Breakthroughs Blog: Malaria

An international research team, led by scientists at the University of Maryland School of Medicine, shared the results of the Phase 1 trial of a novel vaccine designed to protect against typhoid fever and non-typhoidal Salmonella infections, reporting that the vaccine produced a strong immune response and was safe and well-tolerated in a small group of healthy US adults. These encouraging findings pave the way for the next step of evaluating the vaccine in children. A single vaccine that targets Typhoid fever and non-typhoid Salmonella, both leading causes of illness and death in children in Africa, could be a game-changer for pediatric health. The vaccine could also help protect people in the United States and other high-income countries, where some types of Salmonella are common causes of foodborne illness. Following the example of the US military, who often wear uniforms treated with insecticide to repel mosquitoes in malaria-endemic regions, a research team has tested a similar approach to try to protect young children, who face a significant burden of malaria in sub-Saharan Africa. While existing vector control tools, such as insecticide-treated bednets, only protect children while they’re sleeping, a large randomized controlled trial in Uganda tested the efficacy of insecticide-treated baby wraps, used in conjunction with bednets. The trial found that the baby wraps were highly effective at preventing malaria infections. The dramatic scale of the reduction of new infections also suggests that malaria-carrying mosquitoes were biting during the daytime more often than previously thought, which could help guide the development of new vector control tools and approaches. Last week, The Safety of Antimalarials in the FIRst trimEster (SAFIRE) consortium announced that it had enrolled its first patient in Mali, marking the official start of the first-ever Phase 3 adaptive platform trial evaluating the efficacy and safety of antimalarial drugs in the first trimester of pregnancy. The trial is a landmark achievement that could not only help fill the crucial gap of safe and effective options for pregnant women at risk of malaria, but it is also a step toward equity and inclusion for clinical research and drug development in general, which have long excluded pregnant women, fueling the gap in the first place. SAFIRE partners have shared that early formative research in the communities where the trial will take place was a crucial step in ensuring that the design and process were appropriate and acceptable to the communities. The study will continue to progress in Mali, Burkina Faso, and Kenya. 

A Phase 1 clinical trial testing an experimental monoclonal antibody for malaria found that the highest dose of the treatment studied was highly effective in preventing malaria. Researchers from the University of Maryland, Sanaria, the Vital Narrative consultancy, and the Gates Medical Research Institute tested the monoclonal antibody, MAM01, in 37 adults who had never been exposed to malaria, who received either a single dose of varying sizes or a placebo, and then were infected by the bites of infected mosquitoes. None of the three recipients who received the highest dose had malaria parasites in their blood after infection. The monoclonal antibody could prove to be an important treatment option that provides immediate, high-level, and long-lasting protection with just one doseA Japanese research team has isolated natural compounds from marine sponges that demonstrate an ability to kill parasites that cause leishmaniasis, which affects approximately 12 million people around the world. Current treatments are highly toxic, cause serious side effects, and can be prohibitively expensive, leaving patients, particularly in low-income communities, which face a disproportionate burden of leishmaniasis, unable to access or complete treatment. Drug resistance is also complicating leishmaniasis treatment efforts. These findings could guide research into new treatment approaches and could potentially also be applied to other protozoan diseases like Chagas disease and African sleeping sickness. A new CRISPR-based RNA test could help track the parasites that spread Human African trypanosomiasis, or sleeping sickness, which affects around 500 people per year and many more livestock animals. The test can identify parasite species living in an animal’s blood, helping public health workers carry out targeted treatment of infected animals and prevent transmission to humans. This One Health approach to zoonotic or parasitic diseases could also be rolled out to address other diseases, such as Chagas disease or leishmaniasis.  

This month marks 35 years since the World Summit for Children, the first time in history when a meeting of heads of state and government was held exclusively to address the well-being of children. At this landmark event in New York City, world leaders adopted a Declaration on the Survival, Protection, and Development of Children and a Plan of Action for its implementation, which made specific recommendations in a variety of areas, including child and maternal health and family planning. We’ve made significant progress in children’s health globally since then—the total number of deaths of children under five worldwide has declined from 12.8 million in 1990 to 4.8 million in 2023. The number of neonatal deaths (deaths in the first 28 days) has also dropped, although more slowly, from 5.2 million in 1990 to 2.3 million in 2023. However, there are still major challenges in children’s health, especially in the Africa region, where children continue to have the highest risk of dying before reaching age five. Infectious diseases, including acute respiratory infections, diarrhea, and malaria, as well as birth complications, remain among the leading causes of death for children under five. More than half of child deaths are due to conditions that could be prevented and treated with adequate access to health care or other quality of life improvements, particularly in that crucial first month: neonatal deaths make up 47 percent of under-five child deaths.Another challenge is the lack of medicines designed specifically for children—only 30 percent of essential medicines are available in child-appropriate formulations. Instead, children are often treated with imprecise partial doses of medicines that were designed and tested in adults, which can lead to toxicity and complications. This gap results from a variety of barriers: it can take up to 25 years to bring a pediatric medicine to market and only one in ten clinical trials registered between 2000 and 2023 included children. Innovative technologies rolled out since 1990 have already saved millions of lives, and new tools in the pipeline designed with the needs of children, and particularly the most vulnerable kids, in mind could bring down child mortality even more. Diarrheal disease vaccines While diarrheal-disease related deaths among children under five have decreased drastically since 1990, down an estimated 79 percent from 1990 to 2021, they still cause a severe burden; 4.8 million children under five died in 2023. Rotavirus, Shigella, and enterotoxigenic Escherichia coli (ETEC) are among the common pathogens that can lead to diarrheal disease.  The first rotavirus vaccines of the generation still in use today become available just under 20 years ago, approved in the United States in 2006 and later recommended by the World Health Organization for all children. Today, these vaccines are used in more than 110 countries around the world and have contributed to a significant drop in child hospitalizations and deaths from diarrhea. Rotavirus vaccines have had a marked impact on child mortality, preventing 139,000 deaths in children under five between 2006 and 2019. However, rotaviruses are still the leading cause of severe diarrhea in children under five in low- and middle-income countries, pointing to the need for increased access to existing vaccines, as well as new and more effective ones.Unfortunately, approved vaccines don’t yet exist for ETEC and Shigella, though promising candidates are in development. PATH is working with partners to advance vaccines against these bacteria, which could help save thousands of additional lives. For Shigella, PATH is working with the US Naval Medical Research Command and the Walter Reed Army Institute of Research to advance a vaccine candidate, which demonstrated strong safety and efficacy in a recent Phase 1 trial. PATH is also working with these US partners, alongside Sanofi Pasteur and the Infectious Disease Research Institute, to advance an ETEC vaccine candidate, which displayed strong potential in a Phase 1 trial in adults, paving the way for the development of a vaccine for infants and young children, who face the highest risk. If they continue to prove successful, these vaccines could have a tremendous public health impact, not only preventing deaths but also reducing the long-term health and economic effects of malnutrition and developmental delays associated with experiencing severe diarrhea, as well as limiting the growth of antimicrobial resistance.  Pediatric products for malaria and more Children under five account for nearly 80 percent of global malaria deaths. Despite this significant burden, for a long time, there was a lack of a suitable malaria medicines for children, who were treated with crushed tablets designed for adults. The first child-friendly, quality-approved malaria treatment, launched in 2009 by Medicines for Malaria Venture (MMV) and Novartis, is sweet-tasting and quickly dissolves in water. 500 million courses of Coartem® Dispersible have been delivered worldwide as of this April, saving more than 1.8 million lives. MMV also delivered the first malaria treatment for newborn babies and young infants, which is an adapted version of Coartem® that was approved earlier this year. The two first-ever malaria vaccines, approved in the last five years, have been another major game changer for children with malaria, with 21 countries in Africa having introduced them so far, alongside other complementary prevention methods like chemoprevention and vector controlMMV is also working with partner Eyam Health to develop next-generation monoclonal antibody-based approaches to create affordable, long-acting malaria preventative therapies and treatments. Eyam’s technology has the potential to deliver future durable therapies without the need for cold storage and at an extremely low cost, projecting that a single long-acting therapeutic injection could provide protection for more than 50 million children and pregnant women for the months-long rainy season, which is peak time for malaria transmission. This would significantly simplify seasonal malaria chemoprevention, which today involves taking a course of oral drugs monthly for up to five months. Alongside these innovations for malaria, child-friendly medicines for HIV and neglected tropical diseases are also helping address the gap of suitable medicines for children and reduce the burden of treatment for children and their caregivers.  Diagnostics for pre- and postnatal complications and infections Premature birth, birth complications, and neonatal infections are among the leading causes of neonatal deaths, often resulting from limited access to timely screening, particularly in low-resource settings that face a lack of health care services, poor laboratory infrastructure and insufficiently skilled health care workers. Low-cost, easy-to-use diagnostics that can be deployed at the point of care are helping ensure that mothers and babies everywhere have access to routine screening in the pre- and postnatal periods, helping catch and address complications and infections earlier. One innovation is a portable, user-friendly ultrasound developed by Philips that connects to a mobile app on a phone or tablet, helping bring high-quality diagnostics to the point of care. The technology is being rolled out in low- and middle-income countries with the support of the Gates Foundation and has already demonstrated its ability to improve informed decision-making when triaging pregnant women in rural underserved communities.Bacterial infections caused by pneumonia, sepsis, and meningitis are the primary cause of neonatal infections, and most could be averted with adequate access to preventive interventions, early diagnosis, and care. Almost half of sepsis cases occur in children under five. The Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator has awarded funding to Melio, AstraDx, and QuantaMatrix to demonstrate feasibility of their rapid diagnostics for neonatal sepsis, all of which aim to provide results in mere hours, down from days. Early diagnosis is particularly important because the risk of death from neonatal sepsis increases about 7.6 percent every hour treatment is delayed. These innovations have the potential to help greatly reduce the risk of babies and mothers dying from complications and infections during the critical periods before and after birth.  Thirty-five years since the World Summit for Children, we’ve made tremendous progress in children’s health. Investing in innovative technologies specifically designed for children and striving to ensure children and their needs are considered and included in research across health areas will set up future generations for an even healthier future. 

Here in Washington, DC, it’s been an especially buggy summer, with more ticks, mosquitos, and even invasive lanternflies everywhere. In fact, we’re seeing a global rise in mosquito-borne diseases, as rising temperatures, shifting precipitation patterns, and increasing travel and migration bring these critters—and the viruses and parasites they carry—to new places and populations. For example, just last week, a potential case of locally acquired malaria was identified in Washington state, and West Nile virus, a disease transmitted by mosquitoes that was first isolated in Uganda, is now considered endemic in New York state in 2025. Last month, the World Health Organization issued an urgent call for action as chikungunya continues to spread globally again this year, prompting fear of a repeat of the 2004-2005 epidemic. Yellow fever is on the rise too—cases in the Americas during the first few months of 2025 alone more than tripled all cases the region saw last year. 2024 was also the worst year on record for dengue cases. The collective impact of these diseases is striking: globally, mosquito-borne diseases kill more than 1 million people and infect up to 700 million people each year.As conventional vector control methods like insecticide-treated bed nets and indoor residual spraying increasingly face challenges from insecticide resistance and mosquito-borne diseases continue to enter new regions and communities, new and up-and-coming innovations, including in diagnostics, mosquito population modification, and vaccines, will be key to helping minimize the spread of these deadly and debilitating diseases. New diagnostics can help ensure patients start treatment earlierWhile effective tools exist to diagnose mosquito-borne diseases, next-generation tools now in the pipeline could help people receive an accurate diagnosis faster, earlier, at a lower cost, and closer to their home, as well as distinguish between different mosquito-borne infections with similar symptoms. These promising breakthroughs could improve detection and care, particularly in rural and remote areas worldwide.A research team at Institut Pasteur is developing a new rapid diagnostic that can detect the presence of the Plasmodium vivax malaria parasite shortly after the initial mosquito bite—before symptoms arise—, helping patients receive appropriate treatment more quickly. Another team has developed a diagnostic device that uses strips of paper, which could serve as a more affordable, portable diagnostic alternative for detecting malaria infection in asymptomatic people in just 30 minutes.Beyond malaria, a team of Brazilian researchers has developed a novel test that can rapidly identify exposure to all four serotypes of dengue virus, as well as the Zika virus, making it perfectly suitable for regions like Brazil that are endemic to both viruses, where the similarity between symptoms can make it hard to diagnose or assess immunity in patients. This test could also help health care providers and public health workers better pinpoint where treatment and preventive measures need to be implemented.Another new tool developed by scientists at the National Institute of Allergy and Infectious Diseases could also aid surveillance and response. It uses blood samples to identify people who have been bitten by Aedes mosquitoes, which can spread diseases like dengue, Zika, and chikungunya, to identify geographic hot spots for the mosquitoes and monitor exposure in people, helping improve targeted public health interventions. New and innovative tests like these can help identify and minimize the spread of mosquito-borne diseases by connecting people to treatment earlier, as well as informing public health efforts to implement larger-scale vector control measures. Modifying mosquitoes can make it harder for insects to spread diseaseAnother approach to curb mosquito-borne diseases is to directly control the mosquito population by targeting the insect’s ability to transmit viruses or parasites to people through genetic modification or other means. One method establishes a bacterium called Wolbachia, which is commonly found in insects, in an Aedes aegypti mosquito population, blocking viruses like dengue, chikungunya, and Zika from growing inside the insects' bodies. This approach has helped protect more than 13.3 million people as of December 2024. Another research team has found a way to genetically engineer Anopheles stephensi mosquitoes by inserting a gene, which naturally occurs in some mosquitoes, that makes them poor hosts for malaria parasites.Scientists are also exploring approaches that involve inhibiting the reproduction of mosquitoes to reduce population size, and thus, the spread of disease. A Spanish research team is releasing thousands of sterilized tiger mosquitoes, one of the species whose females transmit dengue, to reduce the spread of dengue and other vector-borne diseases. Similar sterilization techniques have been previously used to address other disease vectors, but the Spanish lab is pioneering its use on the tiger mosquito.In an altogether different and novel approach, scientists in the Netherlands are looking into a way to modify mosquitoes so their bite can deliver a vaccine for malaria to humans, with continuous exposure through multiple bites prolonging immunity levels.While some of these methods of targeting mosquito populations have proven effective already and new methods could offer even more precise mechanisms for vector control, the long-term implications on the ecosystem warrant further consideration, so science must move forward cautiously. New vaccines could be game changers, but research has stalled for some diseasesExperts believe that vaccines are essential for drastically reducing the incidence of mosquito-borne diseases, and when used in combination with other prevention methods, could help turn the tide against this growing threat. The world’s first malaria vaccine was approved in 2021, closely followed by a second vaccine in 2023, both of which have already had a huge impact, with 24 million doses delivered across 20 countries. Ongoing research aims to resolve some of the limitations of these first-generation vaccines. One innovative malaria vaccine candidate that is undergoing a clinical trial uses genetically engineered parasites that cannot cause disease but are potent enough to trigger a strong immune response. Preclinical data found that the vaccine could potentially offer higher efficacy at lower doses than current vaccines.The first vaccine for dengue, which could only be used among people who had previous infections, was approved in 2019, but its production is being phased out due to limited use. It was trailed by additional vaccines, including the Qdenga vaccine, which targets all four types of the dengue virus and is safe for use in individuals with and without prior infection. However, it does not provide equal protection against all dengue subtypes and has not been studied enough in people over 16 years old. Researchers in Brazil have developed a single-dose vaccine targeting all dengue subtypes that demonstrated high efficacy in people across ages in recent Phase 3 trials. Its single dose would hopefully also make it easier to administer and scale up production.While these vaccines hold tremendous promise, there are still gaps in the pipeline and a lack of availability of vaccines for certain mosquito-borne diseases. There are no human vaccines for West Nile virus, even though safe and highly effective West Nile vaccines for horses have been around for decades, with research and development efforts in the United States hindered by the sporadic and unpredictable nature of outbreaks. Zika vaccine research has also stalled since the 2015-2016 outbreak, attention dwindling along with cases as people forget the frightening and unexpected nature of the last rise in cases.With trends like climate change, globalization, and migration showing no signs of slowing down, the world’s deadliest animal and the diseases it carries are only going to become a bigger risk to human health. We’ve made tremendous progress against these diseases, but further innovations will better prepare us to take on a buggier future.