Model-based Analysis of Tuberculosis Genotype Clusters in the United States Reveals High Degree of Heterogeneity in Transmission and State-level Differences Across California, Florida, New York, and Texas

BACKGROUND: Reductions in tuberculosis (TB) transmission have been instrumental in lowering TB incidence in the United States. Sustaining and augmenting these reductions are key public health priorities. METHODS: We fit mechanistic transmission models to distributions of genotype clusters of TB cases reported to the Centers for Disease Control and Prevention during 2012-2016 in the United States and separately in California, Florida, New York, and Texas. We estimated the mean number of secondary cases generated per infectious case (R0) and individual-level heterogeneity in R0 at state and national levels and assessed how different definitions of clustering affected these estimates. RESULTS: In clusters of genotypically linked TB cases that occurred within a state over a 5-year period (reference scenario), the estimated R0 was 0.29 (95% confidence interval [CI], .28-.31) in the United States. Transmission was highly heterogeneous; 0.24% of simulated cases with individual R0 >10 generated 19% of all recent secondary transmissions. R0 estimate was 0.16 (95% CI, .15-.17) when a cluster was defined as cases occurring within the same county over a 3-year period. Transmission varied across states: estimated R0s were 0.34 (95% CI, .3-.4) in California, 0.28 (95% CI, .24-.36) in Florida, 0.19 (95% CI, .15-.27) in New York, and 0.38 (95% CI, .33-.46) in Texas. CONCLUSIONS: TB transmission in the United States is characterized by pronounced heterogeneity at the individual and state levels. Improving detection of transmission clusters through incorporation of whole-genome sequencing and identifying the drivers of this heterogeneity will be essential to reducing TB transmission.