Genetic structure of Plasmodium falciparum and elimination of malaria, Comoros archipelago

Abstract

The efficacy of malaria control and elimination on islands may depend on the intensity of new parasite inflow. On the Comoros archipelago, where falciparum malaria remains a major public health problem because of spread of drug resistance and insufficient malaria control, recent interventions for malaria elimination were planned on Moheli, 1 of 4 islands in the Comoros archipelago. To assess the relevance of such a local strategy, we performed a population genetics analysis by using multilocus microsatellite and resistance genotyping of Plasmodium falciparum sampled from each island of the archipelago. We found a contrasted population genetic structure explained by geographic isolation, human migration, malaria transmission, and drug selective pressure. Our findings suggest that malaria elimination interventions should be implemented simultaneously on the entire archipelago rather than restricted to 1 island and demonstrate the necessity for specific chemoresistance surveillance on each of the 4 Comorian islands.

Figure 1

Results of canonical correspondence analysis (CCA) of Plasmodium falciparum populations from the islands of Grande Comore (GC), Moheli (MOH), Anjouan (ANJ), and Mayotte (MAY) and from Marseille, France (MARS), according to 6 microsatellite loci. CCA is used as a 2-dimensional representation of genetic distance between plasmodial populations assessed from 6 microsatellite loci (Pf2689, C4M79, Pf2802, 7A11, TRAP, and C4M69). This representation requires the projection of data from 6-dimensional space to 2-dimensional space. Canonical axes I and II of the new 2-dimensional space are calculated to conserve the highest genetic variance between populations after projection of data, and their significance was tested by Monte Carlo permutation that also enabled estimation of the 95% confidence intervals (ellipses) of the centroid (dots) of each population.

Figure 2

Genetic differentiation (Fst) between Plasmodium falciparum populations from the islands of Grande Comore (GC), Moheli (MOH), Anjouan (ANJ), and Mayotte (MAY) and from Marseille, France (MARS), according to 6 microsatellite loci. Pairwise comparison among sites that used complete dataset (n = 281) and 6 microsatellite loci (Pf2689, C4M79, Pf2802, 7A11, TRAP, and C4M69). Departure of F_ST from 0 tested after 10,000 bootstrap simulations and by using Bonferroni corrected p values obtained after 200 permutations. Difference is significant if adjusted p<0.005. Black arrows indicate negligible (F_ST<0.01) and nonsignificant differentiation. Asterisks (*) and orange arrows indicate moderate (0.01<F_ST<0.1) and/or statistically significant differentiation. Daggers (†) and red arrows indicate important (F_ST >0.1) and significant differentiation. Plain arrows indicate genetic differentiation between the parasite populations of the Comoros islands. Dotted arrows indicate genetic differentiation between the parasite population imported in Marseille (from Comoros) and either the overall parasite population of the entire Comoros archipelago (dotted oval and extreme right arrow) or the parasite populations of each of the 4 islands.

Figure 3

Relationship between geographic and genetic distances for each pair of Comoros islands (top) and between mean percentage of travelers among sampled patients and genetic distance for each pair of Comoros islands (bottom). Genetic distances were calculated as (F_ST/1 – F_ST ), where F_ST is the Wright F statistic. Mean percentage of travelers was calculated from the total number of sampled patients in one site (N_A) with history of recent arrival from another site (N_B) by using the equation ([N_B→A/N_A] + [N_A→B/N_B])/2; data in Table 1. GC, Grande Comore; MOH, Moheli; ANJ, Anjouan; MAY, Mayotte; Ln, logarithmically transformed.