Curing TB in children: more complicated than just drug adherence

Prior to the Covid-19 pandemic, tuberculosis (TB) was the leading cause of death worldwide via a single infectious disease, states The Lancet. Even though a first-line treatment regimen exists, with over 90% efficacy in controlled settings, 10 million people were diagnosed with TB in 2018. Over 1 million cases occurred in children younger than 15 years of age.

In April, the Lancet published an illuminating study from Tanzania showing how malnutrition and gut infections can impact negatively on TB treatments for children. The researchers analysed the causes of pharmacokinetic variability - that is, the difference between patients in the absorption, distribution, elimination and metabolism of a drug - among a paediatric population suffering from TB.

87% malnourished

Children younger than age 15 years were included if they had confirmed or probable TB and had just started, within 72 hours, first-line TB treatment. Of the children enrolled in the study, 87% had moderate or severe malnutrition.

Previous studies have shown an association between malnutrition and lower drug concentration. Enteropathogen frequency - i.e. ongoing damage or irritation and swelling of the small intestine - is associated with childhood malnutrition. Enterpathogen burden, which is defined as the sum of distinct enteropathogens detected in the stool, has not, however, been previously investigated in children treated for TB. Special tests were run to detect 37 bacterial, viral and parasitic species or species groups in stool samples.

Gut pathogens of vital importance

The study found that Tanzanian children undergoing TB treatment rarely attained target drug concentrations. Enteropathogen burden was common and associated with a significant reduction in the concentration of certain antimycobacterial drugs.

Furthermore, the findings showed that enteropathogens are an “important and overlooked aspect of clinical care in children with tuberculosis”. The study has practical implications in that doctors might be able to target the relevant gut pathogens to improve TB treatment outcomes.

Meeting nutritional needs

The Lancet study proposes further research, including conducting research in larger and more diverse paediatric settings in TB endemic regions, and assessing whether treating enteropathogens improves drug treatment.

In essence, this important study shows that malnutrition is underestimated as a contributor to TB. “Blame for failure of tuberculosis treatment historically was placed on the patient and a lack of adherence to medicines,” says Scott Heysell, MD, MPH, Researcher, UVA's Division of Infectious Diseases and International Health. “Instead, the other germs in the gut of children from impoverished areas are leading to suboptimal levels of key medicines even if taken as directed. Some of the same pathogens in the gut that lead to malnutrition and predispose to malnutrition-related tuberculosis make tuberculosis even harder to treat.”

It appears that it’s not sufficient merely to give people drugs to fight TB, without ensuring their nutritional needs have been adequately met, and that gut infections, among children, are properly controlled.

The Lancet Infectious Diseases paper was authored by Pranay Sinha, Knut Lönnroth, Anurag Bhargava, Scott K. Heysell, Sonali Sarkar, Padmini Salgame, William Rudgard, Delia Boccia, Daniel Van Aartsen and Natasha S Hochberg.