Prevailing Plasmodium falciparum dihydrofolate reductase 108-asparagine in Hodeidah, Yemen: A questionable sulfadoxine–pyrimethamine partner within the artemisinin-based combination therapy

Abdul‐Ghani, Rashad; Farag, H.A.; Allam, Amal Farahat; Shawky, Sherine

doi:10.1016/j.actatropica.2013.12.022

Cited by 5 publications

(4 citation statements)

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“…High prevalence (84 %) of Pfdhfr mutant alleles I 51 and N 108 was found among P. falciparum population in Hadhramout. These findings were higher than those from previous reports from western governorates of Yemen [ 11 , 12 ]. Pfdhfr mutant allele R 59 was detected in one isolate of P. falciparum in this study.…”

Section: Discussioncontrasting

confidence: 81%

“…Double mutant genotype of pfdhfr ( I 51 / N 108 ) was reported in 54 % of P. falciparum isolates in Taiz, Dhamar, and Hodeidah governorates in western Yemen [ 11 ]. Pfdhfr mutant allele ( N 108 ) was also reported in 53.2 % of P. falciparum isolates collected from Hodeidah governorate [ 12 ]. However, data on Pfdhfr and Pfdhps mutant alleles and genotypes are not available from the southeastern governorates of Yemen.…”

Section: Introductionmentioning

confidence: 99%

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Frequencies distribution of dihydrofolate reductase and dihydropteroate synthetase mutant alleles associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum population from Hadhramout Governorate, Yemen

Bamaga

Mahdy

Lim

2015

Malar J

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BackgroundMalaria in Yemen is mainly caused by Plasmodium falciparum and 25 % of the population is at high risk. Sulfadoxine–pyrimethamine (SP) had been used as monotherapy against P. falciparum. Emergence of chloroquine resistance led to the shift in anti-malarial treatment policy in Yemen to artemisinin-based combination therapy, that is artesunate (AS) plus SP as first-line therapy for uncomplicated malaria and artemether–lumefantrine as second-line treatment. This study aimed to screen mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes associated with SP resistance among P. falciparum population in Hadhramout governorate, Yemen.MethodsGenomic DNA was extracted from dried blood spots of 137 P. falciparum isolates collected from a community-based study. DNA was amplified using nested polymerase chain reaction (PCR) and subsequently sequenced for Pfdhfr and Pfdhps genes. Sequences were analysed for mutations in Pfdhfr gene codons 51, 59, 108, and 164 and in Pfdhps gene codons 436, 437, and 540.ResultsA total of 128 and 114 P. falciparum isolates were successfully sequenced for Pfdhfr and Pfdhps genes, respectively. Each Pfdhfr mutant allele (I51 and N108) in P. falciparum population had a frequency of 84 %. PfdhfrR59 mutant allele was detected in one isolate. Mutation at codon 437 (G437) in the Pfdhps gene was detected in 44.7 % of falciparum malaria isolates. Frequencies of Pfdhfr double mutant genotype (I51C59N108I164) and Pfdhfr/Pfdhps triple mutant genotype (I51C59N108I164-S436G437K540) were 82.8 and 39.3 %, respectively. One isolate harboured Pfdhfr triple mutant genotype (I51, R59, N108, I164) and Pfdhfr/Pfdhps quadruple mutant genotype (I51R59N108I164-S436G437K540).ConclusionHigh frequencies of Pfdhfr and Pfdhps mutant alleles and genotypes in P. falciparum population in Hadhramout, Yemen, highlight the risk of developing resistance for SP, the partner drug of AS, which subsequently will expose the parasite to AS monotherapy increasing then the potential of the emergence of AS resistance. Study findings necessitate the continuous monitoring of the efficacy of the national anti-malarial drugs policy in Yemen. In addition, monitoring SP efficacy using molecular markers that has shown to be a practical and informative method for monitoring the partner drug of AS.

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Section: Discussioncontrasting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Frequencies distribution of dihydrofolate reductase and dihydropteroate synthetase mutant alleles associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum population from Hadhramout Governorate, Yemen

Bamaga

Mahdy

Lim

2015

Malar J

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“…They suggested that the previous report on the presence of C59 mutation could possibly be explained by inclusion of expatriates in the sample of patients studied. In another study, isolates from 90 patients with microscopically confirmed P. falciparum infection from Al-Hodaida were analysed for the molecular dhfr 108 N by Abdul-Ghani et al [ 29 ]. The mutation was detected among about 61 % of P. falciparum isolates in its pure and mixed-type forms.…”

Section: Discussionmentioning

confidence: 99%

High efficacy of two artemisinin-based combinations: artesunate + sulfadoxine-pyrimethamine and artemether-lumefantrine for falciparum malaria in Yemen

Adeel

Saeed²,

Al-Jasari³

et al. 2015

Malar J

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BackgroundArtesunate + sulfadoxine-pyrimethamine (AS + SP) has been the first-line treatment and artemether-lumefantrine (AL) the second-line treatment for uncomplicated falciparum malaria in Yemen since 2005. This paper reports the results of studies conducted to monitor therapeutic efficacy of these two drugs in sentinel sites in Yemen.MethodsEight therapeutic efficacy studies were conducted in six sentinel sites during the period 2009–2013 in Yemen. Five studies were for the evaluation of AS + SP (total of 465 patients) and three studies (total of 268 patients) for the evaluation of AL. The studies were done according to standard WHO protocol 2009 with 28-day follow-up.ResultsIn the evaluation of AS + SP, the PCR-corrected cure rate was 98 % (95 % CI 92.2–99.5 %) in one site and 100 % in all of the other four sites. In the sites where AL was evaluated, the PCR-corrected cure rate was 100 % in all the sites. All patients were negative for asexual parasitaemia on day 3 in both the AS + SP and the AL groups. There was a higher rate of clearance of gametocytaemia in the AL-treated group when compared with the AS + SP groups from day 7 onwards.ConclusionAS + SP remains the effective drug for uncomplicated falciparum malaria in Yemen. AL is also highly effective and can be an appropriate alternative to AS + SP for the treatment of falciparum malaria. AL demonstrated a higher efficacy in clearing microscopic gametocytaemia than AS + SP.Trial registration: Trial registration number ACTRN12610000696099

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“…Malaria is still a major public health problem in Yemen, with almost 66 % of the population living in areas that suffer from stable malaria transmission [ 1 ]. Plasmodium falciparum is the predominant species and was responsible for almost 99 % of malaria cases in Yemen during 2012, a large number of which consisted of drug-resistant P. falciparum parasites [ 2 , 3 ]. Among 17 countries with malaria-endemic areas in the Middle East and Eurasia region; Pakistan, Afghanistan and Yemen account for more than 99 % of the 56,000 regional deaths due to malaria [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic variation of pfhrp2 in Plasmodium falciparum isolates from Yemen and the performance of HRP2-based malaria rapid diagnostic test

et al. 2015

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BackgroundThe genetic variation in the Plasmodium falciparum histidine-rich protein 2 (pfhrp2) gene that may compromise the use of pfhrp2-based rapid diagnostic tests (RDTs) for the diagnosis of malaria was assessed in P. falciparum isolates from Yemen.MethodsThis study was conducted in Hodeidah and Al-Mahwit governorates, Yemen. A total of 622 individuals with fever were examined for malaria by CareStart™ malaria HRP2-RDT and Giemsa-stained thin and thick blood films. The Pfhrp2 gene was amplified and sequenced from 180 isolates, and subjected to amino acid repeat types analysis.ResultsA total of 188 (30.2 %) participants were found positive for P. falciparum by the RDT. Overall, 12 different amino acid repeat types were identified in Yemeni isolates. Six repeat types were detected in all the isolates (100 %) namely types 1, 2, 6, 7, 10 and 12 while types 9 and 11 were not detected in any of the isolates. Moreover, the sensitivity and specificity of the used PfHRP2-based RDTs were high (90.5 % and 96.1 %, respectively).ConclusionThe present study provides data on the genetic variation within the pfhrp2 gene, and its potential impact on the PfHRP2-based RDTs commonly used in Yemen. CareStart™ Malaria HRP2-based RDT showed high sensitivity and specificity in endemic areas of Yemen.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-015-1008-x) contains supplementary material, which is available to authorized users.

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Prevailing Plasmodium falciparum dihydrofolate reductase 108-asparagine in Hodeidah, Yemen: A questionable sulfadoxine–pyrimethamine partner within the artemisinin-based combination therapy

Cited by 5 publications

References 55 publications

Frequencies distribution of dihydrofolate reductase and dihydropteroate synthetase mutant alleles associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum population from Hadhramout Governorate, Yemen

Frequencies distribution of dihydrofolate reductase and dihydropteroate synthetase mutant alleles associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum population from Hadhramout Governorate, Yemen

High efficacy of two artemisinin-based combinations: artesunate + sulfadoxine-pyrimethamine and artemether-lumefantrine for falciparum malaria in Yemen

Genetic variation of pfhrp2 in Plasmodium falciparum isolates from Yemen and the performance of HRP2-based malaria rapid diagnostic test

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