Plasmodium falciparum: Differential Selection of Drug Resistance Alleles in Contiguous Urban and Peri-Urban Areas of Brazzaville, Republic of Congo

Abstract

The African continent is currently experiencing rapid population growth, with rising urbanization increasing the percentage of the population living in large towns and cities. We studied the impact of the degree of urbanization on the population genetics of Plasmodium falciparum in urban and peri-urban areas in and around the city of Brazzaville, Republic of Congo. This field setting, which incorporates local health centers situated in areas of varying urbanization, is of interest as it allows the characterization of malaria parasites from areas where the human, parasite, and mosquito populations are shared, but where differences in the degree of urbanization (leading to dramatic differences in transmission intensity) cause the pattern of malaria transmission to differ greatly. We have investigated how these differences in transmission intensity affect parasite genetic diversity, including the amount of genetic polymorphism in each area, the degree of linkage disequilibrium within the populations, and the prevalence and frequency of drug resistance markers. To determine parasite population structure, heterozygosity and linkage disequilibrium, we typed eight microsatellite markers and performed haplotype analysis of the msp1 gene by PCR. Mutations known to be associated with resistance to the antimalarial drugs chloroquine and pyrimethamine were determined by sequencing the relevant portions of the crt and dhfr genes, respectively. We found that parasite genetic diversity was comparable between the two sites, with high levels of polymorphism being maintained in both areas despite dramatic differences in transmission intensity. Crucially, we found that the frequencies of genetic markers of drug resistance against pyrimethamine and chloroquine differed significantly between the sites, indicative of differing selection pressures in the two areas.

Surveillance of Molecular Markers of Plasmodium falciparum Resistance to Sulphadoxine-Pyrimethamine 5 Years after the Change of Malaria Treatment Policy in Ghana

“…So far, the studies on transmission intensity and drug resistance have produced conflicting results. Malaria drug resistance often appears first in areas of low transmission intensity, suggesting that the conditions in such areas may enhance the selection of drug resistance 41 and may be related to the modestly higher prevalence of mutants observed in the low transmission intensity forest area of our study. Apart from drug pressure from the use of SP, other antifolates being used in the treatment of respiratory tract infections in children such as co-trimoxazole (trimethoprim and sulfamethoxazole) may also contribute to the selection of resistant parasites because co-infections of bacteria and malaria are common.…”

Little Polymorphism at the K13 Propeller Locus in Worldwide Plasmodium falciparum Populations Prior to the Introduction of Artemisinin Combination Therapies

“…Sampling year, number, and area are described in Table 1. Other detailed sampling information was described previously (9)(10)(11)(12)(13)(14)(15)(16). All studies but one (Bangladesh) were conducted before the first report of artemisinin resistance from west Cambodia in 2006-2007 (3).…”

High Levels of Genetic Diversity of Plasmodium falciparum Populations in Papua New Guinea despite Variable Infection Prevalence

“…2,5,6 However, within these regions, fine-scale variations in transmission occur as a result of factors such as altitude, vector availability, urbanization, and malaria control, and these correspond with differences in genetic diversity. [7][8][9][10][11] Diversity underlies resilience against interventions that directly target the parasite, such as malaria vaccines, which will need to cover all antigenically distinct strains circulating in an endemic area to be effective, 12 and the emergence of resistance to antimalarial drugs. 13 In the context of control programs, a diverse parasite population maintained in the face of falling prevalence would continue to be a significant public health challenge.…”