Genomic sequencing is required for identification of tuberculosis transmission in Hawaii.

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PubMed ID: 30509214

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Koster KJ, Largen A, Foster JT, Drees KP, Qian L, Desmond E, Wan X, Hou S, Douglas JT

BMC Infect Dis. Dec 2018. doi: 10.1186/s12879-018-3502-1

COMMENT: This article highlights the use of next generation whole genome sequencing as a useful tool to resolve Mycobacterium tuberculosis transmission clusters that are indistinguishable by molecular fingerprinting methods.


For this study, we selected 19 apparent TB transmission clusters that were identified by fingerprinting or epidemiological data in Hawaii from 2003 to 2017 and conducted Illumina whole genome sequencing to determine if WGS could be used to further resolve these clusters and identify the transmis- sion connections among isolates.


Nineteen Mtb fingerprinting clusters were either fully (n =15) or partially (n =4) sequenced, with two or more isolates selected for initial sequencing to evaluate the possibility that the fingerprinting cluster represents a direct or recent transmission cluster. Eight of the fingerprinting clusters were determined to represent actual transmission clusters due to isolates in those clusters being separated by fewer than six SNPs. Four clusters were determined to partially represent direct transmission, meaning that while some isolates in the fingerprinting cluster were separated by five or fewer SNPs, other isolates within the fingerprinting cluster were separated by 12 or more SNPs. 

Standard fingerprinting was unable to resolve any of the clusters indicated by WGS. If WGS is designated as the “gold standard” for Mtb typing, then the sensitivity Mtb fingerprinting for identifying actual transmission clusters was found to be 100% (95% CI, 31.0–100%), while its specificity was only 28.6% (95% CI, 5.1–69.7%).


This project demonstrated use of whole genome sequencing to successfully overcome the Beijing and Manila families’ current fingerprinting difficulties, which have been a persistent problem for State of Hawaii tuberculosis control efforts. We identified why even 24-loci MIRU-VNTR fingerprinting fails to effectively resolve Beijing and Manila family clusters, and illustrated the advantage and necessity of utilizing WGS for molecular epidemiology in this region.


Raquel Ruiz-Arroyo