Jonathan Yap

Publications of Jonathan Yap

• 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.

• 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.

• Investigation of causes of oseltamivir chemoprophylaxis failures during influenza A (H1N1-2009) outbreaks.

  Authors: Vernon J Lee, Jonathan Yap, Sebastian Maurer-Stroh, Raphael T C Lee, Frank Eisenhaber, Joshua K Tay, Pei Jun Ting, Jin Phang Loh, Christopher W Wong, Boon Huan Tan, Evelyn S C Koay, Paul M Kelly, Martin L Hibberd

  Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 02/2011; 50(2):104-8.

  Antiviral post-exposure prophylaxis with oseltamivir has been used as a strategy in mitigating the Influenza A (H1N1-2009) pandemic. There have been few reports of well-documented prophylaxisAntiviral post-exposure prophylaxis with oseltamivir has been used as a strategy in mitigating the Influenza A (H1N1-2009) pandemic. There have been few reports of well-documented prophylaxis failures and the reasons for failure. We report herein a series of 10 cases of prophylaxis failures and explore the reasons behind their prophylaxis failure. In the early pandemic phase, the military employed oseltamivir post-exposure ring-prophylaxis of affected units. From June 22 to July 30, 2009, cases of laboratory-confirmed prophylaxis failures were identified. Nasopharyngeal swabs were collected and tested by PCR. Samples with sufficient RNA material were sent for whole genome sequencing, and screened for mutations that confer oseltamivir resistance, especially the H275Y mutation. Ten cases of laboratory-confirmed prophylaxis failure were identified, with a mean age of 22.3 years. One case was asymptomatic; the remaining 9 had fever or cough but without severe complications. The mean duration of exposure before starting oseltamivir was 1.9 days (SD 0.9), while the mean duration of oseltamivir consumption before symptom onset was 1.9 days (SD 1.4). None of the samples had the H275Y mutation or other known mutations that confer resistance. From the whole genome sequencing, several mutations at the HA (T220S, E275V, T333A, D239G); PB2 (K660R, L607V, V292I); NS1 (F103S), and NP (W104G) gene segments were detected, but none of them were likely to result in anti-viral resistance. Primary prophylaxis failures exhibited mild symptoms without complications; all did not have the H275Y mutation and were unlikely to result from other mutations.

• 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.

• Inactivated trivalent seasonal influenza vaccine induces limited cross-reactive neutralizing antibody responses against 2009 pandemic and 1934 PR8 H1N1 strains.

  Authors: Vernon J Lee, Joshua K Tay, Mark I C Chen, M C Phoon, M L Xie, Y Wu, Cynthia X X Lee, Jonathan Yap, K R Sakharkar, M K Sakharkar, Raymond T Lin, Lin Cui, Paul M Kelly, Yee Sin Leo, Yee Joo Tan, Vincent T K Chow

  Vaccine. 10/2010; 28(42):6852-7.

  In June 2009, we conducted a prospective study in Singapore on 51 individuals to determine their serologic responses before and following receipt of the 2009 Southern Hemisphere seasonal influenzaIn June 2009, we conducted a prospective study in Singapore on 51 individuals to determine their serologic responses before and following receipt of the 2009 Southern Hemisphere seasonal influenza vaccine. Paired serum samples were obtained before and 3-4 weeks after vaccination. Virus microneutralization assays were performed to quantify antibodies against A/Brisbane/59/2007 vaccine, pandemic H1N1-2009 and A/Puerto Rico/08/34 H1N1 strains. Post-vaccination, 43%, 12% and 24% of subjects displayed a 4-fold or greater rise in neutralizing antibody titers against the three strains, respectively. There was a positive correlation among individuals who showed increased titers to both pandemic H1N1-2009 and A/Puerto Rico/08/34 (p<0.001). However, this correlation was not observed for A/Brisbane/59/2007 with either strain. The relative conservation and accessibility of predicted B-cell epitopes may explain the limited cross-reactivity of the antibodies directed against common H1N1 epitopes. These results suggest that seasonal influenza vaccination confers a certain degree of cross-protection to other H1N1 strains. The correlation in cross-reactive antibody titers to A/Puerto Rico/08/34 and pandemic H1N1-2009 implies that previous exposure to pre-1957 H1N1 strains may confer some protection against the 2009 pandemic strain.

• 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.

• Knowledge, attitudes and practices towards pandemic influenza among cases, close contacts, and healthcare workers in tropical Singapore: a cross-sectional survey

  Authors: Jonathan Yap, Vernon Lee, Teng Yau, Tze Ng, Phern-Chern Tor

  BMC Public Health. 01/2010;

  Abstract Background Effective influenza pandemic management requires understanding of the factors influencing behavioral changes. We aim to determine the differences in knowledge, attitudes andAbstract 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.

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

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

  BMC Infectious Diseases. 01/2010;

  Abstract Background Anti-viral prophylaxis is used to prevent the transmission of influenza. We studied serological confirmation of 2009 Influenza A (H1N1) infections during oseltamivir prophylaxisAbstract Background 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 cessation of prophylaxis. Methods 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. Results 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. Conclusions 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.

• 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.

• Knowledge, attitudes and practices towards pandemic influenza among cases, close contacts, and healthcare workers in tropical Singapore: a cross-sectional survey.

  Authors: Jonathan Yap, Vernon J Lee, Teng Yan Yau, Tze Pin Ng, Phern-Chern Tor

  BMC public health. 01/2010; 10:442.

  Effective influenza pandemic management requires understanding of the factors influencing behavioral changes. We aim to determine the differences in knowledge, attitudes and practices in variousEffective 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. 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. 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). 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.

• Influenza excess mortality from 1950-2000 in tropical Singapore.

  Authors: Vernon J Lee, Jonathan Yap, Jimmy B S Ong, Kwai Peng Chan, Raymond T P Lin, Siew Pang Chan, Kee Tai Goh, Yee Sin Leo, Mark I-Cheng Chen

  PloS one. 01/2009; 4(12):e8096.

  INTRODUCTION: Tropical regions have been shown to exhibit different influenza seasonal patterns compared to their temperate counterparts. However, there is little information about the burden ofINTRODUCTION: Tropical regions have been shown to exhibit different influenza seasonal patterns compared to their temperate counterparts. However, there is little information about the burden of annual tropical influenza epidemics across time, and the relationship between tropical influenza epidemics compared with other regions. METHODS: Data on monthly national mortality and population was obtained from 1947 to 2003 in Singapore. To determine excess mortality for each month, we used a moving average analysis for each month from 1950 to 2000. From 1972, influenza viral surveillance data was available. Before 1972, information was obtained from serial annual government reports, peer-reviewed journal articles and press articles. RESULTS: The influenza pandemics of 1957 and 1968 resulted in substantial mortality. In addition, there were 20 other time points with significant excess mortality. Of the 12 periods with significant excess mortality post-1972, only one point (1988) did not correspond to a recorded influenza activity. For the 8 periods with significant excess mortality periods before 1972 excluding the pandemic years, 2 years (1951 and 1953) had newspaper reports of increased pneumonia deaths. Excess mortality could be observed in almost all periods with recorded influenza outbreaks but did not always exceed the 95% confidence limits of the baseline mortality rate. CONCLUSION: Influenza epidemics were the likely cause of most excess mortality periods in post-war tropical Singapore, although not every epidemic resulted in high mortality. It is therefore important to have good influenza surveillance systems in place to detect influenza activity.

• Inactivated trivalent seasonal influenza vaccine induces limited cross-reactive neutralizing antibody responses against 2009 pandemic and 1934 PR8 H1N1 strains

  Authors: Vernon J. Lee, Joshua K. Tay, Mark I.C. Chen, M.C. Phoon, M.L. Xie, Y. Wu, Cynthia X.X. Lee, Jonathan Yap, K.R. Sakharkar, M.K. Sakharkar, Raymond T. Lin, Lin Cui, Paul M. Kelly, Yee Sin Leo, Yee Joo Tan, Vincent T.K. Chow

  Vaccine.

  BackgroundIn June 2009, we conducted a prospective study in Singapore on 51 individuals to determine their serologic responses before and following receipt of the 2009 Southern Hemisphere seasonalBackgroundIn June 2009, we conducted a prospective study in Singapore on 51 individuals to determine their serologic responses before and following receipt of the 2009 Southern Hemisphere seasonal influenza vaccine.Materials and methodsPaired serum samples were obtained before and 3–4 weeks after vaccination. Virus microneutralization assays were performed to quantify antibodies against A/Brisbane/59/2007 vaccine, pandemic H1N1-2009 and A/Puerto Rico/08/34 H1N1 strains.ResultsPost-vaccination, 43%, 12% and 24% of subjects displayed a 4-fold or greater rise in neutralizing antibody titers against the three strains, respectively. There was a positive correlation among individuals who showed increased titers to both pandemic H1N1-2009 and A/Puerto Rico/08/34 (p < 0.001). However, this correlation was not observed for A/Brisbane/59/2007 with either strain. The relative conservation and accessibility of predicted B-cell epitopes may explain the limited cross-reactivity of the antibodies directed against common H1N1 epitopes.ConclusionsThese results suggest that seasonal influenza vaccination confers a certain degree of cross-protection to other H1N1 strains. The correlation in cross-reactive antibody titers to A/Puerto Rico/08/34 and pandemic H1N1-2009 implies that previous exposure to pre-1957 H1N1 strains may confer some protection against the 2009 pandemic strain.