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Meta-Analysis
. 2023 Feb 14;227(4):471-482.
doi: 10.1093/infdis/jiac179.

Association Between Cytomegalovirus Infection and Tuberculosis Disease: A Systematic Review and Meta-Analysis of Epidemiological Studies

Kok Pim Kua  1 , Bunchai Chongmelaxme  2 , Shaun Wen Huey Lee  3   4   5   6   7
Affiliations
Meta-Analysis

Association Between Cytomegalovirus Infection and Tuberculosis Disease: A Systematic Review and Meta-Analysis of Epidemiological Studies

Kok Pim Kua et al. J Infect Dis. .

Abstract

Background: Tuberculosis is one of the leading causes of mortality worldwide from an infectious disease. This review aimed to investigate the association between prior cytomegalovirus infection and tuberculosis disease.

Methods: Six bibliographic databases were searched from their respective inception to 31 December 2021. Data were pooled using random-effects meta-analysis.

Results: Of 5476 identified articles, 15 satisfied the inclusion criteria with a total sample size of 38 618 patients. Pooled findings showed that individuals with cytomegalovirus infection had a higher risk of tuberculosis disease compared to those not infected with cytomegalovirus (odds ratio [OR], 3.20; 95% confidence interval [CI], 2.18-4.70). Age was the only covariate that exerted a significant effect on the result of the association. Meta-analysis of risk estimates reported in individual studies showed a marked and significant correlation of cytomegalovirus infection with active tuberculosis (adjusted hazard ratio, 2.92; 95% CI, 1.34-4.51; adjusted OR, 1.14; 95% CI, .71-1.57). A clear dose-response relation was inferred between the levels of cytomegalovirus antibodies and the risks of tuberculosis events (OR for high levels of cytomegalovirus antibodies, 4.07; OR for medium levels of cytomegalovirus antibodies, 3.58).

Conclusions: The results suggest an elevated risk of tuberculosis disease among individuals with a prior cytomegalovirus infection.

Keywords: association; cytomegalovirus; latent infection; mycobacterium; tuberculosis.

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Conflict of interest statement

Potential conflicts of interest . All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
PRISMA 2020 flow diagram for new systematic review, which included searches of databases, registers, and other sources. *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.
Figure 2.
Figure 2.
Risk of tuberculosis disease among individuals with CMV infection. Abbreviations: CI, confidence interval; CMV, cytomegalovirus; M-H: Mantel-Haenszel method.
Figure 3.
Figure 3.
Random-effects meta-analysis of the correlations between cytomegalovirus infection and tuberculosis disease. Abbreviations: CI, confidence interval; ES, effect size.
Figure 4.
Figure 4.
Random-effects meta-analysis of the dose-response relationships between cytomegalovirus infection and tuberculosis disease. Abbreviations: CI, confidence interval; ES, effect size.
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