Antifolates can have a role in the treatment of Plasmodium vivax

Hawkins, Vivian; Joshi, Hema; Rungsihirunrat, Kanchana; Na‐Bangchang, Kesara; Sibley, Carol Hopkins

doi:10.1016/j.pt.2007.03.002

Cited by 94 publications

(112 citation statements)

References 62 publications

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“…The six synonymous point mutations were AAC to AAT (both coding for Asn) at codon 50, and GGT to GGG (both coding for Gly) at codons 89, 94, 95, 100, and 101, respectively. Point mutations at the latter five codons have not been reported 16 and were found in 35 (28.7%) samples. Nonsynonymous mutations were detected at positions 57, 58, 61, and 117, and the point mutation at codon 173 was not observed in our samples ( Table 1 ).…”

Section: Resultsmentioning

confidence: 90%

“…Although antifolate drugs have not been recommended for treating P. vivax malaria, recent studies suggest that this family of drugs may find a role in future treatment of P. vivax malaria in certain regions. 16,37 In this study, we have analyzed pvdhfr and pvdhps mutations in two P. vivax populations from both temperate zone and subtropical provinces of China. Our study showed …”

Section: Discussionmentioning

confidence: 99%

“…16 In Thailand where antifolates have been used heavily since the 1970s as a replacement of CQ for treating P . falciparum malaria, quadruple pvdhfr mutations and double pvdhps mutations have reached prevalences of approximately 60% and 72%, respectively, especially in P. vivax populations along Thailand-Myanmar border areas.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 Because P. vivax cannot be cultured continuously, antifolate resistance studies have relied heavily on molecular genotyping and drug assays in heterologous systems expressing parasite DHFR and DHPS. 16 Molecular genotyping of pvdhfr and pvdhps has been performed in many P . vivax -endemic areas.…”

Section: Introductionmentioning

confidence: 99%

“…vivax -endemic areas. 16 To date, some 20 mutations have been detected in pvdhfr ; among them mutations at codons 57, 58, 61, 117, and 173, corresponding to positions 50, 51, 59, 108 and 164 in pfdhfr , respectively, are associated with pyrimethamine resistance. [17][18][19][20] A structural study has confirmed that the most common mutations (S58R and S117N) cause structural changes in P .…”

Section: Introductionmentioning

confidence: 99%

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Different Allele Prevalence in the Dihydrofolate Reductase and Dihydropteroate Synthase Genes in Plasmodium vivax Populations from China

Miao

Zhou

Cui

et al. 2010

The American Society of Tropical Medicine and Hygiene

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Abstract. Antifolate resistance in Plasmodium vivax is caused by point mutations in genes encoding dihydrofolate reductase ( pvdhfr ) and dihydropteroate synthase ( pvdhps ). In this study, we used direct sequencing to survey pvdhfr and pvdhps mutations in 122 clinical P. vivax isolates from a central and a southern province of China. For pvdhfr , 36.9% were wild-type, whereas mutations were detected at four codons (57, 58, 61, and 117). The S117N/T mutation was the most prevalent (48.4%), followed by the T61M mutation (18.9%). Six pvdhfr mutant alleles were found, ranging from 37.7% to 0.8%. The dramatically different pvdhfr allele frequencies between the two P. vivax populations might be caused by different drug histories or intrinsic difference between temperate and subtropical strains. In contrast, except polymorphisms within a repeat region, no resistance-conferring mutations were detected in pvdhps . Our result suggests that P. vivax populations in China may be relatively susceptible to sulfadoxine-pyrimethamine.

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Section: Resultsmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Different Allele Prevalence in the Dihydrofolate Reductase and Dihydropteroate Synthase Genes in Plasmodium vivax Populations from China

Miao

Zhou

Cui

et al. 2010

The American Society of Tropical Medicine and Hygiene

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NMR‐derived folate‐bound structure of dihydrofolate reductase 1 from the halophile Haloferax volcanii

Boroujerdi

Young

2008

Biopolymers

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Folate binds to dihydrofolate reductase (DHFR) to form a binary complex whose structure maintains the overall configuration of the enzyme; however, some significant changes are evident when a comparison is made to the enzyme. The structure of DHFR1 from the halophilic Halopherax volcanii was solved in its folate-bound form using nuclear magnetic resonance spectroscopy. NOE data obtained from the (15)N-NOESY-HSQC and (13)C-NOESY-HSQC experiments of the triply labeled ((1)H, (13)C, and (15)N) binary complex were used as input for the structure calculation with the Crystallography and Nuclear Magnetic Resonance System program. The resulting family of structures was compared with the enzyme solved by both nuclear magnetic resonance and X-ray crystallography and also to the mesophilic folate-bound enzyme from Escherichia coli. The binary complex exhibited less convergence of structure in the alpha2-helix and differences in the hinge residues D39 and A94. In comparison to the previously reported mesophilic binary complex solved by X-ray crystallography, the halophilic binary complex reported here does not agree with the convergence of the M20 loop to a single structure. The corresponding L21 loop of the halophilic binary complex family of structures solved by nuclear magnetic resonance indicates variability in this region.

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Global scenario of Plasmodium vivax occurrence and resistance pattern

2022

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Malaria caused by Plasmodium vivax is comparatively less virulent than Plasmodium falciparum, which can also lead to severe disease and death. It shows a wide geographical distribution. Chloroquine serves as a drug of choice, with primaquine as a radical cure. However, with the appearance of resistance to chloroquine and treatment has been shifted to artemisinin combination therapy followed by primaquine as a radical cure. Sulphadoxine‐pyrimethamine, mefloquine, and atovaquone‐proguanil are other drugs of choice in chloroquine‐resistant areas, and later resistance was soon reported for these drugs also. The emergence of drug resistance serves as a major hurdle to controlling and eliminating malaria. The discovery of robust molecular markers and regular surveillance for the presence of mutations in malaria‐endemic areas would serve as a helpful tool to combat drug resistance. Here, in this review, we will discuss the endemicity of P. vivax, a historical overview of antimalarial drugs, the appearance of drug resistance and molecular markers with their global distribution along with different measures taken to reduce malaria burden due to P. vivax infection and their resistance.

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Antifolates can have a role in the treatment of Plasmodium vivax

Cited by 94 publications

References 62 publications

Different Allele Prevalence in the Dihydrofolate Reductase and Dihydropteroate Synthase Genes in Plasmodium vivax Populations from China

Different Allele Prevalence in the Dihydrofolate Reductase and Dihydropteroate Synthase Genes in Plasmodium vivax Populations from China

NMR‐derived folate‐bound structure of dihydrofolate reductase 1 from the halophile Haloferax volcanii

Global scenario of Plasmodium vivax occurrence and resistance pattern

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