Malaria

Recent Scientific Findings

Early Trial Results Show New Malaria Vaccine Stimulates Strong Immune Response

A new candidate vaccine to prevent clinical malaria has passed an important hurdle on the development path, according to researchers from the University of Bamako in Mali, West Africa and the University of Maryland School of Medicine’s Center for Vaccine Development. In a new study of the candidate vaccine in young children in Mali, researchers found it stimulated strong and long-lasting immune responses. The antibody levels the vaccine produced in the children were as high or even higher than the antibody levels found in adults who have naturally developed protective immune responses to the parasite over lifelong exposure to malaria.
The new candidate vaccine is based on a single strain of the Plasmodium falciparum parasite—the most common and deadliest form of the protozoa—and targets malaria in the blood stage. The blood stage refers to the period following initial infection by mosquito bite when the parasite multiplies in red blood cells, causing disease and death.
The team tested the vaccine in 100 children ages 1 to 6 in rural Mali. It was shown to be safe and well tolerated, and strong antibody responses were sustained for at least a year. Based on results from this early trial, the research teams will hold a larger trial of 400 Malian children to further evaluate its effectiveness. That study also will examine whether the vaccine—though it is based on a single strain of falciparum malaria—can protect against the other strains of Plasmodium falciparum.
Thera MA, Doumbo OK, Coulibaly D, Laurens MB, Kone AK et al. Safety and Immunogenicity of an AMA1 Malaria Vaccine in Malian Children: Results of a Phase 1 Randomized Controlled Trial. 

Caspar Controls Resistance to Plasmodium falciparum in Diverse Anopheline Species

In this study, researchers studied the interaction between Plasmodium falciparum, the parasite that causes human malaria, and its mosquito host, Anopheles gambiae. They found that a single mosquito gene called caspar, which helps to regulate the mosquito’s immune response, appears to confer resistance to the parasite. When this gene is silenced, Plasmodium falciparum is unable to develop in three different mosquito species that carry malaria to humans. In the future, this gene could be used to develop novel malaria control methods that would apply to different species of Anopheline mosquitoes around the world.
Garver LS, Dong Y, Dimopoulos G. (2009) Caspar control resistant to Plasmodium falciparum in diverse Anopheline species. PLoS Pathogens.

Invasion of mosquito salivary gland requires interaction between malaria parasite and mosquito proteins

The malaria parasite Plasmodium falciparum must undergo a complex series of developmental stages inside the mosquito in order to ensure its transmission to humans. The final stage of development which allows the parasite to be transmitted is the sporozoite, the infectious form of P. falciparum. The sporozoite must be present in the mosquito salivary gland tissue in order to be transmitted to humans during a mosquito’s blood feeding. 
NIAID-supported researchers have recently shed light on the interaction between the sporozoite stage and the mosquito salivary gland. Led by Dr. Anil Ghosh of the Johns Hopkins School of Public Health, scientists identified a protein (saglin) as the receptor for the sporozoite surface protein TRAP. An enhanced understanding of how malaria sporozoites invade mosquito salivary glands is important because if this process can be blocked, no transmission of the parasite from mosquitoes to humans will occur.
Ghosh AK et al. Malaria parasite invasion of the mosquito salivary gland requires interaction between the Plasmodium TRAP and the Anopheles saglin proteins. PLoS Pathog. 2009 Jan;5(1):e1000265.

Two duplicated P450 genes are associated with pyrethroid resistance in Anopheles funestus, a major malaria vector

The Anopheles funestus species of mosquito is an important but understudied vector of malaria in Africa, where more than 300 million acute cases of the disease occur each year. Insecticides, which contain the chemical compound pyrethroid, have been used as an effective tool in controlling mosquito populations. Unfortunately, resistance in mosquitoes to pyrethroid is increasing which has lessened the effectiveness of this insecticide in malaria control efforts. Identification of the genes involved in resistance and development of diagnostic tests that are easily deployed in the field and are sufficiently sensitive to identify the emergence of resistance are essential to developing more effective vector control methods. In a study, supported by NIAID, a research team, led by Dr. Charles Wondji of the Liverpool School of Tropical Medicine, identified the major genes conferring pyrethroid resistance in An. funestus. They identified two specific P450 genes and established that these genes could be used as valid resistance markers in laboratory-raised strains of An. funestus. Studies are underway to establish if these markers will be useful in mosquitoes which are found in the field.
Wondji C et. al. Two duplicated P450 genes are associated with pyrethroid resistance in Anopheles funestus, a major malaria vector. Genome Research. February 5, 2009.