Displaying publications 21 - 40 of 57 in total

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  1. Sit PS, Teh CSJ, Idris N, Ponnampalavanar S
    Infect Genet Evol, 2018 04;59:132-141.
    PMID: 29421224 DOI: 10.1016/j.meegid.2018.01.031
    Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a serious infection that can result in significant morbidity and mortality. A retrospective cohort study was conducted to determine the predictors of mortality in patient with MRSA bacteremia correlating with clinical, phenotypic and genotypic characteristics of the relevant strains. Most of the bacteremia cases were healthcare-associated (P 
  2. Niek WK, Teh CSJ, Idris N, Thong KL, Ponnampalavanar S
    Jpn J Infect Dis, 2019 Jul 24;72(4):228-236.
    PMID: 30814457 DOI: 10.7883/yoken.JJID.2018.289
    Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common nosocomial pathogens, causing mild to severe infections. This study aimed to determine the genotypic and phenotypic characteristics of clinical MRSA isolates collected from a teaching hospital from 2014 - 2015. These isolates were genotyped by multilocus sequence typing, staphylococcal cassette chromosomal mec (SCCmec) typing, virulence genes detection, and pulsed-field gel electrophoresis; they were phenotyped based on their antibiotics susceptibility profiles. The most prevalent sequence type was ST22. ST3547 was identified from a blood isolate from 2015. Three SCCmec types (III in 26.26%, IV in 70.71%, and V in 3.03% isolates) were detected. Agr type I, II, and III were also detected among the isolates. The most prevalent virulence genes found were hemolysin (100%) and intracellular adhesion (91.9%). At least one staphylococcal enterotoxin was detected in 83 (83.8%) isolates. All the isolates were susceptible to vancomycin (minimum inhibitory concentration ≤ 2 μg/mL). Statistical analysis revealed a significant increase in hypertension (p = 0.035), dyslipidemia and obesity (p = 0.046), and previous exposure to any quinolone (p = 0.010) cases over the two-year period. The emergence and circulation of community-associated MRSA variants were observed in our hospital.
  3. Mong I, Ramoo V, Ponnampalavanar S, Chong MC, Wan Nawawi WNF
    J Clin Nurs, 2022 Jan;31(1-2):209-219.
    PMID: 34105196 DOI: 10.1111/jocn.15899
    BACKGROUND: Healthcare-associated infection (HAI) is one of the major threats to patients' safety besides being among the principal causes of patient morbidity and mortality. Catheter-associated urinary tract infection (CAUTI) is reported to be the most common HAI worldwide. CAUTI can be prevented with appropriate practice and care by healthcare personnel, especially nurses, who play the main role in urinary catheter care. Nurses' knowledge and attitude are considered to be important factors that influence their practice.

    OBJECTIVES: To assess nurses' level of knowledge, attitude and perceived practice regarding CAUTI and its preventive measures.

    METHODS: A cross-sectional design was adopted, and a self-administered questionnaire was used to collect data. Nurses from the medical and surgical inpatient wards of a tertiary teaching hospital in Malaysia were recruited in two stages using the stratified and simple random sampling methods. A total of 301 nurses participated. Descriptive analysis, an independent t test, ANOVA and hierarchical multiple regression were employed to analyse the data using SPSS software version 25. In addition, a STROBE checklist was used to report the results of this study.

    RESULTS: Nurses were found to have good knowledge, a positive attitude and good perceived practice regarding CAUTI prevention. Nurses aged above 30 and who had more than ten years of experience reported higher knowledge levels. Knowledge was found to be positively correlated with attitude and perceived practice; however, attitude explained a higher variance in perceived practice of CAUTI prevention compared with knowledge.

    CONCLUSION: Attitude was found to have a higher significant influence on perceived practice in this study. Educators need to emphasise the inculcation of a positive attitude among nurses rather than just knowledge for CAUTI prevention. Since this study assessed perceived practice, examining nurses' actual practice and its impact on patient outcomes is recommended in future studies.

  4. Chong YM, Chan YF, Jamaluddin MFH, Hasan MS, Pang YK, Ponnampalavanar S, et al.
    J Clin Virol, 2021 Dec;145:105000.
    PMID: 34739838 DOI: 10.1016/j.jcv.2021.105000
    BACKGROUND: Reports of co-circulation of respiratory viruses during the COVID-19 pandemic and co-infections with SARS-CoV-2 vary. However, limited information is available from developing countries.

    OBJECTIVES: We aimed to investigate the incidence of respiratory viruses in adult patients with suspected COVID-19 in Kuala Lumpur, Malaysia.

    STUDY DESIGN: We collected 198 respiratory samples from adult patients hospitalized with suspected COVID-19 in a single teaching hospital in Kuala Lumpur in February-May 2020 and tested combined oro-nasopharyngeal swabs with the NxTAG Respiratory Pathogen Panel (Luminex) and Allplex RV Essential (Seegene) assays. Forty-five negative samples further underwent viral metagenomics analysis.

    RESULTS: Of the 198 samples, 74 (37.4%) had respiratory pathogens, including 56 (28.3%) with SARS-CoV-2 and 18 (9.1%) positive for other respiratory pathogens. There were five (2.5%) SARS-CoV-2 co-infections, all with rhinovirus/enterovirus. Three samples (6.7%; 3/45) had viruses identified by metagenomics, including one case of enterovirus D68 and one of Saffold virus genotype 6 in a patient requiring ICU care. Most of the COVID-19 patients (91.1%; 51/56) had mild symptoms but 5.4% (3/56) died.

    CONCLUSION: During the early COVID-19 period, common respiratory viruses other than SARS-CoV-2 only accounted for 9.1% of hospitalization cases with ARI and co-infections with SARS-CoV-2 were rare. Continued surveillance is important to understand the impact of COVID-19 and its associated public health control measures on circulation of other respiratory viruses. Metagenomics can identify unexpected or rare pathogens, such as Saffold virus, which is rarely described in adults.

  5. Lau MY, Ponnampalavanar S, Lee WS, Jabar KA, Chua KH, Idris N, et al.
    J Infect Chemother, 2020 Oct;26(10):1058-1061.
    PMID: 32546330 DOI: 10.1016/j.jiac.2020.05.009
    The emergence of carbapenemase-producing Enterobacteriaceae has become a major global concern. OXA-48-like carbapenemase gene and its variants have been increasingly reported worldwide. This study reported the first OXA-181-producing Klebsiella quasipneumoniae isolate in Malaysia. This bacterium was isolated from blood specimen of a three-year-old boy with Alagille syndrome who had liver biopsy on October 2016. He had undergone liver transplant in India ten months previously. The genotypic and phenotypic characteristics of the strain were elucidated in this study. To our best knowledge, this is the first report of OXA-181-producing K. quasipneumoniae in Malaysia.
  6. Loong LS, Siew Mei Lai P, Jamaluddin NAH, Naina-Mohamed I, Periyasamy P, Lau CL, et al.
    J Infect Dev Ctries, 2022 Dec 31;16(12):1877-1886.
    PMID: 36753656 DOI: 10.3855/jidc.15925
    INTRODUCTION: Malaysia is an upper-middle-income country with national antimicrobial stewardship programs in place. However, hospitals in this country are faced with a high incidence of multidrug-resistant organisms and high usage of broad-spectrum antibiotics. Therefore, this study aimed to use a standardized audit tool to assess clinical appropriateness, guideline compliance, and prescribing patterns of antimicrobial use among medical patients in two tertiary hospitals in Malaysia to benchmark practice.

    METHODOLOGY: A prospective hospital-wide point prevalence survey was carried out by a multidisciplinary team in April 2019 at the University Malaya Medical Centre (UMMC) and the Hospital Canselor Tuanku Muhriz (HCTM), Kuala Lumpur, Malaysia. Data was collected from the patient's electronic medical records and recorded using the Hospital National Antimicrobial Prescribing Survey toolkit developed by the National Centre for Antimicrobial Stewardship, Australia.

    RESULTS: The appropriateness of prescriptions was 60.1% (UMMC) and 67% (HCTM), with no significant difference between the two hospitals. Compliance with guidelines was 60.0% (UMMC) and 61.5% (HCTM). Amoxicillin-clavulanic acid was the most commonly prescribed antimicrobial (UMMC = 16.9%; HCTM = 11.9%).

    CONCLUSIONS: The appropriateness of antimicrobial prescribing in medical wards, compliance with guidelines, and prescribing patterns were similar between the two hospitals in Malaysia. The survey identified several areas of prescribing that would need targeted AMS interventions.

  7. Subakir H, Chong YM, Chan YF, Hasan MS, Jamaluddin MFH, Pang YK, et al.
    J Med Microbiol, 2020 Jan;69(1):49-51.
    PMID: 31750812 DOI: 10.1099/jmm.0.001108
    Introduction.Burkholderia pseudomallei (melioidosis) is an important cause of community-acquired pneumonia (CAP) in the tropics. Selective medium is recommended for laboratory diagnosis with non-sterile respiratory samples, while PCR is not routinely used due to variable reported performance. The effectiveness of these diagnostic modalities varies by site.Aim. To compare selective media and real-time PCR (qPCR) with routine media in detecting B. pseudomallei in CAP respiratory samples in a low-incidence setting in Kuala Lumpur, Malaysia.Methodology. Respiratory samples were routinely cultured on blood, chocolate and MacConkey agar (RESP-ROUTINE), and compared to culture on selective Ashdown medium (RESP-SELECTIVE) and qPCR. The gold standard was routine culture of B. pseudomallei from any site (ALL-ROUTINE).Results.B. pseudomallei was detected in 8/204 (3.9 %) samples. Overall sensitivity rates differed (P=0.03) for qPCR (100%), RESP-SELECTIVE (87.5%) and RESP-ROUTINE (50%). There was a trend towards lower median days to positive culture for RESP-SELECTIVE (1 day) compared to RESP-ROUTINE (2 days, P=0.08) and ALL-ROUTINE (2 days, P=0.06). Reagent costs for each additional detection were USD59 for RESP-SELECTIVE and USD354 for PCR.Conclusions. In a low-incidence setting, selective culture of respiratory samples on Ashdown was more sensitive and allowed quicker identification than routine media, at reasonable cost. Blood cultures are critical, confirming four cases missed by routine respiratory culture. Selective medium is useful in early pneumonia (pre-sepsis) and resource-limited settings where blood cultures are infrequently done. Real-time PCR is costly, but highly sensitive and useful for high-risk patients with diabetes, cancer or immunosuppressants, or requiring ventilation or intensive care.
  8. 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.
  9. Sam IC, Chong YM, Abdullah A, Fu JYL, Hasan MS, Jamaluddin FH, et al.
    J Med Virol, 2021 Nov 10.
    PMID: 34757638 DOI: 10.1002/jmv.27441
    Malaysia has experienced three waves of coronavirus disease 2019 (COVID-19) as of March 31, 2021. We studied the associated molecular epidemiology and SARS-CoV-2 seroprevalence during the third wave. We obtained 60 whole-genome SARS-CoV-2 sequences between October 2020 and January 2021 in Kuala Lumpur/Selangor and analyzed 989 available Malaysian sequences. We tested 653 residual serum samples collected between December 2020 to April 2021 for anti-SARS-CoV-2 total antibodies, as a proxy for population immunity. The first wave (January 2020) comprised sporadic imported cases from China of early Pango lineages A and B. The second wave (March-June 2020) was associated with lineage B.6. The ongoing third wave (from September 2020) was propagated by a state election in Sabah. It is due to lineage B.1.524 viruses containing spike mutations D614G and A701V. Lineages B.1.459, B.1.470, and B.1.466.2 were likely imported from the region and confined to Sarawak state. Direct age-standardized seroprevalence in Kuala Lumpur/Selangor was 3.0%. The second and third waves were driven by super-spreading events and different circulating lineages. Malaysia is highly susceptible to further waves, especially as alpha (B.1.1.7) and beta (B.1.351) variants of concern were first detected in December 2020/January 2021. Increased genomic surveillance is critical.
  10. Sulaiman H, Ismail MD, Jalalonmuhali M, Atiya N, Ponnampalavanar S
    Malar J, 2014;13:341.
    PMID: 25176417 DOI: 10.1186/1475-2875-13-341
    This case report describes a case of presumed acute myocardial infarction in a returned traveler who was later diagnosed to have severe malaria. Emergency coronary angiography was normal and subsequent peripheral blood film was positive for Plasmodium falciparum.
  11. Kong ZX, Karunakaran R, Abdul Jabar K, Ponnampalavanar S, Chong CW, Teh CSJ
    Microb Drug Resist, 2021 Oct;27(10):1319-1327.
    PMID: 33877888 DOI: 10.1089/mdr.2020.0096
    Background: Hypermucoviscous carbapenem-resistant Klebsiella pneumoniae (hmCRKp) is emerging globally and approaching the worst-case scenario in health care system. Aims: The main objective in this study was to determine the hypermucoviscous characteristics among the carbapenem-resistant K. pneumoniae (CRKp) isolated from a teaching hospital in Malaysia. The association of hypermucoviscous phenotype with the virulence traits and clinical presentations were also investigated. Methods: A retrospective study was conducted in University Malaya Medical Centre (UMMC). The presence of hypermucoviscous K. pneumoniae was identified among a collection of CRKp clinical isolates (first isolate per patient) from 2014 to 2015 using string test. Correlation between clinical and microbial characteristics of the hmCRKp was investigated. Results: A total of nine (7.5%) hmCRKp were detected among 120 CRKp isolates. Majority of the isolates were hospital acquired or health care-associated infections. None of the patients had typical pyogenic liver abscess. All of the hmCRKp isolates harbored carbapenemase genes and were multidrug resistant. K1/K serotype, peg-344, allS, and magA were not identified among hmCRKp isolates, whereas aerobactin siderophore receptor gene (iutA), iroB, rmpA, and rmpA2 were detected. Only three hmCRKp isolates were resistant to serum bactericidal. Conclusions: All the isolates presented inconclusive evidence for the interpretation of hypervirulence. Therefore, more study should be performed in the future to have a better understanding of the virulence mechanisms in correlation with the clinical and microbial determinants.
  12. Chong YM, Sam IC, Ponnampalavanar S, Syed Omar SF, Kamarulzaman A, Munusamy V, et al.
    Microbiol Resour Announc, 2020 May 14;9(20).
    PMID: 32409547 DOI: 10.1128/MRA.00383-20
    We sequenced four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Malaysia during the second wave of infection and found unique mutations which suggest local evolution. Circulating Malaysian strains represent introductions from different countries, particularly during the first wave of infection. Genome sequencing is important for understanding local epidemiology.
  13. Tay ST, Lotfalikhani A, Sabet NS, Ponnampalavanar S, Sulaiman S, Na SL, et al.
    Mycopathologia, 2014 Oct;178(3-4):307-14.
    PMID: 25022264 DOI: 10.1007/s11046-014-9778-9
    BACKGROUND: Candida nivariensis and C. bracarensis have been recently identified as emerging yeast pathogens which are phenotypically indistinguishable from C. glabrata. However, there is little data on the prevalence and antifungal susceptibilities of these species.

    OBJECTIVE: This study investigated the occurrence of C. nivariensis and C. bracarensis in a culture collection of 185 C. glabrata isolates at a Malaysian teaching hospital.

    METHODS: C. nivariensis was discriminated from C. glabrata using a PCR assay as described by Enache-Angoulvant et al. (J Clin Microbiol 49:3375-9, 2011). The identity of the isolates was confirmed by sequence analysis of the D1D2 domain and internal transcribed spacer region of the yeasts. The isolates were cultured on Chromogenic CHROMagar Candida (®) agar (Difco, USA), and their biochemical and enzymic profiles were determined. Antifungal susceptibilities of the isolates against amphotericin B, fluconazole, voriconazole and caspofungin were determined using E tests. Clotrimazole MICs were determined using a microbroth dilution method.

    RESULTS: There was a low prevalence (1.1 %) of C. nivariensis in our culture collection of C. glabrata. C. nivariensis was isolated from a blood culture and vaginal swab of two patients. C. nivariensis grew as white colonies on Chromogenic agar and demonstrated few positive reactions using biochemical tests. Enzymatic profiles of the C. nivariensis isolates were similar to that of C. glabrata. The isolates were susceptible to amphotericin B, fluconazole, voriconazole and caspofungin. Clotrimazole resistance is suspected in one isolate.

    CONCLUSION: This study reports for the first time the emergence of C. nivariensis in our clinical setting.

  14. Goh SSL, Lai PSM, Tan ATB, Ponnampalavanar S
    Osteoporos Int, 2018 07;29(7):1683.
    PMID: 29737369 DOI: 10.1007/s00198-018-4379-y
    A meta-analysis was conducted to evaluate the prevalence of osteopenia/osteoporosis in human immunodeficiency virus (HIV)-infected individuals. The prevalence of osteopenia/osteoporosis in HIV-infected and antiretroviral therapy (ART)-treated individuals was significantly higher than respective controls. Evidence regarding bone loss within first year of HIV infection or ART initiation was preliminary.
  15. Goh SSL, Lai PSM, Tan ATB, Ponnampalavanar S
    Osteoporos Int, 2018 03;29(3):595-613.
    PMID: 29159533 DOI: 10.1007/s00198-017-4305-8
    A meta-analysis was conducted to evaluate the prevalence of osteopenia/osteoporosis in human immunodeficiency virus (HIV)-infected individuals. The prevalence of osteopenia/osteoporosis in HIV-infected and antiretroviral therapy (ART)-treated individuals was significantly higher than respective controls. Evidence regarding bone loss within first year of HIV infection or ART initiation was preliminary.

    PURPOSE: The aim of the study is to systematically review published literature on the prevalence of osteopenia/osteoporosis and its associated risk factors in HIV-infected individuals.

    METHODS: A literature search was conducted from 1989 to 2015 in six databases. Full text, English articles on HIV-infected individuals ≥ 18 years, which used dual X-ray absorptiometry to measure BMD, were included. Studies were excluded if the prevalence of osteopenia/osteoporosis was without a comparison group, and the BMD/T-score were not reported.

    RESULTS: Twenty-one cross sectional and eight longitudinal studies were included. The prevalence of osteopenia/osteoporosis was significantly higher in both HIV-infected [odds ratio (OR) = 2.4 (95%Cl: 2.0, 2.8) at lumbar spine, 2.6 (95%Cl: 2.2, 3.0) at hip] and ART-treated individuals [OR = 2.8 (95%Cl: 2.0, 3.8) at lumbar spine, 3.4 (95%Cl: 2.5, 4.7) at hip] when compared to controls. PI-treated individuals had an OR of 1.3 (95%Cl: 1.0, 1.7) of developing osteopenia/osteoporosis compared to controls. A higher proportion of tenofovir-treated individuals (52.6%) had lower BMD compared to controls (42.7%), but did not reach statistical significance (p = 0.248). No significant difference was found in the percent change of BMD at the lumbar spine, femoral neck, or total hip from baseline to follow-up between HIV-infected, PI-treated, tenofovir-treated, and controls. Older age, history of bone fracture, low BMI, low body weight, being Hispanic or Caucasian, low testosterone level, smoking, low CD4 cell count, lipodystrophy, low fat mass, and low lean body mass were associated with low BMD.

    CONCLUSIONS: The prevalence of osteopenia/osteoporosis in HIV-infected and antiretroviral therapy (ART)-treated individuals was two times more compared to controls. However, evidence concerning bone loss within the first year of HIV infection and ART initiation was preliminary.
  16. Lum LC, Syed Omar SF, Sri La Sri Ponnampalavanar S, Tan LH, Sekaran SD, Kamarulzaman A
    PLoS Negl Trop Dis, 2015 Jun;9(6):e0003836.
    PMID: 26047325 DOI: 10.1371/journal.pntd.0003836
    INTRODUCTION: The increasing incidence of dengue among adults in Malaysia and other countries has important implications for health services. Before 2004, in order to cope with the surge in adult dengue admissions, each of the six medical wards in a university hospital took turns daily to admit and manage patients with dengue. Despite regular in-house training, the implementation of the WHO 1997 dengue case management guidelines by the multiple medical teams was piecemeal and resulted in high variability of care. A restructuring of adult dengue inpatient service in 2004 resulted in all patients being admitted to one ward under the care of the infectious disease unit. Hospital and Intensive Care Unit admission criteria, discharge criteria and clinical laboratory testing were maintained unchanged throughout the study period.

    OBJECTIVES: To evaluate the impact of cohorting adult dengue patients on the quality of care and the clinical outcome in a university hospital in Malaysia.

    METHODS: A pre (2003) and post-intervention (2005-6) retrospective study was undertaken.

    INTERVENTION: Cohorting all dengue patients under the care of the Infectious Disease team in a designated ward in 2004.

    RESULTS: The number of patients enrolled was 352 in 2003, 785 in 2005 and 1158 in 2006. The evaluation and detection of haemorrhage remained high (>90%) and unchanged throughout the study period. The evaluation of plasma leakage increased from 35.4% pre-intervention to 78.8% post-intervention (p = <0.001) while its detection increased from 11.4% to 41.6% (p = <0.001). Examination for peripheral perfusion was undertaken in only 13.1% of patients pre-intervention, with a significant increase post-intervention, 18.6% and 34.2% respectively, p = <0.001. Pre-intervention, more patients had hypotension (21.5%) than detected peripheral hypoperfusion (11.4%), indicating that clinicians recognised shock only when patients developed hypotension. In contrast, post-intervention, clinicians recognised peripheral hypoperfusion as an early sign of shock. The highest haematocrit was significantly higher post-intervention but the lowest total white cell counts and platelet counts remained unchanged. A significant and progressive reduction in the use of platelet transfusions occurred, from 21.7% pre-intervention to 14.6% in 2005 and 5.2% in 2006 post-intervention, p<0.001. Likewise, the use of plasma transfusion decreased significantly from 6.1% pre-intervention to 4.0% and 1.6% in the post-intervention years of 2005 and 2006 respectively, p<0.001. The duration of intravenous fluid therapy decreased from 3 days pre-intervention to 2.5 days (p<0.001) post-intervention; the length of hospital stay reduced from 4 days pre- to 3 days (p<0.001) post-intervention and the rate of intensive care admission from 5.8% pre to 2.6% and 2.5% post-intervention, p = 0.005.

    CONCLUSION: Cohorting adult dengue patients under a dedicated and trained team of doctors and nurses led to a substantial improvement in quality of care and clinical outcome.

  17. Chong YM, Sam IC, Chong J, Kahar Bador M, Ponnampalavanar S, Syed Omar SF, et al.
    PLoS Negl Trop Dis, 2020 11;14(11):e0008744.
    PMID: 33253226 DOI: 10.1371/journal.pntd.0008744
    Malaysia had 10,219 confirmed cases of COVID-19 as of September 20, 2020. About 33% were associated with a Tablighi Jamaat religious mass gathering held in Kuala Lumpur between February 27 and March 3, 2020, which drove community transmission during Malaysia's second wave. We analysed genome sequences of SARS-CoV-2 from Malaysia to better understand the molecular epidemiology and spread. We obtained 58 SARS-CoV-2 whole genome sequences from patients in Kuala Lumpur and performed phylogenetic analyses on these and a further 57 Malaysian sequences available in the GISAID database. Nine different SARS-CoV-2 lineages (A, B, B.1, B.1.1, B.1.1.1, B.1.36, B.2, B.3 and B.6) were detected in Malaysia. The B.6 lineage was first reported a week after the Tablighi mass gathering and became predominant (65.2%) despite being relatively rare (1.4%) globally. Direct epidemiological links between lineage B.6 viruses and the mass gathering were identified. Increases in reported total cases, Tablighi-associated cases, and community-acquired B.6 lineage strains were temporally linked. Non-B.6 lineages were mainly travel-associated and showed limited onward transmission. There were also temporally correlated increases in B.6 sequences in other Southeast Asian countries, India and Australia, linked to participants returning from this event. Over 95% of global B.6 sequences originated from Asia Pacific. We also report a nsp3-C6310A substitution found in 47.3% of global B.6 sequences which was associated with reduced sensitivity using a commercial diagnostic real-time PCR assay. Lineage B.6 became the predominant cause of community transmission in Malaysia after likely introduction during a religious mass gathering. This event also contributed to spikes of lineage B.6 in other countries in the Asia-Pacific. Mass gatherings can be significant causes of local and global spread of COVID-19. Shared genomic surveillance can be used to identify SARS-CoV-2 transmission chains to aid prevention and control, and to monitor diagnostic molecular assays. Clinical Trial Registration: COVID-19 paper.
  18. Lau MY, Teng FE, Chua KH, Ponnampalavanar S, Chong CW, Abdul Jabar K, et al.
    Pathogens, 2021 Mar 02;10(3).
    PMID: 33801250 DOI: 10.3390/pathogens10030279
    The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great concern, as carbapenems are the last-line therapy for multidrug-resistant Gram-negative bacteria infections. This study aims to report the epidemiology of CRKP in a teaching hospital in Malaysia based on the molecular genotypic and clinical characteristics of the isolates. Sixty-three CRKP strains were isolated from a tertiary teaching hospital from January 2016 until August 2017. Carbapenemase genes were detected in 55 isolates, with blaOXA-48 (63.5%) as the predominant carbapenemase gene, followed by blaNDM (36.5%). At least one porin loss was detected in nine isolates. Overall, 63 isolates were divided into 30 clusters at similarity of 80% with PFGE analysis. Statistical analysis showed that in-hospital mortality was significantly associated with the usage of central venous catheter, infection or colonization by CRKP, particularly NDM-producers. In comparison, survival analysis using Cox proportional hazards regression identified a higher hazard ratio for patients with a stoma and patients treated with imipenem but a lower hazard ratio for patients with NDM-producing CRKP. OXA-48 carbapenemase gene was the predominant carbapenemase gene in this study. As CRKP infection could lead to a high rate of in-hospital mortality, early detection of the isolates was important to reduce their dissemination.
  19. Low YM, Chong CW, Yap IKS, Chai LC, Clarke SC, Ponnampalavanar S, et al.
    Pathog Glob Health, 2018 10;112(7):378-386.
    PMID: 30380366 DOI: 10.1080/20477724.2018.1538281
    The increasing prevalence of antibiotic resistant pathogens poses a serious threat to global health. However, less emphasis has been placed to co-relate the gene expression and metabolism of antibiotic resistant pathogens. This study aims to elucidate gene expression and variations in metabolism of multidrug resistant Klebsiella pneumoniae after exposure to antibiotics. Phenotypic responses of three genotypically distinct carbapenem resistant Klebsiella pneumoniae (CRKP) strains untreated and treated with sub-lethal concentrations of imipenem were investigated via phenotype microarrays (PM). The gene expression and metabolism of the strain harboring blaNDM-1 before and after exposure to sub-lethal concentration of imipenem were further investigated by RNA-sequencing (RNA-Seq) and 1H NMR spectroscopy respectively. Most genes related to cell division, central carbon metabolism and nucleotide metabolism were downregulated after imipenem treatment. Similarly, 1H NMR spectra obtained from treated CRKP showed decrease in levels of bacterial end products (acetate, pyruvate, succinate, formate) and metabolites involved in nucleotide metabolism (uracil, xanthine, hypoxanthine) but elevated levels of glycerophosphocholine. The presence of anserine was also observed for the treated CRKP while FAPγ-adenine and methyladenine were only present in untreated bacterial cells. As a conclusion, the studied CRKP strain exhibited decrease in central carbon metabolism, cell division and nucleotide metabolism after exposure to sub-lethal concentrations of imipenem. The understanding of the complex biological system of this multidrug resistant bacterium may help in the development of novel strategies and potential targets for the management of the infections.
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