Risk factors affecting treatment outcomes for pulmonary tuberculosis in Finland 2007-2014: a national cohort study.

BACKGROUND: Major transition in tuberculosis (TB) epidemiology is taking place in many European countries including Finland. Monitoring treatment outcome of TB cases is important for identifying gaps in the national TB control program, in order to strengthen the system. The aim of the study was to identify potential risk factors for non-successful TB treatment outcomes, with a particular focus on the impact of comorbidities. We also evaluated the treatment outcome monitoring system. METHODS: All notified microbiologically confirmed pulmonary TB cases in Finland in 2007-2014 were included, except multi-drug resistant (MDR) cases. Nationwide register data were retrieved from: Infectious Diseases Register, Population Register, Cause of Death Register and Hospital Discharge Register. Non-successful outcomes were divided into three groups: death, unsatisfactory outcomes and non-defined outcomes. Logistic regression analyses were used to identify risk factors for non-successful outcomes. RESULTS: Treatment outcomes were notified for 98.6% of study cases (n = 1396/1416). Treatment success rate was 75%. The main reason for non-successful outcome was death (16%), whereas outcomes failed and lost to follow-up were rare (1% together). In a multivariable model, risk factors for death as outcome were increasing age, male gender and Charlson comorbidity index ≥1, for unsatisfactory outcomes non-MDR drug resistance and TB registered in the first study period, and for non-defined outcomes non-MDR drug resistance. Among 50 cases with unsatisfactory outcomes, we observed false outcome allocations in eight (16%), and > 2% of the cases transferred to another country or disappeared before or during treatment. CONCLUSIONS: With a high proportion of older population among tuberculosis cases, death is a common treatment outcome in Finland. Comorbidity is an important factor to be incorporated when interpreting and comparing outcome rates. There was a considerable inconsistency in outcome allocation in the monitoring system, which implies that there is need to review the guidelines and provide further training for outcome assessment.

Recurrent tuberculosis in Finland 1995-2013: a clinical and epidemiological cohort study.

BACKGROUND: We investigated the epidemiology and prevalence of potential risk factors of tuberculosis (TB) recurrence in a population-based registry cohort of 8084 TB cases between 1995 and 2013. METHODS: An episode of recurrent TB was defined as a case re-registered in the National Infectious Disease Register at least 360 days from the date of the initial registration. A regression model was used to estimate risk factors for recurrence in the national cohort. To describe the presence of known risk factors for recurrence, patient records of the recurrent cases were reviewed for TB diagnosis confirmation, potential factors affecting the risk of recurrence, the treatment regimens given and the outcomes of the TB episodes preceding the recurrence. RESULTS: TB registry data included 84 patients, for whom more than 1 TB episode had been registered. After a careful clinical review, 50 recurrent TB cases (0.6%) were identified. The overall incidence of recurrence was 113 cases per 100,000 person-years over a median follow up of 6.1 years. For the first 2 years, the incidence of recurrence was over 200/100000. In multivariate analysis of the national cohort, younger age remained an independent risk factor at all time points, and male gender and pulmonary TB at 18 years of follow-up. Among the 50 recurrent cases, 35 patients (70%) had received adequate treatment for the first episode; in 12 cases (24%) the treating physician and in two cases (4%) the patient had discontinued treatment prematurely. In one case (2%) the treatment outcome could not be assessed. CONCLUSIONS: In Finland, the rate of recurrent TB was low despite no systematic directly observed therapy. The first 2 years after a TB episode had the highest risk for recurrence. Among the recurrent cases, the observed premature discontinuation of treatment in the first episode in nearly one fourth of the recurrent cases calls for improved training of the physicians.

Multidrug-resistant tuberculosis in Finland: treatment outcome and the role of whole-genome sequencing.

Treatment of multidrug-resistant tuberculosis (MDR-TB) is a global challenge requiring long treatment with costly drugs. We assessed treatment combinations, outcome and the utility of whole-genome sequencing (WGS) in MDR-TB cases. Clinical, demographic and microbiological data were obtained of all patients with MDR-TB who started treatment in Finland in 2007-2016. Definitions of MDR, pre-extensively drug-resistant (pre-XDR) and XDR tuberculosis were those applicable at the study period. Treatment outcome was defined according to World Health Organization (WHO) guidelines. Mycobacterium tuberculosis isolates were analysed by WGS in addition to routinely performed phenotypic drug susceptibility testing and genotyping. Among the 47 cases, 35 (74%) had a successful treatment outcome. Risk factors for non-successful outcome were Finnish origin and XDR. Almost 90% of our cases had an adverse event for at least one drug. Phenotypic and WGS drug resistance results were fully concordant for isoniazid, fluoroquinolones and amikacin, and >90% concordant for rifampicin, pyrazinamide, kanamycin and capreomycin. >60% of phenotypically ethambutol-susceptible isolates were genotypically resistant. The results of the rifampicin and isoniazid nucleic acid amplification tests (NAATs) performed for the isolates were identical to the WGS results except for three isolates having uncommon resistance mutations not included in the NAATs. WGS did not reveal unexpected clustering. More training is needed for physicians treating MDR-TB, and especially XDR-TB, to improve treatment outcome. Phenotypic drug susceptibility testing was shown to be unreliable for ethambutol. WGS could aid in the selection of optimal treatment regimen in the future.