Breakthroughs Blog: Malaria

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. A new study published in The Lancet Infectious Diseases ahead of World Malaria Day last week found that adding a low dose of the widely available antimalarial drug primaquine to artemisinin-based combination therapy is safe and effective at blocking Plasmodium falciparum malaria transmission in young children in areas of low- and moderate-to-high transmission. The new study fills a gap in knowledge of the safety and efficacy of this approach for young children, who face the highest burden of clinical malaria and are particularly at risk of artemisinin-resistant strains but could face adverse complications from adult formulations of primaquine. The findings highlight the need for child-friendly formulations of primaquine and support the expanded use of the drug in regions with a moderate-to-high transmission rate and the threat of artemisinin partial resistance.The Drugs for Neglected Diseases initiative, the National Health Service University Hospitals of Liverpool Group, and the University of Liverpool have initiated a clinical trial in Liverpool, United Kingdom to test an oral drug for visceral leishmaniasis, one of the world’s deadliest parasitic diseases. Current treatments for visceral leishmaniasis, which is almost always fatal if left untreated, include daily injections for up to 17 days, which can cause immediate pain, as well as nausea, vomiting, and more serious complications. The new oral drug, DNDI-6899, is easier to store, transport, and administer than current treatments. If proven successful, the drug could help make treatment more accessible to those who need it most.DioSynVax and ACM BioLabs have signed a new deal to jointly develop a next-generation avian flu vaccine with the potential for mucosal vaccine delivery, as the virus continues its worrying spread. The mRNA vaccine targets all major clades of the H5 avian flu subtype and could be scaled for rapid distribution globally in the case of a pandemic. The vaccine is also designed to be delivered via nasal spray, which could help increase uptake; to induce mucosal immunity, which helps fight the pathogen before it starts circulating the body; and to be temperature stable, enabling rollout in lower-resource settings.

In 2001, I traveled to Ghana as a graduate student working on a US Agency for International Development-funded decentralization program. I arrived armed with materials on local governance best practices. But the mayors I met were focused on urgent public health issues: clean water, HIV/AIDS, tuberculosis, and malaria. That trip, meant to be an early lesson in governance, became my first and most personal education in global health. It also nearly killed me. I was taking mefloquine weekly to prevent malaria. Toward the end of our stay, my partner and I set off to explore the country. Somewhere along the way, I developed what I believed to be giardia. That infection likely compromised the absorption of the mefloquine and left me dangerously vulnerable. One night in the village of Kokrobite, I woke with a high fever and chills so intense I could barely stand. A local man saw me and immediately recognized it as malaria. He arranged for a taxi to take me back to Accra. Before I left, he handed me a small, crumpled packet labeled in Chinese characters. Inside was a blister pack of pills. The only word written in English on the package was artesunate. He told me it would help, and, in that moment, sick, scared, and weak, I took it. At the hospital, a blood smear confirmed that I had cerebral malaria caused by Plasmodium falciparum, the deadliest strain. Cerebral malaria can cause brain swelling, coma, and death. I drifted in and out of consciousness for days. At one point, hospital staff told my partner that there was nothing more they could do. I should “go home” and be “as comfortable as possible.”My partner worked relentlessly to get me on one of the next flights back to the United States. I was so sick that the airline nearly refused to let me board. Once we arrived home, I was seen right away by an infectious disease doctor at Johns Hopkins Hospital. After reviewing my labs and the herbal remedy package, he said plainly: this saved your life. The artesunate had bought me enough time to survive the journey and begin treatment. At the time, the World Health Organization had not yet formally endorsed artemisinin-based combination therapies (ACTs) as the global standard for P. falciparum malaria. That came in 2006. But the effectiveness of artesunate alone was already well known in many parts of the world. That medicine saved my life.I missed several weeks of school but made a full recovery. Without that drug and the help of my partner (now my husband) and friends in Accra, I wouldn’t be here today. More than two decades have passed, and we've made tremendous progress. Insecticide-treated bed nets, rapid diagnostic tests, and ACTs have saved millions of lives. Two malaria vaccines, RTS,S and R21/Matrix-M, have been approved. Long-acting monoclonal antibodies are showing promise as seasonal protection for children. Newer insecticide-treated nets help counter resistance. And researchers are exploring RNA-based therapeutics and single-dose cures.Many of these breakthroughs are being developed by members of the Global Health Technologies Coalition, where I now serve as Executive Director. These tools represent our best chance not just to control malaria but to end it.But progress is not guaranteed. Cuts to foreign assistance and global health research and development are already slowing the progress of innovations in the pipeline. Some promising tools may be delayed or abandoned. That means more children at risk, more untreated infections, and more drug-resistant strains emerging. The parasite has evolved before. It will do so again if we let it. And malaria is no longer a disease that happens mostly outside of the United States. In the past two years, locally acquired cases have been reported in Florida, Texas, and Maryland. Climate change, global travel, and changing mosquito habitats are making malaria a threat we can no longer treat as distant. I know how thin the line is between surviving this disease and not. For me, it’s not abstract. It’s the memory of a fevered body, the generosity of strangers, and a medicine in the right place at the right time. This World Malaria Day, I urge leaders and policymakers to stay the course. The science is moving forward. But science alone isn’t enough. If we don’t finish what we’ve started, we risk letting malaria surge back and take more lives with it. Science has given us the tools. The question now is whether we will act in time or let the disease outpace us once again. 

The World Health Organization’s (WHO’s) prequalification (PQ) program plays a critical role in certifying the quality, safety, and efficacy of medical products to expand access to health technologies in low- and middle-income countries (LMICs). In our PQ Pulse interview series, GHTC speaks with stakeholders involved in the PQ process about persistent challenges within this evolving regulatory ecosystem and potential reforms to promote equitable access to innovative medical products.  Our first guest is Pierre Hugo, Vice President of Market Dynamics and Global Supply Security at the Medicines for Malaria Venture (MMV), a nonprofit product development partnership working to advance accessible medicines to treat, prevent, and eliminate malaria. MMV works end-to-end along the research and development pipeline, developing novel products, engaging with regional regulatory bodies, and supporting local manufacturers.In our interview, which has been lightly edited and condensed below, Pierre discusses MMV’s experience navigating WHO PQ and his hopes for the future of the R&D ecosystem.Can you tell us about MMV and the unique role and perspective it brings to product development?We fill the gap and, by and large, are a risk mitigation tool as one of the product development partnerships, or PDPs, within the malaria space to discover, develop, and deliver malaria products. Regarding access, our key ethos is that no drug is a medicine until it's in the hands of the patient. It's all very good and well developing drugs, but if they aren't developed correctly or affordably for the target population and ultimately made available, it's a dead-end game. So, we try to ensure that in the last mile, or the death-mile, drugs are getting to the patients. WHO PQ and organizations like MMV play a very important role.Broadly speaking, how would you describe MMV's experience with engaging in the WHO PQ process?  We’ve got a number of products that are now WHO prequalified, working with our pharmaceutical partners. We see the whole PQ process as a critical mechanism to ensure that quality standards are adhered to and, ultimately, to make quality-assured products available in LMICs, where maybe those regulatory pathways are a little bit less mature. I think what's great to see is that the landscape is changing, with a lot more countries achieving WHO maturity-level 3 status [Editor note: a WHO designation for countries with stable, well-functioning regulatory systems]. Yes, there have been challenges. WHO has been very collaborative, the team has been engaging, and we are grateful for the support that WHO PQ provides.Looking forward, it's going to be critical to see how WHO PQ needs to evolve and change to further strengthen and work more closely with countries’ regulatory mechanisms or pathways.How do you see the regulatory landscape evolving in the coming years, including the potential role of the African Medicines Agency (AMA) and other regional bodies?  The AMA I think is the future; it's critical that it is a success. There's a fair amount of, I wouldn't say pessimism but [questions about] how long it will take for them to be up and running, simply because they just have so many different countries and regional regulatory systems.By and large, the East African collaborative registration or collaborative processes [The Eastern African collaborative registration process is a regional initiative that aims to facilitate the registration of medicines and medical products through a collaborative process, including joint assessments and mutual recognition of regulatory decisions] have been working to some success. There are other regional harmonization networks, but it takes time, and there is still a lot of work that is needed.How do you view recent reforms made to the PQ program? Overall, we are encouraged to see efforts that enable the fast-tracking of innovative product introduction. The new WHO framework for novel products [a reform implemented in 2024 to initiate parallel, rather than sequential, processes for recommending the use of novel products and evaluating them through PQ] is just entering its pilot phase. The new web portal [an online PQ application platform that will provide real-time information for applicants, regulators, and other stakeholders on the status of products in review] will give us greater transparency. The Coordinated Scientific Advice [a new procedure that allows product developers to engage with WHO early on to better understand the evidence that they will need to generate to support PQ review and generation of policy recommendations] should ensure that later review of the finished product is as streamlined as possible.There also needs to be some thought on how AMA will work with the European Medicines Agency, the US Food and Drug Administration, and WHO PQ to avoid complexity for local manufacturers.  If you had a hypothetical magic wand to wave to influence the program, what changes would you make?Something that is critical is to have clarity on timelines and the interaction between PQ and national regulatory bodies and lessons learned. Ultimately, what is the incentive for a manufacturer to go that extra mile to ensure that a product is quality approved [through PQ]? That's where the funders play a critical role in endorsing and supporting the process. Without that support, if you speak to a lot of the manufacturers, they say, “Well, there's no way I'll be going through the WHO PQ process. It's a major investment, and it's an additional long-term commitment that you need to make as a manufacturer.” So, ensuring that there is coordination between normative bodies, funders, procurement partners, and regulators is critical to ensure fast uptake of innovative products.The dream is to have a lot more quality-approved manufacturers in Africa, where over 95 percent of the patient population is. If you look at our new products coming down the line, like single-dose cures or long-acting injectables, greater upfront alignment is key, between WHO PQ and these stringent regulatory authorities, to offer clearer guidance in terms of what those regulatory expectations are for new products. We need to ensure that global procurement agencies, like the Global Fund to Fight AIDS, Tuberculosis and Malaria, the President’s Malaria Initiative, or UNICEF, are working as closely as possible with AMA and with WHO PQ to ensure the rapid uptake of new qualified drugs.I would love to see harmonization between PQ and national regulatory authorities to fast-track important innovation and ensure that new quality-assured drugs get to market faster.Putting on your advocacy hat, where do we, as an advocacy community, need to put our energy in the next couple of years to make some of those improvements become reality?  To unleash the potential [of PQ], we need to simplify the processes for manufacturers, ensure procurement commitments for a clear return on investment, and provide continuous and sustained funding to support manufacturers to embark on the lengthy quality assurance process. If I look at the manufacturers, we did an extensive exercise with the Africa Centres for Disease Control and Prevention to identify manufacturers throughout the whole continent that would want to take malaria products forward to be WHO PQ’d. We only had about 50 manufacturers that were interested in taking part in this initiative [out of 400], so that's a very low number. I mean, we're talking small molecules, not vaccines, and you've got to ask yourself why? They obviously don't see a need to have products WHO PQ’d, which is, on the one hand, a problem. The Africa Centres for Disease Control and Prevention and MMV and other partners believe that the African manufacturing sector can take its place long term alongside manufacturers from India and China, who today supply the vast majority of public health medicines for malaria on the continent.Big Pharma, if anything, is disinvesting in Africa. So, having those in-Africa partners is critical within the malaria space and, obviously, not just for malaria, but for HIV and tuberculosis and so forth.So, I'm just thinking that if manufacturers are going down the WHO PQ route, it might be a really nice carrot to say, “Look, if you are applying for the WHO PQ process, this is a financial incentive in place.” That could be a really nice carrot to keep the Big Pharma guys in the game.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. A research team at the Children's Hospital of Philadelphia has discovered a key process that could provide new insight into designing more effective antimalarial drugs, as rising antimicrobial resistance complicates the ongoing global fight against malaria by rendering current drugs less effective. One promising strategy to combat poor absorption or retention of drugs in the body is the use of prodrugs that can offer a more targeted attack. However, these prodrugs need to be activated, typically by an enzyme. By identifying the primary enzyme that activates multiple antimalarial drugs, these new findings could enable the development of prodrugs for malaria, which, by design, would also be less likely to lead to the emergence of drug resistance.New research shows that wastewater sampling, including in sewer systems and on airplanes, could predict new viral and bacterial outbreaks and the emergence of new variants of pathogens weeks or even months before they become widespread, in addition to being less invasive, more efficient, and faster than current methods. A new study from the US Centers for Disease Control and Prevention demonstrates how it was able to use wastewater sampling to detect the presence of avian flu in 2022 weeks before the virus was detected in poultry and then wild bird populations. Widespread and regular wastewater sampling would enable public health authorities to better surveil population and community health and, on a more micro level, help health care providers provide more accurate diagnoses and care for patients.  Last week, the Pediatric Praziquantel Consortium announced the first administration of its new pediatric schistosomiasis treatment to a preschool-aged child in Uganda, marking a critical step toward closing the long-standing treatment gap for young children for this parasitic disease, which affects millions of children in sub-Saharan Africa. The innovative therapy, designed specifically for children between three months and six years, is also child-friendly, palatable, and heat-stable, making it especially well-suited for this population and region. The rollout is part of a program aimed at integrating the treatment into health care systems and preparing for its broader rollout across the region, starting with Côte d’Ivoire, Kenya, Tanzania, and Senegal.