Evaluating Estimates of Recent Tuberculosis Transmission Using Epidemiologic and Whole-Genome Sequencing Data, Los Angeles County, California, 2014-2018
Clinton J. McDaniel, Sarah Talarico, Kala M. Raz, Steve Kammerer, Shameer Poonja, Sophia Hsu, Julie Higashi, Alicia H. Chang, Tambi Shaw, Martin Cilnis, Wendy Noboa, Jonathan Wortham, Lauren Cowan, James Posey, Benjamin J. SilkObjectives:
Estimating the percentage of tuberculosis cases in a population attributable to recent transmission, compared with reactivation of past infections, is crucial for public health decision-making. This study evaluated a previously published plausible-source case (PSC) method for estimating recent transmission in Los Angeles County (LA County) against a reference standard based on epidemiologic and whole-genome sequencing data.
Methods:
We analyzed tuberculosis cases diagnosed in LA County from 2014 through 2018 using surveillance data. Cases were classified as consistent or inconsistent with recent transmission using the PSC method and a stepwise review of epidemiologic links and single nucleotide polymorphisms (Epi/SNP). We compared classifications from both methods and assessed discrepancies.
Results:
Of 2949 tuberculosis cases in LA County, 650 had epidemiologic and whole-genome sequencing data for evaluating recent transmission; 44 were excluded due to missing genotyping data, including 7 pediatric patients aged <15 years. The Epi/SNP review classified 195 (30%) cases as consistent with recent transmission, while the PSC method attributed 301 (46%) cases to recent transmission. The 2 methods agreed on 454 (70%) cases. Discrepancies arose from genetic diversity, geographic distance, nonmatching genotypes, and diagnosis timing. Performance varied by race and ethnicity, nativity, lineage, history of homelessness, and substance use.
Conclusions:
The PSC method accurately classified more than two-thirds of tuberculosis cases included in a cluster investigation in LA County. However, findings underscore the need to refine the PSC method by integrating whole-genome sequencing data, including nongenotyped cases in pediatric patients, and reevaluating the geographic and timing criteria to enhance completeness and inform public health interventions aimed at interrupting tuberculosis transmission.