scholarly journals Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Abel O. Idowu ◽  
Wellington A. Oyibo ◽  
Sanjib Bhattacharyya ◽  
Manjeet Khubbar ◽  
Udoma E. Mendie ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Clinical Isolates ◽  
Chloroquine Resistance ◽  
Malaria Therapy ◽  
Chloroquine Resistance Transporter ◽  
Rare Mutations ◽  
High Prevalence ◽  
Resistance Markers ◽  
Next Generation Sequencing Ngs ◽  
Effective Drugs

Abstract Background Plasmodium falciparum, the deadliest causative agent of malaria, has high prevalence in Nigeria. Drug resistance causing failure of previously effective drugs has compromised anti-malarial treatment. On this basis, there is need for a proactive surveillance for resistance markers to the currently recommended artemisinin-based combination therapy (ACT), for early detection of resistance before it become widespread. Methods This study assessed anti-malarial resistance genes polymorphism in patients with uncomplicated P. falciparum malaria in Lagos, Nigeria. Sanger and Next Generation Sequencing (NGS) methods were used to screen for mutations in thirty-seven malaria positive blood samples targeting the P. falciparum chloroquine-resistance transporter (Pfcrt), P. falciparum multidrug-resistance 1 (Pfmdr1), and P. falciparum kelch 13 (Pfk13) genes, which have been previously associated with anti-malarial resistance. Results Expectedly, the NGS method was more proficient, detecting six Pfmdr1, seven Pfcrt and three Pfk13 mutations in the studied clinical isolates from Nigeria, a malaria endemic area. These mutations included rare Pfmdr1 mutations, N504K, N649D, F938Y and S967N, which were previously unreported. In addition, there was moderate prevalence of the K76T mutation (34.6%) associated with chloroquine and amodiaquine resistance, and high prevalence of the N86 wild type allele (92.3%) associated with lumefantrine resistance. Conclusion Widespread circulation of mutations associated with resistance to current anti-malarial drugs could potentially limit effective malaria therapy in endemic populations.

Prevalence of Mutant Alleles Responsible for Chloroquine Resistance among Plasmodium falciparum Isolates in North Central, Nigeria

2019 ◽  
pp. 1-8
Author(s):  
H. A. Edogun ◽  
G. O. Daramola ◽  
A. O. Ojerinde ◽  
C. O. Esan ◽  
A. T. Adegbuyi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Artemisinin Combination Therapy ◽  
Chloroquine Resistance ◽  
Current Status ◽  
Self Medication ◽  
Nested Polymerase Chain Reaction ◽  
Chloroquine Resistance Transporter ◽  
Whatman Filter Paper ◽  
High Prevalence ◽  
Detection Of Mutations

Background: Although chloroquine (CQ) has been officially replaced with artemisinin combination therapy (ACT) as first line drug for the treatment of malaria in Nigeria since 2005, a lot of people still believe that chloroquine is more effective chiefly because of the decline in the sensitivity of Plasmodium falciparum to ACT. Thus resulting into unofficial use of CQ for self medication. This study was conducted in order to survey the current status of chloroquine resistant strains of pfcrt and pfmdr1 in view of possible re-introduction of chloroquine for malaria treatment. Methods: DNA was extracted from one hundred (100) microscopically confirmed Plasmodium falciparum positive blood samples spotted on 3 mm Whatman filter paper. The detection of mutations in Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and Plasmodium falciparum multidrug resistance (Pfmdr1) genes was performed by nested polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). Results: Results showed the presence of mutant alleles of Pfcrt and Pfmdr1 in 60% and 41% of the samples respectively. However, there was no significant correlation in the prevalence of mutant alleles (T76/Y86) in relation to gender (p = 0.59/ 0.08) and age (p=0.59/0.93) of participants respectively. Conclusion: The observed high prevalence of chloroquine resistance despite thirteen years of withdrawal calls for serious concern.

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

2013 ◽  
Vol 12 (1) ◽  
pp. 426 ◽  
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

scholarly journals High Prevalence of Markers for Sulfadoxine and Pyrimethamine Resistance in Plasmodium falciparum in the Absence of Drug Pressure in the Ashanti Region of Ghana

2005 ◽  
Vol 49 (3) ◽  
pp. 1101-1105 ◽  
Author(s):  
Florian Marks ◽  
Jennifer Evans ◽  
Christian G. Meyer ◽  
Edmund N. Browne ◽  
Christa Flessner ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
High Frequency ◽  
Parasite Prevalence ◽  
Cross Resistance ◽  
Drug Pressure ◽  
Ashanti Region ◽  
High Prevalence ◽  
Resistance Markers ◽  
High Level ◽  
Weak Trend

ABSTRACT Markers of Plasmodium falciparum resistance to chloroquine (CQ) and pyrimethamine-sulfadoxine (PYR-SDX) are widespread in areas where malaria is endemic. In an area where the use PYR-SDX is negligible, the Ashanti Region of Ghana, West Africa, adult individuals were enrolled in an analysis of CQ- and PYR-SDX-associated molecular resistance markers in 2001 (n = 177) and 2003 (n = 180). Parasite prevalence, as assessed by PCR assays, were 56.5 and 48.8% in 2001 and 2003, respectively. A high frequency of CQ, PYR, and SDX resistance markers was observed, whereby, as a weak trend, the frequency was higher in 2003. The quintuple combination of three pfdhfr mutations and two pfdhps mutations has previously been recognized to be the most important determinant of PYR-SDX resistance. Approximately 60% of parasite carriers harbored fourfold mutated parasites, indicative of a considerable risk for a switch to high-level PYR-SDX resistance in an area where the rate of PYR-SDX use is low. Among the factors contributing to the high frequency of PYR-SDX resistance-associated mutations are background use of PYR-SDX, past use of PYR for malaria prophylaxis, cross-resistance of trimethoprim with PYR, and the sufficient biological fitness of resistant parasites in the absence of drug pressure.

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