scholarly journals Genomic analysis reveals independent evolution of Plasmodium falciparum population in Ethiopia

2020 ◽  
Author(s):  
Deriba Abera ◽  
Caleb Kipkurui Kibet ◽  
Teshome Degefa ◽  
Lucas Amenga-Etego ◽  
Joel L Bargul ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Balancing Selection ◽  
Central Area ◽  
Southeast Asian ◽  
Chloroquine Resistance ◽  
Nucleotide Polymorphisms ◽  
East African ◽  
Whole Genome Analysis ◽  
Host Diversity ◽  
Independent Evolution

Abstract Background Plasmodium falciparum parasite populations have been experiencing local selective pressures from drugs and immunity, leading to evolutionary adaptation. However, there was paucity of data on the genomic characterization and the evolutionary adaptations of P. falciparum isolates from central area of Ethiopia. Method : Whole genome analysis of 25 P. falciparum isolates from central Ethiopia were made to determine their genetic diversity, population structures and signatures of selection in known drug resistance loci against isolates from Cambodia, Thailand, DR Congo and Malawi. Result A total of 18,517 high-quality single-nucleotide polymorphisms (SNPs) were identified with average nucleotide diversity (π = 0.00022) across the genome. About 84% of the Ethiopian P. falciparum isolates had FWS value > 0.95 showing a dominant single genotype infection in most isolates at the time of collection with little potential for out-crossing as expected in areas with low transmission intensity. Within host diversity of Ethiopian infections was significantly different from East African (p < 0.001) but not Southeast Asian infections (P > 0.05). A significant population structure differentiation between Ethiopian parasites and East Africa (Fst < 10%) and Southeast Asia populations (Fst ~ 18%) has been observed, suggesting limited gene flow and the independent evolution of the Ethiopian parasite population. Moreover, a total of 125 genes under balancing selection is identified that included ama1, trap, eba175, and lsa3 previously identified as targets of human host immunity. Recent directional selection analysis using integrated standardized haplotype score (IHS) did not detect any selection signatures in the pfcrt, pfdhfr, pfdhps, pfmdr1, and pfK13 genes. However, mutations analysis showed that at least one SNP marker was fixed in these genes, but not in pfdhps and pfK13. Conclusion Plasmodium falciparum population in central region of Ethiopia were structurally diverged from both southeast Asian and other East African populations. A low within host diversity is noted among the Ethiopian parasites. Indeed, the parasites carry fixed chloroquine resistance markers despite the withdrawal of this drug for the treatment of P. falciparum.

scholarly journals Genomic analysis reveals independent evolution of Plasmodium falciparum populations in Ethiopia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Deriba Abera ◽  
Caleb K. Kibet ◽  
Teshome Degefa ◽  
Lucas Amenga-Etego ◽  
Joel L. Bargul ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Balancing Selection ◽  
Central Area ◽  
Southeast Asian ◽  
Chloroquine Resistance ◽  
East African ◽  
Whole Genome Analysis ◽  
Host Diversity ◽  
Independent Evolution

Abstract Background Plasmodium falciparum parasite populations in Ethiopia have been experiencing local selective pressures from drugs and immunity, leading to evolutionary adaptation. However, there was a paucity of data on genomic characterization and evolutionary adaptations of P. falciparum isolates from the central area of Ethiopia. Methods Whole-genome analysis of 25 P. falciparum isolates from central Ethiopia, specifically from West Arsi, were studied to determine their genetic diversity, population structures, and signatures of selection in known drug resistance alleles against global isolates from Cambodia, Thailand, DR Congo, and Malawi. Results A total of 18,517 high-quality single-nucleotide polymorphisms (SNPs) were identified in Ethiopian P. falciparum isolates. About 84% of the Ethiopian P. falciparum isolates had a FWS value > 0.95 showing a dominant single genotype infection in most isolates at the time of collection with little potential for out-crossing as expected in areas with low transmission intensity. Within-host diversity of Ethiopian infections was significantly different from East African (p < 0.001), but not Southeast Asian infections (P > 0.05). A significant population structure has been observed by PCA and population differentiation between Ethiopian parasites and East African (Fst ~ 10%) and Southeast Asian populations (Fst ~ 18%), suggesting limited gene flow and the independent evolution of the Ethiopian parasite population. Moreover, a total of 125 genes under balancing selection was found that include ama1, trap, eba175, and lsa3, previously identified as targets of human host immunity. Recent directional selection analysis using integrated standardized haplotype score (IHS) did not detect any selection signatures in the Pfcrt, Pfdhfr, Pfdhps, Pfmdr1, and PfK13 genes. However, known drug resistance-conferring mutations analysis showed that at least one SNP marker was fixed in these genes, but not in Pfdhps and PfK13. Conclusion Plasmodium falciparum populations in the central region of Ethiopia was structurally diverged from both Southeast Asian and other East African populations. Malaria infections in Ethiopia had low within-host diversity, and parasites carry fixed chloroquine resistance markers despite the withdrawal of this drug for the treatment of P. falciparum.

scholarly journals Genomic analysis reveals independent evolution of Plasmodium falciparum populations in Ethiopia

2021 ◽  
Author(s):  
Deriba Abera Beyene ◽  
Caleb Kipkurui Kibet ◽  
Teshome Degefa ◽  
Lucas Amenga-Etego ◽  
Joel L Bargul ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Balancing Selection ◽  
Central Area ◽  
Southeast Asian ◽  
Chloroquine Resistance ◽  
East African ◽  
Whole Genome Analysis ◽  
Host Diversity ◽  
Independent Evolution

Abstract Background: Plasmodium falciparumparasite populations in Ethiopia have been experiencing local selective pressures from drugs and immunity, leading to evolutionary adaptation. However, there wasthe paucity of data on the genomic characterization and the evolutionary adaptations of P. falciparum isolates from the central area of Ethiopia. Method: Whole-genome analysis of 25 P. falciparum isolates from central Ethiopia, specifically from West Arsi, were studied to determine theirgenetic diversity, population structures, and signatures of selection in known drug resistance alleles against global isolates from Cambodia, Thailand, DR Congo, and Malawi.Result: A total of 18,517high-quality single-nucleotide polymorphisms (SNPs) were identifiedin Ethiopian P. falciparum isolates.About 84% of the Ethiopian P. falciparum isolates hadan FWS value >0.95showing a dominant single genotype infection in most isolates at the time of collection with little potential for out-crossing as expected in areaswith low transmission intensity. Within host diversity of Ethiopian infectionswas significantly differentfrom East African (p < 0.001) but not Southeast Asian infections (P >0.05). We observed significant population structureby PCA andpopulation differentiation between Ethiopian parasitesand East Africa (Fst~ 10%) and Southeast Asia populations (Fst ~18%), suggesting limited gene flow and the independent evolution of the Ethiopian parasite population. Moreover, we found a total of 125 genes under balancing selection that includedama1, trap, eba175, and lsa3previously identified as targets of human host immunity. Recent directional selection analysis using integrated standardized haplotype score (IHS) did not detect any selection signatures in the Pfcrt,Pfdhfr,Pfdhps, Pfmdr1, and PfK13 genes. However, known drug resistance-conferring mutations analysis showed that at least one SNP marker was fixed in these genes, but not in Pfdhps and PfK13.Conclusion: Plasmodium falciparumpopulation in the central region of Ethiopia wasstructurally diverged from both Southeast Asian and other East African populations. Malaria infections in Ethiopia had low within-host diversity, and parasites carryfixed chloroquine resistance markers despite the withdrawal of this drug for the treatment of P. falciparum.

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

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 ◽  
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.

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

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.

Local differentiation in Plasmodium falciparum drug resistance genes in Sudan

Parasitology ◽  
2003 ◽  
Vol 126 (5) ◽  
pp. 391-400 ◽  
Author(s):  
A. A. ABDEL-MUHSIN ◽  
M. J. MACKINNON ◽  
P. AWADALLA ◽  
E. ALI ◽  
S. SULEIMAN ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Population Structure ◽  
Resistance Genes ◽  
Microsatellite Loci ◽  
Balancing Selection ◽  
Dry Season ◽  
Chloroquine Resistance ◽  
Multi Drug Resistance ◽  
Eastern Region

Studies of population genetic structure of parasites can be used to infer which parasite genes are under selection. Here, the population structure of 4 genes associated with drug resistance of Plasmodium falciparum (the chloroquine resistance transporter, pfcrt, dihydrofolate reductase, dhfr, dihydropteroate synthase, dhps, and multi-drug resistance, pfmdr-1) were examined in parasite populations in 3 villages in eastern Sudan and in an urban area of Khartoum, the capital. In order to differentiate the effects of drug selection from neutral influences on population structure, parasites were also genotyped for 3 putatively neutral microsatellite loci (polyα, TA81 and pfg377), and for 2 antigenic loci that are either under balancing selection or neutral, merozoite surface protein 1 and 2, (MSP-1 and MSP-2). Cross-sectional surveys were carried out during the peak transmission (wet) season and in the ensuing dry season. No significant variation in frequencies of MSP-1 and MSP-2 alleles was seen among villages in the eastern region and between the villages and Khartoum, nor between the wet and dry season. However, the drug resistance genes, pfmdr-1, pfcrt and dhfr and to a lesser extent the microsatellite loci showed high FST values when comparing villages with Khartoum, indicating strong geographical differentiation at these loci. Moreover, variation in frequencies of the drug resistance genes, pfmdr-1, pfcrt and dhfr, was observed between the wet and dry season. These differences most probably reflect the variation in drug pressure between each region, and in drug usage between the wet and dry season in a given region.

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 In silico characterisation of putative Plasmodium falciparum vaccine candidates in African malaria populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
O. Ajibola ◽  
M. F. Diop ◽  
A. Ghansah ◽  
L. Amenga-Etego ◽  
L. Golassa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Vaccine ◽  
Transmembrane Domain ◽  
Vaccine Development ◽  
Balancing Selection ◽  
Immune Recognition ◽  
African Countries ◽  
Vaccine Candidates ◽  
D Values ◽  
Tajima’S D

AbstractGenetic diversity of surface exposed and stage specific Plasmodium falciparum immunogenic proteins pose a major roadblock to developing an effective malaria vaccine with broad and long-lasting immunity. We conducted a prospective genetic analysis of candidate antigens (msp1, ama1, rh5, eba175, glurp, celtos, csp, lsa3, Pfsea, trap, conserved chrom3, hyp9, hyp10, phistb, surfin8.2, and surfin14.1) for malaria vaccine development on 2375 P. falciparum sequences from 16 African countries. We described signatures of balancing selection inferred from positive values of Tajima’s D for all antigens across all populations except for glurp. This could be as a result of immune selection on these antigens as positive Tajima’s D values mapped to regions with putative immune epitopes. A less diverse phistb antigen was characterised with a transmembrane domain, glycophosphatidyl anchors between the N and C- terminals, and surface epitopes that could be targets of immune recognition. This study demonstrates the value of population genetic and immunoinformatic analysis for identifying and characterising new putative vaccine candidates towards improving strain transcending immunity, and vaccine efficacy across all endemic populations.

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.

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