High frequency of PfCRT 76T in two Malian villages and its prevalence in severe relative to non-severe malaria

Wele, Mamadou; Djimdé, Abdoulaye; Guindo, Aldiouma; Béavogui, Abdoul Habib; Traoré, Isaac Z.; Sadou, Aboubacar; Blaise, Dackouo; Diallo, Dapa A.; Wellems, Thomas E.; Doumbo, Ogobara K.

doi:10.1016/j.actatropica.2011.01.002

Cited by 13 publications

(7 citation statements)

References 16 publications

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“…Low levels of resistance have also been reported in Myanmar, South Korea, Vietnam, India, Turkey, Ethiopia, and in regions of Southern Africa and South America [ 3 , 8 , 9 ]. The occurrence of severe vivax malaria and patient’s deaths has been reported in Brazil [ 10 - 12 ] raising the possibility of an association between malaria severity and drug resistance [ 13 ]. In areas of CQ resistance, treatment of uncomplicated P. falciparum malaria is carried out with artemisinin-based combination therapy (ACT) [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Plasmodium vivax and Plasmodium falciparum ex vivo susceptibility to anti-malarials and gene characterization in Rondônia, West Amazon, Brazil

Aguiar

Pereira²,

Amaral

et al. 2014

Malar J

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BackgroundChloroquine (CQ), a cost effective antimalarial drug with a relatively good safety profile and therapeutic index, is no longer used by itself to treat patients with Plasmodium falciparum due to CQ-resistant strains. P. vivax, representing over 90% of malaria cases in Brazil, despite reported resistance, is treated with CQ as well as with primaquine to block malaria transmission and avoid late P. vivax malaria relapses. Resistance to CQ and other antimalarial drugs influences malaria control, thus monitoring resistance phenotype by parasite genotyping is helpful in endemic areas.MethodsA total of 47 P. vivax and nine P. falciparum fresh isolates were genetically characterized and tested for CQ, mefloquine (MQ) and artesunate (ART) susceptibility in vitro. The genes mdr1 and pfcrt, likely related to CQ resistance, were analyzed in all isolates. Drug susceptibility was determined using short-term parasite cultures of ring stages for 48 to 72 hour and thick blood smears counts. Each parasite isolate was tested with the antimalarials to measure the geometric mean of 50% inhibitory concentration.ResultsThe low numbers of P. falciparum isolates reflect the species prevalence in Brazil; most displayed low sensitivity to CQ (IC50 70 nM). However, CQ resistance was rare among P. vivax isolates (IC50 of 32 nM). The majority of P. vivax and P. falciparum isolates were sensitive to ART and MQ. One hundred percent of P. falciparum isolates carried non-synonymous mutations in the pfmdr1 gene in codons 184, 1042 and 1246, 84% in codons 1034 and none in codon 86, a well-known resistance mutation. For the pfcrt gene, mutations were observed in codons 72 and 76 in all P. falciparum isolates. One P. falciparum isolate from Angola, Africa, showing sensitivity to the antimalarials, presented no mutations. In P. vivax, mutations of pvmdr1 and the multidrug resistance gene 1 marker at codon F976 were absent.ConclusionAll P. falciparum Brazilian isolates showed CQ resistance and presented non-synonymous mutations in pfmdr1 and pfcrt. CQ resistant genotypes were not present among P. vivax isolates and the IC50 values were low in all samples of the Brazilian West Amazon.

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Section: Introductionmentioning

confidence: 99%

Plasmodium vivax and Plasmodium falciparum ex vivo susceptibility to anti-malarials and gene characterization in Rondônia, West Amazon, Brazil

Aguiar

Pereira²,

Amaral

et al. 2014

Malar J

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“…Similarly, gene mutations incriminated in CQ and antifolate drug resistance had no association with complicated malaria [208] . In contrast, there was significant association of Pfcrt (codon 76) mutation and malaria severity in both groups of patients (children 5 years or younger and above 5 years) [209] .…”

Section: Virulence Pathogenesis and Clinical Manifestantionsmentioning

confidence: 59%

Gene mutations in parasitic diseases Part II: Parasite gene mutations

Abaza

El-Tonsy

2017

Parasitologists United Journal

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Gene mutation may occur either in the parasite or in the host, which may be beneficial or harmful for each. As we previously discussed, part I covered causes and types of gene mutations as well as their relation(s) to or effect(s) on parasitic diseases; part II deals with parasite gene mutations. The most apparent manifestation is drug resistance especially with anti-malarial drugs for falciparum malaria. The majority of P. falciparum isolates are able to undergo gene mutations in genes encoding enzymes that control drug uptake. Parasite gene mutations are suggested to influence parasite virulence in toxoplasmosis and malignant malaria, and to have impact on the occurrence of malignancy in schistosomiasis and clonorchiasis. It is intended in the present review to present mechanism(s) of drug resistance due to parasite gene mutations, with special emphasis on anti-malarial drugs, albendazole, metronidazole, and other drugs used in treatment of African trypanosomiasis and toxoplasmosis. The review also presents other effects of parasite gene mutations on disease outcome and progress as well as occurrence of false diagnosis in falciparum malaria using ICTs utelizing histidine rich protein.

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“…The association between the pfcrt 76T mutation and the host's age is controversial, where some studies have showed a signi cant association (May and Meyer 2003;Happi et al 2006 As regards a link with parasite density, the current study found that the percentages of the pfcrt 74I and 75E mutations and the CVIET mutant haplotype were signi cantly high in isolates from patients with a low parasitaemia level. Although the reason for these associations is unclear, previous studies reported signi cant associations of pfcrt mutations (particularly 76T) with parasitaemia and severity of infection (Al-Mekhla et al 2011;Wélé et al 2011;Atroosh et al 2012;Acharya et al 2018;Cuu et al 2020). However, another study found no signi cant association (Mayengue et al 2007;Atroosh et al 2016).…”

Section: Discussionmentioning

confidence: 98%

The return of chloroquine-sensitive Plasmodium falciparum parasites in Jazan Region, Southwestern Saudi Arabia over a decade after the adoption of artemisinin-based combination therapy: analysis of genetic mutations in the pfcrt gene

Madkhali

Atroosh

Ghzwani

et al. 2021

Preprint

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This study investigated the polymorphism in the P. falciparum chloroquine resistance transporter (pfcrt) gene 11 years after chloroquine (CQ) cessation in Jazan region, southwestern Saudi Arabia. Two hundred and thirty-five P. falciparum isolates were amplified to detect mutations in the pfcrt gene. The pfcrt 76T molecular marker for CQ resistance was detected in 66.4% (156/235) of the isolates, while the K76 CQ-sensitive wild type was detected in 33.6%. The pfcrt 74I and pfcrt 75E point mutations were each found to be present in 56.2% of isolates, while only four isolates (1.7%) were found to carry the pfcrt 72S mutation. Moreover, four pfcrt haplotypes were identified: the CVIET triple-allele (56.2%), SVMET double-allele (1.7%), and CVMNT single-allele (8.5%) mutant haplotypes, and the CVMNK wild haplotype (33.6%). The analysis also revealed significant associations between the prevalence of mutant pfcrt alleles and haplotypes and the age group, governorate, and nationality of the patients as well as the parasitaemia level (P < 0.05). The findings provide evidence of the potential re-emergence of CQ-susceptible P. falciparum strains in Jazan region over a decade after CQ discontinuation, with about one third of the isolates analysed carrying the pfcrt K76 CQ-sensitive wild allele and the CVMNK ancestral wild haplotype. Although the reintroduction of CQ cannot be recommended at present in Saudi Arabia, these findings support the rationale for a potential future role for CQ in malaria treatment. Therefore, continuous molecular and in-vitro monitoring mutations of pfcrt polymorphism in Jazan region is highly recommended.

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High frequency of PfCRT 76T in two Malian villages and its prevalence in severe relative to non-severe malaria

Cited by 13 publications

References 16 publications

Plasmodium vivax and Plasmodium falciparum ex vivo susceptibility to anti-malarials and gene characterization in Rondônia, West Amazon, Brazil

Plasmodium vivax and Plasmodium falciparum ex vivo susceptibility to anti-malarials and gene characterization in Rondônia, West Amazon, Brazil

Gene mutations in parasitic diseases Part II: Parasite gene mutations

The return of chloroquine-sensitive Plasmodium falciparum parasites in Jazan Region, Southwestern Saudi Arabia over a decade after the adoption of artemisinin-based combination therapy: analysis of genetic mutations in the pfcrt gene

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