Polymorphism Analysis of pfmdr1 and pfcrt from Plasmodium falciparum Isolates in Northwestern Nigeria Revealed the Major Markers Associated with Antimalarial Resistance

Suspicion of failure in the effectiveness of artemisinin-based combination therapies (currently the first-line treatment of malaria, worldwide) is leading to the unofficial use of alternative antimalarials, including chloroquine and sulfadoxine/pyrimethamine, across northern Nigeria. To facilitate evidence-based resistance management, antimalarial resistance mutations were investigated in Plasmodium falciparum multidrug resistance-1 (pfmdr1) and chloroquine resistance transporter (pfcrt), in isolates from Kano, northwestern Nigeria. Out of the 88 samples genotyped for pfmdr1N86Y mutation using PCR/restriction fragment length polymorphism, one sample contained the 86Y mutation (86Yfrequency = 1.14%). The analysis of 610 bp fragments of pfmdr1 from 16 isolates revealed two polymorphic sites and low haplotype diversity (Hd = 0.492), with only 86 Y mutations in one isolate, and 184 F replacements in five isolates (184Ffrequency = 31.25%). The analysis of 267 bp fragments of pfcrt isolates revealed high polymorphism (Hd = 0.719), with six haplotypes and seven non-synonymous polymorphic sites. Eleven isolates (61.11%) were chloroquine-resistant, CQR (C72V73I74E75T76 haplotype), two of which had an additional mutation, D57E. An additional sequence was CQR, but of the C72V73M74E75T76 haplotype, while the rest of the sequences (33.33%) were chloroquine susceptible (C72V73M74N75K76 haplotype). The findings of these well characterized resistance markers should be considered when designing resistance management strategies in the northwestern Nigeria.

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No Plasmodium falciparum Chloroquine Resistance Transporter and Artemisinin Resistance Mutations, Haiti

Emerging Infectious Diseases ◽

10.3201/eid2411.180738 ◽

2018 ◽

Vol 24 (11) ◽

pp. 2124-2126 ◽

Cited By ~ 1

Author(s):

Jeanne P. Vincent ◽

Kanako Komaki-Yasuda ◽

Alexandre V. Existe ◽

Jacques Boncy ◽

Shigeyuki Kano

Keyword(s):

Plasmodium Falciparum ◽

Artemisinin Resistance ◽

Chloroquine Resistance ◽

Resistance Mutations ◽

Chloroquine Resistance Transporter

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Molecular Mechanisms of Drug Resistance in Plasmodium falciparum Malaria

Annual Review of Microbiology ◽

10.1146/annurev-micro-020518-115546 ◽

2020 ◽

Vol 74 (1) ◽

pp. 431-454

Author(s):

Kathryn J. Wicht ◽

Sachel Mok ◽

David A. Fidock

Keyword(s):

Plasmodium Falciparum ◽

Molecular Mechanisms ◽

Artemisinin Resistance ◽

Plasmodium Falciparum Malaria ◽

Drug Binding ◽

Chloroquine Resistance ◽

Digestive Vacuole ◽

Vacuole Membrane ◽

Chloroquine Resistance Transporter ◽

Antimalarial Resistance

Understanding and controlling the spread of antimalarial resistance, particularly to artemisinin and its partner drugs, is a top priority. Plasmodium falciparum parasites resistant to chloroquine, amodiaquine, or piperaquine harbor mutations in the P. falciparum chloroquine resistance transporter (PfCRT), a transporter resident on the digestive vacuole membrane that in its variant forms can transport these weak-base 4-aminoquinoline drugs out of this acidic organelle, thus preventing these drugs from binding heme and inhibiting its detoxification. The structure of PfCRT, solved by cryogenic electron microscopy, shows mutations surrounding an electronegative central drug-binding cavity where they presumably interact with drugs and natural substrates to control transport. P. falciparum susceptibility to heme-binding antimalarials is also modulated by overexpression or mutations in the digestive vacuole membrane–bound ABC transporter PfMDR1 ( P. falciparum multidrug resistance 1 transporter). Artemisinin resistance is primarily mediated by mutations in P. falciparum Kelch13 protein (K13), a protein involved in multiple intracellular processes including endocytosis of hemoglobin, which is required for parasite growth and artemisinin activation. Combating drug-resistant malaria urgently requires the development of new antimalarial drugs with novel modes of action.

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The impact of HIV-associated immunosuppression on the Plasmodium falciparum chloroquine resistance transporter gene (PfCRT) of HIV patients in Akure, Nigeria

Bulletin of the National Research Centre ◽

10.1186/s42269-020-00401-0 ◽

2020 ◽

Vol 44 (1) ◽

Author(s):

Iyabo Adepeju Simon-Oke ◽

Adeola Olanireti Ade-Alao ◽

Foluso Ologundudu

Keyword(s):

Plasmodium Falciparum ◽

Malaria Prevalence ◽

Cd4 Count ◽

Chloroquine Resistance ◽

Hiv Care ◽

Transporter Gene ◽

Hiv Patients ◽

Chloroquine Resistance Transporter ◽

Hiv Test ◽

Low Prevalence

Abstract Background The study evaluated the prevalence of malaria and Plasmodium falciparum chloroquine resistance transporter gene (PfCRT) in HIV patients attending Specialist Hospital, Akure. This study was carried out between April and June 2019. Three hundred and seventeen (317) patients attending the antiretroviral clinic (ART) were involved, out of which 89 (28.08%) were males and 228 (71.92%) were females. HIV test was done using the Unigold® HIV test kit, malaria test was done using thick and thin blood smear, CD4 test was done using the Partec® CD4 counter and PCR was used to detect the presence of plasmodium falciparum mutant gene. The data obtained from this analysis was subjected to Pearson’s Chi-square test. Results The overall result showed low prevalence of malaria (23.03%) in the sampled patients. Highest malaria prevalence (31.0%) was recorded in HIV patients with CD4 count between 200–500 cells/μl of blood, with the males recording 24.7% malaria prevalence. The age group 20–29 years recorded the highest prevalence of 27.3%. A higher prevalence 91.1% of PfCRT gene in HIV-positive and (40.0%) in HIV-negative patients was recorded with 100% prevalence in patients with CD4 count ≤ 200. This shows that the low prevalence of malaria recorded in this study could be credited to good health-seeking attitude of HIV patients and the upscale of HIV care and treatment centres. Conclusion The high prevalence of PfCRT gene shows that treatment of malaria with chloroquine is still being practised despite the availability of artemisinin-based combination therapy (ACTs) as the recommended regimen for malaria treatment.

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Identification of a point mutation in the ace1 gene of Therioaphis trifolli maculata and detection of insecticide resistance by a diagnostic PCR–RFLP assay

Bulletin of Entomological Research ◽

10.1017/s0007485315000668 ◽

2015 ◽

Vol 105 (6) ◽

pp. 712-716

Author(s):

E. AlSuhaibani ◽

C.C. Voudouris ◽

R. Al-Atiyat ◽

A. Kotzamumin ◽

J. Vontas ◽

...

Keyword(s):

Saudi Arabia ◽

Insecticide Resistance ◽

Management Strategies ◽

Resistance Management ◽

Resistance Mutation ◽

Resistance Mechanisms ◽

Effective Control ◽

Agricultural Pests ◽

Resistance Mutations ◽

Diagnostic Pcr

AbstractAphids are important agricultural pests worldwide. Their control is largely based on chemical insecticides. One species that shows important invasive abilities and host-plant-related differences is Therioaphis trifolii (Monell) (Hemiptera: Aphididae). T. trifolii maculata, also known as spotted alfalfa aphid (SAA), can be very injurious to alfalfa crops in certain regions, such as in Saudi Arabia for effective control it is essential to diagnose and monitor the resistance mechanisms in the SAA populations. In the present study, we analysed acetylcholinesterase (ace) target site insensitivity mechanisms. A 650 bp length DNA containing the putative acetylcholinesterase (ace1) precursor was obtained and compared with other Hemipteran species. The sequences of many individual aphids collected from alfalfa crops in Saudi Arabia were analysed for the presence of resistance mutations: no resistance mutations were found at the resistance mutation loci 302; however, the presence of a serine–phenylalanine substitution (S431F) was identified in one individual. The S431F substitution, has been shown to confer significant levels of both organophosphate and carbamate resistance in other aphid species, and is now found for the first time in T. trifolii. We subsequently developed a simple polymerase chain reaction–restriction fragment length polymorphism assays for the S431F mutation, using a TaqI restriction site destroyed by the S431F mutation. The novel diagnostic assay may support the implementation of Insecticide Resistance Management strategies, for the control of SAA in alfalfa crops in the Kingdom of Saudi Arabia, and other countries worldwide.

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Survey of Plasmodium falciparum multidrug resistance-1 and chloroquine resistance transporter alleles in Haiti

Malaria Journal ◽

10.1186/1475-2875-12-426 ◽

2013 ◽

Vol 12 (1) ◽

pp. 426 ◽

Cited By ~ 20

Author(s):

Maha A ElBadry ◽

Alexandre Existe ◽

Yves S Victor ◽

Gladys Memnon ◽

Mark Fukuda ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Multidrug Resistance ◽

Chloroquine Resistance ◽

Chloroquine Resistance Transporter

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Acaricide resistance and mechanisms in Tetranychus urticae populations from greenhouses in Turkey

Systematic and Applied Acarology ◽

10.11158/saa.25.1.12 ◽

2020 ◽

Vol 25 (1) ◽

pp. 155-168

Author(s):

Yasin Nazım Alpkent ◽

Emre İnak ◽

Selçuk Ulusoy ◽

Recep Ay

Keyword(s):

Tetranychus Urticae ◽

Specific Activity ◽

Management Strategies ◽

Resistance Management ◽

Vegetable Production ◽

Resistance Mutations ◽

Climate Conditions ◽

Fast Development ◽

Control Failure ◽

Tetranychus Urticae Koch

Turkey has great potential in vegetable production especially in greenhouses. However, plant pests such as Tetranychus urticae Koch can cause significant yield losses with the contribution of suitable climate conditions of greenhouses that allow to fast development of spider mites. Although synthetic acaricides are the most preferred control tools to manage T. urticae populations in Turkey, control failure has often been reported because of its ability to quickly develop resistance. In this study, bifenthrin and hexythiazox toxicity over five field-collected strains were evaluated and mechanisms of resistance have also been investigated via biochemical and molecular methods. Resistance mutations in voltage gated sodium channel and chitin synthase I which are the target sites of bifenthrin and hexythiazox, respectively, were found in various strains. The specific activity of P450 and GST enzymes was significantly increased in all field-collected strains comparing with susceptible strain. In addition, synergists of P450 and esterase enzymes enhanced the bifenthrin and hexythiazox toxicity, respectively. The results of this study will contribute to design proper resistance management strategies in Turkish greenhouses.

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