among pairs of individuals with tuberculosis and a history of household contact, and the proportion of all tuberculosis disease attributable to recent household transmission.
In this systematic review and meta-analysis, we included empirical studies or systematic reviews published in English from Jan 1, 1985, to Jan 26, 2024, that described at least ten pairs of individuals with a history of household contact, in which both people had active tuberculosis and their isolates were strain-typed using RFLP, mycobacterial interspersed repetitive unit-variable-number tandem repeat, or whole-genome sequencing. We excluded studies that only collected data on residence for isolates of the same strain and studies that used preselection for both index and secondary cases. Searches of MEDLINE, Embase, Global Health, Web of Science, and POPLINE databases were updated on Jan 26, 2024. Titles and abstracts and then full texts were screened, and data were extracted independently, by two reviewers, with disagreements resolved by consensus. Summary data were extracted from published reports; when necessary, we contacted study authors, some of whom reanalysed data. The main outcome was the prevalence of strain discordance among pairs of individuals with tuberculosis and a history of household contact. Our main analyses excluded studies using 12-loci or 15-loci mycobacterial interspersed repetitive unit-variable-number tandem repeat and studies performed during tuberculosis outbreaks, as these were considered to be at high risk of bias. We used an inverse variance heterogeneity model applying a double-arcsine transformation to stabilise variance. The proportion of total variability due to between-study heterogeneity was estimated using I². We estimated the proportion of all tuberculosis attributable to recent household transmission as the product of strain concordance and the proportion of all cases in the community with a history of household exposure to a putative index case, which we derived from external data. Sensitivity analyses assessed robustness to the choice of model and to varying assumptions about household size when estimating the attributable fraction. Our PROSPERO registration number was CRD42024504096.
The updated searches identified an additional 3735 unique records. Thirty studies from 18 countries met the inclusion criteria. Four studies were omitted from the meta-analysis because they were at high risk of bias. The remaining 26 studies comprised 1544 index-secondary patient pairs. A high proportion of total variability was due to between-study heterogeneity (I² 90·3, 95% CI 69·0-95·3%). The overall pooled estimate of the prevalence of strain discordance was 0·47 (95% CI 0·32-0·62). Pooled estimates differed by tuberculosis incidence: 0·30 (0·25-0·34) in low-incidence settings, 0·25 (0·15-0·36) in moderate-incidence settings, and 0·59 (0·41-0·76) in high-incidence settings (p=0·003). The median proportion of tuberculosis disease attributable to recent household transmission was 10·8% (range 1·4-21·1%).
Strain discordance is common, particularly in high-incidence settings. These findings suggest that recent household transmission makes a small contribution to the overall burden of tuberculosis disease. In this study, the number of household pairs and geographical diversity of the studies were strengths. Between-study heterogeneity limited precision. Our estimates of attributable fraction relied on external data. Strain discordance does not necessarily imply discordance in drug susceptibility. These results should motivate a greater focus on social protection and interrupting community transmission.
None.

PMID:
42933451
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.

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