Nationwide analysis of treatment outcomes in children and adolescents routinely treated for tuberculosis in the Netherlands

Abstract

BackgroundAs a vulnerable population, children and adolescents with tuberculosis (TB) are faced with many challenges, even those who live in low TB incidence countries. We aimed to evaluate factors associated with TB treatment outcomes allowing more focused interventions to support this population once diagnosed.MethodsA retrospective cohort study using a nationwide surveillance database was performed in children and adolescents (aged 0–18 years) treated for TB in the Netherlands from 1993 to 2018. Logistic regression analyses were used to estimate adjusted odds ratios (aOR) for associated factors of mortality and loss to follow-up (LTFU).ResultsAmong 3253 eligible patients with known outcomes, 94.4% (95.9% children and 92.8% adolescents) were cured or completed treatment, 0.7% died during treatment and 4.9% were LTFU. There were no reported treatment failures. Risk factors of death included children aged 2–4 years (aOR 10.42), central nervous system TB (aOR 5.14), miliary TB (aOR 10.25), HIV co-infection (aOR 8.60), re-treated TB cases (aOR 10.12) and drug-induced liver injury (aOR 6.50). Active case-finding was a protective factor of death (aOR 0.13). Risk factors of LTFU were adolescents aged 15–18 years (aOR 1.91), illegal immigrants (aOR 4.28), urban domicile (aOR 1.59), unknown history of TB contact (aOR 1.99), drug-resistant TB (aOR 2.31), single adverse drug reaction (aOR 2.12), multiple adverse drug reactions (aOR 7.84) and treatment interruption >14 days (aOR 6.93). Treatment in recent years (aOR 0.94) and supervision by public health nurses (aOR 0.14) were protective factors of LTFU.ConclusionHighly successful treatment outcomes were demonstrated in children and adolescents routinely treated for TB. Special attention should be given to specific risk groups to improve treatment outcomes.

Pediatric tuberculosis in the metropolitan area of Rio de Janeiro

“…However, clinical experience makes us suppose that the score parameters were taken into consideration by physicians at the time of TB diagnosis in children, although not registered in the medical records. We observed a high treatment success rate in the overall sample (85%), lower than that described by European countries (88-100%) (Abubakar et al, 2008;Ziemele et al, 2017;Gafar et al, 2019), but higher than that reported from some African countries (around 77%) (Flick et al, 2016;Wobudeya et al, 2017). The mortality rate in this study (1%) is comparable to the case fatality rate described by Jenkins et al in countries with low HIV prevalence (0.9%) (Jenkins et al, 2017).…”

Towards elimination of childhood and adolescent tuberculosis in the Netherlands: an epidemiological time-series analysis of national surveillance data

“…After these improvements, we expect that the completeness of TB notification has increased over time. Although some EPTB cases such as abdominal TB, osteoarticular TB and urogenital TB could be life-threatening, these forms of EPTB were assumed to be less severe than CNS and miliary TB in our study because EPTB cases other than CNS and miliary TB were not associated with higher risk of mortality in our previous analysis [4]. In addition, this study is limited by its retrospective nature with partly incomplete records for some of the variables.…”

“…In low-and middle-income countries, ACF among household contacts of patients with TB is effective in enhancing TB case detection [41,42], and reducing all-cause mortality [41]. In the Netherlands, ACF interventions also benefit children and adolescents in improving TB treatment outcomes, particularly in reducing all-cause mortality [4]. However, it should be acknowledged that even in a setting where ACF is well implemented like the Netherlands, missed opportunities for prevention persist.…”

“…Towards elimination of childhood and adolescent tuberculosis in the Netherlands: an epidemiological time-series analysis of national surveillance data Introduction Tuberculosis (TB) remains a major global health challenge, with an estimated 1.1 million new cases and 205 000 deaths in children aged <15 years in 2018 [1]. The risk of death is highest in children aged <5 years and among those with HIV co-infection not receiving antiretroviral therapy [2][3][4][5]. While TB is considered treatable and curable, management of childhood TB faces significant challenges, due to the lack of sensitive diagnostic tools, the lack of adaptable treatment approaches for both TB infection and TB disease, and poor access to child-friendly drug formulations with proven efficacy and limited toxicity [6][7][8].…”

Pharmacokinetics and safety/tolerability of isoniazid, rifampicin and pyrazinamide in children and adolescents treated for tuberculous meningitis

“…Our findings on DILI in children with TBM warrant further investigation as DILI has clinical implications in increasing patient morbidity/mortality. 38 The risk of DILI with increased drug dosages requires consideration, but it should be balanced against the need to ensure optimal treatment of a life-threatening illness like TBM. 29 39 Combining therapeutic drug monitoring as a decisive tool for TB treatment, 40 and regular monitoring of LFTs, 19 might benefit to ensure drug efficacy without causing toxicity.…”