Malaria is a vector disease, meaning that the malaria parasite must spend part of its life cycle in the mosquito before being transmitted to humans. Malaria is most common throughout tropical areas and every year it kills millions of people. The latest research shows that perhaps the trigger to malaria may have been found.
The disease is caused by protozoan parasites of the genus Plasmodium and the most common vector for infection is the female Anopheles mosquito. The mosquitoes infect humans after they pierce the skin in order to take blood. The mosquitoes' saliva releases sporozoites, mature Plasmodium cells that then infect their new hosts. These sporozoites travel to the liver, multiply and eventually cause infected cells to burst and release merozoites into the blood. The merozoites infect the red blood cells and then spread throughout the body.
A recent breakthrough by a team of researchers at Hopkins could be the first step towards helping prevent malaria from its earliest stages. The group, led by Marcelo Jacobs-Lorena of the Malaria Research Institute in the Bloomberg School of Public Health, has identified a sugar that is needed for malaria to live in the mosquito before infecting humans. The results of their work may be used for further studies to help advance methods of early detection and prevention of malaria.
The scientists found that one critical point in the parasite life-cycle is its attachment to the lining of the mosquito hindgut. The mosquito becomes the vector for the disease after the ookinete, the fertilized egg cell of the malaria organism, penetrates the stomach of the mosquitoes. The ookinete then forms an oocyst under the mosquito's outer gut lining. The researchers surmised that the key to prevention of malaria is to prohibit the infection of the protozoan into the mosquito. This study dealt with prevention of the parasite's passage from the mosquito from the beginning.
The researchers focused on a protein called TRAP, or thrombospondin-related adhesive protein, which serves as a signal molecule for the protozoan as it enters the mosquito. TRAP is a cell-surface protein with a large attached sugar group that allows specific recognition and tight binding by the malaria parasite. In mosquitoes, it is found predominantly in the cells of the gut.
The researchers studied TRAP binding by feeding different sugars to mosquitoes overnight. They then measured the degree to which each mosquito's gut cells bound to the malaria parasite, specifically in the ookinete stage. The scientists found a strong binding by the sugar chondroitin sulfate E.
To further prove this finding, the scientists inhibited parasite development by repressing synthesis of the sugar by RNA interference. This lowered sugar levels, which caused a significant decrease in the ability of the malaria organism to develop in the mosquito.
The next step from this experiment is to look at ways to prevent the expression of the sugar so that transmission of malaria is reduced and millions of lives may be saved. Experimental therapies that treat the vector rather than the human patient may be next.
