By Joyce Ojanji

With the treatment of multidrug-resistant tuberculosis (MDR-TB) in children still lagging dramatically behind recent advances for those in adults, four key studies presented during the Union World Conference on Lung Health have addressed key evidence gaps that are barriers to access for optimal MDR-TB treatment.

The studies conducted under the Unitaid-funded BENEFIT Kids project led by the Desmond Tutu TB Centre, Stellenbosch University, South Africa inform efforts to produce more child-friendly, better-tasting medicines and formulations, to improve uptake, acceptability and outcomes among children.

The team at Stellenbosch University with partners at the University of California San Francisco pooled data from five previously published studies with more than 240 children receiving levofloxacin. This innovative approach has identified the optimal doses of levofloxacin that can inform pediatric treatment guidelines.

“Children with MDR-TB are a neglected population suffering from a largely neglected disease,” said Anthony Garcia-Prats, the overall Project Principal Investigator, University of Wisconsin-Madison and Stellenbosch University.

“It’s hard to overstate how long and harrowing the treatment journey for children with MDR-TB and their caregivers has been historically. This is not inevitable though. With the right partnerships and investment in innovative and high-priority research and development, it is possible to provide children with MDR-TB treatment that is not only effective but is also safe, well-tolerated, palatable and acceptable.”

This work complements the project’s PERFORM trial, in which researchers compared a new pediatric dispersible tablet formulation of levofloxacin to the current crushed levofloxacin adult tablets, looking at how acceptable the two medicines’ forms were among children. It also looked at the pharmacokinetics—how the children’s bodies interact with the drug, an important consideration given that children process medicines differently than adults.

PERFORM showed that the pediatric formulation was preferred by children and their caregivers and it achieved excellent drug concentrations in young children. The research was conducted in Cape Town, South Africa. Levofloxacin is used both for the prevention and treatment of MDR-TB in children.

In the CATALYST trial, researchers looked at the pharmacokinetics, safety, tolerability and acceptability of new child-friendly formulations of clofazimine and moxifloxacin, key drugs used in treating MDR-TB.

This international multi-country study was conducted in India with partners from B.J. Medical College and Johns Hopkins University, the Philippines with De La Salle Medical and Health Sciences Institute, and South Africa.

The study provided data on the best doses for these medicines in children using the new child-friendly formulations. CATLYST also showed that caregivers could administer these treatments more easily to children than existing adult formulations, and provided economic data showing the costs of MDR-TB treatment regimens across the three countries.

Also, In the ChilPref study, researchers from Stellenbosch University and the TB Alliance evaluated which tastes of formulations of two drugs that are currently critical for MDR-TB treatment, moxifloxacin and linezolid, were preferred by children. This innovative research, conducted in South Africa, asked children themselves to give input on how they think medicines should taste.

The study confirmed the importance of taste in administering medicines to children; the currently available formulation of moxifloxacin, for example, was rejected by most children. Manufacturers now have guidance on how to produce formulations of these important medicines for MDR-TB treatment that patients will accept—improving treatment outcomes and safeguarding the health of entire families.

“Children are not simply ‘little adults’; developing drug formulations for children poses a unique set of challenges and requires a concerted effort,” said Graeme Hoddinott, ChilPref study PI, Stellenbosch University.

“Despite improved access to child-friendly formulations in recent years, many caregivers still need to cut, break, crush and mix foul-tasting tablets that are made for adults and are not designed to disperse or dissolve. Children need child-friendly medicines.”

MDR-TB does not respond to isoniazid and rifampicin, the most important “first-line” medicines used in TB treatment. Every year, an estimated 30,000 children develop MDR-TB, globally, yet fewer than 20% are diagnosed and treated, resulting in substantial preventable morbidity and mortality. When looking at all forms of TB, more than 183,000 children die annually from the disease; more than 95% of these children were under the age of 5 and did not receive any treatment.