Antibiotics may help prevent drug-resistant TB in children

A clinical trial shows that the oral antibiotic levofloxacin reduced the risk of developing drug-resistance tuberculosis (TB) by 56% in children.

New findings from a study led by researchers at Imperial and Stellenbosch University show that giving antibiotics as a precaution to children at high risk of developing drug-resistant TB can help to reduce the incidence of TB disease.

The findings are reported in the New England Journal of Medicine.

Professor James Seddon, Professor of Global Child Health in the Department of Infectious Disease, said: “Multidrug-resistant (MDR) TB, remains challenging to treat, and children have always been the most neglected of all patient groups, with access to newer medicines lagging behind adults.

"In finding a new way to keep children safe when MDR-TB afflicts a family member, we help the whole family recover that much faster from the trauma that the disease inflicts, from a health perspective, and also from economic and mental health perspectives." Dr James Seddon Department of Infectious Disease

“In finding a new way to keep children safe when MDR-TB afflicts a family member, we help the whole family recover that much faster from the trauma that the disease inflicts, from a health perspective, and also from economic and mental health perspectives.”

The trial, called TB-CHAMP, was conducted in South Africa, which has a high burden of TB and MDR-TB. The research focused on children under 5 years of age because young children exposed to TB have a high risk of progressing to TB disease and developing severe symptoms.

TB remains one of the top causes of death in children globally and is a one of the top killers of children below 5 years of age. Fewer than 20% of children with MDR-TB are currently diagnosed and treated, making them one of the most neglected populations affected by TB.

Many of these children with MDR-TB have been in close contact with someone with the disease. Identifying these ‘high risk’ children and the rest of their households, screening them for TB and offering them preventive treatment will be critical to find more cases and to prevent MDR-TB.

In the trial 922 children who had previously been exposed to an adult with MDR-TB in their household were randomised to levofloxacin or placebo. Only five (1.1%) of the 453 who were given levofloxacin developed MDR-TB compared to 12 (2.6%) out of 469 in the group which didn’t receive the drug. The drug (or placebo) was taken every day for six months. While the results showed a decrease in risk of TB for those given levofloxacin, the researchers concluded that the difference between children who received the treatment and those who did not, was not statistically significant.

The researchers found that over these six months there were few side effects from the medicine. While joint pain and tendonitis is a concern, they were very uncommon in the children who had taken the medication, with only one child developing tendonitis.

“There have been major advances around treating MDR-TB disease more effectively and safely in adults and in children, in recent years. However, there has been no rigorous evidence from clinical trials on how to prevent drug-resistant TB,” said Professor Anneke Hesseling, the Principal Investigator of the TB-CHAMP trial at Stellenbosch University.

Findings from Vietnam

A similar study conducted in Vietnam, the VQUIN trial, focusing on adults and adolescents, had similar findings and is also reported in the NEJM this week. In collaboration, investigators from the TB-CHAMP and V-QUIN trials combined data from the two trials and the result of this combined analysis demonstrate a significant effect of levofloxacin in reducing the risk of TB in household contacts of individuals with MDR-TB. This combined analysis is reported in NEJM Evidence this week. The results from these two trials were considered by the World Health Organization and have informed new global guidelines on MDR-TB prevention.

Trinh Duong, TB-CHAMP trial statistician, from MRC Clinical Trials Unit at UCL. “By carefully planning this work in advance, we have been able to present these important findings alongside the main results of the two trials, with even greater impact on global guidelines and policy.”

The TB-CHAMP trial was funded by Unitaid, under the BENEFIT Kids project at Stellenbosch University. The trial was also funded by the South African Medical Research Council and the UKRI Medical Research Council with support from the Department of Health and Social Care (DHSC), the Foreign, Commonwealth & Development Office (FCDO), the Global Challenges Research Fund, the Medical Research Council and Wellcome.