Statement of B.F. (Lee) Hall, M.D., Ph.D., and Anthony S. Fauci, M.D., National Institute of Allergy and Infectious Diseases.
Eliminating malaria — one of the world’s oldest and deadliest diseases — remains a critically important public health and biomedical research challenge. Despite remarkable advances in reducing malaria incidence and deaths since 2000, recent progress has become stagnant and has even reversed in some regions.
The World Health Organization(link is external) (WHO) estimates that in 2017 about 219 million cases of malaria occurred worldwide and approximately 435,000 people died of the disease. Unfortunately, malaria cases increased from 2016 to 2017 in the 10 highest-burden countries in Africa, and the number of cases per 1,000 in populations at risk remained at 59 from 2015 to 2017.
Today, the National Institutes of Health recognizes World Malaria Day and commits to a reinvigorated malaria research program. This year’s World Malaria Day theme, “Zero malaria starts with me,” encourages governments, companies, academic institutions, philanthropies, and others to prioritize malaria, mobilize resources, and empower communities affected by malaria to lead and coordinate response activities. The National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, is working toward “zero malaria” with coordinated global research projects to better understand the disease, improve diagnostics, treatments, and mosquito control interventions, and develop safe and effective vaccines.
NIAID works directly with scientists in malaria-endemic regions to build specialized local clinical research capacity. The NIAID-supported International Centers of Excellence for Malaria Research (ICEMR) program has more than 50 field sites in 17 endemic countries dedicated to multidisciplinary research on the complex interactions between the human host, mosquito vectors, and malaria parasites. ICEMR investigators share genomic and epidemiological data for parasites, mosquitoes, and human hosts through public databases such as PlasmoDB(link is external), VectorBase(link is external), and ClinEpiDB(link is external) to assist researchers in developing drugs, vaccines and diagnostics, and in improving public health programs.
ICEMR researchers are studying how the malaria-causing parasite adapts to antimalarial drug pressure and how that translates to the emergence and spread of drug resistance. Resistance to artemisinin drugs, used in most endemic areas, is emerging in Southeast Asia and appears to be spreading west. The ICEMRs are evaluating how asymptomatic malaria infections may contribute to persistent disease transmission and risk. Investigators also are studying how the behavior of malaria-transmitting mosquitoes is changing in response to insecticide use and environmental and ecosystem changes.
NIAID investigators and NIAID-supported scientists are helping to inform treatment policies in various countries by tracking genetic mutations in malaria parasites that indicate resistance to certain drugs. A team of experts recently identified a molecular marker of resistance to piperaquine (a combination therapy drug) in Cambodia(link is external) using publicly available genome sequence data.
Another international research team supported by NIAID created mutated versions of nearly all of the 5,400 Plasmodium falciparum (P. falciparum) parasite genes to determine which of the organism’s genes are essential to growth and survival. The information will help investigators prioritize targets for future antimalarial drug development. One investigational drug being evaluated, DM1157, is a modified form of the antimalarial drug chloroquine. Similar to chloroquine, it interferes with the malaria parasite’s metabolism; however, it inhibits the parasite’s ability to expel the drug, thereby avoiding the drug resistance seen with chloroquine. A Phase 1 clinical trial to evaluate the drug’s safety began in September 2018.
Cerebral malaria — a severe form of illness that can lead to brain damage, long-term neurological deficits, and death — remains a significant problem in sub-Saharan Africa. ICEMR investigators and their collaborators identified brain swelling as a potential contributor to the high mortality rate among children in Malawi with cerebral malaria. A clinical trial is underway to assess whether measures to reduce brain swelling can improve treatment outcomes. ICEMR investigators in India are studying whether the same findings are seen in adults with cerebral malaria, while NIAID researchers are working to develop novel adjunctive cerebral malaria treatments.
Certain populations, such as pregnant women, are at higher risk of developing severe disease upon contracting malaria. NIAID-supported researchers in Malawi recently found that administering the drug chloroquine as a weekly chemoprophylaxis(link is external) may prevent malaria in pregnancy. NIAID-supported scientists also found that children with high levels of maternal antibodies to the malaria antigen PfSEA-1 at birth have decreased risk of severe malaria during infancy.
NIAID also supports the development of various investigational malaria vaccines. The Institute has conducted and supported multiple early-stage clinical trials of PfSPZ, a candidate malaria vaccine made of weakened immature malaria parasites. It is designed to prevent malaria infection and is now being evaluated in multiple clinical trials in malaria endemic regions, including in infants and children. Another candidate vaccine based on a recombinant protein is currently in a Phase 1 clinical trial.
NIAID researchers also are working on a vaccine designed to block transmission of the malaria parasite from infected humans to mosquitoes. Although a transmission-blocking vaccine would not prevent malaria infection, by limiting further spread it could reduce new malaria infections over time. Results from a clinical trial in Mali indicate that the investigational vaccine, when formulated with an immunity-boosting adjuvant, shows promise. Plans are underway to evaluate the efficacy of the vaccine in a Phase 2 clinical trial in Mali.
NIAID scientists recently developed a monoclonal antibody from a person vaccinated with PfSPZ that potentially could be used for seasonal control and elimination efforts as well as by tourists, health care workers, and military personnel to prevent malaria infection. A trial evaluating the antibody’s safety and efficacy against a controlled human malaria infection (human challenge study) is planned for early 2020. NIAID experts also are collaborating with Malian scientists to discover additional broadly protective monoclonal antibodies.
Although recent data indicate that malaria control efforts may have stalled, numerous historical examples indicate that with enough commitment and ingenuity malaria elimination can be achieved, even after significant setbacks. NIAID-supported investigators, researchers and their collaborators are accelerating progress toward malaria elimination every day. On this World Malaria Day, we reaffirm our commitment to advancing the best research to reach our goal of “zero malaria.”
Lee Hall, M.D., Ph.D., is chief of the Parasitology and International Programs Branch in the NIAID Division of Microbiology and Infectious Diseases. Anthony S. Fauci, M.D., is Director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, Maryland.