Polymorphism in dhfr/dhps genes, parasite density and ex vivo response to pyrimethamine in Plasmodium falciparum malaria parasites in Thies, Senegal

Ndiaye, Daouda; Dièye, Baba; Ndiaye, Yaye Dié; Tyne, Daria Van; Daniels, Rachel F.; Bei, Amy K.; Mbaye, Aminata; Valim, Clarissa; Lukens, Amanda K.; Mboup, Souleymane; Ndir, O.; Wirth, Dyann F.; Volkman, Sarah K.

doi:10.1016/j.ijpddr.2013.07.001

Cited by 27 publications

(27 citation statements)

References 55 publications

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“…Triple and quadruple mutations were not significantly different between the two sites, although they were high for both sample sets. Encouragingly, the quintuple mutation N51I/C59R/S108N dhfr and A437G/K540E dhps gene, which is strongly associated with in vivo and in vitro SP resistance in East and Southern Africa [46, 47] was not observed, consistent with findings from previous studies in Sénégal by Ndiaye et al [48, 49] and Wurtz et al [43]. However, a recent study conducted in Sénégal found a single sample with the quintuple mutation [50], resulting in an overall population prevalence of 1.1%.…”

Section: Discussionsupporting

confidence: 88%

High resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic Plasmodium populations

Ndiaye

Diédhiou

Bei

et al. 2017

Malar J

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BackgroundEmergence and spread of drug resistance to every anti-malarial used to date, creates an urgent need for development of sensitive, specific and field-deployable molecular tools for detection and surveillance of validated drug resistance markers. Such tools would allow early detection of mutations in resistance loci. The aim of this study was to compare common population signatures and drug resistance marker frequencies between two populations with different levels of malaria endemicity and history of anti-malarial drug use: Tanzania and Sénégal. This was accomplished by implementing a high resolution melting assay to study molecular markers of drug resistance as compared to polymerase chain reaction–restriction fragment length polymorphism (PCR/RFLP) methodology.MethodsFifty blood samples were collected each from a lowly malaria endemic site (Sénégal), and a highly malaria endemic site (Tanzania) from patients presenting with uncomplicated Plasmodium falciparum malaria at clinic. Data representing the DHFR were derived using both PCR–RFLP and HRM assay; while genotyping data representing the DHPS were evaluated in Senegal and Tanzania using HRM. Msp genotyping analysis was used to characterize the multiplicity of infection in both countries.ResultsA high prevalence of samples harbouring mutant DHFR alleles was observed in both population using both genotyping techniques. HRM was better able to detect mixed alleles compared to PCR/RFLP for DHFR codon 51 in Tanzania; and only HRM was able to detect mixed infections from Senegal. A high prevalence of mutant alleles in DHFR (codons 51, 59, 108) and DHPS (codon 437) were found among samples from Sénégal while no mutations were observed at DHPS codons 540 and 581, from both countries. Overall, the frequency of samples harbouring either a single DHFR mutation (S108N) or double mutation in DHFR (C59R/S108N) was greater in Sénégal compared to Tanzania.ConclusionHere the results demonstrate that HRM is a rapid, sensitive, and field-deployable alternative technique to PCR–RFLP genotyping that is useful in populations harbouring more than one parasite genome (polygenomic infections). In this study, a high levels of resistance polymorphisms was observed in both dhfr and dhps, among samples from Tanzania and Sénégal. A routine monitoring by molecular markers can be a way to detect emergence of resistance involving a change in the treatment policy.

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Section: Discussionsupporting

confidence: 88%

High resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic Plasmodium populations

Ndiaye

Diédhiou

Bei

et al. 2017

Malar J

Self Cite

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“…Compared to the 17% (20/118) reported by Djaman et al [10] in Abidjan, the prevalence of the triple mutant has increased while the prevalence of the wild type allele decreased from 61% (72/118) to 30.8%. The increase in the number of mutations was associated with an increase in ex vivo resistance to pyrimethamine as previously shown in Sénégal [23], Côte d'Ivoire [10], Gabon [24], and the Central African Republic [25].…”

Section: Discussionsupporting

confidence: 78%

Sulfadoxine-Pyrimethamine Resistant Haplotypes in Asymptomatically and Symptomatically Malaria Infected Individuals in CÃƒÂ´te dÃ¢Â€Â™Ivoire

Aristide¹

2014

Malaria Contr Elimination

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Background: Most studies that assess efficacy of antimalarial drugs focus on the outcome of clinical treatment. However, community surveys of surrogate indicators are often more practical and can provide a wider view of possible changes in drug response, but it has not been clear whether assessment of parasite isolates from patients and asymptomatic individuals are directly comparable. In the present work, we have compared the prevalence of molecular markers associated with resistance to sulfadoxine-pyrimethamine in parasites isolated from asymptomatic and symptomatic individuals.

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“…PfDHFR polymorphism at 51I, 59R and 108N combined mutations of 89% observed in this study was similar to 89-97% documented in western Kenya among pregnant women (10,21). Proportion comparable to these have been reported elsewhere: 97% in Uganda (8); 87% in Equatorial Guinea (22); 98% in Cameroon (29), and 93% in Senegal (30). These frequencies were higher compared to 48% detected in DRC (23) and 54 -74% in Burkina Faso (25,31).…”

Section: Iptp-sp Is An Important Prophylactic Therapy Recommended Forsupporting

confidence: 86%

Prevalence of PfDHFR and PfDHPS Mutations Associated with Drug Resistance Among Pregnant Women Receiving IPTp-SP at Msambweni County Referral Hospital, Kwale County, Kenya

Gikunju

Agola

Ondondo

et al. 2019

Preprint

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Background: Prevention and treatment of malaria during pregnancy is crucial in dealing with maternal mortality and adverse fetal outcomes. WHO’s recommendation to treat all pregnant women with sulphadoxine-pyrimethamine (SP) through antenatal care structures was implemented in Kenya in the year 1998 but concerns about its effectiveness in preventing malaria in pregnancy has arisen due to the spread of parasites resistant to SP. We aimed to determine the prevalence of SP resistance markers in Plasmodium falciparum parasites isolated from pregnant women seeking antenatal care at Msambweni County Referral Hospital, located in coastal Kenya, between the year 2013 and 2015. Methods: This hospital-based study included 106 malaria positive whole blood samples for analysis of SP resistance markers within the PfDHFR gene (codons 51,59 &108) and PfDHPS gene (codons 437 & 540). The venous blood collected from all pregnant women was tested for malaria via light microscopy, then thereafter separated into plasma and red cells and stored in a -86⁰ freezer for further studies. Archived red blood cells were processed for molecular characterization of SP resistance markers within the PfDHFR gene and PfDHPS using real time PCR platform. Results: All samples had at least one mutation in the genes associated with drug resistance; polymorphism prevalence of PfDHFR51I, 59R and 108N was at 88.7%, 78.3% and 93.4%, respectively, while PfDHPS polymorphism accounted for 94.3% and 91.5% at 437G and 540K, respectively. Quintuple mutations (at all the five codons) conferring total SP resistance had the highest prevalence of 86%. Quadruple mutations were observed at a frequency of 10.4%, and 24.5% had a heterogeneous outcome with both wildtype and mutant genotypes in the genes of interest. Conclusion: The data suggest a high prevalence of Pf genetic variations conferring resistance to SP among pregnant women, which may explain reduced efficacy of IPTp treatment in Kenya. There is need for extensive SP resistance profiling in Kenya to inform IPTp drug choices for successful malaria prevention during pregnancy.

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Polymorphism in dhfr/dhps genes, parasite density and ex vivo response to pyrimethamine in Plasmodium falciparum malaria parasites in Thies, Senegal

Cited by 27 publications

References 55 publications

High resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic Plasmodium populations

High resolution melting: a useful field-deployable method to measure dhfr and dhps drug resistance in both highly and lowly endemic Plasmodium populations

Sulfadoxine-Pyrimethamine Resistant Haplotypes in Asymptomatically and Symptomatically Malaria Infected Individuals in CÃƒÂ´te dÃ¢Â€Â™Ivoire

Prevalence of PfDHFR and PfDHPS Mutations Associated with Drug Resistance Among Pregnant Women Receiving IPTp-SP at Msambweni County Referral Hospital, Kwale County, Kenya

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