Displaying publications 41 - 60 of 220 in total

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  1. Lai MY, Ooi CH, Lau YL
    Am J Trop Med Hyg, 2018 03;98(3):700-703.
    PMID: 29260656 DOI: 10.4269/ajtmh.17-0738
    The aim of this study was to develop a recombinase polymerase amplification (RPA) combined with a lateral flow (LF) strip method for specific diagnosis of Plasmodium knowlesi. With incubation at 37°C, the 18S rRNA gene of P. knowlesi was successfully amplified within 12 minutes. By adding a specifically designed probe to the reaction solution, the amplified RPA product can be visualized on a LF strip. The RPA assay exhibited high sensitivity with limits of detection down to 10 parasites/μL of P. knowlesi. Nonetheless, it was demonstrated that all P. knowlesi (N = 41) and other Plasmodium sp. (N = 25) were positive while negative samples (N = 8) were negative. Therefore, a combination of RPA and LF strip detection is a highly promising approach with the potential to be suitable for use in resource-limited settings.
  2. Fong MY, Lau YL
    Parasitol Res, 2004 Jan;92(2):173-6.
    PMID: 14655048
    A gene encoding the larval excretory-secretory antigen TES-120 of the dog ascarid worm Toxocara canis was cloned into the methylotrophic yeast Pichia pastoris. Specificity of the recombinant TES-120 antigen produced by the yeast was investigated. Forty-five human serum samples from patients infected with different()parasitic organisms, including 8 cases of toxocariasis, were tested against the recombinant antigen in immunoblot assays. Results from the assays showed that the recombinant TES-120 antigen reacted with sera from toxocariasis patients only. This highly specific recombinant TES-120 antigen can potentially be used for the development of an inexpensive serodiagnostic assay for human toxocariasis.
  3. Fong MY, Lau YL, Init I, Jamaiah I, Anuar AK, Rahmah N
    PMID: 15115078
    The gene encoding the excretory-secretory antigen TES-120 of dog ascarid worm Toxocara canis was cloned into the bacterium Escherichia coli. The specificity of the recombinant TES-120 antigen produced by the bacterium was investigated. A total of 45 human serum samples from patients infected with differenthelminthes and protozoa, including 8 cases of toxocariasis, were tested against the recombinant antigens in immunoblot assays. The results from the assays revealed that the recombinant TES-120 antigen reacted with sera from toxocariasis patients only. This highly specific recombinant TES-120 antigen can potentially be used for the development of an inexpensive serodiagnostic assay for human toxocariasis.
  4. Ching XT, Lau YL, Fong MY, Nissapatorn V, Andiappan H
    Biomed Res Int, 2014;2014:690529.
    PMID: 24987700 DOI: 10.1155/2014/690529
    Toxoplasma gondii infects all warm-blooded animals, including humans, causing serious public health problems and great economic loss for the food industry. Commonly used serological tests require costly and hazardous preparation of whole Toxoplasma lysate antigens from tachyzoites. Here, we have evaluated an alternative method for antigen production, which involved a prokaryotic expression system. Specifically, we expressed T. gondii dense granular protein-5 (GRA5) in Escherichia coli and isolated it by affinity purification. The serodiagnostic potential of the purified recombinant GRA5 (rGRA5) was tested through Western blot analysis against 212 human patient serum samples. We found that rGRA5 protein was 100% specific for analysis of toxoplasmosis-negative human sera. Also, rGRA5 was able to detect acute and chronic T. gondii infections (sensitivities of 46.8% and 61.2%, resp.).
  5. 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.

  6. Lau YL, Anthony C, Fakhrurrazi SA, Ibrahim J, Ithoi I, Mahmud R
    Parasit Vectors, 2013;6(1):250.
    PMID: 23985047 DOI: 10.1186/1756-3305-6-250
    Amebiasis caused by Entamoeba histolytica is the third leading cause of death worldwide. This pathogenic amoeba is morphologically indistinguishable from E. dispar and E. moshkovskii, the non-pathogenic species. Polymerase chain reaction is the current method of choice approved by World Health Organization. Real-time PCR is another attractive molecular method for diagnosis of infectious diseases as post-PCR analyses are eliminated and turnaround times are shorter. The present work aimed to compare the results of Entamoeba species identification using the real-time assay against the established nested PCR method.
  7. Lai MY, Ooi CH, Lau YL
    Am J Trop Med Hyg, 2017 Nov;97(5):1597-1599.
    PMID: 28820700 DOI: 10.4269/ajtmh.17-0427
    In this study, we developed a recombinase polymerase amplification (RPA) assay for specific diagnosis of Plasmodium knowlesi. Genomic DNA was extracted from whole blood samples using a commercial kit. With incubation at 37°C, the samples were successfully amplified within 20 minutes. The end product of RPA was further examined by loading onto agarose gel and a specific band was observed with a size of 128 bp. The RPA assay exhibited high sensitivity with limits of detection down to one copy of the plasmid. From the specificity experiments, it was demonstrated that all P. knowlesi samples (N = 45) were positive while other Plasmodium spp. (N = 42) and negative samples (N = 6) were negative. Therefore, the RPA assay is a highly promising approach with the potential to be used in resource-limited settings. This assay can be further optimized for bedside and on field application.
  8. Lai MY, Suppiah J, Thayan R, Ismail I, Mustapa NI, Soh TST, et al.
    Trop Med Health, 2022 Jan 04;50(1):2.
    PMID: 34980275 DOI: 10.1186/s41182-021-00396-y
    BACKGROUND: Current diagnosis of SARS-CoV-2 infection relies on RNA purification prior to amplification. Typical extraction methods limit the processing speed and turnaround time for SARS-CoV-2 diagnostic testing.

    METHODS: Here, we applied reverse transcription loop-mediated isothermal amplification directly onto human clinical swabs samples to amplify the RNA from SARS-CoV-2 swab samples after processing with chelating resin.

    RESULTS: By testing our method on 64 samples, we managed to develop an RT-LAMP assay with 95.9% sensitivity (95% CI 86 to 99.5%) and 100% specificity (95% CI 78.2-100%).

    CONCLUSION: The entire process including sample processing can be completed in approximately 50 min. This method has promising potential to be applied as a fast, simple and inexpensive diagnostic tool for the detection of SARS-CoV-2.

  9. Liew JWK, Fong MY, Lau YL
    PeerJ, 2017;5:e3577.
    PMID: 28761783 DOI: 10.7717/peerj.3577
    Quantitative reverse transcription PCR (qRT-PCR) has been an integral part of characterizing the immunity of Anopheles mosquitoes towards Plasmodium invasion. Two anti-Plasmodium factors of Anopheles, thioester-containing protein 1 (TEP1) and nitric oxide synthase (NOS), play a role in the refractoriness of Anopheles towards Plasmodium infection and are generally expressed during infection. However, these are less studied in Anopheles dirus, a dominant malaria vector in Southeast Asia. Furthermore, most studies used a single reference gene for normalization during gene expression analysis without proper validation. This may lead to erroneous quantification of expression levels. Therefore, the present study characterized and investigated the expression profiles of TEP1 and NOS of Anopheles dirus during P. berghei infection. Prior to that, the elongation factor 1-alpha (EF1), actin 1 (Act) and ribosomal protein S7 (S7) genes were validated for their suitability as a set of reference genes. TEP1 and NOS expressions in An. dirus were found to be significantly induced after P. berghei infection.
  10. Mohd Hanapi IR, Sahimin N, Lewis JW, Lau YL, Othman J, Tedong PA, et al.
    Trop Biomed, 2021 Dec 01;38(4):594-604.
    PMID: 35001926 DOI: 10.47665/tb.38.4.103
    The United Nations High Commissioner for Refugees (UNHCR) reports over 80 million people are displaced worldwide with approximately 26.3 million categorized as refugees and over a million residing temporarily in South East Asia. Despite the lack of national legislative framework in place for refugees and asylum seekers (RAS), Malaysia hosts approximately 178,140 as registered with UNHCR and the majority originate from Myanmar. In this review, we examine refugees from South East Asia, particularly from Myanmar that have contributed to the largest influx of refugees to this region with a focus on their health status. The present study traces barriers to the health care of refugees in the country of asylum and also the challenges faced by these communities in accessing health services.
  11. Parthasarathy S, Fong MY, Ramaswamy K, Lau YL
    Am J Trop Med Hyg, 2013 May;88(5):883-7.
    PMID: 23509124 DOI: 10.4269/ajtmh.12-0727
    Toxoplasmosis in humans and other animals is caused by the protozoan parasite Toxoplasma gondii. During the process of host cell invasion and parasitophorous vacuole formation by the tachyzoites, the parasite secretes Rhoptry protein 8 (ROP8), an apical secretory organelle. Thus, ROP8 is an important protein for the pathogenesis of T. gondii. The ROP8 DNA was constructed into a pVAX-1 vaccine vector and used for immunizing BALB/c mice. Immunized mice developed immune response characterized by significant antibody responses, antigen-specific proliferation of spleen cells, and production of high levels of IFN-γ (816 ± 26.3 pg/mL). Challenge experiments showed significant levels of increase in the survival period (29 days compared with 9 days in control) in ROP8 DNA vaccinated mice after a lethal challenge with T. gondii. Results presented in this study suggest that ROP8 DNA is a promising and potential vaccine candidate against toxoplasmosis.
  12. Ooi CH, Phang WK, Liew JWK, Atroosh WM, Lau YL
    Trop Med Int Health, 2023 Jun;28(6):486-500.
    PMID: 37042251 DOI: 10.1111/tmi.13875
    OBJECTIVES: Malaysia has achieved the status of zero indigenous human malaria cases. Nevertheless, imported human malaria has increasingly been reported in Sarawak, Malaysian Borneo. As zoonotic malaria caused by Plasmodium knowlesi remains a major public health problem in Sarawak, the threat of imported malaria must be addressed as it can cause human malaria reintroduction, sustain transmission, and lead to complications. The objectives of this study were to investigate the epidemiological characteristics of imported malaria cases reported in Sarawak and to underline the challenge posed by imported malaria towards malaria elimination efforts.

    METHODS: Imported malaria cases reported in Sarawak from 2011 to 2019 were collected from Sarawak State Health Department and analysed in this longitudinal retrospective study.

    RESULTS: A total of 2058 imported malaria cases were registered in all districts in Sarawak. Highest number of cases were reported in Kapit (n = 559; 27.16%), followed by Sibu (n = 424; 20.6%), and Miri (n = 166; 8.07%). Based on the demographic profile, most of the patients constituted of either male sex (98.49%), age group of 40-49 years (39.6%), Iban ethnic (57.92%), worked in logging industry (88.58%), Malaysian nationals (91.84%), contracted malaria in Papua New Guinea (46.11%), uncomplicated disease (77.89%), or hospitalised cases (97.86%). The most prominent Plasmodium species diagnosed were P. vivax (52.67%) and P. falciparum (35.81%).

    CONCLUSIONS: Surveillance, disease detection, and medical follow-up must be carried out thoroughly for individuals who returned from malaria-endemic countries. It is also necessary to promote pre-travel preventive education as well as chemoprophylaxis to travellers heading to endemic areas.

  13. Meyts I, Bousfiha A, Duff C, Singh S, Lau YL, Condino-Neto A, et al.
    Front Immunol, 2020;11:625753.
    PMID: 33679719 DOI: 10.3389/fimmu.2020.625753
  14. Siti Shafiyyah CO, Jamaiah I, Rohela M, Lau YL, Siti Aminah F
    Trop Biomed, 2012 Dec;29(4):544-50.
    PMID: 23202599 MyJurnal
    A survey was undertaken to investigate the prevalence of intestinal and blood parasites among wild rats in urban area of Kuala Lumpur, Malaysia. A total of 137 stool and blood samples were collected from wild rats from Sentul and Chow Kit areas. Five species of rats were captured and supplied by Kuala Lumpur City Hall. The most common was Rattus rattus diardii (Malayan Black rat), 67%, followed by Rattus norvegicus (Norway rat), 10%, Rattus argentiventer (rice-field rat), 10%, Rattus tiomanicus (Malaysian field rat), 9% and Rattus exulans (Polynesian rat), 4%. Rattus rattus diardii is commonly known to live in human environment and they are normally identified as pests to human community. More male rats were captured (61%) compared to female (39%). Out of 137 samples, 81.8% samples were positive with intestinal parasites, with 86.2% from Sentul area and 78.5% from Chow Kit area. Six different parasites were detected. The most common intestinal helminth parasite detected was Nippostrongylus brasiliensis (80.3%), followed by Hymenolepis nana (23.4%), Capillaria hepatica (13.9%) and Hymenolepis diminuta (2.9%). Intestinal protozoan detected was Entamoeba histolytica/E. dispar (8.8%). Trypanosoma lewisi (1.5%) was the only blood parasite detected.
  15. Mohd Hanapi IR, Sahimin N, Maackara MJB, Annisa AS, Abdul Mutalib RNS, Lewis JW, et al.
    BMC Infect Dis, 2021 Nov 01;21(1):1128.
    PMID: 34724919 DOI: 10.1186/s12879-021-06830-0
    BACKGROUND: Refugees in Malaysia, who are afflicted by poverty, conflict and poor health, are vulnerable to a range of zoonotic infections in the deprived environmental and social conditions under which they live. Exposure to infections such as leptospirosis, for which rodents are primary hosts, is of particular concern.

    METHODS: A wellness program was conducted to determine the presence of antibodies against Leptospira (seroprevalence) in 11 refugee community schools and centers in the Klang Valley, Malaysia. A total of 433 samples were assessed for IgG and IgM antibodies against Leptospira, using enzyme-linked immunosorbent assays (ELISA).

    RESULTS: Overall Leptospira seroprevalence was 24.7%, with 3.0% being seropositive for anti-Leptospira IgG and 21.7% for anti-Leptospira IgM. Factors significantly associated with overall Leptospira seroprevalence included: age, ethnicity, pet ownership, knowledge of disease and awareness of disease fatality. For IgM seroprevalence, significant risk factors included sex, ethnicity, eating habits with hands, pet ownership, the presence of rats, walking in bare feet and water recreation visits.

    CONCLUSIONS: These findings highlight the need for improvements in health and well-being among the refugee community through disease awareness programs and provision of healthy behavior programs, particularly in hygiene and sanitation through community engagement activities.

  16. Noordin NR, Lee PY, Mohd Bukhari FD, Fong MY, Abdul Hamid MH, Jelip J, et al.
    Am J Trop Med Hyg, 2020 09;103(3):1107-1110.
    PMID: 32618263 DOI: 10.4269/ajtmh.20-0268
    Asymptomatic and/or low-density malaria infection has been acknowledged as an obstacle to achieving a malaria-free country. This study aimed to determine the prevalence of asymptomatic and/or low-density malaria infection in previously reported malarious localities using nested PCR in four states, namely, Johor, Pahang, Kelantan, and Selangor, between June 2019 and January 2020. Blood samples (n = 585) were collected and were extracted using a QIAamp blood kit. The DNA was concentrated and subjected to nested PCR. Thin and thick blood smears were examined as well. Of the 585 samples collected, 19 were positive: 10 for Plasmodium knowlesi, eight for Plasmodium vivax, and one for Plasmodium ovale. Asymptomatic and/or low-density malaria infection is a threat to malaria elimination initiatives. Eliminating countries should develop guidance policy on the importance of low-density malaria infection which includes detection and treatment policy.
  17. 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.
  18. 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.
  19. Li LF, Pusadee T, Wedger MJ, Li YL, Li MR, Lau YL, et al.
    Nat Commun, 2024 Feb 21;15(1):1182.
    PMID: 38383554 DOI: 10.1038/s41467-024-45447-0
    High reproductive compatibility between crops and their wild relatives can provide benefits for crop breeding but also poses risks for agricultural weed evolution. Weedy rice is a feral relative of rice that infests paddies and causes severe crop losses worldwide. In regions of tropical Asia where the wild progenitor of rice occurs, weedy rice could be influenced by hybridization with the wild species. Genomic analysis of this phenomenon has been very limited. Here we use whole genome sequence analyses of 217 wild, weedy and cultivated rice samples to show that wild rice hybridization has contributed substantially to the evolution of Southeast Asian weedy rice, with some strains acquiring weed-adaptive traits through introgression from the wild progenitor. Our study highlights how adaptive introgression from wild species can contribute to agricultural weed evolution, and it provides a case study of parallel evolution of weediness in independently-evolved strains of a weedy crop relative.
  20. Turkiewicz A, Manko E, Oresegun DR, Nolder D, Spadar A, Sutherland CJ, et al.
    Sci Rep, 2023 Feb 07;13(1):2142.
    PMID: 36750737 DOI: 10.1038/s41598-023-29368-4
    The zoonotic Plasmodium knowlesi parasite is a growing public health concern in Southeast Asia, especially in Malaysia, where elimination of P. falciparum and P. vivax malaria has been the focus of control efforts. Understanding of the genetic diversity of P. knowlesi parasites can provide insights into its evolution, population structure, diagnostics, transmission dynamics, and the emergence of drug resistance. Previous work has revealed that P. knowlesi fall into three main sub-populations distinguished by a combination of geographical location and macaque host (Macaca fascicularis and M. nemestrina). It has been shown that Malaysian Borneo groups display profound heterogeneity with long regions of high or low divergence resulting in mosaic patterns between sub-populations, with some evidence of chromosomal-segment exchanges. However, the genetic structure of non-Borneo sub-populations is less clear. By gathering one of the largest collections of P. knowlesi whole-genome sequencing data, we studied structural genomic changes across sub-populations, with the analysis revealing differences in Borneo clusters linked to mosquito-related stages of the parasite cycle, in contrast to differences in host-related stages for the Peninsular group. Our work identifies new genetic exchange events, including introgressions between Malaysian Peninsular and M. nemestrina-associated clusters on various chromosomes, including in parasite invasion genes (DBP[Formula: see text], NBPX[Formula: see text] and NBPX[Formula: see text]), and important proteins expressed in the vertebrate parasite stages. Recombination events appear to have occurred between the Peninsular and M. fascicularis-associated groups, including in the DBP[Formula: see text] and DBP[Formula: see text] invasion associated genes. Overall, our work finds that genetic exchange events have occurred among the recognised contemporary groups of P. knowlesi parasites during their evolutionary history, leading to apparent mosaicism between these sub-populations. These findings generate new hypotheses relevant to parasite evolutionary biology and P. knowlesi epidemiology, which can inform malaria control approaches to containing the impact of zoonotic malaria on human communities.
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