Epidemiology, vaccine effectiveness, and risk factors for mortality for pneumococcal disease among hospitalised adults in Singapore: a case-control study.

BACKGROUND: Streptococcus pneumoniae infections can lead to severe morbidity and mortality, especially in patients with invasive pneumococcal disease (IPD). This study evaluated factors associated with pneumococcal disease, pneumococcal vaccine effectiveness, and risk factors for all-cause mortality in hospitalised adults with pneumococcal disease in Singapore. METHODS: Retrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015 to 2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design. RESULTS: We identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1 ± 15.4 years, and 65.5% were male. Compared with controls (N = 9181), IPD patients were younger (mean age 61.5 ± 16.3 years, vs 72.2 ± 16.1 years in controls; p < 0.001) and with less co-morbidities [median Charlson's score 1 (IQR 0-4), vs 3 (1-5) in controls; p < 0.001]. IPD patients also had the highest proportions with intensive care unit (ICU) admission (20.7%), inpatient mortality (26.1%) and longest median length of stay [9 (IQR 8-17) days]. On multivariable analysis, IPD was negatively associated with prior pneumococcal vaccination (adjusted relative risk ratio = 0.20, 95%CI 0.06-0.69; p = 0.011). Risk factors for mortality among pneumococcal disease patients were ICU admission, diagnosis of IPD, age ≥ 85 years and Charlson's score > 3. CONCLUSION: Patients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.

Use of a Real-Time Locating System for Contact Tracing of Health Care Workers During the COVID-19 Pandemic at an Infectious Disease Center in Singapore: Validation Study.

BACKGROUND: In early 2020, coronavirus disease (COVID-19) emerged and spread by community and nosocomial transmission. Effective contact tracing of potentially exposed health care workers is crucial for the prevention and control of infectious disease outbreaks in the health care setting. OBJECTIVE: This study aimed to evaluate the comparative effectiveness of contact tracing during the COVID-19 pandemic through the real-time locating system (RTLS) and review of the electronic medical record (EMR) at the designated hospital for COVID-19 response in Singapore. METHODS: Over a 2-day study period, all admitted patients with COVID-19, their ward locations, and the health care workers rostered to each ward were identified to determine the total number of potential contacts between patients with COVID-19 and health care workers. The numbers of staff-patient contacts determined by EMR reviews, RTLS-based contact tracing, and a combination of both methods were evaluated. The use of EMR-based and RTLS-based contact tracing methods was further validated by comparing their sensitivity and specificity against self-reported staff-patient contacts by health care workers. RESULTS: Of 796 potential staff-patient contacts (between 17 patients and 162 staff members), 104 (13.1%) were identified by both the RTLS and EMR, 54 (6.8%) by the RTLS alone, and 99 (12.4%) by the EMR alone; 539 (67.7%) were not identified through either method. Compared to self-reported contacts, EMR reviews had a sensitivity of 47.2% and a specificity of 77.9%, while the RTLS had a sensitivity of 72.2% and a specificity of 87.7%. The highest sensitivity was obtained by including all contacts identified by either the RTLS or the EMR (sensitivity 77.8%, specificity 73.4%). CONCLUSIONS: RTLS-based contact tracing showed higher sensitivity and specificity than EMR review. Integration of both methods provided the best performance for rapid contact tracing, although technical adjustments to the RTLS and increasing user compliance with wearing of RTLS tags remain necessary.

Determinants of change in intention to receive influenza vaccination among health-care workers in Singapore.

Understanding the change in intention for influenza vaccine among health-care workers (HCWs) is important to increase influenza vaccination uptake. We aimed to investigate the psychosocial beliefs associated with a change in the intention for influenza vaccine. An anonymous cross-sectional survey was distributed to tertiary hospital HCWs in 2016. Of 3007 HCWs, 70% were compliant (vaccinated, with an intention to revaccinate), 8% were resistant (unvaccinated, without intention to vaccinate), 10% had positive change (unvaccinated, but with intention) and 12% had negative change (vaccinated, but without intention). Across HCW groups, medical staff had both the highest proportion receiving all influenza vaccinations in the last 5 years (101, 28.4%), as well as the highest proportion who had never received vaccination (41, 11.5%). With increasing age, HCWs were less likely to have a negative (p = .02) or positive change (p = .06) in intention, compared to the vaccine-resistant group. HCWs were more likely to be compliant or have a positive change in intention to receive influenza vaccine, if they perceived the vaccine as effective, safe, or had a higher frequency of influenza vaccination in the last 5 years (all with p < .05). HCWs who were medical staff, who believed that side effects of the vaccine were common, or had worked for 6 to 10 years (vs 5 years or less) were less likely to be compliant (all with p < .05). In conclusion, older HCWs were more likely to maintain the status quo in their behavior toward influenza vaccination. Influenza vaccination strategies should place emphasis on vaccine effectiveness and safety.

Increasing Influenza and Pneumococcal Vaccination Uptake in Seniors Using Point-of-Care Informational Interventions in Primary Care in Singapore: A Pragmatic, Cluster-Randomized Crossover Trial.

Objectives. To evaluate the effectiveness of point-of-care informational interventions in general practitioner clinics to improve influenza and pneumococcal vaccination uptake among elderly patients.Methods. We conducted a pragmatic, cluster-randomized crossover trial in 22 private general practitioner clinics in Singapore, from November 2017 to July 2018. We included all patients aged 65 years or older. Clinics were assigned to a 3-month intervention (flyers and posters encouraging vaccination) plus 1-month washout period, and a 4-month control period (usual care). Primary outcomes were differences in vaccination uptake rates between periods. Secondary outcomes were identification of other factors associated with vaccination uptake.Results. A total of 4378 and 4459 patients were included in the intervention and control periods, respectively. Both influenza (5.9% vs 4.8%; P = .047) and pneumococcal (5.7% vs 3.7%; P = .001) vaccination uptake rates were higher during the intervention period compared with the control period. On multilevel logistic regression analysis, follow-up for hypertension, diabetes mellitus, hyperlipidemia, or any combination of the 3 was associated with uptake of both vaccines.Conclusions. Point-of-care informational interventions likely contributed to increased influenza and pneumococcal vaccination uptake. Patients on follow-up for hypertension, diabetes mellitus, hyperlipidemia, or any combination of the 3 were more likely to receive influenza and pneumococcal vaccination and should be actively engaged by physicians.Trial Registration. ClinicalTrials.gov Identifier: NCT03445117.

Interaction between Antibiotic Resistance, Resistance Genes, and Treatment Response for Urinary Tract Infections in Primary Care.

Given increasing antimicrobial resistance, we aimed to determine antibiotic susceptibility and presence of resistance genes in uropathogens in primary care, factors associated with resistance to commonly prescribed antibiotics, and effect of treatment on early symptom resolution. We conducted a prospective study of primary care patients with urinary tract infection (UTI) symptoms and culture-confirmed UTI in Singapore from 2015 to 2016. Cohort characteristics and antimicrobial susceptibility of cultured isolates were analyzed. Among Enterobacteriaceae isolates, early symptom resolution (within 3 days) according to antibiotic prescribed and isolate susceptibility and factors associated with antibiotic resistance were evaluated. Of 695 symptomatic patients, 299 were urine culture positive; of these 299 patients, 259 (87%) were female. Escherichia coli was the most common uropathogen (76%). Enterobacteriaceae isolates (n = 283) were highly susceptible to amoxicillin-clavulanate (86%), nitrofurantoin (87%), and fosfomycin (98%), but >20% were resistant to ciprofloxacin and co-trimoxazole. Isolates resistant to appropriate indicator antibiotics were further tested to determine proportions positive for blaCTX-M (14/26, 54%), plasmid-mediated ampC (12/24, 50%), qnr (7/69, 10%), and fos (1/6, 17%) resistance genes. A total of 67% of patients given antibiotics with susceptible isolates reported early resolution versus 45% given antibiotics with nonsusceptible isolates (P = 0.001) and 27% not treated (P = 0.018). On multivariable analysis, Indian ethnicity and diabetes mellitus were associated with amoxicillin-clavulanate resistance. Genitourinary abnormalities, UTI in the past 12 months, and hospitalization in the past 6 months were associated with ciprofloxacin and co-trimoxazole resistance. Patients given active empirical antibiotics were most likely to report early symptom resolution, but correlation with in vitro susceptibility was imperfect. Factors associated with resistance may guide the decision to obtain initial urine culture.

Seasonal influenza-associated intensive care unit admission and death in tropical Singapore, 2011-2015.

BACKGROUND: Seasonal influenza can cause severe illness leading to intensive care unit (ICU) admission and death. OBJECTIVE: To define the clinical and epidemiological features of severe seasonal influenza infection and factors associated with mortality. STUDY DESIGN: A retrospective review was conducted on all patients with laboratory-confirmed influenza infection who were either admitted into the ICU or died in the two largest tertiary hospitals in Singapore from 2011-2015. RESULTS: Of 520 patients included in our study, 423 (81.3%) had influenza A infection and the rest with influenza B. Of patients with influenza A infection, 70.0% (296/423) were subtyped, of whom 24.0% (71/296) had A/H1N1pdm2009 and 76.0% (225/296) had A/H3N2. The median age of patients was 72 years (IQR 61-82). Males constituted 53.1% (276/520). Median Charlson comorbidity index score was 1 (IQR 0-3). About 70% had physical or radiological evidence of pneumonia upon admission. In-hospital mortality was 58.1% (302/520). On multiple logistic regression analysis, factors positively associated with mortality were age ≥65 years (adjusted odds ratio, aOR = 3.64, 95%CI 2.21-5.99, p < 0.001), malignancy (aOR = 2.53, 95%CI 1.12-5.73; p = 0.026), and hypoalbuminemia (aOR = 2.16, 95%CI 1.26-3.73; p = 0.005), while antiviral therapy (aOR = 0.33, 95%CI 0.17-0.63; p < 0.001) and ventilation (aOR = 0.23, 95% CI 0.13-0.39; p < 0.001) were negatively associated. CONCLUSIONS: Patients with severe seasonal influenza infection were characterized by advanced age, hypoalbuminemia and presence of pneumonia on admission. Age ≥65 years, malignancy, and hypoalbuminemia were associated with increased mortality, and antiviral therapy and ventilation with decreased mortality.

Factors influencing seasonal influenza vaccination uptake among health care workers in an adult tertiary care hospital in Singapore: A cross-sectional survey.

BACKGROUND: This study aimed to evaluate the factors influencing seasonal influenza vaccination uptake among different health care professional groups. METHODS: A single-center, cross-sectional survey using a standardized anonymous, self-administered questionnaire to assess knowledge, attitudes, and uptake of seasonal influenza vaccination was used. Associations between respective health care groups and vaccination acceptance were then assessed. RESULTS: In total, 3,873 health care workers completed the questionnaire. Of these, 7% were administrative staff, 17% were allied health staff, 7% were ancillary staff, 11% were medical staff, and 58% were nursing staff. The overall vaccination rate for the Southern Hemisphere 2015 influenza season was 82%. In a multivariate logistic regression model, after controlling for gender and presence of chronic disease, associated factors for accepting influenza vaccination were age, education level of bachelor degree or higher, preference for vaccination provided by mobile teams, having 1-50 patient contacts per week, and belief in the potential severity of influenza and vaccine safety (P < .05). In contrast, factors negatively associated with vaccination acceptance included being a medical staff member or allied health staff member, living with family members under the age of 16, fear of adverse reactions, and disbelief in vaccination effectiveness (P < .05). CONCLUSIONS: Although vaccine coverage in Singapore has been high, our findings provide guidance for the development of strategies to further improve vaccine coverage among different groups of health care workers.

Distinguishing Zika and Dengue Viruses through Simple Clinical Assessment, Singapore.

Dengue virus and Zika virus coexist in tropical regions in Asia where healthcare resources are limited; differentiating the 2 viruses is challenging. We showed in a case-control discovery cohort, and replicated in a validation cohort, that the diagnostic indices of conjunctivitis, platelet count, and monocyte count reliably distinguished between these viruses.

Correlation of clinical illness with viremia in Zika virus disease during an outbreak in Singapore.

BACKGROUND: The first autochthonous Zika virus (ZIKV) outbreak in Singapore was detected in August 2016. We report an analysis of the correlation of clinical illness with viremia and laboratory parameters in this Asian cohort. METHODS: We conducted a prospective longitudinal cohort study of patients with a positive blood ZIKV polymerase chain reaction (PCR) result who were admitted to Tan Tock Seng Hospital, Singapore, for isolation and management. RESULTS: We included 40 patients in our study. Rash was present in all patients, while 80% (32/40) had fever, 62.5% (25/40) myalgia, 60% (24/40) conjunctivitis and 38% (15/40) arthralgia. The median duration of viremia was 3.5 days (IQR: 3-5 days). Patients with viremia of ≥4 days were more likely to have prolonged fever compared to those with viremia of less than 4 days (95% versus 63%, p = 0.01), but had no significant correlation with other clinical signs and symptoms, or laboratory investigations. However, 21 patients (53%) had hypokalemia despite the absence of gastrointestinal symptoms. CONCLUSION: Although fever correlated with duration of viremia, 30% of patients remained viremic despite defervescence. Laboratory abnormalities such as leukopenia or thrombocytopenia were not prominent in this cohort but about half the patients were noted to have hypokalemia.

An unusual outbreak of rotavirus G8P[8] gastroenteritis in adults in an urban community, Singapore, 2016.

BACKGROUND: An outbreak of gastroenteritis (GE) occurred in community-dwelling adults in the Central Region of urban Singapore, in May 2016. OBJECTIVES: To investigate the cause of the outbreak. STUDY DESIGN: We conducted a case-cohort study on GE patients linked to the outbreak who presented to the emergency department of a tertiary-care hospital near the outbreak area, from 18 May to 11 June 2016. Stools were tested for gastrointestinal pathogens including rotavirus antigen and positive rotavirus samples were subject to genotyping. RESULTS: A total of 57 adult GE patients, with a median age of 40 (range 18 to 84) years, were included. Predominant symptoms were diarrhoea (98.2%), vomiting (64.9%), and abdominal discomfort (38.6%). Age 65 years and above (Adjusted OR 21.78, 95% CI 1.49-318.84; P = 0.02) was the only predictor of admission, after adjusting for comorbidities and clinical severity. Molecular microbiological investigations confirmed that the outbreak was caused by a novel human-bovine reassortant strain of rotavirus G8P[8] with DS-1-like backbone. Exposure to the market in the outbreak area was strongly associated with rotavirus infection (OR 46.14; 95% CI 43.04-49.25, P < 0.01). No particular food item could be identified as the outbreak cause. CONCLUSIONS: This is the first report of an outbreak of rotavirus G8P[8] in adults in an urban community that is not waterborne. Transmission was likely through fomites in the market and its surrounding areas, via consumption or contact with contaminated food items purchased from the market, and from person-to-person. The potential for novel G8P[8] strains to cause outbreaks cannot be overemphasized.

Characterisation of bone and joint infections due to Group B Streptococcus serotype III sequence type 283.

In 2015, an epidemic of Group B Streptococcus (GBS) serotype III sequence type 283 (ST283) disease was reported in Singapore, associated with consumption of raw freshwater fish. In this study, we further characterise the characteristics of bone and joint infections associated with ST283 GBS in adults and the differences between ST283 and non-ST283 manifestations. A retrospective study of 54 inpatients with invasive GBS disease involving bones and/or joints from 2010 to 2015 was performed. Archived isolates were identified as GBS serotype III and ST283 positive using PCR methods. Clinical data were collected from a review of clinical charts. Twenty-three cases were ST283 and 31 were non-ST283. ST283 GBS patients were more likely to be of Chinese ethnicity, have lower Charlson comorbidity scores, and have fewer overall comorbidities, including diabetes mellitus with end-organ damage, peripheral vascular disease, and previous stroke, compared to non-ST283 GBS patients. ST283 patients had more oligoarthritis, with greater involvement of the knee, shoulder, and vertebrae, compared to monoarticular joint involvement in non-ST283 patients. Six patients had a unique combination of knee and shoulder joint involvement. All ST283 cases were mono-microbial, compared to a significant proportion of polymicrobial cultures in non-ST283 patients. Non-ST283 patients had a significantly longer length of stay and were more likely to undergo amputation or wound debridement. This study adds to growing evidence of a distinct clinical presentation associated with ST283 GBS, involving predominantly healthier patients without significant comorbidities, and with distinct clinical manifestations with regard to bone and joint disease.

Diagnostic Accuracy of Parameters for Zika and Dengue Virus Infections, Singapore.

Singapore experienced its first documented Zika virus outbreak in 2016. We identified clinical and laboratory parameters that increase the probability for Zika or dengue virus infection. Early during the illness, combinations of key parameters obtained through clinical assessment and hematologic tests can help distinguish between these infections.

A formative research-guided educational intervention to improve the knowledge and attitudes of seniors towards influenza and pneumococcal vaccinations.

BACKGROUND: Adult influenza and pneumococcal vaccination rates in Singapore are low, and factors influencing knowledge and attitudes of seniors towards influenza, pneumonia and their respective vaccines are not well-known. Our study aims to understand the barriers and facilitators towards getting influenza and pneumococcal vaccinations among seniors in Singapore, and subsequently inform the conduct of a relevant community-based educational intervention, as well as evaluate the intervention outcomes. METHODS: We performed a mixed methods study with two components: Firstly, formative research was conducted among community-dwelling seniors, using focus group discussions (FGDs), to understand their knowledge and attitudes towards influenza, pneumonia and their respective vaccines. Next, a quantitative study was conducted to evaluate knowledge of seniors and the effectiveness of an educational intervention. RESULTS: Four FGDs were organised with 32 participants, who were predominantly female, of lower educational background, and residing in government rental flats. Participants had varying levels of knowledge and many misconceptions about influenza, pneumonia and their respective vaccinations, with concerns about side effects and vaccine effectiveness. The formative research results were used to inform a community-based educational intervention for seniors. Our subsequent evaluation included 604 elderly participants, mainly from lower educational and socio-economic strata, who initially demonstrated poor knowledge scores (median score 5 out of 9, IQR 4-5). Following our intervention, median knowledge score improved to 7 (IQR 6-8) (p < .0001). Significant improvements in knowledge scores were observed across genders, age strata, education levels, and housing types. DISCUSSION: Our formative research identified knowledge gaps among community-dwelling seniors which affected their attitudes towards vaccination uptake. Key findings were taken into consideration when implementing the educational intervention. Our community-based intervention was effective in improving knowledge and attitudes, and could be used as a cue to action for short-term behaviour changes.

Outbreak of New Delhi metallo-ß-lactamase-1-producing Enterobacter cloacae in an acute care hospital general ward in Singapore.

BACKGROUND: Autochthonous infections with New Delhi metallo-ß-lactamase-1 (NDM-1)-producing Enterobacteriaceae have been reported in Singapore since 2011, but occurrences of nosocomial transmission have not. We report an outbreak of NDM-1-producing Enterobacter cloacae among adults admitted to an acute hospital's general ward. METHODS: On detecting the index case with a culture specimen positive for NDM-1-producing E cloacae, active case finding was conducted by screening all possible patient contacts. On-site ward assessment was performed, and electronic patient medical records were reviewed to conduct a case-control study to identify factors associated with colonization. RESULTS: Of 55 screened patient contacts, 3 further cases were detected, with isolates genetically related to the index case. None of these 4 cases was housed within the same cubicle. However, 3 were managed by the same medical team. Being managed by this team was positively associated with being a case (adjusted odds ratio = 15.64; 95% confidence interval, 0.91-270.27; P = .06) after adjusting for age, sex, Charlson comorbidity index score, and recent antibiotic use. CONCLUSION: Our report suggests nosocomial transmission of NDM-1-producing E cloacae occurred via health care staff. Improvements in infection control measures, especially pertaining to staff hand hygiene practices and ward staffing, are needed to reduce the spread of highly resistant pathogens, such as NDM-1-producing Enterobacteriaceae.

Alcohol handrubbing and chlorhexidine handwashing are equally effective in removing methicillin-resistant Staphylococcus aureus from health care workers' hands: A randomized controlled trial.

We conducted a randomized controlled trial in a tertiary-care hospital in a real-time setting to evaluate the effectiveness of 3 hand hygiene protocols in reducing hand carriage of methicillin-resistant and methicillin-sensitive Staphylococcus aureus among health care workers. Our study shows that use of alcohol handrub, either covering all hand surfaces in no particular order or using the 7-step technique, and chlorhexidine handwashing were equally effective in removing hand carriage of these pathogens.

Progress towards measles elimination in Singapore.

OBJECTIVE: We describe the epidemiological trends of measles in Singapore in relation to its progress towards measles elimination and identify gaps in fulfilling the World Health Organization Western Pacific Regional Office regional measles elimination criteria. METHODS: Epidemiological data on measles maintained by the Communicable Diseases Division, Ministry of Health from 1981 to 2012 were collated and analysed. Data on measles vaccination coverage were obtained from the National Immunization Registry and School Health Services, Health Promotion Board. To assess the seroprevalence of the population, the findings of periodic seroepidemiological surveys on measles were traced and reviewed. FINDINGS: With the successful implementation of the National Childhood Immunization Programme using the monovalent measles vaccine, measles incidence declined from 88.5 cases per 100,000 in 1984 to 6.9 per 100,000 in 1991. Resurgences were observed in 1992, 1993 and 1997. A 'catch-up' vaccination programme using the trivalent measles, mumps and rubella (MMR) vaccine was conducted in 1997, followed by introduction of the two-dose vaccination schedule in January 1998. Measles incidence subsequently declined sharply to 2.9 per 100,000 in 1998. Vaccination coverage was maintained at 95% for the first dose and 92-94% for the second dose. Seroprevalence surveys showed seropositivity for measles IgG antibodies in over 95% of adults in 2004, and in 83.1% of children aged 1-17 years in 2008-2010. Sporadic cases with occasional clusters of two or more cases continued to occur among the unvaccinated population, especially children aged below 4 years. The predominant measles virus genotype has shifted from D9 to the B3 and G3 genotypes, which are endemic in neighbouring countries. CONCLUSION: Singapore has made good progress towards the elimination of endemic measles. To further eliminate sporadic cases of measles, the national immunisation schedule has recently been amended to vaccinate children with 2 doses of MMR vaccine before 2 years of age.

The burden of diabetes mellitus in elderly patients from an Asian tertiary hospital.

SUMMARY: Diabetes mellitus (DM) has been declared as a global public health threat to society. However, the burden of the disease in elderly Asian patients has not been described. The aim of the study is to assess the disease burden of DM and its associated adverse outcomes in elderly patients from an Asian hospital using the hospital inpatient database. METHODS: Retrospective study of hospital discharge database from 2004 to 2008 to identify patients aged 65 years and above with DM and its associated 'adverse outcomes' using International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Australian Modification (ICD-9-AM) codes. RESULTS: Of 89,875 hospitalized patients aged 65 years and above over the 5 years, 31,124 (34.6%) patients had DM, and the percentage of DM cases increased steadily from 34.3% to 35.6%. Prevalence of DM-associated adverse outcomes was higher in DM patients than in non-DM patients (53.8% vs. 31.5%, p<0.001). For trends over time, the adverse outcomes decreased in both DM patients (58.1% to 53.6%) and non-DM patients (34.3% to 31.4%, all p<0.001). All disease-specific adverse outcomes except renal disease decreased over time both in DM and non-DM patients (all p<0.05). There were increased trends over time for renal disease in both DM patients (16.1% to 23.2%, p<0.001) and non-DM patients (6.7% to 10.4%, p<0.001). CONCLUSION: The burden of DM in this group of elderly patients is high. Elderly patients with DM experienced much higher rates of the adverse outcomes.

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

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.