Biodefence Center

Singapore, Singapore

Biodefence Center

Singapore, Singapore
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Chen M.I.C.,Tan Tock Seng Hospital | Chen M.I.C.,National University of Singapore | Lee V.J.M.,National University of Singapore | Lee V.J.M.,Biodefence Center | And 18 more authors.
JAMA - Journal of the American Medical Association | Year: 2010

Context: Singapore experienced a single epidemic wave of 2009 influenza A(H1N1) with epidemic activity starting in late June 2009 and peaking in early August before subsiding within a month. Objective: To compare the risk and factors associated with H1N1 seroconversion in different adult cohorts. Design, Setting, and Participants: A study with serial serological samples from 4 distinct cohorts: general population (n=838), military personnel (n=1213), staff from an acute care hospital (n=558), and staff as well as residents from long-term care facilities (n=300) from June 22, 2009, to October 15, 2009. Hemagglutination inhibition results of serum samples taken before, during, and after the epidemic and data from symptom questionnaires are presented. Main Outcome Measures: A 4-fold or greater increase in titer between any of the 3 serological samples was defined as evidence of H1N1 seroconversion. Results: Baseline titers of 40 or more were observed in 22 members (2.6%; 95% confidence interval [CI], 1.7%-3.9%) of the community, 114 military personnel (9.4%; 95% CI, 7.9%-11.2%), 37 hospital staff (6.6%; 95% CI, 4.8%-9.0%), and 20 participants from long-term care facilities (6.7%; 95% CI, 4.4%-10.1%). In participants with 1 or more follow-up serum samples, 312 military personnel (29.4%; 95% CI, 26.8%-32.2%) seroconverted compared with 98 community members (13.5%; 95% CI, 11.2%-16.2%), 35 hospital staff (6.5%; 95% CI, 4.7%-8.9%), and only 3 longterm care participants (1.2%; 95% CI, 0.4%-3.5%). Increased frequency of seroconversion was observed for community participants from households in which 1 other member seroconverted (adjusted odds ratio [OR], 3.32; 95% CI, 1.50-7.33), whereas older age was associated with reduced odds of seroconversion (adjusted OR, 0.77 per 10 years; 95% CI, 0.64-0.93). Higher baseline titers were associated with decreased frequency of seroconversion in community (adjusted OR for every doubling of baseline titer, 0.48; 95% CI, 0.27-0.85), military (adjusted OR, 0.71; 95% CI, 0.61-0.81), and hospital staff cohorts (adjusted OR, 0.50; 95% CI, 0.26-0.93). Conclusion: Following the June-September 2009 wave of 2009 influenza A(H1N1), 13% of the community participants seroconverted, and most of the adult population likely remained susceptible. ©2010 American Medical Association. All rights reserved.


Ong J.B.S.,Tan Tock Seng Hospital | Chen M.I.-C.,Tan Tock Seng Hospital | Chen M.I.-C.,National University of Singapore | Cook A.R.,National University of Singapore | And 7 more authors.
PLoS ONE | Year: 2010

Background: Reporting of influenza-like illness (ILI) from general practice/family doctor (GPFD) clinics is an accurate indicator of real-time epidemic activity and requires little effort to set up, making it suitable for developing countries currently experiencing the influenza A (H1N1 -2009) pandemic or preparing for subsequent epidemic waves. Methodology/Principal Findings: We established a network of GPFDs in Singapore. Participating GPFDs submitted returns via facsimile or e-mail on their work days using a simple, standard data collection format, capturing: gender; year of birth; "ethnicity" residential status; body temperature (°C); and treatment (antiviral or not); for all cases with a clinical diagnosis of an acute respiratory illness (ARI). The operational definition of ILI in this study was an ARI with fever of 37.8°C or more. The data were processed daily by the study co-ordinator and fed into a stochastic model of disease dynamics, which was refitted daily using particle filtering, with data and forecasts uploaded to a website which could be publicly accessed. Twenty-three GPFD clinics agreed to participate. Data collection started on 2009-06-26 and lasted for the duration of the epidemic. The epidemic appeared to have peaked around 2009-08-03 and the ILI rates had returned to baseline levels by the time of writing. Conclusions/Significance: This real-time surveillance system is able to show the progress of an epidemic and indicates when the peak is reached. The resulting information can be used to form forecasts, including how soon the epidemic wave will end and when a second wave will appear if at all. © 2010 Ong et al.


Carrasco L.R.,National University of Singapore | Leo Y.S.,Tan Tock Seng Hospital | Leo Y.S.,National University of Singapore | Cook A.R.,National University of Singapore | And 7 more authors.
PLoS Neglected Tropical Diseases | Year: 2014

Background: Dengue causes 50 million infections per year, posing a large disease and economic burden in tropical and subtropical regions. Only a proportion of dengue cases require hospitalization, and predictive tools to triage dengue patients at greater risk of complications may optimize usage of limited healthcare resources. For severe dengue (SD), proposed by the World Health Organization (WHO) 2009 dengue guidelines, predictive tools are lacking.Methods:We undertook a retrospective study of adult dengue patients in Tan Tock Seng Hospital, Singapore, from 2006 to 2008. Demographic, clinical and laboratory variables at presentation from dengue polymerase chain reaction-positive and serology-positive patients were used to predict the development of SD after hospitalization using generalized linear models (GLMs).Principal findings:Predictive tools compatible with well-resourced and resource-limited settings - not requiring laboratory measurements - performed acceptably with optimism-corrected specificities of 29% and 27% respectively for 90% sensitivity. Higher risk of severe dengue (SD) was associated with female gender, lower than normal hematocrit level, abdominal distension, vomiting and fever on admission. Lower risk of SD was associated with more years of age (in a cohort with an interquartile range of 27-47 years of age), leucopenia and fever duration on admission. Among the warning signs proposed by WHO 2009, we found support for abdominal pain or tenderness and vomiting as predictors of combined forms of SD.Conclusions:The application of these predictive tools in the clinical setting may reduce unnecessary admissions by 19% allowing the allocation of scarce public health resources to patients according to the severity of outcomes. © 2014 Carrasco et al.


Carrasco L.R.,National University of Singapore | Jit M.,Public Health England | Chen M.I.,National University of Singapore | Chen M.I.,Tan Tock Seng Hospital | And 4 more authors.
Emerging Themes in Epidemiology | Year: 2013

Background: The volume of influenza pandemic modelling studies has increased dramatically in the last decade. Many models incorporate now sophisticated parameterization and validation techniques, economic analyses and the behaviour of individuals. Methods. We reviewed trends in these aspects in models for influenza pandemic preparedness that aimed to generate policy insights for epidemic management and were published from 2000 to September 2011, i.e. before and after the 2009 pandemic. Results: We find that many influenza pandemics models rely on parameters from previous modelling studies, models are rarely validated using observed data and are seldom applied to low-income countries. Mechanisms for international data sharing would be necessary to facilitate a wider adoption of model validation. The variety of modelling decisions makes it difficult to compare and evaluate models systematically. Conclusions: We propose a model Characteristics, Construction, Parameterization and Validation aspects protocol (CCPV protocol) to contribute to the systematisation of the reporting of models with an emphasis on the incorporation of economic aspects and host behaviour. Model reporting, as already exists in many other fields of modelling, would increase confidence in model results, and transparency in their assessment and comparison. © 2013 Carrasco et al.; licensee BioMed Central Ltd.


Yap J.,Biodefence Center | Lee V.J.,Biodefence Center | Lee V.J.,National University of Singapore | Lee V.J.,Australian National University | And 4 more authors.
BMC Public Health | Year: 2010

Background. Effective influenza pandemic management requires understanding of the factors influencing behavioral changes. We aim to determine the differences in knowledge, attitudes and practices in various different cohorts and explore the pertinent factors that influenced behavior in tropical Singapore. Methods. We performed a cross-sectional knowledge, attitudes and practices survey in the Singapore military from mid-August to early-October 2009, among 3054 personnel in four exposure groups - laboratory-confirmed H1N1-2009 cases, close contacts of cases, healthcare workers, and general personnel. Results. 1063 (34.8%) participants responded. The mean age was 21.4 (SE 0.2) years old. Close contacts had the highest knowledge score (71.7%, p = 0.004) while cases had the highest practice scores (58.8%, p < 0.001). There was a strong correlation between knowledge and practice scores (r = 0.27, p < 0.01) and knowledge and attitudes scores (r = 0.21, p < 0.01). The significant predictors of higher practice scores were higher knowledge scores (p < 0.001), Malay ethnicity (p < 0.001), exposure group (p < 0.05) and lower education level (p < 0.05). The significant predictors for higher attitudes scores were Malay ethnicity (p = 0.014) and higher knowledge scores (p < 0.001). The significant predictor for higher knowledge score was being a contact (p = 0.007). Conclusion. Knowledge is a significant influence on attitudes and practices in a pandemic, and personal experience influences practice behaviors. Efforts should be targeted at educating the general population to improve practices in the current pandemic, as well as for future epidemics. © 2010 Yap et al; licensee BioMed Central Ltd.


Yap J.,Biodefence Center | Tan C.H.,Biodefence Center | Cook A.R.,National University of Singapore | Loh J.P.,Defence Medical and Environmental Research Institute | And 5 more authors.
BMC Infectious Diseases | Year: 2012

Background: Influenza infections may result in different clinical presentations. This study aims to determine the clinical differences between circulating influenza strains in a young healthy adult population in the tropics.Methods: A febrile respiratory illness (FRI) (fever ≥ 37.5°C with cough and/or sore throat) surveillance program was started in 4 large military camps in Singapore on May 2009. Personnel with FRI who visited the camp clinics from 11 May 2009 to 25 June 2010 were recruited. Nasal washes and interviewer-administered questionnaires on demographic information and clinical features were obtained from consenting participants. All personnel who tested positive for influenza were included in the study. Overall symptom load was quantified by counting the symptoms or signs, and differences between strains evaluated using linear models.Results: There were 434 (52.9%) pandemic H1N1-2009, 58 (7.1%) seasonal H3N2, 269 (32.8%) influenza B, and 10 (1.2%) seasonal H1N1 cases. Few seasonal influenza A (H1N1) infections were detected and were therefore excluded from analyses, together with undetermined influenza subtypes (44 (1.5%)), or more than 1 co-infecting subtype (6 (0.2%)). Pandemic H1N1-2009 cases had significantly fewer symptoms or signs (mean 7.2, 95%CI 6.9-7.4, difference 1.6, 95%CI 1.2-2.0, p < 0.001) than the other two subtypes (mean 8.7, 95%CI 8.5-9.0). There were no statistical differences between H3N2 and influenza B (p = 0.58). Those with nasal congestion, rash, eye symptoms, injected pharynx or fever were more likely to have H3N2; and those with sore throat, fever, injected pharynx or rhinorrhoea were more likely to have influenza B than H1N1-2009.Conclusions: Influenza cases have different clinical presentations in the young adult population. Pandemic H1N1 influenza cases had fewer and milder clinical symptoms than seasonal influenza. As we only included febrile cases and had no information on the proportion of afebrile infections, further research is needed to confirm whether the relatively milder presentation of pandemic versus seasonal influenza infections applies to all infections or only febrile illnesses. © 2012 Yap et al; BioMed Central Ltd.


Tan X.Q.,Biodefence Center | Tan X.Q.,National University of Singapore | Zhao X.,National University of Singapore | Lee V.J.,Biodefence Center | And 8 more authors.
BMC Infectious Diseases | Year: 2014

Background: Few studies have comprehensively described tropical respiratory disease surveillance in military populations. There is also a lack of studies comparing clinical characteristics of the non-influenza pathogens with influenza and amongst themselves. Methods: From May 2009 through October 2012, 7733 consenting cases of febrile respiratory illness (FRI) (temperature [greater than or equal to]37.5degreesC with cough or sorethroat) and controls in the Singapore military had clinical data and nasal washes collected prospectively. Nasal washes underwent multiplex PCR, and the analysis was limited to viral mono-infections. Results: 49% of cases tested positive for at least one virus, of whom 10% had multiple infections. 53% of the FRI cases fulfilled the definition of influenza-like illness (ILI), of whom 52% were positive for at least one virus. The most frequent etiologies for mono-infections among FRI cases were Influenza A(H1N1)pdm09 (13%), Influenza B (13%) and coxsackevirus (9%). The sensitivity, specificity, positive predictive value and negative predictive value of ILI for influenza among FRI cases were 72%, 48%, 40% and 69% respectively. On logistic regression, there were marked differences in the prevalence of different symptoms and signs between viruses with fever more prevalent amongst influenza and adenovirus infections than other viruses. Conclusion: There are multiple viral etiologies for FRI and ILI with differing clinical symptoms in the Singapore military. Influenza and coxsackevirus were the most common etiology for FRI, while influenza and adenoviruses displayed the most febrile symptoms. Further studies should explore these differences and possible interventions. © 2014 Tan et al.; licensee BioMed Central Ltd.


Lam P.H.Y.,Biodefence Center | Boon C.S.,Biodefence Center | Yng N.Y.,Biodefence Center | Benjamin S.,Valent BioSciences Corporation
Southeast Asian Journal of Tropical Medicine and Public Health | Year: 2010

A Bacillus thuringiensis israelensis (Bti) formulation, VectoBac®WG (strain AM 65-52), was evaluated for mosquito control in a training area with dense vegetation. Bti was spray applied to target Aedes albopictus larval habitats of 130 ha once every 2 weeks using a motorized back pack mist blower, Stihl® SR420, and a vehicle mounted ultra low volume generator (ULV), IGEBA® U40. Ovitrap index (OI) and larval density (LD) were used to measure the efficacy of larviciding. In the Bti treated area the OI and LD significantly decreased with time (p < 0.05); OI decreased from 84.3 ± 1.7 to 27.5 ± 2.5 (%) and LD decreased from 27.9 ± 1.5 to 3.2 ± 1.8 larvae per ovitrap by 3 months from the start of treatment. During the same period of time there was no significant reduction in OI and LD at the untreated site which was under a conventional mosquito control program. This large scale study indicates larvicidal spraying with Bti of natural breeding sites, was able to reduce Ae. albopictus adult density. This significant reduction was not achieved with conventional manual application methods.


Seah S.G.-K.,National Diagnostics | Lim E.A.-S.,National Diagnostics | Kok-Yong S.,National Diagnostics | Liaw J.C.-W.,National Diagnostics | And 5 more authors.
Journal of Clinical Virology | Year: 2010

Background: Military personnel are highly susceptible to febrile respiratory illnesses (FRI), likely due to crowding, stress and other risk factors present in the military environment. Objective: Our objective was to investigate the viral etiological agents responsible for FRI among military recruits training in a tropical climate in Singapore. Study design: From March 2006 through April 2007, a total of 1354 oropharyngeal (throat) swabs were collected from military recruits who reported sick with an oral temperature of ≥38 °C and a cough and/or sore throat. Real-time polymerase chain reaction (PCR) was used to assay for the presence of influenza A and B viruses and adenoviruses (H-AdV), and conventional PCR used for the remaining respiratory viruses in all specimens. Results: Influenza A virus was the dominant infection with a laboratory-confirmed incidence of 24% (326/1354) and a predominance of the H3N2 subtype. The temporal pattern for influenza A virus infections coincided with the nation-wide pattern in the civilian community. Detection rates of 12% (159/1354) and 2.7% (5/1354) were obtained for influenza B virus and other respiratory viruses, respectively. Conclusions: The laboratory findings identified influenza A virus as the primary causative viral agent for FRI in the Singapore military, in strong contrast to findings from temperate countries and countries where recruits are often vaccinated for influenza. Our results suggest that influenza vaccination should be considered as a requirement to reduce the incidence of influenza infections. This is the first report describing respiratory infections in a tropical military setting, in a developed country in Asia. © 2010 Elsevier B.V.


PubMed | Defence Medical and Environmental Institute, Biodefence Center and London School of Hygiene and Tropical Medicine
Type: | Journal: Singapore medical journal | Year: 2016

Despite several phylogenetic studies on Plasmodium knowlesi (P. knowlesi), only cytochrome oxidase 1 (cox1) gene analysis has shown some geographical differentiation between the isolates of different countries.Phylogenetic analysis of locally acquired P. knowlesi infections, based on the circumsporozoite, small subunit ribosomal ribonucleic acid (SSU rRNA), merozoite surface protein 1 and cox1 gene targets, were performed. The results were compared with the published sequences of regional isolates from Malaysia and Thailand.Phylogenetic analysis of the circumsporozoite, SSU rRNA and merozoite surface protein 1 gene sequences for regional P. knowlesi isolates showed no obvious differentiation that could be attributed to their geographical origin. However, cox1 gene analysis showed that it was possible to differentiate between Singapore-acquired P. knowlesi infections and P. knowlesi infections from Peninsular Malaysia and Sarawak.The ability to differentiate between locally acquired P. knowlesi infections and imported P. knowlesi infections has important utility for the monitoring of P. knowlesi malaria control programmes in Singapore.

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