In the chain of malaria transmission from one human to another a weak link is the sporogonic development of the parasite in the vector mosquito. If a mosquito interrupts the parasite development, the transmission of malaria is blocked. Interference with this development in vector mosquitoes is, therefore, a proposed strategy to block the spread of malaria. To design such strategies, however, an understanding of the parasite development in the vector mosquitoes is essential. The development of malaria parasites in the mosquito is elaborate. After being ingested by a mosquito, the parasite undergoes complex changes that occur in stages. These include development from gamete to zygote, transformation from zygote to ookinete, and development from ookinete to oocyst. Within the oocyst, the parasite multiplies into numerous sporozoites. Sporozoites are infectious to humans and are transmitted by mosquitoes that had previously ingested the parasite from an infected vertebrate. In the mosquito, the parasite's development is compartmentalized. Zygote to ookinete development occurs in the midgut lumen in the presence of the vertebrate blood. Ookinete to oocyst and sporozoites transformation occur in the hemolymph where the parasite is exposed to the immune attack. But in the mosquito parasite remains associated with the midgut for most of its developmental period. Also, mosquito midgut epithelium appears to be the major barrier for the parasite development. Therefore it is likely that molecules related to the parasite/mosquito midgut interaction would be crucial determinants of the malaria transmission. We therefore investigate 1) the developmental changes that occur in the mosquito stages of the parasite, 2) the structural and biochemical features of the mosquito midgut, and 3) the interaction of the parasite with the midgut. Although only mosquitoes transmit malaria, only a few species are successful vectors and of those that transmit malaria, kill more than 99% of the ingested parasites. This suggests that all mosquitoes are inherently refractory for the malaria parasite and respond to the parasite invasion. Therefore a balance of the complex reciprocal manipulations between the parasite and mosquito determines the success of parasite development and malaria transmission. To understand these manipulations we also study the insect response to malaria parasite using mosquito and non-mosquito insect models.
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