Displaying publications 1 - 20 of 56 in total

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  1. Sam IC, Karunakaran R, Kamarulzaman A, Ponnampalavanar S, Syed Omar SF, Ng KP, et al.
    J Hosp Infect, 2012 Apr;80(4):321-5.
    PMID: 22237130 DOI: 10.1016/j.jhin.2011.12.004
    Brucella species are easily transmitted by aerosols and can be acquired in the laboratory.
  2. Yap PSX, Chong CW, Ponnampalavanar S, Ramli R, Harun A, Tengku Jamaluddin TZM, et al.
    PeerJ, 2023;11:e16393.
    PMID: 38047021 DOI: 10.7717/peerj.16393
    BACKGROUND: The high burden of extended-spectrum beta-lactamase-producing (ESBL)-producing Enterobacterales worldwide, especially in the densely populated South East Asia poses a significant threat to the global transmission of antibiotic resistance. Molecular surveillance of ESBL-producing pathogens in this region is vital for understanding the local epidemiology, informing treatment choices, and addressing the regional and global implications of antibiotic resistance.

    METHODS: Therefore, an inventory surveillance of the ESBL-Escherichia coli (ESBL-EC) isolates responsible for infections in Malaysian hospitals was conducted. Additionally, the in vitro efficacy of flomoxef and other established antibiotics against ESBL-EC was evaluated.

    RESULTS: A total of 127 non-repetitive ESBL-EC strains isolated from clinical samples were collected during a multicentre study performed in five representative Malaysian hospitals. Of all the isolates, 33.9% were isolated from surgical site infections and 85.8% were hospital-acquired infections. High rates of resistance to cefotaxime (100%), cefepime (100%), aztreonam (100%) and trimethoprim-sulfamethoxazole (100%) were observed based on the broth microdilution test. Carbapenems remained the most effective antibiotics against the ESBL-EC, followed by flomoxef. Antibiotic resistance genes were identified by PCR. The blaCTX-M-1 was the most prevalent ESBL gene, with 28 isolates (22%) harbouring blaCTX-M-1 only, 27 isolates (21.3%) co-harbouring blaCTX-M-1 and blaTEM, and ten isolates (7.9%) co-harbouring blaCTX-M-1, blaTEM and blaSHV. A generalised linear model showed significant antibacterial activity of imipenem against different types of infection. Besides carbapenems, this study also demonstrated a satisfactory antibacterial activity of flomoxef (81.9%) on ESBL-EC, regardless of the types of ESBL genes.

  3. Kong ZX, N Karunakaran R, Abdul Jabar K, Ponnampalavanar S, Chong CW, Teh CSJ
    PeerJ, 2022;10:e12830.
    PMID: 35223201 DOI: 10.7717/peerj.12830
    BACKGROUND: Carbapenem resistant Enterobacteriaceae (CRE) has rapidly disseminated worldwide and has become a global threat to the healthcare system due to its resistance towards "last line" antibiotics. This study aimed to investigate the prevalence of CRE and the resistance mechanism as well as the risk factors associated with in-hospital mortality.

    METHODS: A total of 168 CRE strains isolated from a tertiary teaching hospital from 2014-2015 were included in this study. The presence of carbapenemase genes and minimum inhibitory concentration of imipenem, meropenem and colistin were investigated. All carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) strains were characterised by PFGE. The risk factors of patients infected by CRE associated with in-hospital mortality were determined statistically.

    RESULTS: The predominant CRE species isolated was K. pneumoniae. The carbapenemases detected were blaOXA-48, blaOXA-232, blaVIM and blaNDM of which blaOXA-48 was the predominant carbapenemase detected among 168 CRE strains. A total of 40 CRE strains harboured two different carbapenemase genes. A total of seven clusters and 48 pulsotypes were identified among 140 CRKp strains. A predominant pulsotype responsible for the transmission from 2014 to 2015 was identified. Univariate statistical analysis identified that the period between CRE isolation and start of appropriate therapy of more than 3 days was statistically associated with in-hospital mortality.

  4. Abdul Aziz SA, Mcstea M, Ahmad Bashah NS, Chong ML, Ponnampalavanar S, Syed Omar SF, et al.
    AIDS, 2018 05 15;32(8):1025-1034.
    PMID: 29547442 DOI: 10.1097/QAD.0000000000001798
    OBJECTIVES: In a clinic-based, treated HIV-infected cohort, we identified individuals with sarcopenia and compared with age, sex and ethnically matched controls; and investigated associated risk factors and health outcomes.

    DESIGN: Sarcopenia (age-related muscle loss) causes significant morbidity to the elderly, leading to frequent hospitalizations, disability and death. Few have characterized sarcopenia in the HIV-infected who experience accelerated aging.

    METHODS: Sarcopenia was defined as low muscle mass with weak grip strength and/or slow gait speed using lower 20th percentiles of controls. Multivariate logistic and linear regression analyses were used to explore risk factors and health-related outcomes associated with sarcopenia among HIV-infected individuals.

    RESULTS: We recruited 315 HIV-infected individuals aged at least 25 years with at least 1-year history of undetectable viral load on treatment (HIV RNA <50 copies/ml). Percentage of sarcopenia in 315 HIV-infected was 8%. Subsequently, 153 of the 315 were paired with age, sex and ethnically matched HIV-uninfected. The percentage of sarcopenia in the HIV-infected (n = 153) compared with uninfected (n = 153) were 10 vs. 6% (P = 0.193) respectively, whereas of those at least 50 years of age among them were 17% vs. 4% (P = 0.049), respectively. Associated risk factors among the HIV-infected include education level, employment status, BMI, baseline CD4 cell count, duration on NRTIs and GGT levels. Identified negative outcomes include mortality risk scores [5.42; 95% CI 1.46-9.37; P = 0.007) and functional disability (3.95; 95% CI 1.57-9.97; P = 0.004).

    CONCLUSION: Sarcopenia is more prevalent in HIV-infected at least 50 years old compared with matched controls. Our findings highlight associations between sarcopenia with loss of independence and greater healthcare burden among treated HIV-infected individuals necessitating early recognition and intervention.

  5. Saeidi A, Tien Tien VL, Al-Batran R, Al-Darraji HA, Tan HY, Yong YK, et al.
    PLoS One, 2015;10(4):e0124659.
    PMID: 25894562 DOI: 10.1371/journal.pone.0124659
    Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8(+) T cells co-expressing the semi-invariant TCR Vα7.2, and are numerous in the blood and mucosal tissues of humans. MAIT cells appear to undergo exhaustion in chronic viral infections. However, their role in human immunodeficiency virus type 1 (HIV-1) mono-infection and HIV/tuberculosis (TB) co-infection have seldom been elaborately investigated. We conducted a cross-sectional study to investigate the frequencies and phenotypes of CD161(++)CD8(+) T cells among anti-retroviral therapy (ART)/anti-TB therapy (ATT) treatment-naïve HIV/TB co-infected, ART/TB treated HIV/TB co-infected, ART naïve HIV-infected, ART-treated HIV-infected patients, and HIV negative healthy controls (HCs) by flow cytometry. Our data revealed that the frequency of MAIT cells was severely depleted in HIV mono- and HIV/TB co-infections. Further, PD-1 expression on MAIT cells was significantly increased in HIV mono- and HIV-TB co-infected patients. The frequency of MAIT cells did not show any significant increase despite the initiation of ART and/or ATT. Majority of the MAIT cells in HCs showed a significant increase in CCR6 expression as compared to HIV/TB co-infections. No marked difference was seen with expressions of chemokine co-receptor CCR5 and CD103 among the study groups. Decrease of CCR6 expression appears to explain why HIV-infected patients display weakened mucosal immune responses.
  6. Karajacob AS, Azizan NB, Al-Maleki ARM, Goh JPE, Loke MF, Khor HM, et al.
    PLoS One, 2023;18(4):e0284043.
    PMID: 37068057 DOI: 10.1371/journal.pone.0284043
    Overgrowth of Candida yeasts in the oral cavity may result in the development of oral thrush in immunocompromised individuals. This study analyzed the diversity and richness of the oral mycobiota of patients clinically diagnosed with oral thrush (OT), follow-up of oral thrush patients after antifungal therapy (AT), and healthy controls (HC). Oral rinse and oral swab samples were collected from 38 OT patients, 21 AT patients, and 41 healthy individuals (HC). Pellet from the oral rinse and oral swab were used for the isolation of oral Candida yeasts on Brilliance Candida Agar followed by molecular speciation. ITS1 amplicon sequencing using Illumina MiSeq was performed on DNA extracted from the oral rinse pellet of 16 OT, 7 AT, and 7 HC oral rinse samples. Trimmed sequence data were taxonomically grouped and analyzed using the CLC Microbial Genomics Module workflow. Candida yeasts were isolated at significantly higher rates from oral rinse and swab samples of OT (68.4%, p < 0.001) and AT (61.9%, p = 0.012) patients, as compared to HC (26.8%). Predominance of Candida albicans specifically, was noted in OT (60.5%, p < 0.001) and AT (42.9%, p = 0.006) vs. HC (9.8%), while non-albicans Candida species was dominant in HC. Analysis of oral mycobiota from OT patients showed the presence of 8 phyla, 222 genera, and 309 fungal species. Low alpha diversity (Shannon index, p = 0.006; Chao-1 biased corrected index, p = 0.01), varied beta diversity (Bray-Curtis, p = 0.01986; Jaccard, p = 0.02766; Weighted UniFrac, p = 0.00528), and increased relative abundance of C. albicans (p = 3.18E-02) was significantly associated with the oral mycobiota of OT vs. HC. This study supported that C. albicans is the main etiological agent in oral thrush and highlights the association of fungal biodiversity with the pathophysiology of oral thrush.
  7. Sulaiman H, Ponnampalavanar S, Mun KS, Italiano CM
    BMC Infect Dis, 2013 Nov 09;13:527.
    PMID: 24209898 DOI: 10.1186/1471-2334-13-527
    BACKGROUND: Infections due to Mycobacterium tuberculosis, Burkholderia pseudomallei and non-typhoidal Salmonella cause significant morbidity and mortality throughout the world. These intracellular pathogens share some common predisposing factors and clinical features. Co-infection with two of these organisms has been reported previously but, to our knowledge, this is the first time that infection with all three has been reported in one person.

    CASE PRESENTATION: In September 2010, a 58-year-old diabetic Malaysian male presented with fever and a fluctuant mass on the right side of his neck. B. pseudomallei was isolated from an aspirate of this lesion and there was radiological evidence of disseminated infection in the liver and spleen. The recurrence of clinical symptoms over ensuing months prompted further aspiration and biopsy of a cervical abscess and underlying lymph nodes. Salmonella enterica serovar Stanley and then M. tuberculosis were identified from these specimens by culture and molecular methods. The patient responded to targeted medical management of each of these infections.

    CONCLUSION: In endemic settings, a high index of suspicion and adequate tissue sampling are imperative in identifying these pathogenic organisms. Diabetes was identified as a predisposing factor in this case while our understanding of other potential risk factors is evolving.

  8. 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.
  9. Lee YQ, Sri La Sri Ponnampalavanar S, Chong CW, Karunakaran R, Vellasamy KM, Abdul Jabar K, et al.
    Antibiotics (Basel), 2022 Nov 21;11(11).
    PMID: 36421313 DOI: 10.3390/antibiotics11111670
    Non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) confers carbapenem resistance through a combination of chromosomal mutations and acquired non-carbapenemase resistance mechanisms. In this study, we aimed to evaluate the clinical and molecular profiles of NC-CRKP isolated from patients in a tertiary teaching hospital in Malaysia from January 2013 to October 2019. During the study period, 54 NC-CRKP-infected/colonised patients' isolates were obtained. Clinical parameters were assessed in 52 patients. The all-cause in-hospital mortality rate among NC-CRKP patients was 46.2% (24/52). Twenty-three (44.2%) patients were infected, while others were colonised. Based on the Charlson Comorbidity Index (CCI) score, 92.3% (48/52) of the infected/colonised patients had a score of ≥ 1. Resistance genes found among the 54 NC-CRKP isolates were blaTEM, blaSHV, blaCTX-M, blaOXA, and blaDHA. Porin loss was detected in 25/54 (46.3%) strains. None of the isolated strains conferred carbapenem resistance through the efflux pumps system. In conclusion, only 25/54 (46.3%) NC-CRKP conferred carbapenem resistance through a combination of porin loss and the acquisition of non-carbapenemase resistance mechanisms. The carbapenem resistance mechanisms for the remaining strains (53.7%) should be further investigated as rapid identification and distinction of the NC-CRKP mechanisms enable optimal treatment and infection control efforts.
  10. Sam IC, Kamarulzaman A, Ong GS, Veriah RS, Ponnampalavanar S, Chan YF, et al.
    Trop Biomed, 2010 Aug;27(2):343-7.
    PMID: 20962735
    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus which causes fever, rash, and arthralgia. In the past, life-threatening complications were very rarely reported. However, during the recent worldwide outbreaks, there have been several reports of unusually severe complications and deaths. Malaysia is experiencing a nationwide outbreak of CHIKV, with over 10 000 patients affected since April 2008. We report the first case of culture-confirmed CHIKV-associated death in Malaysia, in a patient with fever, rash, acute exacerbation of pre-existing heart failure, rhabdomyolysis, and multiple organ failure. CHIKV infections may cause atypical, severe or fatal presentations.
  11. 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.

  12. 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.

  13. Anthony C, Mahmud R, Lau YL, Syedomar SF, Sri La Sri Ponnampalavanar S
    Trop Biomed, 2013 Sep;30(3):459-66.
    PMID: 24189676 MyJurnal
    Battling malaria will be a persistent struggle without the proper means to diagnose the parasitic infection. However, the inherent limitations of microscopy, the conventional method of diagnosing malaria, affect the accuracy of diagnosis. The present study aimed to compare the accuracy of two different set of primers targeting the small subunit ribosomal RNA (ssRNA) and the dihydrofolate reductase-thymidylate synthase linker region (dhfr-ts) in detecting species specific malaria infections by nested PCR. The sensitivity and specificity of nested PCR assay using the two primers were calculated with reference to microscopy as the 'gold standard'. The results show that 18S rRNA primers had 91.9% sensitivity and 100% specificity in detecting human Plasmodium species as opposed to dhfr-ts primers which had 51.4% sensitivity and 100% specificity. The higher sensitivity of 18S rRNA primers suggests that it may be a better diagnostic tool for detecting human malaria.
  14. 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.
  15. Saeidi A, Chong YK, Yong YK, Tan HY, Barathan M, Rajarajeswaran J, et al.
    Cell Immunol, 2015 Sep;297(1):19-32.
    PMID: 26071876 DOI: 10.1016/j.cellimm.2015.05.005
    The role of T-cell immunosenescence and functional CD8(+) T-cell responses in HIV/TB co-infection is unclear. We examined and correlated surrogate markers of HIV disease progression with immune activation, immunosenescence and differentiation using T-cell pools of HIV/TB co-infected, HIV-infected and healthy controls. Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8(+) T cells. Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8(+) T cells, besides diminished expression of CD127 (IL-7Rα) on CD57(+)CD4(+) T cells. Notably, intracellular IFN-γ, perforin and granzyme B levels in HIV-specific CD8(+) T cells of HIV/TB co-infected subjects were diminished. Intracellular CD57 levels in HIV gag p24-specific CD8(+) T cells were significantly increased in HIV/TB co-infection. We suggest that HIV-TB co-infection contributes to senescence associated with chronic immune activation, which could be due to functional insufficiency of CD8(+) T cells.
  16. Rathakrishnan A, Wang SM, Hu Y, Khan AM, Ponnampalavanar S, Lum LC, et al.
    PLoS One, 2012;7(12):e52215.
    PMID: 23284941 DOI: 10.1371/journal.pone.0052215
    BACKGROUND: Dengue is an important medical problem, with symptoms ranging from mild dengue fever to severe forms of the disease, where vascular leakage leads to hypovolemic shock. Cytokines have been implicated to play a role in the progression of severe dengue disease; however, their profile in dengue patients and the synergy that leads to continued plasma leakage is not clearly understood. Herein, we investigated the cytokine kinetics and profiles of dengue patients at different phases of illness to further understand the role of cytokines in dengue disease.

    METHODS AND FINDINGS: Circulating levels of 29 different types of cytokines were assessed by bead-based ELISA method in dengue patients at the 3 different phases of illness. The association between significant changes in the levels of cytokines and clinical parameters were analyzed. At the febrile phase, IP-10 was significant in dengue patients with and without warning signs. However, MIP-1β was found to be significant in only patients with warning signs at this phase. IP-10 was also significant in both with and without warning signs patients during defervescence. At this phase, MIP-1β and G-CSF were significant in patients without warning signs, whereas MCP-1 was noted to be elevated significantly in patients with warning signs. Significant correlations between the levels of VEGF, RANTES, IL-7, IL-12, PDGF and IL-5 with platelets; VEGF with lymphocytes and neutrophils; G-CSF and IP-10 with atypical lymphocytes and various other cytokines with the liver enzymes were observed in this study.

    CONCLUSIONS: The cytokine profile patterns discovered between the different phases of illness indicate an essential role in dengue pathogenesis and with further studies may serve as predictive markers for progression to dengue with warning signs.

  17. Yeo AS, Rathakrishnan A, Wang SM, Ponnampalavanar S, Manikam R, Sathar J, et al.
    Biomed Res Int, 2015;2015:420867.
    PMID: 25815314 DOI: 10.1155/2015/420867
    Dengue virus infection is a common tropical disease which often occurs without being detected. These asymptomatic cases provide information in relation to the manifestation of immunological aspects. In this study, we developed an ELISA method to compare neutralizing effects of dengue prM and E antibodies between dengue patients and their asymptomatic household members. Recombinant D2 premembrane (prM) was constructed, cloned, and tested for antigenicity. The recombinant protein was purified and tested with controls by using an indirect ELISA method. Positive dengue serum samples with their asymptomatic pair were then carried out onto the developed ELISA. In addition, commercially available recombinant envelope (E) protein was used to develop an ELISA which was tested with the same set of serum samples in the prM ELISA. Asymptomatic individuals showed preexisting heterotypic neutralizing antibodies. The recombinant prM was antigenically reactive in the developed ELISA. Dengue patients had higher prM and E antibodies compared to their household members. Our study highlights the neutralizing antibodies levels with respect to dengue prM and E between dengue patients and asymptomatic individuals.
  18. 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.

  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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