Background A recurrent tuberculosis (TB) episode results from exogenous reinfection or relapse after cure. The use of genotyping allows the distinction between both.
Methods We did a systematic review and meta-analysis, using four databases to search for studies in English, French and Spanish published between 1 January 1980 and 30 September 2020 that assessed recurrences after TB treatment success and/or differentiated relapses from reinfections using genotyping. We calculated person years of follow-up and performed random-effects model meta-analysis for estimating pooled recurrent TB incidence rates and proportions of relapses and reinfections. We performed subgroup analyses by clinical–epidemiological factors and by methodological study characteristics.
Findings The pooled recurrent TB incidence rate was 2.26 per 100 person years at risk (95% CI 1.87 to 2.73; 145 studies). Heterogeneity was high (I2=98%). Stratified pooled recurrence rates increased from 1.47 (95% CI 0.87 to 2.46) to 4.10 (95% CI 2.67 to 6.28) per 100 person years for studies conducted in low versus high TB incidence settings. Background HIV prevalence, treatment drug regimen, sample size and duration of follow-up contributed too. The pooled proportion of relapses was 70% (95% CI 63% to 77%; I²=85%; 48 studies). Heterogeneity was determined by background TB incidence, as demonstrated by pooled proportions of 83% (95% CI 75% to 89%) versus 59% (95% CI 42% to 74%) relapse for studies from settings with low versus high TB incidence, respectively.
Interpretation The risk of recurrent TB is substantial and relapse is consistently the most frequent form of recurrence. Notwithstanding, with increasing background TB incidence the proportion of reinfections increases and the predominance of relapses among recurrences decreases.
PROSPERO registration number CRD42018077867
- clinical epidemiology
- respiratory infection
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Contributors LO, CS and VV conceived the presented idea, initiated the project and were responsible for the design of the protocol. SR and VV did the review, data extraction, synthesis of results and quality assessment of studies. PVdS, LO, SR and VV contributed to the analysis of the results. All authors discussed the results and contributed to the final manuscript.
Funding The study received financial support from Institutional Collaboration Framework Agreement IV Institute of Tropical Medicine Antwerp, Belgium - Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia. LO is supported by an Emerging Global Leader Award from the Fogarty International Center at the National Institutes of Health (K43TW011137). The funders had no role in the design and conduction of this study.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval Universidad Peruana Cayetano Heredia Ethics Committee (FWA00000525) waived ethical approval.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.
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