Children With Extensively Drug-Resistant TB Achieve Better Treatment Outcomes Than Adults

Although 30% of adults with XDR TB are successfully cured or complete treatment, a new study has found that children have far more favorable outcomes and lower mortality rates.

Extensively drug-resistant tuberculosis (XDR TB) infections are notoriously difficult to treat in adults, but a new study has found that there is a higher proportion of favorable treatment outcomes among children.

TB is the world’s deadliest infectious disease, killing an estimated 4500 people each day worldwide, according to the World Health Organization (WHO). Antimicrobial resistance is a pernicious problem in the TB epidemic, and about 6.2% of all multidrug-resistant TB (MDR TB) cases are XDR TB, and have resistance to at least 4 of the core anti-TB drugs. These drug-resistant TB cases take substantially longer to treat than ordinary TB and only 30% of adults patients show cure or treatment completion, but a new study published in the journal Emerging Infectious Diseases suggests that children have a higher proportion of favorable treatment outcomes for XDR TB compared to adults.

The new study was led by investigators at Stellenbosch University in Cape Town, South Africa, and details a meta-analysis of 37 children under the age of 15 years who were treated for bacteriologically-confirmed XDR TB from 1999 to 2013. The study builds on limited data on XDR TB treatment outcomes in children and in an interview with Contagion®, study author Muhammad Osman, MBChB, PGDipHM, MSc(Epi), explained why there has been such little research on the topic. “Adult TB is more infectious and drives transmission, warranting a bigger public health response,” said Dr. Osman. “Because of this, pediatric TB has not received the priority adult TB has and this is applicable to XDR TB as well.”

The median age of the 37 children in the study was 11 years, and 32 had pulmonary TB. Additionally, 29 participants had a recorded HIV status and 7 individuals were infected with HIV. The median duration of treatment was 7.0 months for the intensive phase and 12.2 months for the continuation phase. Investigators found that 30 (81%) children had favorable treatment outcomes, 4 (11%) died, 1 (3%) had treatment failure, and 2 (5%) did not complete treatment.

“Despite the limitations in the period we saw better outcomes than adults,” said Dr. Osman. “We saw how limited availability of drugs required the use of many toxic medications for the management of XDR TB and we emphasized the need for newer medications in children.”

Dr. Osman notes that in recent years the emergence of new drugs for the management of XDR TB—including bedaquiline, delamanid, linezolid, and repurposed drugs such as clofazimine—has changed the landscape of XDR TB treatment. In addition, there’s been a move away from the use of injectable agents.

“In recent years we have also seen an increase in pharmacokinetic studies in children improving our understanding of the pediatric doses required and to be used. We have also seen the development of pediatric formulations. Ongoing and future studies need to consider the drugs, doses, combinations, and periods of use especially in pediatrics,” said Dr. Osman.

“There is now an increased awareness of XDR TB and there has been a progressive increase in countries reporting XDR TB, but we do think this still remains under diagnosed,” explained Dr. Osman, noting that while TB diagnostics are somewhat more easily available today than they were 20 years ago when the study period began, this still requires children being sampled and the diagnosis of XDR TB still has many delays. “We have also noted an increased willingness to make the clinical diagnosis of XDR TB and children are now being reported with clinical XDR TB in many regions of the world.”