Multidrug-resistant tuberculosis in children and adolescents: current strategies for prevention and treatment

ABSTRACT

Introduction

An estimated 30,000 children develop multidrug-resistant (MDR) tuberculosis (TB) each year, with only a small proportion diagnosed and treated. This field has historically been neglected due to the perception that children with MDR-TB are challenging to diagnose and treat. Diagnostic and therapeutic developments in adults have improved pediatric management, yet further pediatric-specific research and wider implementation of evidence-based practices are required.

Areas covered

This review combines the most recent data with expert opinion to highlight best practice in the evaluation, diagnosis, treatment, and support of children and adolescents with MDR-TB disease. A literature search of PubMed was carried out on topics related to MDR-TB in children. This review provides practical advice on MDR-TB prevention and gives updates on new regimens and novel treatments. The review also addresses host-directed therapy, comorbid conditions, special populations, psychosocial support, and post-TB morbidity, as well as identifying outstanding research questions.

Expert opinion

Increased availability of molecular diagnostics has the potential to aid with the diagnosis of MDR-TB in children. Shorter MDR-TB disease treatment regimens have made therapy safer and shorter and further developments with novel agents and repurposed drugs should lead to additional improvements. The evidence base for MDR-TB preventive therapy is increasing.

KEYWORDS:

• Tuberculosis
• children
• pediatric
• prevention
• treatment
• resistant
• multidrug-resistant

Article highlights

• Emerging rapid molecular diagnostic tests, including whole genome sequencing, have the potential to make a difference to the diagnosis of MDR-TB in children, but are currently rarely available in high MDR-TB burden settings

• Treatment for MDR-TB disease in children is changing rapidly and all-oral regimens, which incorporate novel and repurposed drugs, have led to shorter and safer treatment

• The principles of treatment for MDR-TB-HIV co-infected children are largely the same as for children without HIV infection. However, HIV remains a major risk factor for poor outcomes in children with MDR-TB

• Malnutrition and diabetes should also be considered as significant co-morbidities, both of which have been shown to increase the risk of developing MDR-TB and both have a negative impact on treatment outcomes

• Adolescents commonly present with severe disease and are more likely to contribute to transmission than young children, yet research in this age group has to date been neglected

• Migrant and refugee children and adolescents with MDR-TB are likely to present specific challenges to health systems and should be considered in health programming and in research

• MDR-TB has substantial long-term impact on psychosocial, neurological, and respiratory health in children and adolescents, yet to date little research has been conducted

• The evidence base for MDR-TB preventive therapy is increasing and prevention trials, evaluating both levofloxacin and delamanid as single-drug regimens, are underway

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

JA Seddon is supported by a Clinician Scientist Fellowship jointly funded by the UK Medical Research Council (MRC) and the UK Department or International Development (DFID) under the MRC/DFID Concordat agreement (MR/R007942/1). M van der Zalm was supported by a career development grant from the EDCTP2 program supported by the European Union (grant number 99726 TB-Lung FACT TMA 2015 CDF – 1012).