MyMedR

Changing trends of genital herpes in Kuala Lumpur, Malaysia, 1982-2008

Chiam CW, Chan YF, Sam IC

Int J STD AIDS, 2010 Jun;21(6):450-1.

PMID: 20606232 DOI: 10.1258/ijsa.2010.009569

Fulltext The neutralizing role of IgM during early Chikungunya virus infection

Chua CL, Sam IC, Chiam CW, Chan YF

PLoS One, 2017;12(2):e0171989.

PMID: 28182795 DOI: 10.1371/journal.pone.0171989

The antibody isotype IgM appears earlier than IgG, within days of onset of symptoms, and is important during the early stages of the adaptive immune response. Little is known about the functional role of IgM during infection with chikungunya virus (CHIKV), a recently reemerging arbovirus that has caused large global outbreaks. In this study, we studied antibody responses in 102 serum samples collected during CHIKV outbreaks in Malaysia. We described the neutralizing role of IgM at different times post-infection and examined the independent contributions of IgM and IgG towards the neutralizing capacity of human immune sera during the early phase of infection, including the differences in targets of neutralizing epitopes. Neutralizing IgM starts to appear as early as day 4 of symptoms, and their appearance from day 6 is associated with a reduction in viremia. IgM acts in a complementary manner with the early IgG, but plays the main neutralizing role up to a point between days 4 and 10 which varies between individuals. After this point, total neutralizing capacity is attributable almost entirely to the robust neutralizing IgG response. IgM preferentially binds and targets epitopes on the CHIKV surface E1-E2 glycoproteins, rather than individual E1 or E2. These findings provide insight into the early antibody responses to CHIKV, and have implications for design of diagnostic serological assays.

Real-time polymerase chain reaction for diagnosis and quantitation of negative strand of chikungunya virus

Chiam CW, Chan YF, Loong SK, Yong SS, Hooi PS, Sam IC

Diagn Microbiol Infect Dis, 2013 Oct;77(2):133-7.

PMID: 23886793 DOI: 10.1016/j.diagmicrobio.2013.06.018

Quantitative real-time polymerase chain reaction (qRT-PCR) is useful for diagnosis and studying virus replication. We developed positive- and negative-strand qRT-PCR assays to detect nsP3 of chikungunya virus (CHIKV), a positive-strand RNA alphavirus that causes epidemic fever, rash, and arthritis. The positive- and negative-strand qRT-PCR assays had limits of quantification of 1 and 3 log10 RNA copies/reaction, respectively. Compared to a published E1 diagnostic assay using 30 laboratory-confirmed clinical samples, the positive-strand nsP3 qRT-PCR assay had higher R(2) and efficiency and detected more positive samples. Peak viral load of 12.9 log(10) RNA copies/mL was reached on day 2 of illness, and RNA was detectable up to day 9, even in the presence of anti-CHIKV IgM. There was no correlation between viral load and persistent arthralgia. The positive-strand nsP3 assay is suitable for diagnosis, while the negative-strand nsP3 assay, which uses tagged primers to increase specificity, is useful for study of active viral replication kinetics.

Immunohistochemical Detection of Chikungunya Virus Antigens in Formalin-Fixed and Paraffin-Embedded Tissues

Chiam CW, Sam IC, Chan YF, Wong KT, Ong KC

Methods Mol Biol, 2016;1426:235-40.

PMID: 27233276 DOI: 10.1007/978-1-4939-3618-2_21

Immunohistochemistry is a histological technique that allows detection of one or more proteins of interest within a cell using specific antibody binding, followed by microscopic visualization of a chromogenic substrate catalyzed by peroxidase and/or alkaline phosphatase. Here, we describe a method to localize Chikungunya virus (CHIKV) antigens in formalin-fixed and paraffin-embedded infected mouse brain.

Fulltext Comparative genetic analysis of VP4, VP1 and 3D gene regions of enterovirus 71 and coxsackievirus A16 circulating in Malaysia between 1997-2008

Chan YF, Wee KL, Chiam CW, Khor CS, Chan SY, Amalina W MZ, et al.

Trop Biomed, 2012 Sep;29(3):451-66.

PMID: 23018509 MyJurnal

Three genomic regions, VP4 capsid, VP1 capsid and 3D RNA polymerase of human enterovirus 71 (EV-71) and coxsackievirus A16 (CV-A16) were sequenced to understand the evolution of these viruses in Malaysia. A total of 42 EV-71 and 36 CV-A16 isolates from 1997- 2008 were sequenced. Despite the presence of many EV-71 subgenotypes worldwide, only subgenotypes B3, B4, B5, C1 and C2 were present in Malaysia. Importation of other subgenotypes such as C3, C4/D and C5 from other countries was infrequent. For CV-A16, the earlier subgenotype B1 was replaced by subgenotypes B2a and the recent B2c. Subgenotype B2a was present throughout the study while B2c only emerged in 2005. No genetic signatures could be attributed to viral virulence suggesting that host factors have a major role in determining the outcome of infection. Only three EV-71 B3 isolates showed non-consistent phylogeny in the 3D RNA polymerase region which indicated occurrence of recombination in EV-71. High genetic diversity was observed in the Malaysian EV-71 but Malaysian CV-A16 showed low genetic diversity in the three genomic regions sequenced. EV-71 showed strong purifying selection, but that occurred to a lesser extent in CV-A16.

Fulltext Genotypic and phenotypic characterization of Chikungunya virus of different genotypes from Malaysia

Sam IC, Loong SK, Michael JC, Chua CL, Wan Sulaiman WY, Vythilingam I, et al.

PLoS One, 2012;7(11):e50476.

PMID: 23209750 DOI: 10.1371/journal.pone.0050476

Mosquito-borne Chikungunya virus (CHIKV) has recently re-emerged globally. The epidemic East/Central/South African (ECSA) strains have spread for the first time to Asia, which previously only had endemic Asian strains. In Malaysia, the ECSA strain caused an extensive nationwide outbreak in 2008, while the Asian strains only caused limited outbreaks prior to this. To gain insight into these observed epidemiological differences, we compared genotypic and phenotypic characteristics of CHIKV of Asian and ECSA genotypes isolated in Malaysia.

Fulltext Antiviral activity of silymarin against chikungunya virus

Lani R, Hassandarvish P, Chiam CW, Moghaddam E, Chu JJ, Rausalu K, et al.

Sci Rep, 2015;5:11421.

PMID: 26078201 DOI: 10.1038/srep11421

The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection.

Fulltext Correction: Epidemiology, clinical presentation and respiratory sequelae of adenovirus pneumonia in children in Kuala Lumpur, Malaysia

Li L, Woo YY, de Bruyne JA, Nathan AM, Kee SY, Chan YF, et al.

PLoS One, 2018;13(12):e0209720.

PMID: 30566518 DOI: 10.1371/journal.pone.0209720

[This corrects the article DOI: 10.1371/journal.pone.0205795.].

Fulltext Epidemiology, clinical presentation and respiratory sequelae of adenovirus pneumonia in children in Kuala Lumpur, Malaysia

Li L, Woo YY, de Bruyne JA, Nathan AM, Kee SY, Chan YF, et al.

PLoS One, 2018;13(10):e0205795.

PMID: 30321228 DOI: 10.1371/journal.pone.0205795

OBJECTIVES: To describe the severity, human adenovirus (HAdV) type and respiratory morbidity following adenovirus pneumonia in children.

METHODOLOGY: Retrospective review of children under 12 years of age, admitted with HAdV pneumonia, between January 2011 and July 2013, in a single centre in Malaysia. HAdV isolated from nasopharyngeal secretions were typed by sequencing hypervariable regions 1-6 of the hexon gene. Patients were reviewed for respiratory complications.

RESULTS: HAdV was detected in 131 children of whom 92 fulfilled inclusion criteria. Median (range) age was 1.1 (0.1-8.0) years with 80% under 2 years. Twenty percent had severe disease with a case-fatality rate of 5.4%. Duration of admission (p = 0.02) was independently associated with severe illness. Twenty-two percent developed respiratory complications, the commonest being bronchiolitis obliterans (15.2%) and recurrent wheeze (5.4%). The predominant type shifted from HAdV1 and HAdV3 in 2011 to HAdV7 in 2013. The commonest types identified were types 7 (54.4%), 1(17.7%) and 3 (12.6%). Four out of the five patients who died were positive for HAdV7. Infection with type 7 (OR 8.90, 95% CI 1.32, 59.89), family history of asthma (OR 14.80, 95% CI 2.12-103.21) and need for invasive or non-invasive ventilation (OR 151.84, 95% CI 9.93-2.32E) were independent predictors of respiratory complications.

CONCLUSIONS: One in five children admitted with HAdV pneumonia had severe disease and 22% developed respiratory complications. Type 7 was commonly isolated in children with severe disease. Family history of asthma need for invasive or non-invasive ventilation and HAdV 7 were independent predictors of respiratory complications.

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