SHORT REPORT: ASSOCIATION BETWEEN CHLOROQUINE AND AMODIAQUINE RESISTANCE AND ALLELIC VARIATION IN THE PLASMODIUM FALCIPARUM MULTIPLE DRUG RESISTANCE 1 GENE AND THE CHLOROQUINE RESISTANCE TRANSPORTER GENE IN ISOLATES FROM THE UPPER NILE IN SOUTHERN SUDAN

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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Rapid Selection of Plasmodium falciparum Chloroquine Resistance Transporter Gene and Multidrug Resistance Gene-1 Haplotypes Associated with Past Chloroquine and Present Artemether-Lumefantrine Use in Inhambane District, Southern Mozambique

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.12-0525 ◽

2013 ◽

Vol 88 (3) ◽

pp. 536-541 ◽

Cited By ~ 35

Author(s):

Thomas T. Thomsen ◽

Ib C. Bygbjerg ◽

Michael Alifrangis ◽

Elsa V. E. Tomás ◽

Derek Charlwood ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Multidrug Resistance ◽

Resistance Gene ◽

Chloroquine Resistance ◽

Transporter Gene ◽

Multidrug Resistance Gene ◽

Chloroquine Resistance Transporter ◽

Selection Of

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Prevalence of chloroquine and antifolate drug resistance alleles in Plasmodium falciparum clinical isolates from three areas in Ghana

AAS Open Research ◽

10.12688/aasopenres.12825.1 ◽

2018 ◽

Vol 1 ◽

pp. 1 ◽

Cited By ~ 2

Author(s):

James Abugri ◽

Felix Ansah ◽

Kwaku P. Asante ◽

Comfort N. Opoku ◽

Lucas A. Amenga-Etego ◽

...

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Chloroquine Resistance ◽

Published Data ◽

Nucleotide Polymorphisms ◽

Triple Mutant ◽

Chloroquine Resistance Transporter ◽

Significant Difference ◽

Quadruple Mutant ◽

Study Sites

Background: The emergence and spread of resistance in Plasmodium falciparum to chloroquine (CQ) and the antifolate drug sulfadoxine-pyrimethamine (SP) necessitated the change from CQ to artemisinin-based combination therapies (ACTs) as first-line drug for the management of uncomplicated malaria in Ghana in 2005. Methods: To examine the prevalence of molecular markers associated with CQ and antifolate drug resistance in Ghana, we genotyped single nucleotide polymorphisms (SNPs) in the P. falciparum chloroquine resistance transporter (pfcrt, PF3D7_0709000), multidrug resistance (pfmdr1, PF3D7_0523000), bifunctional dihydrofolate reductase-thymidylate synthase (pfdhfr, PF3D7_0417200) and dihydropteroate synthase (pfdhps, PF3D7_0810800) genes in children with malaria reporting to hospitals in three different epidemiological areas of Ghana (Accra, Kintampo and Navrongo) between 2012 and 2017. Results: The overall prevalence of the CQ resistance-associated pfcrt 76T allele was 8%, whereas pfmdr1 86Y and 184F alleles were present in 10% and 65% of infections respectively. Most of the isolates harboured the antifolate resistance-associated pfdhfr 51I, 59R and 108N alleles, including 68% of them with the triple mutant pfdhfr I51R59N108 combination. Pfdhps 437G and 540E were detected in 90.6% and 0.7% of infections, respectively. We observed no significant difference across the three study sites for all the polymorphisms except for pfdhps 437G, which was more common in Accra than at the other sites. Across both pfdhfr and pfdhps genes, a large proportion (61%) of the isolates harboured the quadruple mutant combination (I51R59N108/G437). Conclusion: Comparison of the present results to previously published data shows a significant decrease in the prevalence of CQ resistance alleles during the 12 years after CQ withdrawal, but an increase in the alleles that mediate SP resistance, which could be due to the continuous use of antifolate drugs for prophylaxis.

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Prevalence of chloroquine and antifolate drug resistance alleles in Plasmodium falciparum clinical isolates from three areas in Ghana

AAS Open Research ◽

10.12688/aasopenres.12825.2 ◽

2018 ◽

Vol 1 ◽

pp. 1

Author(s):

James Abugri ◽

Felix Ansah ◽

Kwaku P. Asante ◽

Comfort N. Opoku ◽

Lucas A. Amenga-Etego ◽

...

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Intermittent Preventive Treatment ◽

Preventive Treatment ◽

Chloroquine Resistance ◽

Nucleotide Polymorphisms ◽

Chloroquine Resistance Transporter ◽

Significant Difference ◽

Quadruple Mutant ◽

Study Sites

Background: The emergence and spread of resistance in Plasmodium falciparum to chloroquine (CQ) necessitated the change from CQ to artemisinin-based combination therapies (ACTs) as first-line drug for the management of uncomplicated malaria in Ghana in 2005. Sulphadoxine-pyrimethamine (SP) which was the second line antimalarial drug in Ghana, was now adopted for intermittent preventive treatment of malaria in pregnancy (IPTp). Methods: To examine the prevalence of molecular markers associated with CQ and antifolate drug resistance in Ghana, we employed restriction fragment length polymorphism polymerase chain reaction to genotype and compare single nucleotide polymorphisms (SNPs) in the P. falciparum chloroquine resistance transporter ( pfcrt, PF3D7_0709000), multidrug resistance ( pfmdr1, PF3D7_0523000), bifunctional dihydrofolate reductase-thymidylate synthase ( pfdhfr, PF3D7_0417200) and dihydropteroate synthase ( pfdhps, PF3D7_0810800) genes. Parasites were collected from children with malaria reporting to hospitals in three different epidemiological areas of Ghana (Accra, Kintampo and Navrongo) in 2012-2013 and 2016-2017. Results: The overall prevalence of the CQ resistance-associated pfcrt 76T allele was 8%, whereas pfmdr1 86Y and 184F alleles were present in 10.2% and 65.1% of infections, respectively. The majority of the isolates harboured the antifolate resistance-associated pfdhfr alleles 51I (83.4%), 59R (85.9 %) and 108N (90.5%). Pfdhps 437G and 540E were detected in 90.6% and 0.7% of infections, respectively. We observed no significant difference across the three study sites for all the polymorphisms except for pfdhps 437G, which was more common in Accra compared to Kintampo for the 2016-2017 isolates. Across both pfdhfr and pfdhps genes, a large proportion (61%) of the isolates harboured the quadruple mutant combination (I 51 R 59 N 108/ G 437). CQ resistance alleles decreased during the 12 years after CQ withdrawal, but an mediate SP resistance alleles increased. Conclusion: Surveillance of the prevalence of resistance alleles is necessary in monitoring the efficacy of antimalarial drugs.

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