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Singapore offered the BNT162b2 vaccine (tozinameran; Pfizer-BioNTech) to adolescents aged 12-17 years in May 18, 2021, and extended booster vaccines to this group in Jan 21, 2022. Literature on the effectiveness of primary series and booster vaccination among adolescents is scarce outside of Europe and North America. We aimed to determine primary series and booster vaccine effectiveness against SARS-CoV-2 infection and hospitalisation among adolescents in Singapore.For this national cohort study, we assessed the incidence of confirmed SARS-CoV-2 infection and hospitalisation among adolescents aged 12-17 years vaccinated with BNT162b2 in Singapore from Sept 1 to Dec 15, 2021, during the delta (B.1.617.2) variant wave, and from Jan 21 to April 28, 2022, during the omicron (B.1.1.529) variant wave. Data were collected from official databases maintained by the Ministry of Health of Singapore. Individuals were classified as partly vaccinated (those who had received one dose and those who had received the second dose no more than 7 days previously), fully vaccinated (8 days after receiving a second dose), or boosted (8 days after receiving a third dose) and compared with unvaccinated individuals.249 763 individuals aged 12-17 years were included in the study, contributing over 56·2 million person-days of observation. Compared with unvaccinated individuals, two vaccine doses achieved vaccine effectiveness of 66% (95% CI 63-69) against infection with the delta variant and 25% (21-29) against infection with the omicron variant, and 83% (74-89) against delta variant-associated hospitalisation and 75% (56-86) against omicron variant-associated hospitalisation. Booster vaccination with a third dose achieved vaccine effectiveness of 56% (53-58) against infection with the omicron variant and 94% (86-97) against omicron-associated hospitalisation, compared with unvaccinated adolescents. Vaccine effectiveness against infection for both variants after two doses waned over time, whereas vaccine effectiveness against hospitalisation for both variants remained stable; both were increased after three doses.Among adolescents aged 12-17 years, vaccine effectiveness against confirmed SARS-CoV-2 infection after two doses of BNT162b2 decreased over time and increased after a third dose. Boosted adolescents were also the most protected from hospitalisation compared with fully vaccinated, partly vaccinated, and unvaccinated adolescents. Therefore, the booster dose of BNT162b2 can help to reduce the burden on the health-care system and individual morbidity during an omicron wave.None.

We compared the vaccine effectiveness over time of the primary series and booster against infection and severe disease with the Delta, Omicron BA.1, and BA.2 variants in Singapore, an Asian setting with high vaccination coverage.We conducted a test-negative case-control study on all adult residents in Singapore who underwent PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute hospitals. Individuals with a negative PCR from 1 September, 2021, to 30 November, 2021, and 1 December, 2021, to 25 April, 2022, served as controls for the Delta and Omicron variants respectively, and PCR-positive individuals within these two time periods served as cases. Associations between vaccination status and severe SARS-CoV-2 infection and severe disease with the Delta or Omicron variants were measured using Poisson regressions. Vaccine effectiveness was calculated by taking 1 minus risk ratio.There were 68 114 individuals comprising 58 495 controls and 9619 cases for the Delta period, of whom 53 093 completed the primary series and 9161 were boosted. For the Omicron period, 104 601 individuals comprising 80 428 controls, 8643 BA.1 cases, and 15 530 BA.2 cases were included, of whom 29 183 and 71 513 were vaccinated with the primary series and boosted, respectively. The primary series provided greater protection against infection with Delta (45%, 95% CI 40-50%) than against infection with Omicron (21%, 95% CI 7-34% for BA.1; 18%, 95% CI 6-29% for BA.2) at2 months from vaccination. Vaccine effectiveness of the booster was similar against infection with BA.1 (44%, 95% CI 38-50%) and BA.2 (40%, 95% CI 35-40%). Protection against severe disease by the booster for BA.1 (83%, 95% CI 76-88%) and BA.2 (78%, 95% CI 73-82%) was comparable to that by the primary series for Delta (80%, 95% CI 73-85%).Our findings support the use of a booster dose to reduce the risk of severe disease and mitigate the impact on the healthcare system in an Omicron-predominant epidemic.

Summary The severe acute respiratory syndrome (SARS) outbreak in 2003 resulted in more than 8000 cases and 800 deaths. SARS was eventually contained by means of syndromic surveillance, prompt isolation of patients, strict enforcement of quarantine of all contacts, and in some areas top-down enforcement of community quarantine. By interrupting all human-to-human transmission, SARS was effectively eradicated. By contrast, by Feb 28, 2020, within a matter of 2 months since the beginning of the outbreak of coronavirus disease 2019 (COVID-19), more than 82 000 confirmed cases of COVID-19 have been reported with more than 2800 deaths. Although there are striking similarities between SARS and COVID-19, the differences in the virus characteristics will ultimately determine whether the same measures for SARS will also be successful for COVID-19. COVID-19 differs from SARS in terms of infectious period, transmissibility, clinical severity, and extent of community spread. Even if traditional public health measures are not able to fully contain the outbreak of COVID-19, they will still be effective in reducing peak incidence and global deaths. Exportations to other countries need not result in rapid large-scale outbreaks, if countries have the political will to rapidly implement countermeasures.

Objectives: The Ministry of Health (MOH), Singapore, conducted the National Paediatric Seroprevalence Survey 2018 (NPSS 2018) to estimate the latest immunity levels against measles, rubella, varicella, diphtheria, tetanus and hepatitis B, and the seroprevalence of chronic hepatitis B virus (HBV) carriage in children and adolescents in Singapore. Methods: The survey involved prospective collection of residual sera from 1,200 children and adolescents aged 1–17 years in two public acute hospitals. Enzyme-linked immunosorbent assays (EIA) or plague reduction neutralisation tests (PRNT) were used to determine the seroprevalence of the vaccine-preventable diseases. Results: Overall prevalence of measles and rubella antibodies among Singaporean children and adolescents aged 1–17 years were 98.2% (95% CI: 91.2–98.8%) and 94.8% (95% CI: 93.4–95.9%) respectively. 97.1% (95% CI: 96.0–97.9%) of subjects had at least basic protection against diphtheria, while 89.3% (95% CI: 87.5–91.0%) were protected against tetanus. The prevalence of chronic HBV carriage was 0.4% (95% CI: 0.2–1.0%), while 45.7% (95% CI: 42.9–48.5%) were immune against HBV. The seroprevalence for varicella antibodies was 52.9% (95% CI: 50.1–55.7%). Concordance between vaccination status and seroprevalence was observed for measles, rubella, diphtheria and tetanus. Conclusion: Singapore’s children and adolescents are well-protected against measles, rubella, diphtheria and tetanus. Continual efforts in ensuring high vaccination coverage should be sustained. Keywords: Seroprevalence, Survey, Vaccine, Immunity, Children, Adolescents, Singapore, Epidemiology, Public health

Summary Background Three clusters of coronavirus disease 2019 (COVID-19) linked to a tour group from China, a company conference, and a church were identified in Singapore in February, 2020. Methods We gathered epidemiological and clinical data from individuals with confirmed COVID-19, via interviews and inpatient medical records, and we did field investigations to assess interactions and possible modes of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Open source reports were obtained for overseas cases. We reported the median (IQR) incubation period of SARS-CoV-2. Findings As of Feb 15, 2020, 36 cases of COVID-19 were linked epidemiologically to the first three clusters of circumscribed local transmission in Singapore. 425 close contacts were quarantined. Direct or prolonged close contact was reported among affected individuals, although indirect transmission (eg, via fomites and shared food) could not be excluded. The median incubation period of SARS-CoV-2 was 4 days (IQR 3–6). The serial interval between transmission pairs ranged between 3 days and 8 days. Interpretation SARS-CoV-2 is transmissible in community settings, and local clusters of COVID-19 are expected in countries with high travel volume from China before the lockdown of Wuhan and institution of travel restrictions. Enhanced surveillance and contact tracing is essential to minimise the risk of widespread transmission in the community. Funding None.

Influenza outbreaks occur periodically in Long Term Care Facilities (LTCFs) and vaccination is critical in preventing influenza infections. We evaluated the influenza vaccine effectiveness (VE) during respiratory outbreaks in LTCFs reported to the Ministry of Health, Singapore in 2017. A test-negative design was used to estimate the ratio of the odds of testing positive for influenza among vaccinated individuals to the odds among unvaccinated individuals. The VE was calculated as (1-odds ratio) × 100%. For adjusted VE, the estimates were derived using logistic regression adjusted for age group, gender, month of illness, and number of days from date of illness onset till to swab collection date. Estimates by influenza subtypes and post-vaccination time periods (15–180 days & 181–365 days) were also calculated using stratified data. 264 individuals, with 118 laboratory-confirmed influenza cases [32 A(H1N1)pdm09, 75 A(H3N2), 11 A(untypable)], were included in the analysis. No one was identified to be infected with influenza B. The overall adjusted VE estimate was 40.5% (95% CI: −12.2–68.5%), while the subtype-specific adjusted VE estimates were −43.4% (95% CI: −312.4–50.2%) against A(H1N1)pdm09 and 57.1% (95% CI: 5.7–80.5%) against A(H3N2). At 15–180 days post-vaccination period, the adjusted VEs were 59.3% (95% CI: 18.0–79.8%) against all influenza, 35.4% (95% CI: −123.5–81.3%) against A(H1N1)pdm09 and 67.9% (95% CI: 22.5–86.7%) against A(H3N2). Estimates were not significant at 181–365 days post-vaccination. The influenza vaccine showed varying effectiveness among individuals in Singapore’s LTCFs in 2017, with a higher effectiveness among those who were more recently vaccinated. It remains an important tool in preventing influenza infections, especially for those who are at high risk of influenza-related complications.

Background: The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective cohort study, we compared outcomes of patients infected with B.1.1.7, B.1.351, and B.1.617.2 with those with wild-type strains from early 2020. Methods: National surveillance data from 1-January-2021 to 22-May-2021 were obtained from the Ministry of Health, and outcomes in relation to VOC were explored. Detailed patient level data from all SARS-CoV-2 patients with VOC infection admitted to our centre between 20-December-2020 and 12-May-2021 were analysed. Outcomes were compared with a cohort of 846 patients admitted January-April 2020. Findings: There were 838 VOC infections in Singapore in the study period. After adjusting for age and gender, B.1.617.2 infection was associated with higher odds of oxygen requirement, ICU admission, or death (adjusted odds ratio (aOR) 4·90, [95% CI 1·43-30·78]. 157 patients with VOCs were admitted to our centre. After adjusting for age, gender, comorbidities, and vaccination, aOR for pneumonia with B.1.617.2 was 1·88 [95% CI 0·95-3·76]) compared with wild-type. B.1.617.2 was associated with significantly lower PCR Ct values and significantly longer duration of Ct value ≤30 (estimated median duration 18 days for B.1.617.2, 13 days for wild-type). Vaccine breakthrough cases were less severe. Interpretation: There was a signal toward increased severity associated with B.1.617.2. The association of B.1.617.2 with lower Ct value and longer viral shedding provides a potential mechanism for increased transmissibility. These findings provide a strong impetus for the rapid implementation of vaccination programmes. Funding Information: National Medical Research Council grants COVID19RF-001 and COVID19RF-008. Declaration of Interests: BEY reports personal fees from Roche and Sanofi, outside the submitted work. All other authors declare no competing interests. Ethics Approval Statement: Informed consent for retrospective data collection was waived as approved by the institutional review board (NHG-DSRB reference number 2020/01122).

Background: Several countries have controlled the spread of COVID-19 through varying combinations of border restrictions, case finding, contact tracing and careful calibration on the resumption of domestic activities. However, evaluating the effectiveness of these measures based on observed cases alone is challenging as it does not reflect the transmission dynamics of missed infections. Methods: Combining data on notified local COVID-19 cases with known and unknown sources of infections (i.e. linked and unlinked cases) in Singapore in 2020 with a transmission model, we reconstructed the incidence of missed infections and estimated the relative effectiveness of different types of outbreak control. We also examined implications for estimation of key real-time metrics — the reproduction number and ratio of unlinked to linked cases, using observed data only as compared to accounting for missed infections. Findings: Prior to the partial lockdown in Singapore, initiated in April 2020, we estimated 89% (95%CI 75–99%) of the infections caused by notified cases were contact traced, but only 12.5% (95%CI 2–69%) of the infections caused by missed infectors were identified. We estimated that the reproduction number was 1.23 (95%CI 0.98–1.54) after accounting for missed infections but was 0.90 (95%CI 0.79-1.1) based on notified cases alone. At the height of the outbreak, the ratio of missed to notified infections was 34.1 (95%CI 26.0–46.6) but the ratio of unlinked to linked infections was 0.81 (95%CI 0.59–1.36). Our results suggest that when case finding and contact tracing identifies at least 50% and 20% of the infections caused by missed and notified cases respectively, the reproduction number could be reduced by more than 14%, rising to 20% when contact tracing is 80% effective. Interpretation: Depending on the relative effectiveness of border restrictions, case finding and contact tracing, unobserved outbreak dynamics can vary greatly. Commonly used metrics to evaluate outbreak control — typically based on notified data — could therefore misrepresent the true underlying outbreak. Funding: Ministry of Health, Singapore. Declaration of Interests: None to declare.

Asymptomatic cases of COVID-19 are a potential source of substantial spread within the community setting.1Kronbichler A Kresse D Yoon S Lee KH Effenberger M Shin JI Asymptomatic patients as a source of COVID-19 infections: a systematic review and meta-analysis.Int J of Inf Dis. 2020; 98: 180-186Summary Full Text Full Text PDF PubMed Scopus (13) Google Scholar However, little information is available about the infectivity and epidemiological significance of people with asymptomatic COVID-19.2Gao M Yang L Chen X et al.A study on infectivity of asymptomatic SARS-CoV-2 carriers.Respiratory Medicine. 2020; 169: 1-5Summary Full Text Full Text PDF Scopus (26) Google Scholar

The SARS-CoV-2 lineage B.1.617.2, also known as the delta variant, was declared a variant of concern by WHO on the basis of preliminary evidence suggesting faster spread relative to other circulating variants. However, the epidemiological factors contributing to this difference remain unclear. In particular, an increase in observed growth rate of COVID-19 cases could be the result of a shorter generation interval (i.e., the delay from one infection to the next) or an increase in the effective reproduction number, R, of an infected individual (i.e., the average number of secondary cases generated by an infectious individual), or both. Whereas a shorter generation interval would increase the speed but not the number of individual-level transmissions, a larger value of R would require both faster and wider coverage of outbreak control measures such as vaccination or physical distancing to suppress transmission.

Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. We investigated the effect of this deletion on the clinical features of infection. Methods We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study—a prospective observational cohort study conducted at seven public hospitals in Singapore. We collected clinical, laboratory, and radiological data from patients' electronic medical records and serial blood and respiratory samples taken during hospitalisation and after discharge. Individuals infected with the ∆382 variant were compared with those infected with wild-type SARS-CoV-2. Exact logistic regression was used to examine the association between the infection groups and the development of hypoxia requiring supplemental oxygen (an indicator of severe COVID-19, the primary endpoint). Follow-up for the study's primary endpoint is completed. Findings Between Jan 22 and March 21, 2020, 278 patients with PCR-confirmed SARS-CoV-2 infection were screened for the ∆382 deletion and 131 were enrolled onto the study, of whom 92 (70%) were infected with the wild-type virus, ten (8%) had a mix of wild-type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 [0%] of 29 patients) than in the wild-type only group (26 [28%] of 92; absolute difference 28% [95% CI 14–28]). After adjusting for age and presence of comorbidities, infection with the ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 [95% CI 0·00–0·48]) compared with infection with wild-type virus only. Interpretation The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines. Funding National Medical Research Council Singapore.

Summary Background Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an epidemiological investigation that, with use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays, established links between three clusters of COVID-19. Methods In Singapore, active case-finding and contact tracing were undertaken for all COVID-19 cases. Diagnosis for acute disease was confirmed with RT-PCR testing. When epidemiological information suggested that people might have been nodes of disease transmission but had recovered from illness, SARS-CoV-2 IgG serology testing was used to establish past infection. Findings Three clusters of COVID-19, comprising 28 locally transmitted cases, were identified in Singapore; these clusters were from two churches (Church A and Church B) and a family gathering. The clusters in Church A and Church B were linked by an individual from Church A (A2), who transmitted SARS-CoV-2 infection to the primary case from Church B (F1) at a family gathering they both attended on Jan 25, 2020. All cases were confirmed by RT-PCR testing because they had active disease, except for A2, who at the time of testing had recovered from their illness and tested negative. This individual was eventually diagnosed with past infection by serological testing. ELISA assays showed an optical density of more than 1·4 for SARS-CoV-2 nucleoprotein and receptor binding domain antigens in titres up to 1/400, and viral neutralisation was noted in titres up to 1/320. Interpretation Development and application of a serological assay has helped to establish connections between COVID-19 clusters in Singapore. Serological testing can have a crucial role in identifying convalescent cases or people with milder disease who might have been missed by other surveillance methods. Funding National Research Foundation (Singapore), National Natural Science Foundation (China), and National Medical Research Council (Singapore).

Background Respiratory syncytial virus (RSV) is one of the leading causes of acute respiratory tract infections. To optimize control strategies, a better understanding of the global epidemiology of RSV is critical. To this end, we initiated the Global Epidemiology of RSV in Hospitalized and Community care study (GERi). Methods Focal points from 44 countries were approached to join GERi and share detailed RSV surveillance data. Countries completed a questionnaire on the characteristics of their surveillance system. Results Fifteen countries provided granular surveillance data and information on their surveillance system. A median (interquartile range) of 1641 (552–2415) RSV cases per season were reported from 2000 and 2020. The majority (55%) of RSV cases occurred in the Conclusions The high number of cases in the

Background: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. Methods: We conducted an observational cohort study at seven public hospitals in Singapore. Clinical and laboratory data were collected and compared between individuals infected with different SARS-CoV-2 clades. Firth’s logistic regression was used to examine the association between SARS-CoV-2 clade and development of hypoxia, and quasi-Poisson regression to compare transmission rates. Plasma samples were tested for immune mediator levels and the kinetics of viral replication in cell culture were compared. Findings: 319 patients with PCR-confirmed SARS-CoV-2 infection had clinical and virologic data available for analysis. 29 (9%) were infected with clade S, 90 (28%) with clade L/V, 96 (30%) with clade G (containing D614G variant), and 104 (33%) with other clades ‘O’ were assigned to lineage B.6. After adjusting for age and other covariates, infections with clade S (adjusted odds ratio (aOR) 0·030 (95% confidence intervals (CI): 0·0002-0·29)) or clade O (B·6) (aOR 0·26 (95% CI 0·064-0·93)) were associated with lower odds of developing hypoxia requiring supplemental oxygen compared with clade L/V. Patients infected with clade L/V had more pronounced systemic inflammation with higher concentrations of pro-inflammatory cytokines, chemokines and growth factors. No significant difference in the severity of clade G infections was observed (aOR 0·95 (95% CI: 0·35-2·52). Though viral loads were significantly higher, there was no evidence of increased transmissibility of clade G, and replicative fitness in cell culture was similar for all clades. Interpretation: Infection with clades L/V was associated with increased severity and more systemic release of pro-inflammatory cytokines. Infection with clade G was not associated with changes in severity, and despite higher viral loads there was no evidence of increased transmissibility. Funding Statement: This study was funded by grants from the Singapore National Medical Research Council (COVID19RF- 001, COVID19RF2-0001, COVID19RF-007, and COVID19RF-60) and Biomedical Research Council (project number H20/04/g1/006). Declaration of Interests: No conflicts of interest declared. Ethics Approval Statement: The epidemiological investigation was conducted under the Infectious Diseases Act (Singapore). Study protocols were approved by ethics committees of the National Healthcare Group and SingHealth. Written informed consent was obtained from participants for clinical data and biological sample collection as part of the PROTECT study (2012/00917; 2018/3045). A waiver of informed consent for retrospective data collection only was granted for individuals admitted to the National Centre of Infectious Diseases (2020/01122). Healthy donor samples were collected under study numbers 2017/2806 and NUS IRB 04-140.

Background: Residents in nursing homes are at risk of high morbidity and mortality due to coronavirus disease 2019 (COVID-19). We report the first nursing home COVID-19 outbreak linked to a nursing staff’s household transmission through clinical, epidemiological, laboratory and phylogenetic investigations. Methods: Serial point prevalence testing was conducted among the residents and staff following identification of the index case (a symptomatic resident) with SARS-CoV-2 infection. Active contact tracing, screening of close contacts, whole genome sequencing and phylogenetic analysis were conducted to identify the source and extent of the outbreak. Results: Among the 108 residents and 56 healthcare workers (HCW) in the nursing home, 14 (13%) residents and two (3.6%) HCW were diagnosed with COVID-19, with case fatality rate of 28.6% (4/14) among the residents. Five residents were symptomatic (35.7%) and the others were asymptomatic (64.3%) before the point prevalence survey. The genomic virus typing in this nursing home outbreak was lineage B.6 which is rare among other GISAID clades globally but common regionally. Among the family contacts of the two infected healthcare workers, only one member was infected and had recent travel history. Interpretation: Nursing staffs can be a potential source of infection in nursing home. Through prompt active case finding, and infection prevention and control measures, the outbreak can be contained. Minimising community and household contacts among nursing care staffs may reduce the risk of SARS-CoV-2 introduction into nursing home. Funding: None. Conflict of Interest: The authors declared no conflict of interest. Ethical Approval: Data were collected under the Infectious Disease Act for outbreak investigation and approved by Ministry of Health, Singapore.

Background: To demonstrate the use of a cohort for assessing knowledge, perceptions and behaviours of the Singapore population towards infectious disease outbre

From 2014 to 2017, the World Health Organization convened a working group to evaluate influenza disease burden and vaccine efficacy to inform estimates of maternal influenza immunization program impact. The group evaluated existing systematic reviews and relevant primary studies, and conducted four new systematic reviews. There was strong evidence that maternal influenza immunization prevented influenza illness in pregnant women and their infants, although data on severe illness prevention were lacking. The limited number of studies reporting influenza incidence in pregnant women and infants under six months had highly variable estimates and underrepresented low- and middle-income countries. The evidence that maternal influenza immunization reduces the risk of adverse birth outcomes was conflicting, and many observational studies were subject to substantial bias. The lack of scientific clarity regarding disease burden or magnitude of vaccine efficacy against severe illness poses challenges for robust estimation of the potential impact of maternal influenza immunization programs.KeywordsInfluenzaImmunizationPregnancyInfants

Background: Two measles outbreaks occurred in migrant worker dormitories in Singapore in 2019. We report the outbreak investigation and use of ring vaccination to contain transmission. Methods: We collected clinical and epidemiological data from laboratory-confirmed measles cases and conducted field investigations to examine the interactions between dormitory residents. Two measles seroprevalence studies were performed using 1136 residual sera obtained from Bangladeshi, Chinese and Indian workers previously enrolled in 2016-19 for a study on latent tuberculosis and 101 samples prospectively collected from healthy workers residing on the same level as the index cases. We administered measles, mumps and rubella vaccine to close contacts and dormitory residents residing on the same level as a case (ring vaccination). The effectiveness of ring vaccination in a dormitory of varying contact patterns and population immunity was also evaluated using simulation models. Findings: From Jun 14 to Jul 29, 2019, there were 12 laboratory-confirmed cases of measles from two distinct dormitory outbreaks and 214 close contacts along with 1532 dormitory residents were vaccinated. Measles Immunoglobulin G was detected in 99.5% (95% CI 98.9 – 99.8) of the residual sera and in all blood samples. Outbreaks simulated in a dormitory of 24 194 people, with 90% immunity and an average of 25 contacts per person, revealed a significant reduction in the final outbreak size from 2026 (IQR 1986–2058) cases to 8 (IQR 3– 26) cases when ring vaccination was implemented. In addition, vaccinating each person would avert two new cases. At higher population immunity of 93% and an average of 15 contacts per person, the maximum outbreak size was reduced by 50% with ring vaccination. Interpretation: Measles outbreaks can occur in densely populated areas with high contact rates despite high population immunity. Ring vaccination may be a strategy to protect susceptible contacts to minimise the risk of large outbreaks. Funding Statement: The authors stated: "None." Declaration of Interests: The authors declare no competing interest. Ethics Approval Statement: All epidemiological investigations and outbreak containment measures were implemented under the Infectious Diseases Act, which provides for the use of outbreak investigation data for analysis and evaluation.

SummaryBackgroundThe recent H1N1 pandemic virus that emerged in 2009 resulted in high morbidity rates mainly in younger individuals, albeit with relatively low mortality. We investigated both humoral and cellular immune responses against the pandemic H1N1 2009 virus before and after immunization with inactivated H1N1 2009 vaccine.MethodsWe obtained paired blood specimens from a cohort of participants from nursing homes (n=108) and a public hospital (n=60) in Singapore. Serum samples were tested for neutralizing antibodies against H1N1 2009 using microneutralization assays, while peripheral blood mononuclear cells were subjected to interferon-γ enzyme-linked immunosorbent spot (ELISPOT) assays for whole virus-specific T-cell responses.ResultsWe observed significant increases in geometric mean titers of neutralizing antibodies after H1N1 2009 vaccination (from 23.6 pre-vaccination to 94.7 post-vaccination). Approximately 77% and 54% of the cohort exhibited ≥2-fold and ≥4-fold increases in neutralizing antibody titers following vaccination; 89.9% of the cohort had a post-vaccination antibody titer of ≥32. Adjusted for gender, participants aged ≥60 years were less likely to have a ≥4-fold increase in antibody titers after vaccination than those aged

Background 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 prophylaxis failures and the reasons for failure. Objectives We report herein a series of 10 cases of prophylaxis failures and explore the reasons behind their prophylaxis failure. Study design 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. Results 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. Conclusions Primary prophylaxis failures exhibited mild symptoms without complications; all did not have the H275Y mutation and were unlikely to result from other mutations.