Quantifying within-household tuberculosis transmission: a systematic review and prospective cohort study

Area of Science:

• Infectious Disease Epidemiology
• Genomic Epidemiology
• Public Health

Background:

• Household-based studies are crucial for understanding tuberculosis (TB) transmission and intervention effectiveness.
• A key assumption is that TB in household contacts (HHCs) stems from the index patient, but community-acquired infections may introduce bias.
• This study investigates the proportion of genetically linked TB transmission within households and its variation by community TB burden.

Purpose of the Study:

• To evaluate the proportion of genetically linked tuberculosis transmission within households.
• To determine if this proportion varies based on the community's tuberculosis burden.

Main Methods:

• A prospective cohort study in Lima, Peru, involved microbiologically confirmed pulmonary TB index patients and their HHCs, followed for one year.
• Whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) isolates was performed on index patients and HHCs.
• Within-household transmission was defined by a genetic distance of ≤12 single nucleotide polymorphisms (SNPs) between Mtb isolates. A systematic review of genotyping studies was also conducted.

Main Results:

• In the Lima study, 62% (109/175) of index-HHC pairs were classified as within-household transmission.
• A systematic review of 22 studies revealed consistent linkage proportions of ≥61% in settings with TB incidence ≤250 per 100,000 person-years.
• High-burden settings showed more variable proportions of within-household TB transmission.

Conclusions:

• Within-household TB transmission is the predominant mode in moderate- or low-TB-burden settings.
• The relative contribution of within-household transmission in high-incidence TB settings remains uncertain.
• Findings highlight the importance of considering community TB burden when interpreting household TB transmission studies.