ARRA Investments in Malaria
Public Health Burden
Malaria, a parasitic disease, is an urgent threat to global health. Over forty percent of the world’s population is at risk of becoming infected, and malaria causes more than 250 million cases of disease annually in many of the poorest tropical and subtropical regions of Africa, Asia, the Middle East, and Central and South America. Malaria-related death rates have doubled over the last thirty years and nearly 1.3 million people----mostly children under the age of five----die from malaria every year.
Basic Research and Pathogenesis
In the global effort to fight malaria, NIH supports the majority of basic research on this parasitic disease from parasite to mosquito to human host. Increased knowledge of these three elements and the multifaceted interactions between them is critical in the development of effective tools to prevent and control malaria. Furthermore, a better understanding of the biological processes underlying the progression of infection to disease (i.e., malaria pathogenesis) is urgently needed to reduce the morbidity and mortality of malaria. A variety of ARRA awards are focused on the basic biology and pathogenesis of the malaria parasite, including the projects highlighted below.
One project will study malaria-infected red blood cells to advance understanding of the mechanisms by which the most lethal malaria parasite,
, causes disease.
A second project will investigate the role that two large families of proteins play in blood-stage infection. Both protein families are predicted to be conserved among malaria parasite species, and a better understanding of their role may have implications for drug and vaccine development.
Another project will examine the roles of two enzymes called aminopeptidases that help the malaria parasite digest the hemoglobin of its host's red blood cells and could identify potential new drug targets.
Advances made by a project that seeks to identify proteins critical for parasite liver-stage development may also uncover new drug and vaccine targets.
The malaria parasite migrates to the liver and infects liver cells almost immediately after entering the host.
Another project aims to identify drug and vaccine targets for placental malaria, a severe form of the disease that affects pregnant women in malaria-endemic regions.
Vector Biology and Control
Malaria parasites are transmitted to humans by a diverse group of mosquitoes (30-40 species) of the genus
. Vector control tools such as insecticides, environmental modification, and bed nets have contributed to successful malaria control efforts historically, but have faced setbacks in recent years due to the emergence of insecticide resistance in mosquitoes. ARRA funds are supporting the development of new vector control strategies to prevent parasite transmission and reduce the mosquito population.
One project will investigate the role of plants in the success of malaria-transmitting mosquitoes in Africa. In earlier studies, the investigative team unveiled new discoveries about
ecology that could pave the way for novel methods of malaria control.
Antimalarial drugs, in combination with mosquito control programs, have historically played a key role in controlling malaria in endemic areas, resulting in significant reduction in both the burden and the range of malarial disease worldwide. Over the years, however, the emergence and spread of drug-resistant parasites have contributed to a reemergence of malaria, turning back the clock on control efforts. The need for new, effective drugs for malaria and an understanding of the mechanisms by which the parasite has become resistant to existing drugs have become critical priorities on the global malaria research agenda. Examples of projects within this area of research that have received ARRA funds include:
One grant aims to improve our understanding of the genetic factors in the malaria-causing parasite
that contribute to its growing resistance to current antimalarial drugs
, while another seeks to establish a novel genetic system to identify genes in the malaria parasite that are involved in drug-resistance.
A project focused on the design of an innovative compound could potentially expand, enhance, and sustain effective anti-malarial drug combinations.
Research focused on increasing our understanding of the function of certain enzymes in
may aid in identifying novel targets for malaria drugs.
Investigators have made progress in the design of potent inhibitors of malaria parasite growth. ARRA funds will aid the investigators’ efforts to improve the medicinal chemistry of these inhibitors in an effort to develop therapeutics that could be effective in treatment against malaria and other parasitic diseases.
Another award will support preclinical development of a class of compounds with potent antimalarial activity, including activity against multi-drug resistant malaria.
The development of a safe and effective vaccine against malaria will be critical in malaria control, prevention, and eradication efforts. Currently, no licensed vaccine against malaria (or any parasitic disease that afflicts humans) exists. The complexity of the
parasite and the lack of understanding of critical processes, such as host immune protection and disease pathogenesis, have hampered vaccine development efforts. ARRA funding will aid investigators in the identification and development of malaria vaccine candidates and adjuvants to boost the host’s immune response.
One project aims to develop an inexpensive oral vaccine that protects against infection by
, the main parasite that causes malaria.
Another project will evaluate the ability of a recombinant protein called flagellin as a novel immune enhancer (adjuvant) to boost the immune response and augment the effectiveness of a malaria vaccine candidate.
An additional project seeks to develop a novel strategy to enhance the efficacy of malaria vaccines by employing glycolipids as immune-enhancing compounds (adjuvants).
-- Microfluidics for Malaria Pathogenesis in Africa -- Rathod, Pradipsinh K (WA)
-- The Plasmodium 2TM and PHIST Protein Families -- Templeton, Thomas J (NY)
-- Roles of Two Aminopeptidases in Peptide Catabolism in the Malaria Parasite -- Klemba, Michael (VA)
-- Exploring the Exportome of Malaria Liver Stages -- Tarun, Alice S (WA)
-- Molecular Mechanisms of Plasmodium Falciparum Adherence to the Human Placenta -- Fisher, Susan (CA
-- The Floral Dimension of African Malaria -- Foster, Woodbridge A (OH)
-- Genome Surveillance for drug resistant malaria -- Wirth, Dyann F (MA)
-- Forward genetic screens for identifying antimalarial resistance genes -- Duraisingh, Manoj T (MA)
-- Dual Function Acridones as A New Antimalarial Chemotype -- Kelly, Jane X (OR)
-- Chemical Genetics of Plasmodium Kinases -- Chakrabarti, Debopam (FL)
-- Biochemistry of Protein Prenylation -- Buckner, Frederick Simmons; Gelb, Michael H. (contact); Van Voorhis, Wesley C.; Verlinde, Christophe L.M.J (WA)
-- Development of a Chloroquine Replacement Drug -- Riscoe, Michael Kevin (OR)
-- Oral Immunization Against Malaria with Recombinant Adenoviruses -- Ketner, Gary W (MD)
-- Malaria vaccines modified with TLR agonist adjuvant -- Nardin, Elizabeth H (NY)
-- CD1d/NKT-binding Glycolipids as an Adjuvant for a T cell-based Malaria Vaccine -- Tsuji, Moriya
Page Last Updated on June 30, 2018
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