Quantitative measures of human Cytomegalovirus infection and their associations with tuberculosis disease progression and Mycobacterium tuberculosis infection

Interactions between human cytomegalovirus (HCMV) and the host immune response to Mycobacterium tuberculosis (M.tb) may influence the risk of tuberculosis (TB) disease progression. Data on an association between HCMV and risk of initial infection with M.tb are lacking. In this correlation analysis, serological measures of HCMV were investigated in two cohorts: a TB case-control study nested within a Ugandan general population epidemiology cohort with serum samples from 25 TB disease cases up to 10 years prior to diagnosis, and a paediatric M.tb infection study with 22 matched pairs of highly-TB-exposed children from The Gambia, where one of each pair was infected with M.tb and the other was not (as determined by a tubeculin skin test (TST)). Among individuals in the Ugandan case-control study, we found a relationship between odds of progression to active TB disease and (i) increased levels of HCMV IgM (odds ratio (OR) 2.5 (99% CI 0.84-7.54) for medium tertile, and OR 3.55 (1.27-9.96) for high tertile), (ii) HCMV IgG avidity (OR 2.82 (0.88-9.01) for medium and OR 3.08 (1.25-11.82) for high), and (iii) C-reactive protein (CRP) levels (OR 1.70 (0.58-5.00) for medium and OR 3.59 (1.20-10.74) for high tertile of response). Among Gambian children, no association was found between TB infection and measures of HCMV exposure. Further evaluation of such associations in larger prospective studies and experimental testing for a causal relationship are needed. This article is part of the discussion meeting issue 'The indirect effects of cytomegalovirus infection: mechanisms and consequences'.