scholarly journals Analysis of gene mutations involved in chloroquine resistance in Plasmodium falciparum parasites isolated from patients in the southwest of Saudi Arabia

2010 ◽  
Vol 30 (3) ◽  
pp. 187-192 ◽  
Author(s):  
Saad M. Bin Dajem ◽  
Ahmed Al-Qahtani
Keyword(s):  
Plasmodium Falciparum ◽  
Saudi Arabia ◽  
Gene Mutations ◽  
Chloroquine Resistance

scholarly journals Molecular Analysis of Targeted Insecticide Resistance Gene Mutations in Field-Caught Mosquitos of Medical Importance From Saudi Arabia

2021 ◽  
Author(s):  
Yuan Fang ◽  
Ernest Tambo ◽  
Jing-Bo Xue ◽  
Yi Zhang ◽  
Xiao-Nong Zhou ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Insecticide Resistance ◽  
Resistance Gene ◽  
Phylogenetic Analyses ◽  
Gene Mutations ◽  
Mosquito Vector ◽  
Dengue Disease ◽  
The Status ◽  
History Of ◽  
Exon 20

Abstract Gene mutations on target sites can be a valuable indicator of the status of insecticide resistance. Jeddah, a global commercial and major port-of-entry city, is bearing the brunt of dengue disease burden in Saudi Arabia. In the current study, six genotypes of three codon combinations (989, 1016, and 1534) were observed on voltage-gated sodium channel (VGSC) gene in Jeddah’s Aedes aegypti population, with PGF/PGC as the dominant one. Two types of introns between exon 20 and 21 on VGSC have been identified for the first time in Ae. aegypti in Saudi Arabia. Statistical and phylogenetic analyses showed that the intron type was significantly associated with the 1016 allele and may reflect the history of insecticide treatment in different continents. In addition, fixation of the L1014F allele on VGSC and G119S on acetylcholinesterase 1 gene was detected in local Culex quinquefasciatus populations, with frequencies of 95.24 and 100%, respectively. To the best of our knowledge, this is the first report of resistant-associated mutations in field-caught Cx. quinquefasciatus in Saudi Arabia. The high prevalence of insecticide resistance gene mutations in local primary mosquito vector species highlights the urgent need to carry out comprehensive insecticide resistance surveillance in Saudi Arabia.

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

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.

scholarly journals Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Ommer Mohammed Dafalla ◽  
Mohammed Alzahrani ◽  
Ahmed Sahli ◽  
Mohammed Abdulla Al Helal ◽  
Mohammad Mohammad Alhazmi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Saudi Arabia ◽  
Parasite Clearance ◽  
Sub Saharan Africa ◽  
Local Alignment ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Synonymous Mutations ◽  
Search Tool ◽  
Sub Saharan

Abstract Background Artemisinin-based combination therapy (ACT) is recommended at the initial phase for treatment of Plasmodium falciparum, to reduce morbidity and mortality in all countries where malaria is endemic. Polymorphism in portions of P. falciparum gene encoding kelch (K13)-propeller domains is associated with delayed parasite clearance after ACT. Of about 124 different non-synonymous mutations, 46 have been identified in Southeast Asia (SEA), 62 in sub-Saharan Africa (SSA) and 16 in both the regions. This is the first study designed to analyse the prevalence of polymorphism in the P. falciparum k13-propeller domain in the Jazan region of southwest Saudi Arabia, where malaria is endemic. Methods One-hundred and forty P. falciparum samples were collected from Jazan region of southwest Saudi Arabia at three different times: 20 samples in 2011, 40 samples in 2016 and 80 samples in 2020 after the implementation of ACT. Plasmodium falciparum kelch13 (k13) gene DNA was extracted, amplified, sequenced, and analysed using a basic local alignment search tool (BLAST). Results This study obtained 51 non-synonymous (NS) mutations in three time groups, divided as follows: 6 single nucleotide polymorphisms (SNPs) ‘11.8%’ in samples collected in 2011 only, 3 (5.9%) in 2011and 2016, 5 (9.8%) in 2011 and 2020, 5 (9.8%) in 2016 only, 8 (15.7%) in 2016 and 2020, 14 (27.5%) in 2020 and 10 (19.6%) in all the groups. The BLAST revealed that the 2011 isolates were genetically closer to African isolates (53.3%) than Asian ones (46.7%). Interestingly, this proportion changed completely in 2020, to become closer to Asian isolates (81.6%) than to African ones (18.4%). Conclusions Despite the diversity of the identified mutations in the k13-propeller gene, these data did not report widespread artemisinin-resistant polymorphisms in the Jazan region where these samples were collected. Such a process would be expected to increase frequencies of mutations associated with the resistance of ACT.

scholarly journals Emergence and Spread of kelch13 Mutations Associated with Artemisinin Resistance in Plasmodium falciparum Parasites in 12 Thai Provinces from 2007 to 2016

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Theerayot Kobasa ◽  
Eldin Talundzic ◽  
Rungniran Sug-aram ◽  
Patcharida Boondat ◽  
Ira F. Goldman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Gene Mutations ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
Resistance Mutations ◽  
Content Type ◽  
Artemisinin Derivatives ◽  
Reduced Ring ◽  
Control And Prevention ◽  
Greater Mekong Subregion

ABSTRACT Artemisinin-based combination therapy (ACT) is the most effective and widely used treatment for uncomplicated Plasmodium falciparum malaria and is a cornerstone for malaria control and prevention globally. Resistance to artemisinin derivatives has been confirmed in the Greater Mekong Subregion (GMS) and manifests as slow parasite clearance in patients and reduced ring stage susceptibility to artemisinins in survival assays. The P. falciparum kelch13 gene mutations associated with artemisinin-resistant parasites are now widespread in the GMS. We genotyped 277 samples collected during an observational study from 2012 to 2016 from eight provinces in Thailand to identify P. falciparum kelch13 mutations. The results were combined with previously reported genotyping results from Thailand to construct a map illustrating the evolution of P. falciparum kelch13 mutations from 2007 to 2016 in that country. Different mutant alleles were found in strains with different geographical origins. The artemisinin resistance-conferring Y493H and R539T mutations were detected mainly in eastern Thailand (bordering Cambodia), while P574L was found only in western Thailand and R561H only in northwestern Thailand. The C580Y mutation was found across the entire country and was nearing fixation along the Thai-Cambodia border. Overall, the prevalence of artemisinin resistance mutations increased over the last 10 years across Thailand, especially along the Thai-Cambodia border. Molecular surveillance and therapeutic efficacy monitoring should be intensified in the region to further assess the extent and spread of artemisinin resistance.

scholarly journals The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics

2007 ◽  
Vol 6 (1) ◽  
pp. 108 ◽  
Author(s):  
Ishraga E A-Elbasit ◽  
Michael Alifrangis ◽  
Insaf F Khalil ◽  
Ib C Bygbjerg ◽  
Emad M Masuadi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dihydrofolate Reductase ◽  
Gene Mutations

Role of pfmdr1 mutations on chloroquine resistance in Plasmodium falciparum isolates with pfcrt K76T from Papua New Guinea

Acta Tropica ◽  
2006 ◽  
Vol 98 (2) ◽  
pp. 137-144 ◽  
Author(s):  
Toshihiro Mita ◽  
Akira Kaneko ◽  
Francis Hombhanje ◽  
Ilomo Hwaihwanje ◽  
Nobuyuki Takahashi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Papua New Guinea ◽  
New Guinea ◽  
Chloroquine Resistance

scholarly journals Piperaquine resistant Cambodian Plasmodium falciparum clinical isolates: in vitro genotypic and phenotypic characterization

2020 ◽  
Author(s):  
Nonlawat Boonyalai ◽  
Brian A Vesely ◽  
Chatchadaporn Thamnurak ◽  
Chantida Praditpol ◽  
Watcharintorn Fagnark ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Copy Number ◽  
Drug Susceptibility ◽  
Antagonistic Activity ◽  
Drug Combinations ◽  
Chloroquine Resistance ◽  
Phenotypic Characterization ◽  
Field Isolates

Abstract Background High rates of dihydroartemisinin-piperaquine (DHA-PPQ) treatment failures have been documented for uncomplicated Plasmodium falciparum in Cambodia. The genetic markers plasmepsin 2 ( pfpm2 ), exonuclease ( pfexo ) and chloroquine resistance transporter ( pfcrt ) genes are associated with PPQ resistance and are used for monitoring the prevalence of drug resistance and guiding malaria drug treatment policy.Methods To examine the relative contribution of each marker to PPQ resistance, in vitro culture and the PPQ survival assay were performed on seventeen P. falciparum isolates from northern Cambodia, and the presence of E415G-Exo and pfcrt mutations (T93S, H97Y, F145I, I218F, M343L, C350R, and G353V) as well as pfpm2 copy number polymorphisms were determined. Parasites were then cloned by limiting dilution and the cloned parasites were tested for drug susceptibility. Isobolographic analysis of several drug combinations for standard clones and newly cloned P. falciparum Cambodian isolates was also determined.Results The characterization of culture-adapted isolates revealed that the presence of novel pfcrt mutations (T93S, H97Y, F145I, and I218F) with E415G-Exo mutation can confer PPQ-resistance, in the absence of pfpm2 amplification. In vitro testing of PPQ resistant parasites demonstrated a bimodal dose-response, the existence of a swollen digestive vacuole phenotype, and an increased susceptibility to quinine, chloroquine, mefloquine and lumefantrine. To further characterize drug sensitivity, parental parasites were cloned in which a clonal line, 14-B5, was identified as sensitive to artemisinin and piperaquine, but resistant to chloroquine. Assessment of the clone against a panel of drug combinations revealed antagonistic activity for six different drug combinations. However, mefloquine-proguanil and atovoquone-proguanil combinations revealed synergistic antimalarial activity.Conclusions Surveillance for PPQ resistance in regions relying on DHA-PPQ as the first-line treatment is dependent on the monitoring of molecular markers of drug resistance. P. falciparum harbouring novel pfcrt mutations with E415G-exo mutations displayed PPQ resistant phenotype. The presence of pfpm2 amplification was not required to render parasites PPQ resistant suggesting that the increase in pfpm2 copy number alone is not the sole modulator of PPQ resistance. Genetic background of circulating field isolates appear to play a role in drug susceptibility and biological responses induced by drug combinations. The use of latest field isolates may be necessary for assessment of relevant drug combinations against P. falciparum strains and when down-selecting novel drug candidates.

scholarly journals Reduced Polymorphism in the Kelch Propeller Domain in Plasmodium vivax Isolates from Cambodia

2014 ◽  
Vol 59 (1) ◽  
pp. 730-733 ◽  
Author(s):  
Jean Popovici ◽  
Sokheng Kao ◽  
Leanghor Eal ◽  
Sophalai Bin ◽  
Saorin Kim ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Preliminary Data ◽  
Mutant Allele ◽  
Chloroquine Resistance ◽  
Wild Type ◽  
Nonsynonymous Mutation ◽  
Content Type

ABSTRACTPolymorphism in the ortholog gene of thePlasmodium falciparumK13 gene was investigated inPlasmodium vivaxisolates collected in Cambodia. All of them were Sal-1 wild-type alleles except two (2/284, 0.7%), andP. vivaxK12 polymorphism was reduced compared to that of theP. falciparumK13 gene. Both mutant allele isolates had the same nonsynonymous mutation at codon 552 (V552I) and were from Ratanak Kiri province. These preliminary data should encourage additional studies for associating artemisinin or chloroquine resistance and K12 polymorphism.

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