Identifying Tuberculosis Transmission from Smear-Negative Patients Using Genotype and Epidemiologic Links - Suburban Cook County, Illinois, 2009-2015

BACKGROUND:  Active tuberculosis (TB) patients with sputum smears that are negative for acid-fast bacilli are less likely to transmit TB than patients with positive sputum smears. Smear status is routinely used by TB control programs to make decisions regarding isolation and extent of contact investigations. Recent studies using genotyping suggest the proportion of TB transmission attributable to smear negative patients ranges from 13-30% but only one of these studies also took into account known epidemiologic links between patients. Patients linked by genotype alone may represent several different transmission scenarios or immigration patterns from areas of the world where certain TB strains are common. Epidemiologic links clarify chains of transmission. Our objective was to use both genotyping and epidemiologic links to determine the contribution of smear negative patients to TB transmission in suburban Cook County.

METHODS:  TB cases with available data, beginning in 2009, were organized into genotype clusters based on spoligotype and 24-locus Mycobacterial Interspersed Repetitive Units - Variable Numbers of Tandem Repeat (MIRU-VNTR). Cases in each cluster were ordered chronologically based on symptom onset date. In the genotyping only analysis, secondary cases were attributed to smear negative transmission if only smear negative cases preceded them in the cluster. When epidemiologic information was incorporated, secondary cases were attributed to smear negative transmission only when they had a matching genotype and were epidemiologically linked to a smear negative source case. In each scenario, the proportion of secondary cases attributed to smear negative transmission and the relative transmission rate when compared to smear positive cases were calculated.

RESULTS:  Of 478 cases diagnosed after 1/1/2009, 278 (58%) had both spoligotype and 24-locus MIRU-VNTR available. Of these 278, 246 (88%) had unique genotypes and 32 (12%) were in 15 genotype clusters. Based on genotype data alone, 5 of 17 secondary patients, or 29%, were infected by smear negative patients. The relative transmission rate was 0.37, meaning that smear negative patients are 37% as likely as smear positive patients to transmit TB. However, when epidemiologic links were included, only 1 secondary patient (6%) was attributable to smear negative transmission. This reduced the relative transmission rate of smear negative patients to 0.22 when compared to smear positive patients. 

CONCLUSIONS:  Introduction of epidemiological data into genotyping results reduced the proportion of smear negative TB transmission in suburban Cook County by 23%. Additional research is critical to assist TB control programs in interpreting genotype clusters in the absence of epidemiologic links.