Validation of genotype cluster investigations for Mycobacterium tuberculosis: application results for 44 clusters from four heterogeneous United States jurisdictions

Abstract

BackgroundTracking the dissemination of specific Mycobacterium tuberculosis (Mtb) strains using genotyped Mtb isolates from tuberculosis patients is a routine public health practice in the United States. The present study proposes a standardized cluster investigation method to identify epidemiologic-linked patients in Mtb genotype clusters. The study also attempts to determine the proportion of epidemiologic-linked patients the proposed method would identify beyond the outcome of the conventional contact investigation.MethodsThe study population included Mtb culture positive patients from Georgia, Maryland, Massachusetts and Houston, Texas. Mtb isolates were genotyped by CDC’s National TB Genotyping Service (NTGS) from January 2006 to October 2010. Mtb cluster investigations (CLIs) were conducted for patients whose isolates matched exactly by spoligotyping and 12-locus MIRU-VNTR. CLIs were carried out in four sequential steps: (1) Public Health Worker (PHW) Interview, (2) Contact Investigation (CI) Evaluation, (3) Public Health Records Review, and (4) CLI TB Patient Interviews. Comparison between patients whose links were identified through the study’s CLI interviews (Step 4) and patients whose links were identified earlier in CLI (Steps 1–3) was conducted using logistic regression.ResultsForty-four clusters were randomly selected from the four study sites (401 patients in total). Epidemiologic links were identified for 189/401 (47 %) study patients in a total of 201 linked patient-pairs. The numbers of linked patients identified in each CLI steps were: Step 1 - 105/401 (26.2 %), Step 2 - 15/388 (3.9 %), Step 3 - 41/281 (14.6 %), and Step 4 - 28/119 (30 %). Among the 189 linked patients, 28 (14.8 %) were not identified in previous CI. No epidemiologic links were identified in 13/44 (30 %) clusters.ConclusionsWe validated a standardized and practical method to systematically identify epidemiologic links among patients in Mtb genotype clusters, which can be integrated into the TB control and prevention programs in public health settings. The CLI interview identified additional epidemiologic links that were not identified in previous CI. One-third of the clusters showed no epidemiologic links despite being extensively investigated, suggesting that some improvement in the interviewing methods is still needed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1937-9) contains supplementary material, which is available to authorized users.

A Prospective Cohort Study on the Prevalent and Recurrent Tuberculosis Isolates Using the MIRU-VNTR Typing

“…We categorized M.tb strains into five groups, and the dominant isolates were category IV, accounting for 77.46% of all isolates. We observed that the RD105 deletion (Beijing family) contributed to the predominant infection, which was consistent with findings by Larry D. Teeter (23) and Carlo Garzelli (24). In addition, we found a significant association between non-dominant strains and pulmonary cavitation, which was consistent with the report by Lazzarini (25).…”

Drivers of Tuberculosis Transmission

“…A key goal is to detect and interrupt transmission early enough to prevent incident genotypes from becoming epidemiologically entrenched in the population. In the United States, molecular surveillance [ 99 ] to detect and characterize clusters that may represent recent transmission has facilitated progress toward this goal [ 100 ]. In tandem, rapid uptake of technologies for WGS and phylogenetic analysis of select clusters that likely represent recent transmission has shown considerable promise in more precisely identifying outbreaks and outbreak-related cases.…”

Evaluation of 24-locus MIRU-VNTR genotyping in Mycobacterium tuberculosis cluster investigations in four jurisdictions in the United States, 2006–2010

“…From 44 PCRType clusters randomly selected in our previous study [17], fifty-nine patients with incomplete MIRU24 results (including 13 patients for the entire clusters 3 and 31 from MD and GA respectively) were excluded from the analysis. In total, 42 clusters consisting of 342 patients having complete MIRU24 results were included in the current study (Appendix A).…”

“…For patients in selected PCRType-based study clusters with Mtb isolates characterized prior to the 2009 transition to MIRU24, retrospective MIRU24 typing was performed. The study sample selection has been described in detail elsewhere [17]. Briefly, PCRType clusters were defined as two or more TB patients with the same PCRType in a given public health jurisdiction during the study period.…”

“…As mentioned in the parent study, we focused on PCRTypes having three or more patients. Therefore, only PCRType clusters consisting of at least three TB patients residing in the same given public health jurisdiction, whose TB status were reported between January 1, 2006 and the time of cluster evaluation, were eligible for the sample’s random selection [17]. Clustering by GENType was defined as two or more patients with indistinguishable spoligotype and MIRU24 pattern in a given county during the study timeframe.…”