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Master Thesis

Drug-resistant tuberculosis in Île-de-France children under eighteen years of age : descriptive observational retrospective study in Île-de-France over a period of five years

Abstract : Background. Paediatric drug-resistant tuberculosis (DR-TB) is a neglected concern and evidence-based guidance regarding management and outcome is lacking. Microbiologically-confirmed diagnosis is hard and a large proportion of pediatric cases is thus diagnosed on anamnestic and clinical criteria. Furthermore, litterature offers limited assessment of the second-line anti-tuberculosis drugs safety in children. Methods. In a retrospective descriptive cohort study conducted in Paris and île de France hospitals, we analysed demographic, clinical, microbiological and radiological features, management and outcome in children treated for drug-resistant tuberculosis (DR-TB). All patients under 18 years of age with a confirmed or probable diagnosis were included from 1 january 2011 to 31december 2015, with a follow-up documented until 31 June 2017. Data were collected through folder review and CNR-MyrMA microbiological database. For each patient, the related DR-TB index case, if existed, was reported. Standardised definitions were used for diagnosis, adverse reactions and outcome. Results. The 24 children with DR-TB included had a median age of 10,7 years old (interquartile range IQR, 3.4-14.2 years) with a sex ratio 1/1; 3 (12.5%) had tuberculosis history, 17 (70.9%) declared BCG vaccinated, none had HIV infection. Twelve patients (50.0%) were symptomatic but most of cases (62.5%) were diagnosed by systematic contact tracing. Of 16 drug-resistant strains, 8 (50.0% of strains – 10 children of 24, 41.6%) were imported from countries with an increasing incidence of DR-TB. A confirmed diagnosis was made in 13 children (54.2%) and 11 (45.8%) had probable diagnosis;15 children (62.5%) had multidrug-resistant (MDR) strain, 8 (33.3%) monoresistant(mDR)-to-isoniazid strains and 1 a pre-extensively drug-resistant (pre-XDR) strain. The median delay from microbiological diagnosis to onset of appropriate DR-TB treatment was 78.0 days (IQR 40.5-119.5) for all cases ; Eleven source cases were found and reported. Ten children (41.7%) were treated with an injectable drug and the total treatment duration was a median of 12.0 months (IQR 9.3-16.0) with 18.6 months for the pre-XDR case, 13.3 months (IQR 12.0-18.0) for MDR cases and 8.1 months (IQR 6.0-9.3) for mDR cases. Twelve children (50.0%) were cured, 11(45.8%) probably cured. Five (20.8%) were lost to follow-up. No death was reported. Conclusion. A confirmed diagnosis of DR-TB is not possible in all cases but should not impede the treatment of DR-TB in children. Systematic screening around source case and contact-cases follow-up is crucial for DR-TB management in paediatric cases. More than 90% of children with DR-TB can be successfully treated. However, pharmacokinetic studies are missing for the understanding of child's metabolism and the adaptation of treatment’s doses.
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Annabelle Brunelin-Bourassi. Drug-resistant tuberculosis in Île-de-France children under eighteen years of age : descriptive observational retrospective study in Île-de-France over a period of five years. Pediatrics. 2017. ⟨dumas-01721804⟩

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