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Meta-Analysis
. 2024 Mar 13;11(1):e002281.
doi: 10.1136/bmjresp-2023-002281.

Risk factors for pulmonary tuberculosis recurrence, relapse and reinfection: a systematic review and meta-analysis

Victor Vega  1 , Javier Cabrera-Sanchez  2 , Sharon Rodríguez  3 , Kristien Verdonck  4 , Carlos Seas  5   3   6 , Larissa Otero  5   2 , Patrick Van der Stuyft  7
Affiliations
Meta-Analysis

Risk factors for pulmonary tuberculosis recurrence, relapse and reinfection: a systematic review and meta-analysis

Victor Vega et al. BMJ Open Respir Res. .

Abstract

Background: The rate of pulmonary tuberculosis (TB) recurrence is substantial. Identifying risk factors can support the development of prevention strategies.

Methods: We retrieved studies published between 1 January 1980 and 31 December 2022 that assessed factors associated with undifferentiated TB recurrence, relapse or reinfection. For factors reported in at least four studies, we performed random-effects meta-analysis to estimate a pooled relative risk (RR). We assessed heterogeneity, risk of publication bias and certainty of evidence.

Results: We included 85 studies in the review; 81 documented risk factors for undifferentiated recurrence, 17 for relapse and 10 for reinfection. The scope for meta-analyses was limited given the wide variety of factors studied, inconsistency in control for confounding and the fact that only few studies employed molecular genotyping. Factors that significantly contributed to moderately or strongly increased pooled risk and scored at least moderate certainty of evidence were: for undifferentiated recurrence, multidrug resistance (MDR) (RR 3.49; 95% CI 1.86 to 6.53) and fixed-dose combination TB drugs (RR 2.29; 95% CI 1.10 to 4.75) in the previous episode; for relapse, none; and for reinfection, HIV infection (RR 4.65; 95% CI 1.71 to 12.65). Low adherence to treatment increased the pooled risk of recurrence 3.3-fold (95% CI 2.37 to 4.62), but the certainty of evidence was weak.

Conclusion: This review emphasises the need for standardising methods for TB recurrence research. Actively pursuing MDR prevention, facilitating retention in treatment and providing integrated care for patients with HIV could curb recurrence rates. The use of fixed-dose combinations of TB drugs under field conditions merits further attention.

Prospero registration number: CRD42018077867.

Keywords: Clinical Epidemiology; Respiratory Infection; Tuberculosis.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Flowchart of study selection
Figure 2
Figure 2
Risk of bias assessment with the QUIPS Tool for studies of undifferentiated recurrence. QUIPS, Quality In Prognostic Factor Studies.
Figure 3
Figure 3
Risk of bias assessment with the QUIPS Tool for studies of relapse and/or reinfection. QUIPS, Quality In Prognostic Factor Studies.
See this image and copyright information in PMC

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