Using Genotyping and Geospatial Scanning to Estimate Recent Mycobacterium tuberculosis Transmission, United States

Patrick K. Moonan

, Smita Ghosh, John E. Oeltmann, J. Steven Kammerer, Lauren S. Cowan, and Thomas R. Navin

Author affiliations: US Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Abstract

To determine the proportion of reported tuberculosis (TB) cases due to recent transmission in the United States, we conducted a cross-sectional study to examine culture-positive TB cases with complete genotype results (spoligotyping and 12-locus mycobacterial interspersed repetitive unit–variable-number tandem repeat typing) reported during January 2005–December 2009. Recently transmitted cases were defined as cases with matching results reported within statistically significant geospatial zones (identified by a spatial span statistic within a sliding 3-year window). Approximately 1 in 4 TB cases reported in the United States may be attributed to recent transmission. Groups at greatest risk for recent transmission appear to be men, persons born in the United States, members of a minority race or ethnic group, persons who abuse substances, and the homeless. Understanding transmission dynamics and establishing strategies for rapidly detecting recent transmission among these populations are essential for TB elimination in the United States.

Molecular characterization of Mycobacterium tuberculosis complex has been available for >2 decades in the United States. As a tool to enhance programmatic activities, tuberculosis (TB) genotyping is a useful adjunct to epidemiologic field investigations by defining outbreaks (1,2), discerning episodes of reactivation and relapse (3,4), confirming suspected laboratory contamination (5,6), and evaluating and monitoring TB control program performance (7). TB genotyping results, when combined with epidemiologic data, help identify persons with TB disease who are involved in the same chain of recent transmission (8). Previous analytic studies have used TB genotyping data in conjunction with epidemiologic data to assess correlates of recent TB transmission within localized populations (9–15). A basic assumption of this approach is that recent TB transmission is localized in place and time, that is, progression to TB disease from an infection acquired within the past few years and in the same jurisdiction.
Population-based molecular epidemiologic studies are often subject to several biases and methodologic limitations that impede the ability of investigators to make valid statements about recent TB transmission events in the absence of direct data regarding interpersonal contacts (16). Estimating recent TB transmission is often limited by abbreviated study periods, convenience isolate sampling, and ambiguous geographic boundaries defined for jurisdictional or geopolitical reasons (17,18). TB transmission is not likely to be bound by these artifacts, however. Spatial scanning to detect disease clusters has been successfully applied in multiple settings and for various diseases (19). Using this method in a multiyear, nationally representative database of both genotype and routinely collected TB surveillance data may offer a better solution for accurately defining recent TB transmission.
In 2004, the US Centers for Disease Control and Prevention (CDC) offered universal access to TB genotyping through the National Tuberculosis Genotyping Service (NTGS) to routinely characterize at least 1 M. tuberculosis complex isolate from every TB case-patient in the United States (20). Although the intent of this system is to support local TB programs for public health action, data collected from this system offer a unique opportunity to explore and describe the molecular epidemiology of TB and establish comprehensive molecular TB surveillance in the United States. In this analysis, our goals were to estimate the proportion of TB in the United States attributable to recent transmission and to assess clinical, demographic, and epidemiologic factors associated with recent TB transmission.