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

Area of Science:

• Genomics
• Epidemiology
• Public Health

Background:

• Understanding the causes of recurrent tuberculosis (rTB) is crucial for effective control strategies.
• Conventional genotyping methods had limited resolution for distinguishing relapse from reinfection in rTB cases.
• Whole genome sequencing (WGS) offers improved genetic resolution for rTB etiology studies.

Purpose of the Study:

• To characterize the etiology of rTB in American Indian and Alaska Native (AIAN) persons in Alaska from 2008 to 2020.
• To evaluate the utility of whole genome single-nucleotide polymorphism (wgSNP) distances and phylogenetic analyses in determining rTB causes.
• To compare WGS-based attribution with conventional genotyping methods.

Main Methods:

• Applied systematic evaluation of wgSNP distances and phylogenetic analyses to rTB cases in AIAN individuals in Alaska.
• Conducted descriptive analyses of surveillance data and a literature search for WGS-based rTB etiology studies.
• Compared attribution of recurrent episodes to reinfection using wgSNP distances, phylogenetic analyses, and conventional genotyping.

Main Results:

• Tuberculosis cases in AIAN persons in Alaska had a 11.8% rTB rate, three times the national average.
• WGS with phylogenetic analysis attributed 65.8% of 38 rTB episodes to reinfection, the highest proportion among published estimates.
• Reinfection attribution was 28.9% using wgSNP distances alone and 15.8% with conventional genotyping.

Conclusions:

• WGS, combined with genetic distance and relatedness criteria, effectively elucidates rTB etiology.
• High proportions of rTB among Alaskan AIAN persons are attributable to reinfection.
• Findings underscore the importance of active surveillance and control measures in Alaskan AIAN communities to limit tuberculosis transmission.