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 nested case-control analysis 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. Cases (n=98) and HIV status frequency matched controls (n=199) basing on mycobacterial culture and or GeneXpert Ultra were included in the study. HCMV DNAemia was detected by qPCR well as current HCMV reactivation or reinfection and recent HCMV infection, reactivation or reinfection were categorized using PCR and serology (IgM and IgG avidity ELISA) results. The median age of all participants was 37 years (IQR 29-47), 164 (55.2%) were male and 119 (40.1%) had previous TB treatment. Overall, 21 (7.1%) had HCMV DNAemia, 19 (6.4%) had positive HCMV IgM and 2 (0.7%) had low HCMV avidity. In a logistic regression model adjusting for age, gender, HIV status and BMI, TB disease was associated with current HCMV reactivation or reinfection [adjusted odds ratio (aOR) 4.88, 95%CI 1.59-16.31, p=0.007]. There was no association with recent HCMV infection, reactivation or reinfection. Unlike recent HCMV infection, reactivation or reinfection, active HCMV replication although not frequent was associated with TB disease which suggests that TB disease or an underlying common factor reactivates HCMV replication in this population.