Molecular Epidemiology of Plasmodium falciparum Chloroquine Resistance Transporter Genes among School Children in Kwara State, Southwestern Nigeria

Background: Plasmodium falciparum existence continues to develop resistance to conventional antimalaria drugs in malaria endemic areas. Plasmodia often prevent drugs from interacting with the target site, hence, developing resistance to antimalaria drugs. Mutations in the Plasmodium falciparum chloroquine resistance transporter (Pfcrt), are the major determinant of chloroquine resistance in human malaria parasite. Methodology: Malaria infection, Pfcrt and Pfmdr1 genes of isolates among school students within the age range of 11-22 years from four selected rural communities of Kwara state were studied. One hundred and eighty seven subjects (187) were selected for the study. Blood samples were collected by finger prick method for malaria screening. Nested PCR and restriction fragment length polymorphism (RFLP) were done to detect alleles of pfcrt at codon 76 and pfmdr1 at codon 86. DNA of isolates was appropriately extracted from the filter paper blots using the methanol fixation method. Logistic regression was performed on the binary observations obtained while linear regression was conducted on the fifty (50) subjects that tested positive to malaria. Results: Out of 187 subjects screened, 26.7% (50) were positive to P. falciparum. Highest malaria parasite count of 36.4% was recorded in 14-16 years age group while 20-22 years age group had the least malaria parasite count (15.4%). The result of the studied isolates indicated that out of 50 isolates analyzed for Pfcrt gene, wild type alleles accounted for 32% (16) while mutant alleles accounted for 68% (34). Alakuko Community accounted for the least number of T76 mutant alleles 10% (5) while Apado community recorded the highest number of T76 mutant gene 22% (11). For Pfmdr1 gene analysis at codon 86, isolates from Apado community showed the highest mutant type alleles (Y86) of 22% (11), while Igbonla community in Ifelodun local government had the least mutant alleles, 6% (3). Conclusion: The overall result revealed existence of mutant alleles in both the Pfcrt and Pfmdr1 genes which was higher than the wild type gene in both cases. The presence of chloroquine resistance genes among the studied population implies that alternative antimalaria drugs should be designed by pharmaceutical industry.

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1H-NMR metabolite profiles of different strains of Plasmodium falciparum

Bioscience Reports ◽

10.1042/bsr20140134 ◽

2014 ◽

Vol 34 (6) ◽

Cited By ~ 18

Author(s):

Rongwei Teng ◽

Adele M. Lehane ◽

Markus Winterberg ◽

Sarah H. Shafik ◽

Robert L. Summers ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Amino Acid ◽

Red Blood Cells ◽

Blood Cells ◽

Malaria Parasite ◽

Chloroquine Resistance ◽

Chloroquine Resistance Transporter ◽

Metabolite Profiles ◽

Amino Acid Profiles ◽

Different Strains

The metabolite profiles of red blood cells infected with different malaria parasite strains were compared. Amino acid profiles varied with the chloroquine resistance status of the strain, and this was linked specifically to mutations in the parasite's chloroquine resistance transporter.

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Plasmodium falciparum chloroquine resistance transporter is a H+-coupled polyspecific nutrient and drug exporter

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1417102112 ◽

2015 ◽

Vol 112 (11) ◽

pp. 3356-3361 ◽

Cited By ~ 45

Author(s):

Narinobu Juge ◽

Sawako Moriyama ◽

Takaaki Miyaji ◽

Mamiyo Kawakami ◽

Haruka Iwai ◽

...

Keyword(s):

Amino Acids ◽

Plasmodium Falciparum ◽

Amino Acid ◽

Amino Acid Transport ◽

Malaria Parasite ◽

Proton Gradient ◽

Chloroquine Resistance ◽

Acid Transport ◽

Chloroquine Resistance Transporter ◽

Physiological Relevance

Extrusion of chloroquine (CQ) from digestive vacuoles through the Plasmodium falciparum CQ resistance transporter (PfCRT) is essential to establish CQ resistance of the malaria parasite. However, the physiological relevance of PfCRT and how CQ-resistant PfCRT gains the ability to transport CQ remain unknown. We prepared proteoliposomes containing purified CQ-sensitive and CQ-resistant PfCRTs and measured their transport activities. All PfCRTs tested actively took up tetraethylammonium, verapamil, CQ, basic amino acids, polypeptides, and polyamines at the expense of an electrochemical proton gradient. CQ-resistant PfCRT exhibited decreased affinity for CQ, resulting in increased CQ uptake. Furthermore, CQ competitively inhibited amino acid transport. Thus, PfCRT is a H+-coupled polyspecific nutrient and drug exporter.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03908-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 730-733 ◽

Cited By ~ 13

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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