One of the greatest public health challenges worldwide, malaria continues to have a profound impact on sub-Saharan Africa, where it accounts for the greatest burden of disease, particularly among young children. Estimates from 2014 indicate that malaria caused over 200 million infections that year, with children under the age of five being the most severely affected group. Child-focused antimalarial medicines are part of a broad strategy to control the spread of the disease and reduce mortality among the youngest and most vulnerable patients. In this article, we review activity in the arena of R&D of child-focused antimalarial medicines, describe recent successes, and challenges, and provide insight into the future of this vital medical research.
The Importance of Child-Focused Antimalarial Medications
Children are the primary victims of severe malaria, thanks to their underdeveloped immune systems. Malaria in a child can rapidly progress to cerebral malaria, which can lead to death or permanent neurological damage. Therefore, safe, effective antimalarial medicines suited for children are important because they:
- Lowering Mortality and Morbidity: Clinically effective treatments dramatically lower the risk of complications and death from malaria.
- Compliance: Children need formulations that are palatable and easy to administer to achieve compliance with their treatment.
- Adaptation to pharmacokinetics is crucial because children process medications differently than adults. Therefore, healthcare providers must prescribe and dose drugs appropriately to ensure they are safe and effective for young patients.
Advancements in Child-Focused Antimalarial Medications
Fixed-dose combinations (FDCs) of antimalarial drugs, like artemisinin-based combination therapies (ACTs), now come in pediatric formulations such as dispersible tablets. These formulations reduce the number of pills children need to take and enhance treatment efficacy. For example, the combination of artesunate and amodiaquine has been adapted into a dispersible tablet format specifically for children.
- Dispersible tablets: To overcome the issue of palatability and also ease of administration, dispersible tablets were developed. These tablets would dissolve within a few seconds when added to water for young children to take. Thus, children would be able to take their drugs without any difficulty and in a more consistent manner.
- Extended-Release Formulations New extended-release formulations are emerging that aim to extend the duration of activity while requiring fewer doses, which can improve adherence to treatment and help us fight malaria more effectively in resource-limited settings.
- Novel Drug Candidates: This leads to additional children’s drug candidates being discovered or developed, like new single-dose candidates for children and those with fewer side effects, such as newer drugs for malaria.
Current Research and Development Efforts
- Artemisinin-Based Combination Therapies (ACTs): ACTs are the mainstay of malaria therapy and are the focus of important ongoing research for improved pediatric formulations – those that are easier to administer, more efficacious, and with fewer side effects. Pediatric formulations of ACTs, such as artemether-lumefantrine (AL), are one such recent success.
- Next Generation Antimalarial Agents: New antimalarial agents that should enable a better balance between efficacy and safety in children are currently under clinical development. For example, combinations of compounds including pyronaridine-artesunate, tafenoquine, and others are promising candidates for the treatment of pediatric malaria.
- Vaccine development: Vaccines themselves are not ‘medication’, but they are essential for the prevention of malaria. The RTS, S/AS01 malaria vaccine, which was promising in clinical trials, is undergoing further scrutiny as to its ability to prevent malaria in children. Continued research on new vaccine candidates is an important area of study.
- Combination therapies can enhance the efficacy of antimalarial agents by incorporating various medications. This approach may involve combining different antimalarials that target distinct pathways or using an antimalarial alongside new agents when their mechanisms of action are still being clarified. At present, we are trying to identify optimal treatments for children that will prove efficacious and less likely to develop resistance in the field. We are also investigating strategies to combine existing drugs with new agents or to tweak dosing regimens to enhance efficacy.
Challenges in Developing Child-Focused Antimalarial Medications
- Dosage and Formulation: Children require specific dosing regimens (ie, tablets crushed into tiny pieces) based on age and weight. Developing forms efficacious and safe for all age groups is a challenge. When you are developing a drug that requires children to take 10mg and children range in weight from 5-20 kg, it is essential to consider the dosing.
- Safety and Efficacy: Clinical trials to determine the safety and efficacy of a planned new drug must include children as a portion of the participants, so the drug is not only safe but appropriate for children.
- Regulatory and Approval Challenges: Regulatory pathways to approve new drugs in pediatric populations are complicated and take time. While treatment drugs must meet the standards set by the FDA or EMA, it can take time to do so.
- Access and Affordability: Simply developing new child-focused medicines will not be sufficient if we cannot also ensure that they are affordable and accessible to populations in need. This, too, is a question of partnership – both with international health organizations, governments, and the private sector.
- Resistance and efficacy: Malaria parasites are becoming increasingly resistant to drugs. Regular monitoring of drug efficacy and mapping of resistance is essential to gather the necessary data for adjusting drug use or designing new medications that can overcome resistance.
Future Directions
- Enhanced Collaboration: By building on the successes of US and NIH-sponsored initiatives, a collaboration between various government, nongovernmental, pharmaceutical, and academic research bodies will continue to improve child-friendly efforts on antimalarial R D. Partnerships help bring more assets to bear in the global fight against malaria, such as additional resources and knowledge of the local context. These partnerships can facilitate the development of new treatments.
- Increased funding: we urgently need to spend on research and development to target pediatric malaria treatments Increased funding and investment in clinical trials, formulation development, access, and research initiatives are crucial to developing the diagnostics and drugs that children urgently need.
- Community Engagement: Introducing new treatments and policies is more likely to succeed if you can consult with communities to find out what they’ll support – and why not. Involving communities in decision-making during the development process would likely also help to overcome structural issues that can make medications and settings inaccessible.
- Make it global: Support from global health initiatives and organizations, such as the World Health Organization (WHO) and the Global Fund, can provide essential infrastructure and resources to ensure that new treatments are widely available and effectively reach the children who need them most.
Research and development of child-friendly antimalarial medications is also crucial for treating children, especially those under five years of age. Improvements in drug formulations, fixed-dose combinations, and new agents could help to combat the parasites. However, overcoming challenges with dosing, safety, field trials, infrastructure, and access will also be necessary. A concerted approach among research funders, drug companies, regulatory agencies, and communities could lay the groundwork for a world without malaria in children.
