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Search Results: 1 - 10 of 480311 matches for " Paul A. Tambyah "
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Differing clinical characteristics between influenza strains among young healthy adults in the tropics
Jonathan Yap, Chi Tan, Alex R Cook, Jin Loh, Paul A Tambyah, Boon Tan, Vernon J Lee
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-12
Abstract: 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.Influenza infections arising from different influenza strains may result in different c
microRNAs in Circulation Are Altered in Response to Influenza A Virus Infection in Humans
Paul A. Tambyah, Sugunavathi Sepramaniam, Jaminah Mohamed Ali, Siaw Ching Chai, Priyadharshini Swaminathan, Arunmozhiarasi Armugam, Kandiah Jeyaseelan
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076811
Abstract: Changes in microRNA expression have been detected in vitro in influenza infected cells, yet little is known about them in patients. microRNA profiling was performed on whole blood of H1N1 patients to identify signature microRNAs to better understand the gene regulation involved and possibly improve diagnosis. Total RNA extracted from blood samples of influenza infected patients and healthy controls were subjected to microRNA microarray. Expression profiles of circulating microRNAs were altered and distinctly different in influenza patients. Expression of highly dysregulated microRNAs were validated using quantitative PCR. Fourteen highly dysregulated miRNAs, identified from the blood of influenza infected patients, provided a clear distinction between infected and healthy individuals. Of these, expression of miR-1260, -26a, -335*, -576-3p, -628-3p and -664 were consistently dysregulated in both whole blood and H1N1 infected cells. Potential host and viral gene targets were identified and the impact of microRNA dysregulation on the host proteome was studied. Consequences of their altered expression were extrapolated to changes in the host proteome expression. These highly dysregulated microRNAs may have crucial roles in influenza pathogenesis and are potential biomarkers of influenza.
Seroconversion and asymptomatic infections during oseltamivir prophylaxis against Influenza A H1N1 2009
Vernon J Lee, Jonathan Yap, Joshua K Tay, Ian Barr, Qiuhan Gao, Hanley J Ho, Boon Tan, Paul M Kelly, Paul A Tambyah, Anne Kelso, Mark I Chen
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-164
Abstract: 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.Anti-viral prophylaxis has been used as a strategy to prevent the transmission and spread of influenza. Post-exposure prophylaxis with oseltamivir, a commonly used neuraminidase-inhibitor, has been shown to be effective in preventing the development of clinical disease against seasonal influenza when used against household contacts [1,2].
Economic Analysis of Pandemic Influenza Vaccination Strategies in Singapore
Vernon J. Lee, Mei Yin Tok, Vincent T. Chow, Kai Hong Phua, Eng Eong Ooi, Paul A. Tambyah, Mark I. Chen
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0007108
Abstract: Background 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.
Galactomannan testing of bronchoalveolar lavage fluid is useful for diagnosis of invasive pulmonary aspergillosis in hematology patients
Li-Yang Hsu, Ying Ding, Jason Phua, Liang-Piu Koh, Douglas S Chan, Kay-Leong Khoo, Paul A Tambyah
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-44
Abstract: We performed a prospective case-control study to determine an optimal BAL galactomannan OD cutoff for IPA in at-risk patients with hematological diagnoses. Cases were subjects with hematological diagnoses who met established definitions for proven or probable IPA. There were two control groups: subjects with hematological diagnoses who did not meet definitions for proven or probable IPA and subjects with non-hematological diagnoses who had no evidence of aspergillosis. Following bronchoscopy and BAL, galactomannan testing was performed using the Platelia Aspergillus seroassay in accordance with the manufacturer's instructions.There were 10 cases and 52 controls. Cases had higher BAL fluid galactomannan OD indices (median 4.1, range 1.1-7.7) compared with controls (median 0.3, range 0.1-1.1). ROC analysis demonstrated an optimum OD index cutoff of 1.1, with high specificity (98.1%) and sensitivity (100%) for diagnosing IPA.Our results also support BAL galactomannan testing as a reasonably safe test with higher sensitivity compared to serum galactomannan testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid over-diagnosis of IPA, and a standardized method of collection should be established before results can be compared between centers.Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in immunocompromised patients, particularly those with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplantation [1]. Early diagnosis and therapy of IPA has been shown to improve outcomes [2], but reaching a definitive diagnosis quickly can be problematic in view of the lack of an exceptional diagnostic test, even with improved guidelines and newer test kits such as the Platelia Aspergillus seroassay (Bio-Rad Laboratories, Hercules, California, USA) and Fungitell 1,3 beta-D-glucan chromogenic assay (Associates of Cape Cod Inc., East Falmouth, Massachusetts,
Use of multiple methods for genotyping Fusarium during an outbreak of contact lens associated fungal keratitis in Singapore
Roland Jureen, Tse H Koh, Grace Wang, Louis YA Chai, Ai L Tan, Tracy Chai, Yong W Wong, Yue Wang, Paul A Tambyah, Roger Beuerman, Donald Tan
BMC Infectious Diseases , 2008, DOI: 10.1186/1471-2334-8-92
Abstract: We assessed the genetic diversity of the isolates using AFLP, Rep-PCR, and ERIC-PCR and compared the usefulness of these typing schemes to characterize the isolates.AFLP was the most discriminative typing scheme and appears to group FSSC from eye infections and from other infections differently.There was a high genomic heterogeneity among the isolates confirming that this was not a point source outbreak.Fusarium spp. are filamentous fungi commonly isolated from environmental sources such as soil, plant roots, plant debris and water systems [1,2]. They may cause invasive infections predominantly in immunocompromised persons [2]. Fusarium species can also cause ocular infections, usually keratitis or endophtalmitis, in immunocompetent persons usually associated with trauma [3-6]. Several morphologically similar species are grouped together in the Fusariun solani species complex (FSSC), but further genotypic characterization of species within this complex is laborious and is usually not done routinely in clinical laboratories. Members of this species complex are usually reported in the literature as Fusarim solani [7]. Nucleic acid based methods are often used in laboratories to identify Fusarium spp. [8-10].Several different methods have been used for molecular typing of fungal isolates associated with outbreaks. Godoy et. al. showed that an enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) and PCR restriction fragment length polymorphism (PCR-RFLP) were useful for genotyping Fusarium isolates [5]. Other methods that have been used include REP-PCR [11], amplified fragment length polymorphism (AFLP) [12,13], and multilocus sequence typing (MLST) [3,14]. Recently, microsphere array-based genotyping was also described [7].In Singapore, there was an outbreak of fungal keratitis caused by members of the FSSC from March 2005 to May 2006 involving 66 patients. Epidemiological investigations in Singapore and the U.S. indicated that improper contact lens wear and
Effectiveness of Pandemic H1N1-2009 Vaccination in Reducing Laboratory Confirmed Influenza Infections among Military Recruits in Tropical Singapore
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 , 2011, DOI: 10.1371/journal.pone.0026572
Abstract: Background 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 reducing influenza cases in Singapore. Methods 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. Results 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). Conclusions Pandemic vaccination reduced H1N1-2009 disease burden among military recruits. Routine seasonal influenza vaccination should be considered.
Epidemiology and outcomes of community-onset methicillin-susceptible Staphylococcus aureus bacteraemia in a university hospital in Singapore
Jonathan Chia, Li-Yang Hsu, Louis Chai, Paul Tambyah
BMC Infectious Diseases , 2008, DOI: 10.1186/1471-2334-8-14
Abstract: A single-centre retrospective case series profiling all patients with community onset-MSSA bacteraemia presenting between March 2005 and February 2006 to a tertiary acute-care university hospital in Singapore. In addition to epidemiological and clinical data collection, risk factors for complicated bacteremia and attributable mortality were analysed.A total of 100 patients met the case definition. Patients were more likely to be male (65%) and below 65 years of age (69%). Seventeen patients were intravenous drug abusers, while 38 had diabetes mellitus. There were 18 cases of endocarditis, with 11 occurring in intravenous buprenorphine abusers. Attributable mortality was 11%, and 46% of patients developed complicated bacteremia. On multivariate analysis, age > 65 years and presence of chronic pulmonary disease were the only significant risk factors for the former, while valvular heart disease was a significant risk factor for the latter.MSSA bacteraemia is associated with a significant risk of serious complications in Singapore. Other Asian cities should be alert to the risk factors for adverse outcomes for this important cause of morbidity and mortality.Staphylococcus aureus bacteraemia remains a common cause of mortality and morbidity both in spite of and as a consequence of medical advances. Although the mortality rate has declined in some countries as a result of improved quality of care [1], the overall prevalence has increased in line with increasing use of intravascular devices and an expanding "at-risk" population [1,2].The focus in recent years has been on infections caused by methicillin-resistant S. aureus (MRSA), especially with regards to its clinical and economic impact in comparison with methicillin-susceptible S. aureus (MSSA) [3,4]. The rapid rise of infections caused by community-associated MRSA (CA-MRSA) has further directed attention towards MRSA [5,6]. Nevertheless, CA-MRSA is still relatively rare on a global basis, whereas MSSA is a more common
A Clinical Diagnostic Model for Predicting Influenza among Young Adult Military Personnel with Febrile Respiratory Illness in Singapore
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 , 2012, DOI: 10.1371/journal.pone.0017468
Abstract: 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 respiratory illness (FRI) to determine predictors of influenza infection.
Real-Time Epidemic Monitoring and Forecasting of H1N1-2009 Using Influenza-Like Illness from General Practice and Family Doctor Clinics in Singapore
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 , 2012, DOI: 10.1371/journal.pone.0010036
Abstract: Reporting of influenza-like illness (ILI) from general practice/family doctor (GPFD) clinics is an accurate indicator of real-time epidemic activity and requires little effort to set up, making it suitable for developing countries currently experiencing the influenza A (H1N1 -2009) pandemic or preparing for subsequent epidemic waves.
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