NIAID Commemorates World Malaria Day 2024

Malaria, the fifth most deadly infectious disease, remains a public health priority. On April 25, World Malaria Day, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), joins with the global health community in reaffirming our commitment to ending this ancient parasitic disease. This year's theme, "Accelerating the fight against malaria for a more equitable world," spotlights the inequity of the impact of the mosquito-borne disease: although the United States eliminated malaria more than 70 years ago, the disease annually kills more than 600,000 people worldwide, with 80 percent of these deaths, tragically, among children under the age of 5 years in Africa. An estimated 249 million new malaria cases occurred in 2022-the third consecutive year that the case count has increased after more than 20 years of decline, according to the World Health Organization (WHO). Each year, 2,000 Americans develop malaria, according to the Centers for Disease Control and Prevention.

Uncomplicated malaria cases include debilitating cycles of high fever, intense chills, fatigue and sweating. In areas of the world where malaria is prevalent, repeated bouts of infection are not uncommon. Severe malaria infection can lead to coma, organ failure, respiratory distress, seizures, severe anemia, shock and death. Among pregnant women, malaria infection can cause premature delivery, miscarriage, and stillbirth.

NIAID's International Centers of Excellence for Malaria Research (ICEMR) are a cornerstone of our malaria efforts. The program, which began in 2010 and was recently renewed, is a global network of independent research centers in malaria-endemic countries working to conduct malaria research in the areas of epidemiology, transmission, and pathogenesis in diverse geographic settings to better understand, control and ultimately prevent malaria. The multidisciplinary research infrastructure at ICEMR sites allows for large-scale randomized trials that efficiently generate data about the efficacy of both new and established malaria interventions. The Centers have been integral in the identification and tracking of the spread of artemisinin-resistant malaria parasites across Africa and generating new reference genomes for Plasmodium vivax parasites based on samples acquired from different parts of the world, including Africa.

Tracking parasite resistance to existing malaria treatments is essential to ensuring the availability of effective medications. In addition to the ICEMR's work, researchers from the NIAID-funded Genomic Centers for Infectious Diseases recently discovered the emergence of piperaquine resistance in Guyana and neighboring countries, as well as distinct genetic markers from Southeast Asia and South American countries suggesting caution with dihydroartemisinin-piperaquine use.

With increased drug resistance to first-line malaria treatments comes the need for new, safe and effective medications. To that end, NIAID scientists and grantees continue to work to identify and develop novel malaria treatments For example, NIAID-funded scientists have identified genetic markers associated with resistance to multiple first-line malaria drugs and highlighted the potential for combination piperaquine with lumefantrine as an effective treatment. Also, NIAID-funded researchers recently identified an Open-Source Malaria compound, called OSM-S-106, that showed effectiveness against malaria parasites by prohibiting their protein synthesis and also suggesting a low propensity for the development of drug resistance.

While the development of new malaria treatments is important, prevention of malaria is vital. One promising development in this area include monoclonal antibodies (mAbs) capable of rapidly neutralizing parasites once they enter the bloodstream and before reaching the liver to cause disease. Findings are expected soon from a Phase 2 clinical trial examining one dose of an investigational mAb subcutaneously injected into the skin of children in Mali to protect against malaria disease during the country's intense six-month malaria season. The investigational product, called L9LS, was developed by scientists at NIAID's Vaccine Research Center (VRC) and is also undergoing additional clinical testing in infants in Kenya. These studies follow an earlier generation NIAID-developed monoclonal, called CIS43L3, which was 88 percent effective at preventing malaria infection in pregnant adults when administered intravenously. If successful, the monoclonals could offer a level of protection for the people most vulnerable to malaria infection.

NIAID also continues to pursue the development of malaria vaccines, including PfSPZ malaria vaccine candidates. These experimental vaccines contain live parasites in the sporozoite, or SPZ, phase of their lifecycle that have either been weakened via radiation or the removal of specific genes, so that they cannot cause serious infection but still prompt a protective immune response. Another approach involves introducing live parasites in combination with either of two widely used antimalarial drugs, which kill the parasites once they have progressed to the liver or blood stage of their development. This combination approach demonstrated high levels of durable protection in early-phase studies. NIAID scientists have also developed a vaccine candidate that has demonstrated an ability to reduce malaria transmission and are working with the Serum Institute of India to test the vaccine in combination with the R21 malaria vaccine currently in use among young children in malaria-endemic areas.

In concert with activities to develop new malaria prevention tools and treatments are efforts to develop improved diagnostics to replace failing rapid diagnostic tests and mosquito management and control strategies, such as the use of bacteria or fungi to suppress mosquitoes or genetically modified mosquitoes to reduce or eliminate their ability to transmit malaria parasites.

Progress is being made in the search to control malaria, but the disease remains a daunting challenge. On this World Malaria Day, NIAID applauds the world's scientists, public health officials, and clinical trial participants who continue to work to end this terrible disease.