Drug resistance–virulence relationship in Plasmodium falciparum causing severe malaria in an area of seasonal and unstable transmission

Giha, Hayder A.; Elbashir, Mustafa I.; A-Elbasit, Ishraga E.; A-Elgadir, Thoraya M.E.; ElGhazali, Gehad; Mackinnon, Margaret J.; Babiker, Hamza A.

doi:10.1016/j.actatropica.2005.10.004

Cited by 30 publications

(30 citation statements)

References 40 publications

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“…It is interesting to note that the FC27 parasites had significantly higher prevalence of pfcrt and pfmdr1 mutant alleles (data not shown). These data support our previous observation, which showed that the mortality is associated with the wild types of pfcrt and pfmdr1 genes (Giha et al 2006).…”

Section: Discussionsupporting

confidence: 82%

Allelic polymorphism of MSP2 gene in severe P. falciparum malaria in an area of low and seasonal transmission

et al. 2007

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The severe malaria (SM) and uncomplicated malaria (UM) infections are expected to have different genetic makeup. In this study, blood samples were obtained from 325 donors with SM and UM and malaria-free donors (including asymptomatic submicroscopic malaria--ASUM), from Eastern Sudan. The SM group included patients with cerebral malaria (CM), severe malarial anemia (SMA), and other complications. The MSP2 locus was exploited for parasite genotyping. We found that the genetic diversity of the parasite population was marked (51 genotypes). The overall multiplicity of infection (MOI) was 1.5, and it was comparable between SM and UM. However, the MOI in ASUM (1.0) and fatal CM (1.14) was comparable and significantly lower than in UM (1.53), SMA (1.52), and nonfatal CM (1.7). The ratio of the IC1 to FC27 allele families was comparable between SM and UM, and the distribution of the allele sizes was correlated (correlation coefficient = 0.59 and 0.718; P < 0.001). It is interesting to note that the FC27 genotype was overrepresented in ASUM (68.2%) and was not recognized in fatal CM, while in mixed-clone infections, the clearance of IC1 after quinine treatment was faster than FC27 clearance. Finally, the composition of the multiclone infections (IC1 and FC27) was suggesting a stronger cross-immunity within rather than between MSP2 gene families.

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Section: Discussionsupporting

confidence: 82%

Allelic polymorphism of MSP2 gene in severe P. falciparum malaria in an area of low and seasonal transmission

et al. 2007

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“…An association of point mutations in the Pfmdr1 and Pfcrt genes with the severe manifestation of the disease, which might be due to progression of uncomplicated to severe disease after treatment failure or to increased virulence of CQ resistant parasites, has been reported from Kenya, India and The Gambia (Omar et al 2001;Ranjit et al 2004;Meerman et al 2005). In our work, we did not find any selection of Pfmdr1 point mutations associated with the severity of the disease, as was also recently shown in Sudan (Giha et al 2006).…”

Section: Discussionsupporting

confidence: 78%

“…Recently, Meerman et al (2005) found that mutant alleles of the Pfcrt and Pfmdr1 genes associated with chloroquine resistant parasites were detected with a higher frequency in Gambian patients presenting with severe malaria anaemia. By contrast, no similar findings were reported in a comparable study carried out in Sudan (Giha et al 2006).…”

Section: Introductioncontrasting

confidence: 76%

No variation in the prevalence of point mutations in the Pfcrt and Pfmdr1 genes in isolates from Gabonese patients with uncomplicated or severe Plasmodium falciparum malaria

et al. 2006

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In Lambaréné (Gabon), where a high level of Plasmodium falciparum resistance to chloroquine has been reported, we assessed the relationship between polymorphisms in the P. falciparum chloroquine resistance transporter (Pfcrt) and multidrug resistance-1 (Pfmdr1) genes and the clinical severity of malaria. Ninety-one and 60 P. falciparum isolates from children with uncomplicated or severe malaria were collected in 1996 and 2002, respectively. Single nucleotide mutations at codon 76 in the Pfcrt gene and at codons 86, 184, 1034, 1042, and 1246 in the Pfmdr1 gene were assessed by PCR-RFLP. All P. falciparum isolates presented the Pfcrt K76T mutation, whatever the clinical status. A high prevalence (>80%) of the Pfmdr1 86Tyr and 184Phe mutations was detected at both time points and in both clinical groups. We did not identify any specific mutation in the Pfmdr1 gene associated with the severity of disease, and the multiplicity of P. falciparum infection was also similar in both groups. Our results showed no change in the polymorphism of Pfcrt and Pfmdr1 genes in P. falciparum isolates collected in 1996 and 2002, and the severity of the disease was not associated with specific mutations neither in the Pfcrt nor in the Pfmdr1 genes in the study site.

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“…Other SM patients had convulsions (n = 14), SMA (n = 14), hypotension (n = 9) and multiple complications (n = 5); the details have been presented before [Giha et al, 2006]. Of the patients with SM, parasite DNA was obtained from 47 patients.…”

Section: Clinical Datamentioning

confidence: 99%

“…The study population and design together with the clinical data have been reported before [Giha et al, 2006]. In brief, the suspected malaria patients were seen in the outpatient clinic and investigated for malaria infection by microscopy.…”

Section: Study Populationmentioning

confidence: 99%

Genetic Fingerprints of Parasites Causing Severe Malaria in a Setting of Low Transmission in Sudan

et al. 2007

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In this study we intended to examine the extent of genetic diversity of Plasmodium falciparum parasites causing severe malaria (SM). For this purpose, 100 parasite isolates were obtained from patients with SM and uncomplicated malaria, from an area of low and unstable malaria transmission in Sudan. The diversity of infection (DOI) was estimated by relating the number of the different parasite genotypes that were detected to the total number of parasites that were genotyped (parasite population/subpopulation). We used different molecular markers individually (pfcrt-76, pfmr1-86, GLURP size and MSP2 family and size) and as a group to set a multilocus genetic profile for each parasite isolate. The DOI as estimated by MSP2 and GLURP was 0.553 and 0.435, respectively. However, combination of all four molecular markers (multilocus genetic profile) revealed a fingerprint pattern of genetic diversity with a DOI of 0.936, indicating that in SM infection, diversity is the rule and homogeny is the exception. Furthermore, our clinical data suggest that the virulence markers might also be more diverse than expected. In conclusion, the results are unexpected and overturn the assumption that parasites causing SM are a limited subpopulation of virulent parasites or of a clonal nature. However, it was more likely that there was a genetically unique parasite in each infection.

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Drug resistance–virulence relationship in Plasmodium falciparum causing severe malaria in an area of seasonal and unstable transmission

Cited by 30 publications

References 40 publications

Allelic polymorphism of MSP2 gene in severe P. falciparum malaria in an area of low and seasonal transmission

Allelic polymorphism of MSP2 gene in severe P. falciparum malaria in an area of low and seasonal transmission

No variation in the prevalence of point mutations in the Pfcrt and Pfmdr1 genes in isolates from Gabonese patients with uncomplicated or severe Plasmodium falciparum malaria

Genetic Fingerprints of Parasites Causing Severe Malaria in a Setting of Low Transmission in Sudan

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