Displaying publications 1 - 20 of 29 in total

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  1. Fulltext Clinical diagnosis of early dengue infection by novel one-step multiplex real-time RT-PCR targeting NS1 gene
    Kim JH, Chong CK, Sinniah M, Sinnadurai J, Song HO, Park H
    J Clin Virol, 2015 Apr;65:11-9.
    PMID: 25766980 DOI: 10.1016/j.jcv.2015.01.018
    BACKGROUND: Dengue is a mosquito-borne disease that causes a public health problem in tropical and subtropical countries. Current immunological diagnostics based on IgM and/or nonstructural protein 1 (NS1) antigen are limited for acute dengue infection due to low sensitivity and accuracy.
    OBJECTIVES: This study aimed to develop a one-step multiplex real-time RT-PCR assay showing higher sensitivity and accuracy than previous approaches.
    STUDY DESIGN: Serotype-specific primers and probes were designed through the multiple alignment of NS1 gene. The linearity and limit of detection (LOD) of the assay were determined. The assay was clinically validated with an evaluation panel that was immunologically tested by WHO and Malaysian specimens.
    RESULTS: The LOD of the assay was 3.0 log10 RNA copies for DENV-1, 2.0 for DENV-3, and 1.0 for DENV-2 and DENV-4. The assay showed 95.2% sensitivity (20/21) in an evaluation panel, whereas NS1 antigen- and anti-dengue IgM-based immunological assays exhibited 0% and 23.8-47.6% sensitivities, respectively. The assay showed 100% sensitivity both in NS1 antigen- and anti-dengue IgM-positive Malaysian specimens (26/26). The assay provided the information of viral loads and serotype with discrimination of heterotypic mixed infection.
    CONCLUSIONS: The assay could be clinically applied to early dengue diagnosis, especially during the first 5 days of illness and approximately 14 days after infection showing an anti-dengue IgM-positive response.
  2. Fulltext Evaluation of the Elecsys(®) Anti-HCV II assay for routine hepatitis C virus screening of different Asian Pacific populations and detection of early infection
    Yoo SJ, Wang LL, Ning HC, Tao CM, Hirankarn N, Kuakarn S, et al.
    J Clin Virol, 2015 Mar;64:20-7.
    PMID: 25728074 DOI: 10.1016/j.jcv.2014.12.015
    Early diagnosis of hepatitis C virus (HCV) infection is essential to allow appropriate treatment and prevent transmission.
  3. Chikungunya, a paradigm of neglected tropical disease that emerged to be a new health global risk
    Rougeron V, Sam IC, Caron M, Nkoghe D, Leroy E, Roques P
    J Clin Virol, 2015 Mar;64:144-52.
    PMID: 25453326 DOI: 10.1016/j.jcv.2014.08.032
    Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family that causes chronic and incapacitating arthralgia in human populations. Since its discovery in 1952, CHIKV was responsible for sporadic and infrequent outbreaks. However, since 2005, global Chikungunya outbreaks have occurred, inducing some fatalities and associated with severe and chronic morbidity. Chikungunya is thus considered as an important re-emerging public health problem in both tropical and temperate countries, where the distribution of the Aedes mosquito vectors continues to expand. This review highlights the most recent advances in our knowledge and understanding of the epidemiology, biology, treatment and vaccination strategies of CHIKV.
  4. Human adenovirus type 8: the major agent of epidemic keratoconjunctivitis (EKC)
    Adhikary AK, Banik U
    J Clin Virol, 2014 Dec;61(4):477-86.
    PMID: 25464969 DOI: 10.1016/j.jcv.2014.10.015
    Human adenovirus type 8 (HAdV-8) is the most common causative agent of a highly contagious eye disease known as epidemic keratoconjunctivitis (EKC). HAdV-8 strains have been classified into genome types HAdV-8A to 8K and HAdV/D1 to D12 according to restriction endonuclease analysis. This review focuses on the significance of HAdV-8 as an agent of EKC. Molecular analysis of HAdV-8 genome types HAdV-53 and HAdV-54 was performed to reveal potential genetic variation in the hexon and fiber, which might affect the antigenicity and tropism of the virus, respectively. On the basis of the published data, three patterns of HAdV-8 genome type distribution were observed worldwide: (1) genome types restricted to a microenvironment, (2) genome types distributed within a country, and (3) globally dispersed genome types. Simplot and zPicture showed that the HAdV-8 genome types were nearly identical to each other. HAdV-54 is very close to the HAdV-8P, B and E genomes, except in the hexon. In a restriction map, HAdV-8P, B, and E share a very high percentage of restriction sites with each other. Hypervariable regions (HVRs) of the hexon were conserved and were 100% identical among the genome types. The fiber knob of HAdV-8P, A, E, J and HAdV-53 were 100% identical. In phylogeny, HVRs of the hexon and fiber knob of the HAdV-8 genome types segregated into monophyletic clusters. Neutralizing antibodies against one genome type will provide protection against other genome types, and the selection of future vaccine strains would be simple due to the stable HVRs. Molecular analysis of whole genomes, particularly of the capsid proteins of the remaining genome types, would be useful to substantiate our observations.
  5. Fulltext Peginterferon alfa-2b in the treatment of Chinese patients with HBeAg-positive chronic hepatitis B: a randomized trial
    Cheng J, Wang Y, Hou J, Luo D, Xie Q, Ning Q, et al.
    J Clin Virol, 2014 Dec;61(4):509-16.
    PMID: 25200354 DOI: 10.1016/j.jcv.2014.08.008
    In mainland China, peginterferon (PEG-IFN) alfa-2b 1.0μg/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B.
  6. Inflammation of the external ear in acute chikungunya infection: Experience from the outbreak in Johor Bahru, Malaysia, 2008
    Javelle E, Tiong TH, Leparc-Goffart I, Savini H, Simon F
    J Clin Virol, 2014 Apr;59(4):270-3.
    PMID: 24556566 DOI: 10.1016/j.jcv.2014.01.011
    The re-emerging invalidating chikungunya disease has recently extended to temperate areas. Other alphaviruses can also present with febrile arthalgias. Dengue virus transmitted by the same species of mosquitoes may cocirculate, leading to dual infections and concurrent epidemics. Although these diseases share similar clinical features, their prognoses considerably differ. Prominent and prolonged articular disorders are more consistent with chikungunya virus, whereas haemorrhages make the gravity of dengue infection. Specific symptoms are required, especially when diagnostic tests are not available or performable at a large scale. Indeed, early clinical suspicion of a vector-borne disease is crucial to isolate the first cases in the course of an outbreak, and discrimination between arboviruses help to optimal management of patients. No specific chikungunya clinical sign has been yet reported. We highlight here the high prevalence (about 25%) of acute ear redness in infected people during the 2008 chikungunya outbreak in Jahor Bahru in Malaysia. Nine consenting patients are more precisely described. Ear chondritis could be sensitive diagnostic criterion of the acute stage of chikungunya, every physician - even in occidental non endemic areas - should be aware of.
  7. Fulltext Biodiversity and clinico-demographic characteristics of human rhinoviruses from hospitalized children with acute lower respiratory tract infections in Malaysia
    Etemadi MR, Othman N, Savolainen-Kopra C, Sekawi Z, Wahab N, Sann LM
    J Clin Virol, 2013 Dec;58(4):671-7.
    PMID: 23932333 DOI: 10.1016/j.jcv.2013.05.017
    BACKGROUND: There is accumulating evidence that human rhinovirus (HRV) causes acute lower respiratory tract infections (ALRTI). Recently, HRV-C was identified as a new species of HRV, but its spectrum of clinical disease is not well understood.

    OBJECTIVES: We investigated the molecular epidemiology, demographic and clinical characteristics of HRVs among hospitalized children with ALRIs.

    STUDY DESIGN: One hundred and sixty-five nasopharangeal aspirates taken from children <5 years hospitalized with ALRTIs in Serdang Hospital, Malaysia, were subject to reverse transcriptase-PCR for HRV. Phylogenetic analysis on VP4/VP2 and 5'-NCR regions was used to further characterize HRV. Other respiratory viruses were also investigated using semi-nested multiplex RT-PCR assay. Clinical parameters were analyzed between HRV, RSV and IFV-A mono-infections and between HRV species.

    RESULTS: HRV was detected in 54 (33%) patients for both single (36 samples) and multiple (18 samples) infections, 61.1% (22/36) represents HRV-A strains while the remaining 14 HRV-C. Strain P51 was the first reported representative of HRV98. The majority of the single HRV cases were in the second half of infancy; HRV-C occurred among older children compared with HRV-A. HRV children were admitted significantly earlier and less febrile than RSV and IFV-A infection. HRV-C infected children were more likely to have rhonchi and vomiting as compared to HRV-A. Pneumonia was the most common discharge diagnosis followed by bronchiolitis and post-viral wheeze in HRV patients.

    CONCLUSION: Our study showed high prevalence of HRVs and detection of HRV-C among hospitalized children with ALRTIs in Malaysia. Analysis of clinical parameters suggested specific features associated with HRVs infections and specific HRV groups.

  8. Clinical significance of plasma Epstein-Barr Virus DNA loads in a large cohort of Malaysian patients with nasopharyngeal carcinoma
    Chai SJ, Pua KC, Saleh A, Yap YY, Lim PV, Subramaniam SK, et al.
    J Clin Virol, 2012 Sep;55(1):34-9.
    PMID: 22739102 DOI: 10.1016/j.jcv.2012.05.017
    Nasopharyngeal carcinoma (NPC) is an Epstein-Barr Virus (EBV)-associated cancer that is the fifth most common cancer in Malaysia. Early and accurate diagnoses are critical for patient prognosis. Unfortunately, early detection of NPC is still a challenge and the cost of more accurate imaging protocols is prohibitive in developing countries like Malaysia.
  9. Hemophagocytosis in dengue: comprehensive report of six cases
    Tan LH, Lum LC, Omar SF, Kan FK
    J Clin Virol, 2012 Sep;55(1):79-82.
    PMID: 22789140 DOI: 10.1016/j.jcv.2012.06.005
    Hemophagocytic syndrome is a potentially fatal disorder. It is being increasingly reported but remained under-recognized in dengue. Most reported cases were in association with plasma leakage and shock but multi-organ impairment was also observed. We describe the time-lines of 6 cases of confirmed dengue with varying severities of hemophagocytosis. All had persistent fever, cytopenia and elevated transaminases with markedly elevated ferritin levels during and beyond the plasma leakage phase. Acute renal failure and central nervous system manifestation were observed in two patients. Morphological hemophagocytosis was demonstrated in three patients. All survivors showed clinical and biochemical resolution of hemophagocytosis indicating its transient nature. Persistence of fever and cytopenia together with multi-organ dysfunction, out of proportion to and beyond the plasma leakage phase should prompt clinicians to consider this phenomenon.
  10. Chikungunya virus of Asian and Central/East African genotypes in Malaysia
    Sam IC, Chan YF, Chan SY, Loong SK, Chin HK, Hooi PS, et al.
    J Clin Virol, 2009 Oct;46(2):180-3.
    PMID: 19683467 DOI: 10.1016/j.jcv.2009.07.016
    BACKGROUND: Chikungunya virus (CHIKV) of the Central/East African genotype has caused large outbreaks worldwide in recent years. In Malaysia, limited CHIKV outbreaks of the endemic Asian and imported Central/East African genotypes were reported in 1998 and 2006. Since April 2008, an unprecedented nationwide outbreak has affected Malaysia.
    OBJECTIVE: To study the molecular epidemiology of the current Malaysian CHIKV outbreak, and to evaluate cross-neutralisation activity of serum from infected patients against isolates of Asian and Central/East African genotypes.
    STUDY DESIGN: Serum samples were collected from 83 patients presenting in 2008, and tested with PCR for the E1 gene, virus isolation, and for IgM. Phylogenetic analysis was performed on partial E1 gene sequences of 837bp length. Convalescent serum from the current outbreak and Bagan Panchor outbreak (Asian genotype, 2006) were tested for cross-neutralising activity against representative strains from each outbreak.
    RESULTS: CHIKV was confirmed in 34 patients (41.0%). The current outbreak strain has the A226V mutation in the E1 structural protein, and grouped with Central/East African isolates from recent global outbreaks. Serum cross-neutralisation activity against both Central/East African and Asian genotypes was observed at titres from 40 to 1280.
    CONCLUSIONS: The CHIKV strain causing the largest Malaysian outbreak is of the Central/East African genotype. The presence of the A226V mutation, which enhances transmissibility of CHIKV by Aedes albopictus, may explain the extensive spread especially in rural areas. Serum cross-neutralisation of different genotypes may aid potential vaccines and limit the effect of future outbreaks.
  11. Fulltext Absence of Melaka-virus in European children with respiratory disease
    Schildgen V, Rüngeler E, Tillmann R, Schildgen O
    J Clin Virol, 2008 Jul;42(3):295-6.
    PMID: 18359270 DOI: 10.1016/j.jcv.2008.02.003
  12. The emergence of Nipah virus, a highly pathogenic paramyxovirus
    Lo MK, Rota PA
    J Clin Virol, 2008 Dec;43(4):396-400.
    PMID: 18835214 DOI: 10.1016/j.jcv.2008.08.007
    Nipah virus first emerged in Malaysia and Singapore between 1998 and 1999, causing severe febrile encephalitis in humans with a mortality rate of close to 40%. In addition, a significant portion of those recovering from acute infection had relapse encephalitis and long-term neurological defects. Since its initial outbreak, there have been numerous outbreaks in Bangladesh and India, in which the mortality rate rose to approximately 70%. These subsequent outbreaks were distinct from the initial outbreak, both in their epidemiology and in their clinical presentations. Recent developments in diagnostics may expedite disease diagnosis and outbreak containment, while progress in understanding the molecular biology of Nipah virus could lead to novel therapeutics and vaccines for this deadly pathogen.
  13. Clinicians' diagnostic practice of dengue infections
    Ng CF, Lum LC, Ismail NA, Tan LH, Tan CP
    J Clin Virol, 2007 Nov;40(3):202-6.
    PMID: 17928264 DOI: 10.1016/j.jcv.2007.08.017
    BACKGROUND: Difficulties in the classification of dengue infection have been documented. Such difficulties could be due to the low awareness of the World Health Organization diagnostic guidelines among clinicians.
    OBJECTIVE: To study the diagnostic practices of clinicians in classifying patients as dengue fever (DF) or dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS) at the time of discharge during an outbreak.
    METHODS: A prospective descriptive study of clinical features and disease classification in adult and pediatric dengue patients in the University of Malaya Medical Centre.
    RESULTS: Five hundred and twenty adult and 191 pediatric patients were enrolled. Thrombocytopenia and evidence of plasma leakage were present in 8% of adult and 19% of pediatric patients. Of these, 93% and 49%, respectively, were given the discharge diagnoses of DF instead of DHF/DSS. Hemoconcentration, serous effusion and thrombocytopenia were not recognized in clinicians' discharge diagnosis of DHF/DSS for adult patients. The receiver operating characteristic (ROC) curve suggested a lack of consistency in the use of WHO guidelines in establishing DHF/DSS in adult patients, while implying otherwise for pediatric patients.
    CONCLUSION: DHF/DSS is an under-recognized condition by clinicians managing these patients. This can affect the case fatality rate of DHF/DSS and the economic burden of the disease. The lack of awareness in disease manifestations especially plasma leakage, can lead to delayed recognition of DHF/DSS.
    Study site: Outpatient department and inpatients, adult medical and pediatric wards, University Malaya Medical Center (UMMC), Kuala Lumpur, Malaysia
  14. A phage-displayed single chain variable fragment that interacts with hepatitis B core antigen: library construction, selection and diagnosis
    Tan GH, Yusoff K, Seow HF, Tan WS
    J Clin Virol, 2007 Jan;38(1):49-56.
    PMID: 17074533
    Phage display is an alternative method for constructing and selecting antibodies with desired specificity towards an antigen.
  15. Chikungunya infection in Malaysia: comparison with dengue infection in adults and predictors of persistent arthralgia
    Mohd Zim MA, Sam IC, Omar SF, Chan YF, AbuBakar S, Kamarulzaman A
    J Clin Virol, 2013 Feb;56(2):141-5.
    PMID: 23201456 DOI: 10.1016/j.jcv.2012.10.019
    Chikungunya virus (CHIKV) and dengue virus (DENV) co-circulate in areas endemic with the Aedes mosquito vectors. Both viruses cause similar illnesses which may be difficult to distinguish clinically. CHIKV is also associated with persistent arthralgia.
  16. Characterization of species B adenoviruses isolated from fecal specimens taken from poliomyelitis-suspected cases
    de Azevedo JP, Nascimento LR, Cortinovis MC, Oliveira SS, da Costa EV, da Silva EE
    J Clin Virol, 2004 Dec;31(4):248-52.
    PMID: 15494264 DOI: 10.1016/j.jcv.2004.04.007
    BACKGROUND: Human adenoviruses are classified into six species, A-F, and 51 serotypes are recognized. Adenoviruses can cause a broad range of diseases. Serotypes 3, 7 and 21 are most commonly associated with CNS disease. Serotype 21 (specie B) was isolated from brain tissue and CSF of patients with acute flaccid paralysis (AFP) in Malaysia.
    OBJECTIVES: Characterize, by molecular methods, species B adenoviruses isolated from poliomyelitis-suspected cases and investigate the possible etiological role of adenoviruses in acute flaccid paralysis (AFP).
    STUDY DESIGN: 622 virus isolates, including Sabin-related polioviruses, non-polio enteroviruses (NPEV) and adenoviruses, were recovered from fecal specimens in our laboratory during the period of 1997-2002 from AFP cases occurring in Brazil, Peru and Bolivia. Negative controls consisted of 528 fecal specimens collected from healthy children <==5 of age. Of these, 478 were contacts of AFP negative cases and 50 were from a day-care center.
    RESULTS: Sixty-four adenovirus strains isolated in HEp2 (human laryngeal tumor cells) cells were confirmed as such by an adenovirus-group specific PCR. Nucleotide sequencing identified the following adenovirus species: A (3 isolates), B (20 isolates), C (38 isolates), D (2 isolates) and E (1 isolate). The following serotypes belonging to the species B were identified: Ad3 (1 strain), Ad7 (17 strains) and, Ad16 (2 strains).
    CONCLUSION: Other viral agents became more recognized in association with CNS diseases in areas where wild polioviruses have been eradicated. The possible role of species B adenoviruses in the etiology of AFP cases similar to that caused by wild poliovirus is discussed.
  17. A phage-displayed cyclic peptide that interacts tightly with the immunodominant region of hepatitis B surface antigen
    Tan WS, Tan GH, Yusoff K, Seow HF
    J Clin Virol, 2005 Sep;34(1):35-41.
    PMID: 16087122
    The surface antigen (HBsAg) of hepatitis B virus (HBV) is highly conformational and generally evokes protective humoral immune response in human. A disulfide constrained random heptapeptide library displayed on the coat protein III of filamentous bacteriophage M13 was employed to select specific ligands that interact with HBsAg subtype ad. Fusion phages carrying the amino acid sequence ETGAKPH and other related sequences were isolated. The binding site of peptide ETGAKPH was located on the immunodominant region of HBsAg. An equilibrium binding assay in solution showed that the phage binds tightly to HBsAg with a relative dissociation constant (KDrel) of 2.9+/-0.9 nM. The phage bearing this peptide has the potential to be used as a diagnostic reagent and two assays for detecting HBsAg in blood samples are described.
  18. Dengue infection associated hemophagocytic syndrome: Therapeutic interventions and outcome
    Wan Jamaludin WF, Periyasamy P, Wan Mat WR, Abdul Wahid SF
    J Clin Virol, 2015 Aug;69:91-5.
    PMID: 26209387 DOI: 10.1016/j.jcv.2015.06.004
    Infection associated hemophagocytic syndrome is increasingly recognized as a potentially fatal complication of dengue fever. It should be suspected with prolonged fever beyond seven days associated with hepatosplenomegaly, hyperferritinemia, worsening cytopenias and development of multiorgan dysfunction. Surge of similar pro-inflammatory cytokines observed in dengue associated hemophagocytic syndrome and multiorgan dysfunction may indicate they are part of related inflammatory spectrum. A proportion of patients recovered with supportive therapy, however most required interventions with corticosteroids, intravenous immunoglobulin or chemotherapy. We report three cases of dengue associated IAHS with good outcome following early recognition and treatment with dexamethasone and intravenous immunoglobulin.
  19. Nipah virus outbreak in Malaysia
    Chua KB
    J Clin Virol, 2003 Apr;26(3):265-75.
    PMID: 12637075
    Nipah virus, a novel paramyxovirus, closely related to Hendra virus emerged in northern part of Peninsular Malaysia in 1998. The virus caused an outbreak of severe febrile encephalitis in humans with a high mortality rate, whereas, in pigs, encephalitis and respiratory diseases but with a relatively low mortality rate. The outbreak subsequently spread to various regions of the country and Singapore in the south due to the movement of infected pigs. Nipah virus caused systemic infections in humans, pigs and other mammals. Histopathological and radiological findings were characteristic of the disease. Fruitbats of Pteropid species were identified as the natural reservoir hosts. Evidence suggested that climatic and anthropogenic driven ecological changes coupled with the location of piggeries in orchard and the design of pigsties allowed the spill-over of this novel paramyxovirus from its reservoir host into the domestic pigs and ultimately to humans and other animals.
  20. Diagnosis of nipah virus encephalitis by electron microscopy of cerebrospinal fluid
    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.

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