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Fulltext Evolution of Influenza B Virus in Kuala Lumpur, Malaysia, between 1995 and 2008

Sam IC, Su YC, Chan YF, Nor'E SS, Hassan A, Jafar FL, et al.

J Virol, 2015 Sep;89(18):9689-92.
PMID: 26136576 DOI: 10.1128/JVI.00708-15

Influenza B virus causes significant disease but remains understudied in tropical regions. We sequenced 72 influenza B viruses collected in Kuala Lumpur, Malaysia, from 1995 to 2008. The predominant circulating lineage (Victoria or Yamagata) changed every 1 to 3 years, and these shifts were associated with increased incidence of influenza B. We also found poor lineage matches with recommended influenza virus vaccine strains. While most influenza B virus lineages in Malaysia were short-lived, one circulated for 3 to 4 years.
Fulltext SARS-CoV-2 multiplex RT-PCR to detect variants of concern (VOCs) in Malaysia, between January to May 2021

Fu JYL, Chong YM, Sam IC, Chan YF

J Virol Methods, 2022 Mar;301:114462.
PMID: 35026305 DOI: 10.1016/j.jviromet.2022.114462

Emerging SARS-CoV-2 variants of concern (VOC) have been associated with enhanced transmissibility and immune escape. Next-generation sequencing (NGS) of the whole genome is the gold standard for variant identification for surveillance but is time-consuming and costly. Rapid and cost-effective assays that detect SARS-CoV-2 variants are needed. We evaluated Allplex SARS-CoV-2 Master Assay and Variants I Assay to detect HV69/70 deletion, Y144 deletion, E484K, N501Y, and P681H spike mutations in 248 positive samples collected in Kuala Lumpur, Malaysia, between January and May 2021. Spike variants were detected in 78/248 (31.5 %), comprising 60 VOC B.1.351 (beta) and 18 B.1.1.7 (alpha). With NGS as reference for 115 samples, the sensitivity for detecting the spike mutations was 98.7 % with the Master Assay and 100 % with the Variants I Assay. The emergence of beta variants correlated with increasing COVID-19 infections in Malaysia. The prevalence of alpha VOC and lineage B.1.466.2 was low. These assays detect mutations present in alpha, beta and gamma VOCs. Of the VOCs which have subsequently emerged, the assays should detect omicron (B.1.1.529) but not B.1.617.2 (delta). In conclusion, spike variant PCR assays can be used to rapidly monitor selected SARS-CoV-2 VOCs in resource-limited settings, but require updates as new variants emerge.
Characterisation of mouse monoclonal antibodies targeting linear epitopes on Chikungunya virus E2 glycoprotein

Chua CL, Chan YF, Sam IC

J Virol Methods, 2014 Jan;195:126-33.
PMID: 24134938 DOI: 10.1016/j.jviromet.2013.10.015

Chikungunya virus (CHIKV) is a mosquito-borne arbovirus which has recently re-emerged globally and poses a major threat to public health. Infection leads to severe arthralgia, and disease management remains supportive in the absence of vaccines and anti-viral interventions. The high specificities of monoclonal antibodies (mAbs) have been exploited in immunodiagnostics and immunotherapy in recent decades. In this study, eight different clones of mAbs were generated and characterised. These mAbs targeted the linear epitopes on the CHIKV E2 envelope glycoprotein, which is the major target antigen during infection. All the mAbs showed binding activity against the purified CHIKV virion or recombinant E2 when analysed by immunofluorescence, ELISA and Western blot. The epitopes of each mAb were mapped by overlapping synthetic peptide-based ELISA. The epitopes are distributed at different functional domains of E2 glycoprotein, namely at domain A, junctions of β-ribbons with domains A and B, and domain C. Alignment of mAb epitope sequences revealed that some are well-conserved within different genotypes of CHIKV, while some are identical to and likely to cross-react with the closely-related alphavirus O'nyong-nyong virus. These mAbs with their mapped epitopes are useful for the development of diagnostic or research tools, including immunofluorescence, ELISA and Western blot.
Fulltext Epidemic dynamics, interactions and predictability of enteroviruses associated with hand, foot and mouth disease in Japan

Takahashi S, Metcalf CJE, Arima Y, Fujimoto T, Shimizu H, Rogier van Doorn H, et al.

J R Soc Interface, 2018 09 12;15(146).
PMID: 30209044 DOI: 10.1098/rsif.2018.0507

Outbreaks of hand, foot and mouth disease have been documented in Japan since 1963. This disease is primarily caused by the two closely related serotypes of Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16). Here, we analyse Japanese virologic and syndromic surveillance time-series data from 1982 to 2015. As in some other countries in the Asia Pacific region, EV-A71 in Japan has a 3 year cyclical component, whereas CV-A16 is predominantly annual. We observe empirical signatures of an inhibitory interaction between the serotypes; virologic lines of evidence suggest they may indeed interact immunologically. We fit the time series to mechanistic epidemiological models: as a first-order effect, we find the data consistent with single-serotype susceptible-infected-recovered dynamics. We then extend the modelling to incorporate an inhibitory interaction between serotypes. Our results suggest the existence of a transient cross-protection and possible asymmetry in its strength such that CV-A16 serves as a stronger forcing on EV-A71. Allowing for asymmetry yields accurate out-of-sample predictions and the directionality of this effect is consistent with the virologic literature. Confirmation of these hypothesized interactions would have important implications for understanding enterovirus epidemiology and informing vaccine development. Our results highlight the general implication that even subtle interactions could have qualitative impacts on epidemic dynamics and predictability.
Cellular proteome alterations in response to enterovirus 71 and coxsackievirus A16 infections in neuronal and intestinal cell lines

Chan SY, Sam IC, Lai JK, Chan YF

J Proteomics, 2015 Jul 1;125:121-30.
PMID: 26003530 DOI: 10.1016/j.jprot.2015.05.016

Hand, foot and mouth disease is mainly caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), but EV-A71 is also associated with severe neurological complications. Host factors may contribute to the different clinical outcomes of EV-A71 and CV-A16 infections. A neurovirulent EV-A71 strain (EV-A71/UH1) from a fatal case, a non-neurovirulent EV-A71 strain (EV-A71/Sha66) and a CV-A16 strain (CV-A16/22159) from cases of uncomplicated HFMD were used. Replication of the viruses in SK-N-MC (neuronal) and HT-29 (intestinal) cell lines correlated with the severity of clinical disease associated with each virus. EV-A71/UH1 showed the greatest replication in neuronal cells. In HT-29 cells, both EV-A71 strains replicated well, but CV-A16/22159 showed no effective replication. The proteomes of mock and infected SK-N-MC and HT-29 cell lines were compared by 2D-SDS-PAGE. The differentially expressed proteins were identified by MALDI-TOF/TOF analysis. There were 46 and 44 differentially expressed proteins identified from SK-N-MC and HT-29 cells, respectively, categorized under apoptosis, stress, cytoskeletal, energy metabolism proteins and others. Western blot validation showed that EV-A71/UH1 and CV-A16 also differentially induced proteins involved in viral RNA translation and host cell stress responses in neuronal and intestinal cell lines.
Chikungunya encephalopathy and pneumonia in a young infant presenting with septic shock

Chee YS, Ahamad Fouzi N, Chong YM, Sam IC, Chan YF, Chua CL, et al.

J Paediatr Child Health, 2022 Feb 17.
PMID: 35175651 DOI: 10.1111/jpc.15858
Fulltext An Overview of the Genetic Variations of the SARS-CoV-2 Genomes Isolated in Southeast Asian Countries

Yap PSX, Tan TS, Chan YF, Tee KK, Kamarulzaman A, Teh CSJ

J Microbiol Biotechnol, 2020 Jul 28;30(7):962-966.
PMID: 32627759 DOI: 10.4014/jmb.2006.06009

Monitoring the mutation dynamics of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical in understanding its infectivity, virulence and pathogenicity for development of a vaccine. In an "age of mobility," the pandemic highlights the importance and vulnerability of regionalization and labor market interdependence in Southeast Asia. We intend to characterize the genetic variability of viral populations within the region to provide preliminary information for regional surveillance in the future. By analyzing 142 complete genomes from South East Asian (SEA) countries, we identified three central variants distinguished by nucleotide and amino acid changes.
Seroprevalence of seasonal and pandemic influenza a in Kuala Lumpur, Malaysia in 2008-2010

Sam IC, Shaw R, Chan YF, Hooi PS, Hurt AC, Barr IG

J Med Virol, 2013 Aug;85(8):1420-5.
PMID: 23765779 DOI: 10.1002/jmv.23622

Relatively little is known about the burden of influenza in tropical countries. The seroprevalence of pandemic influenza A (H1N1) 2009, seasonal H1N1 and H3N2 was determined in Kuala Lumpur, Malaysia. Pre- and post-pandemic residual laboratory sera were tested by hemagglutination-inhibition. The seroprevalence of A(H1N1)pdm09 increased from 3.7% pre-pandemic to 21.9% post-pandemic, giving an overall cumulative incidence of 18.1% (95% CI, 13.8-22.5%), mainly due to increases in those <5, 5-17, and 18-29 years old. In contrast with findings from USA, Europe, and Australia, pre-existing seroprevalence to A(H1N1)pdm09 was low at 5.6% in the elderly age group of >55 years. A(H1N1)pdm09 affected almost a third of those <30 years in Kuala Lumpur. Pre-pandemic seroprevalence was 14.7% for seasonal H1N1 and 21.0% for H3N2, and these rates did not change significantly after the pandemic. Seasonal and pandemic influenza cause a considerable burden in tropical Malaysia, particularly in children and young adults.
Evaluation of rapid influenza diagnostic tests for influenza A and B in the tropics

Chong YM, Tan XH, Hooi PS, Lee LM, Sam IC, Chan YF

J Med Virol, 2019 08;91(8):1562-1565.
PMID: 31032971 DOI: 10.1002/jmv.25495

Rapid diagnosis of influenza is important for early treatment and institution of control measures. In developing tropical countries such as Malaysia, influenza occurs all year round, but molecular assays and conventional techniques (such as immunofluorescence and culture) for diagnosis are not widely available. Rapid influenza diagnostic tests (RIDTs) may be useful in this setting. A total of 552 fresh respiratory specimens were assessed from patients with respiratory symptoms at a teaching hospital in Kuala Lumpur, Malaysia from November 2017 to March 2018. Two digital immunoassays (DIAs), STANDARD F Influenza A/B Fluorescence Immunoassay (STANDARD F) and Sofia Influenza A + B Fluorescence Immunoassay (Sofia) and one conventional RIDT (immunochromatographic assay), SD Bioline Influenza Ag A/B/A(H1N1) Pandemic rapid test kit (SD Bioline) were evaluated in comparison with a WHO-recommended reverse transcription quantitative PCR (RT-qPCR). Of the 552 samples, influenza A virus was detected in 47 (8.5%) and influenza B virus in 7 (1.3%). The digital immunoassays STANDARD F and Sofia had significantly higher overall sensitivity rates (71.7% and 70.6%, respectively) than the conventional RIDT SD Bioline and immunofluorescence/viral culture (55.8% and 52.8%, respectively). Sensitivity rates were higher for influenza A than influenza B, and specificity rates were uniformly high, ranging from 98% to 100%. Digital readout RIDTs can be used in tropical settings with year-round influenza if PCR is unavailable.
Fulltext Low postpandemic wave SARS-CoV-2 seroprevalence in Kuala Lumpur and Selangor, Malaysia

Sam IC, Chong YM, Tan CW, Chan YF

J Med Virol, 2021 02;93(2):647-648.
PMID: 32790206 DOI: 10.1002/jmv.26426
Seasonal influenza activity based on laboratory surveillance in Malaysia, 2011-2016

Sam IC, Noraini W, Sandhu SS, Norizah I, Selvanesan S, Thayan R, et al.

J Med Virol, 2019 03;91(3):498-502.
PMID: 30199092 DOI: 10.1002/jmv.25313

Influenza seasonality in equatorial countries is little understood. Seasonal and alert influenza thresholds were determined for Malaysia, using laboratory-based data obtained from the Malaysia Influenza Surveillance System and a major teaching hospital, from 2011 to 2016. Influenza was present year-round, with no clear annual seasons. Variable periods of higher transmission occurred inconsistently, in November to December, January to March, July to September, or a combination of these. These coincide with seasons in the nearby southeast Asian countries or winter seasons of the northern and southern hemispheres. Changes in the predominant circulating influenza type were only sometimes associated with increased transmission. The data can provide public health interventions such as vaccines.
Seroepidemiology of enterovirus D68 infection in Kuala Lumpur, Malaysia between 2013-2015

Chan YF, Sam IC, Nayan E, Tan XH, Yogarajah T

J Med Virol, 2021 Oct 07.
PMID: 34617599 DOI: 10.1002/jmv.27381

Enterovirus D68 (EV-D68) is an emerging respiratory pathogen since the 2014 outbreak in USA. A low level of virus circulation has been reported in Kuala Lumpur, Malaysia in the past. However, the extent of the infection in Malaysia is not known. In the present study, we determine the seroepidemiology of EV-D68 in Kuala Lumpur, Malaysia before and after the USA outbreak in Aug 2014. A luciferase-based seroneutralization test was developed using a clone-derived prototype Fermon strain carrying a nanoluciferase marker. We screened the neutralization capacity of 450 serum samples from children and adults (1-89 years old) collected between 2013 to 2015. EV-D68 seropositivity increased with age, with children aged 1-3 showing significantly lower seroprevalence compared to adults. Multivariate analysis showed that older age groups 13-49 years (odds ratio [OR] 4.78 [95% CI 2.69-8.49], p<0.0001) and >50 years (OR 3.83 [95% CI 2.19-6.68], p<0.0001) were more likely to be EV-D68 seropositive than children <13 years. Sampling post-Sept 2014 compared to pre-Sept 2014 also predicted seropositivity (OR 1.66 [95% CI 1.04-2.65]). Presence of neutralizing antibodies against EV-D68 in the study population suggests that EV-D68 was circulating prior to 2014. A higher seropositivity post-Sept 2014 suggests that Malaysia also experienced an upsurge in EV-D68 infections after the USA outbreaks in Aug 2014. A low seropositivity rate observed in children, especially those aged 1-3 years old, suggests that they are at risk and should be prioritized for future vaccination. This article is protected by copyright. All rights reserved.
Changing predominant SARS-CoV-2 lineages drives successive COVID-19 waves in Malaysia, February 2020 to March 2021

Sam IC, Chong YM, Abdullah A, Fu JYL, Hasan MS, Jamaluddin FH, et al.

J Med Virol, 2021 Nov 10.
PMID: 34757638 DOI: 10.1002/jmv.27441

Malaysia has experienced three waves of coronavirus disease 2019 (COVID-19) as of March 31, 2021. We studied the associated molecular epidemiology and SARS-CoV-2 seroprevalence during the third wave. We obtained 60 whole-genome SARS-CoV-2 sequences between October 2020 and January 2021 in Kuala Lumpur/Selangor and analyzed 989 available Malaysian sequences. We tested 653 residual serum samples collected between December 2020 to April 2021 for anti-SARS-CoV-2 total antibodies, as a proxy for population immunity. The first wave (January 2020) comprised sporadic imported cases from China of early Pango lineages A and B. The second wave (March-June 2020) was associated with lineage B.6. The ongoing third wave (from September 2020) was propagated by a state election in Sabah. It is due to lineage B.1.524 viruses containing spike mutations D614G and A701V. Lineages B.1.459, B.1.470, and B.1.466.2 were likely imported from the region and confined to Sarawak state. Direct age-standardized seroprevalence in Kuala Lumpur/Selangor was 3.0%. The second and third waves were driven by super-spreading events and different circulating lineages. Malaysia is highly susceptible to further waves, especially as alpha (B.1.1.7) and beta (B.1.351) variants of concern were first detected in December 2020/January 2021. Increased genomic surveillance is critical.
Identification and characterization of neutralization epitopes at VP2 and VP1 of enterovirus A71

NikNadia N, Tan CW, Ong KC, Sam IC, Chan YF

J Med Virol, 2018 06;90(6):1164-1167.
PMID: 29457642 DOI: 10.1002/jmv.25061

Enterovirus A71 (EV-A71) neutralization escape mutants were generated with monoclonal antibody MAB979 (Millipore). The VP2-T141I and VP1-D14N substitutions were identified. Using reverse genetics, infectious clones with these substitutions were constructed and tested by neutralization assay with immune sera from mice and humans. The N-terminus VP1-14 is more important than EF loop VP2-141 in acute human infection, mainly because it recognised IgM present in acute infection. The N-terminus VP1 could be a useful target for diagnostics and therapeutic antibodies in acute infection.
Selective media and real-time PCR improves diagnosis of melioidosis in community-acquired pneumonia in a low-incidence setting in Kuala Lumpur, Malaysia

Subakir H, Chong YM, Chan YF, Hasan MS, Jamaluddin MFH, Pang YK, et al.

J Med Microbiol, 2020 Jan;69(1):49-51.
PMID: 31750812 DOI: 10.1099/jmm.0.001108

Introduction.Burkholderia pseudomallei (melioidosis) is an important cause of community-acquired pneumonia (CAP) in the tropics. Selective medium is recommended for laboratory diagnosis with non-sterile respiratory samples, while PCR is not routinely used due to variable reported performance. The effectiveness of these diagnostic modalities varies by site.Aim. To compare selective media and real-time PCR (qPCR) with routine media in detecting B. pseudomallei in CAP respiratory samples in a low-incidence setting in Kuala Lumpur, Malaysia.Methodology. Respiratory samples were routinely cultured on blood, chocolate and MacConkey agar (RESP-ROUTINE), and compared to culture on selective Ashdown medium (RESP-SELECTIVE) and qPCR. The gold standard was routine culture of B. pseudomallei from any site (ALL-ROUTINE).Results.B. pseudomallei was detected in 8/204 (3.9 %) samples. Overall sensitivity rates differed (P=0.03) for qPCR (100%), RESP-SELECTIVE (87.5%) and RESP-ROUTINE (50%). There was a trend towards lower median days to positive culture for RESP-SELECTIVE (1 day) compared to RESP-ROUTINE (2 days, P=0.08) and ALL-ROUTINE (2 days, P=0.06). Reagent costs for each additional detection were USD59 for RESP-SELECTIVE and USD354 for PCR.Conclusions. In a low-incidence setting, selective culture of respiratory samples on Ashdown was more sensitive and allowed quicker identification than routine media, at reasonable cost. Blood cultures are critical, confirming four cases missed by routine respiratory culture. Selective medium is useful in early pneumonia (pre-sepsis) and resource-limited settings where blood cultures are infrequently done. Real-time PCR is costly, but highly sensitive and useful for high-risk patients with diabetes, cancer or immunosuppressants, or requiring ventilation or intensive care.
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.
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.
Fulltext Detection of respiratory viruses in adults with suspected COVID-19 in Kuala Lumpur, Malaysia

Chong YM, Chan YF, Jamaluddin MFH, Hasan MS, Pang YK, Ponnampalavanar S, et al.

J Clin Virol, 2021 Dec;145:105000.
PMID: 34739838 DOI: 10.1016/j.jcv.2021.105000

BACKGROUND: Reports of co-circulation of respiratory viruses during the COVID-19 pandemic and co-infections with SARS-CoV-2 vary. However, limited information is available from developing countries.
OBJECTIVES: We aimed to investigate the incidence of respiratory viruses in adult patients with suspected COVID-19 in Kuala Lumpur, Malaysia.
STUDY DESIGN: We collected 198 respiratory samples from adult patients hospitalized with suspected COVID-19 in a single teaching hospital in Kuala Lumpur in February-May 2020 and tested combined oro-nasopharyngeal swabs with the NxTAG Respiratory Pathogen Panel (Luminex) and Allplex RV Essential (Seegene) assays. Forty-five negative samples further underwent viral metagenomics analysis.
RESULTS: Of the 198 samples, 74 (37.4%) had respiratory pathogens, including 56 (28.3%) with SARS-CoV-2 and 18 (9.1%) positive for other respiratory pathogens. There were five (2.5%) SARS-CoV-2 co-infections, all with rhinovirus/enterovirus. Three samples (6.7%; 3/45) had viruses identified by metagenomics, including one case of enterovirus D68 and one of Saffold virus genotype 6 in a patient requiring ICU care. Most of the COVID-19 patients (91.1%; 51/56) had mild symptoms but 5.4% (3/56) died.
CONCLUSION: During the early COVID-19 period, common respiratory viruses other than SARS-CoV-2 only accounted for 9.1% of hospitalization cases with ARI and co-infections with SARS-CoV-2 were rare. Continued surveillance is important to understand the impact of COVID-19 and its associated public health control measures on circulation of other respiratory viruses. Metagenomics can identify unexpected or rare pathogens, such as Saffold virus, which is rarely described in adults.
Fulltext Recent developments in antiviral agents against enterovirus 71 infection

Tan CW, Lai JK, Sam IC, Chan YF

J Biomed Sci, 2014;21:14.
PMID: 24521134 DOI: 10.1186/1423-0127-21-14

Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.
Fulltext Clinical features of Malaysian children hospitalized with community-acquired seasonal influenza

Sam IC, Abdul-Murad A, Karunakaran R, Rampal S, Chan YF, Nathan AM, et al.

Int J Infect Dis, 2010 Sep;14 Suppl 3:e36-40.
PMID: 20153233 DOI: 10.1016/j.ijid.2009.10.005

OBJECTIVES: The clinical impact of seasonal influenza is understudied in tropical countries. The aim of this study was to describe the clinical features and seasonal pattern of influenza in children hospitalized in Malaysia, and to identify predictors of severe disease.
METHODS: Children hospitalized with community-acquired, laboratory-confirmed influenza at a teaching hospital in Kuala Lumpur, Malaysia during 2002-2007 were identified retrospectively. Clinical data were collected, and predictors of severe disease were identified by multivariate logistic regression. All influenza cases from 1982 to 2007 were also analyzed for seasonal patterns.
RESULTS: A total of 132 children were included in the study, 48 (36.4%) of whom had underlying medical conditions. The mean age was 2.5 years and 116 (87.9%) were <5 years old. The most common presenting features were fever or history of fever, cough, rhinitis, vomiting, and pharyngitis. Severe influenza was seen in 16 patients (12.1%; nine previously healthy), including 12 (9.1%; eight previously healthy) requiring intensive care. There were three (2.3%) deaths. Severe disease was associated with age <12 months, female sex, and absence of rhinitis on admission. Influenza was seen year-round, with peaks in November-January and May-July.
CONCLUSIONS: Seasonal influenza has a considerable impact on children hospitalized in Malaysia, in both the healthy and those with underlying medical conditions.

Study site: University Malaya Medical Centre (UMMC)

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