Displaying publications 41 - 60 of 220 in total

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  1. 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.].
  2. Song BK, Pan MZ, Lau YL, Wan KL
    Genet. Mol. Res., 2014;13(3):5803-14.
    PMID: 25117339 DOI: 10.4238/2014.July.29.8
    Commercial flocks infected by Eimeria species parasites, including Eimeria maxima, have an increased risk of developing clinical or subclinical coccidiosis; an intestinal enteritis associated with increased mortality rates in poultry. Currently, infection control is largely based on chemotherapy or live vaccines; however, drug resistance is common and vaccines are relatively expensive. The development of new cost-effective intervention measures will benefit from unraveling the complex genetic mechanisms that underlie host-parasite interactions, including the identification and characterization of genes encoding proteins such as phosphatidylinositol 4-phosphate 5-kinase (PIP5K). We previously identified a PIP5K coding sequence within the E. maxima genome. In this study, we analyzed two bacterial artificial chromosome clones presenting a ~145-kb E. maxima (Weybridge strain) genomic region spanning the PIP5K gene locus. Sequence analysis revealed that ~95% of the simple sequence repeats detected were located within regions comparable to the previously described feature-rich segments of the Eimeria tenella genome. Comparative sequence analysis with the orthologous E. maxima (Houghton strain) region revealed a moderate level of conserved synteny. Unique segmental organizations and telomere-like repeats were also observed in both genomes. A number of incomplete transposable elements were detected and further scrutiny of these elements in both orthologous segments revealed interesting nesting events, which may play a role in facilitating genome plasticity in E. maxima. The current analysis provides more detailed information about the genome organization of E. maxima and may help to reveal genotypic differences that are important for expression of traits related to pathogenicity and virulence.
  3. Zulzahrin Z, Wong ML, Naziri MRA, Lau YL, Vythilingam I, Lee WC
    Heliyon, 2024 Feb 15;10(3):e25207.
    PMID: 38322922 DOI: 10.1016/j.heliyon.2024.e25207
    Wing measurement is an important parameter in many entomological studies. However, the methods of measuring wings vary with studies, and a gold standard method was not available for this procedure. This in turn limits researchers from confidently comparing their research findings with published data collected by other means of measurement. This study investigated the interchangeability of three commonly available methods for wing measurement, namely the calliper method, stereomicroscope-assisted photography method, and digital microscope-assisted photography method, using the laboratory colony of Aedes aegypti. It was found that the calliper method and the photography-based methods yielded similar results, hence the good interchangeability of these methods. Nevertheless, the digital microscope-assisted photography method yielded more accurate measurements, due to the higher resolution of the captured photos, and minimal technical bias during the data collection, as compared to the calliper-based and stereomicroscope-assisted photography methods. This study served as a reference for researchers to select the most suitable measurement method in future studies.
  4. Ramli AH, Swain P, Mohd Fahmi MSA, Abas F, Leong SW, Tejo BA, et al.
    Heliyon, 2024 Mar 15;10(5):e27462.
    PMID: 38495201 DOI: 10.1016/j.heliyon.2024.e27462
    Malaria remains a major public health problem worldwide, including in Southeast Asia. Chemotherapeutic agents such as chloroquine (CQ) are effective, but problems with drug resistance and toxicity have necessitated a continuous search for new effective antimalarial agents. Here we report on a virtual screening of ∼300 diarylpentanoids and derivatives, in search of potential Plasmodium falciparum lactate dehydrogenase (PfLDH) inhibitors with acceptable drug-like properties. Several molecules with binding affinities comparable to CQ were chosen for in vitro validation of antimalarial efficacy. Among them, MS33A, MS33C and MS34C are the most promising against CQ-sensitive (3D7) with EC50 values of 1.6, 2.5 and 3.1 μM, respectively. Meanwhile, MS87 (EC50 of 1.85 μM) shown the most active against the CQ-resistant Gombak A strain, and MS33A and MS33C the most effective P. knowlesi inhibitors (EC50 of 3.6 and 5.1 μM, respectively). The in vitro cytotoxicity of selected diarylpentanoids (MS33A, MS33C, MS34C and MS87) was tested on Vero mammalian cells to evaluate parasite selectivity (SI), showing moderate to low cytotoxicity (CC50 > 82 μM). In addition, MS87 exhibited a high SI and the lowest resistance index (RI), suggesting that MS87 may exert effective parasite inhibition with low resistance potential in the CQ-resistant P. falciparum strain. Furthermore, the in vivo toxicity of the molecules on early embryonic development, the cardiovascular system, heart rate, motor activity and apoptosis were assessed in a zebrafish animal model. The overall results indicate the preliminary potential of diarylpentanoids, which need further investigation for their development as new antimalarial agents.
  5. Molineros JE, Yang W, Zhou XJ, Sun C, Okada Y, Zhang H, et al.
    Hum Mol Genet, 2017 03 15;26(6):1205-1216.
    PMID: 28108556 DOI: 10.1093/hmg/ddx026
    We recently identified ten novel SLE susceptibility loci in Asians and uncovered several additional suggestive loci requiring further validation. This study aimed to replicate five of these suggestive loci in a Han Chinese cohort from Hong Kong, followed by meta-analysis (11,656 cases and 23,968 controls) on previously reported Asian and European populations, and to perform bioinformatic analyses on all 82 reported SLE loci to identify shared regulatory signatures. We performed a battery of analyses for these five loci, as well as joint analyses on all 82 SLE loci. All five loci passed genome-wide significance: MYNN (rs10936599, Pmeta = 1.92 × 10-13, OR = 1.14), ATG16L2 (rs11235604, Pmeta = 8.87 × 10 -12, OR = 0.78), CCL22 (rs223881, Pmeta = 5.87 × 10-16, OR = 0.87), ANKS1A (rs2762340, Pmeta = 4.93 × 10-15, OR = 0.87) and RNASEH2C (rs1308020, Pmeta = 2.96 × 10-19, OR = 0.84) and co-located with annotated gene regulatory elements. The novel loci share genetic signatures with other reported SLE loci, including effects on gene expression, transcription factor binding, and epigenetic characteristics. Most (56%) of the correlated (r2 > 0.8) SNPs from the 82 SLE loci were implicated in differential expression (9.81 × 10-198 
  6. Amir A, Cheong FW, de Silva JR, Liew JWK, Lau YL
    Infect Drug Resist, 2018;11:1145-1155.
    PMID: 30127631 DOI: 10.2147/IDR.S148664
    Originally known to cause simian malaria, Plasmodium knowlesi is now known as the fifth human malaria species. Since the publishing of a report that largely focused on human knowlesi cases in Sarawak in 2004, many more human cases have been reported in nearly all of the countries in Southeast Asia and in travelers returning from these countries. The zoonotic nature of this infection hinders malaria elimination efforts. In order to grasp the current perspective of knowlesi malaria, this literature review explores the different aspects of the disease including risk factors, diagnosis, treatment, and molecular and functional studies. Current studies do not provide sufficient data for an effective control program. Therefore, future direction for knowlesi research is highlighted here with a final aim of controlling, if not eliminating, the parasite.
  7. Tan JH, Ding HX, Fong MY, Lau YL
    Infect Genet Evol, 2023 Oct;114:105490.
    PMID: 37595939 DOI: 10.1016/j.meegid.2023.105490
    Plasmodium knowlesi is the leading cause of malaria in Malaysia. Serine Repeat Antigens (SERAs) have an essential role in the parasite life cycle. However, genetic characterization on P. knowlesi SERA3 Ag2 (PkSERA3 Ag2) is lacking. In the present study, nucleotide diversity, natural selection, and haplotypes of PkSERA3 Ag2 in clinical samples from Peninsular Malaysia and Malaysian Borneo were investigated. A total of 50 P. knowlesi clinical samples were collected from Peninsular Malaysia and Malaysian Borneo. The PkSERA3 Ag2 gene was amplified using PCR, and subsequently cloned and sequenced. Genetic diversity, haplotype, natural selection as well as genetic structure and differentiation of PkSERA3 Ag2 were analysed. In addition, in silico analyses were performed to identify repeat motifs, B-cell epitopes, and antigenicity indices of the protein. Analysis of 114 PkSERA3 Ag2 sequences revealed high nucleotide diversity of the gene in Malaysia. A codon-based Z-test indicated that the gene underwent purifying selection. Haplotype and population structure analyses identified two distinct PkSERA3 Ag2 clusters (K = 2, ΔK = 721.14) but no clear genetic distinction between PkSERA3 Ag2 from Peninsular Malaysia and Malaysian Borneo. FST index indicated moderate differentiation of the gene. In silico analyses revealed unique repeat motifs among PkSERA3 Ag2 isolates. Moreover, the amino acid sequence of PkSERA3 Ag2 exhibited potential B-cell epitopes and possessed high antigenicity indices. These findings enhance the understanding of PkSERA3 Ag2 gene as well as its antigenic properties. Further validation is necessary to ascertain the utility of PkSERA3 Ag2 as a serological marker for P. knowlesi infection.
  8. van Schalkwyk DA, Blasco B, Davina Nuñez R, Liew JWK, Amir A, Lau YL, et al.
    PMID: 30831468 DOI: 10.1016/j.ijpddr.2019.02.004
    New antimalarial agents are identified and developed after extensive testing on Plasmodium falciparum parasites that can be grown in vitro. These susceptibility studies are important to inform lead optimisation and support further drug development. Until recently, little was known about the susceptibility of non-falciparum species as these had not been adapted to in vitro culture. The recent culture adaptation of P. knowlesi has therefore offered an opportunity to routinely define the drug susceptibility of this species, which is phylogenetically closer to all other human malarias than is P. falciparum. We compared the in vitro susceptibility of P. knowlesi and P. falciparum to a range of established and novel antimalarial agents under identical assay conditions. We demonstrated that P. knowlesi is significantly less susceptible than P. falciparum to six of the compounds tested; and notably these include three ATP4 inhibitors currently under development as novel antimalarial agents, and one investigational antimalarial, AN13762, which is 67 fold less effective against P. knowlesi. For the other compounds there was a less than two-fold difference in susceptibility between species. We then compared the susceptibility of a recent P. knowlesi isolate, UM01, to that of the well-established, older A1-H.1 clone. This recent isolate showed similar in vitro drug susceptibility to the A1-H.1 clone, supporting the ongoing use of the better characterised clone to further study drug susceptibility. Lastly, we used isobologram analysis to explore the interaction of a selection of drug combinations and showed similar drug interactions across species. The species differences in drug susceptibility reported by us here and previously, support adding in vitro drug screens against P. knowlesi to those using P. falciparum strains to inform new drug discovery and lead optimisation.
  9. Phang WK, Hamid MHA, Jelip J, Mudin RN, Chuang TW, Lau YL, et al.
    PMID: 33322414 DOI: 10.3390/ijerph17249271
    The life-threatening zoonotic malaria cases caused by Plasmodium knowlesi in Malaysia has recently been reported to be the highest among all malaria cases; however, previous studies have mainly focused on the transmission of P. knowlesi in Malaysian Borneo (East Malaysia). This study aimed to describe the transmission patterns of P. knowlesi infection in Peninsular Malaysia (West Malaysia). The spatial distribution of P. knowlesi was mapped across Peninsular Malaysia using Geographic Information System techniques. Local indicators of spatial associations were used to evaluate spatial patterns of P. knowlesi incidence. Seasonal autoregressive integrated moving average models were utilized to analyze the monthly incidence of knowlesi malaria in the hotspot region from 2012 to 2017 and to forecast subsequent incidence in 2018. Spatial analysis revealed that hotspots were clustered in the central-northern region of Peninsular Malaysia. Time series analysis revealed the strong seasonality of transmission from January to March. This study provides fundamental information on the spatial distribution and temporal dynamic of P. knowlesi in Peninsular Malaysia from 2011 to 2018. Current control policy should consider different strategies to prevent the transmission of both human and zoonotic malaria, particularly in the hotspot region, to ensure a successful elimination of malaria in the future.
  10. Lai MY, Bukhari FDM, Zulkefli NZ, Ismail I, Mustapa NI, Soh TST, et al.
    Int J Infect Dis, 2022 Jul;120:132-134.
    PMID: 35472524 DOI: 10.1016/j.ijid.2022.04.036
    OBJECTIVES: Preventing reverse transcription loop-mediated isothermal amplification (RT-LAMP) carryover contamination could be solved by adding deoxyuridine triphosphate (dUTP) and uracil-DNA glycosylase (UDG) into the reaction master mix.

    METHODS: RNA was extracted from nasopharyngeal swab samples by a simple RNA extraction method.

    RESULTS: Testing of 77 samples demonstrated 91.2% sensitivity (95% confidence interval [CI]: 78-98.2%) and 100% specificity (95% confidence interval: 92-100%) using UDG RT-LAMP.

    CONCLUSION: This colorimetric UDG RT-LAMP is a simple-to-use, fast, and easy-to-interpret method, which could serve as an alternative for diagnosis of SARS-CoV-2 infection, especially in remote hospitals and laboratories with under-equipped medical facilities.

  11. Mu AK, Bee PC, Lau YL, Chen Y
    Int J Mol Sci, 2014;15(11):19952-61.
    PMID: 25372941 DOI: 10.3390/ijms151119952
    Malaria is caused by parasitic protozoans of the genus Plasmodium and is one of the most prevalent infectious diseases in tropical and subtropical regions. For this reason, effective and practical diagnostic methods are urgently needed to control the spread of malaria. The aim of the current study was to identify a panel of new malarial markers, which could be used to diagnose patients infected with various Plasmodium species, including P. knowlesi, P. vivax and P. falciparum. Sera from malaria-infected patients were pooled and compared to control sera obtained from healthy individuals using the isobaric tags for relative and absolute quantitation (iTRAQ) technique. Mass spectrometry was used to identify serum proteins and quantify their relative abundance. We found that the levels of several proteins were increased in pooled serum from infected patients, including cell adhesion molecule-4 and C-reactive protein. In contrast, the serum concentration of haptoglobin was reduced in malaria-infected individuals, which we verified by western blot assay. Therefore, these proteins might represent infectious markers of malaria, which could be used to develop novel diagnostic tools for detecting P. knowlesi, P. vivax and P. falciparum. However, these potential malarial markers will need to be validated in a larger population of infected individuals.
  12. Mohd Fadil NF, Tengku-Idris TIN, Shahari S, Fong MY, Lau YL
    Iran J Parasitol, 2020 2 27;14(4):623-630.
    PMID: 32099565
    Background: The genus Sarcocystis consists of intracellular coccidian protozoan parasites with the ability to invade muscle tissue and mature into sarcocysts, causing the zoonotic disease sarcocystosis. These parasites have an obligatory two-host life cycle, which correlates with prey-predator relationship. The distribution and prevalence of Sarcocystis in reptiles remains unclear, despite several previous reports. The aim of this study was to identify the genetic assemblage of the species of Sarcocystis infecting Malaysian snakes and lizards by screening stool samples.

    Methods: Overall, 54 fecal samples of various snake species and four fecal samples of several lizard species in Malaysia were taken within the course of August 2015 to January 2016 from Seremban, Melaka, Tioman Island, Pahang, Klang and Langkawi Wildlife Park located in Malaysia. The samples were examined for Sarcocystis through PCR amplification of the 18S rDNA sequence at the Department of Parasitology, University of Malaya.

    Results: Fourteen snake fecal samples were positive via PCR; however, only eight samples (14%) were found positive for Sarcocystis species, whereas four were positive for other genera and the identity of another three samples was unable to be determined. Further phylogenetic analysis of the 18S rDNA sequences revealed that the snakes were infected with either S. singaporensis, S. lacertae, or undefined Sarcocystis species closely related to either S. singaporensis or S. zuoi. Sarcocystis nesbitti infection was not identified in any of the infected snakes.

    Conclusion: This is the first report of identification of S. lacertae in the black-headed cat snake.

  13. Wong YP, Othman S, Lau YL, Radu S, Chee HY
    J Appl Microbiol, 2018 Mar;124(3):626-643.
    PMID: 29165905 DOI: 10.1111/jam.13647
    Loop-mediated isothermal amplification (LAMP) amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions by using a DNA polymerase with high displacement strand activity and a set of specifically designed primers to amplify targeted DNA strands. Following its first discovery by Notomi et al. ( Nucleic Acids Res 28: E63), LAMP was further developed over the years which involved the combination of this technique with other molecular approaches, such as reverse transcription and multiplex amplification for the detection of infectious diseases caused by micro-organisms in humans, livestock and plants. In this review, available types of LAMP techniques will be discussed together with their applications in detection of various micro-organisms. Up to date, there are varieties of LAMP detection methods available including colorimetric and fluorescent detection, real-time monitoring using turbidity metre and detection using lateral flow device which will also be highlighted in this review. Apart from that, commercialization of LAMP technique had also been reported such as lyophilized form of LAMP reagents kit and LAMP primer sets for detection of pathogenic micro-organisms. On top of that, advantages and limitations of this molecular detection method are also described together with its future potential as a diagnostic method for infectious disease.
  14. Geier CB, Ellison M, Cruz R, Pawar S, Leiss-Piller A, Zmajkovicova K, et al.
    J Clin Immunol, 2022 Nov;42(8):1748-1765.
    PMID: 35947323 DOI: 10.1007/s10875-022-01312-7
    Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.
  15. Lau YL, Meganathan P, Sonaimuthu P, Thiruvengadam G, Nissapatorn V, Chen Y
    J Clin Microbiol, 2010 Oct;48(10):3698-702.
    PMID: 20660217 DOI: 10.1128/JCM.00462-10
    Loop-mediated isothermal amplification (LAMP), a rapid nucleic acid amplification method, was developed for the clinical diagnosis of toxoplasmosis. Three LAMP assays based on the SAG1, SAG2, and B1 genes of Toxoplasma gondii were developed. The sensitivities and specificities of the LAMP assays were evaluated by comparison with the results of conventional nested PCR. The LAMP assays were highly sensitive and had a detection limit of 0.1 tachyzoite, and no cross-reactivity with the DNA of other parasites was observed. Blood was collected from 105 individuals to test the LAMP assays: 40 patients with active toxoplasmosis, 40 negative controls, and 25 patients with other parasitic infections. The SAG2-based LAMP (SAG2-LAMP) had a greater sensitivity (87.5%) than the SAG1-LAMP (80%), B1-LAMP (80%), and nested PCR (62.5%). All the LAMP assays and nested PCR were 100% specific. This is the first report of a study which applied the LAMP method to diagnose toxoplasmosis from human blood samples. Due to its simplicity, sensitivity, and specificity, LAMP is suggested as an appropriate method for routine diagnosis of active toxoplasmosis in humans.
  16. Fong MY, Lau YL, Jelip J, Ooi CH, Cheong FW
    J Genet, 2019 Sep;98.
    PMID: 31544794
    Plasmodium knowlesi contributes to the majority of human malaria incidences in Malaysia. Its uncontrollable passage among the natural monkey hosts can potentially lead to zoonotic outbreaks. The merozoite of this parasite invades host erythrocytes through interaction between its erythrocyte-binding proteins (EBPs) and their respective receptor on the erythrocytes. The regionII of P. knowlesi EBP, P. knowlesi beta (PkβII) protein is found to be mediating merozoite invasion into monkey erythrocytes by interacting with sialic acid receptors. Hence, the objective of this study was to investigate the genetic diversity, natural selection and haplotype grouping of PkβII of P. knowlesi isolates in Malaysia. Polymerase chain reaction amplifications of PkβII were performed on archived blood samples from Malaysia and 64 PkβII sequences were obtained. Sequence analysis revealed length polymorphism, and its amino acids at critical residues indicate the ability of PkβII to mediate P. knowlesi invasion into monkey erythrocytes. Low genetic diversity (π = 0.007) was observed in the PkβII of Malaysia Borneo compared to Peninsular Malaysia (π = 0.015). The PkβII was found to be under strong purifying selection to retain infectivity in monkeys and it plays a limited role in the zoonotic potential of P. knowlesi. Its haplotypes could be clustered into Peninsular Malaysia and Malaysia Borneo groups, indicating the existence of two distinct P. knowlesi parasites in Malaysia as reported in an earlier study.
  17. Mokhtar AS, Braima KA, Peng Chin H, Jeffery J, Mohd Zain SN, Rohela M, et al.
    J Med Entomol, 2016 Apr 25.
    PMID: 27113101 DOI: 10.1093/jme/tjw014
    We report a case of human intestinal myiasis in a 41-yr-old female patient presented at a clinic in Seri Kembangan, Selangor, Malaysia. Larvae passed out in the patient's feces were sent to the Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. DNA barcoding confirmed the second case of intestinal myiasis in Malaysia involving the larvae of Clogmia albipunctatus (Duckhouse) (Diptera: Psychodidae). We review reported cases of myiasis and discuss the present case of intestinal myiasis in an urban patient.
  18. Mokhtar AS, Sridhar GS, Mahmud R, Jeffery J, Lau YL, Wilson JJ, et al.
    J Med Entomol, 2016 Sep 01;53(5):1234-1237.
    PMID: 27208008 DOI: 10.1093/jme/tjw071
    We report an unusual cause of gastrointestinal infection occurring in a 1-year-old infant patient who was brought to a public hospital in Kuala Lumpur, Malaysia. Larvae passed out in the patient's feces were confirmed by DNA barcoding as belonging to the species, Lasioderma serricorne (F.), known as the cigarette beetle. We postulate that the larvae were acquired from contaminated food and were responsible for gastrointestinal symptoms in the patient. To our knowledge, this the first report of human canthariasis caused by larvae of L. serricorne.
  19. Liew JW, Mahmud R, Tan LH, Lau YL
    Malar J, 2016;15:8.
    PMID: 26738724 DOI: 10.1186/s12936-015-1070-z
    Plasmodium ovale is rare and not exactly known to be autochthonous in Malaysia. There are two distinct forms of the parasite, namely P. ovale curtisi (classic form) and P. ovale wallikeri (variant form). Here, the first sequence confirmed case of an imported P. ovale wallikeri infection in Malaysia is presented. Microscopy found Plasmodium parasites with morphology similar to P. ovale or Plasmodium vivax in the blood films. Further confirmation using polymerase chain reaction (PCR) targeting the small-subunit rRNA gene of the parasite was unsuccessful. Genus-specific PCR was then performed and the product was sequenced and analysed. Sequence analyses confirmed the aetiological agent as P. ovale wallikeri. New species-specific primers (rOVA1v and rOVA2v) were employed and P. ovale wallikeri was finally confirmed. The findings highlight the need to look out for imported malaria infections in Malaysia and the importance of a constantly updated and validated diagnostic technique.
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