Mark I Chen

Publications of Mark I Chen

• Comparability of different methods for estimating influenza infection rates over a single epidemic wave.

  Authors: Vernon J Lee, Mark I Chen, Jonathan Yap, Jocelyn Ong, Wei-Yen Lim, Raymond T P Lin, Ian Barr, Jimmy B S Ong, Tze Minn Mak, Lee Gan Goh, Yee Sin Leo, Paul M Kelly, Alex R Cook

  American journal of epidemiology. 06/2011; 174(4):468-78.

  Estimation of influenza infection rates is important for determination of the extent of epidemic spread and for calculation of severity indicators. The authors compared estimated infection rates fromEstimation of influenza infection rates is important for determination of the extent of epidemic spread and for calculation of severity indicators. The authors compared estimated infection rates from paired and cross-sectional serologic surveys, rates of influenza like illness (ILI) obtained from sentinel general practitioners (GPs), and ILI samples that tested positive for influenza using data from similar periods collected during the 2009 H1N1 epidemic in Singapore. The authors performed sensitivity analyses to assess the robustness of estimates to input parameter uncertainties, and they determined sample sizes required for differing levels of precision. Estimates from paired seroconversion were 17% (95% Bayesian credible interval (BCI): 14, 20), higher than those from cross-sectional serology (12%, 95% BCI: 9, 17). Adjusted ILI estimates were 15% (95% BCI: 10, 25), and estimates computed from ILI and laboratory data were 12% (95% BCI: 8, 18). Serologic estimates were least sensitive to the risk of input parameter misspecification. ILI-based estimates were more sensitive to parameter misspecification, though this was lessened by incorporation of laboratory data. Obtaining a 5-percentage-point spread for the 95% confidence interval in infection rates would require more than 1,000 participants per serologic study, a sentinel network of 90 GPs, or 50 GPs when combined with laboratory samples. The various types of estimates will provide comparable findings if accurate input parameters can be obtained.

• Strategies for antiviral stockpiling for future influenza pandemics: a global epidemic-economic perspective.

  Authors: Luis R Carrasco, Vernon J Lee, Mark I Chen, David B Matchar, James P Thompson, Alex R Cook

  Journal of the Royal Society, Interface / the Royal Society. 02/2011; 8(62):1307-13.

  Influenza pandemics present a global threat owing to their potential mortality and substantial economic impacts. Stockpiling antiviral drugs to manage a pandemic is an effective strategy to offsetInfluenza pandemics present a global threat owing to their potential mortality and substantial economic impacts. Stockpiling antiviral drugs to manage a pandemic is an effective strategy to offset their negative impacts; however, little is known about the long-term optimal size of the stockpile under uncertainty and the characteristics of different countries. Using an epidemic-economic model we studied the effect on total mortality and costs of antiviral stockpile sizes for Brazil, China, Guatemala, India, Indonesia, New Zealand, Singapore, the UK, the USA and Zimbabwe. In the model, antivirals stockpiling considerably reduced mortality. There was greater potential avoidance of expected costs in the higher resourced countries (e.g. from $55 billion to $27 billion over a 30 year time horizon for the USA) and large avoidance of fatalities in those less resourced (e.g. from 11.4 to 2.3 million in Indonesia). Under perfect allocation, higher resourced countries should aim to store antiviral stockpiles able to cover at least 15 per cent of their population, rising to 25 per cent with 30 per cent misallocation, to minimize fatalities and economic costs. Stockpiling is estimated not to be cost-effective for two-thirds of the world's population under current antivirals pricing. Lower prices and international cooperation are necessary to make the life-saving potential of antivirals cost-effective in resource-limited countries.

• Effectiveness of pandemic H1N1-2009 vaccination in reducing laboratory confirmed influenza infections among military recruits in tropical Singapore.

  Authors: Vernon J Lee, Chi Hsien Tan, Jonathan Yap, Alex R Cook, Pei-Jun Ting, Jin-Phang Loh, Qiuhan Gao, Mark I Chen, Wee Lee Kang, Boon Huan Tan, Paul A Tambyah

  PloS one. 01/2011; 6(10):e26572.

  Limited information is available about pandemic H1N1-2009 influenza vaccine effectiveness in tropical communities. We studied the effectiveness of a pandemic H1N1 vaccination program in reducingLimited information is available about pandemic H1N1-2009 influenza vaccine effectiveness in tropical communities. We studied the effectiveness of a pandemic H1N1 vaccination program in reducing influenza cases in Singapore. A surveillance study was conducted among military personnel presenting with febrile respiratory illness from mid-2009 to mid-2010. Consenting individuals underwent nasal washes, which were tested with RT-PCR and subtyped. A vaccination program (inactivated monovalent Panvax H1N1-2009 vaccine) was carried out among recruits. A Bayesian hierarchical model was used to quantify relative risks in the pre- and post-vaccination periods. An autoregressive generalised linear model (GLM) was developed to minimise confounding. Of 2858 participants, 437 (15.3%), 60 (2.1%), and 273 (9.6%) had pandemic H1N1, H3N2, and influenza B. The ratio of relative risks for pandemic H1N1 infection before and after vaccination for the recruit camp relative to other camps was 0.14 (0.016,0.49); for H3N2, 0.44 (0.035,1.8); and for influenza B, 18 (0.77,89). Using the GLM for the recruit camp, post-vaccination weekly cases decreased by 54% (37%,67%, p<0.001) from that expected without vaccination; influenza B increased by 66 times (9-479 times, p<0.001); with no statistical difference for H3N2 (p = 0.54). Pandemic vaccination reduced H1N1-2009 disease burden among military recruits. Routine seasonal influenza vaccination should be considered.

• A clinical diagnostic model for predicting influenza among young adult military personnel with febrile respiratory illness in Singapore.

  Authors: Vernon J Lee, Jonathan Yap, Alex R Cook, Chi Hsien Tan, Jin-Phang Loh, Wee-Hong Koh, Elizabeth A S Lim, Jasper C W Liaw, Janet S W Chew, Iqbal Hossain, Ka Wei Chan, Pei-Jun Ting, Sock-Hoon Ng, Qiuhan Gao, Paul M Kelly, Mark I Chen, Paul A Tambyah, Boon Huan Tan

  PloS one. 01/2011; 6(3):e17468.

  Influenza infections present with wide-ranging clinical features. We aim to compare the differences in presentation between influenza and non-influenza cases among those with febrile respiratoryInfluenza infections present with wide-ranging clinical features. We aim to compare the differences in presentation between influenza and non-influenza cases among those with febrile respiratory illness (FRI) to determine predictors of influenza infection. Personnel with FRI (defined as fever ≥ 37.5 °C, with cough or sore throat) were recruited from the sentinel surveillance system in the Singapore military. Nasal washes were collected, and tested using the Resplex II and additional PCR assays for etiological determination. Interviewer-administered questionnaires collected information on patient demographics and clinical features. Univariate comparison of the various parameters was conducted, with statistically significant parameters entered into a multivariate logistic regression model. The final multivariate model for influenza versus non-influenza cases was used to build a predictive probability clinical diagnostic model. 821 out of 2858 subjects recruited from 11 May 2009 to 25 Jun 2010 had influenza, of which 434 (52.9%) had 2009 influenza A (H1N1), 58 (7.1%) seasonal influenza A (H3N2) and 269 (32.8%) influenza B. Influenza-positive cases were significantly more likely to present with running nose, chills and rigors, ocular symptoms and higher temperature, and less likely with sore throat, photophobia, injected pharynx, and nausea/vomiting. Our clinical diagnostic model had a sensitivity of 65% (95% CI: 58%, 72%), specificity of 69% (95% CI: 62%, 75%), and overall accuracy of 68% (95% CI: 64%, 71%), performing significantly better than conventional influenza-like illness (ILI) criteria. Use of a clinical diagnostic model may help predict influenza better than the conventional ILI definition among young adults with FRI.

• Republished paper: Populations and partnerships: insights from metapopulation and pair models into the epidemiology of gonorrhoea and other sexually transmitted infections.

  Authors: Mark I Chen, Azra C Ghani

  Sexually transmitted infections. 12/2010; 86 Suppl 3:iii63-69.

  Models of sexually transmitted infection (STI) transmission can offer insights as to why gonorrhoea and other STIs are disproportionately concentrated in epidemiologically distinct subpopulations. WeModels of sexually transmitted infection (STI) transmission can offer insights as to why gonorrhoea and other STIs are disproportionately concentrated in epidemiologically distinct subpopulations. We highlight two different constructs for modelling STIs by drawing on previously published work on pair and metapopulation models, and reanalysed partnership data from the National Survey of Sexual Attitudes and Lifestyles II (NATSAL II) in the UK. Pair models account for intrapair reinfections and are necessary to illustrate the importance of partnership dynamics. The pair modelling framework suggests that a key determinant of transmission is the length of time or 'gap' between partnerships, and that partnerships of medium length can potentially be more efficient for gonococcal transmission than the shortest partnerships. As for the metapopulation framework, one key insight is that the epidemiology of gonorrhoea is possibly being driven by subpopulations with higher than average concentrations of individuals with high sexual risk activity. The reanalysis of data on sexual behaviour in the UK shows that well recognised population subgroups at higher risk of gonorrhoea do also have higher levels of risk behaviour, such as a higher average number of new partners per year, as well as a higher prevalence of concurrent partnerships and short gaps before partnerships. The concentration of risk behaviour in key population subgroups may be leading to self-sustaining pockets of transmission for STIs. Combinations of partnership behaviours at the level of population subgroups should be a subject of future empirical research as well as modelling efforts.

• Effectiveness of public health measures in mitigating pandemic influenza spread: a prospective sero-epidemiological cohort study.

  Authors: Vernon J Lee, Jonathan Yap, Alex R Cook, Mark I Chen, Joshua K Tay, Ian Barr, Anne Kelso, Boon Huan Tan, Jin Phang Loh, Raymond Lin, Lin Cui, Paul M Kelly, Yee Sin Leo, Kee Seng Chia, Wee Lee Kang, Paul A Tambyah, Benjamin Seet

  The Journal of infectious diseases. 11/2010; 202(9):1319-26.

  Few studies have validated the effectiveness of public health interventions in reducing influenza spread in real‐life settings. We aim to validate these measures used during the 2009 pandemic. FromFew studies have validated the effectiveness of public health interventions in reducing influenza spread in real‐life settings. We aim to validate these measures used during the 2009 pandemic. From 22 June to 9 October 2009, we performed a prospective observational cohort study using paired serum samples and symptom review among 3 groups of Singapore military personnel. "Normal" units were subjected to prevailing pandemic response policies. "Essential" units and health care workers had additional public health interventions (eg, enhanced surveillance with isolation, segregation, personal protective equipment). Samples were tested by hemagglutination inhibition; the principal outcome was seroconversion to 2009 influenza A(H1N1). In total, 1015 individuals in 14 units completed the study, with 29% overall seroconversion. Seroconversion among essential units (17%) and health care workers (11%) was significantly lower than that in normal units (44%) (P = .001). Symptomatic illness attributable to influenza was also lower in essential units (5%) and health care workers (2%) than in normal units (12%) (P = .06). Adjusted for confounders, unit type was the only significant variable influencing overall seroconversion ( P < .05). From multivariate analysis within each unit, age (P < .001) and baseline antibody titer (P = .012 ) were inversely related to seroconversion risk. Public health measures are effective in limiting influenza transmission in closed environments.

• Populations and partnerships: insights from metapopulation and pair models into the epidemiology of gonorrhoea and other sexually transmitted infections.

  Authors: Mark I Chen, Azra C Ghani

  Sexually transmitted infections. 11/2010; 86(6):433-9.

  Models of sexually transmitted infection (STI) transmission can offer insights as to why gonorrhoea and other STIs are disproportionately concentrated in epidemiologically distinct subpopulations. WeModels of sexually transmitted infection (STI) transmission can offer insights as to why gonorrhoea and other STIs are disproportionately concentrated in epidemiologically distinct subpopulations. We highlight two different constructs for modelling STIs by drawing on previously published work on pair and metapopulation models, and reanalyzed partnership data from the National Survey of Sexual Attitudes and Lifestyles II (NATSAL II) in the UK. Pair models account for intrapair reinfections and are necessary to illustrate the importance of partnership dynamics. The pair modelling framework suggests that a key determinant of transmission is the length of time or 'gap' between partnerships, and that partnerships of medium length can potentially be more efficient for gonococcal transmission than the shortest partnerships. As for the metapopulation framework, one key insight is that the epidemiology of gonorrhoea is possibly being driven by subpopulations with higher than average concentrations of individuals with high sexual risk activity. The reanalysis of data on sexual behaviour in the UK shows that well recognised population subgroups at higher risk of gonorrhoea do also have higher levels of risk behaviour, such as a higher average number of new partners per year, as well as a higher prevalence of concurrent partnerships and short gaps before partnerships. The concentration of risk behaviour in key population subgroups may be leading to self-sustaining pockets of transmission for STIs. Combinations of partnership behaviours at the level of population subgroups should be a subject of future empirical research as well as modelling efforts.

• Oseltamivir ring prophylaxis for containment of 2009 H1N1 influenza outbreaks.

  Authors: Vernon J Lee, Jonathan Yap, Alex R Cook, Mark I Chen, Joshua K Tay, Boon Huan Tan, Jin Phang Loh, Seok Wei Chew, Wee Hong Koh, Raymond Lin, Lin Cui, Charlie W H Lee, Wing-Kin Sung, Christopher W Wong, Martin L Hibberd, Wee Lee Kang, Benjamin Seet, Paul A Tambyah

  The New England journal of medicine. 06/2010; 362(23):2166-74.

  From June 22 through June 25, 2009, four outbreaks of infection with the pandemic influenza A (H1N1) virus occurred in Singapore military camps. We report the efficacy of ring chemoprophylaxisFrom June 22 through June 25, 2009, four outbreaks of infection with the pandemic influenza A (H1N1) virus occurred in Singapore military camps. We report the efficacy of ring chemoprophylaxis (geographically targeted containment by means of prophylaxis) with oseltamivir to control outbreaks of 2009 H1N1 influenza in semiclosed environments. All personnel with suspected infection were tested and clinically isolated if infection was confirmed. In addition, we administered postexposure ring chemoprophylaxis with oseltamivir and segregated the affected military units to contain the spread of the virus. All personnel were screened three times weekly both for virologic infection, by means of nasopharyngeal swabs and reverse-transcriptase-polymerase-chain-reaction assay with sequencing, and for clinical symptoms, by means of questionnaires. A total of 1175 personnel were at risk across the four sites, with 1100 receiving oseltamivir prophylaxis. A total of 75 personnel (6.4%) were infected before the intervention, and 7 (0.6%) after the intervention. There was a significant reduction in the overall reproductive number (the number of new cases attributable to the index case), from 1.91 (95% credible interval, 1.50 to 2.36) before the intervention to 0.11 (95% credible interval, 0.05 to 0.20) after the intervention. Three of the four outbreaks showed a significant reduction in the rate of infection after the intervention. Molecular analysis revealed that all four outbreaks were derived from the New York lineage of the 2009 H1N1 virus and that cases within each outbreak were due to transmission rather than unrelated episodes of infection. Of the 816 personnel treated with oseltamivir who were surveyed, 63 (7.7%) reported mild, nonrespiratory side effects of the drug, with no severe adverse events. Oseltamivir ring chemoprophylaxis, together with prompt identification and isolation of infected personnel, was effective in reducing the impact of outbreaks of 2009 H1N1 influenza in semiclosed settings.

• Pandemic (H1N1) 2009: clinical and laboratory findings of the first fifty cases in Singapore.

  Authors: Monica Chan, Mark I Chen, Angela Chow, Caroline P S Lee, Adriana S H Tan, David Chien Lye, Yee Sin Leo

  Annals of the Academy of Medicine, Singapore. 04/2010; 39(4):267-6.

  Since the fi rst imported case on 26 May 2009, pandemic (H1N1) 2009 has spread from travellers and has resulted in sustained community transmission. Singapore began with a strict containment policySince the fi rst imported case on 26 May 2009, pandemic (H1N1) 2009 has spread from travellers and has resulted in sustained community transmission. Singapore began with a strict containment policy where all suspected and confirmed cases of pandemic (H1N1) 2009 were admitted for testing. We describe here the clinical and laboratory characteristics of the fi rst 50 adult cases with confirmed pandemic (H1N1) 2009. A review was conducted of medical notes of adult patients with confirmed pandemic (H1N1) 2009 by polymerase chain reaction assay from combined nasal and throat swabs admitted to the Communicable Disease Centre, Tan Tock Seng Hospital. From 26 May to 18 June 2009, 50 patients with a median age of 27 years old were admitted at a median of 3 days from illness onset. Half were male and all were travellers arriving in Singapore. Non-Singaporean citizens (38%) and other ethnic groups (40%) were over-represented. History of fever was reported in 90% and respiratory symptoms in 92%. Gastrointestinal symptoms were uncommon, present in 4% only. Temperatures on presentation of >or=38.0 degrees C, >or=37.8 degrees C and >or=37.5 degrees C were present in 48%, 56% and 76%, respectively. Only 46% of patients met the United States Centers for Disease Control and Prevention (US CDC) case definition of influenza-like illness (ILI). Clinical and laboratory findings were unremarkable for the majority. All cases were treated with oseltamivir and had uncomplicated recovery. Pandemic (H1N1) 2009 had mild clinical and laboratory findings in immunocompetent patients. Use of the US CDC ILI criteria alone would have detected less than half of confirmed cases.

• Serological response in RT-PCR confirmed H1N1-2009 influenza a by hemagglutination inhibition and virus neutralization assays: an observational study.

  Authors: Mark I Chen, Ian G Barr, Gerald C H Koh, Vernon J Lee, Caroline P S Lee, Robert Shaw, Cui Lin, Jonathan Yap, Alex R Cook, Boon Huan Tan, Jin Phang Loh, Timothy Barkham, Vincent T K Chow, Raymond T P Lin, Yee-Sin Leo

  PloS one. 01/2010; 5(8):e12474.

  We describe the serological response following H1N1-2009 influenza A infections confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The study included patients admitted toWe describe the serological response following H1N1-2009 influenza A infections confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The study included patients admitted to hospital, subjects of a seroepidemiologic cohort study, and participants identified from outbreak studies in Singapore. Baseline (first available blood sample) and follow-up blood samples were analyzed for antibody titers to H1N1-2009 and recently circulating seasonal influenza A virus strains by hemagglutination inhibition (HI) and virus micro-neutralization (VM) assays. 267 samples from 118 cases of H1N1-2009 were analyzed. Geometric mean titers by HI peaked at 123 (95% confidence interval, CI 43-356) between days 30 to 39. The chance of observing seroconversion (four-fold or greater increase of antibodies) was maximized when restricting analysis to 45 participants with baseline sera collected within 5 days of onset and follow-up sera collected 15 or more days after onset; for these participants, 82% and 89% seroconverted to A/California/7/2009 H1N1 by HI and VM respectively. A four-fold or greater increase in cross-reactive antibody titers to seasonal A/Brisbane/59/2007 H1N1, A/Brisbane/10/2007 H3N2 and A/Wisconsin/15/2009 H3N2 occurred in 20%, 18% and 16% of participants respectively. Appropriately timed paired serology detects 80-90% RT-PCR confirmed H1N1-2009; Antibodies from infection with H1N1-2009 cross-reacted with seasonal influenza viruses.

• Seroconversion and asymptomatic infections during oseltamivir prophylaxis against Influenza A H1N1 2009.

  Authors: Vernon J Lee, Jonathan Yap, Joshua K Tay, Ian Barr, Qiuhan Gao, Hanley J Ho, Boon Huan Tan, Paul M Kelly, Paul A Tambyah, Anne Kelso, Mark I Chen

  BMC infectious diseases. 01/2010; 10:164.

  Anti-viral prophylaxis is used to prevent the transmission of influenza. We studied serological confirmation of 2009 Influenza A (H1N1) infections during oseltamivir prophylaxis and after cessationAnti-viral prophylaxis is used to prevent the transmission of influenza. We studied serological confirmation of 2009 Influenza A (H1N1) infections during oseltamivir prophylaxis and after cessation of prophylaxis. Between 22 Jun and 16 Jul 09, we performed a cohort study in 3 outbreaks in the Singapore military where post-exposure oseltamivir ring chemoprophylaxis (75 mg daily for 10 days) was administered. The entire cohort was screened by RT-PCR (with HA gene primers) using nasopharyngeal swabs three times a week. Three blood samples were taken for haemagglutination inhibition testing--at the start of outbreak, 2 weeks after completion of 10 day oseltamivir prophylaxis, and 3 weeks after the pandemic's peak in Singapore. Questionnaires were also administered to collect clinical symptoms. 237 personnel were included for analysis. The overall infection rate of 2009 Influenza A (H1N1) during the three outbreaks was 11.4% (27/237). This included 11 index cases and 16 personnel (7.1%) who developed four-fold or higher rise in antibody titres during oseltamivir prophylaxis. Of these 16 personnel, 8 (3.5%) were symptomatic while the remaining 8 personnel (3.5%) were asymptomatic and tested negative on PCR. Post-cessation of prophylaxis, an additional 23 (12.1%) seroconverted. There was no significant difference in mean fold-rise in GMT between those who seroconverted during and post-prophylaxis (11.3 vs 11.7, p = 0.888). No allergic, neuropsychiatric or other severe side-effects were noted. Post-exposure oseltamivir prophylaxis reduced the rate of infection during outbreaks, and did not substantially increase subsequent infection rates upon cessation. Asymptomatic infections occur during prophylaxis, which may confer protection against future infection. Post-exposure prophylaxis is effective as a measure in mitigating pandemic influenza outbreaks.

• Economic analysis of pandemic influenza vaccination strategies in Singapore.

  Authors: Vernon J Lee, Mei Yin Tok, Vincent T Chow, Kai Hong Phua, Eng Eong Ooi, Paul A Tambyah, Mark I Chen

  PloS one. 01/2009; 4(9):e7108.

  BACKGROUND: All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares theBACKGROUND: All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore. METHODOLOGY: We analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling) compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay) depending on the perceived risk of the next pandemic occurring. PRINCIPAL FINDINGS: The treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4-0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups. CONCLUSIONS: The actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines.

• Improving the clinical diagnosis of influenza--a comparative analysis of new influenza A (H1N1) cases.

  Authors: Adrian K Ong, Mark I Chen, Li Lin, Adriana S Tan, Ni Win Nwe, Timothy Barkham, Seow Yian Tay, Yee Sin Leo

  PloS one. 01/2009; 4(12):e8453.

  The presentation of new influenza A(H1N1) is broad and evolving as it continues to affect different geographic locations and populations. To improve the accuracy of predicting influenza infection inThe presentation of new influenza A(H1N1) is broad and evolving as it continues to affect different geographic locations and populations. To improve the accuracy of predicting influenza infection in an outpatient setting, we undertook a comparative analysis of H1N1(2009), seasonal influenza, and persons with acute respiratory illness (ARI) in an outpatient setting. Comparative analyses of one hundred non-matched cases each of PCR confirmed H1N1(2009), seasonal influenza, and ARI cases. Multivariate analysis was performed to look for predictors of influenza infection. Receiver operating characteristic curves were constructed for various combinations of clinical and laboratory case definitions. The initial clinical and laboratory features of H1N1(2009) and seasonal influenza were similar. Among ARI cases, fever, cough, headache, rhinorrhea, the absence of leukocytosis, and a normal chest radiograph positively predict for both PCR-confirmed H1N1-2009 and seasonal influenza infection. The sensitivity and specificity of current WHO and CDC influenza-like illness (ILI) criteria were modest in predicting influenza infection. However, the combination of WHO ILI criteria with the absence of leukocytosis greatly improved the accuracy of diagnosing H1N1(2009) and seasonal influenza (positive LR of 7.8 (95%CI 3.5-17.5) and 9.2 (95%CI 4.1-20.3) respectively). The clinical presentation of H1N1(2009) infection is largely indistinguishable from that of seasonal influenza. Among patients with acute respiratory illness, features such as a temperature greater than 38 degrees C, rhinorrhea, a normal chest radiograph, and the absence of leukocytosis or significant gastrointestinal symptoms were all positively associated with H1N1(2009) and seasonal influenza infection. An enhanced ILI criteria that combines both a symptom complex with the absence of leukocytosis on testing can improve the accuracy of predicting both seasonal and H1N1-2009 influenza infection.

• A metapopulation modelling framework for gonorrhoea and other sexually transmitted infections in heterosexual populations.

  Authors: Mark I Chen, Azra C Ghani, W John Edmunds

  Journal of the Royal Society, Interface / the Royal Society. 12/2008;

  Gonorrhoea continues to be a public health problem in the UK, and is the second most common bacterial sexually transmitted infection (STI) after chlamydia. In the UK, gonorrhoea is disproportionatelyGonorrhoea continues to be a public health problem in the UK, and is the second most common bacterial sexually transmitted infection (STI) after chlamydia. In the UK, gonorrhoea is disproportionately concentrated in epidemiologically distinct subpopulations, with much higher incidence rates in young people, some ethnic minorities and inner city subpopulations. The original model of STI transmission proposed by Hethcote and Yorke explained some of these features through the concept of the 'core group'. Since then, several authors have modified the original model approach to include multiple sexual activity classes, but found this modelling approach to be inadequate when applied to low-prevalence settings such as the UK. We present a metapopulation framework for modelling gonorrhoea and other STIs. The model proposes that the epidemiology of gonorrhoea is largely driven by subpopulations with higher than average concentrations of individuals with high sexual risk activity. We show how this conceptualization of gonococcal epidemiology overcomes key limitations associated with some of the prior efforts to model gonorrhoea. We also use the model to explain several epidemiological features of gonorrhoea, such as its asymmetric distribution across subpopulations, and the contextual risk experienced by members of at-risk subpopulations. Finally, we extend the model to explain the distribution of other STIs, using chlamydia as an example of a more ubiquitous bacterial STI.

• Twentieth century influenza pandemics in singapore.

  Authors: Vernon J Lee, Chia Siong Wong, Paul A Tambyah, Jeffery Cutter, Mark I Chen, Kee Tai Goh

  Annals of the Academy of Medicine, Singapore. 07/2008; 37(6):470-7.

  Introduction: Singapore was substantially affected by three 20th Century pandemics. This study describes the course of the pandemics, and the preventive measures adopted. Materials and Methods: WeIntroduction: Singapore was substantially affected by three 20th Century pandemics. This study describes the course of the pandemics, and the preventive measures adopted. Materials and Methods: We reviewed and researched a wide range of material including peer-reviewed journal articles, Ministry of Health reports, Straits Settlements reports and newspaper articles. Monthly mortality data were obtained from various official sources in Singapore. Results: The 1918 epidemic in Singapore occurred in 2 waves - June to July, and October to November - resulting in up to 3500 deaths. The 1957 epidemic occurred in May, and resulted in widespread morbidity, with 77,000 outpatient attendances in government clinics alone. The 1968 epidemic occurred in August and lasted a few weeks, with outpatient attendances increasing by more than 65%. The preventive measures instituted by the Singapore government during the pandemics included the closure of schools, promulgation of public health messages, setting up of influenza treatment centres, and screening at ports. Students, businessmen and healthcare workers were all severely affected by the pandemics. Conclusions: Tropical cities should be prepared in case of a future pandemic. Some of the preventive measures used in previous pandemics may be applicable during the next pandemic.

• Mind the gap: the role of time between sex with two consecutive partners on the transmission dynamics of gonorrhea.

  Authors: Mark I Chen, Azra C Ghani, John Edmunds

  Sexually transmitted diseases. 06/2008; 35(5):435-44.

  OBJECTIVE: Both the duration of sexual partnerships and the time between two consecutive partnerships (gap length) varies between populations. We use a mathematical model with multiple partnershipOBJECTIVE: Both the duration of sexual partnerships and the time between two consecutive partnerships (gap length) varies between populations. We use a mathematical model with multiple partnership durations and gap lengths to identify the types of relationship cycles that sustain gonorrhea transmission in the United Kingdom. STUDY DESIGN: A mathematical model for gonorrhea transmission was constructed which tracks the duration of partnerships and their preceding gap lengths. The National Survey of Sexual Attitudes and Lifestyles was used to parameterize the model population into 5 different partnership lengths (mean of 1 day, 2 weeks, 8 weeks, 30 weeks, and 10 years) and 3 preceding gap lengths (14 days, 8 weeks, and 1.5 years). RESULTS: The model was able to reproduce patterns of gonococcal infection in the United Kingdom. Assortative (like-with-like) mixing of individuals with short gaps between partnerships was required for gonorrhea infection to persist. Prevalence was highest in individuals with short (>1 day-<1 month) and midterm partnership durations (>1 month-<3 months). Interventions (such as increased condom use) targeted at those with medium-term partnerships were most effective at reducing prevalence; in contrast targeting interventions at those with short partnerships but longer gap lengths (i.e., the group with the highest number of sexual partners) had relatively less impact. CONCLUSION: Our model suggests that gonorrhea is sustained by the presence of a small group of individuals with short gap lengths and medium length partnerships. Interventions targeted at this group are more effective than those targeted at individuals with high numbers of sexual partners but longer gap lengths.

• Influenza pandemics in Singapore, a tropical, globally connected city.

  Authors: Vernon J Lee, Mark I Chen, Slew Pang Chan, Chia Siong Wong, Jeffery Cutter, Kee Tai Goh, Paul Anath Tambyah

  Emerging infectious diseases. 08/2007; 13(7):1052-7.

  Tropical cities such as Singapore do not have well-defined influenza seasons but have not been spared from influenza pandemics. The 1918 epidemic in Singapore, which was then already a major globalTropical cities such as Singapore do not have well-defined influenza seasons but have not been spared from influenza pandemics. The 1918 epidemic in Singapore, which was then already a major global trading hub, occurred in 2 waves, June-July, and October-November, and resulted in > or = 2,870 deaths. The excess mortality rate was higher than that for industrialized nations in the Northern Hemisphere but lower than that for less industrialized countries in Asia and Africa. The 1957 epidemic occurred in May and resulted in widespread illness. The 1968 epidemic occurred in August and lasted a few weeks, again with widespread illness. Tropical cities may be affected early in a pandemic and have higher mortality rates. With the increase in travel and trade, a future pandemic may reach a globally connected city early and spread worldwide. Preparedness and surveillance plans must be developed to include the megacities of the tropical world.

• Fatal dengue hemorrhagic fever in adults during a dengue epidemic in Singapore.

  Authors: Adrian Ong, Mya Sandar, Mark I Chen, Leo Yee Sin

  International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 06/2007; 11(3):263-7.

  BACKGROUND: Dengue fever has seen a significant re-emergence in Southeast Asia. Associated with the rise of dengue has been the increase in dengue-associated mortality. To better understand theBACKGROUND: Dengue fever has seen a significant re-emergence in Southeast Asia. Associated with the rise of dengue has been the increase in dengue-associated mortality. To better understand the predictors of mortality, we conducted a review of hospitalized adult dengue infections within our institution. METHODS: This was a retrospective case-control study of dengue-associated deaths at a large tertiary care hospital. RESULTS: In 2004, of 3186 cases of dengue fever (DF)/hemorrhagic dengue fever (DHF) admitted to our institution, there were 130 cases of DHF and seven dengue-associated deaths (case-fatality rate 5.4%). At least three of the seven fatal cases had serological evidence of primary dengue infection. All dengue-mortality cases had rapidly progressive clinical deterioration at an average of day 4 of fever with intensive care admission occurring on a mean of 5.6 days of fever. Adult respiratory distress syndrome, disseminated intravascular coagulopathy, and multi-organ failure were the most common causes of death despite early hospitalization, intravenous fluid, and blood-product support. CONCLUSION: Dengue is associated with severe disease, and deaths do occur despite current supportive management. Fatal DHF/dengue shock syndrome (DSS) does occur in adults and in primary dengue infection. Better early predictors of disease severity and clinical interventions are needed.

• Effectiveness of neuraminidase inhibitors for preventing staff absenteeism during pandemic influenza.

  Authors: Vernon J Lee, Mark I Chen

  Emerging infectious diseases. 03/2007; 13(3):449-57.

  We used a deterministic SEIR (susceptible-exposed-infectious-removed) meta-population model, together with scenario, sensitivity, and simulation analyses, to determine stockpiling strategies forWe used a deterministic SEIR (susceptible-exposed-infectious-removed) meta-population model, together with scenario, sensitivity, and simulation analyses, to determine stockpiling strategies for neuraminidase inhibitors that would minimize absenteeism among healthcare workers. A pandemic with a basic reproductive number (R0) of 2.5 resulted in peak absenteeism of 10%. Treatment decreased peak absenteeism to 8%, while 8 weeks' prophylaxis reduced it to 2%. For pandemics with higher R0, peak absenteeism exceeded 20% occasionally and 6 weeks' prophylaxis reduced peak absenteeism by 75%. Insufficient duration of prophylaxis increased peak absenteeism compared with treatment only. Earlier pandemic detection and initiation of prophylaxis may render shorter prophylaxis durations ineffective. Eight weeks' prophylaxis substantially reduced peak absenteeism under a broad range of assumptions for severe pandemics (peak absenteeism > 10%). Small investments in treatment and prophylaxis, if adequate and timely, can reduce absenteeism among essential staff.

• Using autoregressive integrated moving average (ARIMA) models to predict and monitor the number of beds occupied during a SARS outbreak in a tertiary hospital in Singapore.

  Authors: Arul Earnest, Mark I Chen, Donald Ng, Leo Yee Sin

  BMC health services research. 02/2005; 5:36.

  BACKGROUND: The main objective of this study is to apply autoregressive integrated moving average (ARIMA) models to make real-time predictions on the number of beds occupied in Tan Tock SengBACKGROUND: The main objective of this study is to apply autoregressive integrated moving average (ARIMA) models to make real-time predictions on the number of beds occupied in Tan Tock Seng Hospital, during the recent SARS outbreak. METHODS: This is a retrospective study design. Hospital admission and occupancy data for isolation beds was collected from Tan Tock Seng hospital for the period 14th March 2003 to 31st May 2003. The main outcome measure was daily number of isolation beds occupied by SARS patients. Among the covariates considered were daily number of people screened, daily number of people admitted (including observation, suspect and probable cases) and days from the most recent significant event discovery. We utilized the following strategy for the analysis. Firstly, we split the outbreak data into two. Data from 14th March to 21st April 2003 was used for model development. We used structural ARIMA models in an attempt to model the number of beds occupied. Estimation is via the maximum likelihood method using the Kalman filter. For the ARIMA model parameters, we considered the simplest parsimonious lowest order model. RESULTS: We found that the ARIMA (1,0,3) model was able to describe and predict the number of beds occupied during the SARS outbreak well. The mean absolute percentage error (MAPE) for the training set and validation set were 5.7% and 8.6% respectively, which we found was reasonable for use in the hospital setting. Furthermore, the model also provided three-day forecasts of the number of beds required. Total number of admissions and probable cases admitted on the previous day were also found to be independent prognostic factors of bed occupancy. CONCLUSION: ARIMA models provide useful tools for administrators and clinicians in planning for real-time bed capacity during an outbreak of an infectious disease such as SARS. The model could well be used in planning for bed-capacity during outbreaks of other infectious diseases as well.