Displaying publications 1 - 20 of 104 in total

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  1. Thergarajan G, Sekaran SD
    Expert Rev Mol Diagn, 2023;23(8):643-651.
    PMID: 37417532 DOI: 10.1080/14737159.2023.2234815
    INTRODUCTION: Every year, a significant rise in dengue incidence observed is responsible for 10% of fever episodes in children and adolescents in endemic countries. Considering that the symptoms of dengue are similar to those of many other viruses, early diagnosis of the disease has long been difficult, and lack of sensitive diagnostic tools may be another factor contributing to a rise in dengue incidence.

    AREAS COVERED: This review will highlight dengue diagnostics strategies and discuss other possible targets for dengue diagnosis. Understanding the dynamics of the immune response and how it affects viral infection has enabled informed diagnosis. As more technologies emerge, precise assays that include some clinical markers need to be included.

    EXPERT OPINION: Future diagnostic strategies will require the use both viral and clinical markers in a serial manner with the use of artificial intelligence technology to determine from the first point of illness to better determine severity status and management. A definitive endpoint is not in the horizon as the disease as well as the virus is constantly evolving and hence many developed assays need to be constantly changing some of their reagents periodically as newer genotypes and probably too serotypes emerge.

  2. Jusof FF, Lim CK, Aziz FN, Soe HJ, Raju CS, Sekaran SD, et al.
    J Infect Dis, 2022 Nov 28;226(11):1964-1973.
    PMID: 35767283 DOI: 10.1093/infdis/jiac273
    BACKGROUND: The resolution or aggravation of dengue infection depends on the patient's immune response during the critical phase. Cytokines released by immune cells increase with the worsening severity of dengue infections. Cytokines activate the kynurenine pathway (KP) and the extent of KP activation then influences disease severity.

    METHODS: KP metabolites and cytokines in plasma samples of patients with dengue infection (dengue without warning signs [DWS-], dengue with warning signs [DWS+], or severe dengue) were analyzed. Cytokines (interferon gamma [IFN-ɣ], tumor necrosis factor, interleukin 6, CXCL10/interferon-inducile protein 10 [IP-10], interleukin 18 [IL-18], CCL2/monocyte chemoattractant protein-1 [MCP-1], and CCL4/macrophage inflammatory protein-1beta [MIP-1β] were assessed by a Human Luminex Screening Assay, while KP metabolites (tryptophan, kynurenine, anthranilic acid [AA], picolinic acid, and quinolinic acid) were assessed by ultra-high-performance liquid chromatography and Gas Chromatography Mass Spectrophotometry [GCMS] assays.

    RESULTS: Patients with DWS+ had increased activation of the KP where kynurenine-tryptophan ratio, anthranilic acid, and picolinic acid were elevated. These patients also had higher levels of the cytokines IFN-ɣ, CXCL10, CCL4, and IL-18 than those with DWS-. Further receiver operating characteristic analysis identified 3 prognostic biomarker candidates, CXCL10, CCL2, and AA, which predicted patients with higher risks of developing DWS+ with an accuracy of 97%.

    CONCLUSIONS: The data suggest a unique biochemical signature in patients with DWS+. CXCL10 and CCL2 together with AA are potential prognostic biomarkers that discern patients with higher risk of developing DWS+ at earlier stages of infection.

  3. Sekaran SD, Ismail AA, Thergarajan G, Chandramathi S, Rahman SKH, Mani RR, et al.
    PMID: 36159640 DOI: 10.3389/fcimb.2022.975222
    Dengue is a major public health concern, affecting almost 400 million people worldwide, with about 70% of the global burden of disease in Asia. Despite revised clinical classifications of dengue infections by the World Health Organization, the wide spectrum of the manifestations of dengue illness continues to pose challenges in diagnosis and patient management for clinicians. When the Zika epidemic spread through the American continent and then later to Africa and Asia in 2015, researchers compared the characteristics of the Zika infection to Dengue, considering both these viruses were transmitted primarily through the same vector, the Aedes aegypti female mosquitoes. An important difference to note, however, was that the Zika epidemic diffused in a shorter time span compared to the persisting feature of Dengue infections, which is endemic in many Asian countries. As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been proposed as biomarkers to predict the risk of the disease progression to a severe form, at a much earlier stage of the illness. However, the findings for most biomarkers are highly discrepant between studies. Meanwhile, the cross-reactivity of CD8+ and CD4+ T cells response to Dengue and Zika viruses provide important clues for further development of potential treatments. This review discusses similarities between Dengue and Zika infections, comparing their disease transmissions and vectors involved, and both the innate and adaptive immune responses in these infections. Consideration of the genetic identity of both the Dengue and Zika flaviviruses as well as the cross-reactivity of relevant T cells along with the actions of CD4+ cytotoxic cells in these infections are also presented. Finally, a summary of the immune biomarkers that have been reported for dengue and Zika viral infections are discussed which may be useful indicators for future anti-viral targets or predictors for disease severity. Together, this information appraises the current understanding of both Zika and Dengue infections, providing insights for future vaccine design approaches against both viruses.
  4. Looi KW, Matsui Y, Kono M, Samudi C, Kojima N, Ong JX, et al.
    Int J Infect Dis, 2021 Sep;110:187-194.
    PMID: 34302960 DOI: 10.1016/j.ijid.2021.07.048
    OBJECTIVES: Progression of dengue is often associated with thrombocytopenia resulting from viral-induced bone marrow suppression and immune-mediated peripheral platelet consumption. Immature platelet fraction (IPF), which can be measured using a haematology analyser, is a precursor indicating platelet formation in the bone marrow. This study evaluated the trend of IPF as an early recovery indicator of platelets in dengue patients with thrombocytopenia, and its relationship with severe dengue in conjunction with reticulocyte count.

    METHODS: Hospitalized patients with dengue were enrolled and followed-up daily until discharge. Blood investigations included daily full blood counts and IPF measured using a haematology analyser.

    RESULTS: In total, 287 patients with confirmed dengue were enrolled in this study, 25 of whom had severe dengue. All patients had a decreasing trend in platelet count in the first week of illness, concomitant with an increasing trend in the percentage of immature platelets to total platelets (IPF%) for more than 3 days prior to platelet recovery. IPF% was significantly increased in patients with severe dengue compared with patients with non-severe dengue on days 3-5 after the onset of fever. Reticulocyte count increased significantly in patients with severe dengue on day 5.

    CONCLUSIONS: IPF can be utilized as an early recovery indicator of platelets in patients with dengue and thrombocytopenia.

  5. Guad RM, Mangantig E, Low WY, Taylor-Robinson AW, Azzani M, Sekaran SD, et al.
    BMC Infect Dis, 2021 Aug 31;21(1):893.
    PMID: 34465288 DOI: 10.1186/s12879-021-06606-6
    BACKGROUND: Several studies have reported a significant association of knowledge, attitude and preventive practice (KAP) regarding dengue infection among community's resident in endemic areas. In this study we aimed to assess and develop a reliable and valid KAP survey on the subject of dengue that is suitable for the resident population of Sabah, Malaysia.

    METHODS: A community-based cross-sectional study was conducted from October 2019 to February 2020 involving 468 respondents. Information on the socio-demographic characteristics of the participants (six items), their KAP (44, 15 and 18 items on knowledge, attitude and practice, respectively) and treatment-seeking behaviour (five items) towards dengue was collected using a structured questionnaire. Data analysis was performed using SPSS and R software in the R Studio environment. The knowledge section was analysed by two-parameter logistic item response theory (2-PL IRT) using ltm package. The construct validity and reliability of items for sections on attitude, practice and treatment-seeking behaviour were analysed using psy package.

    RESULTS: For the knowledge section, only 70.5% (31/44) of items were within or close to the parameter acceptable range of -3 to + 3 of difficulty. In terms of discrimination, 65.9% (29/44) of items were within or close to the acceptable range of 0.35 to 2.5, and 24 items (54.5%) failed to fit the 2-PL IRT model (P  0.7, while based on the communalities, 11 items in the attitude section were excluded due to very low h2, factor loading values and low correlation with the total ( 0.7. The communalities of the practice section showed that seven items had low h2 values (

  6. Guad RM, Wu YS, Aung YN, Sekaran SD, Wilke ABB, Low WY, et al.
    PMID: 33922427 DOI: 10.3390/ijerph18094474
    This review provided a systematic overview of the questionnaire-related dengue studies conducted in Malaysia and evaluated their reliability and validity used in the questionnaires. An extensive literature search was conducted using various electronic databases, including PubMed, EMBASE, Medline, and ScienceDirect. Systematic reviews and meta-analysis (PRISMA) were selected as the preferred item reporting method. Out of 88 identified dengue-related, 57 published from 2000 to April 2020 met the inclusion criteria and were included. Based on the meta-analysis, a poor mean score was obtained for knowledge (49%), attitude (44%), and preventive practice (55%). The study showed that the level of knowledge on cardinal signs and modes of transmission for dengue virus were highest among health care workers, followed by students (international and local) and lastly community residents. In treatment-seeking behaviours, only half of the respondents (50.8%) would send their child to the nearest health clinics or hospitals when a child became restless or lethargic. The acceptance rate for dengue vaccine, bacteria (Wolbachia), as a vector for dengue control and self-test diagnostic kit for dengue showed considerably high (88.4%, 70%, and 44.8%, respectively). Health belief model (HBM) constructs, such as perceived barriers, perceived severity, perceived susceptibility, self-efficacy, and perceived benefit influence prevention practices. Lastly, only 23 articles (40.3%) had piloted or pretested the questionnaire before surveying, in which three reported Cronbach's alpha coefficient (0.70-0.90). A need for active participation of communities and healthcare personnel, promotion of awareness, and safe complementary medicines, as well as assessment of psychometric properties of questionnaire use in dengue surveys in Malaysia, in order for assessing dengue reliably and valid.
  7. Chong ZL, Soe HJ, Ismail AA, Mahboob T, Chandramathi S, Sekaran SD
    Biosensors (Basel), 2021 Apr 22;11(5).
    PMID: 33921935 DOI: 10.3390/bios11050129
    Dengue is a major threat to public health globally. While point-of-care diagnosis of acute/recent dengue is available to reduce its mortality, a lack of rapid and accurate testing for the detection of previous dengue remains a hurdle in expanding dengue seroepidemiological surveys to inform its prevention, especially vaccination, to reduce dengue morbidity. This study evaluated ViroTrack Dengue Serostate, a biosensors-based semi-quantitative anti-dengue IgG (immunoglobulin G) immuno-magnetic agglutination assay for the diagnosis of previous and recent dengue in a single test. Blood samples were obtained from 484 healthy participants recruited randomly from two communities in Petaling district, Selangor, Malaysia. The reference tests were Panbio Dengue IgG indirect and capture enzyme-linked immunosorbent assays, in-house hemagglutination inhibition assay, and focus reduction neutralization test. Dengue Serostate had a sensitivity and specificity of 91.1% (95%CI 87.8-93.8) and 91.1% (95%CI 83.8-95.8) for the diagnosis of previous dengue, and 90.2% (95%CI 76.9-97.3) and 93.2% (95%CI 90.5-95.4) for the diagnosis of recent dengue, respectively. Its positive predictive value of 97.5% (95%CI 95.3-98.8) would prevent most dengue-naïve individuals from being vaccinated. ViroTrack Dengue Serostate's good point-of-care diagnostic accuracy can ease the conduct of dengue serosurveys to inform dengue vaccination strategy and facilitate pre-vaccination screening to ensure safety.
  8. Guad RM, Carandang RR, Solidum JN, W Taylor-Robinson A, Wu YS, Aung YN, et al.
    PLoS One, 2021;16(12):e0261412.
    PMID: 34929011 DOI: 10.1371/journal.pone.0261412
    BACKGROUND: Dengue is the most rapidly spreading mosquito-borne viral disease of humans worldwide, including southeast Asia region. This review provides a comprehensive overview of questionnaire-related dengue studies conducted in the Philippines and evaluates their reliability and validity in these surveys.

    METHODS: A review protocol constructed by a panel of experienced academic reviewers was used to formulate the methodology, research design, search strategy and selection criteria. An extensive literature search was conducted between March-June 2020 in various major electronic biomedical databases including PubMed, EMBASE, MEDLINE and ScienceDirect. A systematic review and meta-analysis (PRISMA) were selected as the preferred item reporting method.

    RESULTS: Out of a total of 34 peer-reviewed dengue-related KAP studies that were identified, 15 published from 2000 to April 2020 met the inclusion criteria. Based on the meta-analysis, a poor mean score was obtained for each of knowledge (68.89), attitude (49.86) and preventive practice (64.69). Most respondents were equipped with a good knowledge of the major clinical signs of dengue. Worryingly, 95% of respondents showed several negative attitudes towards dengue prevention, claiming that this was not possible and that enacting preventive practices was not their responsibility. Interestingly, television or radio was claimed as the main source of gaining dengue information (range 50-95%). Lastly, only five articles (33.3%) piloted or pretested their questionnaire before surveying, of which three reported Cronbach's alpha coefficient (range 0.70 to 0.90).

    CONCLUSION: This review indicates that to combat the growing public health threat of dengue to the Philippines, we need the active participation of resident communities, full engagement of healthcare personnel, promotion of awareness campaigns, and access to safe complementary and alternative medicines. Importantly, the psychometric properties of each questionnaire should be assessed rigorously.

  9. Jindal HM, Chandramathi S, Sekaran SD, Suresh K
    Trop Biomed, 2020 Sep 01;37(3):626-636.
    PMID: 33612777 DOI: 10.47665/tb.37.3.626
    Hand hygiene is the topmost crucial procedure to prevent hospital-acquired infections. Choosing an effective hand disinfectant is necessary in enforcing good hand hygiene practice especially in hospital settings. The aim of the study was to investigate the efficacy of Aaride AGT-1 as a hand disinfectant for the inhibition of pathogenic microorganisms' transmission among both patients and personnel in the health care system compared to other commercially available disinfectants. In the present study, a new hand disinfectant Aaride AGT-1 was tested against several bacterial and viral pathogens to evaluate its antimicrobial activity profile. The results revealed that Aaride AGT-1 displayed the highest antibacterial activity against five pathogenic bacteria including MRSA when compared to other commercially available hand sanitizers. Aaride AGT-1 showed the lowest percentage needed to inhibit the growth of bacterial pathogens. In addition, results obtained from time killing assay revealed that Aaride AGT-1 demonstrated the best killing kinetics, by eradicating the bacterial cells rapidly within 0.5 min with 6 log reduction (>99.99% killing). Also, Aaride AGT1 was able to reduce 100% plaque formed by three viruses namely HSV-1, HSV-2 and EV-71. In conclusion, Aaride AGT-1 is capable of killing wide-spectrum of pathogens including bacteria and viruses compared to other common disinfectants used in hospital settings. Aaride AGT-1's ability to kill both bacteria and viruses contributes as valuable addition to the hand disinfection portfolio.
  10. Mahboob T, Nawaz M, de Lourdes Pereira M, Tian-Chye T, Samudi C, Sekaran SD, et al.
    Sci Rep, 2020 06 02;10(1):8954.
    PMID: 32488154 DOI: 10.1038/s41598-020-65728-0
    Acanthamoeba, a genus that contains at least 24 species of free-living protozoa, is ubiquitous in nature. Successful treatment of Acanthamoeba infections is always very difficult and not always effective. More effective drugs must be developed, and medicinal plants may have a pivotal part in the future of drug discovery. Our research focused on investigating the in vitro anti- acanthamoebic potential of Leea indica and its constituent gallic acid in different concentrations. Water and butanol fractions exhibited significant amoebicidal activity against trophozoites and cysts. Gallic acid (100 µg/mL) revealed 83% inhibition of trophozoites and 69% inhibition of cysts. The butanol fraction induced apoptosis in trophozoites, which was observed using tunnel assay. The cytotoxicity of the fractions and gallic acid was investigated against MRC-5 and no adverse effects were observed. Gallic acid was successfully loaded within poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles with 82.86% encapsulation efficiency, while gallic acid showed 98.24% in vitro release at 48 hours. Moreover, the gallic acid encapsulated in the PLGA nanoparticles exhibited 90% inhibition against trophozoites. In addition, gallic acid encapsulated nanoparticles showed reduced cytotoxicity towards MRC-5 compared to gallic acid, which evidenced that natural product nanoencapsulation in polymeric nanoparticles could play an important role in the delivery of natural products.
  11. Chong ZL, Sekaran SD, Soe HJ, Peramalah D, Rampal S, Ng CW
    BMC Infect Dis, 2020 Mar 12;20(1):210.
    PMID: 32164538 DOI: 10.1186/s12879-020-4911-5
    BACKGROUND: Dengue is an emerging infectious disease that infects up to 390 million people yearly. The growing demand of dengue diagnostics especially in low-resource settings gave rise to many rapid diagnostic tests (RDT). This study evaluated the accuracy and utility of ViroTrack Dengue Acute - a new biosensors-based dengue NS1 RDT, SD Bioline Dengue Duo NS1/IgM/IgG combo - a commercially available RDT, and SD Dengue NS1 Ag enzyme-linked immunosorbent assay (ELISA), for the diagnosis of acute dengue infection.

    METHODS: This prospective cross-sectional study consecutively recruited 494 patients with suspected dengue from a health clinic in Malaysia. Both RDTs were performed onsite. The evaluated ELISA and reference tests were performed in a virology laboratory. The reference tests comprised of a reverse transcription-polymerase chain reaction and three ELISAs for the detection of dengue NS1 antigen, IgM and IgG antibodies, respectively. The diagnostic performance of evaluated tests was computed using STATA version 12.

    RESULTS: The sensitivity and specificity of ViroTrack were 62.3% (95%CI 55.6-68.7) and 95.0% (95%CI 91.7-97.3), versus 66.5% (95%CI 60.0-72.6) and 95.4% (95%CI 92.1-97.6) for SD NS1 ELISA, and 52.4% (95%CI 45.7-59.1) and 97.7% (95%CI 95.1-99.2) for NS1 component of SD Bioline, respectively. The combination of the latter with its IgM and IgG components were able to increase test sensitivity to 82.4% (95%CI 76.8-87.1) with corresponding decrease in specificity to 87.4% (95%CI 82.8-91.2). Although a positive test on any of the NS1 assays would increase the probability of dengue to above 90% in a patient, a negative result would only reduce this probability to 23.0-29.3%. In contrast, this probability of false negative diagnosis would be further reduced to 14.7% (95%CI 11.4-18.6) if SD Bioline NS1/IgM/IgG combo was negative.

    CONCLUSIONS: The performance of ViroTrack Dengue Acute was comparable to SD Dengue NS1 Ag ELISA. Addition of serology components to SD Bioline Dengue Duo significantly improved its sensitivity and reduced its false negative rate such that it missed the fewest dengue patients, making it a better point-of-care diagnostic tool. New RDT like ViroTrack Dengue Acute may be a potential alternative to existing RDT if its combination with serology components is proven better in future studies.

  12. Soe HJ, Manikam R, Raju CS, Khan MA, Sekaran SD
    PLoS One, 2020;15(8):e0237141.
    PMID: 32764789 DOI: 10.1371/journal.pone.0237141
    Severe dengue can be lethal caused by manifestations such as severe bleeding, fluid accumulation and organ impairment. This study aimed to investigate the role of dengue non-structural 1 (NS1) protein and host factors contributing to severe dengue. Electrical cell-substrate impedance sensing system was used to investigate the changes in barrier function of microvascular endothelial cells treated NS1 protein and serum samples from patients with different disease severity. Cytokines and metabolites profiles were assessed using a multiplex cytokine assay and liquid chromatography mass spectrometry respectively. The findings showed that NS1 was able to induce the loss of barrier function in microvascular endothelium in a dose dependent manner, however, the level of NS1 in serum samples did not correlate with the extent of vascular leakage induced. Further assessment of host factors revealed that cytokines such as CCL2, CCL5, CCL20 and CXCL1, as well as adhesion molecule ICAM-1, that are involved in leukocytes infiltration were expressed higher in dengue patients in comparison to healthy individuals. In addition, metabolomics study revealed the presence of deregulated metabolites involved in the phospholipid metabolism pathway in patients with severe manifestations. In conclusion, disease severity in dengue virus infection did not correlate directly with NS1 level, but instead with host factors that are involved in the regulation of junctional integrity and phospholipid metabolism. However, as the studied population was relatively small in this study, these exploratory findings should be confirmed by expanding the sample size using an independent cohort to further establish the significance of this study.
  13. Ismail AA, Mahboob T, Samudi Raju C, Sekaran SD
    Trop Biomed, 2019 Dec 01;36(4):888-897.
    PMID: 33597462
    Zika virus (ZIKV) is a mosquito-borne Flaviviruses. ZIKV is known to cause birth defect in pregnant women, especially microcephaly in the fetus. Hence, more study is required to understand the infection of Zika virus towards human brain microvascular endothelial cells (MECs). In this study, brain MECs were infected with ZIKV at MOI of 1 and 5 in vitro. The changes in barrier function and membrane permeability of ZIKV-infected brain MECs were determined using electric cell-substrate impedance sensing (ECIS) system followed by gene expression of ZIKV-infected brain MECs at 24 hours post infection using one-color gene expression microarray. The ECIS results demonstrated that ZIKV infection enhances vascular leakage by increasing cell membrane permeability via alteration of brain MECs barrier function. This was further supported by high expression of proinflammatory cytokine genes (lnc-IL6-2, TNFAIP1 and TNFAIP6), adhesion molecules (CERCAM and ESAM) and growth factor (FIGF). Overall, findings of this study revealed that ZIKV infection could alter the barrier function of brain MECs by altering adhesion molecules and inflammatory response.
  14. Pourshahrestani S, Zeimaran E, Kadri NA, Gargiulo N, Jindal HM, Hasikin K, et al.
    Mater Sci Eng C Mater Biol Appl, 2019 May;98:1022-1033.
    PMID: 30812986 DOI: 10.1016/j.msec.2019.01.022
    A novel series of silver-doped mesoporous bioactive glass/poly(1,8-octanediol citrate) (AgMBG/POC) elastomeric biocomposite scaffolds were successfully constructed by a salt-leaching technique for the first time and the effect of inclusion of different AgMBG contents (5, 10, and 20 wt%) on physicochemical and biological properties of pure POC elastomer was evaluated. Results indicated that AgMBG particles were uniformly dispersed in the POC matrix and increasing the AgMBG concentration into POC matrix up to 20 wt% enhanced thermal behaviour, mechanical properties and water uptake ability of the composite scaffolds compared to those from POC. The 20%AgMBG/POC additionally showed higher degradation rate in Tris(hydroxymethyl)-aminomethane-HCl (Tris-HCl) compared with pure POC and lost about 26% of its initial weight after soaking for 28 days. The AgMBG phase incorporation also significantly endowed the resulting composite scaffolds with efficient antibacterial properties against Escherichia coli and Staphylococcus aureus bacteria while preserving their favorable biocompatibility with soft tissue cells (i.e., human dermal fibroblast cells). Taken together, our results suggest that the synergistic effect of both AgMBG and POC make these newly designed AgMBG/POC composite scaffold an attractive candidate for soft tissue engineering applications.
  15. Tang SS, Prodhan ZH, Biswas SK, Le CF, Sekaran SD
    Phytochemistry, 2018 Oct;154:94-105.
    PMID: 30031244 DOI: 10.1016/j.phytochem.2018.07.002
    Antimicrobial peptides (AMPs), the self-defence products of organisms, are extensively distributed in plants. They can be classified into several groups, including thionins, defensins, snakins, lipid transfer proteins, glycine-rich proteins, cyclotides and hevein-type proteins. AMPs can be extracted and isolated from different plants and plant organs such as stems, roots, seeds, flowers and leaves. They perform various physiological defensive mechanisms to eliminate viruses, bacteria, fungi and parasites, and so could be used as therapeutic and preservative agents. Research on AMPs has sought to obtain more detailed and reliable information regarding the selection of suitable plant sources and the use of appropriate isolation and purification techniques, as well as examining the mode of action of these peptides. Well-established AMP purification techniques currently used include salt precipitation methods, absorption-desorption, a combination of ion-exchange and reversed-phase C18 solid phase extraction, reversed-phase high-performance liquid chromatography (RP-HPLC), and the sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) method. Beyond these traditional methods, this review aims to highlight new and different approaches to the selection, characterisation, isolation, purification, mode of action and bioactivity assessment of a range of AMPs collected from plant sources. The information gathered will be helpful in the search for novel AMPs distributed in the plant kingdom, as well as providing future directions for the further investigation of AMPs for possible use on humans.
  16. Jindal HM, Ramanathan B, Le CF, Gudimella R, Razali R, Manikam R, et al.
    J Biomed Sci, 2018 Feb 15;25(1):15.
    PMID: 29448938 DOI: 10.1186/s12929-018-0414-8
    BACKGROUND: Streptococcus pneumoniae or pneumococcus is a leading cause of morbidity and mortality worldwide, specifically in relation to community-acquired pneumonia. Due to the overuse of antibiotics, S. pneumoniae has developed a high degree of resistance to a wide range of antibacterial drugs.

    METHODS: In this study, whole genome sequencing (WGS) was performed for 10 clinical strains of S. pneumoniae with different levels of sensitivity to standard antibiotics. The main objective was to investigate genetic changes associated with antibiotic resistance in S. pneumoniae.

    RESULTS: Our results showed that resistant isolates contain a higher number of non-synonymous single nucleotide polymorphisms (SNPs) as compared to susceptible isolates. We were able to identify SNPs that alter a single amino acid in many genes involved in virulence and capsular polysaccharide synthesis. In addition, 90 SNPs were only presented in the resistant isolates, and 31 SNPs were unique and had not been previously reported, suggesting that these unique SNPs could play a key role in altering the level of resistance to different antibiotics.

    CONCLUSION: Whole genome sequencing is a powerful tool for comparing the full genome of multiple isolates, especially those closely related, and for analysing the variations found within antibiotic resistance genes that lead to differences in antibiotic sensitivity. We were able to identify specific mutations within virulence genes related to resistant isolates. These findings could provide insights into understanding the role of single nucleotide mutants in conferring drug resistance.

    Study site: University Malaya Medical Centre (UMMC)
  17. Darwish NT, Sekaran SD, Alias Y, Khor SM
    J Pharm Biomed Anal, 2018 Feb 05;149:591-602.
    PMID: 29197806 DOI: 10.1016/j.jpba.2017.11.064
    The sharp increase in incidence of dengue infection has necessitated the development of methods for the rapid diagnosis of this deadly disease. Here we report the design and development of a reliable, sensitive, and specific optical immunosensor for the detection of the dengue nonstructural protein 1 (NS1) biomarker in clinical samples obtained during early stages of infection. The present optical NS1 immunosensor comprises a biosensing surface consisting of specific monoclonal NS1 antibody for immunofluorescence-based NS1 antigen determination using fluorescein isothiocyanate (FITC) conjugated to IgG antibody. The linear range of the optical immunosensor was from 15-500ngmL-1, with coefficient of determination (R2) of 0.92, high reproducibility (the relative standard deviation obtained was 2%), good stability for 21days at 4°C, and low detection limit (LOD) at 15ngmL-1. Furthermore, the optical immunosensor was capable of detecting NS1 analytes in plasma specimens from patients infected with the dengue virus, with low cross-reaction with plasma specimens containing the Japanese encephalitis virus (JEV) and Zika virus. No studies have been performed on the reproducibility and cross-reactivity regarding NS1 specificity, which is thus a limitation for optical NS1 immunosensors. In contrast, the present study addressed these limitations carefully where these two important experiments were conducted to showcase the robustness of our newly developed optical-based fluorescence immunosensor, which can be practically used for direct NS1 determination in any untreated clinical sample.
  18. Soe HJ, Yong YK, Al-Obaidi MMJ, Raju CS, Gudimella R, Manikam R, et al.
    Medicine (Baltimore), 2018 Feb;97(5):e9713.
    PMID: 29384851 DOI: 10.1097/MD.0000000000009713
    Dengue virus is one of the most widespread flaviviruses that re-emerged throughout recent decades. The progression from mild dengue to severe dengue (SD) with the complications such as vascular leakage and hemorrhage increases the fatality rate of dengue. The pathophysiology of SD is not entirely clear. To investigate potential biomarkers that are suggestive of pathogenesis of SD, a small panel of serum samples selected from 1 healthy individual, 2 dengue patients without warning signs (DWS-), 2 dengue patients with warning signs (DWS+), and 5 patients with SD were subjected to a pilot analysis using Sengenics Immunome protein array. The overall fold changes of protein expressions and clustering heat map revealed that PFKFB4, TPM1, PDCL3, and PTPN20A were elevated among patients with SD. Differential expression analysis identified that 29 proteins were differentially elevated greater than 2-fold in SD groups than DWS- and DWS+. From the 29 candidate proteins, pathways enrichment analysis also identified insulin signaling and cytoskeleton pathways were involved in SD, suggesting that the insulin pathway may play a pivotal role in the pathogenesis of SD.
  19. Lee SH, Atiya N, Wang SM, Manikam R, Raju CS, Sekaran SD
    Intervirology, 2018;61(4):193-203.
    PMID: 30541013 DOI: 10.1159/000495180
    OBJECTIVE: Herpes simplex virus infection through the neuronal route is the most well-studied mode of viral encephalitis that can persists in a human host for a lifetime. However, the involvement of other possible infection mechanisms by the virus remains underexplored. Therefore, this study aims to determine the temporal effects and mechanisms by which the virus breaches the human brain micro-vascular endothelial cells of the blood-brain barrier.

    METHOD: An electrical cell-substrate impedance-sensing tool was utilized to study the real-time cell-cell barrier or morphological changes in response to the virus infection.

    RESULTS: Herpes simplex virus, regardless of type (i.e., 1 or 2), reduced the cell-cell barrier resistance almost immediately after virus addition to endothelial cells, with negligible involvement of cell-matrix adhesion changes. There is no exclusivity in the infection ability of endothelial cells. From 30 h after HSV infection, there was an increase in cell membrane capacitance with a subsequent loss of cell-matrix adhesion capability, indicating a viability loss of the infected endothelial cells.

    CONCLUSION: This study shows for the first time that destruction of human brain micro-vascular endothelial cells as an in vitro model of the blood-brain barrier could be an alternative invasion mechanism during herpes simplex virus infection.

  20. Mahboob T, Azlan AM, Shipton FN, Boonroumkaew P, Nor Azman NS, Sekaran SD, et al.
    Exp Parasitol, 2017 Dec;183:160-166.
    PMID: 28916456 DOI: 10.1016/j.exppara.2017.09.002
    Acanthamoeba species are pathogenic protozoa which account for amoebic keratitis, conjunctivitis and granulomatous amoebic encephalitis. These amoebae form cysts which resist drugs and more effective acanthamoebicidal agents are needed. Medicinal plants could be useful in improving the current treatment strategies for Acanthamoeba infections. In the present study, we examined the amoebicidal effects of Pericampylus glaucus (Lam.) Merr., a medicinal plant used for the treatment of conjunctivitis in Malaysia. Pathogenic Acanthamoeba triangularis were isolated from environmental water samples and treated with different concentrations of fractions obtained from Pericampylus glaucus (Lam.) Merr. as well as main constituents for 24-72 h. Chlorhexidine was used as a reference drug. Ethanol fraction of stem showed significant (p 
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