MyMedR

Fulltext Zika virus and its potential re-emergence in Malaysia

Sam JI, Chan YF, Vythilingam I, Wan Sulaiman WY

Med J Malaysia, 2016 04;71(2):66-8.

Zika virus (ZIKV) has re-emerged to cause explosive epidemics in the Pacific and Latin America, and appears to be associated with severe neurological complications including microcephaly in babies. ZIKV is transmitted to humans by Aedes mosquitoes, principally Ae. aegypti, and there is historical evidence of ZIKV circulation in Southeast Asia. It is therefore clear that Malaysia is at risk of similar outbreaks. Local and international guidelines are available for surveillance, diagnostics, and management of exposed and infected individuals. ZIKV is the latest arbovirus to have spread globally beyond its initial restricted niche, and is unlikely to be the last. Innovative new methods for surveillance and control of vectors are needed to target mosquito-borne diseases as a whole.

Fulltext Varicella-zoster virus seroprevalence in healthcare workers in Kuala Lumpur, Malaysia

Sam IC, Tariman H, Chan YF, Bador MK, Yusof MY, Hassan H

Med J Malaysia, 2008 Dec;63(5):429-30.

PMID: 19803311 MyJurnal

Varicella-zoster virus (VZV) infections are a particular problem in healthcare settings. A survey of chickenpox was carried out amongst healthcare workers (HCWs) following potential ward exposures. A prior history of chickenpox was given by 61/98 (62.2%). Of 64 HCWs tested for VZV IgG, 10 (15.6%) were seronegative, indicating susceptibility. The sensitivity, specificity, positive predictive value, and negative predictive value of a history of prior chickenpox were 57.4%, 90%, 96.4%, and 31.0%, respectively. VZV screening of HCWs without a history of chickenpox, and vaccination of susceptible HCWs should be undertaken in this hospital.

Fulltext Virucidal activity of Virkon S on human enterovirus

Chan YF, Abu Bakar S

Med J Malaysia, 2005 Jun;60(2):246-8.

PMID: 16114171

The efficacy of Virkon S, a commercial disinfectant as a virucidal spray against human enterovirus 71 (HEV71), the causative agent of the fatal form of hand, foot and mouth disease was examined. At least one log10 reduction of HEV71 titer was achieved when one spray of Virkon (1% or 2%) with ten minutes of contact time was applied. The infectivity was completely lost when four sprays of 1% or 2% Virkon were applied, suggesting that at least four sprays of 1% Virkon to the surface bound HEV71 was necessary to completely inactivate the virus. These findings suggest that Virkon S at the proper concentration is suitable to be used as an effective and easy to use disinfectant against HEV71.

Metastatic tumours of the jaws

Chan YF

Med J Malaysia, 1972 Sep;27(1):48-51.

PMID: 35158536

No abstract available.

Hyperosmolar non-ketotic diabetic coma following leptospitosis

Chan YF

Med J Malaysia, 1972 Mar;26(3):211-214.

PMID: 35158524

No abstract available.

Metastatic tumours of the jaws

Chan YF

Med J Malaya, 1972 Sep;27(1):48-51.

PMID: 4264825

Hyperosmolar non-ketotic diabetic coma following leptospirosis--a case report

Chan YF

Med J Malaya, 1972 Mar;26(3):211-4.

PMID: 5031019

Enterovirus 71 infection induces apoptosis in Vero cells

Chan YF, Abubakar S

Malays J Pathol, 2003 Jun;25(1):29-35.

PMID: 16196375

The effects of Enterovirus 71 (HEV71) infection on African green monkey kidney cells (Vero) were investigated. It was found that the infected cells showed progressive cellular morphological changes characteristic in apoptotic cells within 10 hours post-infection. The number of apoptotic cells correlated significantly with the number of HEV71 antigen positive cells when cells were labeled using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and stained for HEV71 antigen. Approximately 11, 26, 45 and 50% of the infected cells were apoptotic at 12, 24, 48 and 72 hours post-infection, respectively. Internucleosomal DNA fragmentation, characteristic in the late stage of apoptosis was noted beginning on day 2 post-infection. The DNA fragmentation, however, was absent in cells treated with the heat- and ultraviolet light-inactivated virus inocula. These results demonstrate the capacity of HEV71 to induce apoptosis in the infected cells. The induction, however, requires high level of HEV71 infectivity and the presence of live virus particles, suggesting the need for the presence of specific viral proteins for apoptosis to occur.

Fulltext Serology surveillance of SARS-CoV-2 antibodies among healthcare workers in COVID-19 designated facilities in Malaysia

Woon YL, Lee YL, Chong YM, Ayub NA, Krishnabahawan SL, Lau JFW, et al.

Lancet Reg Health West Pac, 2021 Apr;9:100123.

PMID: 33778796 DOI: 10.1016/j.lanwpc.2021.100123

Background: Asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections are well documented. Healthcare workers (HCW) are at increased risk of infection due to occupational exposure to infected patients. We aim to determine the prevalence of SARS-CoV-2 antibodies among HCW who did not come to medical attention.

Methods: We prospectively recruited 400 HCW from the National Public Health Laboratory and two COVID-19 designated public hospitals in Klang Valley, Malaysia between 13/4/2020 and 12/5/2020. Quota sampling was used to ensure representativeness of HCW involved in direct and indirect patient care. All participants answered a self-administered questionnaire and blood samples were taken to test for SARS-CoV-2 antibodies by surrogate virus neutralization test.

Findings: The study population comprised 154 (38.5%) nurses, 103 (25.8%) medical doctors, 47 (11.8%) laboratory technologists and others (23.9%). A majority (68.9%) reported exposure to SARS-CoV-2 in the past month within their respective workplaces. Adherence to personal protection equipment (PPE) guidelines and hand hygiene were good, ranging from 91-100% compliance. None (95% CI: 0, 0.0095) of the participants had SARS-CoV-2 antibodies detected, despite 182 (45.5%) reporting some symptoms one month prior to study recruitment. One hundred and fifteen (29%) of participants claimed to have had contact with known COVID-19 persons outside of their workplace.

Interpretation: Zero seroprevalence among HCW suggests a low incidence of undiagnosed COVID-19 infection in our healthcare setting during the first local wave of SARS-CoV-2 infection. The occupational risk of SARS-CoV-2 transmission within healthcare facilities can be prevented by adherence to infection control measures and appropriate use of PPE.

Diverse human rhinoviruses A and C from children with respiratory infections in Kuala Lumpur, Malaysia

Chan YF, Jafar FL, Nathan AM, de Bruyne JA, Hassan A, Nor'e SS, et al.

J Infect, 2012 Jun;64(6):633-6.

PMID: 22425558 DOI: 10.1016/j.jinf.2012.03.011

Emergence of dengue virus type 4 genotype IIA in Malaysia

AbuBakar S, Wong PF, Chan YF

J Gen Virol, 2002 Oct;83(Pt 10):2437-2442.

PMID: 12237425 DOI: 10.1099/0022-1317-83-10-2437

Phylogenetic analyses of the envelope (E) gene sequence of five recently isolated dengue virus type 4 (DENV-4) suggested the emergence of a distinct geographical and temporal DENV-4 subgenotype IIA in Malaysia. Four of the isolates had direct ancestral lineage with DENV-4 Indonesia 1973 and showed evidence of intra-serotypic recombination with the other recently isolated DENV-4, MY01-22713. The E gene of isolate MY01-22713 had strong evidence of an earlier recombination involving DENV-4 genotype II Indonesia 1976 and genotype I Malaysia 1969. These results suggest that intra-serotypic recombination amongst DENV-4 from independent ancestral lineages may have contributed to the emergence of DENV-4 subgenotype IIA in Malaysia.

An amino acid change in nsP4 of chikungunya virus confers fitness advantage in human cell lines rather than in Aedes albopictus

Fu JYL, Chua CL, Vythilingam I, Sulaiman WYW, Wong HV, Chan YF, et al.

J Gen Virol, 2019 11;100(11):1541-1553.

PMID: 31613205 DOI: 10.1099/jgv.0.001338

Chikungunya virus (CHIKV) has caused large-scale epidemics of fever, rash and arthritis since 2004. This unprecedented re-emergence has been associated with mutations in genes encoding structural envelope proteins, providing increased fitness in the secondary vector Aedes albopictus. In the 2008-2013 CHIKV outbreaks across Southeast Asia, an R82S mutation in non-structural protein 4 (nsP4) emerged early in Malaysia or Singapore and quickly became predominant. To determine whether this nsP4-R82S mutation provides a selective advantage in host cells, which may have contributed to the epidemic, the fitness of infectious clone-derived CHIKV with wild-type nsP4-82R and mutant nsP4-82S were compared in Ae. albopictus and human cell lines. Viral infectivity, dissemination and transmission in Ae. albopictus were not affected by the mutation when the two variants were tested separately. In competition, the nsP4-82R variant showed an advantage over nsP4-82S in dissemination to the salivary glands, but only in late infection (10 days). In human rhabdomyosarcoma (RD) and embryonic kidney (HEK-293T) cell lines coinfected at a 1 : 1 ratio, wild-type nsP4-82R virus was rapidly outcompeted by nsP4-82S virus as early as one passage (3 days). In conclusion, the nsP4-R82S mutation provides a greater selective advantage in human cells than in Ae. albopictus, which may explain its apparent natural selection during CHIKV spread in Southeast Asia. This is an unusual example of a naturally occurring mutation in a non-structural protein, which may have facilitated epidemic transmission of CHIKV.

Replication and innate immune responses of two chikungunya virus genotypes in human monocyte-derived macrophages

Lau JZH, Chua CL, Chan YF, Nadarajan VS, Lee CLL, Sam IC

J Gen Virol, 2023 Apr;104(4).

PMID: 37043371 DOI: 10.1099/jgv.0.001842

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus, which causes epidemics of fever, joint pain and rash. There are three genotypes: West African, East/Central/South/Africa (ECSA) and Asian, with the latter two predominant globally. Genotype-specific differences in clinical presentations, virulence and immunopathology have been described. Macrophages are key cells in immune responses against CHIKV. Circulating blood monocytes enter tissue to differentiate into monocyte-derived macrophages (MDMs) in response to CHIKV infection at key replication sites such as lymphoid organs and joints. This study analyses differences in replication and induced immune mediators following infection of MDMs with Asian and ECSA CHIKV genotypes. Primary human MDMs were derived from residual blood donations. Replication of Asian (MY/06/37348) or ECSA (MY/08/065) genotype strains of CHIKV in MDMs was measured by plaque assay. Nineteen immune mediators were measured in infected cell supernatants using multiplexed immunoassay or ELISA. MY/08/065 showed significantly higher viral replication at 24 h post-infection (h p.i.) but induced significantly lower expression of proinflammatory cytokines (CCL-2, CCL-3, CCL-4, RANTES and CXCL-10) and the anti-inflammatory IL-1Ra compared to MY/06/37348. No differences were seen at later time points up to 72 h p.i. During early infection, MY/08/065 induced lower proinflammatory immune responses in MDMs. In vivo, this may lead to poorer initial control of viral infection, facilitating CHIKV replication and dissemination to other sites such as joints. This may explain the consistent past findings that the ECSA genotype is associated with greater viremia and severity of symptoms than the Asian genotype. Knowledge of CHIKV genotype-specific immunopathogenic mechanisms in human MDMs is important in understanding of clinical epidemiology, biomarkers and therapeutics in areas with co-circulation of different genotypes.

Some medical conditions in relation to dentistry

Chan YF

Dent J Malaysia Singapore, 1972 May;12(1):35-8.

PMID: 4507355

Detection of Persistent Chikungunya Virus RNA but not Infectious Virus in Experimental Vertical Transmission in Aedes aegypti from Malaysia

Wong HV, Vythilingam I, Sulaiman WY, Lulla A, Merits A, Chan YF, et al.

Am J Trop Med Hyg, 2016 Jan;94(1):182-6.

PMID: 26598564 DOI: 10.4269/ajtmh.15-0318

Vertical transmission may contribute to the maintenance of arthropod-borne viruses, but its existence in chikungunya virus (CHIKV) is unclear. Experimental vertical transmission of infectious clones of CHIKV in Aedes aegypti mosquitoes from Malaysia was investigated. Eggs and adult progeny from the second gonotrophic cycles of infected parental mosquitoes were tested. Using polymerase chain reaction (PCR), 56.3% of pooled eggs and 10% of adult progeny had detectable CHIKV RNA, but no samples had detectable infectious virus by plaque assay. Transfected CHIKV RNA from PCR-positive eggs did not yield infectious virus in BHK-21 cells. Thus, vertical transmission of viable CHIKV was not demonstrated. Noninfectious CHIKV RNA persists in eggs and progeny of infected Ae. aegypti, but the mechanism and significance are unknown. There is insufficient evidence to conclude that vertical transmission exists in CHIKV, as positive results reported in previous studies were almost exclusively based only on viral RNA detection.

Fulltext Seroprevalence survey of Chikungunya virus in Bagan Panchor, Malaysia

Ayu SM, Lai LR, Chan YF, Hatim A, Hairi NN, Ayob A, et al.

Am J Trop Med Hyg, 2010 Dec;83(6):1245-8.

PMID: 21118929 DOI: 10.4269/ajtmh.2010.10-0279

In 2006, an outbreak of Chikungunya virus (CHIKV) of the Asian genotype affected over 200 people in Bagan Panchor village in Malaysia. One year later, a post-outbreak survey was performed to determine attack rate, asymptomatic rate, and post-infection sequelae. Findings were compared with recent CHIKV outbreaks of the Central/East African genotype. A total of 180 residents were interviewed for acute symptoms and post-infection physical quality of life and depressive symptoms. Sera from 72 residents were tested for CHIKV neutralizing antibodies. The estimated attack rate was 55.6%, and 17.5% of infected residents were asymptomatic. Arthralgia was reported up to 3 months after infection, but there were no reports of long-term functional dependence or depression. Symptomatic and seropositive residents were significantly more likely to live in the area with the most dense housing and commercial activities. CHIKV had a high attack rate and considerable clinical impact during the Bagan Panchor outbreak.

Fulltext Genetic diversity, seasonality and transmission network of human metapneumovirus: identification of a unique sub-lineage of the fusion and attachment genes

Chow WZ, Chan YF, Oong XY, Ng LJ, Nor'E SS, Ng KT, et al.

Sci Rep, 2016 06 09;6:27730.

PMID: 27279080 DOI: 10.1038/srep27730

Human metapneumovirus (HMPV) is an important viral respiratory pathogen worldwide. Current knowledge regarding the genetic diversity, seasonality and transmission dynamics of HMPV among adults and children living in tropical climate remains limited. HMPV prevailed at 2.2% (n = 86/3,935) among individuals presented with acute respiratory tract infections in Kuala Lumpur, Malaysia between 2012 and 2014. Seasonal peaks were observed during the northeast monsoon season (November-April) and correlated with higher relative humidity and number of rainy days (P

Fulltext Performance of a Taqman Assay for Improved Detection and Quantification of Human Rhinovirus Viral Load

Ng KT, Chook JB, Oong XY, Chan YF, Chan KG, Hanafi NS, et al.

Sci Rep, 2016 10 10;6:34855.

PMID: 27721388 DOI: 10.1038/srep34855

Human rhinovirus (HRV) is the major aetiology of respiratory tract infections. HRV viral load assays are available but limitations that affect accurate quantification exist. We developed a one-step Taqman assay using oligonucleotides designed based on a comprehensive list of global HRV sequences. The new oligonucleotides targeting the 5'-UTR region showed high PCR efficiency (E = 99.6%, R2 = 0.996), with quantifiable viral load as low as 2 viral copies/μl. Assay evaluation using an External Quality Assessment (EQA) panel yielded a detection rate of 90%. When tested on 315 human enterovirus-positive specimens comprising at least 84 genetically distinct HRV types/serotypes (determined by the VP4/VP2 gene phylogenetic analysis), the assay detected all HRV species and types, as well as other non-polio enteroviruses. A commercial quantification kit, which failed to detect any of the EQA specimens, produced a detection rate of 13.3% (42/315) among the clinical specimens. Using the improved assay, we showed that HRV sheds in the upper respiratory tract for more than a week following acute infection. We also showed that HRV-C had a significantly higher viral load at 2-7 days after the onset of symptoms (p = 0.001). The availability of such assay is important to facilitate disease management, antiviral development, and infection control.

Fulltext Cytokine and Chemokine Profiling in Patients with Hand, Foot and Mouth Disease in Singapore and Malaysia

Teo FMS, Nyo M, Wong AA, Tan NWH, Koh MT, Chan YF, et al.

Sci Rep, 2018 03 06;8(1):4087.

PMID: 29511232 DOI: 10.1038/s41598-018-22379-6

Hand, foot and mouth disease (HFMD) is a prevalent contagious childhood disease typically associated with fever, oral lesions and limb exanthema. While HFMD is caused by a plethora of serotypes of viruses under the genus Enterovirus within the Picornaviridae family, Coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV-A71) are considered the main etiological agents. In recent years however, other viruses have also been isolated in considerable numbers from infected individuals in many regions, joining the legion commonly associated with HFMD. The present study investigated the cytokine and chemokine profiles of HFMD patients from Singapore and Malaysia for the first time. Comparative cohort studies of EV-A71-associated HFMD cases revealed that the Malaysia cohort had a distinct profile from the Singapore cohort, and this could be partly attributed by different EV-A71 genotypes. As the isolation of CV-A6, instead of CV-A16, had become prevalent in the Singapore cohort, it was also of particular interest to study the differential cytokine and chemokine profiles. Our data revealed that overlapping as well as unique profiles exist between the two major causative clinical isolates in the Singapore cohort. Having a better understanding of the respective immunological profiles could be useful for more accurate HFMD diagnosis, which is imperative for disease transmission control until multi-valent vaccines and/or broad-spectrum anti-viral drugs become available.

Immune responses against enterovirus A71 infection: Implications for vaccine success

Aw-Yong KL, NikNadia NMN, Tan CW, Sam IC, Chan YF

Rev Med Virol, 2019 09;29(5):e2073.

PMID: 31369184 DOI: 10.1002/rmv.2073

Enterovirus A71 (EV-A71) from the Picornaviridae family is an important emerging pathogen causing hand, foot, and mouth disease (HFMD) outbreaks worldwide. EV-A71 also caused fatal neurological complications in young children especially in Asia. On the basis of seroepidemiological studies from many Asian countries, EV-A71 infection is very common. Children of very young age are particularly vulnerable. Large-scale epidemics that occur every 3 to 4 years are associated with accumulation of an immunologically naive younger population. Capsid proteins especially VP1 with the presence of major B- and T-cell epitopes are the most antigenic proteins. The nonstructural proteins mainly contribute to T-cell epitopes that induce cross-reactive immune responses against other enteroviruses. Dominant epitopes and their neutralization magnitudes differ in mice, rabbits, and humans. Neutralizing antibody is sufficient for immune protection, but poorer cellular immunity may lead to severe neurological complications and deaths. Some chemokines/cytokines are consistently found in severely ill patients, for example, IL-6, IL-10, IL-17A, MCP-1, IL-8, MIG, IP-10, IFN-γ, and G-CSF. An increase in white cell counts is a risk factor for severe HFMD. Recent clinical trials on EV-A71 inactivated vaccine showed >90% efficacy and a robust neutralization response that was protective, indicating neutralizing antibody correlates for protection. No protection against other enteroviruses was observed. A comprehensive understanding of the immune responses to EV-A71 infection will benefit the development of diagnostic tools, potential therapeutics, and subunit vaccine candidates. Future development of a multivalent enterovirus vaccine will require knowledge of correlates of protection, understanding of cross-protection and memory T-cell responses among enteroviruses.

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