Tuberculosis disease in immunocompromised children and adolescents: a pTBnet multi-centre case-control study.

BACKGROUND: In high-resource settings the survival of immunocompromised (IC) children has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools and outcome of IC children with TB in Europe. METHODS: Multicentre, matched case-control study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), capturing TB cases <18 years diagnosed 2000-2020. RESULTS: 417 TB cases were included, comprising 139 children with IC (HIV, inborn errors of immunity, drug-induced immunosuppression and other immunocompromising conditions) and 278 non-IC children as controls. Non-respiratory TB was more frequent among cases than controls (32.4% vs. 21.2%; p = 0.013). IC patients had an increased likelihood of presenting with severe disease (57.6% vs. 38.5%; p < 0.001; OR [95% CI]: 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs. 6.0%; p < 0.001) and QuantiFERON-TB Gold assay (30.0% vs. 7.3%; p < 0.001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs. 49.3%; p = 0.083). Although the mortality in IC children was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs. 6.1%; p = 0.004). CONCLUSIONS: IC children with TB disease in Europe have increased rates of non-respiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in IC patients, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.

Evaluation of the latent tuberculosis screening and treatment strategy for asylum seekers in Stockholm, Sweden 2015-2018: a record linkage study of the care cascade.

INTRODUCTION: About 90% of active tuberculosis (TB) cases in Sweden are foreign born and are mainly due to latent TB infection (LTBI) reactivation. The aim of this study was to assess the current migrant LTBI screening programme with regards to test results and completion of the care cascade. METHOD: A retrospective cohort of all 14173 individuals attending a health examination was established for the Stockholm Region 2015-2018 through record-linkage of data extracted from the Swedish Migration Authority and medical records. Screening results, referrals to specialist care and treatment initiation were ascertained through automated data extraction for the entire cohort. Detailed cascade steps, including treatment completion, were analysed through manual data extraction for a subsample of all persons referred to specialist care in the period 2016-2017. RESULTS: Of 5470 patients screened with an interferon-gamma release assay (IGRA), 1364 (25%) were positive, of whom 358 (26%) initiated LTBI treatment. An increased trend in IGRA-positivity was seen for increased age and TB-incidence in country of origin. Among the IGRA positive patients, 604 (44%) were referred to specialist care. Lower age was the main referral predictor. In the subsample of 443 patients referred to specialist care in 2016-2017, 386 (87%) were invited, of whom 366 (95%) attended. Of 251 patients (69%) recommended for LTBI treatment, 244 (97%) started such treatment and of those 221 (91%) completed it. CONCLUSION: The low attrition in patient-dependent cascade steps shows that the voluntary approach works well. Low LTBI treatment attainment is due to the current conservative local treatment policy, which means the vast majority are IGRA-tested without an intention to treat for LTBI.

Diagnostic pathways and delay among tuberculosis patients in Stockholm, Sweden: a retrospective observational study.

BACKGROUND: Asylum seekers in Sweden are offered tuberculosis (TB) screening at a voluntary post-arrival health examination. The role of this screening in improving the TB diagnostic pathway has not been previously evaluated. The aim of this study was to determine diagnostic pathways for active TB cases and compare diagnostic delays between different pathways. METHODS: Retrospective review of medical records of patients reported with active TB in Stockholm in 2015, using a structured and pre-coded form. RESULTS: Seventy-one percent of patients actively sought health care due to symptoms. As for source of referral to TB specialist clinic, 15% came from screening of eligible migrants, of whom the majority were asymptomatic. Among asylum seekers, 69% were identified through screening at a health examination (HE). The main sources of referral to TB clinics were emergency departments (27%) and primary health care centers (20%). Median health care provider delay was significantly longer in patients identified through migrant screening in health examination. CONCLUSIONS: Screening at a health examination was the main pathway of active TB detection among mainly asymptomatic and non-contagious asylum seekers but contributed modestly to total overall TB case detection. In these patients TB was diagnosed early in a non-contagious phase of the disease. Further research is required to assess the effectiveness and cost-effectiveness of HE TB screening as well as inclusion of other groups of migrants from high incidence countries in the screening program in terms of impact on delay, transmission and treatment outcomes.

Elevated transaminases are common in children on prophylactic treatment for tuberculosis.

AIM: The aim of this study was to assess the prevalence of elevated transaminase levels in children undergoing prophylactic treatment for tuberculosis (TB) infection. METHODS: All children living in a geographically defined area, who started TB prophylaxis during 2009-2011, were included. Data on background factors, treatment regimes and transaminase levels at baseline and follow-up were collected retrospectively. RESULTS: Of the 277 children who were treated, 113 (41%) had elevated transaminase levels. Of these, 97 (35%) had levels that were less than three times the upper limit of the normal range and 16 (6%) had levels that were more than three times the normal range. Four patients had to discontinue isoniazid treatment and were successfully switched to rifampicin. In 17 patients, the highest transaminase peak did not occur until after 6 months of treatment. Elevated transaminases were significantly more common in patients below 9 years of age (62%) than in those aged 10-18 years (28%). Transaminases were elevated in 44% of all boys and 36% of all girls (p = 0.17). CONCLUSION: Transaminase elevation was common in children receiving prophylactic treatment for TB and started at different points throughout the treatment period. Younger patients faced an increased risk. Regular blood tests are recommended throughout treatment.

Pediatric tuberculosis in Stockholm: a mirror to the world.

BACKGROUND: Increasing international migration has changed the epidemiology of tuberculosis (TB) in Europe. Little is published on clinical manifestations and epidemiology in children in this new era. METHODS: Clinical and laboratory data on all children with TB in Stockholm between 2000 and 2009 were entered into a database and retrospectively completed with information from case records. Population data, including parents' country of birth, were obtained from Statistics Sweden. RESULTS: TB was diagnosed in 147 children <18 years of age (78 confirmed, 12 probable, 57 possible). Fifty-six children (38%) presented clinically, and 91 were identified by screening procedures. Ninety children (61%) were born in high-endemic countries and 38 in Sweden to parents from such countries. The incidence was 451/100,000 person years among children born in Somalia, 44 among those born in other high-endemic countries, and 13 among Swedish-born children with parents from high-endemic countries. All but 1 of the 19 Swedish-born children with Swedish parents belonged to a single outbreak. Median age was 12 years. Severe, adult-type TB was predominantly observed in adolescents, whereas young children presented mild, primary disease that was diagnosed at the time of screening. The 78 positive cultures were traced back to 67 strains. Resistance to any first-line drug was present in 25% of the strains, of which 4 were multidrug resistant. CONCLUSIONS: Active TB in Stockholm is common in children born in high-endemic countries, especially Somalia. The most severe cases are seen in adolescents. The high prevalence of antimicrobial resistance is a cause for concern.