Search

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 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 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.

Background Although glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is the most common inherited disorder in the Chinese population, there is scarce evidence regarding the epidemiology, evolutionary origin, and malaria‐induced positive selection effects of G6PD‐deficient alleles in various Chinese ethnic populations. Methods We performed a large population‐based screening (n = 15,690) to examine the impact of selection on human nucleotide diversity and to infer the evolutionary history of the most common deficiency alleles in Chinese populations. Results The frequencies of G6PD deficiency ranged from 0% to 11.6% in 12 Chinese ethnic populations. A frequency map based on geographic information showed that G6PD deficiency was highly correlated with historical malaria prevalence in China and was affected by altitude and latitude. The five most frequently occurring G6PD gene variants were NM_001042351.3:c.1376G>T, NM_001042351.3:c.1388G>A, NM_001042351.3:c.95A>G, NM_001042351.3:c.1311T>C, and NM_001042351.3:c.1024C>T, which were distributed with ethnic features. A pathogenic but rarely reported variant site (NM_001042351.3:c.448G>A) was identified in this study. Bioinformatic analysis revealed a strong and recent positive selection targeting the NM_001042351.3:c.1376G>T allele that originated in the past 3125 to 3750 years and another selection targeting the NM_001042351.3:c.1388G>A allele that originated in the past 5000 to 6000 years. Additionally, both alleles originated from a single ancestor. Conclusion These results indicate that malaria has had a major impact on the Chinese genome since the introduction of rice agriculture., Strong and recent positive selection have targeted on the c.1376 G>T allele with the past 3125–3750 years and c.1388 G>A allele with the past 5000–6000 years. Malaria has had a major impact on Chinese genome since the introduction of rice agriculture.

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 pfcsp displayed the various mutation patterns and obvious geographic differentiation among populations from four continents (p 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.

Background Glucose‐6‐phosphate dehydrogenase (G6PD) is an essential enzyme that protects red blood cells from oxidative damage. Although G6PD‐deficient alleles appear to confer a protective effect of malaria, the link with clinical protection against Plasmodium infection is conflicting. Methods A case–control study was conducted on Bioko Island, Equatorial Guinea and further genotyping analysis used to detect natural selection of the G6PD A‐ allele. Results Our results showed G6PD A‐ allele could significantly reduce the risk of Plasmodium falciparum infection in male individuals (adjusted odds ratio [AOR], 0.43; 95% confidence interval [CI], 0.20–0.93; p, In this work, we firstly analysed a large case–control study of 342 malaria cases and 1,287 health controls on Bioko Island, Equatorial Guinea. Our findings demonstrate G6PD A‐ allele could reduce the risk of Plasmodium falciparum infection in African population and indicate malaria has recent positive selection on G6PD A‐ allele.

Artemisinin (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 in vitro and in vivo monitoring for ART derivatives and ACT partner drugs should be regularly performed on Bioko Island, Equatorial Guinea.

Objective To design and fabricate canine rib prosthesis with full geometric shape using computed tomography (CT) scan combined with computer-aided design (CAD) and stereo lithographic (SLA) technologies and to evaluate the accuracy of this method. Methods After scanned on 64 rows helical CT, the cortex part of the right 7th rib was selected as the prototype for design and manufacture of the rib prosthesis and image data were stored as DICOM format. Three-dimensional (3D) surface reconstruction was applied to produce 3D image of the 7th rib and results were outputted as STL format which were then modified by UG software for establishment of CAD model. Results The rib prosthesis with full geometric shape was obtained based on CT scanning and SLA technique. About 30,000 point cloud data were acquired after 3D laser scan of the ribs. When comparing the rib prosthesis with the rib prototype, the maximum positive deviation, maximum negative deviation, average deviation and standard deviation were 1.764 mm, −2.126 mm, 0.183/−0.253 mm and 0.346 mm, respectively. There were about 88.17% of the point cloud data within the range of ±0.5 mm. Conclusion It is feasible to design and fabricate rib prosthesis with full geometric shape by using CT scanning technology combined with CAD and SLA technologies. This method is fast, convenient and precise for manufacturing prosthesis. Optimization and improvement could be processed based on the deviation suggested by the scanning.