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Household-based studies are commonly used to investigate tuberculosis (TB) transmission and evaluate preventive interventions. These studies typically assume that household contacts (HHCs) who develop TB disease were infected by the identified index patient. However, community-acquired infections may challenge this assumption, potentially biasing findings. Here, we evaluated the proportion of genetically linked index-HHC pairs and examined whether this proportion varied based on the TB burden in the community.

We conducted a prospective cohort study in Lima, Peru, enrolling microbiologically confirmed pulmonary TB index patients and their HHCs who were followed for 1 year. Mycobacterium tuberculosis (Mtb) isolates from culture-positive index patients and HHCs underwent whole-genome sequencing (WGS). We defined index-HHC patient pairs as resulting from within-household transmission when the genetic distance between their Mtb isolates was ≤12 single nucleotide polymorphisms. To contextualize our findings, we conducted a systematic review of Mtb genotyping studies that used spoligotyping, restriction fragment length polymorphisms , mycobacterial interspersed repetitive units-variable number tandem repeats, or WGS to assess within-household TB infection transmission among index-HHC patient pairs.

In our Lima study, among 175 index-HHC patient pairs, 109 (62%) were classified as within-household transmission. The systematic review identified 22 qualifying studies from settings with TB burdens ranging from 6.7 to 845 cases per 100 000 person-years. Studies in settings with TB incidence of ≤250 per 100 000 person-years consistently reported linkage proportions of ≥61%, whereas high-burden settings exhibited greater variability.

Our findings suggest that, among individuals exposed to TB at home, within-household transmission predominates in moderate- or low-TB-burden settings. However, its relative contribution in high-incidence settings remains unclear.