Antifolate antimalarial resistance in southeast Africa: a population-based analysis

Roper, Cally; Pearce, R. P.; Bredenkamp, B. L. F.; Gumede, Jonathan; Drakeley, Chris; Mosha, Frank; Chandramohan, Daniel; Sharp, Brian

doi:10.1016/s0140-6736(03)12951-0

Cited by 284 publications

(309 citation statements)

References 25 publications

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“…There is evidence of recent selective sweeps across specific regions of the genome, presumably as a consequence of recent drug pressure (Wootton et al, 2002;Nair et al, 2003;Roper, 2003;Roper, 2004). Older selective sweeps as a consequence of natural selection may have occurred across the genome, but identification of these regions might require a genome-wide haplotype map and analysis of linkage disequilibrium.…”

Section: Discussionmentioning

confidence: 99%

“…Regions of the genome that have undergone recent selective sweeps include regions of chromosome 7 surrounding the pfcrt locus (Wootton et al, 2002) and regions of chromosome 4 surrounding the dhfr (Nair et al, 2003;Roper et al, 2003) and dhps (Roper et al, 2004) loci. These selective sweeps are recent in the evolutionary history of P. falciparum, presumably because they are a consequence of recently applied drug pressure.…”

Section: Introductionmentioning

confidence: 99%

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Genomic heterogeneity in the density of noncoding single-nucleotide and microsatellite polymorphisms in Plasmodium falciparum

Volkman

Lozovsky

Barry

et al. 2007

Gene

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The density and distribution of single-nucleotide polymorphisms (SNPs) across the genome has important implications for linkage disequilibrium mapping and association studies, and the level of simple-sequence microsatellite polymorphisms has important implications for the use of oligonucleotide hybridization methods to genotype SNPs. To assess the density of these types of polymorphisms in P. falciparum, we sampled introns and noncoding DNA upstream and downstream of coding regions among a variety of geographically diverse parasites. Across 36,229 base pairs of noncoding sequence representing 41 genetic loci, a total of 307 polymorphisms including 248 polymorphic microsatellites and 39 SNPs were identified. We found a significant excess of microsatellite polymorphisms having a repeat unit length of one or two, compared to those with longer repeat lengths, as well as a nonrandom distribution of SNP polymorphisms. Almost half of the SNPs localized to only three of the 41 genetic loci sampled. Furthermore, we find significant differences in the frequency of polymorphisms across the two chromosomes (2 and 3) examined most extensively, with an excess of SNPs and a surplus of polymorphic microsatellites on chromosome 3 as compared to chromosome 2 (P = 0.0001). Furthermore, at some individual genetic loci we also find a nonrandom distribution of polymorphisms between coding and flanking noncoding sequences, where completely monomorphic regions may flank highly polymorphic genes. These data, combined with our previous findings of nonrandom distribution of SNPs across chromosome 2, suggest that the Plasmodium falciparum genome may be a mosaic with regard to genetic diversity, containing chromosomal regions that are highly polymorphic interspersed with regions that are much less polymorphic.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genomic heterogeneity in the density of noncoding single-nucleotide and microsatellite polymorphisms in Plasmodium falciparum

Volkman

Lozovsky

Barry

et al. 2007

Gene

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“…They detected several selective sweeps associated with CQ resistance, including the previously described region on chromosome 7 containing pfcrt, as well as loci on chromosomes 5 (harboring the multidrug resistance gene homolog pfmdr1) and 11. Focusing on pyrimethamine resistant clones, they were able to detect two candidate selective sweeps on chromosomes 13 and 14, which were of particular interest because they demonstrated a stronger signal than the previously identified sweep at the dhfr locus on chromosome 4 [9,13,14].…”

Section: Genomic Studies Using Polymorphisms To Identify Resistance Locimentioning

confidence: 95%

Advances in understanding the genetic basis of antimalarial drug resistance

Ekland

Fidock

2007

Current Opinion in Microbiology

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SummaryThe acquisition of drug resistance by Plasmodium falciparum has severely curtailed global efforts to control malaria. Our ability to define resistance has been greatly enhanced by recent advances in Plasmodium genetics and genomics. Sequencing and microarray studies have identified thousands of polymorphisms in the P. falciparum genome, and linkage disequilibrium analyses have exploited these to rapidly identify known and novel loci that influence parasite susceptibility to antimalarials such as chloroquine, quinine, and sulfadoxine-pyrimethamine. Genetic approaches have also been designed to predict determinants of in vivo resistance to new antimalarials such as the artemisinins. Transfection methodologies have defined the role of determinants including pfcrt, pfmdr1 and dhfr. This knowledge can be leveraged to develop more efficient methods of surveillance and treatment.

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“…[25] Retrospective genetic analyses on samples collected during a community-based prevalence survey in 2000 confirmed the presence of highly SP-resistant parasites, with 47% of all parasites analysed in carrying the SP quintuple mutation associated with SP treatment failure. [26] This high prevalence of SP-resistant parasites most likely enhanced transmission, as individuals infected with SP-resistant parasites have increased gametocyte loads, [27] which are more infectious to mosquitoes than SP-sensitive gametocytes.…”

Section: Antimalarial Drug Resistance Across Sa and Neighbouring Counmentioning

confidence: 99%

“…Resistance to both CQ and SP arose in Southeast Asia and spread into Africa via gene flow rather than evolving de novo, [26,36] highlighting the need for regional malaria control, and more importantly, a clear understanding of the malaria epidemiology in neighbouring countries. As the movement of both the malaria vector and parasite is not restricted by national boundaries regional drug pressure can influence drug efficacy within countries, as seen in KZN Province, SA [20] and Maputo Province, Mozambique.…”

Section: Regional Drug Pressurementioning

confidence: 99%

Case management of malaria: Treatment and chemoprophylaxis

et al. 2013

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Corresponding author: D Moonasar (moonad@health.gov.za)Malaria case management is a vital component of programmatic strategies for malaria control and elimination. Malaria case management encompasses prompt and effective treatment to minimise morbidity and mortality, reduce transmission and prevent the emergence and spread of antimalarial drug resistance. Malaria is an acute illness that may progress rapidly to severe disease and death, especially in non-immune populations, if not diagnosed early and promptly treated with effective drugs. In this article, the focus is on malaria case management, addressing treatment, monitoring for parasite drug resistance, and the impact of drug resistance on treatment policies; it concludes with chemoprophylaxis and treatment strategies for malaria elimination in South Africa.

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Antifolate antimalarial resistance in southeast Africa: a population-based analysis

Cited by 284 publications

References 25 publications

Genomic heterogeneity in the density of noncoding single-nucleotide and microsatellite polymorphisms in Plasmodium falciparum

Genomic heterogeneity in the density of noncoding single-nucleotide and microsatellite polymorphisms in Plasmodium falciparum

Advances in understanding the genetic basis of antimalarial drug resistance

Case management of malaria: Treatment and chemoprophylaxis

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