Displaying publications 1 - 20 of 220 in total

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  1. Synthesis and biological evaluation of hydantoin derivatives as potent antiplasmodial agents
    Chin EZ, Chang WJ, Tan HY, Liew SY, Lau YL, Ng YL, et al.
    Bioorg Med Chem Lett, 2024 May 01;103:129701.
    PMID: 38484804 DOI: 10.1016/j.bmcl.2024.129701
    Malaria, a devastating disease, has claimed numerous lives and caused considerable suffering, with young children and pregnant women being the most severely affected group. However, the emergence of multidrug-resistant strains of Plasmodium and the adverse side effects associated with existing antimalarial drugs underscore the urgent need for the development of novel, well-tolerated, and more efficient drugs to combat this global health threat. To address these challenges, six new hydantoins derivatives were synthesized and evaluated for their in vitro antiplasmodial activity. Notably, compound 2c exhibited excellent inhibitory activity against the tested Pf3D7 strain, with an IC50 value of 3.97 ± 0.01 nM, three-fold better than chloroquine. Following closely, compound 3b demonstrated an IC50 value of 27.52 ± 3.37 µM against the Pf3D7 strain in vitro. Additionally, all the hydantoins derivatives tested showed inactive against human MCR-5 cells, with an IC50 value exceeding 100 μM. In summary, the hydantoin derivative 2c emerges as a promising candidate for further exploration as an antiplasmodial compound.
  2. Recombinase-Aided Loop-Mediated Isothermal Amplification on Human Plasmodium knowlesi
    Lai MY, Abdul Hamid MH, Jelip J, Mudin RN, Lau YL
    Am J Trop Med Hyg, 2024 Apr 03;110(4):648-652.
    PMID: 38412548 DOI: 10.4269/ajtmh.23-0572
    Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification technique that can amplify specific nucleic acids at a constant temperature (63-65°C) within a short period (<1 hour). In this study, we report the utilization of recombinase-aided LAMP to specifically amplify the 18S sRNA of Plasmodium knowlesi. The method was built on a conventional LAMP assay by inclusion of an extra enzyme, namely recombinase, into the master mixture. With the addition of recombinase into the LAMP assay, the assay speed was executed within a time frame of less than 28 minutes at 65°C. We screened 55 P. knowlesi samples and 47 non-P. knowlesi samples. No cross-reactivity was observed for non-P. knowlesi samples, and the detection limit for recombinase-aided LAMP was one copy for P. knowlesi after LAMP amplification. It has been reported elsewhere that LAMP can be detected through fluorescent readout systems. Although such systems result in considerable limits of detection, the need for sophisticated equipment limits their use. Hence, we used here a colorimetric detection platform for the evaluation of the LAMP assay's performance. This malachite green-based recombinase-aided LAMP assay enabled visualization of results with the naked eye. Negative samples were observed by a change in color from green to colorless, whereas positive samples remained green. Our results demonstrate that the LAMP assay developed here is a convenient, sensitive, and useful diagnostic tool for the rapid detection of knowlesi malaria parasites. This method is suitable for implementation in remote healthcare settings, where centralized laboratory facilities, funds, and clinicians are in short supply.
  3. Fulltext Preliminary insight on diarylpentanoids as potential antimalarials: In silico, in vitro pLDH and in vivo zebrafish toxicity assessment
    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.
  4. Fulltext The prevalence of simian malaria in wild long-tailed macaques throughout Peninsular Malaysia
    Shahari S, Bin Abdullah ML, Binti Isman Rohimly AA, Binti Ashrat N, Amir A, Atroosh WMM, et al.
    Sci Rep, 2024 Mar 12;14(1):6023.
    PMID: 38472278 DOI: 10.1038/s41598-024-54981-2
    The parasite Plasmodium knowlesi has been the sole cause of malaria in Malaysia from 2018 to 2022. The persistence of this zoonotic species has hampered Malaysia's progress towards achieving the malaria-free status awarded by the World Health Organisation (WHO). Due to the zoonotic nature of P. knowlesi infections, it is important to study the prevalence of the parasite in the macaque host, the long-tailed macaque (Macaca fascicularis). Apart from P. knowlesi, the long-tailed macaque is also able to harbour Plasmodium cynomolgi, Plasmodium inui, Plasmodium caotneyi and Plasmodium fieldi. Here we report the prevalence of the 5 simian malaria parasites in the wild long-tailed macaque population in 12 out of the 13 states in Peninsular Malaysia using a nested PCR approach targeting the 18s ribosomal RNA (18s rRNA) gene. It was found that all five Plasmodium species were widely distributed throughout Peninsular Malaysia except for states with major cities such as Kuala Lumpur and Putrajaya. Of note, Pahang reported a malaria prevalence of 100% in the long-tailed macaque population, identifying it as a potential hotspot for zoonotic transmission. Overall, this study shows the distribution of the 5 simian malaria parasite species throughout Peninsular Malaysia, the data of which could be used to guide future malaria control interventions to target zoonotic malaria.
  5. A visualized hybrid PCR-LAMP assay for the detection of human Plasmodium species
    Lai MY, Ponnampalavanar SSS, Omar SFS, Lau YL
    Acta Trop, 2024 Mar;251:107120.
    PMID: 38199452 DOI: 10.1016/j.actatropica.2024.107120
    Combining the advantages of PCR and LAMP, we described a new technique, namely PCR-LAMP, for malaria diagnosis. The whole process of DNA amplification can be completed in 35 min. This hybrid amplification technique markedly improved the sensitivity of detection compared to the classic single PCR or LAMP assay alone. PCR-LAMP assay had a detection limit of 1 copy/µL for P. knowlesi and P. ovale, 0.1 copy/µL for P. vivax, P. falciparum and P. malariae, respectively. To facilitate the endpoint detection, xylenol orange was added. Positive samples were indicated in orange while negative reactions were violet. The inclusion of xylenol orange into the LAMP reaction mix significantly reduces the post-amplification workload. Without relying on the use of specific instruments, the color changes of the amplicons could be visualized directly through the naked eye. In conclusion, PCR-LAMP poses the potential to be developed as a new malaria molecular diagnosis tool.
  6. Fulltext Porous borders at the wild-crop interface promote weed adaptation in Southeast Asia
    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.
  7. Fulltext Digital microscope-assisted photography improves the accuracy of mosquito wing measurement
    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.
  8. Corrigendum to "Genetic polymorphism of circumsporozoite protein (CSP) in Plasmodium malariae isolates from Malaysia" [Parasitology International Volume 87, April 2022, 102519]
    Phang WK, Bukhari FDM, Zen LPY, Jaimin JJ, Dony JJF, Lau YL
    Parasitol Int, 2024 Feb;98:102811.
    PMID: 37827924 DOI: 10.1016/j.parint.2023.102811
  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. Intestinal parasitic infections and risk analysis among urban refugees in the Klang Valley, Malaysia
    Mohd Hanapi IR, Behnke JM, Sahimin N, Saifulazmi NF, Golam Mohammad Khan ASJ, Abdul Mutalib RNS, et al.
    Trans R Soc Trop Med Hyg, 2024 Jan 02;118(1):18-32.
    PMID: 37497742 DOI: 10.1093/trstmh/trad047
    BACKGROUND: Global studies show intestinal parasitic infections (IPIs) have been introduced and spread with refugee inflows from low to high socio-economic countries. However, there is relatively limited information on the prevalence of infections among the community.

    METHODS: A 2-year cross-sectional study was conducted to determine the prevalence and associated risk factors for infections among urban refugees in the Klang Valley, Malaysia. A total of 418 faecal samples were collected and examined by microscopy.

    RESULTS: Faecal screening revealed moderate levels (32.3%) of infections in the community. Three nematode (Ascaris lumbricoides, Trichuris trichiura and hookworm) and three protozoan species (Entamoeba, Giardia and Cryptosporidium) were recorded, with the highest prevalence being A. lumbricoides (20.6%) followed by T. trichiura (10.3%), while other infections were <5%. Statistical analysis found that young males with less education were more likely to be infected with helminths. Additionally, living near waste disposal sites, the presence of stray animals, eating with bare hands, bare footedness, poor handwashing practices and no anthelmintic treatment constituted significant risk factors for helminth infections. Protozoan infections were linked to drinking tap water or from water dispensers and poor handwashing practices.

    CONCLUSIONS: These findings emphasize the importance of health education in addition to introduction of biannual anthelmintic treatment to promote community health and well-being.

  11. Corrigendum to: "Detection of Plasmodium knowlesi using recombinase polymerase amplification (RPA) combined with SYBR Green I" [volume 208, article number ACTROP_105511]
    Lai MY, Lau YL
    Acta Trop, 2023 Dec;248:107029.
    PMID: 37777354 DOI: 10.1016/j.actatropica.2023.107029
  12. Simian malaria: a narrative review on emergence, epidemiology and threat to global malaria elimination
    Fornace KM, Zorello Laporta G, Vythilingham I, Chua TH, Ahmed K, Jeyaprakasam NK, et al.
    Lancet Infect Dis, 2023 Dec;23(12):e520-e532.
    PMID: 37454671 DOI: 10.1016/S1473-3099(23)00298-0
    Simian malaria from wild non-human primate populations is increasingly recognised as a public health threat and is now the main cause of human malaria in Malaysia and some regions of Brazil. In 2022, Malaysia became the first country not to achieve malaria elimination due to zoonotic simian malaria. We review the global distribution and drivers of simian malaria and identify priorities for diagnosis, treatment, surveillance, and control. Environmental change is driving closer interactions between humans and wildlife, with malaria parasites from non-human primates spilling over into human populations and human malaria parasites spilling back into wild non-human primate populations. These complex transmission cycles require new molecular and epidemiological approaches to track parasite spread. Current methods of malaria control are ineffective, with wildlife reservoirs and primarily outdoor-biting mosquito vectors urgently requiring the development of novel control strategies. Without these, simian malaria has the potential to undermine malaria elimination globally.
  13. Correction: RNA purification-free detection of SARS-CoV-2 using reverse transcription loop-mediated isothermal amplification (RT-LAMP)
    Lai MY, Suppiah J, Thayan R, Ismail I, Mustapa NI, Soh TST, et al.
    Trop Med Health, 2023 Nov 22;51(1):66.
    PMID: 37993919 DOI: 10.1186/s41182-023-00555-3
  14. Correction to: Clinical testing on SARS-CoV-2 swab samples using reverse-transcription loop-mediated isothermal amplification (RT-LAMP) & Two extraction-free reverse transcription loop-mediated isothermal amplification assays for detection of SARS-CoV-2
    Lau YL
    BMC Infect Dis, 2023 Nov 16;23(1):755.
    PMID: 37968620 DOI: 10.1186/s12879-023-08738-3
  15. Fulltext Corrigendum to "Colorimetric detection of SARS-CoV-2 by uracil-DNA glycosylase (UDG) reverse transcription loop-mediated isothermal amplification (RT-LAMP)" [International Journal of Infectious Diseases 120 (2023) Pages 132-134]
    Lai MY, Bukhari FDM, Zulkefli NZ, Ismail I, Mustapa NI, Soh TST, et al.
    Int J Infect Dis, 2023 Nov;136:91.
    PMID: 37774600 DOI: 10.1016/j.ijid.2023.09.011
  16. Fulltext Correction: Droplet digital polymerase chain reaction (ddPCR) for the detection of Plasmodium knowlesi and Plasmodium vivax
    Mahendran P, Liew JWK, Amir A, Ching XT, Lau YL
    Malar J, 2023 Oct 25;22(1):324.
    PMID: 37880730 DOI: 10.1186/s12936-023-04733-w
  17. Correction: Plasmodium knowlesi: the game changer for malaria eradication
    Lee WC, Cheong FW, Amir A, Lai MY, Tan JH, Phang WK, et al.
    Malar J, 2023 Oct 19;22(1):316.
    PMID: 37858164 DOI: 10.1186/s12936-023-04732-x
  18. Fulltext Correction: Validation of SYBR green I based closed-tube loop-mediated isothermal amplification (LAMP) assay for diagnosis of knowlesi malaria
    Lai MY, Ooi CH, Lau YL
    Malar J, 2023 Oct 18;22(1):314.
    PMID: 37853443 DOI: 10.1186/s12936-023-04731-y
  19. Fulltext Genetic diversity and in silico analysis of Plasmodium knowlesi Serine Repeat Antigen (SERA) 3 antigen 2 in Malaysia
    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.
  20. 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.
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