Endogenous reactivation and true treatment failure as causes of recurrent tuberculosis in a high incidence setting with a low HIV infection

Abstract

Summaryobjective To determine the relative frequencies of reinfection vs. reactivation or treatment failure in patients from a high tuberculosis incidence setting with a low prevalence of HIV infection.method We performed DNA fingerprinting on serial isolates from one and multiple TB episodes from 97 retreatment patients; 35 patients had been previously cured, whereas 62 had not.results DNA fingerprinting patterns of recurrence Mycobacterium tuberculosis isolates of 5 of the 35 previously cured patients did not match with those of the corresponding initial isolates, indicating reinfection. We did not document reinfection during treatment. Isolates from each of the remaining 30 previously cured patients had identical DNA fingerprinting results, indicating reactivation. DNA fingerprinting patterns of isolates from the 62 patients with persistently positive sputum smears were identical, suggesting treatment failure.conclusion These findings suggest that reinfection is not a common cause of relapse and treatment failure in this rural predominantly HIV-free population despite the high incidence of TB.

Interferon γ Responses to Mycobacterial Antigens Protect against Subsequent HIV‐Associated Tuberculosis

“…The IFN-γ responses to mycobacterial antigens detected in this study were associated with protection from either reactivation or reinfection TB [32–34]. The INH we administered to 312 placebo subjects with a positive TST would have reduced but not eliminated the risk of reactivation, and such protection wanes with time [35].…”

Drug resistance pattern and outcome of treatment in recurrent episodes of tuberculosis

“…In low TB incidence communities, the most frequent cause of recurrence is true relapse or treatment failure [9,10], whereas in high TB incidence populations reinfection is the most common mechanism for recurrence of disease [11,12]. Therefore, efficacy of the CAT II regimen in recurrent cases may be dependent on the frequency of drug-resistant strains in the community, the primary mechanisms of recurrent disease and the efficiency of the national TB programmes [5].…”

Genetic Diversity of Mycobacterium tuberculosis Isolates from a Tertiary Care Tuberculosis Hospital in South Korea

“…MIRU-VNTR is based on analysis of tandemly repeated sequences of multiple loci that are amplified using primers flanking regions of each locus, followed by size determination of the resulting PCR products, which indicates the numbers of the targeted MIRU-VNTR copies. A set of loci has been standardized (34) and favorably evaluated (4,23,28,39) for discriminating clinical isolates of M. tuberculosis. To date, studies of the application of DNA typing methods in differentiating clinical isolates of M. tuberculosis in the Republic of Korea are rare or old, and the usefulness of the recommended MIRU-VNTR loci has not been evaluated.…”

“…DNA fingerprinting has contributed significantly to the understanding of the epidemiology and control of TB by providing information on transmission dynamics (19,21,38), determining the importance of reactivation versus exogenous reinfection (10,34), investigating/confirming outbreaks (29), and confirmation of laboratory cross contamination (2). The most widely applied and current standard method for comparing the genetic relatedness of M. tuberculosis strains is IS6110-based restriction fragment length polymorphism (RFLP) (41).…”