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Displaying publications 41 - 49 of 49 in total

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Tioman virus infection in experimentally infected mouse brain and its association with apoptosis

Yaiw KC, Ong KC, Chua KB, Bingham J, Wang L, Shamala D, et al.

J Virol Methods, 2007 Aug;143(2):140-6.
PMID: 17442409

Tioman virus is a newly described bat-urine derived paramyxovirus isolated in Tioman Island, Malaysia in 2001. Hitherto, neither human nor animal infection by this virus has been reported. Nonetheless, its close relationship to another paramyxovirus, the Menangle virus which had caused diseases in humans and pigs [Philbey, A.W., Kirkland, P.D., Ross, A.D., Davis, R.J., Gleeson, A.B., Love, R.J., Daniels, P.W., Gould, A.R., Hyatt, A.D., 1998. An apparently new virus (family Paramyxoviridae) infectious for pigs, humans, and fruit bats. Emerg. Infect. Dis. 4, 269-271], raises the possibility that it may be potentially pathogenic. In this study, mice were experimentally infected with Tioman virus by intraperitoneal and intracerebral routes, and the cellular targets and topographical distribution of viral genome and antigens were examined using in situ hybridization and immunohistochemistry, respectively. The possible association between viral infection and apoptosis was also investigated using the TUNEL assay and immunohistochemistry to FasL, Caspase-3, Caspase-8, Caspase-9 and bcl-2. The results showed that Tioman virus inoculated intracerebrally was neurotropic causing plaque-like necrotic areas, and appeared to preferentially replicate in the neocortex and limbic system. Viral infection of inflammatory cells was also demonstrated. TUNEL and Caspase-3 positivity was found in inflammatory cells but not in neurons, while FasL, Caspase-8 and Caspase-9 were consistently negative. This suggests that neuronal infection was associated with necrosis rather than apoptosis. Moreover, the data suggest that there may be an association between viral infection and apoptosis in inflammatory cells, and that it could, at least in part, involve Caspase-independent pathways. Bcl-2 was expressed in some neurons and inflammatory cells indicating its possible role in anti-apoptosis. There was no evidence of central nervous system infection via the intraperitoneal route.
Tonsillar crypt epithelium is an important extra-central nervous system site for viral replication in EV71 encephalomyelitis

He Y, Ong KC, Gao Z, Zhao X, Anderson VM, McNutt MA, et al.

Am J Pathol, 2014 Mar;184(3):714-20.
PMID: 24378407 DOI: 10.1016/j.ajpath.2013.11.009

Enterovirus 71 (EV71; family Picornaviridae, species human Enterovirus A) usually causes hand, foot, and mouth disease, which may rarely be complicated by fatal encephalomyelitis. We investigated extra-central nervous system (extra-CNS) tissues capable of supporting EV71 infection and replication, and have correlated tissue infection with expression of putative viral entry receptors, scavenger receptor B2 (SCARB2), and P-selectin glycoprotein ligand-1 (PSGL-1). Formalin-fixed, paraffin-embedded CNS and extra-CNS tissues from seven autopsy cases were examined by IHC and in situ hybridization to evaluate viral antigens and RNA. Viral receptors were identified with IHC. In all seven cases, the CNS showed stereotypical distribution of inflammation and neuronal localization of viral antigens and RNA, confirming the clinical diagnosis of EV71 encephalomyelitis. In six cases in which tonsillar tissues were available, viral antigens and/or RNA were localized to squamous epithelium lining the tonsillar crypts. Tissues from the gastrointestinal tract, pancreas, mesenteric nodes, spleen, and skin were all negative for viral antigens/RNA. Our novel findings strongly suggest that tonsillar crypt squamous epithelium supports active viral replication and represents an important source of viral shedding that facilitates person-to-person transmission by both the fecal-oral or oral-oral routes. It may also be a portal for viral entry. A correlation between viral infection and SCARB2 expression appears to be more significant than for PSGL-1 expression.
Diabetic foot infection and surgical treatment in a secondary health care centre in Malaysia

Ng BW, Muhammad Firdaus A, Mohd Syafiqq Al Hakim HR, Nur Sa'idah MS, Loi KW, Ong KC, et al.

Med J Malaysia, 2020 01;75(1):29-32.
PMID: 32008016

INTRODUCTION: Diabetic foot infection is often associated with high morbidity, disability and poor quality of life. This study focuses on the demography, the number of repetitive surgery and length of stay in hospital of patients with diabetic foot infection.
METHOD: This is a retrospective observational study. Patients who were admitted to the Orthopaedic ward of Hospital Segamat (HS), Johor, Malaysia from January 2016 to December 2018 and required surgical intervention were included in the study. Data was collected from the computer system of HS and medical notes of patients.
RESULTS: 35.6% of the total orthopaedic emergency surgeries performed were for patients with diabetic foot infection, 25% of the surgical procedures performed were major amputations of lower limb and 40% of the patients with diabetic foot infection required more than one surgical operation.
DISCUSSION: The demographics of the patients is consistent with the demographics of Malaysia where majority of them are Malays followed by Chinese, Indians and others. Despite being only 10% of total admission to the department, this group of patients contributed to 35.6% of the total emergency surgeries performed. The amputation rate in the centre is comparable to the other local studies. The average length of stay in hospital was found to be shorter compared to overseas due to different rehabilitation protocols.
Quality of life and psychological status in survivors of severe acute respiratory syndrome at 3 months postdischarge

Kwek SK, Chew WM, Ong KC, Ng AW, Lee LS, Kaw G, et al.

J Psychosom Res, 2006 May;60(5):513-9.
PMID: 16650592

BACKGROUND: Little is known about the long-term consequence of severe acute respiratory syndrome (SARS). We carried out an assessment on SARS patients after their recovery from their acute illness.
METHOD: Postal survey comprising Health-Related Quality of Life (HRQoL) questionnaires and anxiety and depression measures was sent to them at 3 months' postdischarge.
RESULTS: There was a significant impairment in both the HRQoL and mental functioning. Forty-one percent had scores indicative of a posttraumatic stress disorder (PTSD); about 30% had likely anxiety and depression.
CONCLUSION: SARS has significant impact on HRQoL and psychological status at 3 months.
Fulltext Electrostatic interactions at the five-fold axis alter heparin-binding phenotype and drive enterovirus A71 virulence in mice

Tee HK, Tan CW, Yogarajah T, Lee MHP, Chai HJ, Hanapi NA, et al.

PLoS Pathog, 2019 11;15(11):e1007863.
PMID: 31730673 DOI: 10.1371/journal.ppat.1007863

Enterovirus A71 (EV-A71) causes hand, foot and mouth disease epidemics with neurological complications and fatalities. However, the neuropathogenesis of EV-A71 remains poorly understood. In mice, adaptation and virulence determinants have been mapped to mutations at VP2-149, VP1-145 and VP1-244. We investigate how these amino acids alter heparin-binding phenotype and shapes EV-A71 virulence in one-day old mice. We constructed six viruses with varying residues at VP1-98, VP1-145 (which are both heparin-binding determinants) and VP2-149 (based on the wild type 149K/98E/145Q, termed KEQ) to generate KKQ, KKE, KEE, IEE and IEQ variants. We demonstrated that the weak heparin-binder IEE was highly lethal in mice. The initially strong heparin-binding IEQ variant acquired an additional mutation VP1-K244E, which confers weak heparin-binding phenotype resulting in elevated viremia and increased virus antigens in mice brain, with subsequent high virulence. IEE and IEQ-244E variants inoculated into mice disseminated efficiently and displayed high viremia. Increasing polymerase fidelity and impairing recombination of IEQ attenuated the virulence, suggesting the importance of population diversity in EV-A71 pathogenesis in vivo. Combining in silico docking and deep sequencing approaches, we inferred that virus population diversity is shaped by electrostatic interactions at the five-fold axis of the virus surface. Electrostatic surface charges facilitate virus adaptation by generating poor heparin-binding variants for better in vivo dissemination in mice, likely due to reduced adsorption to heparin-rich peripheral tissues, which ultimately results in increased neurovirulence. The dynamic switching between heparin-binding and weak heparin-binding phenotype in vivo explained the neurovirulence of EV-A71.
Fulltext Pathogenesis of Plasmodium berghei ANKA infection in the gerbil (Meriones unguiculatus) as an experimental model for severe malaria

Junaid QO, Khaw LT, Mahmud R, Ong KC, Lau YL, Borade PU, et al.

Parasite, 2017;24:38.
PMID: 29034874 DOI: 10.1051/parasite/2017040

BACKGROUND: As the quest to eradicate malaria continues, there remains a need to gain further understanding of the disease, particularly with regard to pathogenesis. This is facilitated, apart from in vitro and clinical studies, mainly via in vivo mouse model studies. However, there are few studies that have used gerbils (Meriones unguiculatus) as animal models. Thus, this study is aimed at characterizing the effects of Plasmodium berghei ANKA (PbA) infection in gerbils, as well as the underlying pathogenesis.
METHODS: Gerbils, 5-7 weeks old were infected by PbA via intraperitoneal injection of 1 × 106 (0.2 mL) infected red blood cells. Parasitemia, weight gain/loss, hemoglobin concentration, red blood cell count and body temperature changes in both control and infected groups were monitored over a duration of 13 days. RNA was extracted from the brain, spleen and whole blood to assess the immune response to PbA infection. Organs including the brain, spleen, heart, liver, kidneys and lungs were removed aseptically for histopathology.
RESULTS: Gerbils were susceptible to PbA infection, showing significant decreases in the hemoglobin concentration, RBC counts, body weights and body temperature, over the course of the infection. There were no neurological signs observed. Both pro-inflammatory (IFNγ and TNF) and anti-inflammatory (IL-10) cytokines were significantly elevated. Splenomegaly and hepatomegaly were also observed. PbA parasitized RBCs were observed in the organs, using routine light microscopy and in situ hybridization.
CONCLUSION: Gerbils may serve as a good model for severe malaria to further understand its pathogenesis.
Enterovirus 71 encephalomyelitis and Japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and RNA

Wong KT, Ng KY, Ong KC, Ng WF, Shankar SK, Mahadevan A, et al.

Neuropathol. Appl. Neurobiol., 2012 Aug;38(5):443-53.
PMID: 22236252 DOI: 10.1111/j.1365-2990.2011.01247.x

To investigate if two important epidemic viral encephalitis in children, Enterovirus 71 (EV71) encephalomyelitis and Japanese encephalitis (JE) whose clinical and pathological features may be nonspecific and overlapping, could be distinguished.
Fulltext Immunity and clinical efficacy of an inactivated enterovirus 71 vaccine in healthy Chinese children: a report of further observations

Liu L, Mo Z, Liang Z, Zhang Y, Li R, Ong KC, et al.

BMC Med, 2015;13:226.
PMID: 26381232 DOI: 10.1186/s12916-015-0448-7

To investigate the long-term effects on immunity of an inactivated enterovirus 71 (EV71) vaccine and its protective efficacy.
Fulltext A generic assay for whole-genome amplification and deep sequencing of enterovirus A71

Tan le V, Tuyen NT, Thanh TT, Ngan TT, Van HM, Sabanathan S, et al.

J Virol Methods, 2015 Apr;215-216:30-6.
PMID: 25704598 DOI: 10.1016/j.jviromet.2015.02.011

Enterovirus A71 (EV-A71) has emerged as the most important cause of large outbreaks of severe and sometimes fatal hand, foot and mouth disease (HFMD) across the Asia-Pacific region. EV-A71 outbreaks have been associated with (sub)genogroup switches, sometimes accompanied by recombination events. Understanding EV-A71 population dynamics is therefore essential for understanding this emerging infection, and may provide pivotal information for vaccine development. Despite the public health burden of EV-A71, relatively few EV-A71 complete-genome sequences are available for analysis and from limited geographical localities. The availability of an efficient procedure for whole-genome sequencing would stimulate effort to generate more viral sequence data. Herein, we report for the first time the development of a next-generation sequencing based protocol for whole-genome sequencing of EV-A71 directly from clinical specimens. We were able to sequence viruses of subgenogroup C4 and B5, while RNA from culture materials of diverse EV-A71 subgenogroups belonging to both genogroup B and C was successfully amplified. The nature of intra-host genetic diversity was explored in 22 clinical samples, revealing 107 positions carrying minor variants (ranging from 0 to 15 variants per sample). Our analysis of EV-A71 strains sampled in 2013 showed that they all belonged to subgenogroup B5, representing the first report of this subgenogroup in Vietnam. In conclusion, we have successfully developed a high-throughput next-generation sequencing-based assay for whole-genome sequencing of EV-A71 from clinical samples.