Variations in frequencies of drug resistance in Plasmodium falciparum

摘要: Continual exposure of malarial parasite populations to different drugs may have selected not only for resistance individual but also genetic traits that favor initiation novel unrelated antimalarials. To test this hypothesis, Plasmodium falciparum clones having varying numbers preexisting mechanisms were treated with two new antimalarial agents: 5-fluoroorotate and atovaquone. All equally susceptible in small numbers. However, when large these challenged either the compounds, significant variations frequencies became apparent. On one extreme, clone D6 from West Africa, which was sensitive all traditional agents, failed develop under simple nonmutagenic conditions vitro. In sharp contrast, Indochina W2, known be resistant drugs, independently acquired both compounds as much a 1,000 times more frequently than D6. Additional some (but all) agents atovaquone at high frequency, 5-fluoroorotate. These findings unexpected surprising based on current views evolution drug P. populations. Such phenotypes, named accelerated multiple (ARMD), raise important questions about biochemical related parasites. Some potential underlying ARMD phenotypes public health implications are ominous.