Active CMV linked with tuberculosis in South African adults

Researchers led by Willy Ssengooba investigated a possible connection between human cytomegalovirus (HCMV) exposure and tuberculosis (TB) disease in adults who presented with TB symptoms. Recent studies had raised the question that HCMV exposure might increase TB risk, so the team performed a nested case-control analysis using stored plasma and serum samples from adults aged 18 and older who self-presented to primary care clinics in the Kraaifontein District in Cape Town, South Africa. Cases (n=98) were defined by positive mycobacterial culture and/or GeneXpert Ultra results, and they were compared with HIV status frequency matched controls (n=199). The participants had a median age of 37 years (IQR 29-47); 164 (55.2%) were male and 119 (40.1%) reported previous TB treatment. By focusing on people already presumed to have TB, the study aimed to see whether markers of active HCMV infection or recent HCMV exposure were more common in those with confirmed TB disease than in those without.

To detect HCMV activity the study used molecular and serologic tools. HCMV DNAemia was detected by qPCR to indicate active viral replication, while PCR together with serology (IgM and IgG avidity ELISA) were used to categorize current HCMV reactivation or reinfection and recent HCMV infection, reactivation or reinfection. Overall, 21 participants (7.1%) had HCMV DNAemia, 19 (6.4%) had positive HCMV IgM, and 2 (0.7%) had low HCMV avidity. The authors applied a logistic regression model that adjusted for age, gender, HIV status and BMI. In that analysis, TB disease was associated with current HCMV reactivation or reinfection, with an adjusted odds ratio (aOR) of 4.88 (95% CI 1.59-16.31, p=0.007). There was no detected association between TB disease and recent HCMV infection, reactivation or reinfection as defined by the serologic criteria.

The study finds that active HCMV replication, although uncommon in this cohort, was linked to TB disease in adults with presumptive TB. Importantly, the association applied to evidence of current HCMV reactivation or reinfection detected by qPCR rather than to markers of recent HCMV exposure by IgM or low IgG avidity. The authors suggest that this pattern could mean either that TB disease promotes reactivation of HCMV or that a common underlying factor increases the likelihood of both TB disease and HCMV replication in this population. Because the analysis was conducted among clinic attendees already suspected of TB, the findings point to a need for careful interpretation and further study, but they highlight the potential importance of considering active HCMV replication when studying TB disease dynamics in high-burden settings.