To investigate the association between mycobacterial genotype and disease phenotype in children.

We describe hospitalised children diagnosed with culture-confirmed tuberculosis (TB) in South Africa, a high TB burden setting. Disease phenotype was classified as intrathoracic or extrathoracic based on mycobacterial culture site. Mycobacterial genotyping was completed using spoligotyping.

We analysed 421 isolates from 392 children (median age 2 years, range 0.1–12). Intrathoracic disease was present in 294 (75%) children and extrathoracic disease in 98 (25%). The Beijing genotype was the most prevalent (32.9%), followed by the Latin American Mediterranean (LAM, 28.8%), and S genotypes (6.4%). Age was significantly associated with genotype. Children with the Beijing (OR = 2.36, 95%CI 1.21– 4.60) and S genotypes (OR = 3.47, 95%CI 1.26–9.56) were more likely to have extrathoracic disease compared to children infected with the LAM genotype, in analyses adjusted for age and drug resistance.

TB genotype and disease phenotype in children were associated. Beijing and S genotypes were more frequently cultured from extrathoracic cultures, indicating potential improved ability to disseminate. Strain-related phenotypes could explain different disease spectra in geographic settings where certain strains are successful. Studies of mycobacterial human interaction should consider host immune responses, clinical and epidemiological factors.