scholarly journals Genetic polymorphism of Plasmodium falciparum circumsporozoite protein on Bioko Island, Equatorial Guinea and global comparative analysis

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Hui-Ying Huang ◽  
Xue-Yan Liang ◽  
Li-Yun Lin ◽  
Jiang-Tao Chen ◽  
Carlos Salas Ehapo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Comparative Analysis ◽  
Genetic Polymorphism ◽  
Circumsporozoite Protein ◽  
Equatorial Guinea ◽  
Bioko Island

scholarly journals Genetic polymorphism of Plasmodium falciparum circumsporozoite protein on Bioko Island, Equatorial Guinea and global comparative analysis

2020 ◽  
Author(s):  
Hui-Ying Huang ◽  
Xue-Yan Liang ◽  
Li-Yun Lin ◽  
Jiang-Tao Chen ◽  
Carlos Salas Ehapo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Comparative Analysis ◽  
Natural Selection ◽  
Genetic Polymorphism ◽  
Malaria Vaccine ◽  
Repetitive Sequences ◽  
Circumsporozoite Protein ◽  
T Cell Epitopes ◽  
Major Barrier ◽  
Bioko Island

Abstract Background Plasmodium falciparum circumsporozoite protein (PfCSP) is a potential malaria vaccine candidate, but various polymorphisms of the pfcsp gene among global P. falciparum population become the major barrier to the effectiveness of vaccines. This study aimed to investigate the genetic polymorphisms and natural selection of pfcsp in Bioko and the comparison among global P. falciparum population.Methods From January 2011 to December 2018, 148 blood samples were collected from P. falciparum infected Bioko patients and 96 monoclonal sequences of them were successfully acquired and analysed with 2200 global pfcsp sequences mined from MalariaGEN Pf3k Database and NCBI. Results In Bioko, the N-terminus of pfcsp showed limited genetic variations and the numbers of repetitive sequences (NANP/NVDP) were mainly found as 40 (35%) and 41 (34%) in central region. Most polymorphic characters were found in Th2R/Th3R region, where natural selection (p>0.05) and recombination occurred. The overall pattern of Bioko pfcsp gene had no obvious deviation from African mainland pfcsp (Fst=0.00878, p<0.05). The comparative analysis of Bioko and global pfcsp displayed the various mutation patterns and obvious geographic differentiation among populations from four continents (p<0.05). The global pfcsp C-terminal sequences were clustered into 138 different haplotypes (H_1 to H_138). Only 3.35% of sequences matched 3D7 strain haplotype (H_1). Conclusions The genetic polymorphism phenomena of pfcsp were found universal in Bioko and global isolates and the majority mutations located at T cell epitopes. Global genetic polymorphism and geographical characteristics were recommended to be considered for future improvement of malaria vaccine design.

scholarly journals Genetic polymorphism of Plasmodium falciparum circumsporozoite protein (PfCSP) and mismatches against RTS, S/AS01 malaria vaccine observed on Bioko Island, Equatorial Guinea and globally

2020 ◽  
Author(s):  
Hui-Ying Huang ◽  
Xue-Yan Liang ◽  
Li-Yun Lin ◽  
Jiang-Tao Chen ◽  
Carlos Salas Ehapo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Genetic Polymorphism ◽  
Genetic Polymorphisms ◽  
Vaccine Efficacy ◽  
Malaria Vaccine ◽  
Repetitive Sequences ◽  
Circumsporozoite Protein ◽  
Bioko Island ◽  
Selection Of

Abstract Backgroud RTS, S/AS01 is a Plasmodium falciparum circumsporozoite protein ( PfCSP ) based anti-malaria vaccine, but various genetic polymorphisms of PfCSP among global P. falciparum population could lead to mismatch against the PfCSP - based vaccine and reduce vaccine efficacy. This study aimed to investigate the genetic polymorphisms and natural selection of PfCSP in Bioko as well as global P. falciparum population. Methods From January 2011 to December 2018, 148 blood samples were collected from P. falciparum infected Bioko patients and 96 monoclonal sequences of them were successfully acquired and analyzed with 2200 global PfCSP sequences mined from MalariaGEN Pf3k Database and NCBI. Results In Bioko, the N-terminus of PfCSP showed limited genetic variations and the numbers of repetitive sequences (NANP/NVDP) were mainly found as 40 (35%) and 41 (34%) in central region. Most polymorphic characters were found in Th2R/Th3R region, where natural selection (p>0.05) and recombination occurred. The overall pattern of Bioko PfCSP gene had no obvious deviation from African mainland PfCSP (Fst=0.00878, p<0.05). The comparative analysis of Bioko and global PfCSP displayed the various mutation patterns and obvious geographic differentiation among populations from four continents (p<0.05). The global PfCSP C-terminal sequences were clustered into 138 different haplotypes (H_1 to H_138). Only 3.35% of sequences matched 3D7 vaccine strain haplotype (H_1). Conclusions The genetic polymorphism phenomena of PfCSP were found universal. The overall vaccine efficacy might be influenced by the low proportion of vaccine-matched isolates in global parasites population. Genetic polymorphism and geographical characteristics should be considered for future improvement of RTS, S/AS01.

scholarly journals Genetic polymorphism of Plasmodium falciparum circumsporozoite protein (PfCSP) on Bioko Island, Equatorial Guinea and global comparative analysis

2020 ◽  
Author(s):  
Hui-Ying Huang ◽  
Xue-Yan Liang ◽  
Li-Yun Lin ◽  
Jiang-Tao Chen ◽  
Carlos Salas Ehapo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Comparative Analysis ◽  
Natural Selection ◽  
Genetic Polymorphism ◽  
Genetic Polymorphisms ◽  
Malaria Vaccine ◽  
Repetitive Sequences ◽  
Circumsporozoite Protein ◽  
T Cell Epitopes ◽  
Major Barrier

Abstract Background Plasmodium falciparum circumsporozoite protein (PfCSP) is a potential malaria vaccine candidate, but various genetic polymorphisms of PfCSP among global P. falciparum population become the major barrier to the effectiveness of vaccines. This study aimed to investigate the genetic polymorphisms and natural selection of PfCSP in Bioko and the comparison among global P. falciparum population.Methods From January 2011 to December 2018, 148 blood samples were collected from P. falciparum infected Bioko patients and 96 monoclonal sequences of them were successfully acquired and analyzed with 2200 global PfCSP sequences mined from MalariaGEN Pf3k Database and NCBI. Results In Bioko, the N-terminus of PfCSP showed limited genetic variations and the numbers of repetitive sequences (NANP/NVDP) were mainly found as 40 (35%) and 41 (34%) in central region. Most polymorphic characters were found in Th2R/Th3R region, where natural selection (p>0.05) and recombination occurred. The overall pattern of Bioko PfCSP gene had no obvious deviation from African mainland PfCSP (Fst=0.00878, p<0.05). The comparative analysis of Bioko and global PfCSP displayed the various mutation patterns and obvious geographic differentiation among populations from four continents (p<0.05). The global PfCSP C-terminal sequences were clustered into 138 different haplotypes (H_1 to H_138). Only 3.35% of sequences matched 3D7 strain haplotype (H_1). Conclusions The genetic polymorphism phenomena of PfCSP were found universal in Bioko and global isolates and the majority mutations located at T cell epitopes. Global genetic polymorphism and geographical characteristics were recommended to be considered for future improvement of malaria vaccine design.

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 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 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 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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