Association of viral exposure with tuberculosis disease progression: A systematic review

Introduction: Viral infections have been found to affect the outcome of bacterial infections, but for the case of tuberculosis, much emphasis has been on HIV and less attention has been given to other viruses. We conducted a systematic review to identify studies that investigated the association of viral infection other than HIV and HIV coinfection with tuberculosis disease susceptibility and progression. Methods: We searched PubMed, Ovid Embase, and Scopus electronic databases using search terms “tuberculosis, viral disease, not HIV, TB, virus” in text words and MeSH terms for cohort and cross-sectional case-control studies by design that associated virus infections other than HIV-1 and HIV-2 with the development of TB disease. Results: Ten articles (three for cohort and seven for cross-sectional case-control studies) were included in this review. An association with TB disease was established for infections with Human Cytomegalovirus (HCMV, 3 studies), Human T-Lymphotropic virus type 1 (HTLV-1, 3), Hepatitis C virus (HCV, 2) and Human Herpesvirus-8 virus (HHV-8, 1). Published studies failed to establish an association with Herpes Simplex virus-1 and 2 (1), Epstein Barr virus (2), and Influenza A virus (1). Majority of these studies (7 studies) were scored high quality in appraisal, one intermediate and two were scored low. The variation in viral pathogens, study designs and methods of measurement precluded meta-analysis. Conclusion: This limited data suggests that infections with HCMV, HTLV-1, HCV and possibly HHV-8 may be associated with TB disease, either through increasing susceptibility to infection or through enhancing progression from infection to disease. More data are needed on the potential role of other viral infections than HIV in tuberculosis disease progression, in order to be considered in the programmatic control of tuberculosis disease.