Pediatric multi-drug-resistant tuberculosis in Germany – diagnostic and therapeutic challenges of an “orphan disease”

Delay in diagnosing multidrug-resistant tuberculosis (MDR-pTB) in children prolongs time to effective treatment. Data on risk factors for pediatric MDR from low-incidence countries are scarce. Retrospective nationwide case–control study to analyze MDR-pTB cases in Germany between 2010 and 2020 in comparison to a drug-susceptible (DS)-pTB group. We included 52 MDR cases (24 tuberculosis (TB), 28 TB infection (TBI); mean age 7.3 years) and 56 DS cases (31 TB, 26 TBI; mean age 7.9 years). Groups were similar for sex, household size, and migration background. Compared to the DS group, more children with MDR were born in the Commonwealth of Independent States (CIS) (22% MDR-pTB vs. 13% DS-pTB, n.s.) and had more MDR index cases (94% MDR-pTB, 5% DS-pTB, p < 0.001). The interval between first healthcare contact and initiation of effective therapy was significantly longer in MDR-pTB (47 days) than in DS-pTB (11 days, p < 0.001), correlating with disease progression. Treatment for MDR-pTB was successful in 74%, but 22% experienced long-term adverse effects (e.g., hepatopathy, hearing loss). Conclusions: Close contact to MDR cases or birth in MDR-TB-high-incidence countries are risk factors for MDR-pTB. Early identification of potential MDR index cases by contact investigation, and susceptibility testing in children from high-burden MDR-TB countries are essential for timely diagnosis and treatment, reducing the severity of disease and treatment side effects. Trial Registration: Deutsches Register Klinischer Studien (https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023817), DRKS00023817, 2020–09-08.