Breakthroughs Blog: Malaria

Last week, Cepheid announced that its Xpert Hemorrhagic Fever Panel test has received Emergency Use Listing from the World Health Organization, enabling the technology to be deployed to help identify suspected cases and support outbreak containment in the rapidly growing outbreak of Bundibugyo Ebola in the Democratic Republic of the Congo. The molecular panel test detects and identifies Ebola virus (multiple strains, including Bundibugyo), Crimean-Congo hemorrhagic fever, Marburg virus, and Lassa virus, providing results in around an hour. The test runs on Cepheid’s GeneXpert diagnostic technology system, which is already widely used across Africa, helping enable rapid implementation. Cepheid previously donated an initial shipment of tests cleared by the US Food and Drug Administration through the Department of War, and the new listing now enables further deployment. A Phase 2 clinical trial led by the Serum Institute of India found that an experimental monoclonal antibody for dengue virus was safe, well-tolerated, and provided evidence of efficacy in a Phase 2 clinical trial. Dengue affects more than 200 million people each year and is a growing global threat due to the expanding range of the virus-carrying mosquito species. There are several licensed vaccines for dengue but no licensed antiviral drugs. The experimental antibody previously neutralized all four serotypes of dengue virus in animal studies and demonstrated safety in a Phase 1 trial in healthy adults. Researchers at the National Institutes of Health (NIH) have discovered rare antibodies that could inform the development of a therapeutic or preventive intervention for alpha-gal syndrome, an emerging tick-bite-associated condition behind a growing number of cases in the United States and globally, which can lead to allergic reactions to a molecule in red meat and other animal products. The discovery was made through malaria research—the scientists were originally trying to find antibodies that could target alpha-gal (a sugar molecule) on malaria parasites as a potential strategy for malaria prevention. In laboratory tests, the rare antibodies successfully hindered human allergic antibodies from binding to red meat allergens. There are currently no specific treatments or preventions for alpha-gal syndrome.

Every year, World Mosquito Day brings renewed attention to mosquito-borne diseases like malaria. But attention is not enough. What matters now is whether we are using the tools we have effectively and whether those tools will still work tomorrow. Malaria drug resistance is not new. Until the early 2000s, chloroquine was the backbone of treatment. It was widely available and highly effective until resistance spread and treatments began to fail. Health systems were caught off guard, deaths rose, and the world learned a painful lesson: once resistance takes hold, recovery is slow, costly, and measured in lives lost. Today, we are seeing warning signs again. Resistance to existing first-line drugs is emerging in parts of East Africa, the Horn of Africa, Southeast Asia, and South America. At the same time, malaria deaths rose to 610,000 in 2024, up from 597,000 the year before, a trend unfolding against a backdrop of severe financing shortfalls. Global funding reached only $3.9 billion in 2024, less than half the $9.3 billion required. Sustained underinvestment has well-documented consequences: fewer preventive measures, overstretched health systems, and reduced capacity to respond when resistance emerges. The economic case for doing more is equally stark. According to a recently published analysis, reducing malaria cases by 90 percent by 2030 could increase Africa's GDP by $126 billion and expand global trade by $80.7 billion. Now urgency matters more than ever. We cannot afford to wait for existing tools to fail before acting. In the words of Dr. Brenda Akia, Africa representative and Vice Chair of the Committee on the United Nations Convention on the Elimination of All Forms of Discrimination against Women: "Malaria was killing people even when the drugs were working. Now that the drugs are failing, we are cooked if we do not act fast." Cooked, mingled and served as gourmet food at the banquet where the mosquitoes will gather to celebrate their victory over humanity. This is not an exaggeration. The impact of chloroquine resistance—the memories of the increasing death tolls, the desperation to save lives with a tool that was becoming blunt— still lingers on. The response must be twofold. We need sustained financial commitment to ensure countries can procure and deliver existing tools through their health systems, and we need investment in new tools to stay ahead of resistance. Both are essential, and neither is optional. On the innovation front, there is encouraging progress. New medicines are advancing through development to better protect those most at risk. Through the work of Medicines for Malaria Venture and its partners, triple combination therapies designed to preserve the effectiveness of existing drugs are in development. In addition, ganaplacide-lumefantrine, a novel combination therapy developed with Novartis, has completed a Phase 3 trial with positive results. Looking ahead, long-acting injectable medicines that could provide protection against malaria for up to six months are also in development. Beyond new medicines, innovations in vector control are further strengthening the fight against malaria. These include new spatial emanator repellents that can provide protection for up to 12 months and dual-insecticide nets designed to combat insecticide resistance. Together, these advances reinforce our belief that ending malaria within a generation is within reach.However, as Brazil's Minister of Health Alexandre Padilha said recently, "Innovations that are not in the hands of those who need them are no good." As was done for the COVID-19 response, we must accelerate regulatory processes for innovations. Mechanisms must be put in place to make these critical innovations affordable and accessible. The health workforce must also be trained to deploy them effectively, and civil society organizations and community groups must also lead the way in raising awareness of the threat posed by drug resistance and the need for new tools. Countries are already showing leadership. For example, Thailand is strengthening its national strategy with a focus on surveillance and resistance response. Kenya is deepening community engagement. Rwanda is investing in stronger data systems. Uganda is supporting local manufacturing. These are concrete actions, not intentions. Countries have the capacity, but they need sustained and predictable financing to deliver new tools effectively. This is the moment for malaria elimination. Progress will not be secured by innovation alone, nor by financing alone, but by aligning both with strong country delivery systems. We call on the entire global health ecosystem to unite under one final “Big Push.” It is time to turn hope into well-funded action and finally take us across the finish line to a malaria-free world.

Last week, the Serum Institute of India announced that it will manufacture a promising tuberculosis (TB) vaccine candidate in late-stage development under an agreement with the Gates Medical Research Institute (Gates MRI). The candidate, M72/AS01E, which is currently being evaluated in a late-stage clinical trial, was originally developed by GSK before being licensed to the Gates Foundation. It could become the first TB shot in more than 100 years if approved. The agreement aims to build up manufacturing capacity to ensure adequate supply of the vaccine for rapid, widespread scale-up in key communities, if it is eventually approved. The Gates MRI will transfer the technology and know-how to the Serum Institute, which will invest more than $100 million to scale up manufacturing capacity. A Phase 1 trial evaluating a potential fast-acting, single-dose malaria treatment found promising results, as the growing threat of resistance of the malaria parasite to first-line therapies has underscored the continuous need for new antimalarials. The trial, conducted by QIMR Berghofer in collaboration with UniSC Clinical Trials and sponsored by Medicines for Malaria Venture (MMV) and GSK, found that the novel drug MMV367/GSK3772701 rapidly killed malaria parasites and was generally well tolerated in infected volunteers, appearing to work by blocking two enzymes critical to the survival of the malaria parasite in red blood cells. The treatment candidate belongs to an entirely new class of antimalarials that work differently to existing treatments, making it less susceptible to resistance. It also has the potential to be administered as a single-dose therapy in the right combination with other anti-malaria compounds.A Phase 1 trial of a Bundibugyo ebolavirus vaccine candidate launched last week, making it the first vaccine candidate to enter clinical testing in the response to the ongoing outbreak in the Democratic Republic of Congo. The Coalition for Epidemic Preparedness Innovations (CEPI)-backed candidate was developed by University of Oxford scientists and uses the same viral vector platform as the Oxford/AstraZeneca COVID-19 vaccine. Since the early days of the outbreak, CEPI, the University of Oxford, and the Serum Institute have been working together to urgently advance the development of the investigational vaccine into clinical trials. The trial will be conducted in Oxford, United Kingdom among 50 healthy adults aged 18-55 years, evaluating the candidate’s safety and immune response. There are currently no approved vaccines or treatments for the virus. 

Last week, SC Johnson; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and the US Department of State announced a new agreement to accelerate access to an innovative malaria vector control tool in high-burden countries. This marks the second such partnership between the State Department, the Global Fund, and a US company to expand global access to new products under the department’s global health strategy, after one with Gilead for lenacapavir for HIV prevention. This initiative will scale up the SC Johnson Guardian™ spatial repellant tool, a small mesh fabric sealed inside a pouch that is hung indoors, releasing an active ingredient that repels mosquitoes for up to a year. The tool was recommended by the World Health Organization last year, the first new category of vector control products to be recommended in 25 years. The partners aim to reach 60 million people across ten-high burden countries with 30 million products over three years, with manufacturing based in Nairobi, Kenya. A new observational study found that even with only moderate levels of malaria vaccine coverage achieved, the initial introduction of the RTS,S/AS01 malaria vaccine in high-burden African countries has contributed to a significant reduction in deaths among children. Specifically, despite only moderate uptake of three doses and low uptake of the fourth, the vaccine was found to have saved the lives of one in eight eligible children in the first three African countries to offer the vaccine from 2019-2023, which represents a 13.2 percent reduction in death. These results add to the evidence supporting continued scale-up of RTS,S—one of two malaria vaccines now included in national immunization schedules in 25 sub-Saharan African countries—and underscore the promise of continued investment in developing new and improved malaria vaccines. Nonprofit Caring Cross has shared an early copy of data showing that, in a small study, a single infusion of engineered immune cells suppressed HIV long term in several patients, offering proof-of-concept for a single-shot functional cure. The approach, adapted from cancer research, involves extracting immune cells from participants living with HIV, engineering the cells to carry molecules that simultaneously kill infected cells and prevent the immune cells from becoming infected, and injecting them back into participants. HIV is notoriously hard to control because the virus persists in hard-to-eliminate latent reservoirs, requiring lifelong ongoing treatment to suppress the virus.  This research could pave the way for the development of a single, low-cost intervention that could sustain viral suppression without the need for regular therapy. The research, which is still in the very early stages, is scheduled to be presented at an upcoming scientific conference.