B. Fenton Hall, M.D., Ph.D., and Anthony S. Fauci, M.D.
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Significant global progress has been made since 2000 to reduce the incidence and mortality of malaria. However, recent evidence suggests that the trend toward fewer malaria cases and deaths has stalled, or in some regions of the world, reversed course. As a global community, we cannot afford to cede the hard-fought gains in the battle to control and eliminate this devastating mosquito-borne disease. On World Malaria Day 2018, the National Institutes of Health reaffirms and renews its long-standing commitment to conducting and supporting the innovative scientific research needed to end malaria.
Improved prevention and control measures have helped several countries reduce the burden of malaria. In 2016, 44 countries reported fewer than 10,000 malaria cases, compared to 37 countries in 2010, according to the World Health Organization (WHO). However, while some countries with ongoing malaria transmission are making progress, others are experiencing setbacks due to insufficient funding and inadequate access to malaria prevention, diagnostic and treatment tools. In 2016, an estimated 216 million new malaria cases and 445,000 deaths occurred, largely among children living in sub-Saharan Africa.
This year’s World Malaria Day theme is “Ready to Beat Malaria.” The National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, is working to achieve this goal with our comprehensive research program. NIAID scientists and grantees are conducting research to further understand the biology of malaria parasites, including how they cause disease, and the mosquitoes that transmit them; determine how resistance to anti-malaria drugs and insecticides develops and spreads; improve the medical management of clinical malaria, particularly severe malaria; and develop novel diagnostics, treatments, vaccines and methods for reducing or interrupting malaria transmission.
Much of the NIAID malaria research effort is implemented through the International Centers of Excellence in Malaria Research (ICEMRs), a collaborative network of research centers established in 2010 to conduct multidisciplinary studies in endemic regions and strengthen local research capacity. The 11 ICEMRs perform research in 17 countries in Africa, Asia, Latin America and the Western Pacific region. They have played a key role in sequencing the genomes of malaria-carrying mosquitoes and malaria-causing parasites, and releasing that information into the public domain to assist other researchers.
The ICEMRs and NIAID scientists also have tracked the spread of parasite resistance to artemisinin, the key drug component in approved combination malaria treatments. For example, their work found that frontline malaria treatments combining fast-acting dihydroartemisinin and long-acting piperaquine have failed in Cambodia because of the rapid spread of drug-resistant parasites. This discovery together with the growing resistance to other effective combination therapy (artesunate-mefloquine) prompted WHO to change its frontline treatment guidelines for Cambodia. NIAID scientists also have identified a new genetic marker strongly associated with parasitic resistance to piperaquine. This genetic marker is now being tracked throughout Southeast Asia to monitor the spread of resistance and determine where alternative therapies should be used. Furthermore, NIAID-funded researchers have identified genetic factors of insecticide resistance across mosquito species and mapped their spread across Africa.
Last year, NIAID awarded a multi-project grant to study anti-malaria drug resistance that combines systems biology with a breakthrough technology for creating experimental genetic crosses of the malaria parasite in humanized mice. These studies could potentially lead to new ways to block drug resistance and predict and optimize therapeutics for combination malaria therapy.
The continued threat of drug resistance drives NIAID to find new and effective anti-malaria drugs. NIAID is supporting the development of four anti-malaria drugs currently in preclinical and clinical testing and participates in partnerships to accelerate malaria research and advance development of new interventions. A single dose of a novel anti-malaria drug called DSM265, protected volunteers in a human challenge study from infection with Plasmodium falciparum malaria, the deadliest form of the disease. Additionally, the NIAID-supported investigational malaria drug SJ733 performed well in Phase 1 testing and is expected to undergo further testing this year. NIAID also is supporting a clinical trial in Malawi to determine whether hypertonic saline or early mechanical ventilation as adjunctive therapy to standard treatment might improve mortality compared to standard treatment alone for children presenting with cerebral malaria, a major cause of death for African children.
NIAID also is pursuing research on malaria vaccines that could serve a critical role in future malaria control efforts. The Institute is supporting seven malaria vaccine candidates in various stages of clinical testing. In early-stage clinical trials, one experimental malaria vaccine candidate called PfSPZ elicited high levels of protection in malaria-naïve adults in the U.S. and Europe against controlled human malaria infection with the same parasite strain occurring within a few months of immunization, and moderate levels of protection persisted up to one year after immunization. A lower level of protection against a different parasite strain was also observed in the short-term. When adult volunteers in malaria-endemic Mali were immunized, the vaccine candidate also elicited a protective response against locally acquired malaria, although at a lower rate than that seen in individuals without any prior history of malaria exposure. The protection persisted for a 24-week follow-up period despite intense malaria transmission. Additional clinical testing is continuing in infants and adults in multiple studies throughout Africa. Further testing is also underway for a second-generation, nanoparticle-based malaria transmission-blocking vaccine (TBV) developed by NIAID scientists.
NIAID scientists recently developed a human monoclonal antibody that protects mice from infection with P. falciparum. This antibody, called CIS43, was derived from a person vaccinated with the PfSPZ vaccine candidate. It will be administered to human volunteers to determine if it can protect them against a controlled human malaria infection. If safe and effective, the antibody potentially could be used among tourists, health care workers, and military personnel to prevent malaria infection for up to six months or be used in malaria elimination campaigns in conjunction with drug therapy.
Further progress against malaria requires a sustained commitment and effort among global partners. On World Malaria Day, we thank the clinical trial volunteers who have participated in malaria research and reaffirm our commitment to the broad biomedical research efforts necessary to control, eliminate and, ultimately, eradicate this disease.
B. Fenton (“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.