Displaying publications 41 - 60 of 220 in total

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  1. Fulltext Genetic Diversity and Clustering of the Rhoptry Associated Protein-1 of Plasmodium knowlesi from Peninsular Malaysia and Malaysian Borneo
    Azlan UW, Lau YL, Fong MY
    Korean J Parasitol, 2022 Dec;60(6):393-400.
    PMID: 36588415 DOI: 10.3347/kjp.2022.60.6.393
    Human infection with simian malaria Plasmodium knowlesi is a cause for concern in Southeast Asian countries, especially in Malaysia. A previous study on Peninsular Malaysia P. knowlesi rhoptry associated protein-1 (PkRAP1) gene has discovered the existence of dimorphism. In this study, genetic analysis of PkRAP1 in a larger number of P. knowlesi samples from Malaysian Borneo was conducted. The PkRAP1 of these P. knowlesi isolates was PCR-amplified and sequenced. The newly obtained PkRAP1 gene sequences (n = 34) were combined with those from the previous study (n = 26) and analysed for polymorphism and natural selection. Sequence analysis revealed a higher genetic diversity of PkRAP1 compared to the previous study. Exon II of the gene had higher diversity (π = 0.0172) than exon I (π = 0.0128). The diversity of the total coding region (π = 0.0167) was much higher than those of RAP1 orthologues such as PfRAP-1 (π = 0.0041) and PvRAP1 (π = 0.00088). Z-test results indicated that the gene was under purifying selection. Phylogenetic tree and haplotype network showed distinct clustering of Peninsular Malaysia and Malaysian Borneo PkRAP1 haplotypes. This geographical-based clustering of PkRAP1 haplotypes provides further evidence of the dimorphism of the gene and possible existence of 2 distinct P. knowlesi lineages in Malaysia.
  2. Fulltext Genetic polymorphism of the thrombospondin-related apical merozoite protein (TRAMP) of Plasmodium knowlesi in Malaysia
    Ng YL, Lau YL, Hamid MHA, Jelip J, Ooi CH, Mudin RN, et al.
    Parasitol Res, 2023 Jan;122(1):195-200.
    PMID: 36378331 DOI: 10.1007/s00436-022-07716-z
    Plasmodium knowlesi is a simian malaria parasite that causes significant zoonotic infections in Southeast Asia, particularly in Malaysia. The Plasmodium thrombospondin-related apical merozoite protein (TRAMP) plays an essential role in the invasion of the parasite into its host erythrocyte. The present study investigated the genetic polymorphism and natural selection of the full length PkTRAMP from P. knowlesi clinical isolates from Malaysia. Blood samples (n = 40) were collected from P. knowlesi malaria patients from Peninsular Malaysia and Malaysian Borneo. The PkTRAMP gene was amplified using PCR, followed by cloning into a plasmid vector and sequenced. Results showed that the nucleotide diversity of PkTRAMP was low (π: 0.009). Z-test results indicated negative (purifying) selection of PkTRAMP. The alignment of the deduced amino acid sequences of PkTRAMP of Peninsular Malaysia and Malaysian Borneo revealed 38 dimorphic sites. A total of 27 haplotypes were identified from the amino acid sequence alignment. Haplotype analysis revealed that there was no clustering of PkTRAMP from Peninsular Malaysia and Malaysian Borneo.
  3. Genetic diversity of secreted protein with an altered thrombospondin repeat (SPATR) of Plasmodium knowlesi clinical isolates from Malaysia
    Azlan UW, Lau YL, Hamid MHA, Jelip J, Ooi CH, Mudin RN, et al.
    Trop Biomed, 2022 Dec 01;39(4):504-510.
    PMID: 36602208 DOI: 10.47665/tb.39.4.006
    The Plasmodium knowlesi secreted protein with an altered thrombospondin repeat (PkSPATR) is an important protein that helps in the parasite's invasion into the host cell. This protein has been regarded as one of the potential vaccine candidates against P. knowlesi infection. This study investigates the genetic diversity and natural selection of PkSPATR gene of P. knowlesi clinical isolates from Malaysia. PCR amplification of the full length PkSPATR gene was performed on 60 blood samples of infected P. knowlesi patients from Peninsular Malaysia and Malaysian Borneo. The amplified PCR products were cloned and sequenced. Sequence analysis of PkSPATR from Malaysia showed higher nucleotide diversity (CDS p: 0.01462) than previously reported Plasmodium vivax PvSPATR (p = 0.0003). PkSPATR from Peninsular Malaysia was observed to have slightly higher diversity (CDS p: 0.01307) than those from Malaysian Borneo (CDS p: 0.01212). Natural selection analysis on PkSPATR indicated significant purifying selection. Multiple amino acid sequence alignment revealed 69 polymorphic sites. The phylogenetic tree and haplotype network did not show any distinct clustering of PkSPATR. The low genetic diversity level, natural selection and absence of clustering implied functional constrains of the PkSPATR protein.
  4. Fulltext The Impact of Geographical Variation in Plasmodium knowlesi Apical Membrane Protein 1 (PkAMA-1) on Invasion Dynamics of P. knowlesi
    Ng YL, Lee WC, Lau YL, Fong MY
    Trop Med Infect Dis, 2023 Jan 10;8(1).
    PMID: 36668963 DOI: 10.3390/tropicalmed8010056
    Plasmodium knowlesi has emerged as an important zoonotic parasite that causes persistent symptomatic malaria in humans. The signs and symptoms of malaria are attributed to the blood stages of the parasites, which start from the invasion of erythrocytes by the blood stage merozoites. The apical membrane protein 1 (AMA-1) plays an important role in the invasion. In this study, we constructed and expressed recombinant PkAMA-1 domain II (PkAMA-1-DII) representing the predominant haplotypes from Peninsular Malaysia and Malaysian Borneo and raised specific antibodies against the recombinant proteins in rabbits. Despite the minor amino acid sequence variation, antibodies raised against haplotypes from Peninsular Malaysia and Malaysian Borneo demonstrated different invasion inhibition (46.81% and 39.45%, respectively) to P. knowlesi A1-H.1, a reference strain derived from Peninsular Malaysia. Here, we demonstrated how a minor variation in a conserved parasite protein could cast a significant impact on parasite invasion biology, suggesting a complex host-switching of P. knowlesi from different locations. This may challenge the implementation of a standardized One Health approach against the transmission of knowlesi malaria.
  5. Fulltext Predicting Plasmodium knowlesi transmission risk across Peninsular Malaysia using machine learning-based ecological niche modeling approaches
    Phang WK, Hamid MHBA, Jelip J, Mudin RNB, Chuang TW, Lau YL, et al.
    Front Microbiol, 2023;14:1126418.
    PMID: 36876062 DOI: 10.3389/fmicb.2023.1126418
    The emergence of potentially life-threatening zoonotic malaria caused by Plasmodium knowlesi nearly two decades ago has continued to challenge Malaysia healthcare. With a total of 376 P. knowlesi infections notified in 2008, the number increased to 2,609 cases in 2020 nationwide. Numerous studies have been conducted in Malaysian Borneo to determine the association between environmental factors and knowlesi malaria transmission. However, there is still a lack of understanding of the environmental influence on knowlesi malaria transmission in Peninsular Malaysia. Therefore, our study aimed to investigate the ecological distribution of human P. knowlesi malaria in relation to environmental factors in Peninsular Malaysia. A total of 2,873 records of human P. knowlesi infections in Peninsular Malaysia from 1st January 2011 to 31st December 2019 were collated from the Ministry of Health Malaysia and geolocated. Three machine learning-based models, maximum entropy (MaxEnt), extreme gradient boosting (XGBoost), and ensemble modeling approach, were applied to predict the spatial variation of P. knowlesi disease risk. Multiple environmental parameters including climate factors, landscape characteristics, and anthropogenic factors were included as predictors in both predictive models. Subsequently, an ensemble model was developed based on the output of both MaxEnt and XGBoost. Comparison between models indicated that the XGBoost has higher performance as compared to MaxEnt and ensemble model, with AUCROC values of 0.933 ± 0.002 and 0.854 ± 0.007 for train and test datasets, respectively. Key environmental covariates affecting human P. knowlesi occurrence were distance to the coastline, elevation, tree cover, annual precipitation, tree loss, and distance to the forest. Our models indicated that the disease risk areas were mainly distributed in low elevation (75-345 m above mean sea level) areas along the Titiwangsa mountain range and inland central-northern region of Peninsular Malaysia. The high-resolution risk map of human knowlesi malaria constructed in this study can be further utilized for multi-pronged interventions targeting community at-risk, macaque populations, and mosquito vectors.
  6. Fulltext Corrigendum: Predicting Plasmodium knowlesi transmission risk across Peninsular Malaysia using machine learning-based ecological niche modeling approaches
    Phang WK, Hamid MHBA, Jelip J, Mudin RNB, Chuang TW, Lau YL, et al.
    Front Microbiol, 2023;14:1178864.
    PMID: 37007492 DOI: 10.3389/fmicb.2023.1178864
    [This corrects the article DOI: 10.3389/fmicb.2023.1126418.].
  7. Multiplicity of infection of Plasmodium knowlesi in Malaysia: an application of Pkmsp-1 block IV
    Noordin NR, Azhar A, Lau YL, Cheong FW, Fong MY
    Trop Biomed, 2023 Sep 01;40(3):295-300.
    PMID: 37897161 DOI: 10.47665/tb.40.3.004
    In Malaysia presently, the main cause of human malaria is by the zoonotic monkey parasite Plasmodium knowlesi. A previous study has suggested that the P. knowlesi merozoite surface protein 1 (Pkmsp-1) block IV to be a suitable multiplicity of infection (MOI) genotyping marker for knowlesimalaria. This study therefore aimed to investigate the usefulness of Pkmsp-1 block IV in assessing the MOI of P. knowlesi in clinical isolates from Malaysia. Two allele-specific PCR primer pairs targeting the two allelic families of block IV (T1 and T2) were designed, and used to genotype P. knowlesi in 200 blood samples (100 from Peninsular Malaysia and 100 from Malaysian Borneo). Results showed that the mean MOI in Malaysian Borneo was slightly higher as compared to Peninsular Malaysia (1.58 and 1.40, respectively). Almost half of the total blood samples from Malaysian Borneo (52%) had polyclonal infections (i.e., more than one allele of any family type) as compared to Peninsular Malaysia (33%) samples. The T1 allelic family was more prevalent in Peninsular Malaysia (n=75) than in Malaysian Borneo (n=60). The T2 allelic family, however, was more prevalent in the Malaysian Borneo (n=87 vs n=53 respectively). This study shows that the single locus Pkmsp-1 block IV can serve as a simple alternative genetic marker for estimating knowlesi malaria MOI in a population. Future MOI studies should focus on macaque populations as macaques are the natural host of P. knowlesi.
  8. Plasmodium knowlesi circumsporozoite protein: genetic characterisation and predicted antigenicity of the central repeat region
    Tan JH, Cheong FW, Lau YL, Fong MY
    Trop Biomed, 2023 Mar 01;40(1):37-44.
    PMID: 37356002 DOI: 10.47665/tb.40.1.004
    Circumsporozoite protein (CSP) central repeat region is one of the main target regions of the RTS,S/AS01 vaccine for falciparum infection as it consists of immunodominant B cell epitopes. However, there is a lack of study for P. knowlesi CSP central repeat region. This study aims to characterise the CSP repeat motifs of P. knowlesi isolates in Peninsular Malaysia. CSP repeat motifs of 64 P. knowlesi isolates were identified using Rapid Automatic Detection and Alignment of Repeats (RADAR). Antigenicity of the repeat motifs and linear B cell epitopes were predicted using VaxiJen 2.0, BepiPred-2.0 and BCPred, respectively. A total of 35 dominant repeat motifs were identified. The repeat motif "AGQPQAQGDGANAGQPQAQGDGAN" has the highest repeat frequency (n=15) and antigenicity index of 1.7986. All the repeat regions were predicted as B cell epitopes. In silico approaches revealed that all repeat motifs were antigenic and consisted of B cell epitopes which could be designed as knowlesi malaria vaccine.
  9. Genetic polymorphism and clustering of the Plasmodium cynomolgi Duffy binding protein 1 region II of recent macaque isolates from Peninsular Malaysia
    Latif ENM, Noordin NR, Shahari S, Amir A, Lau YL, Cheong FW, et al.
    Parasitol Res, 2024 Jan 19;123(1):105.
    PMID: 38240877 DOI: 10.1007/s00436-024-08125-0
    Plasmodium cynomolgi is a simian malaria parasite that has been increasingly infecting humans. It is naturally present in the long-tailed and pig-tailed macaques in Southeast Asia. The P. cynomolgi Duffy binding protein 1 region II [PcDBP1(II)] plays an essential role in the invasion of the parasite into host erythrocytes. This study investigated the genetic polymorphism, natural selection and haplotype clustering of PcDBP1(II) from wild macaque isolates in Peninsular Malaysia. The genomic DNA of 50 P. cynomolgi isolates was extracted from the macaque blood samples. Their PcDBP1(II) gene was amplified using a semi-nested PCR, cloned into a plasmid vector and subsequently sequenced. The polymorphism, natural selection and haplotypes of PcDBP1(II) were analysed using MEGA X and DnaSP ver.6.12.03 programmes. The analyses revealed high genetic polymorphism of PcDBP1(II) (π = 0.026 ± 0.004; Hd = 0.996 ± 0.001), and it was under purifying (negative) selection. A total of 106 haplotypes of PcDBP1(II) were identified. Phylogenetic and haplotype analyses revealed two groups of PcDBP1(II). Amino acid length polymorphism was observed between the groups, which may lead to possible phenotypic difference between them.
  10. Fulltext Genotyping of the Duffy blood group among Plasmodium knowlesi-infected patients in Malaysia
    De Silva JR, Lau YL, Fong MY
    PLoS One, 2014;9(9):e108951.
    PMID: 25268233 DOI: 10.1371/journal.pone.0108951
    The Duffy blood group is of major interest in clinical medicine as it plays an important role in Plasmodium knowlesi and Plasmodium vivax infection. In the present study, the distribution of Duffy blood group genotypes and allelic frequencies among P. knowlesi infected patients as well as healthy individuals in Peninsular Malaysia were determined. The blood group of 60 healthy blood donors and 51 P. knowlesi malaria patients were genotyped using allele specific polymerase chain reaction (ASP-PCR). The data was analyzed using Fisher's exact test in order to assess the significance of the variables. Our results show a high proportion of the FY*A/FY*A genotype (>85% for both groups) and a high frequency of the FY*A allele (>90% for both groups). The FY*A/FY*A genotype was the most predominant genotype in both infected and healthy blood samples. The genotype frequency did not differ significantly between the donor blood and the malaria patient groups. Also, there was no significant correlation between susceptibility to P. knowlesi infection with any Duffy blood genotype.
  11. Influenza vaccine concurrently administered with a combination measles, mumps, and rubella vaccine to young children
    Lum LC, Borja-Tabora CF, Breiman RF, Vesikari T, Sablan BP, Chay OM, et al.
    Vaccine, 2010 Feb 10;28(6):1566-74.
    PMID: 20003918 DOI: 10.1016/j.vaccine.2009.11.054
    Children aged 11 to <24 months received 2 intranasal doses of live attenuated influenza vaccine (LAIV) or placebo, 35+/-7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV+Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).
  12. Fulltext A Sensitive Reverse Transcription Loop-Mediated Isothermal Amplification Assay for Direct Visual Detection of SARS-CoV-2
    Lau YL, Ismail IB, Izati Binti Mustapa N, Lai MY, Tuan Soh TS, Hassan AH, et al.
    Am J Trop Med Hyg, 2020 Dec;103(6):2350-2352.
    PMID: 33098286 DOI: 10.4269/ajtmh.20-1079
    A simple and rapid reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the detection of SARS-CoV-2. The RT-LAMP assay was highly specific for SARS-CoV-2 and was able to detect one copy of transcribed SARS-CoV-2 RNA within 24 minutes. Assay validation performed using 50 positive and 32 negative clinical samples showed 100% sensitivity and specificity. The RT-LAMP would be valuable for clinical diagnosis and epidemiological surveillance of SARS-CoV-2 infection in resource-limited areas as it does not require the use of sophisticated and costly equipment.
  13. Fulltext Real-time reverse transcription loop-mediated isothermal amplification for rapid detection of SARS-CoV-2
    Lau YL, Ismail I, Mustapa NI, Lai MY, Tuan Soh TS, Hassan A, et al.
    PeerJ, 2020;8:e9278.
    PMID: 32547882 DOI: 10.7717/peerj.9278
    Background: Highly sensitive real-time reverse transcription polymerase chain reaction (RT-qPCR) methods have been developed for the detection of SARS-CoV-2. However, they are costly. Loop-mediated isothermal amplification (LAMP) assay has emerged as a novel alternative isothermal amplification method for the detection of nucleic acid.

    Methods: A rapid, sensitive and specific real-time reverse transcription LAMP (RT-LAMP) assay was developed for SARS-CoV-2 detection.

    Results: This assay detected one copy/reaction of SARS-CoV-2 RNA in 30 min. Both the clinical sensitivity and specificity of this assay were 100%. The RT-LAMP showed comparable performance with RT-qPCR. Combining simplicity and cost-effectiveness, this assay is therefore recommended for use in resource resource-limited settings.

  14. Fulltext Development of a reverse transcription recombinase polymerase amplification assay for rapid and direct visual detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
    Lau YL, Ismail IB, Mustapa NIB, Lai MY, Tuan Soh TS, Haji Hassan A, et al.
    PLoS One, 2021;16(1):e0245164.
    PMID: 33406112 DOI: 10.1371/journal.pone.0245164
    Rapid diagnosis is an important intervention in managing the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbreak. Real time reverse transcription polymerase chain reaction (RT-qPCR) remains the primary means for diagnosing the new virus strain but it is time consuming and costly. Recombinase polymerase amplification (RPA) is an isothermal amplification assay that does not require a PCR machine. It is an affordable, rapid, and simple assay. In this study, we developed and optimized a sensitive reverse transcription (RT)-RPA assay for the rapid detection of SARS-CoV-2 using SYBR Green I and/or lateral flow (LF) strip. The analytical sensitivity and specificity of the RT-RPA assay were tested by using 10-fold serial diluted synthetic RNA and genomic RNA of similar viruses, respectively. Clinical sensitivity and specificity of the RT-RPA assay were carried out using 78 positive and 35 negative nasopharyngeal samples. The detection limit of both RPA and RT-qPCR assays was 7.659 and 5 copies/μL RNA, respectively with no cross reactivity with other viruses. The clinical sensitivity and specificity of RT-RPA were 98% and 100%, respectively. Our study showed that RT-RPA represents a viable alternative to RT-qPCR for the detection of SARS-CoV-2, especially in areas with limited infrastructure.
  15. Fulltext Identification of circulating biomarkers in sera of Plasmodium knowlesi-infected malaria patients--comparison against Plasmodium vivax infection
    Chen Y, Chan CK, Kerishnan JP, Lau YL, Wong YL, Gopinath SC
    BMC Infect Dis, 2015;15:49.
    PMID: 25656928 DOI: 10.1186/s12879-015-0786-2
    Plasmodium knowlesi was identified as the fifth major malaria parasite in humans. It presents severe clinical symptoms and leads to mortality as a result of hyperparasitemia in a short period of time. This study aimed to improve the current understanding of P. knowlesi and identify potential biomarkers for knowlesi malaria.
  16. Fulltext In vitro invasion inhibition assay using antibodies against Plasmodium knowlesi Duffy binding protein alpha and apical membrane antigen protein 1 in human erythrocyte-adapted P. knowlesi A1-H.1 strain
    Muh F, Lee SK, Hoque MR, Han JH, Park JH, Firdaus ER, et al.
    Malar J, 2018 Jul 27;17(1):272.
    PMID: 30049277 DOI: 10.1186/s12936-018-2420-4
    BACKGROUND: The rapid process of malaria erythrocyte invasion involves ligand-receptor interactions. Inducing antibodies against specific ligands or receptors that abrogate the invasion process is a key challenge for blood stage vaccine development. However, few candidates were reported and remain to be validated for the discovery of new vaccine candidates in Plasmodium knowlesi.

    METHODS: In order to investigate the efficacy of pre-clinical vaccine candidates in P. knowlesi-infected human cases, this study describes an in vitro invasion inhibition assay, using a P. knowlesi strain adapted to in vitro growth in human erythrocytes, PkA1-H.1. Recombinant proteins of P. knowlesi Duffy binding protein alpha (PkDBPα) and apical membrane antigen 1 (PkAMA1) were produced in Escherichia coli system and rabbit antibodies were generated from immune animals.

    RESULTS: PkDBPα and PkAMA1 recombinant proteins were expressed as insoluble and produced as a functional refolded form for this study. Antibodies against PkDBPα and PkAMA1 specifically recognized recombinant proteins and native parasite proteins in schizont-stage parasites on the merozoite organelles. Single and combination of anti-PkDBPα and anti-PkAMA1 antibodies elicited strong growth inhibitory effects on the parasite in concentration-dependent manner. Meanwhile, IgG prevalence of PkDBPα and PkAMA1 were observed in 13.0 and 46.7% in human clinical patients, respectively.

    CONCLUSION: These data provide support for the validation of in vitro growth inhibition assay using antibodies of DBPα and AMA1 in human-adapted P. knowlesi parasite PkA1-H.1 strain.

  17. Fulltext Cross-species reactivity of antibodies against Plasmodium vivax blood-stage antigens to Plasmodium knowlesi
    Muh F, Kim N, Nyunt MH, Firdaus ER, Han JH, Hoque MR, et al.
    PLoS Negl Trop Dis, 2020 06;14(6):e0008323.
    PMID: 32559186 DOI: 10.1371/journal.pntd.0008323
    Malaria is caused by multiple different species of protozoan parasites, and interventions in the pre-elimination phase can lead to drastic changes in the proportion of each species causing malaria. In endemic areas, cross-reactivity may play an important role in the protection and blocking transmission. Thus, successful control of one species could lead to an increase in other parasite species. A few studies have reported cross-reactivity producing cross-immunity, but the extent of cross-reactive, particularly between closely related species, is poorly understood. P. vivax and P. knowlesi are particularly closely related species causing malaria infections in SE Asia, and whilst P. vivax cases are in decline, zoonotic P. knowlesi infections are rising in some areas. In this study, the cross-species reactivity and growth inhibition activity of P. vivax blood-stage antigen-specific antibodies against P. knowlesi parasites were investigated. Bioinformatics analysis, immunofluorescence assay, western blotting, protein microarray, and growth inhibition assay were performed to investigate the cross-reactivity. P. vivax blood-stage antigen-specific antibodies recognized the molecules located on the surface or released from apical organelles of P. knowlesi merozoites. Recombinant P. vivax and P. knowlesi proteins were also recognized by P. knowlesi- and P. vivax-infected patient antibodies, respectively. Immunoglobulin G against P. vivax antigens from both immune animals and human malaria patients inhibited the erythrocyte invasion by P. knowlesi. This study demonstrates that there is extensive cross-reactivity between antibodies against P. vivax to P. knowlesi in the blood stage, and these antibodies can potently inhibit in vitro invasion, highlighting the potential cross-protective immunity in endemic areas.
  18. Fulltext Cross-species analysis of apical asparagine-rich protein of Plasmodium vivax and Plasmodium knowlesi
    Muh F, Ahmed MA, Han JH, Nyunt MH, Lee SK, Lau YL, et al.
    Sci Rep, 2018 04 10;8(1):5781.
    PMID: 29636493 DOI: 10.1038/s41598-018-23728-1
    The Plasmodium falciparum apical asparagine (Asn)-rich protein (AARP) is one of malarial proteins, and it has been studied as a candidate of malaria subunit vaccine. Basic characterization of PvAARP has been performed with a focus on its immunogenicity and localization. In this study, we further analyzed the immunogenicity of PvAARP, focusing on the longevity of the antibody response, cross-species immunity and invasion inhibitory activity by using the primate malaria parasite Plasmodium knowlesi. We found that vivax malaria patient sera retained anti-PvAARP antibodies for at least one year without re-infection. Recombinant PvAARP protein was strongly recognized by knowlesi malaria patients. Antibody raised against the P. vivax and P. knowlesi AARP N-termini reacted with the apical side of the P. knowlesi merozoites and inhibited erythrocyte invasion by P. knowlesi in a concentration-dependent manner, thereby suggesting a cross-species nature of anti-PvAARP antibody against PkAARP. These results can be explained by B cell epitopes predicted in conserved surface-exposed regions of the AARP N-terminus in both species. The long-lived anti-PvAARP antibody response, cross-reactivity, and invasion inhibitory activity of anti-PvAARP support a critical role of AARP during the erythrocyte invasion and suggest that PvAARP induces long-lived cross-species protective immunity against P. vivax and P. knowlesi.
  19. Fulltext Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi
    Moon RW, Sharaf H, Hastings CH, Ho YS, Nair MB, Rchiad Z, et al.
    Proc Natl Acad Sci U S A, 2016 Jun 28;113(26):7231-6.
    PMID: 27303038 DOI: 10.1073/pnas.1522469113
    The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.
  20. Comparative analysis of ITS1 nucleotide sequence reveals distinct genetic difference between Brugia malayi from Northeast Borneo and Thailand
    Fong MY, Noordin R, Lau YL, Cheong FW, Yunus MH, Idris ZM
    Parasitology, 2013 Jan;140(1):39-45.
    PMID: 22917270 DOI: 10.1017/S0031182012001242
    Brugia malayi is one of the parasitic worms which causes lymphatic filariasis in humans. Its geographical distribution includes a large part of Asia. Despite its wide distribution, very little is known about the genetic variation and molecular epidemiology of this species. In this study, the internal transcribed spacer 1 (ITS1) nucleotide sequences of B. malayi from microfilaria-positive human blood samples in Northeast Borneo Island were determined, and compared with published ITS1 sequences of B. malayi isolated from cats and humans in Thailand. Multiple alignment analysis revealed that B. malayi ITS1 sequences from Northeast Borneo were more similar to each other than to those from Thailand. Phylogenetic trees inferred using Neighbour-Joining and Maximum Parsimony methods showed similar topology, with 2 distinct B. malayi clusters. The first cluster consisted of Northeast Borneo B. malayi isolates, whereas the second consisted of the Thailand isolates. The findings of this study suggest that B. malayi in Borneo Island has diverged significantly from those of mainland Asia, and this has implications for the diagnosis of B. malayi infection across the region using ITS1-based molecular techniques.
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