Displaying publications 21 - 40 of 84 in total

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  1. Oyomopito RA, Li PC, Sungkanuparph S, Phanuphak P, Tee KK, Sirisanthana T, et al.
    J Acquir Immune Defic Syndr, 2013 Mar 01;62(3):293-300.
    PMID: 23138836 DOI: 10.1097/QAI.0b013e31827a2e8f
    BACKGROUND: HIV-1 group M viruses diverge 25%-35% in envelope, important for viral attachment during infection, and 10%-15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunological, or virological treatment responses differed by genotype in treatment-naive patients initiating first-line therapy.

    METHODS: Prospectively collected longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan, and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count, and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of Centers for Disease Control and Prevention category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post therapy, evaluated by linear and logistic regression, respectively.

    RESULTS: Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median: 413 days, interquartile range: 169-672 days). Patients >40 years demonstrated smaller immunological increases (P = 0.002) and higher risk of clinical deterioration (hazard ratio = 2.17; P = 0.008). Patients with baseline CD4 cell counts >200 cells per microliter had lower risk of clinical deterioration (hazard ratio = 0.373; P = 0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (P = 0.024). A total of 530 patients (48.0% of eligible) were included in virological analyses with no differences in response found between genotypes.

    CONCLUSIONS: Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared with subtype B-infected counterparts. Clinical deterioration was associated with low baseline CD4 counts and older age. The lack of differences in virologic outcomes suggests that all patients have opportunities for virological suppression.

  2. Oong XY, Ng KT, Takebe Y, Ng LJ, Chan KG, Chook JB, et al.
    Emerg Microbes Infect, 2017 Jan 04;6(1):e3.
    PMID: 28050020 DOI: 10.1038/emi.2016.132
    Human coronavirus OC43 (HCoV-OC43) is commonly associated with respiratory tract infections in humans, with five genetically distinct genotypes (A to E) described so far. In this study, we obtained the full-length genomes of HCoV-OC43 strains from two previously unrecognized lineages identified among patients presenting with severe upper respiratory tract symptoms in a cross-sectional molecular surveillance study in Kuala Lumpur, Malaysia, between 2012 and 2013. Phylogenetic, recombination and comparative genomic analyses revealed two distinct clusters diverging from a genotype D-like common ancestor through recombination with a putative genotype A-like lineage in the non-structural protein (nsp) 10 gene. Signature amino acid substitutions and a glycine residue insertion at the N-terminal domain of the S1 subunit of the spike gene, among others, exhibited further distinction in a recombination pattern, to which these clusters were classified as genotypes F and G. The phylogeographic mapping of the global spike gene indicated that the genetically similar HCoV-OC43 genotypes F and G strains were potentially circulating in China, Japan, Thailand and Europe as early as the late 2000s. The transmission network construction based on the TN93 pairwise genetic distance revealed the emergence and persistence of multiple sub-epidemic clusters of the highly prevalent genotype D and its descendant genotypes F and G, which contributed to the spread of HCoV-OC43 in the region. Finally, a more consistent nomenclature system for non-recombinant and recombinant HCoV-OC43 lineages is proposed, taking into account genetic recombination as an important feature in HCoV evolution and classification.
  3. Oong XY, Chook JB, Ng KT, Chow WZ, Chan KG, Hanafi NS, et al.
    Virol J, 2018 05 23;15(1):91.
    PMID: 29792212 DOI: 10.1186/s12985-018-1005-8
    BACKGROUND: Human metapneumovirus (HMPV) is established as one of the causative agents of respiratory tract infections. To date, there are limited reports that describe the effect of HMPV genotypes and/or viral load on disease pathogenesis in adults. This study aims to determine the role of HMPV genetic diversity and nasopharyngeal viral load on symptom severity in outpatient adults with acute respiratory tract infections.
    METHODS: Severity of common cold symptoms of patients from a teaching hospital was assessed by a four-category scale and summed to obtain the total symptom severity score (TSSS). Association between the fusion and glycoprotein genes diversity, viral load (quantified using an improved RT-qPCR assay), and symptom severity were analyzed using bivariate and linear regression analyses.
    RESULTS: Among 81/3706 HMPV-positive patients, there were no significant differences in terms of demographics, number of days elapsed between symptom onset and clinic visit, respiratory symptoms manifestation and severity between different HMPV genotypes/sub-lineages. Surprisingly, elderly patients (≥65 years old) had lower severity of symptoms (indicated by TSSS) than young and middle age adults (p = 0.008). Nasopharyngeal viral load did not correlate with nor predict symptom severity of HMPV infection. Interestingly, at 3-5 days after symptom onset, genotype A-infected patients had higher viral load compared to genotype B (4.4 vs. 3.3 log10 RNA copies/μl) (p = 0.003).
    CONCLUSIONS: Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission.
    Study site: Primary Care Clinic, University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  4. Oong XY, Ng KT, Tan JL, Chan KG, Kamarulzaman A, Chan YF, et al.
    PLoS One, 2017;12(1):e0170610.
    PMID: 28129386 DOI: 10.1371/journal.pone.0170610
    Reassortment of genetic segments between and within influenza B lineages (Victoria and Yamagata) has been shown to generate novel reassortants with unique genetic characteristics. Based on hemagglutinin (HA) and neuraminidase (NA) genes, recent surveillance study has identified reassortment properties in B/Phuket/3073/2013-like virus, which is currently used in the WHO-recommended influenza vaccine. To understand the potential reassortment patterns for all gene segments, four B/Phuket/3073/2013-like viruses and two unique reassortants (one each from Yamagata and Victoria) detected in Malaysia from 2012-2014 were subjected to whole-genome sequencing. Each gene was phylogenetically classified into lineages, clades and sub-clades. Three B/Phuket/3073/2013-like viruses from Yamagata lineage were found to be intra-clade reassortants, possessing PA and NA genes derived from Stockholm/12-like sub-clade, while the remaining genes from Wisconsin/01-like sub-clade (both sub-clades were within Yamagata Clade 3/Yam-3). However, the other B/Phuket/3073/2013-like virus had NS gene that derived from Stockholm/12-like sub-clade instead of Wisconsin/01-like sub-clade. One inter-clade reassortant had Yamagata Clade 2/Yam-2-derived HA and NP, and its remaining genes were Yam-3-derived. Within Victoria Clade 1/Vic-1 in Victoria lineage, one virus had intra-clade reassortment properties: HA and PB2 from Vic-1B sub-clade, MP and NS from a unique sub-clade "Vic-1C", and the remaining genes from Vic-1A sub-clade. Although random reassortment event may generate unique reassortants, detailed phylogenetic classification of gene segments showed possible genetic linkage between PA and NA genes in B/Phuket/3073/2013-like viruses, which requires further investigation. Understanding on reassortment patterns in influenza B evolution may contribute to future vaccine design.
  5. Oong XY, Ng KT, Lam TT, Pang YK, Chan KG, Hanafi NS, et al.
    PLoS One, 2015;10(8):e0136254.
    PMID: 26313754 DOI: 10.1371/journal.pone.0136254
    Epidemiological and evolutionary dynamics of influenza B Victoria and Yamagata lineages remained poorly understood in the tropical Southeast Asia region, despite causing seasonal outbreaks worldwide. From 2012-2014, nasopharyngeal swab samples collected from outpatients experiencing acute upper respiratory tract infection symptoms in Kuala Lumpur, Malaysia, were screened for influenza viruses using a multiplex RT-PCR assay. Among 2,010/3,935 (51.1%) patients infected with at least one respiratory virus, 287 (14.3%) and 183 (9.1%) samples were tested positive for influenza A and B viruses, respectively. Influenza-positive cases correlate significantly with meteorological factors-total amount of rainfall, relative humidity, number of rain days, ground temperature and particulate matter (PM10). Phylogenetic reconstruction of haemagglutinin (HA) gene from 168 influenza B viruses grouped them into Yamagata Clade 3 (65, 38.7%), Yamagata Clade 2 (48, 28.6%) and Victoria Clade 1 (55, 32.7%). With neuraminidase (NA) phylogeny, 30 intra-clade (29 within Yamagata Clade 3, 1 within Victoria Clade 1) and 1 inter-clade (Yamagata Clade 2-HA/Yamagata Clade 3-NA) reassortants were identified. Study of virus temporal dynamics revealed a lineage shift from Victoria to Yamagata (2012-2013), and a clade shift from Yamagata Clade 2 to Clade 3 (2013-2014). Yamagata Clade 3 predominating in 2014 consisted of intra-clade reassortants that were closely related to a recent WHO vaccine candidate strain (B/Phuket/3073/2013), with the reassortment event occurred approximately 2 years ago based on Bayesian molecular clock estimation. Malaysian Victoria Clade 1 viruses carried H274Y substitution in the active site of neuraminidase, which confers resistance to oseltamivir. Statistical analyses on clinical and demographic data showed Yamagata-infected patients were older and more likely to experience headache while Victoria-infected patients were more likely to experience nasal congestion and sore throat. This study describes the evolution of influenza B viruses in Malaysia and highlights the importance of continuous surveillance for better vaccination policy in this region.
  6. Ong LY, Razak SN, Lee YM, Sri La Sri Ponnampalavanar S, Syed Omar SF, Azwa RI, et al.
    J Med Virol, 2014 Jan;86(1):38-44.
    PMID: 24127302 DOI: 10.1002/jmv.23772
    Expansion of antiretroviral treatment programs have led to the growing concern for the development of antiretroviral drug resistance. The aims were to assess the prevalence of drug resistant HIV-1 variants and to identify circulating subtypes among HAART-naïve patients. Plasma specimens from N = 100 HIV+ HAART-naïve adult were collected between March 2008 and August 2010 and viral RNA were extracted for nested PCR and sequenced. PR-RT sequences were protein aligned and checked for transmitted drug resistance mutations. Phylogenetic reconstruction and recombination analysis were performed to determine the genotypes. Based on the WHO consensus guidelines, none of the recruited patients had any transmitted drug resistance mutations. When analyzed against the Stanford guidelines, 35% of patients had at least one reported mutation that may reduce drug susceptibility to PI (24%), NRTI (5%), and NNRTI (14%). The commonly detected mutation that may affect current first line therapy was V179D (3%), which may lead to reduced susceptibility to NNRTI. The predominant circulating HIV-1 genotypes were CRF01_AE (51%) and CRF33_01B (17%). The prevalence of unique recombinant forms (URF) was 7%; five distinct recombinant structures involving CRF01_AE and subtype B' were observed, among them a cluster of three isolates that could form a novel circulating recombinant form (CRF) candidate. Transmitted drug resistance prevalence among HAART-naïve patients was low in this cohort of patients in Kuala Lumpur despite introduction of HAART 5 years ago. Owing to the high genetic diversity, continued molecular surveillance can identify the persistent emergence of HIV-1 URF and novel CRF with significant epidemiological impact.
  7. Ng QR, Tee KK, Binley JM, Tong T
    AIDS Res Hum Retroviruses, 2022 Feb;38(2):162-172.
    PMID: 34006141 DOI: 10.1089/AID.2020.0299
    Human immunodeficiency virus type-1 (HIV-1) antigenic variation poses a great challenge for vaccine immunogen design to elicit broadly neutralizing antibodies (bNAbs). Over the last 10-15 years, great progress has been made to understand the conserved sites of sensitivity on HIV envelope glycoprotein spikes targeted by bNAbs. Plasma neutralization mapping and monoclonal antibody isolation efforts have revealed five major conserved epitope clusters. Most of this work has focused on subtype B and C-infected Caucasian or African donors. It is not clear if the same epitopes and epitope rank order preferences are also true in donors infected with different HIV-1 subtypes and with different racial backgrounds. To investigate this point, in this study we report the first attempt to profile the bNAb specificities of CRF01_AE-infected Malaysian plasmas. We first measured neutralization titers of 21 plasmas against a subtype A, B, and AE pseudovirus panel. This revealed that 14% (3 of 21) plasmas had cross-clade breadth. Focusing on the cross-neutralizing plasma P9, we used AE and JR-FL mutant pseudoviruses, gp120 monomer interference, and native polyacrylamide gel electrophoresis to better understand the neutralization specificity. P9 demonstrates CD4-binding-site specificity with trimer dependence and D368 independence.
  8. Ng KT, Ng KY, Chen JH, Ng OT, Kamarulzaman A, Tee KK
    Clin Infect Dis, 2014 Sep 15;59(6):910-1.
    PMID: 24944233 DOI: 10.1093/cid/ciu480
  9. Ng KT, Ng KY, Khong WX, Chew KK, Singh PK, Yap JK, et al.
    PLoS One, 2013;8(12):e80884.
    PMID: 24312505 DOI: 10.1371/journal.pone.0080884
    HIV-1 subtype B and CRF01_AE are the predominant infecting subtypes among men who have sex with men (MSM) in Singapore. The genetic history, population dynamics and pattern of transmission networks of these genotypes remain largely unknown. We delineated the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and the recently characterized CRF51_01B strains circulating among the MSM population in Singapore. A total of 105 (49.5%) newly-diagnosed treatment-naïve MSM were recruited between February 2008 and August 2009. Phylogenetic reconstructions of the protease gene (HXB2: 2239 - 2629), gp120 (HXB2: 6942 - 7577) and gp41 (HXB2: 7803 - 8276) of the env gene uncovered five monophyletic transmission networks (two each within subtype B and CRF01_AE and one within CRF51_01B lineages) of different sizes (involving 3 - 23 MSM subjects, supported by posterior probability measure of 1.0). Bayesian coalescent analysis estimated that the emergence and dissemination of multiple sub-epidemic networks occurred between 1995 and 2005, driven largely by subtype B and later followed by CRF01_AE. Exponential increase in effective population size for both subtype B and CRF01_AE occurred between 2002 to 2007 and 2005 to 2007, respectively. Genealogical estimates suggested that the novel CRF51_01B lineages were probably generated through series of recombination events involving CRF01_AE and multiple subtype B ancestors. Our study provides the first insight on the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and CRF51_01B viral strains circulating among MSM in Singapore.
  10. Ng KT, Ong LY, Lim SH, Takebe Y, Kamarulzaman A, Tee KK
    PLoS One, 2013;8(6):e67286.
    PMID: 23840653 DOI: 10.1371/journal.pone.0067286
    HIV-1 epidemics among men who have sex with men (MSM) continue to expand in developed and developing countries. Although HIV infection in MSM is amongst the highest of the key affected populations in many countries in Southeast Asia, comprehensive molecular epidemiological study of HIV-1 among MSM remains inadequate in the region including in Malaysia. Here, we reported the phylodynamic profiles of HIV-1 genotypes circulating among MSM population in Kuala Lumpur, Malaysia. A total of n = 459 newly-diagnosed treatment-naïve consenting subjects were recruited between March 2006 and August 2012, of whom 87 (18.9%) were self-reported MSM. Transmitted drug resistance mutations were absent in these isolates. Cumulatively, phylogenetic reconstructions of the pro-rt gene (HXB2∶2253-3275) showed that HIV-1 subtype B and CRF01_AE were predominant and contributed to approximately 80% of the total HIV-1 infection among MSM. In addition to numerous unique transmission lineages within these genotypes, twelve monophyletic transmission clusters of different sizes (2-7 MSM sequences, supported by posterior probability value of 1) were identified in Malaysia. Bayesian coalescent analysis estimated that the divergence times for these clusters were mainly dated between 1995 and 2005 with four major transmission clusters radiating at least 12 years ago suggesting that active spread of multiple sub-epidemic clusters occurred during this period. The changes in effective population size of subtype B showed an exponential growth within 5 years between 1988 and 1993, while CRF01_AE lineage exhibited similar expansion between 1993 and 2003. Our study provides the first insight of the phylodynamic profile of HIV-1 subtype B and CRF01_AE circulating among MSM population in Kuala Lumpur, Malaysia, unravelling the importance of understanding transmission behaviours as well as evolutionary history of HIV-1 in assessing the risk of outbreak or epidemic expansion.
  11. Ng KT, Ong LY, Takebe Y, Kamarulzaman A, Tee KK
    J Virol, 2012 Oct;86(20):11405-6.
    PMID: 22997423
    We report here the first novel HIV-1 circulating recombinant form (CRF) 54_01B (CRF54_01B) isolated from three epidemiologically unlinked subjects of different risk groups in Malaysia. These recently sampled recombinants showed a complex genome organization composed of parental subtype B' and CRF01_AE, with identical recombination breakpoints observed in the gag, pol, and vif genes. Such a discovery highlights the ongoing active generation and spread of intersubtype recombinants involving the subtype B' and CRF01_AE lineages and indicates the potential of the new CRF in bridging HIV-1 transmission among different risk groups in Southeast Asia.
  12. Ng KT, Lee YM, Al-Darraji HA, Xia X, Takebe Y, Chan KG, et al.
    Genome Announc, 2013 Jan;1(1).
    PMID: 23409272 DOI: 10.1128/genomeA.00168-12
    We report the full genome sequence of hepatitis C virus (HCV) subtype 6n from Kuala Lumpur, Malaysia. Phylogenetic analysis of the isolate 10MYKJ032 suggests that Southeast Asia might be the origin for the HCV subtype 6n and highlights the possible spread of this lineage from Southeast Asia to other regions.
  13. Ng KT, Takebe Y, Chook JB, Chow WZ, Chan KG, Abed Al-Darraji HA, et al.
    Sci Rep, 2015;5:15198.
    PMID: 26459957 DOI: 10.1038/srep15198
    Co-infections with human immunodeficiency virus type 1 (HIV-1) and human pegivirus (HPgV) are common in hepatitis C virus (HCV)-infected individuals. However, analysis on the evolutionary dynamics and transmission network profiles of these viruses among individuals with multiple infections remains limited. A total of 228 injecting drug users (IDUs), either HCV- and/or HIV-1-infected, were recruited in Kuala Lumpur, Malaysia. HCV, HIV-1 and HPgV genes were sequenced, with epidemic growth rates assessed by the Bayesian coalescent method. Based on the sequence data, mono-, dual- and triple-infection were detected in 38.8%, 40.6% and 20.6% of the subjects, respectively. Fifteen transmission networks involving HCV (subtype 1a, 1b, 3a and 3b), HIV-1 (CRF33_01B) and HPgV (genotype 2) were identified and characterized. Genealogical estimates indicated that the predominant HCV, HIV-1 and HPgV genotypes were introduced into the IDUs population through multiple sub-epidemics that emerged as early as 1950s (HCV), 1980s (HIV-1) and 1990s (HPgV). By determining the difference in divergence times between viral lineages (ΔtMRCA), we also showed that the frequency of viral co-transmission is low among these IDUs. Despite increased access to therapy and other harm reduction interventions, the continuous emergence and coexistence of new transmission networks suggest persistent multiple viral transmissions among IDUs.
  14. Ng KT, Takebe Y, Kamarulzaman A, Tee KK
    Arch Virol, 2021 Jan;166(1):225-229.
    PMID: 33084935 DOI: 10.1007/s00705-020-04855-5
    Genome sequences of members of a potential fourth rhinovirus (RV) species, provisionally denoted as rhinovirus A clade D, from patients with acute respiratory infection were determined. Bayesian coalescent analysis estimated that clade D emerged around the 1940s and diverged further around 2006-2007 into two distinctive sublineages (RV-A8-like and RV-A45-like) that harbored unique "clade-defining" substitutions. Similarity plots and bootscan mapping revealed a recombination breakpoint located in the 5'-UTR region of members of the RV-A8-like sublineage. Phylogenetic reconstruction revealed the distribution of clade D viruses in the Asia Pacific region and in Europe, underlining its worldwide distribution.
  15. Ng KT, Chook JB, Oong XY, Chan YF, Chan KG, Hanafi NS, et al.
    Sci Rep, 2016 10 10;6:34855.
    PMID: 27721388 DOI: 10.1038/srep34855
    Human rhinovirus (HRV) is the major aetiology of respiratory tract infections. HRV viral load assays are available but limitations that affect accurate quantification exist. We developed a one-step Taqman assay using oligonucleotides designed based on a comprehensive list of global HRV sequences. The new oligonucleotides targeting the 5'-UTR region showed high PCR efficiency (E = 99.6%, R2 = 0.996), with quantifiable viral load as low as 2 viral copies/μl. Assay evaluation using an External Quality Assessment (EQA) panel yielded a detection rate of 90%. When tested on 315 human enterovirus-positive specimens comprising at least 84 genetically distinct HRV types/serotypes (determined by the VP4/VP2 gene phylogenetic analysis), the assay detected all HRV species and types, as well as other non-polio enteroviruses. A commercial quantification kit, which failed to detect any of the EQA specimens, produced a detection rate of 13.3% (42/315) among the clinical specimens. Using the improved assay, we showed that HRV sheds in the upper respiratory tract for more than a week following acute infection. We also showed that HRV-C had a significantly higher viral load at 2-7 days after the onset of symptoms (p = 0.001). The availability of such assay is important to facilitate disease management, antiviral development, and infection control.
  16. Ng KT, Oong XY, Lim SH, Chook JB, Takebe Y, Chan YF, et al.
    Clin Infect Dis, 2018 07 02;67(2):261-268.
    PMID: 29385423 DOI: 10.1093/cid/ciy063
    Background: Rhinovirus (RV) is one of the main viral etiologic agents of acute respiratory illnesses. Despite the heightened disease burden caused by RV, the viral factors that increase the severity of RV infection, the transmission pattern, and seasonality of RV infections remain unclear.

    Methods: An observational study was conducted among 3935 patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014.

    Results: The VP4/VP2 gene was genotyped from all 976 RV-positive specimens, where the predominance of RV-A (49%) was observed, followed by RV-C (38%) and RV-B (13%). A significant regression in median nasopharyngeal viral load (VL) (P < .001) was observed, from 883 viral copies/µL at 1-2 days after symptom onset to 312 viral copies/µL at 3-4 days and 158 viral copies/µL at 5-7 days, before declining to 35 viral copies/µL at ≥8 days. In comparison with RV-A (median VL, 217 copies/µL) and RV-B (median VL, 275 copies/µL), RV-C-infected subjects produced higher VL (505 copies/µL; P < .001). Importantly, higher RV VL (median, 348 copies/µL) was associated with more severe respiratory symptoms (Total Symptom Severity Score ≥17, P = .017). A total of 83 phylogenetic-based transmission clusters were identified in the population. It was observed that the relative humidity was the strongest environmental predictor of RV seasonality in the tropical climate.

    Conclusions: Our findings underline the role of VL in increasing disease severity attributed to RV-C infection, and unravel the factors that fuel the population transmission dynamics of RV.

  17. Ng CK, How KY, Tee KK, Chan KG
    Genes (Basel), 2019 04 08;10(4).
    PMID: 30965610 DOI: 10.3390/genes10040282
    Quorum sensing (QS) is a cell-to-cell communication system that uses autoinducers as signaling molecules to enable inter-species and intra-species interactions in response to external stimuli according to the population density. QS allows bacteria such as Acinetobacter baumannii to react rapidly in response to environmental changes and hence, increase the chances of survival. A. baumannii is one of the causative agents in hospital-acquired infections and the number of cases has increased remarkably in the past decade. In this study, A. baumannii strain 863, a multidrug-resistant pathogen, was found to exhibit QS activity by producing N-acyl homoserine lactone. We identified the autoinducer synthase gene, which we named abaI, by performing whole genome sequencing analysis of A. baumannii strain 863. Using high resolution tandem triple quadrupole mass spectrometry, we reported that abaI of A. baumannii strain 863 produced 3-hydroxy-dodecanoyl-homoserine lactone. A gene deletion mutant was constructed, which confirmed the functionality of abaI. A growth defect was observed in the QS-deficient mutant strain. Transcriptome profiling was performed to determine the possible genes regulated by QS. Four groups of genes that showed differential expression were discovered, namely those involved in carbon source metabolism, energy production, stress response and the translation process.
  18. Md Nadzri MN, Md Zamri ASS, Singh S, Sumarni MG, Lai CH, Tan CV, et al.
    Front Public Health, 2024;12:1289622.
    PMID: 38544725 DOI: 10.3389/fpubh.2024.1289622
    INTRODUCTION: Since the COVID-19 pandemic began, it has spread rapidly across the world and has resulted in recurrent outbreaks. This study aims to describe the COVID-19 epidemiology in terms of COVID-19 cases, deaths, ICU admissions, ventilator requirements, testing, incidence rate, death rate, case fatality rate (CFR) and test positivity rate for each outbreak from the beginning of the pandemic in 2020 till endemicity of COVID-19 in 2022 in Malaysia.

    METHODS: Data was sourced from the GitHub repository and the Ministry of Health's official COVID-19 website. The study period was from the beginning of the outbreak in Malaysia, which began during Epidemiological Week (Ep Wk) 4 in 2020, to the last Ep Wk 18 in 2022. Data were aggregated by Ep Wk and analyzed in terms of COVID-19 cases, deaths, ICU admissions, ventilator requirements, testing, incidence rate, death rate, case fatality rate (CFR) and test positivity rate by years (2020 and 2022) and for each outbreak of COVID-19.

    RESULTS: A total of 4,456,736 cases, 35,579 deaths and 58,906,954 COVID-19 tests were reported for the period from 2020 to 2022. The COVID-19 incidence rate, death rate, CFR and test positivity rate were reported at 1.085 and 0.009 per 1,000 populations, 0.80 and 7.57%, respectively, for the period from 2020 to 2022. Higher cases, deaths, testing, incidence/death rate, CFR and test positivity rates were reported in 2021 and during the Delta outbreak. This is evident by the highest number of COVID-19 cases, ICU admissions, ventilatory requirements and deaths observed during the Delta outbreak.

    CONCLUSION: The Delta outbreak was the most severe compared to other outbreaks in Malaysia's study period. In addition, this study provides evidence that outbreaks of COVID-19, which are caused by highly virulent and transmissible variants, tend to be more severe and devastating if these outbreaks are not controlled early on. Therefore, close monitoring of key epidemiological indicators, as reported in this study, is essential in the control and management of future COVID-19 outbreaks in Malaysia.

  19. Low WF, Ngeow YF, Chook JB, Tee KK, Ong SK, Peh SC, et al.
    Expert Rev Mol Med, 2022 Nov 16;25:e11.
    PMID: 36380484 DOI: 10.1017/erm.2022.38
    Hepatitis B virus (HBV) infection led to 66% liver deaths world-wide in year 2015. Thirty-seven per cent of these deaths were the result of chronic hepatitis B (CHB)-associated hepatocellular carcinoma (HCC). Although early diagnosis of HCC improves survival, early detection is rare. Methylation of HBV DNA including covalently closed circular DNA (cccDNA) is more often encountered in HCC cases than those in CHB and cirrhosis. Three typical CpG islands within the HBV genome are the common sites for methylation. The HBV cccDNA methylation affects the viral replication and protein expression in the course of infection and may associate with the disease pathogenesis and HCC development. We review the current findings in HBV DNA methylation that provide insights into its role in HCC diagnosis.
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