BackgroundThe recurrence of tuberculosis (TB) disease in treated patients can serve as a marker of the efficacy of TB control programs. Recurrent disease represents either endogenous reactivation with the same strain of Mycobacterium tuberculosis due to non-compliance or inadequate therapy or exogenous reinfection with a new strain. Genotyping or whole genome sequencing (WGS) of M. tuberculosis isolates from initial and recurrent cases can differentiate between reinfection and reactivation. This study examined cases of recurrent TB in New South Wales, Australia, using genotyping and WGS.MethodsCulture-confirmed TB cases diagnosed at least 12 months apart between January 2011 and December 2016 were included. Isolates of M. tuberculosis from patients were compared using 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-24) typing and WGS.ResultsEighteen cases of recurrent disease were identified but isolates from only 15 (83%) were available for study. MIRU-24 findings classified 13 (13/15; 87%) as reactivation and two (13%), as reinfection. Sequencing 13 cultivable paired isolates demonstrated 11 reactivations and two reinfections. There was genomic similarity in 10 out of 13 pairs while one case (1/13; 8%) had 12 SNPS differences. Two other cases (2/13;15%) had > 200 SNPs differences and were classified as reinfection. No phenotypic or genomic evidence of drug resistance was observed.ConclusionTB control programs can achieve consistently low rates of recurrent disease in low incidence settings. WGS of implicated isolates augments the differentiation between reactivation and reinfection and indicates that the majority of recurrences are due to reactivation rather than reinfection. Predominance of reactivation over reinfection indicates high-quality public health practices and a low risk of local transmission.Trial registrationThis study was approved by the Western Sydney Local Health District (WSLHD) Human Research Ethics Committee (HREC Ref: AU RED LNR/17/WMEAD/190; SSA Ref: LNR SSA/17/WMEAD/191).
Treatment of latent tuberculosis infection (LTBI) is an important component of strategies to achieve global tuberculosis (TB) elimination, but implementation is rarely monitored. This is a retrospective review of TB contact tracing outcomes at one of the busiest TB clinics in Australia, measured against the Centre for Disease Control and Prevention performance indicators. In total, 45 of 53 (85%) pulmonary TB cases had 171 close contacts, of whom 139 (81%) were evaluated with a tuberculin skin test (TST); 58 of 139 (42%) were positive at baseline. Among 57 close contacts of 16 sputum smear-positive TB cases, the elicitation, evaluation, initiation of LTBI treatment and completion rates were 93%, 86%, 14% and 100%, and among 114 close contacts of 37 sputum smear-negative pulmonary TB cases 81%, 83%, 16% and 89%, respectively. Of 79 contacts with an initial negative TST, 19 of 47 (40%) demonstrated TST conversion when retested; 5 of 19 (26%) were offered LTBI treatment. Four secondary TB cases were identified. One incident TB case developed a pleural effusion 5 months after TST conversion, despite LTBI treatment. Apart from young children, LTBI treatment was inconsistently initiated in household TB contacts. Safe and pragmatic treatment options, as well as functional monitoring frameworks, are essential to improve LTBI treatment implementation.
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