Abstract:
Background. In high-resource settings, the survival of children with immunocompromise (IC) 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 tuberculosis (TB) in Europe.
Methods. Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group,
capturing TB cases <18 years diagnosed 2000–2020.
Results. A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn
errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P = .013). Patients with IC had an
increased likelihood of presenting with severe disease (57.6% vs 38.5%; P < .001; odds ratio [95% confidence interval], 2.073
[1.37–3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P < .001) and
QuantiFERON-TB Gold assay (30.0% vs 7.3%; P < .001) results at diagnosis. Overall, the microbiological confirmation rate was
similar in IC and non-IC cases (58.3% vs 49.3%; P = .083). Although the mortality in children with IC was <1%, the rate of
long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P = .004).
Conclusions. Children with IC and TB in Europe have increased rates of nonrespiratory 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 patients with IC, and determining the reasons for the increased risk of long-term
sequelae, with the aim to design preventive management strategies.
