ArticlesTreatment outcomes for children with multidrug-resistant tuberculosis: a systematic review and meta-analysis
Introduction
An estimated 12 million people worldwide have tuberculosis, of whom about 650 000 have multidrug-resistant (MDR) disease.1 Childhood tuberculosis is estimated to account for 10–15% of the global tuberculosis burden,2 and probably accounts for a similar proportion when considering only drug-resistant disease. The highest rates of paediatric MDR tuberculosis are reported in low-income countries,2 and in some regions the incidence of MDR tuberculosis has risen sharply in the past two decades—eg, in the Western Cape, South Africa, the proportion of culture-confirmed cases of tuberculosis with multidrug-resistance has tripled in the past 15 years from 2·3% to 7·3%.3
MDR tuberculosis is underdetected in children. Diagnosis of drug resistance needs mycobacterial culture and drug susceptibility testing (DST),4 but the difficulty in obtaining respiratory secretions, such as sputum or gastric aspirates, or specimens of extrapulmonary tuberculosis from young children,5 along with the fact that up to half of all children with a clinical diagnosis of tuberculosis disease are smear-negative and culture-negative, makes microbiological confirmation challenging.6 Strict programmatic requirements for microbiological confirmation of drug resistance combined with insufficient recognition of the importance of taking into account DST patterns from adult source cases can lead to substantial delays in diagnosis and initiation of appropriate treatment.7 These delays could lead to progression of disease, increased risk of infectiousness of children, greater risk of disease complications such as tuberculous meningitis, and higher rates of morbidity and mortality.8, 9
Paediatric drug-resistant tuberculosis is a neglected concern, with few children being treated relative to the estimated disease burden.10 WHO guidelines for the treatment of drug-resistant tuberculosis in adults are based on evidence from meta-analyses of individual patients' data.11 However, recommendations for children are based on expert opinion, drawing on data from case series and cohort studies,12, 13 often with small sample sizes. Consequently, variation exists in programmatic choices of treatment regimens, with the choice of drugs informed by previous drug exposure and DST results.14 Because of uncertainties about diagnosis and the best treatment regimens, and concerns about the toxic effects associated with MDR tuberculosis treatment, health-care providers are cautious about treating paediatric MDR tuberculosis.
We did a systematic review and meta-analysis of the available evidence for treatment outcomes in children with MDR tuberculosis, and assessed the characteristics of patients and studies that could have affected treatment success.
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Search strategy and selection criteria
We searched for publications in PubMed, Ovid, Embase, Cochrane Library, PsychINFO, and BioMedCentral databases up to Oct 31, 2011. We developed a highly sensitive search strategy, using a combination of the search terms “tuberculosis”, “multidrug resistance”, “multidrug-resistant”, “treatment outcomes”, and “children”, both as exploded MESH headings and free-text terms. We reviewed the bibliographies of all retrieved articles. We also searched all electronically available conference abstracts
Results
The eight studies included in our analysis (figure 1) came from individual treatment programmes from five countries (Peru,20 Spain,21 the USA,22, 23 South Africa,7, 24, 25 and Latvia26) and reported on treatment outcomes for a range of eight patients21 to 111 patients.24 One study was a conference abstract;26 the rest were published as full text articles.
Studies were done in a range of settings, including countries with high7, 21, 24, 25 and low17, 22, 23, 26 MDR tuberculosis burdens. The
Discussion
Our systematic review suggests that MDR tuberculosis can be successfully treated in children, with the overall proportion of children achieving treatment success as good as, if not better than, that reported for adults receiving individualised treatment regimens (64%).15 Mortality and defaulting seemed to be lower for children than for adults, but these differences were not statistically significant.
Detailed data for adverse events were absent from some studies, and adverse events were not
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2020, International Journal of Infectious DiseasesCitation Excerpt :The pooled treatment success (cured plus completed) is 81.7% (Ettehad et al. 2012). A systematic review and meta-analysis reported by Isaakidis et.al (Isaakidis et al. 2015) is also indicated high treatment success (83.4%) and death (11.4%) but, lower lost to follow up (3.9%) proportions in comparison with the findings of previous review (Ettehad et al. 2012). Moreover, a recently published review study that pooled data on 975 children is indicated 78% of children treated successfully (Harausz et al. 2018).
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2023, European Journal of Pediatrics
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