Alex R Cook

Publications of Alex R Cook

• Differing clinical characteristics between influenza strains among young healthy adults in the tropics.

  Authors: Jonathan Yap, Chi Hsien Tan, Alex R Cook, Jin Phang Loh, Paul A Tambyah, Boon Huan Tan, Vernon J Lee

  BMC infectious diseases. 01/2012; 12(1):12.

  ABSTRACT: Influenza infections may result in different clinical presentations. This study aims to determine the clinical differences between circulating influenza strains in a young healthy adultABSTRACT: 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. 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. 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. 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.

• Risk factors for cluster outbreaks of avian influenza A H5N1 infection, Indonesia.

  Authors: Tjandra Y Aditama, Gina Samaan, Rita Kusriastuti, Wilfried H Purba, Misriyah, Hari Santoso, Arie Bratasena, Anas Maruf, Elvieda Sariwati, Vivi Setiawaty, Alex R Cook, Mark S Clements, Kamalini Lokuge, Paul M Kelly, I Nyoman Kandun

  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 12/2011; 53(12):1237-44.

  By 30 July 2009, Indonesia had reported 139 outbreaks of avian influenza (AI) H5N1 infection in humans. Risk factors for case clustering remain largely unknown. This study assesses risk factors forBy 30 July 2009, Indonesia had reported 139 outbreaks of avian influenza (AI) H5N1 infection in humans. Risk factors for case clustering remain largely unknown. This study assesses risk factors for cluster outbreaks and for secondary case infection. The 113 sporadic and 26 cluster outbreaks were compared on household and individual level variables. Variables assessed include those never reported previously, including household size and genealogical relationships between cases and their contacts. Cluster outbreaks had larger households and more blood-related contacts, especially first-degree relatives, compared with sporadic case outbreaks. Risk factors for cluster outbreaks were the number of first-degree blood-relatives to the index case (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI]: 1.20-1.86) and index cases having direct exposure to sources of AI H5N1 virus (aOR, 3.20; 95% CI: 1.15-8.90). Risk factors for secondary case infection were being aged between 5 and 17 years (aOR, 8.32; 95% CI: 1.72-40.25), or 18 and 30 years (aOR, 6.04; 95% CI: 1.21-30.08), having direct exposure to sources of AI H5N1 virus (aOR, 3.48; 95% CI: 1.28-9.46), and being a first-degree relative to an index case (aOR, 11.0; 95% CI: 1.43-84.66). Siblings to index cases were 5 times more likely to become secondary cases (OR, 4.72; 95% CI: 1.67-13.35). The type of exposure and the genealogical relationship between index cases and their contacts impacts the risk of clustering. The study adds evidence that AI H5N1 infection is influenced by, and may even depend on, host genetic susceptibility.

• Economic impact of dengue illness and the cost-effectiveness of future vaccination programs in Singapore.

  Authors: Luis R Carrasco, Linda K Lee, Vernon J Lee, Eng Eong Ooi, Donald S Shepard, Tun L Thein, Victor Gan, Alex R Cook, David Lye, Lee Ching Ng, Yee Sin Leo

  PLoS neglected tropical diseases. 12/2011; 5(12):e1426.

  Dengue illness causes 50-100 million infections worldwide and threatens 2.5 billion people in the tropical and subtropical regions. Little is known about the disease burden and economic impact ofDengue illness causes 50-100 million infections worldwide and threatens 2.5 billion people in the tropical and subtropical regions. Little is known about the disease burden and economic impact of dengue in higher resourced countries or the cost-effectiveness of potential dengue vaccines in such settings. We estimate the direct and indirect costs of dengue from hospitalized and ambulatory cases in Singapore. We consider inter alia the impacts of dengue on the economy using the human-capital and the friction cost methods. Disease burden was estimated using disability-adjusted life years (DALYs) and the cost-effectiveness of a potential vaccine program was evaluated. The average economic impact of dengue illness in Singapore from 2000 to 2009 in constant 2010 US$ ranged between $0.85 billion and $1.15 billion, of which control costs constitute 42%-59%. Using empirically derived disability weights, we estimated an annual average disease burden of 9-14 DALYs per 100 000 habitants, making it comparable to diseases such as hepatitis B or syphilis. The proportion of symptomatic dengue cases detected by the national surveillance system was estimated to be low, and to decrease with age. Under population projections by the United Nations, the price per dose threshold for which vaccines stop being more cost-effective than the current vector control program ranged from $50 for mass vaccination requiring 3 doses and only conferring 10 years of immunity to $300 for vaccination requiring 2 doses and conferring lifetime immunity. The thresholds for these vaccine programs to not be cost-effective for Singapore were $100 and $500 per dose respectively. Dengue illness presents a serious economic and disease burden in Singapore. Dengue vaccines are expected to be cost-effective if reasonably low prices are adopted and will help to reduce the economic and disease burden of dengue in Singapore substantially.

• Risk factors for pandemic (H1N1) 2009 seroconversion among adults, Singapore, 2009.

  Authors: Wei-Yen Lim, Cynthia H J Chen, Yi Ma, Mark I C Chen, Vernon J M Lee, Alex R Cook, Linda W L Tan, Norberto Flores Tabo, Ian Barr, Lin Cui, Raymond T P Lin, Yee Sin Leo, Kee Seng Chia

  Emerging infectious diseases. 08/2011; 17(8):1455-62.

  A total of 828 community-dwelling adults were studied during the course of the pandemic (H1N1) 2009 outbreak in Singapore during June-September 2009. Baseline blood samples were obtained before theA total of 828 community-dwelling adults were studied during the course of the pandemic (H1N1) 2009 outbreak in Singapore during June-September 2009. Baseline blood samples were obtained before the outbreak, and 2 additional samples were obtained during follow-up. Seroconversion was defined as a >4-fold increase in antibody titers to pandemic (H1N1) 2009, determined by using hemagglutination inhibition. Men were more likely than women to seroconvert (mean adjusted hazards ratio [HR] 2.23, mean 95% confidence interval [CI] 1.26-3.93); Malays were more likely than Chinese to seroconvert (HR 2.67, 95% CI 1.04-6.91). Travel outside Singapore during the study period was associated with seroconversion (HR 1.76, 95% CI 1.11-2.78) as was use of public transport (HR 1.81, 95% CI 1.05-3.09). High baseline antibody titers were associated with reduced seroconversion. This study suggests possible areas for intervention to reduce transmission during future influenza outbreaks.

• 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.

• 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.

• Internet search limitations and pandemic influenza, Singapore.

  Authors: Alex R Cook, Mark I C Chen, Raymond Tzer Pin Lin

  Emerging infectious diseases. 10/2010; 16(10):1647-9.

  To the Editor: In the past few years, several publications have reported that Internet search queries may usefully supplement other, traditional surveillance programs for infectious diseases (1-3).To the Editor: In the past few years, several publications have reported that Internet search queries may usefully supplement other, traditional surveillance programs for infectious diseases (1-3). The philanthropic arm of Google offers Flu Trends, a site that provides up-to-date estimates of influenza activity in 20 countries of the Pacific Rim and Europe (4) by using data mining techniques to find good predictors of historic influenza indicators (1).

• Risk factors for pandemic (H1N1) 2009 virus seroconversion among hospital staff, Singapore.

  Authors: Mark I C Chen, Vernon J M Lee, Ian Barr, Cui Lin, Rachelle Goh, Caroline Lee, Baldev Singh, Jessie Tan, Wei Yen Lim, Alex R Cook, Brenda Ang, Angela Chow, Boon Huan Tan, Jimmy Loh, Robert Shaw, Kee Seng Chia, Raymond T P Lin, Yee Sin Leo

  Emerging infectious diseases. 10/2010; 16(10):1554-61.

  We describe incidence and risk factors for pandemic (H1N1) 2009 virus infection in healthcare personnel during the June-September 2009 epidemic in Singapore. Personnel contributed 3 serologic samplesWe describe incidence and risk factors for pandemic (H1N1) 2009 virus infection in healthcare personnel during the June-September 2009 epidemic in Singapore. Personnel contributed 3 serologic samples during June-October 2009, with seroconversion defined as a ≥4-fold increase in hemagglutination inhibition titers to pandemic (H1N1) 2009. Of 531 participants, 35 showed evidence of seroconversion. Seroconversion rates were highest in nurses (28/290) and lowest in allied health staff (2/116). Significant risk factors on multivariate analysis were being a nurse (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] 1.0-19.6) and working in pandemic (H1N1) 2009 isolation wards (aOR 4.5, 95% CI 1.3-15.6). Contact with pandemic (H1N1) 2009-infected colleagues (aOR 2.5, 95% CI 0.9-6.6) and larger household size (aOR 1.2, 95% CI 1.0-1.4) were of borderline significance. Our study suggests that seroconversion was associated with occupational and nonoccupational risk factors.

• 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.

• 2009 influenza A(H1N1) seroconversion rates and risk factors among distinct adult cohorts in Singapore.

  Authors: Mark I C Chen, Vernon J M Lee, Wei-Yen Lim, Ian G Barr, Raymond T P Lin, Gerald C H Koh, Jonathan Yap, Lin Cui, Alex R Cook, Karen Laurie, Linda W L Tan, Boon Huan Tan, Jimmy Loh, Robert Shaw, Chris Durrant, Vincent T K Chow, Anne Kelso, Kee Seng Chia, Yee Sin Leo

  JAMA : the journal of the American Medical Association. 04/2010; 303(14):1383-91.

  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. To compare theSingapore 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. To compare the risk and factors associated with H1N1 seroconversion in different adult cohorts. 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. A 4-fold or greater increase in titer between any of the 3 serological samples was defined as evidence of H1N1 seroconversion. 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 long-term 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). 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.

• 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.

• Real-time epidemic monitoring and forecasting of H1N1-2009 using influenza-like illness from general practice and family doctor clinics in Singapore.

  Authors: Jimmy Boon Som Ong, Mark I-Cheng Chen, Alex R Cook, Huey Chyi Lee, Vernon J Lee, Raymond Tzer Pin Lin, Paul Ananth Tambyah, Lee Gan Goh

  PloS one. 01/2010; 5(4):e10036.

  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 itReporting 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. 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 (degrees 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 degrees 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. 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.