Displaying all 14 publications

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  1. Chow VT, Tambyah PA, Yeo WM, Phoon MC, Howe J
    J Clin Virol, 2000 Dec;19(3):143-7.
    PMID: 11090749
    BACKGROUND: between 1998 and 1999, an outbreak of potentially fatal viral encephalitis erupted among pig farm workers in West Malaysia, and later spread to Singapore where abattoir workers were afflicted. Although Japanese encephalitis virus was initially suspected, the predominant aetiologic agent was subsequently confirmed to be Nipah virus, a novel paramyxovirus related to but distinct from Hendra virus.

    OBJECTIVE: to describe a case of Nipah virus encephalitis in a pig farm worker from Malaysia.

    STUDY DESIGN: the clinical, laboratory and radiological findings of this patient were scrutinized. Special emphasis was placed on the electron microscopic analysis of the cerebrospinal fluid (CSF) specimen from this patient.

    RESULTS: the neurological deficits indicative of cerebellar involvement were supported by the magnetic resonance imaging that showed prominent cerebellar and brainstem lesions. CSF examination provided further evidence of viral encephalitis. Complement fixation and/or RT-PCR assays were negative for Japanese encephalitis, herpes simplex, measles and mumps viruses. ELISA for detecting IgM and IgG antibodies against Hendra viral antigens were equivocal for the CSF specimen, and tested initially negative for the first serum sample but subsequently positive for the repeat serum sample. Transmission electron microscopy of negatively-stained preparations of CSF revealed enveloped virus-like structures fringed with surface projections as well as nucleocapsids with distinctive helical and herringbone patterns, features consistent with those of other paramyxoviruses, including Hendra virus.

    CONCLUSION: this case report reiterates the relevant and feasible role of diagnostic electron microscopy for identifying and/or classifying novel or emerging viral pathogens for which sufficiently specific and sensitive tests are lacking.

  2. Ong AK, Tambyah PA, Ooi S, Kumarasinghe G, Chow C
    Singapore Med J, 2001 Dec;42(12):549-52.
    PMID: 11989574
    Singapore is a modern urban city and endemic typhus is thought to be a disease of the past. This may be due to lack of specific serological testing as indirect immunoperoxidase testing using specific rickettsial antigens (U.S. Army Medical Research Unit, Institute of Medical Research, Kuala Lumpur, Malaysia) has only recently become available. In the last fourteen months, twenty-one cases of endemic typhus were diagnosed in patients hospitalised for acute febrile illnesses at the National University Hospital. We conducted a case control study to define the clinical and laboratory features of endemic typhus in Singapore.
  3. Harris PN, Yin M, Jureen R, Chew J, Ali J, Paynter S, et al.
    PMID: 25932324 DOI: 10.1186/s13756-015-0055-6
    Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae are often susceptible in vitro to β-lactam/β-lactamase inhibitor (BLBLI) combination antibiotics, but their use has been limited by concerns of clinical inefficacy. We aimed to compare outcomes between patients treated with BLBLIs and carbapenems for bloodstream infection (BSI) caused by cefotaxime non-susceptible (likely ESBL- or AmpC β-lactamase-producing) Escherichia coli and Klebsiella pneumoniae.
  4. Rajahram GS, Hameed AA, Menon J, William T, Tambyah PA, Yeo TW
    BMC Infect Dis, 2017 03 04;17(1):188.
    PMID: 28257622 DOI: 10.1186/s12879-017-2294-z
    BACKGROUND: Streptococcus Suis (S.suis) is increasingly being recognised as a potentially preventable emerging zoonotic infection in humans with a global distribution. It is a major cause of meningitis especially among those in contact with pigs and has also been associated with a toxic shock syndrome.

    CASE PRESENTATIONS: We report the first two human cases from Sabah, Borneo, Malaysia which expands the global reach of this important pathogen. Here, we illustrate their epidemiological risk factors, clinical presentation and resulting sequelae of both patients.

    CONCLUSION: The continued public health threat of zoonotic infections such as S.suis, highlights the need for accurate epidemiological surveillance, regulation of pig farming, slaughtering and continued advocacy of best practices for pork preparation and consumption.

  5. Lysaght T, Capps B, Bailey M, Bickford D, Coker R, Lederman Z, et al.
    PLoS One, 2017;12(1):e0170967.
    PMID: 28129409 DOI: 10.1371/journal.pone.0170967
    BACKGROUND: One Health (OH) is an interdisciplinary collaborative approach to human and animal health that aims to break down conventional research and policy 'silos'. OH has been used to develop strategies for zoonotic Emerging Infectious Diseases (EID). However, the ethical case for OH as an alternative to more traditional public health approaches is largely absent from the discourse. To study the ethics of OH, we examined perceptions of the human health and ecological priorities for the management of zoonotic EID in the Southeast Asia country of Singapore.

    METHODS: We conducted a mixed methods study using a modified Delphi technique with a panel of 32 opinion leaders and 11 semi-structured interviews with a sub-set of those experts in Singapore. Panellists rated concepts of OH and priorities for zoonotic EID preparedness planning using a series of scenarios developed through the study. Interview data were examined qualitatively using thematic analysis.

    FINDINGS: We found that panellists agreed that OH is a cross-disciplinary collaboration among the veterinary, medical, and ecological sciences, as well as relevant government agencies encompassing animal, human, and environmental health. Although human health was often framed as the most important priority in zoonotic EID planning, our qualitative analysis suggested that consideration of non-human animal health and welfare was also important for an effective and ethical response. The panellists also suggested that effective pandemic planning demands regional leadership and investment from wealthier countries to better enable international cooperation.

    CONCLUSION: We argue that EID planning under an OH approach would benefit greatly from an ethical ecological framework that accounts for justice in human, animal, and environmental health.

  6. Rajahram GS, Hale G, Bhatnagar J, Hiu J, Thayan R, William T, et al.
    Int J Infect Dis, 2019 06;83:163-166.
    PMID: 30763620 DOI: 10.1016/j.ijid.2019.01.047
  7. William T, Thevarajah B, Lee SF, Suleiman M, Jeffree MS, Menon J, et al.
    Emerg Infect Dis, 2015 Jan;21(1):142-5.
    PMID: 25531078 DOI: 10.3201/eid2101.141092
    Of the ≈400 cases of avian influenza (H7N9) diagnosed in China since 2003, the only travel-related cases have been in Hong Kong and Taiwan. Detection of a case in a Chinese tourist in Sabah, Malaysia, highlights the ease with which emerging viral respiratory infections can travel globally.
  8. Lim CC, Lee WL, Leo YS, Lee KE, Chan KP, Ling AE, et al.
    J Neurol Neurosurg Psychiatry, 2003 Jan;74(1):131-3.
    PMID: 12486285
    The Nipah virus is a newly identified paramyxovirus responsible for an outbreak of fatal encephalitis in Malaysia and Singapore. This paper reports the follow up clinical and magnetic resonance imaging findings in 22 affected subjects. Of 13 patients with encephalitis, one died, one was lost to follow up, and seven recovered. Among the four remaining patients, one had residual sixth nerve palsy, another suffered from severe clinical depression, and a third patient had evidence of retinal artery occlusion. One patient with delayed onset Horner syndrome had a single lesion in the cervical spinal cord. The brain magnetic resonance findings were stable or improved in nine patients over 18 months of follow up. Among a second group of nine asymptomatic seropositive abattoir workers, magnetic resonance examination in seven subjects revealed discrete small lesions in the brain; similar to those detected in encephalitis patients. These findings suggest that in addition to encephalitis, the newly discovered Nipah virus affects the spinal cord and the retina. Late clinical and radiological findings can occur in Nipah virus infections as with other paramyxoviruses.
  9. Lim CC, Sitoh YY, Hui F, Lee KE, Ang BS, Lim E, et al.
    AJNR Am J Neuroradiol, 2000 Mar;21(3):455-61.
    PMID: 10730635
    BACKGROUND AND PURPOSE: An epidemic of suspected Japanese encephalitis occurred in Malaysia in 1998-1999 among pig farmers. In neighboring Singapore, an outbreak occurred among pig slaughterhouse workers. It was subsequently established that the causative agent in the outbreak was not the Japanese encephalitis virus but a previously unknown Hendra-like paramyxovirus named Nipah virus.

    METHODS: The brain MR images of eight patients with Nipah virus infection were reviewed. All patients tested negative for acute Japanese encephalitis virus. Seven patients had contrast-enhanced studies and six had diffusion-weighted examinations.

    RESULTS: All patients had multiple small bilateral foci of T2 prolongation within the subcortical and deep white matter. The periventricular region and corpus callosum were also involved. In addition to white matter disease, five patients had cortical lesions, three had brain stem involvement, and a single thalamic lesion was detected in one patient. All lesions were less than 1 cm in maximum diameter. In five patients, diffusion-weighted images showed increased signal. Four patients had leptomeningeal enhancement and four had enhancement of parenchymal lesions.

    CONCLUSION: The brain MR findings in patients infected with the newly discovered Nipah paramyxovirus are different from those of patients with Japanese encephalitis. In a zoonotic epidemic, this striking difference in the appearance and distribution of lesions is useful in differentiating these diseases. Diffusion-weighted imaging was advantageous in increasing lesion conspicuity.

  10. Lai CC, Lee K, Xiao Y, Ahmad N, Veeraraghavan B, Thamlikitkul V, et al.
    J Glob Antimicrob Resist, 2014 Sep;2(3):141-147.
    PMID: 27873720 DOI: 10.1016/j.jgar.2014.02.007
    The rapid development of antimicrobial resistance among micro-organisms is a serious public health concern. Moreover, the dissemination of antibiotic-resistant bacteria makes this issue a global problem, and Asia is no exception. For example, since New Delhi metallo-β-lactamase (NDM)-producing Enterobacteriaceae were identified in India, further spread of NDM has become a worldwide threat. However, the epidemiology of antibiotic-resistant bacteria in Asia may be different to other regions, and clinical condition may be worse than in western countries. Antibiotic-resistant bacteria, including community-acquired and hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), vancomycin-resistant enterococci, macrolide- and penicillin-resistant Streptococcus pneumoniae, extend-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa and Acinetobacter spp., are becoming prevalent in many countries in Asia. Moreover, the prevalence of each antibiotic-resistant bacterium in each country is not identical. This review provides useful information regarding the critical condition of antibiotic resistance in Asia and emphasises the importance of continuous surveillance of resistance data.
  11. Archuleta S, Chia PY, Wei Y, Syed-Omar SF, Low JG, Oh HM, et al.
    Clin Infect Dis, 2020 07 11;71(2):383-389.
    PMID: 31626692 DOI: 10.1093/cid/ciz850
    BACKGROUND: Platelet transfusion is common in dengue patients with thrombocytopenia. We previously showed in a randomized clinical trial that prophylactic platelet transfusion did not reduce clinical bleeding. In this study, we aimed to characterize the predictors and clinical outcomes of poor platelet recovery in transfused and nontransfused participants.

    METHODS: We analyzed patients from the Adult Dengue Platelet Study with laboratory-confirmed dengue with ≤20 000 platelets/μL and without persistent mild bleeding or any severe bleeding in a post hoc analysis. Poor platelet recovery was defined as a platelet count of ≤20 000/μL on Day 2. We recruited 372 participants from 5 acute care hospitals located in Singapore and Malaysia between 29 April 2010 and 9 December 2014. Of these, 188 were randomly assigned to the transfusion group and 184 to the control group.

    RESULTS: Of 360 patients, 158 had poor platelet recovery. Age, white cell count, and day of illness at study enrollment were significant predictors of poor platelet recovery after adjustment for baseline characteristics and platelet transfusion. Patients with poor platelet recovery had longer hospitalizations but no significant difference in other clinical outcomes, regardless of transfusion. We found a significant interaction between platelet recovery and transfusion; patients with poor platelet recovery were more likely to bleed if given a prophylactic platelet transfusion (odds ratio 2.34, 95% confidence interval 1.18-4.63).

    CONCLUSIONS: Dengue patients with thrombocytopenia who were older or presented earlier and with lower white cell counts were more likely to have poor platelet recovery. In patients with poor platelet recovery, platelet transfusion does not improve outcomes and may actually increase the risk of bleeding. The mechanisms of poor platelet recovery need to be determined.

    CLINICAL TRIALS REGISTRATION: NCT01030211.

  12. Lye DC, Archuleta S, Syed-Omar SF, Low JG, Oh HM, Wei Y, et al.
    Lancet, 2017 Apr 22;389(10079):1611-1618.
    PMID: 28283286 DOI: 10.1016/S0140-6736(17)30269-6
    BACKGROUND: Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia.
    METHODS: We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per μL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per μL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed.
    FINDINGS: Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to 5·34]; relative risk 0·81 [95% CI 0·56 to 1·17]; p=0·16). 13 adverse events occurred in the transfusion group and two occurred in the control group (5·81% [-4·42 to 16·01]; 6·26 [1·43 to 27·34]; p=0·0064). Adverse events that were possibly, probably, or definitely related to transfusion included three cases of urticaria, one maculopapular rash, one pruritus, and one chest pain, as well as one case each of anaphylaxis, transfusion-related acute lung injury, and fluid overload that resulted in serious adverse events. No death was reported.
    INTERPRETATION: In adult patients with dengue and thrombocytopenia, prophylactic platelet transfusion was not superior to supportive care in preventing bleeding, and might be associated with adverse events.
    FUNDING: National Medical Research Council, Singapore.
    Study site: Hospitals, Singapore; University Malaya Medical Centre (UMMC). Kuala Lumpur, Malaysia
    Study protocol: https://clinicaltrials.gov/ct2/show/NCT01030211
  13. Ng OT, Thoon KC, Chua HY, Tan NW, Chong CY, Tee NW, et al.
    Emerg Infect Dis, 2015 Jul;21(7):1192-6.
    PMID: 26079293 DOI: 10.3201/eid2107.141443
    During November 2012-July 2013, a marked increase of adenovirus type 7 (Ad7) infections associated with severe disease was documented among pediatric patients in Singapore. Phylogenetic analysis revealed close genetic links with severe Ad7 outbreaks in China, Taiwan, and other parts of Asia.
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