Molecular Determinants of Sulfadoxine-Pyrimethamine Resistance in Plasmodium falciparum Isolates from Central Africa between 2016 and 2021: Wide Geographic Spread of Highly Mutated
            <i>Pfdhfr</i>
            and
            <i>Pfdhps</i>
            Alleles

Wang, Xiaoxiao; Zhang, Xuan; Chen, Hualiang; Lu, Qiaoyi; Ruan, Weibin; Chen, Zhiping

doi:10.1128/spectrum.02005-22

Cited by 7 publications

(4 citation statements)

References 39 publications

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“…Moreover, the novel Pfdhps I 431 V allele previously detected in Nigeria and observed to be spreading across Central Africa ( 25 , 26 ) including Chad and the Democratic Republic of Congo was identified in this study at a frequency of 27.1%. This allele exhibited similar frequency (30.8%) in the H/T and human stages although lower in the midgut stage (18.1%), possibly because of sporozoite population expansion in the salivary gland from ruptured oocyst that successfully traversed the midgut barrier ( 20 ).…”

Section: Discussionsupporting

confidence: 57%

Geographical emergence of sulfadoxine-pyrimethamine drug resistance-associated P. falciparum and P. malariae alleles in co-existing Anopheles mosquito and asymptomatic human populations across Cameroon

Nkemngo,

Raissa,

Nguete

et al. 2023

Antimicrob Agents Chemother

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Malaria molecular surveillance remains critical in detecting and tracking emerging parasite resistance to anti-malarial drugs. The current study employed molecular techniques to determine Plasmodium species prevalence and characterize the genetic diversity of Plasmodium falciparum and Plasmodium malariae molecular markers of sulfadoxine-pyrimethamine resistance in humans and wild Anopheles mosquito populations in Cameroon. Anopheles mosquito collections and parasitological survey were conducted in villages to determine Plasmodium species infection, and genomic phenotyping of anti-folate resistance was accomplished by sequencing the dihydrofolate-reductase ( dhfr ) and dihydropteroate-synthase ( dhps ) genes of naturally circulating P. falciparum and P. malariae isolates. The malaria prevalence in Elende was 73.5% with the 5–15 years age group harboring significant P. falciparum (27%) and P. falciparum + P. malariae (19%) infections. The polymorphism breadth of the pyrimethamine-associated Pfdhfr marker revealed a near fixation (94%) of the triple-mutant -A 16 I 51 R 59 N 108 I 164 . The Pfdhps backbone mediating sulfadoxine resistance reveals a high frequency of the V 431 A 436 G 437 K 540 A 581 A 613 alleles (20.8%). Similarly, the Pmdhfr N 50 K 55 L 57 R 58 S 59 S 114 F 168 I 170 haplotype (78.4%) was predominantly detected in the asexual blood stage. In contrast, the Pmdhps – S 436 A 437 occured at 37.2% frequency. The combined quadruple N 50 K 55 L 57 R 58 S 59 S 114 F 168 I 170 _ S 436 G 437 K 540 A 581 A 613 (31.9%) was the major circulating haplotype with similar frequency in humans and mosquitoes. This study highlights the increasing frequency of the P. malariae parasite mostly common in asymptomatic individuals with apparent P. falciparum infection. Interventions directed at reducing malaria transmission such as the scaling-up of SP are favoring the emergence and spread of multiple drug-resistant alleles between the human and mosquito host systems.

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Section: Discussionsupporting

confidence: 57%

Geographical emergence of sulfadoxine-pyrimethamine drug resistance-associated P. falciparum and P. malariae alleles in co-existing Anopheles mosquito and asymptomatic human populations across Cameroon

Nkemngo,

Raissa,

Nguete

et al. 2023

Antimicrob Agents Chemother

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“…The Pfdhfr mutant alleles N51I, C59R, and S108N have been found to be highly prevalent and widespread in Africa, as well as the triple mutant Pfdhfr I 51 R 59 N 108 haplotype. Almost all had a prevalence of over 90% 17,[24][25][26][27] . Previous research also showed the mutant Pfdhfr I164L had a high frequency in Asia, with relatively low prevalence in Africa [28][29][30] .…”

Section: Discussionmentioning

confidence: 99%

“…Most studies have indicated that SP resistance is related to mutations at codons S436A/F, A437G, K540E, A581G, and A613S/T in Pfdhps genes and N51I, C59R, S108N, and I164L in Pfdhfr genes [10][11][12][13] . A novel mutation I431V in Pfdhps genes was rst detected in Nigeria in 2007, then in some other countries of West and Central Africa [14][15][16][17] . In most cases, the mutation I431V occurs simultaneously with four other Pfdhps mutations: S436A, A437G, A581G, and A613S, forming a quintuple mutant V 431 A 436 G 437 K 540 G 581 S 613 18 .…”

Section: Introductionmentioning

confidence: 99%

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Prevalence of Molecular Markers of Sulfadoxine-pyrimethamine Resistance in Plasmodium falciparum Isolates from West Africa during 2012–2022

Zhou,

Li,

et al. 2024

Preprint

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Sulfadoxine-pyrimethamine (SP) is a key drug recommended by the World Health Organization for the chemoprevention of malaria. However, the strategy is affected by the parasite resistance to SP. This study evaluated Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, associated with SP resistance, from 508 P. falciparum isolates imported from West African countries to Henan Province, China, during 2012–2022. High mutant prevalence of the genes Pfdhfr (94.7%) and Pfdhps (96.8%) was observed. The mutants Pfdhfr N51I, C59R, S108N, and Pfdhps A437G were at high frequency in all countries analyzed. The overall prevalence of the mutant Pfdhps K540E was low (3.4%), but with a high frequency in Liberia (24.3%). The frequency of mutants Pfdhps I431V, A581G, and A613S was 11.7%, 9.8%, and 16.2%, respectively, all of which had the highest mutant prevalence in Nigeria. The mutant Pfdhps A581G and A613S were identified in the absence of K540E. The partially resistant haplotype (I51R59N108 - G437) was the most common (72.6%), and the fully resistant haplotype (I51R59N108 - G437E540) had a low prevalence of 3.4% and mainly occurred in Liberia. No super resistant haplotype was identified. The mutant Pfdhps I431V and the octuple mutant haplotype I51R59N108 - V431A436G437G581S613 deserve more attention. It is important to continuously monitor the molecular markers associated with SP resistance to better implement intermittent preventive treatment policies in pregnancy (IPTp) and infants (IPTi).

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Prevalence of molecular markers of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates from West Africa during 2012–2022

Zhou,

Li,

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Sulfadoxine-pyrimethamine (SP) is a key drug recommended by the World Health Organization for the chemoprevention of malaria. However, the strategy is affected by the parasite resistance to SP. This study evaluated Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, associated with SP resistance, from 508 P. falciparum isolates imported from West African countries to Henan Province, China, during 2012–2022. High mutant prevalence of the genes Pfdhfr (94.7%) and Pfdhps (96.8%) was observed. The mutants Pfdhfr N51I, C59R, S108N, and Pfdhps A437G were at high frequency in all countries analyzed. The overall prevalence of the mutant Pfdhps K540E was low (3.4%), but with a high frequency in Liberia (24.3%). The frequency of mutants Pfdhps I431V, A581G, and A613S was 11.7%, 9.8%, and 16.2%, respectively, all of which had the highest mutant prevalence in Nigeria. The mutant Pfdhps A581G and A613S were identified in the absence of K540E. The partially resistant haplotype (I51R59N108 - G437) was the most common (72.6%), and the fully resistant haplotype (I51R59N108 - G437E540) had a low prevalence of 3.4% and mainly occurred in Liberia. No super resistant haplotype was identified. The mutant Pfdhps I431V and the octuple mutant haplotype I51R59N108 - V431A436G437G581S613 deserve more attention. In areas of high SP resistance, the intervention still reduces low birthweight and maternal anaemia. SP should continue to be used in areas of high SP resistance until more effective alternatives for malaria chemoprevention are found. It is important to continuously monitor the molecular markers associated with SP resistance to better implement intermittent preventive treatment policies in pregnancy (IPTp) and infants (IPTi).

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Molecular Determinants of Sulfadoxine-Pyrimethamine Resistance in Plasmodium falciparum Isolates from Central Africa between 2016 and 2021: Wide Geographic Spread of Highly Mutated Pfdhfr and Pfdhps Alleles

Cited by 7 publications

References 39 publications

Geographical emergence of sulfadoxine-pyrimethamine drug resistance-associated P. falciparum and P. malariae alleles in co-existing Anopheles mosquito and asymptomatic human populations across Cameroon

Geographical emergence of sulfadoxine-pyrimethamine drug resistance-associated P. falciparum and P. malariae alleles in co-existing Anopheles mosquito and asymptomatic human populations across Cameroon

Prevalence of Molecular Markers of Sulfadoxine-pyrimethamine Resistance in Plasmodium falciparum Isolates from West Africa during 2012–2022

Prevalence of molecular markers of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates from West Africa during 2012–2022

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