Human Cytomegalovirus Immunoglobulin G Response and Pulmonary Tuberculosis in Adolescents: A Case-Control Study

Abstract

Abstract Background Emerging evidence suggests a link between infection with herpes viruses, particularly human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), and progression to tuberculosis disease. Methods An unmatched case-control study was conducted among adolescents aged 10–19 years enrolled in an observational study (Teen TB) between November 2020 and November 2021, in Cape Town, South Africa. Fifty individuals with pulmonary tuberculosis and 51 healthy tuberculosis-exposed individuals without tuberculosis were included. Demographics and clinical data were obtained, and serum samples collected at enrolment were tested for HCMV immunoglobulin G (IgG) and EBV nuclear antigen (EBNA) IgG using 2 automated enzyme immunoassays. Odds ratios were estimated using unconditional logistic regression. Results The median age of 101 participants was 15 years (interquartile range, 13–17 years); 55 (54%) were female. All participants were HCMV IgG seropositive, and 95% were EBNA IgG seropositive. Individuals with tuberculosis had higher HCMV IgG titers than healthy controls (P = .04). Individuals with upper-tertile HCMV IgG titers had 3.67 times greater odds of pulmonary tuberculosis than those with IgG titers in the lower tertile (95% confidence interval, 1.05–12.84; P = .04). There was a trend for increasing odds of pulmonary tuberculosis with increasing titers of HCMV IgG (P = .04). In contrast, there was no association between tuberculosis and higher EBNA IgG values. Conclusions There is a high prevalence of sensitization to HCMV and EBV among adolescents in this high-tuberculosis-burden setting. Higher HCMV IgG titers were associated with pulmonary tuberculosis in adolescents.