Groundbreaking progress has been made in the fight against multidrug-resistant tuberculosis (MDR-TB) in children, with the presentation of findings from four pivotal studies by the Unitaid-funded BENEFIT Kids project. These studies, led by the Desmond Tutu TB Centre at Stellenbosch University, South Africa, address crucial evidence gaps and aim to overcome barriers to accessing optimal MDR-TB treatment for children.
The studies seek to pave the way for the production of more child-friendly and palatable medicines and formulations, thereby enhancing their uptake, acceptability, and overall outcomes among children. This initiative is particularly significant considering the stark disparity between the progress in adult MDR-TB treatment and the considerably less advanced treatment options available for children.
Anthony Garcia-Prats, the overall Project Principal Investigator from the University of Wisconsin-Madison and Stellenbosch University, emphasized the dire situation of children with MDR-TB, a group that has been largely neglected in the battle against this disease. He highlighted the arduous and prolonged treatment journey historically endured by these children and their caregivers. Nevertheless, he expressed optimism that with the right partnerships and investment in innovative research and development, it is not only feasible but imperative to provide children with MDR-TB treatment that is both effective and well-tolerated.
One of the key studies, conducted at Stellenbosch University in collaboration with partners at the University of California San Francisco, pooled data from five previously published studies involving over 240 children receiving levofloxacin. This innovative approach has led to the identification of optimal levofloxacin doses, which can significantly inform paediatric treatment guidelines.
The PERFORM trial, part of the project’s endeavors, compared a new paediatric dispersible tablet formulation of levofloxacin with the current crushed levofloxacin adult tablets. It assessed the acceptability of the two medicine forms among children and delved into the pharmacokinetics of the drug, taking into consideration the different ways in which children’s bodies process medicines compared to adults.
Remarkably, the PERFORM trial revealed that the paediatric formulation was more favored by both children and their caregivers, while also demonstrating excellent drug concentrations in young children. The study, carried out in Cape Town, South Africa, solidifies the significance of levofloxacin, used for both the prevention and treatment of MDR-TB in children.
Adding to these findings are the results of the phase 3 TB-CHAMP trial, which showcased the effectiveness and safety of levofloxacin in preventing MDR-TB in children who had been exposed to adults with MDR-TB. Furthermore, data from the TB-CHAMP trial was presented at the Union Conference.
The CATALYST trial, an international multi-country study conducted in India and the Philippines, as well as South Africa, delved into the pharmacokinetics, safety, tolerability, and acceptability of new child-friendly formulations of clofazimine and moxifloxacin, crucial drugs in treating MDR-TB. This study not only provided insights into the best medication doses for children using these new formulations but also underscored the ease of administration by caregivers and shed light on the costs of MDR-TB treatment regimens across the three countries.
The ChilPref study, another significant exploration led by researchers from Stellenbosch University and the TB Alliance, evaluated the preferred tastes of formulations of two essential drugs, moxifloxacin and linezolid, used in MDR-TB treatment, directly involving the children in the process. This innovative research, conducted in South Africa, emphasised the crucial role of taste in administering medicines to children and led to guidance for the production of more acceptable formulations, ultimately improving treatment outcomes and protecting the well-being of entire families.
Anneke Hesseling, Project co-PI and Director of the Desmond Tutu TB Centre, stressed the need for pharmaceutical companies to not only focus on the safety and effectiveness of medicines meant for children but also ensure that the formulations taste good and are easy to administer. Only then can children access the most acceptable medications and treatments, a critical factor in the battle against a serious disease like MDR-TB.
The groundbreaking work of the BENEFIT Kids project, underwritten by Unitaid, has brought together a global consortium of partners to address crucial evidence gaps and expedite access to improved MDR-TB treatments for children worldwide. By generating essential evidence on dosing, safety, effectiveness, acceptability, and cost, this initiative aims to inform WHO policy recommendations and bridge the gaps in child-friendly formulations, ultimately enhancing access to better MDR-TB treatment and prevention for children and their families.
In conclusion, the strides made through these studies and initiatives have the potential to revolutionize the landscape of MDR-TB treatment for children, making it more effective, tolerable, and targeted, ultimately saving the lives of countless young individuals from this debilitating disease.
