Abstract
Tuberculosis caused by concurrent infection with multiple Mycobacterium tuberculosis strains (i.e., mixed infection) challenges clinical and epidemiologic paradigms. We explored possible transmission mechanisms of mixed infection in a population-based, molecular epidemiology study in Botswana during 2012–2016. We defined mixed infection as multiple repeats of alleles at >2 loci within a discrete mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) result. We compared mixed infection MIRU-VNTR results with all study MIRU-VNTR results by considering all permutations at each multiple allele locus; matched MIRU-VNTR results were considered evidence of recently acquired strains and nonmatched to any other results were considered evidence of remotely acquired strains. Among 2,051 patients, 34 (1.7%) had mixed infection, of which 23 (68%) had recently and remotely acquired strains. This finding might support the mixed infection mechanism of recent transmission and simultaneous remote reactivation. Further exploration is needed to determine proportions of transmission mechanisms in settings where mixed infections are prevalent.
Highlights
Tuberculosis caused by concurrent infection with multiple Mycobacterium tuberculosis strains challenges clinical and epidemiologic paradigms
Tuberculosis (TB) caused by concurrent infection with multiple strains of Mycobacterium tuberculosis during 1 episode is commonly referred to as mixed infection
Infections caused by multiple M. tuberculosis strains can occur after simultaneous transmission of multiple strains during a single transmission episode or by sequential infections of >2 strains acquired at different times, resulting in superinfection [10]
Summary
Tuberculosis caused by concurrent infection with multiple Mycobacterium tuberculosis strains (i.e., mixed infection) challenges clinical and epidemiologic paradigms. We explored possible transmission mechanisms of mixed infection in a population-based, molecular epidemiology study in Botswana during 2012–2016. Among 2,051 patients, 34 (1.7%) had mixed infection, of which 23 (68%) had recently and remotely acquired strains. Tuberculosis (TB) caused by concurrent infection with multiple strains of Mycobacterium tuberculosis during 1 episode is commonly referred to as mixed infection. Despite the clinical importance of mixed infection, its potential leading mechanisms of transmission have not been examined using empirical data. Infections caused by multiple M. tuberculosis strains can occur after simultaneous transmission of multiple strains during a single transmission episode (i.e., the index patient transmits multiple strains) or by sequential infections of >2 strains acquired at different times, resulting in superinfection [10]. Our objective was to explore possible transmission mechanisms leading to mixed
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