scholarly journals Genetic diversity and allele frequencies of Plasmodium falciparum msp1 and msp2 in parasite isolates from Bioko Island, Equatorial Guinea

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Jiang-Tao Chen ◽  
Jian Li ◽  
Guang-Cai Zha ◽  
Guang Huang ◽  
Zhi-Xiu Huang ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Allele Frequencies ◽  
Equatorial Guinea ◽  
Bioko Island

scholarly journals Population Genetic Analysis of the Plasmodium Falciparum Erythrocyte Binding Antigen-175 (EBA-175) Gene in Equatorial Guinea

2021 ◽  
Author(s):  
Pei-Kui Yang ◽  
Xue-Yan Liang ◽  
Min Lin ◽  
Jiang-Tao Chen ◽  
Hui-Ying Huang ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Malaria Vaccine ◽  
Blood Stage ◽  
Equatorial Guinea ◽  
Bioko Island ◽  
Erythrocyte Binding ◽  
Region Ii ◽  
Blood Stage Malaria

Abstract Background: Plasmodium falciparum erythrocyte binding antigen-175 (PfEBA-175) is a candidate antigen for a blood-stage malaria vaccine, while various polymorphisms in the PfEBA-175 gene among global P. falciparum populations have prevented the development of effective vaccines based on this gene. At the same time, the dimorphism of the F- and C-fragments associated with high endemic of severe malaria has been described. This study aimed to investigate the dimorphism of PfEBA-175 on both the Bioko island and continent of Equatorial Guinea, as well as the genetic polymorphism and natural selection of global PfEBA-175.Methods: A total of 218 blood samples were collected from patients with P. falciparum malaria on Bioko Island and Bata district in 2018 and 2019. The allelic dimorphism of PfEBA-175 region II was investigated by nested polymerase chain reaction and sequencing. Polymorphic characteristics and the effect of natural selection were analyzed using MEGA 7.0, DnaSP 6.0 and PopART programs. Genetic diversity in 312 global PfEBA-175 region II sequences was also analyzed. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 and Foldx program.Results: Allelic dimorphism of PfEBA-175 was identified in the study area, and the frequency of the F-fragment was higher than that of the C-fragment in both Bioko Island and Bata district populations. Additionally, single infections (87.80%) were more frequent than mixed infections (12.20%). A total of 49 monoclonal PfEBA-175 region II sequences of Bioko Island and Bata district were sequenced successfully. PfEBA-175 of Bioko Island and Bata district isolates showed a high degree of genetic variability and heterogeneity, with π values of 0.00407 & 0.00411 and Hd values of 0.958 & 0.976 for nucleotide diversity, respectively. The values of Tajima's D of PfEBA-175 on Bata district and Bioko Island were 0.56395 and -0.27018, respectively. Globally, PfEBA-175 isolates from Asia were more diverse than those from Africa and South America, and genetic differentiation quantified by the fixation index between Asian and South American countries populations was significant (Fst>0.15, P<0.05). A total of 312 global isolates clustered in 92 haplotypes, and only one cluster contained isolates from three continents. The mutations A34T, K109E, D278Y, K301N, L305V and D329N were predicted as probably damaging by PolyPhen-2. Among them, mutations A34T, K301N and L305V led to significant increases in the free energy difference (ΔΔG>1), indicating destabilization of the protein structure.Conclusions: This study proved the dimorphism of PfEBA-175, and also demonstrated that the F-fragment was remarkably predominant in the study area. The distribution patterns and genetic diversity of PfEBA-175 in Equatorial Guinea isolates were similar to those of isolates worldwide. High levels of recombination events were observed in PfEBA-175 isolates globally, suggesting that natural selection and intragenic recombination might be the main drivers of genetic diversity in global PfEBA-175. These results have important reference value for the development of blood-stage malaria vaccine based on this antigen.

scholarly journals Population genetic analysis of the Plasmodium falciparum erythrocyte binding antigen-175 (EBA-175) gene in Equatorial Guinea

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Pei-Kui Yang ◽  
Xue-Yan Liang ◽  
Min Lin ◽  
Jiang-Tao Chen ◽  
Hui-Ying Huang ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Malaria Vaccine ◽  
Blood Stage ◽  
Equatorial Guinea ◽  
Fixation Index ◽  
Bioko Island ◽  
Erythrocyte Binding ◽  
Blood Stage Malaria

Abstract Background Plasmodium falciparum erythrocyte binding antigen-175 (PfEBA-175) is a candidate antigen for a blood-stage malaria vaccine, while various polymorphisms and dimorphism have prevented to development of effective vaccines based on this gene. This study aimed to investigate the dimorphism of PfEBA-175 on both the Bioko Island and continent of Equatorial Guinea, as well as the genetic polymorphism and natural selection of global PfEBA-175. Methods The allelic dimorphism of PfEBA-175 region II of 297 bloods samples from Equatorial Guinea in 2018 and 2019 were investigated by nested polymerase chain reaction and sequencing. Polymorphic characteristics and the effect of natural selection were analyzed using MEGA 7.0, DnaSP 6.0 and PopART programs. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 and Foldx program. Results Both Bioko Island and Bata district populations, the frequency of the F-fragment was higher than that of the C-fragment of PfEBA-175 gene. The PfEBA-175 of Bioko Island and Bata district isolates showed a high degree of genetic variability and heterogeneity, with π values of 0.00407 & 0.00411 and Hd values of 0.958 & 0.976 for nucleotide diversity, respectively. The values of Tajima's D of PfEBA-175 on Bata district and Bioko Island were 0.56395 and − 0.27018, respectively. Globally, PfEBA-175 isolates from Asia were more diverse than those from Africa and South America, and genetic differentiation quantified by the fixation index between Asian and South American countries populations was significant (FST > 0.15, P < 0.05). A total of 310 global isolates clustered in 92 haplotypes, and only one cluster contained isolates from three continents. The mutations A34T, K109E, D278Y, K301N, L305V and D329N were predicted as probably damaging. Conclusions This study demonstrated that the dimorphism of F-fragment PfEBA-175 was remarkably predominant in the study area. The distribution patterns and genetic diversity of PfEBA-175 in Equatorial Guinea isolates were similar another region isolates. And the levels of recombination events suggested that natural selection and intragenic recombination might be the main drivers of genetic diversity in global PfEBA-175. These results have important reference value for the development of blood-stage malaria vaccine based on this antigen.

scholarly journals Incidence of Plasmodium falciparum malaria infection in 6-month to 45-year-olds on selected areas of Bioko Island, Equatorial Guinea

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Vicente Urbano Nsue Ndong Nchama ◽  
Ali Hamad Said ◽  
Ali Mtoro ◽  
Gertrudis Owono Bidjimi ◽  
Marta Alene Owono ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Control ◽  
Malaria Infection ◽  
Age Groups ◽  
Control Measures ◽  
Equatorial Guinea ◽  
Safety And Efficacy ◽  
Bioko Island ◽  
Malaria Vaccines

Abstract Background Extensive malaria control measures have been implemented on Bioko Island, Equatorial Guinea over the past 16 years, reducing parasite prevalence and malaria-related morbidity and mortality, but without achieving elimination. Malaria vaccines offer hope for reducing the burden to zero. Three phase 1/2 studies have been conducted successfully on Bioko Island to evaluate the safety and efficacy of whole Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccines. A large, pivotal trial of the safety and efficacy of the radiation-attenuated Sanaria® PfSPZ Vaccine against P. falciparum is planned for 2022. This study assessed the incidence of malaria at the phase 3 study site and characterized the influence of socio-demographic factors on the burden of malaria to guide trial design. Methods A cohort of 240 randomly selected individuals aged 6 months to 45 years from selected areas of North Bioko Province, Bioko Island, was followed for 24 weeks after clearance of parasitaemia. Assessment of clinical presentation consistent with malaria and thick blood smears were performed every 2 weeks. Incidence of first and multiple malaria infections per person-time of follow-up was estimated, compared between age groups, and examined for associated socio-demographic risk factors. Results There were 58 malaria infection episodes observed during the follow up period, including 47 first and 11 repeat infections. The incidence of malaria was 0.25 [95% CI (0.19, 0.32)] and of first malaria was 0.23 [95% CI (0.17, 0.30)] per person per 24 weeks (0.22 in 6–59-month-olds, 0.26 in 5–17-year-olds, 0.20 in 18–45-year-olds). Incidence of first malaria with symptoms was 0.13 [95% CI (0.09, 0.19)] per person per 24 weeks (0.16 in 6–59-month-olds, 0.10 in 5–17-year-olds, 0.11 in 18–45-year-olds). Multivariate assessment showed that study area, gender, malaria positivity at screening, and household socioeconomic status independently predicted the observed incidence of malaria. Conclusion Despite intensive malaria control efforts on Bioko Island, local transmission remains and is spread evenly throughout age groups. These incidence rates indicate moderate malaria transmission which may be sufficient to support future larger trials of PfSPZ Vaccine. The long-term goal is to conduct mass vaccination programmes to halt transmission and eliminate P. falciparum malaria.

scholarly journals Genetic diversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum on Bioko Island, Equatorial Guinea and global comparative analysis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Li-Yun Lin ◽  
Hui-Ying Huang ◽  
Xue-Yan Liang ◽  
Dong-De Xie ◽  
Jiang-Tao Chen ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Protein Structure ◽  
Transmembrane Protein ◽  
Fixation Index ◽  
Bioko Island ◽  
Adhesive Protein ◽  
Trap Gene ◽  
Selection Of

Abstract Background Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. Methods 153 blood spot samples from Bioko malaria patients were collected during 2016–2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. Results A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN–dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. Conclusions Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.

scholarly journals Genetic diversity and differentiation in natural Plasmodium falciparum populations inferred by molecular typing of the merozoite surface proteins 1 and 2

2002 ◽  
Vol 35 (5) ◽  
pp. 527-530 ◽  
Author(s):  
Fabrício J.T. Pereira ◽  
José A. Cordeiro ◽  
Erika H.E. Hoffmann ◽  
Marcelo U. Ferreira
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Population Differentiation ◽  
Molecular Typing ◽  
Allele Frequencies ◽  
Surface Proteins ◽  
Transmission Dynamics ◽  
Polymorphic Genes

Genetic diversity and differentiation, inferred by typing the polymorphic genes coding for the merozoite surface proteins 1 (Msp-1) and 2 (Msp-2), were compared for 345 isolates belonging to seven Plasmodium falciparum populations from three continents. Both loci yielded similar estimates of genetic diversity for each population, but rather different patterns of between-population differentiation, suggesting that natural selection on these loci, rather than the transmission dynamics of P. falciparum, determines the variation in allele frequencies among populations.

scholarly journals REDUCTION IN INFECTION WITH PLASMODIUM FALCIPARUM ONE YEAR AFTER THE INTRODUCTION OF MALARIA CONTROL INTERVENTIONS ON BIOKO ISLAND, EQUATORIAL GUINEA

2006 ◽  
Vol 74 (6) ◽  
pp. 972-978 ◽  
Author(s):  
IMMO KLEINSCHMIDT ◽  
JAISHREE RAMAN ◽  
BRIAN SHARP ◽  
LUIS E. BENAVENTE ◽  
JOSEPH CARTER ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Control ◽  
Equatorial Guinea ◽  
Bioko Island ◽  
One Year

scholarly journals Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Mónica Guerra ◽  
Rita Neres ◽  
Patrícia Salgueiro ◽  
Cristina Mendes ◽  
Nicolas Ndong-Mabale ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Microsatellite Loci ◽  
Point Mutations ◽  
Artemisinin Resistance ◽  
Equatorial Guinea ◽  
Content Type ◽  
Before And After

ABSTRACT Efforts to control malaria may affect malaria parasite genetic variability and drug resistance, the latter of which is associated with genetic events that promote mechanisms to escape drug action. The worldwide spread of drug resistance has been a major obstacle to controlling Plasmodium falciparum malaria, and thus the study of the origin and spread of associated mutations may provide some insights into the prevention of its emergence. This study reports an analysis of P. falciparum genetic diversity, focusing on antimalarial resistance-associated molecular markers in two socioeconomically different villages in mainland Equatorial Guinea. The present study took place 8 years after a previous one, allowing the analysis of results before and after the introduction of an artemisinin-based combination therapy (ACT), i.e., artesunate plus amodiaquine. Genetic diversity was assessed by analysis of the Pfmsp2 gene and neutral microsatellite loci. Pfdhps and Pfdhfr alleles associated with sulfadoxine-pyrimethamine (SP) resistance and flanking microsatellite loci were investigated, and the prevalences of drug resistance-associated point mutations of the Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps genes were estimated. Further, to monitor the use of ACT, we provide the baseline prevalences of K13 propeller mutations and Pfmdr1 copy numbers. After 8 years, noticeable differences occurred in the distribution of genotypes conferring resistance to chloroquine and SP, and the spread of mutated genotypes differed according to the setting. Regarding artemisinin resistance, although mutations reported as being linked to artemisinin resistance were not present at the time, several single nucleotide polymorphisms (SNPs) were observed in the K13 gene, suggesting that closer monitoring should be maintained to prevent the possible spread of artemisinin resistance in Africa.

scholarly journals Kelch13 and MDR1 Polymorphisms, and Drug Effectiveness at Day 3 after Dihydroartemisinin-Piperaquine Treatment for Plasmodium falciparum Malaria on Bioko Island, Equatorial Guinea: 2014-2017

2019 ◽  
Author(s):  
Yu-Zhong Zheng ◽  
Jiang-Tao Chen ◽  
Xue-Yan Liang ◽  
Carlos Salas Ehapo ◽  
Urbano Monsuy Eyi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Falciparum Malaria ◽  
Parasite Clearance ◽  
Equatorial Guinea ◽  
Mdr1 Gene ◽  
Clearance Time ◽  
Bioko Island ◽  
Drug Effectiveness

ABSTRACTArtemisinin (ART) combination therapies were introduced on malaria endemic Bioko Island in 2004 through Bioko Island Malaria Control Project. Recently, ART-resistant Plasmodium falciparum strain with Kelch13 (K13) propeller M579I mutation originating from Equatorial Guinea was observed as an increased parasite clearance time on day 3 after dihydroartemisinin-Piperaquine (DHA-PIP) treatment (D3 positivity). Here, we surveyed DHA-PIP effectiveness and molecular markers of drug resistance at D3 after DHA-PIP treatment on Bioko Island from 2014 to 2017. Among the 371 uncomplicated P. falciparum patients, 86.3% (320/471) were successfully followed up at D3. 5.9% (19/320) of patients showed D3 positivity. K13 and MDR1 gene were successfully sequenced from 46 patients collected at D0 (baseline population) and 19 D3-positivity patients. Five non-synonymous K13 mutations (H136N; K189N; K248N; K326E; K332N) were found. There was no statistical difference in the frequency of these K13 mutations between baseline population and D3-positivity samples (p>0.05). Additionally, none of the K13 propeller polymorphisms known to be involved in ART-resistance in Asia or Africa were detected. For MDR1 gene, 38.5% (25/65) carried N86Y mutation; 73.8% (48/65) the Y184F mutation. Parasites surviving DHA-PIP at D3 post-treatment were significantly more likely than the baseline population to carry the N86Y (p <0.05). These results suggest that K13 is not the best predictive molecular marker for ART resistance in Africa. More isolates from cases with delayed parasite clearance after DHA-PIP treatment indicated that in vitro and in vivo monitoring for ART derivatives and ACT partner drugs should be regularly performed on Bioko Island, Equatorial Guinea.

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