The population genetic structure of Plasmodium falciparum, the agent of malignant malaria, has been shown to be predominantly ''clonal'' (i.e., highly inbred) in regions of low infectivity; in highinfectivity regions, it is often thought to be panmictic, or nearly so, although there is little supporting evidence for this. The matter can be settled by investigating the parasite's genetic makeup in the midgut oocysts of the mosquito vector, where the products of meiosis can directly be observed. The developmental stages of P. falciparum are haploid, except in the oocysts of infected mosquito vectors, where two gametes fuse, diploidy occurs, and meiosis ensues. We have investigated genetic polymorphisms at seven microsatellite loci located on five chromosomes by assaying 613 oocysts in 145 mosquitoes sampled from 11 localities of Kenya, where malignant malaria is perennial and intense. There is considerable allelic variation, 16.3 ؎ 2.1 alleles per locus, and considerable inbreeding, Ϸ50% on the average. The inbreeding is caused by selfing (Ϸ25%) and nonrandom genotype distribution of oocysts among mosquito guts (35%). The observed frequency of heterozygotes is 0.43 ؎ 0.03; the expected frequency, assuming random mating, is 0.80 ؎ 0.05. Linkage disequilibrium is statistically significant for all 21 pairwise comparisons between loci, even though 19 comparisons are between loci in different chromosomes, which is consistent with strong deviation from panmixia and the consequent reproduction of genomes as clones, without recombination between gene loci. This is of considerable evolutionary significance and of epidemiological consequence, concerning the spread of multilocus drug and vaccine resistance.epidemiology ͉ evolutionary genetics ͉ parasitism ͉ population genetics

We investigated patterns of genetic diversity of Plasmodium falciparum associated with its two main African vectors: Anopheles gambiae and Anopheles funestus. We dissected 10,296 wildcaught mosquitoes from three tropical sites, two in Cameroon (Simbock and Tibati, separated by 320 km) and one in Kenya (Rota, >2,000 km from the other two sites). We assayed seven microsatellite loci in 746 oocysts from 183 infected mosquito guts. Genetic polymorphism was very high in parasites isolated from both vector species. The expected heterozygosity (HE) was 0.79 in both species; the observed heterozygosities (HO) were 0.32 in A. funestus and 0.42 in A. gambiae, indicating considerable inbreeding within both vector species. Mean selfing (s) between genetically identical gametes was s ‫؍‬ 0.33. Differences in the rate of inbreeding were statistically insignificant among sites and between the two vector species. As expected, because of the high rate of inbreeding, linkage disequilibrium was very high; it was significant for all 21 loci pairs in A. gambiae and for 15 of 21 pairs in A. funestus, although only two pairwise comparisons were between loci on the same chromosome. Overall, the genetic population structure of P. falciparum, as evaluated by F statistics, was predominantly clonal rather than panmictic, a population structure that facilitates the spread of antimalarial drug and vaccine resistance and thus may impair the effectiveness of malaria control efforts. malaria ͉ epidemiology ͉ evolutionary genetics ͉ Cameroon ͉ Kenya M alaria is the most significant and widespread vectortransmitted human disease, accounting yearly for several hundred million clinical cases and Ͼ2 million deaths, mostly affecting young children and pregnant women in subSaharan Africa (1). Prevention and cure of the disease are major publichealth challenges that are tackled by using several strategies, among them vector control. The transmission of Plasmodium falciparum, the agent of malignant malaria, involves a complex vectorial system consisting of Ϸ10 Anopheles species, colonizing different ecoclimatic settings, regions, and seasons in strongly variable relative abundances (2-5).The two most important vectors of malignant malaria in Africa are Anopheles gambiae and Anopheles funestus because of their widespread distribution, highly anthropophilic and endophilic behavior, and long life spans (6, 7). A. gambiae is the most important vector throughout Africa and the most extensively studied Anopheles species (8). The effectiveness of malaria transmission emerges from the complementary ecoclimatic attributes and seasonal patterns of both species. A. funestus breeds in permanent larval sites that enable this species, in regions of seasonal transmission, to extend parasite transmission far into the dry season, after the temporary breeding pools of A. gambiae have dried out (7, 9-11).Differences in the biology and ecology of these two main vectors might entail a differential impact on the genetic composition of the P. falciparum populations they harbo...