Naveen Manchanda, MD
Malaria infects 500 million annually; one million die from this infection and countless others have their daily lives and livelihood abbreviated due to this disease. Currently, 40 percent of the world’s population is exposed to the malarial parasite; just a few decades ago this affected three-fourths of the populace. The interplay and interconnectedness of the dual host species (Anopheles and Hominids) and the parasite (Plasmodium) appear to have evolved in a coordinated fashion where good intentions are perverted, no good deed goes unpunished, and no regulatory cycle is left untouched.
Dr. John G. Quigley spoke about a newly identified pathway of heme detoxification in the mosquito. Upon ingestion of a blood meal, the Anopheline mosquito takes up the parasite bathed in blood into the GI tract. Heme is generated in the small intestinal cells where it is transported to the gut lumen or the hemolymph by an analog of the feline leukemia virus-C receptor (FLVCR). His previous research had shown that heme export was essential to cell survival and that human cells of the erythropoietic lineage also process excess heme left over from hemoglobin synthesis; this is exported to the exterior bound to the FLVCR analog in the cells (Quigley JG et al. Cell. 2004:118;757-766). FLVCR was subsequently identified in several human organ systems where it played an effective scavenger for intracellular toxic heme.
The question arose whether the FLVCR protein in the mosquito small intestinal cells could be inhibited thus rendering high heme concentrations in the gut cells leading to cell death and diminished uptake of the plasmodium parasite.
Dr. Quigley presented fascinating new data on this subject. Indeed, mosquitos administered anti-FLVCR antibody or inhibitory RNA showed diminished heme egress, increased reactive oxygen species, and decreased cell survival. The intriguing possibility remains whether this pathway in the mosquito can be targeted therapeutically and lead to the desired clinical benefit of inhibiting transmission of the parasite.
Once again there is hope that the perfidy of Plasmodium can be countered by products of such research targeting novel antigens in the mosquito vector. Will this be the last hurrah for this disease? One can certainly hope so.
Dr. Manchanda indicated no relevant conflicts of interest.