An outbreak of tuberculosis occurred over a 3-year period in a medium-size community in British Columbia, Canada. The results of mycobacterial interspersed repetitive unit–variable-number ...tandem-repeat (MIRU-VNTR) genotyping suggested the outbreak was clonal. Traditional contact tracing did not identify a source. We used whole-genome sequencing and social-network analysis in an effort to describe the outbreak dynamics at a higher resolution.
Mycobacterium tuberculosis
is an important infectious disease even in developed countries with extensive control programs. This is the case in British Columbia, Canada, where the 2007 incidence rate of 6.4 cases per 100,000 population exceeded the national average of 4.7 cases per 100,000 population.
1
In May 2006, a case of smear-negative pleural tuberculosis was diagnosed in an adult in a medium-size community in British Columbia. A second case, manifested as disseminated tuberculosis, was reported in an infant in July 2006. Reverse contact tracing identified nine additional cases between August and October 2006, when the British Columbia Centre for Disease Control . . .
Background Recent data have demonstrated that healthcare use after treatment for respiratory tuberculosis (TB) remains elevated in the years following treatment completion. However, it remains ...unclear which TB survivors are high healthcare users and whether any variation exists within this population. Thus, the primary objective of this study was to identify distinct profiles of high healthcare-use TB survivors to help inform post-treatment support and care. Methods Using linked health administrative data from British Columbia, Canada, we identified foreign-born individuals who completed treatment for incident respiratory TB between 1990 and 2019. We defined high healthcare-use TB survivors as those in the top 10% of annual emergency department visits, hospital admissions, or general practitioner visits among the study population during the five-year period immediately following TB treatment completion. We then used latent class analysis to categorize the identified high healthcare-use TB survivors into subgroups. Results Of the 1,240 people who completed treatment for respiratory TB, 258 (20.8%) people were identified as high post- TB healthcare users. Latent class analysis results in a 2-class solution. Class 1 (n = 196; 76.0%) included older individuals (median age 71.0; IQR 59.8, 79.0) with a higher probability of pre-existing hypertension and diabetes (41.3% and 33.2%, respectively). Class 2 (n = 62; 24.0%) comprised of younger individuals (median age 31.0; IQR 27.0, 41.0) with a high probability (61.3%) of immigrating to Canada within five years of their TB diagnosis and a low probability (11.3%) of moderate to high continuity of primary care. Discussion Our findings suggest that foreign-born high healthcare-use TB survivors in a high-resource setting may be categorized into distinct profiles to help guide the development of person-centred care strategies targeting the long-term health impacts TB survivors face.
Nearly one quarter of the global population has been infected with
Mycobacterium tuberculosis
, and there are more than 10 million new infections per year. In an open-label trial, 9 months of ...isoniazid was compared with 4 months of rifampin as therapy for latent tuberculosis infection.
The link between chronic kidney disease (CKD) and tuberculosis (TB) has been known for more than 40 years, but the interaction between these 2 diseases is still poorly understood. Dialysis and renal ...transplant patients appear to be at a higher risk of TB, in part related to immunosuppression along with socioeconomic, demographic, and comorbid factors. Meanwhile, TB screening and diagnostic test performance is suboptimal in the CKD population, and there is limited evidence to guide protocols. Given the increasing prevalence of CKD in TB endemic areas, a merging of CKD and TB epidemics could have significant public health implications, especially in low- to middle-income countries such as India and China, that are experiencing rapid increases in CKD prevalence and account for more than one-third of global TB prevalence. To begin addressing TB-CKD, a clear understanding of the relationship between these 2 conditions needs to be established, and consistent, evidence-based screening and treatment guidelines need to be developed.
Abstract
Background
The safety and efficacy of rifampin among people living with human immunodeficiency virus (PLHIV) or other health conditions is uncertain. We assessed completion, safety, and ...efficacy of 4 months of rifampin vs 9 months of isoniazid among PLHIV or other health conditions.
Methods
We conducted post hoc analysis of 2 randomized trials that included 6859 adult participants with Mycobacterium tuberculosis infection. Participants were randomized 1:1 to 10 mg/kg/d rifampin or 5 mg/kg/d isoniazid. We report completion, drug-related adverse events (AE), and active tuberculosis incidence among people living with HIV; with renal failure or receiving immunosuppressants; using drugs or with hepatitis; with diabetes mellitus; consuming >1 alcoholic drink per week or current/former smokers; and with no health condition.
Results
Overall, 270 (3.9%) people were living with HIV (135 receiving antiretroviral therapy), 2012 (29.3%) had another health condition, and 4577 (66.8%) had no condition. Rifampin was more often or similarly completed to isoniazid in all populations. AEs were less common with rifampin than isoniazid among PLHIV (risk difference, −2.1%; 95% confidence interval CI, −5.9 to 1.6). This was consistent for others except people with renal failure or on immunosuppressants (2.1%; 95% CI, −7.2 to 11.3). Tuberculosis incidence was similar among people receiving rifampin or isoniazid. Among participants receiving rifampin living with HIV, incidence was comparable to those with no health condition (rate difference, 4.1 per 1000 person-years; 95% CI, −6.4 to 14.7).
Conclusions
Rifampin appears to be safe and as effective as isoniazid across many populations with health conditions, including HIV.
Clinical Trials Registration
NCT00170209; NCT00931736.
Among people living with human immunodeficiency virus or health conditions, rifampin appears as effective as isoniazid. Adverse events were relatively common with isoniazid; events were generally less common with rifampin, but highest among people with renal failure or receiving immunosuppressants.
An important problem limiting treatment of latent tuberculosis infection is the occurrence of adverse events with isoniazid. We combined populations from phase 2 and phase 3 open-label, randomised ...controlled trials, to establish risk factors for adverse events during latent tuberculosis infection treatment.
We did a post-hoc safety analysis based on data from two open-label, randomised controlled trials done in health-care facilities in Australia, Benin, Brazil, Canada, Ghana, Guinea, Indonesia, Saudi Arabia, and South Korea. Participants were consenting adults (aged ≥18 years) with a positive latent tuberculosis infection diagnostic test, indication for treatment, and without contraindications to rifampicin or isoniazid. Patients were centrally randomly assigned 1:1 to 4 months of daily 10 mg/kg rifampicin or 9 months of daily 5 mg/kg isoniazid. The primary outcome evaluated was adverse events (including grade 1–2 rash and all events of grade 3–5) resulting in permanent discontinuation of study medication and judged possibly or probably related to study drug by a masked, independent, three-member adjudication panel (trial registration: NCT00170209; NCT00931736).
Participants were recruited from April 27, 2004, up until Jan 31, 2007 (phase 2), and Oct 1, 2009, up until Dec 31, 2014 (phase 3). The safety populations for each group comprised 3205 individuals receiving isoniazid and 3280 receiving rifampicin. Among those receiving isoniazid, 86 (2·7%) of 3205 had grade 1–2 rash or any grade 3–5 adverse events, more than the 50 (1·5%) of 3280 who had these events with rifampicin (risk difference −1·2%, 95% CI −1·9 to −0·5). Age was associated with adverse events in adults receiving isoniazid. Compared with individuals aged 18–34 years, the adjusted odds ratio (OR) for adverse events was 1·8 (95% CI 1·1–3·0) for individuals aged 35–64 years and 3·0 (1·2–6·8) for individuals aged 65–90 years. With rifampicin, adverse events were associated with inconsistent medication adherence (adjusted OR 2·0, 1·1–3·6) and concomitant medication use (2·8, 1·5–5·2), but not age, with an adjusted OR of 1·1 (0·6–2·1) for individuals aged 35–64 years and 1·7 (0·5–4·7) for individuals aged 65–90 years. One treatment-related death occurred in the isoniazid group.
In patients without a contraindication, rifampicin is likely to be the safest latent tuberculosis infection treatment option. With more widespread use of rifampicin, rare, but serious adverse events might be seen. However, within these randomised trials, rifampicin was safer than isoniazid and adverse events were not associated with older age. Therefore, rifampicin should become a primary treatment option for latent tuberculosis infection based on its safety.
Canadian Institutes of Health Research.
There is increasing evidence that community-based treatment of drug resistant tuberculosis (DRTB) is a feasible and cost-effective alternative to centralized, hospital-based care. Although several ...large programs have reported favourable outcomes from community-based treatment, to date there has been no systematic assessment of community-based DRTB treatment program outcomes. The objective of this study was to synthesize available evidence on treatment outcomes from community based multi-drug resistant (MDRTB) and extensively drug resistant tuberculosis (XDRTB) treatment programs.
We performed a systematic review and meta-analysis of the published literature to examine treatment outcomes from community-based MDRTB and XDRTB treatment programs. Studies reporting outcomes from programs using community-based treatment strategies and reporting outcomes consistent with WHO guidelines were included for analysis. Treatment outcomes, including treatment success, default, failure, and death were pooled for analysis. Meta-regression was performed to examine for associations between treatment outcomes and program or patient factors.
Overall 10 studies reporting outcomes on 1288 DRTB patients were included for analysis. Of this population, 65% 95% CI 59-71% of patients had a successful outcome, 15% 95% CI 12-19% defaulted, 13% 95% CI 9-18% died, and 6% 95% CI 3-11% failed treatment for a total of 35% 95% CI 29-41% with unsuccessful treatment outcome. Meta-regression failed to identify any factors associated with treatment success, including study year, age of participants, HIV prevalence, XDRTB prevalence, treatment regimen, directly observed therapy (DOT) location or DOT provider.
Outcomes of community-based MDRTB and XDRTB treatment outcomes appear similar to overall treatment outcomes published in three systematic reviews on MDRTB therapy. Work is needed to delineate program characteristics associated with improved treatment outcomes.
The majority of tuberculosis in migrants to Canada occurs due to reactivation of latent TB infection. Risk of tuberculosis in those with latent tuberculosis infection can be significantly reduced ...with treatment. Presently, only 2.4% of new migrants are flagged for post-landing surveillance, which may include latent tuberculosis infection screening; no other migrants receive routine latent tuberculosis infection screening. To aid in reducing the tuberculosis burden in new migrants to Canada, we determined the cost-effectiveness of using different latent tuberculosis infection interventions in migrants under post-arrival surveillance and in all new migrants.
A discrete event simulation model was developed that focused on a Canadian permanent resident cohort after arrival in Canada, utilizing a ten-year time horizon, healthcare system perspective, and 1.5% discount rate. Latent tuberculosis infection interventions were evaluated in the population under surveillance (N = 6100) and the total cohort (N = 260,600). In all evaluations, six different screening and treatment combinations were compared to the base case of tuberculin skin test screening followed by isoniazid treatment only in the population under surveillance. Quality adjusted life years, incident tuberculosis cases, and costs were recorded for each intervention and incremental cost-effectiveness ratios were calculated in relation to the base case.
In the population under surveillance (N = 6100), using an interferon-gamma release assay followed by rifampin was dominant compared to the base case, preventing 4.90 cases of tuberculosis, a 4.9% reduction, adding 4.0 quality adjusted life years, and saving $353,013 over the ensuing ten-years. Latent tuberculosis infection screening in the total population (N = 260,600) was not cost-effective when compared to the base case, however could potentially prevent 21.8% of incident tuberculosis cases.
Screening new migrants under surveillance with an interferon-gamma release assay and treating with rifampin is cost saving, but will not significantly impact TB incidence. Universal latent tuberculosis infection screening and treatment is cost-prohibitive. Research into using risk factors to target screening post-landing may provide alternate solutions.
Prospective migrants to countries where the incidence of tuberculosis (TB) is low (low-incidence countries) receive TB screening; however, screening for latent TB infection (LTBI) before immigration ...is rare. We evaluated the cost-effectiveness of mandated and sponsored preimmigration LTBI screening for migrants to low-incidence countries. We used discrete event simulation to model preimmigration LTBI screening coupled with postarrival follow-up and treatment for those who test positive. Preimmigration interferon-gamma release assay screening and postarrival rifampin treatment was preferred in deterministic analysis. We calculated cost per quality-adjusted life-year gained for migrants from countries with different TB incidences. Our analysis provides evidence of the cost-effectiveness of preimmigration LTBI screening for migrants to low-incidence countries. Coupled with research on sustainability, acceptability, and program implementation, these results can inform policy decisions.
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