Characterizing the Etiology of Recurrent Tuberculosis Using Whole Genome Sequencing: Alaska, 2008–2020

Abstract

Abstract Background Understanding the etiology of recurrent tuberculosis (rTB) is important for effective tuberculosis control. Prior to the advent of whole genome sequencing (WGS), attributing rTB to relapse or reinfection using genetic information was complicated by the limited resolution of conventional genotyping methods. Methods We applied a systematic method of evaluating whole genome single-nucleotide polymorphism (wgSNP) distances and results of phylogenetic analyses to characterize the etiology of rTB in American Indian and Alaska Native (AIAN) persons in Alaska during 2008 to 2020. We contextualized our findings through descriptive analyses of surveillance data and results of a literature search for investigations that characterized rTB etiology using WGS. Results The percentage of tuberculosis cases in AIAN persons in Alaska classified as recurrent episodes (11.8%) was 3 times the national percentage (3.9%). Of 38 recurrent episodes included in genetic analyses, we attributed 25 (65.8%) to reinfection based on wgSNP distances and phylogenetic analyses; this proportion was the highest among 16 published point estimates identified through the literature search. By comparison, we attributed 11 (28.9%) and 6 (15.8%) recurrent episodes to reinfection based on wgSNP distances alone and on conventional genotyping methods, respectively. Conclusions WGS and attribution criteria involving genetic distances and patterns of relatedness can provide an effective means of elucidating rTB etiology. Our findings indicate that rTB occurs at high proportions among AIAN persons in Alaska and is frequently attributable to reinfection, reinforcing the importance of active surveillance and control measures to limit the spread of tuberculosis disease in Alaskan AIAN communities.