Development and evaluation of baculovirus-expressed Chikungunya virus E1 envelope proteins for serodiagnosis of Chikungunya infection.

Population-based serosurveillance studies provide critical estimates on community-level immunity and the potential for future outbreaks. Currently, serological assays, such as IgG enzyme-linked immunosorbent assays (ELISAs) and indirect immunofluorescence tests (IIFT) based on the inactivated whole virus are used to determine past Chikungunya virus (CHIKV) infection. However, these commercially available tests have variable sensitivities. To develop and evaluate recombinant based CHIKV-specific IgG antibody capture ELISAs (GAC-ELISAs), baculoviruses carrying wild-type (E1-A226, named WT) or mutant (E1-A226V, named MUT) E1 envelope protein genes of CHIKV were generated. The seroreactivity of recombinant CHIKV WT and MUT envelope proteins were determined using residual blood, collected from CHIKV-confirmed patients. The sensitivities of both recombinant CHIKV envelope proteins were 83.0% as measured by GAC-ELISAs. The specificities of both recombinant proteins were 87.8%. These GAC-ELISAs were also able to detect the persistence of anti-CHIKV IgG antibodies up to 6 months after the disease onset, together with rise in sensitivities with increasing time. These results suggest that the baculovirus purified recombinant CHIKV envelope proteins react with anti-CHIKV IgG antibodies and may be useful in population-based seroprevalence surveys. In addition, these GAC-ELISAs offer good diagnostic value to determine the recent/past CHIKV infection status in non-endemic populations.

Rates and predictors for influenza vaccine prescriptions among HIV-infected clinic patients in Singapore

<p><b>INTRODUCTION</b>Although Singapore national guidelines recommend influenza vaccination for individuals with comorbidities, the vaccine uptake remains relatively low. This study examines the rates of influenza vaccine prescriptions in a clinic population, and patient, doctor and clinic factors that could affect the vaccine prescribing rates.</p><p><b>MATERIALS AND METHODS</b>This retrospective review utilised electronic medical records from HIV-infected patients seen in an infectious disease (ID) specialist clinic. Data from 40 randomly selected patients per physician were analysed for the outcome of influenza vaccine prescriptions from 1 January to 31 December 2007. All 7 consultants and the 6 ID registrars who had spent at least 4 months in the Department during 2007 were included. Data analysed included patient, physician, and clinic characteristics, and clinically relevant outcomes of admission within a year, and the length of hospital stay.</p><p><b>RESULTS</b>Of the 461 HIV-infected patients analysed for this study, only 107 (23%) were prescribed influenza vaccine in 2007. Vaccine prescribing rates by individual physicians ranged from 0% to 77%. The outcome of vaccine prescribing was analysed by patient demographics (age >40 years, gender, race), physician characteristics (doctor grade, gender and training), and clinic volumes (number of patients per clinic session). Multivariate analysis demonstrated that patients with female doctors (OR 1.8, 95% CI, 1.1 to 3.0, P = 0.017), and doctors with overseas medical training (OR 11.6, 95% CI, 6.0 to 22.2, P <0.001) were significantly more likely to have influenza vaccine prescribed. On univariate analysis, patients were more likely to be admitted if they were male (OR 2.1, 95% CI, 1.0 to 5.1, P = 0.041), and over 40 years old (OR 2.1, 95% CI, 1.1 to 4.5, P = 0.024). Patients prescribed influenza vaccine showed a non-significant trend for protection against admission (OR 0.7, P = 0.288), and shorter length of stay (median 5 vs 9 days, P = 0.344).</p><p><b>CONCLUSION</b>Influenza vaccine prescribing for HIV-infected outpatients in 2007 was only 23%, even in an ID specialist clinic. There was substantial variability in prescribing rates by individual physicians. Neither patient demographics nor patient volumes per clinic session had an impact on the prescribing rates, but significant predictors included physician gender and medical school training. Patients prescribed influenza vaccine had fewer admissions and shorter hospital lengths of stay, although these trends were non-significant.</p>

Prevalence of and risk factors for MRSA colonization in HIV-positive outpatients in Singapore.

BACKGROUND: Whilst there have been studies on the risks and outcomes of MRSA colonization and infections in HIV-positive patients, local data is limited on the risk factors for MRSA colonization among these patients. We undertook this study in a tertiary HIV care centre to document the risk factors for colonization and to determine the prevalence of MRSA colonization among HIV-positive outpatients in Singapore. METHODS: This was a cross-sectional study in which factors associated with MRSA positivity among patients with HIV infection were evaluated. A set of standardized questionnaire and data collection forms were available to interview all recruited patients. Following the interview, trained nurses collected swabs from the anterior nares/axilla/groin (NAG), throat and peri-anal regions. Information on demographics, clinical history, laboratory results and hospitalization history were retrieved from medical records. RESULTS: MRSA was detected in swab cultures from at least 1 site in 15 patients (5.1%). Inclusion of throat and/or peri-anal swabs increased the sensitivity of NAG screening by 20%. Predictors for MRSA colonization among HIV-positive patients were age, history of pneumonia, lymphoma, presence of a percutaneous device within the past 12 months, history of household members hospitalized more than two times within the past 12 months, and a most recent CD4 count less than 200. CONCLUSIONS: This study highlights that a proportion of MRSA carriers would have been undetected without multiple-site screening cultures. This study could shed insight into identifying patients at risk of MRSA colonization upon hospital visit and this may suggest that a risk factor-based approach for MRSA surveillance focusing on high risk populations could be considered.

Causes of death and factors associated with early death among human immunodeficiency virus (HIV)-infected persons in Singapore: pre-highly active antiretroviral therapy (HAART) and Peri-HAART

<p><b>INTRODUCTION</b>Highly active antiretroviral therapy (HAART) has greatly changed the epidemiology of human immunodefi ciency virus (HIV) mortality. The aim of this study is to compare the causes of death and factors associated with early death in HIV-infected persons in the pre- and peri-highly active antiretroviral therapy (HAART) periods.</p><p><b>MATERIALS AND METHODS</b>We conducted a retrospective review of 483 HIV-infected persons who were diagnosed with HIV from 1985 to 2000, and had died within 5 years of the diagnosis. We examined the temporal change in the primary causes of death between those who were diagnosed in the pre-HAART (1985 to 1995) and peri-HAART (1996 to 2000) periods, and compared the demographic and clinical characteristics of the 2 groups.</p><p><b>RESULTS</b>During the peri-HAART period, HIV encephalopathy, cryptococcal meningitis, and lymphoma were no longer the leading causes of death. Opportunistic infections remained important causes of death. Early deaths from the peri-HAART period were older (60 years and above) at diagnosis (Adj OR 7.50; 95% CI, 1.78 to 31.58), more likely to be divorced (Adj OR 5.05, 95% CI, 1.96 to 13.02) and tended to have a low baseline CD4 cell count of <50 cells/ uL (Adj OR 2.18, 95% CI, 1.14 to 4.16) , and were more likely to have received HAART (Adj OR 5.19; 95% CI, 2.22 to 12.12) than early deaths from the pre-HAART period.</p><p><b>CONCLUSION</b>In the peri-HAART era, HIV-infected persons who died within 5 years of diagnosis were those who were older (≥60 years), divorced, or who presented with very late-stage disease (CD4 <50) at diagnosis. More targeted public health interventions, such as targeted public health messages and outreach to increase access to HIV testing and treatment should be developed for these subpopulations.</p>

Influenza B outbreak among influenza-vaccinated welfare home residents in Singapore

<p><b>INTRODUCTION</b>Outbreaks of acute respiratory illness occur commonly in long-term care facilities (LTCF), due to the close proximity of residents. Most influenza outbreak reports have been from temperate countries. This study reports an outbreak of influenza B among a highly immunised resident population in a welfare home in tropical Singapore, and discusses vaccine efficacy and the role of acute respiratory illness surveillance for outbreak prevention and control.</p><p><b>MATERIALS AND METHODS</b>During the period from 16 to 21 March 2007, outbreak investigations and active case finding were carried out among residents and nursing staff at the welfare home. Interviews and medical notes review were conducted to obtain epidemiological and clinical data. Hospitalised patients were tested for respiratory pathogens. Further genetic studies were also carried out on positive respiratory samples.</p><p><b>RESULTS</b>The overall clinical attack rate was 9.4% (17/180) in residents and 6.7% (2/30) in staff. All infected residents and staff had received influenza immunisation. Fifteen residents were hospitalised, with 2 developing severe complications. Genetic sequencing revealed that the outbreak strain had an 8.2% amino acid difference from B/Malaysia/2506/2004, the 2006 southern hemisphere influenza vaccine strain, which the residents and staff had earlier received.</p><p><b>CONCLUSIONS</b>A mismatch between the vaccine and circulating influenza virus strains can result in an outbreak in a highly immunised LTCF resident population. Active surveillance for acute respiratory illness in LTCFs could be implemented for rapid detection of antigenic drift. Enhanced infection control and other preventive measures can then be deployed in a timely manner to mitigate the effect of any outbreaks.</p>

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

<p><b>INTRODUCTION</b>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 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.</p><p><b>MATERIALS AND METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>