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Methods for assessment of antimalarial activity in the different phases of the Plasmodium life cycle

Malaria is a mosquito-borne disease caused by parasites of the genus Plasmodium. In humans, parasites multiply in the liver and then infect red blood cells. The Plasmodium life cycle consists of a sexual phase in the mosquito vector (sporogony) and an asexual phase in the vertebrate host (schizogony); both life cycle phases can be detected in assays. In general, in vivo and in vitro are the two basic approaches routinely used to evaluate the antimalarial activity of compounds. The antimalarial activity measured in an in vivo test results from a variety of factors associated with both the parasite and the host. Conversely, in vitro tests reflect more accurately the “isolated” effects of the compounds on parasite metabolism. In vivo assessment of antiplasmodial activity can be achieved using rodent models and by assessing transmission-blocking activity using mosquitoes. There are several in vitro tests for the assessment of antimalarial activity based upon observation of parasite development in blood cells through thick films, isotopic assays, quantification of parasite proteins and DNA dye intercalation assays. Besides antimalarial activity, a promising antimalarial compound should also lack toxicity to host cells; the degree of selectivity of a compound towards the malaria parasite includes such assessment. In this manuscript, we intend to summarize the most frequently used methods for assessing the antimalarial activity of compounds in the different stages of the Plasmodium life cycle.

Methods for assessment of antimalarial activity in the different phases of the Plasmodium life cycle

Malaria is a mosquito-borne disease caused by parasites of the genus Plasmodium. In humans, parasites multiply in the liver and then infect red blood cells. The Plasmodium life cycle consists of a sexual phase in the mosquito vector (sporogony) and an asexual phase in the vertebrate host (schizogony); both life cycle phases can be detected in assays. In general, in vivo and in vitro are the two basic approaches routinely used to evaluate the antimalarial activity of compounds. The antimalarial activity measured in an in vivo test results from a variety of factors associated with both the parasite and the host. Conversely, in vitro tests reflect more accurately the “isolated” effects of the compounds on parasite metabolism. In vivo assessment of antiplasmodial activity can be achieved using rodent models and by assessing transmission-blocking activity using mosquitoes. There are several in vitro tests for the assessment of antimalarial activity based upon observation of parasite development in blood cells through thick films, isotopic assays, quantification of parasite proteins and DNA dye intercalation assays. Besides antimalarial activity, a promising antimalarial compound should also lack toxicity to host cells; the degree of selectivity of a compound towards the malaria parasite includes such assessment. In this manuscript, we intend to summarize the most frequently used methods for assessing the antimalarial activity of compounds in the different stages of the Plasmodium life cycle.