Pediatric and adolescent tuberculosis in Latvia, 2011-2014 : Case detection, diagnosis and treatment

Publisher Copyright: © 2017 The Union.Objective: To perform a comprehensive analysis of case detection, diagnosis and treatment of tuberculosis (TB) in children and adolescents in Latvia, and to evaluate the utility of the current approach. Design : A retrospective study of all Latvian children and adolescents diagnosed with TB from 1 January 2011 to 31 December 2014. Results : Of 3081 patients diagnosed with TB during 2011-2014, 250 (8%) were aged ,18 years, and 80% were identified through contact investigation. Pulmonary TB was diagnosed in 77% of the patients. TB was confirmed bacteriologically in 21% of patients; chest Xray (CXR) was consistent with TB in 42% of study participants, while 58% of cases were diagnosed with subclinical TB using low-dose computed tomography (CT) after being missed by CXR. Patients with visible abnormalities on CXR had a higher rate of bacteriological confirmation and were more often clinically symptomatic, which indicates active disease. Early diagnosis had a treatment success rate of 100% for drug-resistant and 99% for drug-susceptible TB. conclusion : TB case detection through contact investigation provided early diagnosis and excellent treatment outcomes in children and adolescents in Latvia. CT was able to identify pathology consistent with subclinical TB in children with a history of exposure.publishersversionPeer reviewe

Multi- and extensively drug-resistant tuberculosis in Latvia : Trends, characteristics and treatment outcomes

Publisher Copyright: © 2014, The Union.Setting: Drug-resistant tuberculosis (TB) is an important public health problem in Latvia. Objective: To document trends, characteristics and treatment outcomes of registered patients with multidrug- resistant (MDR-) and extensively drug-resistant (XDR-) TB in Latvia from 2000 to 2010. Design: A retrospective national cohort study. Results: Of 1779 patients, 1646 (92%) had MDR- and 133 (8%) XDR-TB. Over 11 years, the proportion of XDR-TB among MDR-TB patients increased from 2% to 18%. Compared to MDR-TB patients, those with XDR-TB were significantly more likely to have failed MDR-TB treatment (OR 8.4, 95%CI 4.3–16.2), have human immunodeficiency virus infection (OR 3.2, 95%CI 1.8–5.7), be illegal drug users (OR 5.7, 95%CI 2.6–11.6) or have had contact with MDR-TB patients (OR 1.9, 95%CI 1.3– 2.8). Cure rates for XDR-TB were 50%. Compared with MDR-TB patients, those with XDR-TB had a higher risk of treatment failure (29% vs. 8%, respectively, P < 0.001). Unfavourable treatment outcomes were significantly associated with being male; having smear-positive disease; pulmonary cavities; failure, default or relapse after previous MDR-TB treatment; and a history of incarceration. Conclusion: More MDR-TB in Latvia is now also XDR-TB. This study identified several risk factors for XDR-TB and, for unfavourable treatment outcomes, highlighting the importance of early diagnosis and appropriate management of MDR-/XDR-TB.publishersversionPeer reviewe

Mycobacterium tuberculosis acquires limited genetic diversity in prolonged infections, reactivations and transmissions involving multiple hosts

Publisher Copyright: © 2018 Herranz, Pole, Ozere, Chiner-Oms, Martínez-Lirola, Pérez-García, Gijón, Serrano, Romero, Cuevas, Comas, Bouza, Pérez-Lago and García-de-Viedma.Background: Mycobacterium tuberculosis (MTB) has limited ability to acquire variability. Analysis of its microevolution might help us to evaluate the pathways followed to acquire greater infective success. Whole-genome sequencing (WGS) in the analysis of the transmission of MTB has elucidated the magnitude of variability in MTB. Analysis of transmission currently depends on the identification of clusters, according to the threshold of variability (<5 SNPs) between isolates. Objective: We evaluated whether the acquisition of variability in MTB, was more frequent in situations which could favor it, namely intrapatient, prolonged infections or reactivations and interpatient transmissions involving multiple sequential hosts. Methods: We used WGS to analyze the accumulation of variability in sequential isolates from prolonged infections or translations from latency to reactivation. We then measured microevolution in transmission clusters with prolonged transmission time, high number of involved cases, simultaneous involvement of latency and active transmission. Results: Intrapatient and interpatient acquisition of variability was limited, within the ranges expected according to the thresholds of variability proposed, even though bursts of variability were observed. Conclusions: The thresholds of variability proposed for MTB seem to be valid in most circumstances, including those theoretically favoring acquisition of variability. Our data point to multifactorial modulation of microevolution, although further studies are necessary to elucidate the factors underlying this modulation.publishersversionPeer reviewe

Treatment outcomes in global systematic review and patient meta-analysis of children with extensively drug-resistant tuberculosis

Extensively drug-resistant tuberculosis (XDR TB) has extremely poor treatment outcomes in adults. Limited data are available for children. We report on clinical manifestations, treatment, and outcomes for 37 children (<15 years of age) with bacteriologically confirmed XDR TB in 11 countries. These patients were managed during 1999–2013. For the 37 children, median age was 11 years, 32 (87%) had pulmonary TB, and 29 had a recorded HIV status; 7 (24%) were infected with HIV. Median treatment duration was 7.0 months for the intensive phase and 12.2 months for the continuation phase. Thirty (81%) children had favorable treatment outcomes. Four (11%) died, 1 (3%) failed treatment, and 2 (5%) did not complete treatment. We found a high proportion of favorable treatment outcomes among children, with mortality rates markedly lower than for adults. Regimens and duration of treatment varied considerably. Evaluation of new regimens in children is required

Encouraging treatment outcomes among children with extensively drug-resistant tuberculosis: a global systematic review and individual patient meta-analysis

Extensively drug-resistant (XDR) tuberculosis (TB) has extremely poor treatment outcomes in adults and very limited pediatric data are available. We report on the presentation, treatment and outcome of children (<15 years) with bacteriologically confirmed XDR-TB, from 11 countries managed between 1999 and 2013. Among the 37 children, the median age was 11 years, 32 (87%) children had pulmonary TB and 29 had a recorded HIV status with seven (24%) HIV-infected. Treatment duration was 7.0 months for the intensive, and 12.2 months for the continuation phase. Thirty (81%) children had favorable treatment outcomes. Four (11%) died, one (3%) failed treatment and 2 (5%) were lost to follow-up during treatment. We demonstrate a high proportion of favorable treatment outcomes with mortality markedly lower than in adults. Regimens and the duration of treatment varied considerably. Evaluation of new regimens in children is required

Tuberculosis disease in children and adolescents on therapy with antitumor necrosis factor - A agents: A collaborative, multicenter paediatric tuberculosis network European Trials Group (ptbnet) Study

Background. In adults, anti–tumor necrosis factor-α (TNF-α) therapy is associated with progression of latent tuberculosis (TB) infection (LTBI) to TB disease, but pediatric data are limited. Methods. Retrospective multicenter study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti–TNF-α therapy. Results. Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified: Crohn’s disease (n = 8; 42%) and juvenile idiopathic arthritis (n = 6; 32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-γ release assay) was performed in 15 patients before commencing anti–TNF-α therapy but only identified 1 LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti–TNF-α therapy and TB diagnosis was 13.1 (IQR, 7.1–20.3) months. All cases presented with severe disease, predominantly miliary TB (n = 14; 78%). One case was diagnosed postmortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR, 46–66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae. Conclusions. LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti–TNF-α therapy are prone to severe TB disease and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low-TB-prevalence settings