Association of Human Cytomegalovirus exposure with tuberculosis disease in South African adults with presumptive tuberculosis

Recent studies suggested that human cytomegalovirus (HCMV) exposure may increase tuberculosis (TB) disease risk. We assessed the association between active HCMV infection and recent HCMV exposure with tuberculosis (TB) disease among TB-presumptive South African adults. This was a cross-sectional case-control study that utilized stored plasma and serum samples collected from adults (≥18 years) with presumptive TB self-presenting to primary care clinics in in the Kraaifontein District in Cape Town, South Africa. This study analyzed TB Cases (n = 98) who were mycobacterial culture and or GeneXpert Ultra positive and controls (n = 199) who were frequency matched by HIV status. Current HCMV infection (including reactivation or reinfection) and recent infection were defined using qPCR and serology (IgM and IgG avidity ELISA), while HCMV DNAemia was defined by a positive qPCR result alone. In a logistic regression model adjusting for age, gender, HIV status and BMI, TB disease was associated with HCMV DNAemia [adjusted odds ratio (aOR) 4.99, 95%CI 1.63-16.99, p = 0.007]. A similar association was observed for current HCMV infection, whereas no association was found for recent HCMV infection. These results indicate that active HCMV replication although not frequent may impair immune response to TB disease, TB disease could be leading to HCMV replication or an underlying common factor reactivates HCMV and Mtb replication in this population.