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  1. Lim PL, Oh HM, Ooi EE
    J Travel Med, 2009 Jul-Aug;16(4):289-91.
    PMID: 19674272 DOI: 10.1111/j.1708-8305.2009.00313.x
    Chikungunya infections were detected in Singapore among returning travelers who had visited friends and relatives (VFR) in India and Malaysia. These sporadic imported cases occurred over a year before the 2008 chikungunya outbreaks in Singapore, demonstrating the potential for introducing this emerging viral infection into new areas via VFR travel.
  2. Lee KE, Umapathi T, Tan CB, Tjia HT, Chua TS, Oh HM, et al.
    Ann Neurol, 1999 Sep;46(3):428-32.
    PMID: 10482278 DOI: 10.1002/1531-8249(199909)46:3<428::AID-ANA23>3.0.C
    A novel Hendra-like paramyxovirus named Nipah virus (NiV) was the cause of an outbreak among workers from one abattoir who had contact with pigs. Two patients had only respiratory symptoms, while 9 patients had encephalitis, 7 of whom are described in this report. Neurological involvement was diverse and multifocal, including aseptic meningitis, diffuse encephalitis, and focal brainstem involvement. Cerebellar signs were relatively common. Magnetic resonance imaging scans of the brain showed scattered lesions. IgM antibodies against Hendra virus (HeV) were present in the serum of all patients. Two patients recovered completely. Five had residual deficits 8 weeks later.
  3. 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.

  4. 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.

  5. 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
  6. 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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