Displaying publications 21 - 40 of 49 in total

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  1. Fulltext Meta-Analysis of Dengue Severity during Infection by Different Dengue Virus Serotypes in Primary and Secondary Infections
    Soo KM, Khalid B, Ching SM, Chee HY
    PLoS One, 2016;11(5):e0154760.
    PMID: 27213782 DOI: 10.1371/journal.pone.0154760
    INTRODUCTION: Dengue virus (DENV) infection is currently a major cause of morbidity and mortality in the world; it has become more common and virulent over the past half-century and has gained much attention. Thus, this review compared the percentage of severe cases of both primary and secondary infections with different serotypes of dengue virus.

    METHODS: Data related to the number of cases involving dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) or severe dengue infections caused by different serotypes of dengue virus were obtained by using the SCOPUS, the PUBMED and the OVID search engines with the keywords "(dengue* OR dengue virus*) AND (severe dengue* OR severity of illness index* OR severity* OR DF* OR DHF* OR DSS*) AND (serotypes* OR serogroup*)", according to the MESH terms suggested by PUBMED and OVID.

    RESULTS: Approximately 31 studies encompassing 15,741 cases reporting on the dengue serotypes together with their severity were obtained, and meta-analysis was carried out to analyze the data. This study found that DENV-3 from the Southeast Asia (SEA) region displayed the greatest percentage of severe cases in primary infection (95% confidence interval (CI), 31.22-53.67, 9 studies, n = 598, I2 = 71.53%), whereas DENV-2, DENV-3, and DENV-4 from the SEA region, as well as DENV-2 and DENV-3 from non-SEA regions, exhibited the greatest percentage of severe cases in secondary infection (95% CI, 11.64-80.89, 4-14 studies, n = 668-3,149, I2 = 14.77-96.20%). Moreover, DENV-2 and DENV-4 from the SEA region had been found to be more highly associated with dengue shock syndrome (DSS) (95% CI, 10.47-40.24, 5-8 studies, n = 642-2,530, I2 = 76.93-97.70%), while DENV-3 and DENV-4 from the SEA region were found to be more highly associated with dengue hemorrhagic fever (DHF) (95% CI, 31.86-54.58, 9 studies, n = 674-2,278, I2 = 55.74-88.47%), according to the 1997 WHO dengue classification. Finally, DENV-2 and DENV-4 from the SEA region were discovered to be more highly associated with secondary infection compared to other serotypes (95% CI, 72.01-96.32, 9-12 studies, n = 671-2,863, I2 = 25.01-96.75%).

    CONCLUSION: This study provides evidence that the presence of certain serotypes, including primary infection with DENV-3 from the SEA region and secondary infection with DENV-2, DENV-3, and DENV-4 also from the SEA region, as well as DENV-2 and DENV-3 from non SEA regions, increased the risk of severe dengue infections. Thus, these serotypes are worthy of special consideration when making clinical predictions upon the severity of the infection.

    SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015026093 (http://www.crd.york.ac.uk/PROSPERO).

  2. Putative apolipoprotein A-I, natural killer cell enhancement factor and lysozyme g are involved in the early immune response of brown-marbled grouper, Epinephelus fuscoguttatus, Forskal, to Vibrio alginolyticus
    Low CF, Shamsudin MN, Chee HY, Aliyu-Paiko M, Idrus ES
    J Fish Dis, 2014 Aug;37(8):693-701.
    PMID: 24304156 DOI: 10.1111/jfd.12153
    The gram-negative bacterium, Vibrio alginolyticus, has frequently been identified as the pathogen responsible for the infectious disease called vibriosis. This disease is one of the major challenges facing brown-marbled grouper aquaculture, causing fish farmers globally to suffer substantial economic losses. The objective of this study was to investigate the proteins involved in the immune response of brown-marbled grouper fingerlings during their initial encounter with pathogenic organisms. To achieve this objective, a challenge experiment was performed, in which healthy brown-marbled grouper fingerlings were divided into two groups. Fish in the treated group were subjected to intraperitoneal injection with an infectious dose of V. alginolyticus suspended in phosphate-buffered saline (PBS), and those in the control group were injected with an equal volume of PBS. Blood samples were collected from a replicate number of fish from both groups at 4 h post-challenge and analysed for immune response-related serum proteins via two-dimensional gel electrophoresis. The results showed that 14 protein spots were altered between the treated and control groups; these protein spots were further analysed to determine the identity of each protein via MALDI-TOF/TOF. Among the altered proteins, three were clearly overexpressed in the treated group compared with the control; these were identified as putative apolipoprotein A-I, natural killer cell enhancement factor and lysozyme g. Based on these results, these three highly expressed proteins participate in immune response-related reactions during the initial exposure (4 h) of brown-marbled grouper fingerling to V. alginolyticus infection.
  3. Fulltext Comparative Genetic Analyses of Human Rhinovirus C (HRV-C) Complete Genome from Malaysia
    Khaw YS, Chan YF, Jafar FL, Othman N, Chee HY
    Front Microbiol, 2016;7:543.
    PMID: 27199901 DOI: 10.3389/fmicb.2016.00543
    Human rhinovirus-C (HRV-C) has been implicated in more severe illnesses than HRV-A and HRV-B, however, the limited number of HRV-C complete genomes (complete 5' and 3' non-coding region and open reading frame sequences) has hindered the in-depth genetic study of this virus. This study aimed to sequence seven complete HRV-C genomes from Malaysia and compare their genetic characteristics with the 18 published HRV-Cs. Seven Malaysian HRV-C complete genomes were obtained with newly redesigned primers. The seven genomes were classified as HRV-C6, C12, C22, C23, C26, C42, and pat16 based on the VP4/VP2 and VP1 pairwise distance threshold classification. Five of the seven Malaysian isolates, namely, 3430-MY-10/C22, 8713-MY-10/C23, 8097-MY-11/C26, 1570-MY-10/C42, and 7383-MY-10/pat16 are the first newly sequenced complete HRV-C genomes. All seven Malaysian isolates genomes displayed nucleotide similarity of 63-81% among themselves and 63-96% with other HRV-Cs. Malaysian HRV-Cs had similar putative immunogenic sites, putative receptor utilization and potential antiviral sites as other HRV-Cs. The genomic features of Malaysian isolates were similar to those of other HRV-Cs. Negative selections were frequently detected in HRV-Cs complete coding sequences indicating that these sequences were under functional constraint. The present study showed that HRV-Cs from Malaysia have diverse genetic sequences but share conserved genomic features with other HRV-Cs. This genetic information could provide further aid in the understanding of HRV-C infection.
  4. Identification of enterovirus 71 isolates from an outbreak of hand, foot and mouth disease (HFMD) with fatal cases of encephalomyelitis in Malaysia
    AbuBakar S, Chee HY, Al-Kobaisi MF, Xiaoshan J, Chua KB, Lam SK
    Virus Res, 1999 May;61(1):1-9.
    PMID: 10426204
    Thirteen enterovirus 71 (EV71) isolates were obtained from both fatal and non-fatal infections of patients seen in Peninsula Malaysia and in Sarawak during an outbreak of hand, foot and mouth disease (HFMD) in Malaysia in 1997, with incidences of fatal brainstem encephalomyelitis. The isolates were identified using immunofluorescence staining, neutralization assays, and partial sequencing of the 5' untranslated regions (UTR). Assessment of the potential genetic relationships of the isolates using the partial 5'UTR sequences suggested clustering of the isolates into at least two main clusters. Isolates from Peninsula Malaysia were found in both clusters whereas Sarawak-derived isolates clustered only in cluster II. Isolates derived from fatal infections, however, occurred in both clusters and no distinctive nucleotide sequences could be attributed to the fatal isolates. Examination of the nucleotide sequences revealed at least 13 nucleotide positions in all the isolates which differ completely from the previously reported EV71 5'UTR sequences. In addition, at least 11 nucleotide position differences within the 5'UTR were noted which differentiated cluster I from cluster II. Predicted secondary RNA structures drawn using the nucleotide sequences also suggested differences between isolates from the two clusters. These findings suggest the presence of at least two potentially virulent EV71 co-circulating in Malaysia during the 1997 HFMD outbreak.
  5. Fulltext Comparison of Knowledge, Attitude, and Practice among Communities Living in Hotspot and Non-Hotspot Areas of Dengue in Selangor, Malaysia
    Ghani NA, Shohaimi S, Hee AK, Chee HY, Emmanuel O, Alaba Ajibola LS
    Trop Med Infect Dis, 2019 Feb 15;4(1).
    PMID: 30781369 DOI: 10.3390/tropicalmed4010037
    BACKGROUND: Dengue has affected more than one-third of the world population and Malaysia has recorded an increase in the number of dengue cases since 2012. Selangor state recorded the highest number of dengue cases in Malaysia. Most of the dengue infections occur among people living in hotspot areas of dengue. This study aims to compare Knowledge, Attitude, and Practice among communities living in hotspot and non-hotspot dengue areas.

    METHOD: Communities living in 20 hotspot and 20 non-hotspot areas in Selangor were chosen in this study where 406 participants were randomly selected to answer questionnaires distributed at their housing areas. Total marks of each categories were compared using t-test.

    RESULT: Results show that there were significant mean differences in marks in Knowledge (p value: 0.003; 15.41 vs. 14.55) and Attitude (p value: < 0.001; 11.41 vs. 10.33), but not Practice (p value 0.101; 10.83 vs. 10.47) categories between communities of non-hotspot and hotspot areas. After considering two confounding variables which are education level and household income, different mean marks are found to be significant in Knowledge when education level acts as a covariate and Attitude when both act as covariates.

    CONCLUSION: Overall results show that people living in non-hotspot areas had better knowledge and attitude than people living in hotspot areas, but no difference was found in practice. This suggests that public health education should be done more frequently with people with a low education background and low household income, especially in hotspot areas to fight dengue outbreak and make dengue cases decrease effectively.

  6. Fulltext Synthesis, characterization and evaluation of antidengue activity of enantiomeric Schiff bases derived from S-substituted dithiocarbazate
    Maryam M, Tan SL, Crouse KA, Mohamed Tahir MI, Chee HY
    Turk J Chem, 2020;44(5):1395-1409.
    PMID: 33488239 DOI: 10.3906/kim-2006-22
    A series of Schiff bases have been successfully synthesized through the acid-catalyzed condensation of S-substituted dithiocarbazates and three enantiomerically pure monoterpenes, (1 R )-(+)-camphor, (1 S )-(-)-camphor, (1 R )-(-)-camphorquinone, (1 S )-(+)-camphorquinone, ( R )-(-)-carvone and ( S )-(+)-carvone. Spectroscopic results revealed that the Schiff bases containing camphor or carvone likely adopted an E -configuration along the characteristic imine bond while those containing camphorquinone assumed a Z -configuration. The antidengue potential of these compounds was evaluated based on DENV 2 caused cytopathic effect (CPE) reduction-based in vitro evaluation. The compounds were validated through secondary foci forming unit reduction assay (FFURA). Compounds were also tested for their cytotoxicity against Vero cells. The compounds showed variable degrees of antiviral activity with the camphor compounds displaying the highest antidengue potential. The enantiomers of the compounds behaved almost similarly during the antiviral evaluation.
  7. Fulltext Geographical distribution and spatio-temporal patterns of hospitalization due to dengue infection at a leading specialist hospital in Malaysia
    Low GKK, Papapreponis P, Isa RM, Gan SC, Chee HY, Te KK, et al.
    Geospat Health, 2018 05 07;13(1):642.
    PMID: 29772885 DOI: 10.4081/gh.2018.642
    Increasing numbers of dengue infection worldwide have led to a rise in deaths due to complications caused by this disease. We present here a cross-sectional study of dengue patients who attended the Emergency and Trauma Department of Ampang Hospital, one of Malaysia's leading specialist hospitals. The objective was to search for potential clustering of severe dengue, in space and/or time, among the annual admissions with the secondary objective to describe the spatio-temporal pattern of all dengue cases admitted to this hospital. The dengue status of the patients was confirmed serologically with the geographic location of the patients determined by residency, but not more specific than the street level. A total of 1165 dengue patients were included in the analysis using SaTScan software. The mean age of these patients was 27.8 years, with a standard deviation of 14.2 years and an age range from 1 to 77 years, among whom 54 (4.6%) were cases of severe dengue. A cluster of general dengue cases was identified occurring from October to December in the study year of 2015 but the inclusion of severe dengue in that cluster was not statistically significant (P=0.862). The standardized incidence ratio was 1.51. General presence of dengue cases was, however, detected to be concentrated at the end of the year, which should be useful for hospital planning and management if this pattern holds.
  8. Fulltext Immunological Analysis of the Hepatitis B Virus "a" Determinant Displayed on Chimeric Virus-Like Particles of Macrobrachium rosenbergii Nodavirus Capsid Protein Produced in Sf9 Cells
    Ninyio NN, Ho KL, Ong HK, Yong CY, Chee HY, Hamid M, et al.
    Vaccines (Basel), 2020 Jun 04;8(2).
    PMID: 32512923 DOI: 10.3390/vaccines8020275
    Chimeric virus-like particles (VLPs) have been widely exploited for various purposes including their use as vaccine candidates, particularly due to their ability to induce stronger immune responses than VLPs consisting of single viral proteins. In the present study, VLPs of the Macrobrachium rosenbergii nodavirus (MrNV) capsid protein (Nc) displaying the hepatitis B virus "a" determinant (aD) were produced in Spodoptera frugiperda (Sf9) insect cells. BALB/c mice immunised with the purified chimeric Nc-aD VLPs elicited a sustained titre of anti-aD antibody, which was significantly higher than that elicited by a commercially available hepatitis B vaccine and Escherichia coli-produced Nc-aD VLPs. Immunophenotyping showed that the Sf9-produced Nc-aD VLPs induced proliferation of cytotoxic T-lymphocytes and NK1.1 natural killer cells. Furthermore, enzyme-linked immunospot (ELISPOT)analysis showed the presence of antibody-secreting memory B cells in the mice splenocytes stimulated with the synthetic aD peptide. The significant humoral, natural killer cell and memory B cell immune responses induced by the Sf9-produced Nc-aD VLPs suggest that they present good prospects for use as a hepatitis B vaccine candidate.
  9. Distribution of pathogenic Leptospira in environmental water and soils of selected recreational forests in Perak, Malaysia
    Yap ML, Chew LJ, Pritpal Singh SS, Sekawi Z, Chee HY, Ong HKO, et al.
    Trop Biomed, 2021 Jun 01;38(2):122-128.
    PMID: 34172700 DOI: 10.47665/tb.38.2.047
    Leptospirosis is an emerging zoonotic disease endemic in tropical regions. Aiming at assessing the potential infection risks via recreational exposure, the molecular prevalence of pathogenic Leptospira in 14 amenity forests in five selected districts of the state of Perak was determined. Water and soil samples along streams and waterfalls were subjected to culture of leptospires and the pathogenic Leptospira spp. was detected by lipL32-based polymerase chain reaction (PCR). Twenty out of 154 samples (13%) that tested positive for leptospires were mostly soils and still water recorded with tolerable temperatures (22.2- 26.5°C) and pHs (5.73-6.70). The localised prevalence was highly varied among eight positive forests (6.7-41.7%), particularly higher in Kampar and Kinta districts which are the more populated urban areas. The importance of public health surveillance should not be underrated given the high prevalence of Leptospira spp. in forests in close proximity to indigenous settlements, even where the places are clean. Overall, this study discovered a wide distribution of pathogenic Leptospira spp. in recreational areas.
  10. Fulltext Gene expression patterns induced at different stages of rhinovirus infection in human alveolar epithelial cells
    Reza Etemadi M, Ling KH, Zainal Abidin S, Chee HY, Sekawi Z
    PLoS One, 2017;12(5):e0176947.
    PMID: 28558071 DOI: 10.1371/journal.pone.0176947
    Human rhinovirus (HRV) is the common virus that causes acute respiratory infection (ARI) and is frequently associated with lower respiratory tract infections (LRTIs). We aimed to investigate whether HRV infection induces a specific gene expression pattern in airway epithelial cells. Alveolar epithelial cell monolayers were infected with HRV species B (HRV-B). RNA was extracted from both supernatants and infected monolayer cells at 6, 12, 24 and 48 hours post infection (hpi) and transcriptional profile was analyzed using Affymetrix GeneChip and the results were subsequently validated using quantitative Real-time PCR method. HRV-B infects alveolar epithelial cells which supports implication of the virus with LRTIs. In total 991 genes were found differentially expressed during the course of infection. Of these, 459 genes were up-regulated whereas 532 genes were down-regulated. Differential gene expression at 6 hpi (187 genes up-regulated vs. 156 down-regulated) were significantly represented by gene ontologies related to the chemokines and inflammatory molecules indicating characteristic of viral infection. The 75 up-regulated genes surpassed the down-regulated genes (35) at 12 hpi and their enriched ontologies fell into discrete functional entities such as regulation of apoptosis, anti-apoptosis, and wound healing. At later time points of 24 and 48 hpi, predominated down-regulated genes were enriched for extracellular matrix proteins and airway remodeling events. Our data provides a comprehensive image of host response to HRV infection. The study suggests the underlying molecular regulatory networks genes which might be involved in pathogenicity of the HRV-B and potential targets for further validations and development of effective treatment.
  11. Fulltext Meta-analysis of biomarkers for severe dengue infections
    Soo KM, Khalid B, Ching SM, Tham CL, Basir R, Chee HY
    PeerJ, 2017;5:e3589.
    PMID: 28929009 DOI: 10.7717/peerj.3589
    BACKGROUND: Dengue viral infection is an acute infection that has the potential to have severe complications as its major sequela. Currently, there is no routine laboratory biomarker with which to predict the severity of dengue infection or monitor the effectiveness of standard management. Hence, this meta-analysis compared biomarker levels between dengue fever (DF) and severe dengue infections (SDI) to identify potential biomarkers for SDI.

    METHODS: Data concerning levels of cytokines, chemokines, and other potential biomarkers of DF, dengue hemorrhagic fever, dengue shock syndrome, and severe dengue were obtained for patients of all ages and populations using the Scopus, PubMed, and Ovid search engines. The keywords "(IL1* or IL-1*) AND (dengue*)" were used and the same process was repeated for other potential biomarkers, according to Medical Subject Headings terms suggested by PubMed and Ovid. Meta-analysis of the mean difference in plasma or serum level of biomarkers between DF and SDI patients was performed, separated by different periods of time (days) since fever onset. Subgroup analyses comparing biomarker levels of healthy plasma and sera controls, biomarker levels of primary and secondary infection samples were also performed, as well as analyses of different levels of severity and biomarker levels upon infection by different dengue serotypes.

    RESULTS: Fifty-six studies of 53 biomarkers from 3,739 dengue cases (2,021 DF and 1,728 SDI) were included in this meta-analysis. Results showed that RANTES, IL-7, IL-8, IL-10, IL-18, TGF-b, and VEGFR2 levels were significantly different between DF and SDI. IL-8, IL-10, and IL-18 levels increased during SDI (95% CI, 18.1-253.2 pg/mL, 3-13 studies, n = 177-1,909, I(2) = 98.86%-99.75%). In contrast, RANTES, IL-7, TGF-b, and VEGFR2 showed a decrease in levels during SDI (95% CI, -3238.7 to -3.2 pg/mL, 1-3 studies, n = 95-418, I(2) = 97.59%-99.99%). Levels of these biomarkers were also found to correlate with the severity of the dengue infection, in comparison to healthy controls. Furthermore, the results showed that IL-7, IL-8, IL-10, TGF-b, and VEGFR2 display peak differences between DF and SDI during or before the critical phase (day 4-5) of SDI.

    DISCUSSION: This meta-analysis suggests that IL-7, IL-8, IL-10, TGF-b, and VEGFR2 may be used as potential early laboratory biomarkers in the diagnosis of SDI. This can be used to predict the severity of dengue infection and to monitor the effectiveness of treatment. Nevertheless, methodological and reporting limitations must be overcome in future research to minimize variables that affect the results and to confirm the findings.
  12. Global dengue death before and after the new World Health Organization 2009 case classification: A systematic review and meta-regression analysis
    Low GK, Ogston SA, Yong MH, Gan SC, Chee HY
    Acta Trop, 2018 Jun;182:237-245.
    PMID: 29545158 DOI: 10.1016/j.actatropica.2018.03.014
    BACKGROUND: Since the introduction of 2009 WHO dengue case classification, no literature was found regarding its effect on dengue death. This study was to evaluate the effect of 2009 WHO dengue case classification towards dengue case fatality rate.

    METHODS: Various databases were used to search relevant articles since 1995. Studies included were cohort and cross-sectional studies, all patients with dengue infection and must report the number of death or case fatality rate. The Joanna Briggs Institute appraisal checklist was used to evaluate the risk of bias of the full-texts. The studies were grouped according to the classification adopted: WHO 1997 and WHO 2009. Meta-regression was employed using a logistic transformation (log-odds) of the case fatality rate. The result of the meta-regression was the adjusted case fatality rate and odds ratio on the explanatory variables.

    RESULTS: A total of 77 studies were included in the meta-regression analysis. The case fatality rate for all studies combined was 1.14% with 95% confidence interval (CI) of 0.82-1.58%. The combined (unadjusted) case fatality rate for 69 studies which adopted WHO 1997 dengue case classification was 1.09% with 95% CI of 0.77-1.55%; and for eight studies with WHO 2009 was 1.62% with 95% CI of 0.64-4.02%. The unadjusted and adjusted odds ratio of case fatality using WHO 2009 dengue case classification was 1.49 (95% CI: 0.52, 4.24) and 0.83 (95% CI: 0.26, 2.63) respectively, compared to WHO 1997 dengue case classification. There was an apparent increase in trend of case fatality rate from the year 1992-2016. Neither was statistically significant.

    CONCLUSIONS: The WHO 2009 dengue case classification might have no effect towards the case fatality rate although the adjusted results indicated a lower case fatality rate. Future studies are required for an update in the meta-regression analysis to confirm the findings.

  13. Sensitive Leptospira DNA detection using tapered optical fiber sensor
    Zainuddin NH, Chee HY, Ahmad MZ, Mahdi MA, Abu Bakar MH, Yaacob MH
    J Biophotonics, 2018 08;11(8):e201700363.
    PMID: 29570957 DOI: 10.1002/jbio.201700363
    This paper presents the development of tapered optical fiber sensor to detect a specific Leptospira bacteria DNA. The bacteria causes Leptospirosis, a deadly disease but with common early flu-like symptoms. Optical single mode fiber (SMF) of 125 μm diameter is tapered to produce 12 μm waist diameter and 15 cm length. The novel DNA-based optical fiber sensor is functionalized by incubating the tapered region with sodium hydroxide (NaOH), (3-Aminopropyl) triethoxysilane and glutaraldehyde. Probe DNA is immobilized onto the tapered region and subsequently hybridized by its complementary DNA (cDNA). The transmission spectra of the DNA-based optical fiber sensor are measured in the 1500 to 1600 nm wavelength range. It is discovered that the shift of the wavelength in the SMF sensor is linearly proportional with the increase in the cDNA concentrations from 0.1 to 1.0 nM. The sensitivity of the sensor toward DNA is measured to be 1.2862 nm/nM and able to detect as low as 0.1 fM. The sensor indicates high specificity when only minimal shift is detected for non-cDNA testing. The developed sensor is able to distinguish between actual DNA of Leptospira serovars (Canicola and Copenhageni) against Clostridium difficile (control sample) at very low (femtomolar) target concentrations.
  14. Fulltext Systematic review and meta-analysis of the efficacy and safety of oseltamivir (Tamiflu) in the treatment of Coronavirus Disease 2019 (COVID-19)
    Aliyu B, Raji YE, Chee HY, Wong MY, Sekawi ZB
    PLoS One, 2022;17(12):e0277206.
    PMID: 36454880 DOI: 10.1371/journal.pone.0277206
    Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral drug used for treating influenza A and B viruses, as a trial drug for COVID-19. However, available evidence from clinical studies has shown conflicting results on the effectiveness of oseltamivir in COVID-19 treatment. Therefore, this systematic review and meta-analysis was performed to assess the clinical safety and efficacy of oseltamivir for treating COVID-19. The study was conducted according to the PRISMA guidelines, and the priori protocol was registered in PROSPERO (CRD42021270821). Five databases were searched, the identified records were screened, and followed by the extraction of relevant data. Eight observational studies from four Asian countries were included. A random-effects model was used to pool odds ratios (ORs), mean differences (MD), and their 95% confidence intervals (CI) for the study analysis. Survival was not significantly different between all categories of oseltamivir and the comparison groups analysed. The duration of hospitalisation was significantly shorter in the oseltamivir group following sensitivity analysis (MD -5.95, 95% CI -9.91--1.99 p = 0.003, heterogeneity I2 0%, p = 0.37). The virological, laboratory and radiological response rates were all not in favour of oseltamivir. However, the electrocardiographic safety parameters were found to be better in the oseltamivir group. However, more studies are needed to establish robust evidence on the effectiveness or otherwise of oseltamivir usage for treating COVID-19.
  15. Fulltext Detection of dengue using PAMAM dendrimer integrated tapered optical fiber sensor
    Mustapha Kamil Y, Al-Rekabi SH, Yaacob MH, Syahir A, Chee HY, Mahdi MA, et al.
    Sci Rep, 2019 09 17;9(1):13483.
    PMID: 31530893 DOI: 10.1038/s41598-019-49891-7
    The exponential escalation of dengue cases has indeed become a global health crisis. This work elaborates on the development of a biofunctionalized tapered optical fiber (TOF) based sensor with the integration of polyamidoamine (PAMAM) dendrimer for the detection of dengue E protein. The dimension of the TOF generated an evanescent field that was sensitive to any changes in the external medium while the integration of PAMAM promoted more adhesion of bio-recognition molecules; anti-DENV II E protein antibodies; that were complementary to the targeted protein. This in return created more active sites for the absorption of DENV II E proteins onto the tapered region. The resolution and detection limit of the sensor are 19.53 nm/nM and 1 pM, respectively with Kd = 1.02 × 10-10 M.
  16. Fulltext Chimeric Virus-Like Particles of Prawn Nodavirus Displaying Hepatitis B Virus Immunodominant Region: Biophysical Properties and Cytokine Response
    Ninyio NN, Ho KL, Yong CY, Chee HY, Hamid M, Ong HK, et al.
    Int J Mol Sci, 2021 Feb 15;22(4).
    PMID: 33672018 DOI: 10.3390/ijms22041922
    Hepatitis B is a major global health challenge. In the absence of an effective treatment for the disease, hepatitis B vaccines provide protection against the viral infection. However, some individuals do not have positive immune responses after being vaccinated with the hepatitis B vaccines available in the market. Thus, it is important to develop a more protective vaccine. Previously, we showed that hepatitis B virus (HBV) 'a' determinant (aD) displayed on the prawn nodavirus capsid (Nc) and expressed in Spodoptera frugiperda (Sf9) cells (namely, Nc-aD-Sf9) self-assembled into virus-like particles (VLPs). Immunisation of BALB/c mice with the Nc-aD-Sf9 VLPs showed significant induction of humoral, cellular and memory B-cell immunity. In the present study, the biophysical properties of the Nc-aD-Sf9 VLPs were studied using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy. Enzyme-linked immunosorbent assay (ELISA) was used to determine the antigenicity of the Nc-aD-Sf9 VLPs, and multiplex ELISA was employed to quantify the cytokine response induced by the VLPs administered intramuscularly into BALB/c mice (n = 8). CD spectroscopy of Nc-aD-Sf9 VLPs showed that the secondary structure of the VLPs predominantly consisted of beta (β)-sheets (44.8%), and they were thermally stable up to ~52 °C. ELISA revealed that the aD epitope of the VLPs was significantly antigenic to anti-HBV surface antigen (HBsAg) antibodies. In addition, multiplex ELISA of serum samples from the vaccinated mice showed a significant induction (p < 0.001) of IFN-γ, IL-4, IL-5, IL-6, IL-10, and IL-12p70. This cytokine profile is indicative of natural killer cell, macrophage, dendritic cell and cytotoxic T-lymphocyte activities, which suggests a prophylactic innate and adaptive cellular immune response mediated by Nc-aD-Sf9 VLPs. Interestingly, Nc-aD-Sf9 induced a more robust release of the aforementioned cytokines than that of Nc-aD VLPs produced in Escherichia coli and a commercially used hepatitis B vaccine. Overall, Nc-aD-Sf9 VLPs are thermally stable and significantly antigenic, demonstrating their potential as an HBV vaccine candidate.
  17. Fulltext Clinical predictors of dengue fever co-infected with leptospirosis among patients admitted for dengue fever - a pilot study
    Suppiah J, Chan SY, Ng MW, Khaw YS, Ching SM, Mat-Nor LA, et al.
    J Biomed Sci, 2017 Jun 28;24(1):40.
    PMID: 28659189 DOI: 10.1186/s12929-017-0344-x
    BACKGROUND: Dengue and leptospirosis infections are currently two major endemics in Malaysia. Owing to the overlapping clinical symptoms between both the diseases, frequent misdiagnosis and confusion of treatment occurs. As a solution, the present work initiated a pilot study to investigate the incidence related to co-infection of leptospirosis among dengue patients. This enables the identification of more parameters to predict the occurrence of co-infection.

    METHOD: Two hundred sixty eight serum specimens collected from patients that were diagnosed for dengue fever were confirmed for dengue virus serotyping by real-time polymerase chain reaction. Clinical, laboratory and demographic data were extracted from the hospital database to identify patients with confirmed leptospirosis infection among the dengue patients. Thus, frequency of co-infection was calculated and association of the dataset with dengue-leptospirosis co-infection was statistically determined.

    RESULTS: The frequency of dengue co-infection with leptospirosis was 4.1%. Male has higher preponderance of developing the co-infection and end result of shock as clinical symptom is more likely present among co-infected cases. It is also noteworthy that, DENV 1 is the common dengue serotype among all cases identified as dengue-leptospirosis co-infection in this study.

    CONCLUSION: The increasing incidence of leptospirosis among dengue infected patients has posed the need to precisely identify the presence of co-infection for the betterment of treatment without mistakenly ruling out either one of them. Thus, anticipating the possible clinical symptoms and laboratory results of dengue-leptospirosis co-infection is essential.

  18. Fulltext Mast cell stabilizing effect of a geranyl acetophenone in dengue virus infection using in vitro model of DENV3-induced RBL-2H3 cells
    Tan JW, Wan Zahidi NF, Kow ASF, Soo KM, Shaari K, Israf DA, et al.
    Biosci Rep, 2019 06 28;39(6).
    PMID: 31110077 DOI: 10.1042/BSR20181273
    Mast cells (MCs), a type of immune effector cell, have recently become recognized for their ability to cause vascular leakage during dengue virus (DENV) infection. Although MC stabilizers have been reported to attenuate DENV induced infection in animal studies, there are limited in vitro studies on the use of MC stabilizers against DENV induced MC degranulation. 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA) has been reported to be a potential MC stabilizer by inhibiting IgE-mediated MC activation in both cellular and animal models. The present study aims to establish an in vitro model of DENV3-induced RBL-2H3 cells using ketotifen fumarate as a control drug, as well as to determine the effect of tHGA on the release of MC mediators upon DENV infection. Our results demonstrated that the optimal multiplicities of infection (MOI) were 0.4 × 10-2 and 0.8 × 10-2 focus forming units (FFU)/cell. Ketotifen fumarate was proven to attenuate DENV3-induced RBL-2H3 cells degranulation in this in vitro model. In contrast, tHGA was unable to attenuate the release of both β-hexosaminidase and tumor necrosis factor (TNF)-α. Nonetheless, our study has successfully established an in vitro model of DENV3-induced RBL-2H3 cells, which might be useful for the screening of potential MC stabilizers for anti-dengue therapies.
  19. Fulltext Effect of Smartphone App's Intervention on Consumers' Knowledge, Attitude, Practice, and Perception of Food Poisoning Prevention When Dining Out at Selected Rural Areas in Terengganu
    Zaujan NAM, Ali A, Osman M, Chee HY, Ithnin NR, Misni N, et al.
    Int J Environ Res Public Health, 2021 09 29;18(19).
    PMID: 34639593 DOI: 10.3390/ijerph181910294
    (1) Background: Lack of food safety awareness and preventive behaviour when dining out increases the risk of food poisoning. Furthermore, food poisoning cases among rural communities have been rising in recent years. However, the health-related mobile application is a promising tool in improving food poisoning prevention knowledge, attitude, practice, and perception (KAP2) among consumers. Therefore, the current study developed a novel smartphone app, MyWarung©, and determined its efficacy in increasing awareness, attitude, practice, and perception of food poisoning and its prevention when dining out, especially among rural consumers. (2) Methods: A quasi-experimental pre-and post-intervention study with a control and intervention group were performed on 100 consumers in Terengganu. (3) Results: The intervention's inter-group outcomes were analysed using the Mann-Whitney test, while the within-group effects were ascertained using the Wilcoxon sign rank test via the SPSS software. It was found that the control group had higher median scores in knowledge (30.0, IQR 7.0), attitude (46.0, IQR 5.0), and practice (34.0, IQR 3.0) than the intervention group before intervention. After the intervention programme, the intervention group showed significant improvement in food poisoning knowledge (p = 0.000), attitude (p = 0.001), and practice (p = 0.000). However, the intervention group's perceived barriers (p = 0.129) and susceptibility (p = 0.069) and the control group's perceived barriers (p = 0.422) did not show any significant improvement. (4) Conclusion: The findings indicated that the MyWarung© mobile app usage enhanced the food poisoning knowledge, preventive attitude, and practice among consumers when dining out.
  20. A Multi-landscape Assessment of Leptospira Prevalence on a Diversity of Small Mammals
    Rosli MZ, Mohd-Taib FS, Khoo JJ, Chee HY, Wong YP, Shafie NJ, et al.
    Ecohealth, 2023 Jun;20(2):208-224.
    PMID: 37103759 DOI: 10.1007/s10393-023-01637-8
    Leptospirosis is a major zoonotic disease, especially in the tropics, and rodents were known to be carriers of this bacterium. There was established information on Leptospira prevalence among animal reservoirs in human-dominated landscapes from previous literature. However, there was very little focus given comparing the prevalence of Leptospira in a wide range of habitats. An extensive sampling of small mammals from various landscapes was carried out, covering oil palm plantations, paddy fields, recreational forests, semi-urbans, and wet markets in Peninsular Malaysia. This study aims to determine the prevalence of pathogenic Leptospira in a diversity of small mammals across different landscapes. Cage-trapping was deployed for small mammals' trappings, and the kidneys of captured individuals were extracted, for screening of pathogenic Leptospira by polymerase chain reaction (PCR) using LipL32 primer. Eight microhabitat parameters were measured at each study site. Out of 357 individuals captured, 21 (5.9%) were positive for pathogenic Leptospira of which recreational forest had the highest prevalence (8.8%) for landscape types, whereas Sundamys muelleri shows the highest prevalence (50%) among small mammals' species. Microhabitat analysis reveals that rubbish quantity (p 
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