Diagnosis and Management of Multidrug-Resistant Tuberculosis in Children: A Practical Approach
- 195 Downloads
Approximately 25,000 children develop multidrug-resistant (MDR) tuberculosis (TB) each year, but few of them are diagnosed and appropriately treated for MDR-TB. New diagnostic tools have improved our ability to diagnose children with bacteriologically confirmed TB earlier. However, the majority of childhood TB cases are not bacteriologically confirmed; therefore a high index of suspicion is needed, and taking a detailed history of contact with drug-resistant source cases and previous TB treatment is important to identify presumed MDR-TB cases. Treatment for MDR-TB is rapidly changing with the addition of new and repurposed drugs, the introduction of shorter regimens and the move towards injectable-free, all-oral MDR-TB treatment regimens. Children have been neglected in the introduction of the new drugs, but drug dosing and safety studies are now being completed. This article presents a practical approach in deciding which regimen to use in individual children in need of MDR-TB treatment. Outcomes in those treated are generally good, but only <5% of children with MDR-TB are currently diagnosed and appropriately treated. Diagnosing children with MDR-TB and getting them on to correct treatment regimens should now be our main focus.
KeywordsTuberculosis Multidrug-resistant Children. Diagnosis Management
The author acknowledges the help of Dr. Anthony J. Garcia–Prats for critically reviewing the manuscript.
Compliance with Ethical Standards
Conflict of Interest
HS Schaaf is co-investigator on a dose-finding and safety trial of Delamanid in children for which Stellenbosch University receives a per patient grant from Otsuka.
Source of Funding
HS Schaaf received financial support from the National Research Foundation (South Africa) for his research.
- 1.World Health Organization, Geneva, Switzerland. Global Tuberculosis Report 2017. Available at: http://apps.who.int/iris/bitstream/10665/259366/1/9789241565516-eng.pdf?ua=1. Accessed 5 October 2018.
- 20.World Health Organization, Geneva, Switzerland. WHO treatment guidelines for drug-resistant tuberculosis 2016 update WHO/HTM/TB/201604 Available at: http://apps.who.int/iris/bitstream/handle/10665/250125/9789241549639-eng.pdf?sequence=1. Accessed 11 June 2018.
- 22.World Health Organization. Rapid communication: key changes to treatment of multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). WHO/CDS/TB/2018.18.Available at: www.who.int/tb/publications/2018/rapid_communications_MDR/en/. Accessed 1 Oct 2018.
- 25.Garcia-Prats AJ, Rose PC, Draper HR, et al. Effect of co-administration of lidocaine on the pain and pharmacokinetics of intramuscular amikacin in children with multidrug-resistant tuberculosis: a randomized crossover trial. Pediatr Infect Dis J. Published ahead of print, 14 Mar 2018. https://doi.org/10.1097/INF.0000000000001983 PMID: 29561515.
- 26.DR-TB STAT. Phase III Clinical trial results at the 48th union world conference on lung health: implications for the field.Available at: https://www.ghdonline.org/uploads/Updated_November_12_2017_STAT_phaseIII_Union_summary.pdf.Accessed 6 Oct 2018.
- 28.Statement on injectable-free regimens for children under the age of 12 years with rifampicin-resistant Tuberculosis. Available at: http://sentinel-project.org/wp-content/uploads/2018/07/Recommendations-for-Injectible-Free-Regimens-in-Children-with-Rif-Resistant-TB.pdf. Accessed 4 Oct 2018.
- 29.Seddon JA, Thee S, Jacobs K, Ebrahim A, Hesseling AC, Schaaf HS. Hearing loss in children treated for multidrug-resistant tuberculosis. J Inf Secur. 2013;66:320–9.Google Scholar
- 30.Zhao Y, Fox T, Manning K, et al. Improved treatment outcomes with bedaquiline when substituted for second-line injectable agents in multidrug-resistant tuberculosis: a retrospective cohort study. Clin Infect Dis. 2018 Aug 24. https://doi.org/10.1093/cid/ciy727.
- 34.Osman M, Harausz EP, Garcia-Prats AJ, et al. For the collaborative Group for Meta-Analysis of Paediatric individual patient data in MDR-TB. Encouraging treatment outcomes among children with extensively drug-resistant tuberculosis: a global systematic review and individual patient meta-analysis. Emerg Infect Dis. 2018; in press.Google Scholar
- 36.Harausz EP, Garcia-Prats AJ, Law S, et al. Collaborative Group for Meta-Analysis of Paediatric individual patient data in MDR-TB. Treatment and outcomes in children with multidrug-resistant tuberculosis: a systematic review and individual patient data meta-analysis. PLoS Med. 2018;15:e1002591.CrossRefPubMedPubMedCentralGoogle Scholar