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

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 (TB) disease. Methods An unmatched case-control study was conducted amongst 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 TB and 51 healthy TB-exposed individuals without TB were included. Demographics and clinical data were obtained, and serum samples collected at enrolment were tested for HCMV IgG and EBV Nuclear Antigen (EBNA) IgG using two automated enzyme immunoassays. Odds ratios (ORs) were estimated using unconditional logistic regression. Results The median age of 101 participants was 15 years (interquartile range [IQR] 13 to 17); 55 (54%) were female. All participants were HCMV IgG seropositive and 95% were EBNA IgG seropositive. Individuals with TB had higher HCMV IgG titres than healthy controls (p=0.04). Individuals with upper tertile HCMV IgG titres had a 3.7 times greater odds of pulmonary TB compared to those with IgG titres in the lower tertile (95%CI: 1.05–12.84; p=0.04). There was a trend for increasing odds of pulmonary TB with increasing titres of HCMV IgG (p=0.04). In contrast, there was no association between TB and higher EBNA IgG values. Conclusions There is a high prevalence of sensitisation to HCMV and EBV amongst adolescents in this high-TB burden setting. Higher HCMV IgG titres were associated with pulmonary TB in adolescents.