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Background: Enterovirus (EV) outbreaks often coincide with seasonal peaks in the community. However, they may also sporadically occur in neonatal units. Identification of EV infection in neonates can be challenging, as they tend to present with mild or nonspecific symptoms. This study reports an EV outbreak in the Neonatal Unit at KK Women's and Children's Hospital, Singapore., Methods: This is a single-center, retrospective cohort study of neonates who had positive results for EV during the outbreak. Demographic characteristics, clinical presentations and outcomes were analyzed. Control measures used to limit the spread of infection are reported., Results: A total of 7 cases of EV infection were identified. Their median birth weight and gestational age were 1240 g (750 -2890 g) and 28 weeks (26-35 weeks), respectively. Symptoms occurred at a median age of 48 days (9-103 days). All cases presented initially with recurrent apnea and 4 needed assisted ventilator support with CPAP (2) and mechanical ventilation (2). Serious complications occurred in 3 infants (2 with necrotizing enterocolitis and 1 with meningitis) and none died. EV was detected from rectal swabs (n = 6), CSF (n = 2) and nasopharyngeal swabs (n = 2). Viral subtyping uniformly revealed echovirus 25. Surveillance of all exposed infants by nasopharyngeal swabs was implemented, along with strict contact precautions and cohorting measures., Conclusions: Premature infants with EV are more prone to serious complications, which can lead to significant morbidity. Thus, early recognition of symptoms, rapid diagnosis and prompt implementation of infection control measures are key to prevent further spread of infection., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs)., Methods: A 15-year retrospective review was conducted in KK Women's and Children's Hospital in Singapore, from January 2003 to October 2017., Results: Ten patients were identified, the majority male (60.0%). The median age at presentation of symptoms of BCG infections was 3.8 (0.8 - 7.4) months. All the patients had likely underlying PIDS - four with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), one with combined immunodeficiency (CID), and one with STAT-1 gain-of-function mutation. Definitive BCGosis was confirmed in all patients by the identification of Mycobacterium bovis subsp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsp BCG are as follows: Rifampicin (88.9%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent hematopoietic stem cell transplant (HSCT), of which three (60%) have recovered. Overall mortality was 50.0%., Conclusion: Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: In this study, a comparison of clinical, epidemiological and laboratory parameters between symptomatic and asymptomatic children with SARS-CoV-2 infection was performed., Materials and Methods: Data from all children with laboratory confirmed SARS-CoV-2 infection admitted to KK Women's and Children's Hospital (KKH), Singapore, from January to May 2020 were analysed., Results: Of the 39 COVID-19 children included, 38.5% were asymptomatic. Household transmission accounted for 95% of cases. The presenting symptoms of symptomatic children were low-grade fever (54.2%), rhinorrhoea (45.8%), sore throat (25%), diarrhoea (12.5%) and acute olfactory dysfunction (5.4%). Children of Chinese ethnicity (37.5% vs 6.7%), complete blood count (45.8% vs 6.7%) and liver enzyme abnormalities (25% vs 7.7%) were more common in symptomatic versus asymptomatic children. All children had a mild disease course and none required oxygen supplementation or intensive care., Conclusions: The high proportion of asymptomatic infected children coupled with household transmission as the main source of paediatric COVID-19 infection underscores the importance of early screening and isolation of children upon detection of an index case of COVID-19 in a household. Symptomatic children were more likely to have abnormal laboratory parameters but they did not have a poorer outcome compared to asymptomatic cases.

A well 6-month-old infant with coronavirus disease 2019 (COVID-19) had persistently positive nasopharyngeal swabs up to day 16 of admission. This case highlights the difficulties in establishing the true incidence of COVID-19, as asymptomatic individuals can excrete the virus. These patients may play important roles in human-to-human transmission in the community., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected from at least 1 buccal specimen in 9 of 11 coronavirus disease 2019 (COVID-19)-infected children (81.8%). Viral loads in buccal specimens were substantially lower than those in nasopharyngeal specimens. Buccal swabs are not good as COVID-19 screening specimens in children., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Serratia marcescens (S. marcescens) is associated with nosocomial infections with significant morbidity and mortality in the neonatal intensive care units (NICU). We describe the control of a multi-clonal S. marcescens infections outbreak in our tertiary-level NICU and the application of molecular typing using repetitive element palindromic PCR (rep-PCR) and next generation sequencing (NGS) in the investigation., Methods: Outbreak investigation was performed where clinical, spatial and epidemiologic links were established. Screening of all infants in the NICU and the environment was performed. Rep-PCR and NGS methods were used to identify potential environmental sources of infections and clustering among cases., Results: Eleven cases were detected during the outbreak period: mean gestational age 27 weeks (range: 24-32), predominantly male (82%), mean age of infection 24 days (range: 6-51). Six infants were treated for conjunctivitis and one for bacteraemia. Identification of colonized infant via a point prevalence survey and cohorting of all infected/colonized patients were implemented. We performed environmental swabbing of surfaces, water outlets, chlorhexidine hand wash solutions and hand hygiene hand rubs. Both rep-PCR and NGS classified the 11 case isolates into 5 types. No point source was identified except for a single positive environmental isolate from a sink which was clonally distinct from the cases., Conclusion: Identification and cohorting of infected/colonized patient was important in the control of S. marcescens outbreak in the NICU. The utility of rep-PCR was comparable to NGS in providing molecular information to develop S. marcescens outbreak control strategies., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Respiratory syncytial virus (RSV) is the most common cause of pediatric acute lower respiratory tract infection worldwide. Detailed data on the health and economic burden of RSV disease are lacking from tropical settings with year-round RSV transmission. We developed a statistical and economic model to estimate the annual incidence and healthcare cost of medically attended RSV disease among young children in Singapore, using Monte Carlo simulation to account for uncertainty in model parameters. RSV accounted for 708 hospitalizations in children <6 months of age (33.5/1,000 child-years) and 1,096 in children 6-29 months of age (13.2/1,000 child-years). The cost of hospitalization was SGD 5.7 million (US $4.3 million) at 2014 prices; patients bore 60% of the cost. RSV-associated disease burden in tropical settings in Asia is high and comparable to other settings. Further work incorporating efficacy data from ongoing vaccine trials will help to determine the potential cost-effectiveness of different vaccination strategies.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background: The concurrent sampling design was developed for case-control studies of recurrent events. It involves matching for time. Standard conditional logistic-regression (CLR) analysis ignores the dependence among recurrent events. Existing methods for clustered observations for CLR do not fit the complex data structure arising from the concurrent sampling design., Methods: We propose to break the matches, apply unconditional logistic regression with adjustment for time in quintiles and residual time within each quintile, and use a robust standard error for observations clustered within persons. We conducted extensive simulation to evaluate this approach and compared it with methods based on CLR. We analysed data from a study of childhood pneumonia to illustrate the methods., Results: The proposed method and CLR methods gave very similar point estimates of association and showed little bias. The proposed method produced confidence intervals that achieved the target level of coverage probability, whereas the CLR methods did not, except when disease incidence was low., Conclusions: The proposed method is suitable for the analysis of case-control studies with recurrent events., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Studies investigating timeliness for childhood vaccination are limited especially in Asia. We examined the timeliness of vaccine administration and associated factors among infant and young children in Singapore. A total of 782 children born between November 2009 and July 2011 from a prospective cohort in Singapore were studied. Vaccination records from birth to 24 months of age were obtained from the National Immunization Registry of Singapore. Multivariable logistic regression models were performed. By 2 years of age, 92.8% of children in our cohort experienced a delay in receiving 1 or more vaccine doses according to the recommended national immunization schedule. When vaccinations were reviewed by series for each vaccine, 15.6% received all vaccine series outside the recommended age ranges. Factors associated with receiving vaccination series outside the recommended ages included maternal aged ≤ 35 years (OR 2.00; 95% CI 1.09, 3.66), Malay (1.71; 1.01, 2.89) or Indian ethnicity (2.06; 1.19, 3.59), low monthly household income (1.91; 1.14, 3.18), having at least four children (3.46; 1.62, 7.38) and private (3.42; 1.80, 6.48) and multiple vaccination providers (3.91; 1.23, 12.48). These findings show an unacceptably high proportion of children experienced a delay in the receipt of their vaccinations. The identification of several demographic, socioeconomic, health-seeking behavioural and vaccine provider factors provides opportunities for targeted interventions to enhance the timeliness of childhood vaccination in Singapore.

Severe haze episodes originating from biomass burning are common in Southeast Asia. However, there is a paucity of data on the personal exposure and characteristics of Particulate Matter (PM) present in ambient air during haze and non-haze periods. Aims of this study were to monitor 24 h ambulatory exposure to PM among school children in Singapore; characterize haze and non-haze PM for their physicochemical properties, cytotoxicity and inflammatory potential, using bronchial epithelial cell culture model (BEAS-2B). Forty-six children had ambulatory PM exposure monitored using portable Aethalometer and their hourly activity recorded. The mean (±SE) PM exposure on a typical school day was 3343 (±174.4) ng/m 3 /min. Higher PM exposure was observed during haze periods and during commuting to and from the school. Characterization of PM collected showed a drastic increase in the proportion of ultrafine particle (UFP) in haze PM. These PM fraction showed higher level of sulphur, potassium and trace metals in comparison to those collected during non-haze periods. Dose dependent increases in abiotic reactive oxygen species generation, activation of NF-κB and cytotoxicity were observed for both haze and non-haze PM. Generally, haze PM induced significantly higher release of IL-6, IL-8 and TNFα by BEAS-2B cells in comparison to non-haze PM. In summary, this study provides experimental evidence for higher PM exposure during haze period which has the potential to elicit oxidative stress and pro-inflammatory cytokine release from airway epithelial cells., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: In tropical Singapore, influenza occurs all year-round. This study of influenza-confirmed hospitalized pediatric patients compared clinical characteristics and complications by age-group and differences between influenza A and B., Methods: This was a retrospective study of pediatric inpatients from January 2013 to December 2014. Patients were grouped into: <6 months, 6 months to <5 years, 5- to <10-year and ≥10 years. Complications were classified into neurologic, pulmonary, and other. We also calculated the incidence of hospitalized influenza cases per 100 000 age-related population., Results: There were a total of 1272 patients with a median age of 37 months. The highest hospitalization rates were in the <6 months age-group. Majority (75.2%) had no comorbidity; 25.6% had complications: neurologic 11.9%, pulmonary 9.6%, other 4.1%. Patients with other complications were older, male, and had the highest influenza B rates and the longest length of stay. Influenza A comprised 76.9% of cases and had higher complication rates especially neurologic, compared to influenza B. Influenza B patients were older and were more likely to develop other complications. The 6-month to <5-year-age-group had the highest complication rate (30.6%), especially neurologic. However, ≥10 years old had the highest other complications, ICU/ high-dependency admissions and influenza B Victoria rates., Conclusions: Infants <6 months had the highest hospitalization rates for influenza. The 6-month to <5-year-age-group had the highest complication rate especially neurologic. Influenza A patients were younger, had higher seizure rates and complications compared to influenza B., (© 2019 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Epstein-Barr virus (EBV) spreads through bodily fluids, especially saliva, and can cause infectious mononucleosis. EBV immunity and infection status can be assessed by testing EBV viral capsid antigen and nuclear antigen (EBNA) antibodies in blood. In this study, we investigated the seroprevalence and force of infection (FOI) of EBV antibodies among children and young people in 3 ethnic groups in Singapore., Methods: Eight hundred ninety-six residual serum samples at a tertiary hospital were tested for viral capsid antigen (IgG and IgM) and EBNA IgG antibodies using Abbott Architect assays. We calculated the EBV seroprevalence using catalytic models to estimate the EBV force of infection from age-stratified seroprevalence data, both overall and by ethnic group., Results: Overall seropositivity was 68.3% (n = 612). Seropositivity was higher in Malays (81.8%) compared with both Chinese (64.2%) and Indians (58.4%). EBV FOI was consistently higher in Malays, with an estimated annual rate of seroconversion of 25% in children 1 year, of age compared with 14% among Chinese and Indians at the same age., Conclusions: The seroprevalence patterns of EBV antibodies in the Chinese and Indian, but not Malay children in Singapore by 19 years of age resemble those previously reported in developed countries. Ideally, any future EBV vaccination strategy would need to target infants <1 year of age for maximum population benefit.

Kawasaki disease (KD) is a systemic vasculitis mainly affecting young children and the leading cause of acquired heart disease in developed countries. We performed a self-controlled case series analysis to investigate the association between PCV13 and KD. All hospitalized KD cases <2 y old from our hospital in Singapore from 2010 to 2014 were included. Complete KD cases were classified based on the definitions of the American Heart Association. During the study period, 288 KD cases were identified. A total of 21 KD cases (12 were classified as Complete KD) had date of onset within the risk interval of day 1 to day 28 post PCV13. The age-adjusted Relative Incidence (RI) for KD following PCV13 dose 1, dose 2 and dose 3 were 1.40 (95%CI, 0.72 to 2.71), 1.23 (95% CI, 0.62 to 2.44) and 0.34 (95% CI, 0.08 to 1.40) respectively. There were seven Complete KD cases with onset during the risk interval after dose 1 of PCV13 (age-adjusted RI 2.59, 95%confidence interval (CI), 1.16 to 5.81). We did not detect a significant increased risk for overall KD among PCV13 recipients. However, a significant association between PCV13 and Complete KD was noted following receipt of the first dose of PCV13.

In Asia, the public health burden of influenza is significant despite the existence of efficacious influenza vaccines. Annual seasonal influenza vaccination can reduce the incidence of influenza significantly, yet influenza vaccination coverage remains low in this part of the world. As a densely populated region with varying climatic zones and a larger proportion of developing countries compared to the West, Asia is at increased risk of influenza. To provide a more comprehensive and nuanced understanding of the Asian region, the key objective of this systematic review is to examine the determinants of vaccination uptake in Asia, beyond that of existing studies that have largely been western-centric. We carried out a systematic review of peer-reviewed scientific research, examining the key determinants, acceptance and uptake of influenza vaccinations across Asia. A comprehensive search strategy was defined to capture studies that met the inclusion criteria of articles published in English, from 2008 to 2018, focusing on adult populations within Asia. A total of 83 relevant studies were appraised in this review. Analyses of the extant data confirmed that vaccination rates within Asia are low, and that most countries lack scientific research on vaccination behaviours. Studies were categorised into four different population groups: healthcare workers, high risk groups, general population and uniform groups. The motivators and deterrents for vaccine uptake varied according to population groups and characteristics. Both general populations and healthcare workers were concerned with vaccine safety and efficacy, and recommendations from health authorities were influential in vaccine uptake within the other populations. The findings suggest that further research is needed within a broader range of Asian countries to garner greater in-depth knowledge of vaccination behaviours in the region. In particular, influenza vaccination programs within Asia should focus on improving engagement more effectively, through greater relatability and transparency of data when educating the public., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Elizabethkingia meningoseptica is a multi-drug-resistant organism that is associated with high mortality and morbidity in newborn and immunocompromised patients. This study aimed to identify the best antimicrobial therapy for treating this infection., Methods: A retrospective descriptive study was conducted from 2010 to 2017 in a tertiary paediatric hospital in Singapore. Paediatric patients aged 0 to 18 years old with a positive culture for E. meningoseptica from any sterile site were identified from the hospital laboratory database. The data collected included clinical characteristics, antimicrobial susceptibility and treatment, and clinical outcomes., Results: Thirteen cases were identified in this study. Combination therapy with piperacillin/tazobactam and trimethoprim/sulfamethoxazole or a fluoroquinolone resulted in a cure rate of 81.8  %. The mortality rate was 15.4  % and neurological morbidity in patients with bacteraemia and meningitis remained high (75 %)., Conclusions: Treatment with combination therapy of piperacillin/tazobactam and trimethoprim/sulfamethoxazole or a fluroquinolone was effective in this study, with low mortality rates being observed.

Background: Pregnant women are at increased risk of influenza-related complications. The World Health Organisation recommends influenza vaccination to this high-risk population as highest priority. However, achieving high influenza vaccine coverage among pregnant women remains challenging. We conducted a cross-sectional survey to estimate the coverage and determinants of influenza vaccination among pregnant women in Singapore., Methods: Between September and November 2017, pregnant women aged ≥21 years were recruited at two public hospitals in Singapore. Participants completed an anonymous, self-administered online questionnaire assessing participants' influenza vaccination uptake, knowledge of and attitudes towards influenza and the influenza vaccine, vaccination history, willingness to pay for the influenza vaccine, and external cues to vaccination. We estimated vaccine coverage and used multivariable Poisson models to identify factors associated with vaccine uptake., Results: Response rate was 61% (500/814). Only 49 women (9.8, 95% Confidence Interval (CI): 7.3-12.7%) reported receiving the vaccine during their current pregnancy. A few misconceptions were identified among participants, such as the belief that influenza can be treated with antibiotics. The most frequent reason for not being vaccinated was lack of recommendation. Women who were personally advised to get vaccinated against influenza during pregnancy were 7 times more likely to be vaccinated (prevalence ratio (PR) = 7.11; 95% CI: 3.92-12.90). However, only 12% of women were personally advised to get vaccinated. Other factors associated with vaccine uptake were vaccination during a previous pregnancy (PR = 2.51; 95% CI: 1.54-4.11), having insurance to cover the cost of the vaccine (PR = 2.32; 95% CI: 1.43-3.76), and higher vaccine confidence (PR = 1.62; 95% CI: 1.30-2.01)., Conclusions: Influenza vaccination uptake among pregnant women in Singapore is low. There is considerable scope for improving vaccination coverage in this high-risk population through vaccination recommendations from healthcare professionals, and public communication targeting common misconceptions about influenza and influenza vaccines.

Background: Antibody titres and vaccine effectiveness decline within 6 months after influenza vaccination in older adults. Biannual vaccination may be necessary to provide year-round protection in the tropics, where influenza circulates throughout the year., Methods: Tropical Influenza Control Strategies (TROPICS1) was a single-center, 1:1 randomized, observer-blinded, active-comparator-controlled, superiority study in 200 community-resident adults aged ≥65 years. Participants received a standard-dose trivalent inactivated influenza vaccination (IIV3) at enrollment, and either tetanus-diphtheria-pertussis vaccination or IIV3 6 months later. The primary outcome was the proportion of participants with haemagglutination-inhibition (HI) geometric mean titre (GMT) ≥1:40 1 month after the second vaccination (month 7). Secondary outcomes included GMTs to month 12, the incidence of influenza-like illness (ILI), and adverse reactions after vaccination., Results: At month 7, the proportion of participants with an HI tire ≥1:40 against A/H1N1 increased by 21.4% (95% confidence interval [CI] 8.6-33.4) in the semiannual vaccination group. This proportion was not significantly higher for A/H3N2 (4.3, 95% CI -1.1-10.8) or B (2.1, 95% CI -2.0-7.3). Semiannual vaccination significantly increased GMTs against A/H1N1 and A/H3N2, but not B, at month 7. Participants receiving a repeat vaccination of IIV3 reported a significantly lower incidence of ILI in the 6 months after the second vaccination (relative vaccine effectiveness 57.1%, 95% CI 0.6-81.5). The frequency of adverse events was similar after the first and second influenza vaccinations., Conclusions: Semiannual influenza vaccination in older residents of tropical countries has the potential to improve serological measures of protection against infection. Alternative vaccination strategies should also be studied., Clinical Trials Registration: NCT02655874., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The burden of respiratory viral infections (RVIs) among preterm infants in the first few years of life, especially those living in the tropics with year-long transmissions of respiratory viruses, remains unknown. We aimed to describe the clinical epidemiology and associated risk factors for RVIs among symptomatic preterm infants ≤32 weeks up to 2 years of life., Methods: We performed a data linkage analysis of clinical and hospital laboratory databases for preterm infants born at KK Women's and Children's Hospital, Singapore, from 2005 to 2015. RVI episodes during initial admission and subsequent hospital readmissions were included., Results: Of 1854 infants in the study, 270 (14.5%) infants were diagnosed with at least 1 RVI. A total of 285 (85.3%) episodes were diagnosed postdischarge, with the highest risk for RVIs being from 3 to 5 months of age. The incidence of RVI in this population was 116 per 1000 infant-years and respiratory syncytial virus was the main overall causative pathogen. Infants with RVIs were more likely to be born at ≤27 weeks' gestational age (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.3), to have received postnatal steroids (OR, 1.5; 95% CI, 1.0-2.1), and to be diagnosed with bronchopulmonary dysplasia (OR, 1.7; 95% CI, 1.2-2.4)., Conclusions: The burden of RVIs is high in preterm infants in the tropics, affecting >1 of 10 infants born at ≤32 weeks' gestation before 2 years of age. Respiratory syncytial virus was the main causative pathogen identified. Risk factors for RVI included extremely low gestational age, receipt of postnatal steroids, and bronchopulmonary dysplasia.

We report an Elizabethkingia anophelis case cluster associated with contaminated aerators and tap water in a children's intensive care unit in Singapore in 2017. We demonstrate a likely transmission route for E. anophelis to patients through acquisition of the bacteria on hands of healthcare workers via handwashing.

Background: Influenza vaccine acceptance among healthcare workers (HCWs) is a worldwide problem, but relatively little research has focussed on Asia, including Singapore. Despite widespread access and recommendations from public health authorities, influenza vaccine uptake remains suboptimal among HCWs., Methods: Our qualitative study used focus group discussions to identify and explain factors limiting influenza vaccine acceptance among HCWs in Singapore. A total of 73 doctors, nurses, allied health and ancillary staff across three public hospitals were included., Results: Challenges identified include a fear of contracting influenza from vaccination exacerbated by negative anecdotes regarding vaccine safety and efficacy, distrust of published efficacy data, uncertainty regarding relevance of existing data for Singapore, reluctance to introduce chemicals or overmedicate, pain from injection, low risk attributed to influenza and limited awareness of influenza transmission with a preference for alternatives in patient protection. Differences in attitudes were observed across vocational groups. Lack of overt promotion by hospital leadership in some institutions, perceived vaccine hesitancy among doctors, access, and work culture that implicitly encourages working through illness were further barriers., Conclusion: Our findings highlight a combination of misperceptions about influenza vaccination and cognitive biases at the individual level, and challenges at the institutional level limiting uptake. Findings indicate an urgent need to provide targeted education and communication. Rather than providing more data, we recommend a widely-disseminated, locally-compiled synthesis addressing specific concerns of hesitant HCWs. Tailoring interventions to specific vocational groups should be considered. Institutional norms and culture may have a powerful influence in setting default behaviours: more effort is needed in improving influenza vaccine promotion and priority at some institutions, integrating vaccine-related communication with other infection control communication and addressing influenza vaccine hesitancy among doctors as a priority. Finally, further study of strategies to address cognitive biases affecting influenza vaccine acceptance in Singapore is desirable., (Copyright © 2018. Published by Elsevier Ltd.)

This systematic review and meta-analysis quantified the protective effect of facemasks and respirators against respiratory infections among healthcare workers. Relevant articles were retrieved from Pubmed, EMBASE, and Web of Science. Meta-analyses were conducted to calculate pooled estimates. Meta-analysis of randomized controlled trials (RCTs) indicated a protective effect of masks and respirators against clinical respiratory illness (CRI) (risk ratio [RR] = 0.59; 95% confidence interval [CI]:0.46-0.77) and influenza-like illness (ILI) (RR = 0.34; 95% CI:0.14-0.82). Compared to masks, N95 respirators conferred superior protection against CRI (RR = 0.47; 95% CI: 0.36-0.62) and laboratory-confirmed bacterial (RR = 0.46; 95% CI: 0.34-0.62), but not viral infections or ILI. Meta-analysis of observational studies provided evidence of a protective effect of masks (OR = 0.13; 95% CI: 0.03-0.62) and respirators (OR = 0.12; 95% CI: 0.06-0.26) against severe acute respiratory syndrome (SARS). This systematic review and meta-analysis supports the use of respiratory protection. However, the existing evidence is sparse and findings are inconsistent within and across studies. Multicentre RCTs with standardized protocols conducted outside epidemic periods would help to clarify the circumstances under which the use of masks or respirators is most warranted., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Pertussis causes the highest complication rates and deaths in the infant group. Our study explored risk factors for ICU/high dependency (HD) admissions and intubation/non-invasive ventilation (NIV)., Methods: A retrospective review of pertussis admissions over 10 years from 2007 to 2016 was done at KK Women's and Children's Hospital, Singapore. To understand risk factors for severe pertussis infection, we compared cases requiring ICU/HD care with controls admitted to the general ward. Risk factors for intubation/NIV were also studied. Vaccine efficacy for protection against ICU/HD admission or intubation/NIV was also calculated., Results: There were 200 pertussis patients with a median age of 2.75 months. Sixty-one % were ≤3 months and 14.5% were <6 weeks old. Majority of patients (77%) had no prior pertussis vaccination. After removing 3 patients with missing vaccination records, 20 cases were compared with 177 controls. On univariate analysis, risk factors for ICU/HD admission comprised: Age ≤3 months, contact history, underlying co-morbidity, prematurity, absent DTaP vaccination, lymphocytosis, hyperleukocytosis (wbc ≥50×10 9 /L), thrombocytosis (platelet ≥500×10 9 /L), and pneumonia. Multivariate analysis revealed that age ≤3 months (OR 40, 95% CI 4.57-1111.11, p=.007), co-morbidity (OR 8.46 (95% CI 1.47-56.89, p=.019), pneumonia (OR 18.08, 95% CI 3.22-132.15, p=.002), white cell count (OR 1.07, 95% CI 1.01-1.14, p=.023) and cyanosis (OR 5.09, 95% CI 1.31-24.71, p=.026) were risk factors for ICU/HD admission. Prior DTaP vaccination had a vaccine effectiveness of 86.5% in preventing ICU/HD admission and 82.1% in preventing intubation/NIV., Conclusions: As the majority of pertussis patients were infants ≤3 months old who are at high risk for ICU/HD admission and intubation/NIV, prevention is key to reducing pertussis morbidity. Even though not statistically significant, DTaP vaccination had a role in preventing ICU/HD admission and intubation/NIV., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: With the global outbreak of Zika virus and its association with microcephaly, an up-to-date fetal head circumference (HC) nomogram is crucial to offer a reference standard in order to make an accurate diagnosis. This study was conducted to revise the local fetal HC nomogram., Materials and Methods: In this retrospective study, ultrasound data was used for construction of the fetal HC nomogram from a total of 6155 pregnancies in the ethnic Chinese population with low risk profile at KK Women's and Children's Hospital over a 10-year period. Regression model was fitted to calculate the mean and standard deviation of HC at each gestational age (GA). Comparison of HC between ethnic groups (no significant differences) and genders were made. The revised chart was compared with another commonly used reference chart (Hadlock). In an independent test population, different reference charts were used to estimate number of cases with microcephaly., Results: A statistically significant difference of HC between the genders was observed across all gestational ages. Gender-specific reference charts and equation were computed. Our revised fetal HC chart showed a different distribution from the Hadlock chart. Compared with the gender-specific charts, the Hadlock HC chart would significantly under-report microcephaly cases in male fetuses, and tend to over-report in female fetuses., Conclusion: This study provides a new set of gender-specific fetal HC charts in the Singaporean population for antenatal ultrasound surveillance of microcephaly.

In the first reported pediatric case series of virologically confirmed Zika virus (ZIKV) infections from Southeast Asia, ZIKV infection was generally mild. Routine screening of children with suspected ZIKV infection for dengue virus coinfection should be considered in dengue-endemic countries., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: We report the results of a rapid assessment of Zika virus awareness among key clinical specialties in Singapore., Methods: Between June 6 and June 19, 2016 we conducted an online survey of doctors working in obstetrics and gynaecology, neonatology and paediatrics in Singapore. The survey included 15 multiple choice questions to measure respondents' knowledge of Zika virus in four domains covering clinical and public health., Results: A total of 110 survey responses (15% response rate) were obtained, 82% of respondents worked in the public sector. Overall, the median respondent score was 9.4 (Max score=15), with substantial variation (range: 3.5 - 14.7). Microcephaly and Guillain-Barré syndrome were recognised as causal complications of Zika virus infection by 99% and 50% of respondents respectively.  Clinical features which could help differentiate Zika from Dengue were less well understood with 50% and 68% correctly identifying conjunctivitis and low grade fever respectively. Worryingly, 14% favoured non-steroidal anti-inflammatory drugs as part of treatment, without first excluding dengue as a diagnosis. Also, only 36% of respondents were aware of the current recommendation for preventing sexual transmission of Zika virus. Fewer than 50% were aware of the need for ophthalmological evaluation as part of congenital Zika virus infection., Discussion: Our assessment demonstrates that there is good awareness of the clinical manifestation of Zika virus disease among key specialty doctors, but confusion with Dengue disease remains. It also highlights knowledge gaps in the prevention of sexually-transmitted Zika virus infection and the clinical management of congenital Zika virus infection in newborns. Our study identified strategic areas to improve communication to front-line doctors during public health response to the Zika epidemic.

Singapore is a hotspot for emerging infectious diseases and faces a constant risk of pandemic outbreaks as a major travel and health hub for Southeast Asia. With an increasing penetration of smart phone usage in this region, Singapore's pandemic preparedness framework can be strengthened by applying a mobile-based approach to health surveillance and control, and improving upon existing ideas by addressing gaps, such as a lack of health communication. FluMob is a digitally integrated syndromic surveillance system designed to assist health authorities in obtaining real-time epidemiological and surveillance data from health-care workers (HCWs) within Singapore, by allowing them to report influenza incidence using smartphones. The system, integrating a fully responsive web-based interface and a mobile interface, is made available to HCW using various types of mobile devices and web browsers. Real-time data generated from FluMob will be complementary to current health-care- and laboratory-based systems. This paper describes the development of FluMob, as well as challenges faced in the creation of the system.

Background: The seasonal influenza vaccine is less effective in older people and a single dose is unlikely to provide the year-round protection necessary for tropical climates which have year-round influenza virus activity. This study aims to assess the effect of a trivalent inactivated influenza vaccine (IIV3) booster at 180 days on haemagglutination-inhibition (HI) antibody titres for each of the influenza strains present in the administered vaccine in older people aged 65 years or above in Singapore., Methods/design: This is a single-centre, randomised, observer-blind, active-comparator controlled, parallel-group, phase IV trial in 200 adults aged 65 years or older. Study participants will be assigned to one of two groups in a 1:1 ratio and followed for 1 year, with five scheduled visits. The control group will receive IIV3 at day 1, and an active comparator (Tetanus-diphtheria-pertussis vaccine) at day 180. Participants in the experimental group will receive IIV3 containing the same strains at day 1 and day 180. Endpoints are immunological, and include measures of HI titres, microneutralisation titres (MN) and cell-mediated immunity from first vaccination up to day 360., Discussion: If superiority of 6-monthly influenza vaccination is demonstrated, this study could form the basis for a larger clinical trial with influenza infection as the primary endpoint., Trial Registration: ClinicalTrials.gov, ID: NCT02655874 . Registered on 12 January 2016.

Introduction: The epidemiology of naturally occurring intussusception is known to increase significantly between the ages of 3 and 8 months. Post-licensure studies have reported a fivefold and twofold increase in intussusception in the first week after the first dose and second dose, respectively, of current rotavirus vaccines (RVs)., Purpose: We carried out a public health risk analysis to model the impact of age at first vaccination in relation to rotavirus vaccination and risk of intussusception in infants., Method: We created a static model for a birth cohort followed until 1 year old to estimate the number of excess intussusception hospitalizations which could be caused by three different infant rotavirus vaccination schedules. A relative risk of 5.45 in the first 7 days after the first dose and 1.75 in the first 7 days after the second dose was used in the model., Result: We estimated that the risk of intussusception would be the lowest at about 1 in 49,000 if both first and second dose RVs were given at <3 months of age followed by 1 in 41,000 if first dose RVs were given at <3 months and second dose RVs were given at 3-5 months. It would be highest at about 1 in 11,000 if infants received both doses when >3 months old., Conclusion: Our epidemiological example illustrates the importance of ensuring that the first two doses of RVs are administered in infants <3 months old whenever possible to minimize the risk of intussusception as an adverse event following rotavirus vaccination.

Background: Understanding changes in the ecology and epidemiology of dengue is important to ensure resource intensive control programmes are targeted effectively as well as to inform future dengue vaccination strategies., Methods: We analyzed data from a multicentre longitudinal prospective study of fever in adults using a nested test negative case control approach to identify epidemiological risk factors for dengue disease in Singapore. From April 2005 to February 2013, adult patients presenting with fever within 72 h at selected public primary healthcare clinics and a tertiary hospital in Singapore were recruited. Acute and convalescent blood samples were collected and used to diagnose dengue using both PCR and serology methods. A dengue case was defined as having a positive RT-PCR result for DENV OR evidence of serological conversion between acute and convalescent blood samples. Similarly, controls were chosen from patients in the cohort who tested negative for dengue using the same laboratory methods., Results: The host epidemiological factors which increased the likelihood of dengue disease amongst adults in Singapore were those aged between 21 and 40 years old (2 fold increase) while in contrast, Malay ethnicity was protective (OR 0.57, 95%CI 0.35 to 0.91) against dengue disease. Spatial factors which increased the odds of acquiring dengue was residing at a foreign workers dormitory or hostel (OR 3.25, 95 % CI 1.84 to 5.73) while individuals living in the North-West region of the country were less likely to get dengue (OR 0.50, 95%CI 0.29 to 0.86). Other factors such as gender, whether one primarily works indoors or outdoors, general dwelling type or floor, the type of transportation one uses to work, travel history, as well as self-reported history of mosquito bite or household dengue/fever were not useful in helping to inform a diagnosis of dengue., Conclusions: We have demonstrated a test negative study design to better understand the epidemiological risk factors of adult dengue over multiple seasons. We were able to discount other previously speculated factors such as gender, whether one primarily works indoors or outdoors, dwelling floor in a building and the use of public transportation as having no effect on one's risk of getting dengue.

Background: Protection after meningococcal C (MenC) conjugate (MCC) vaccination in early childhood is short-lived. Boosting with a quadrivalent vaccine in teenage years, a high-risk period for MenC disease, should protect against additional serogroups but might compromise MenC response. The carrier protein in the primary MCC vaccine determines the response to MCC booster in toddlers, but the relationship between primary vaccine and booster given later is unclear. This study compared responses to a CRM-conjugated or tetanus toxoid (TT)-conjugated MenACWY vaccine in teenagers primed with different MCC vaccines at preschool age., Methods: Ninety-three teenagers (16-19 years), who were previously randomized at age 3-6 years to receive single-dose MCC-CRM or MCC-TT, were randomized to receive either MenACWY-CRM or MenACWY-TT booster. Serum bactericidal antibodies (SBA, protective titer ≥ 8) were measured before, 1 month and 6 or 9 months after boosting., Results: Preboosting, MCC-TT-primed teenagers had significantly higher MenC SBA titers than those MCC-CRM-primed (P = 0.02). Postboosting, both MenACWY vaccines induced protective SBA titers to all 4 serogroups in most participants (≥ 98% at 1 month and ≥ 90% by 9 months postboost). The highest MenC SBA titers were seen in those MCC-TT-primed and MenACWY-TT-boosted [geometric mean titer (GMT) ~ 22,000] followed by those boosted with MenACWY-CRM irrespective of priming (GMT ~ 12,000) and then those MCC-CRM-primed and MenACWY-TT-boosted (GMT ~ 5500). The estimated postbooster MenC SBA decline beyond 1 month was ~40% as time since booster doubles. Both vaccines were well tolerated with no attributable serious adverse events., Conclusion: Both MenACWY vaccines safely induced protective sustained antibody responses against all targeted serogroups in MCC-primed teenagers.

Objective: To investigate the association between monovalent human rotavirus vaccine (RV1) and intussusception among Asian infants and the impact of older age of vaccination. To perform risk-benefit analysis of RV1 vaccination programs in Singapore., Study Design: We performed a self-controlled case series by extracting intussusception cases in infants aged <12 months from hospital databases (2005-2012) and with vaccination histories from a national immunization registry. Relative incidences were calculated by comparing incidence during defined risk periods after vaccination with times outside these periods. In the risk benefit analysis, we estimated excess intussusception hospitalization in relation to the number of infants vaccinated for hypothetical vaccination coverage scenarios., Results: There were 86 infants hospitalized with intussusception; 20 cases had received at least 1 dose of RV1. Nearly all (19) had received their first dose at age >12 weeks old. The age-adjusted relative incidence of intussusception in the 1- to 7-day period post dose one was 8.36 (95% CI 2.42-28.96). Of all childhood hospitalizations because of rotavirus, 71% (570 cases) could be prevented with 90% vaccination coverage. There would be approximately 1 excess intussusception case per 65,000 infants vaccinated., Conclusions: Risk of intussusception increases about 8-fold during 1-7 days after receipt of first dose RV1 in infants of Chinese, Malay, and Indian ethnicity in Singapore, Asia. High vaccine coverage program in Singapore would be beneficial with only a low risk of excess intussusception. The relative risk of intussusception post-RV1 vaccination is not higher in Asia despite differences in background intussusception incidence compared with US and Australia, or older age of vaccination., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Studies on serotype-specific features of dengue and disease severity on adults are limited. We prospectively recruited adult febrile patients without alternate diagnosis to dengue from April 2005 to December 2011. Outcomes were defined using both the World Health Organization (WHO) 1997 and 2009 criteria; Dengue hemorrhagic fever (DHF) and severe dengue (SD). Infecting serotype was identified in 469 dengue-confirmed patients comprising 22.0% dengue virus serotype 1 (DENV-1), 57.1% DENV-2, 17.1% DENV-3, and 3.8% DENV-4. Cases infected with DENV-1 were more likely to present with red eyes whereas presence of joint pain and lower platelet count was associated with DENV-2 cases. After adjusting for potential confounders, DENV-1 was associated with both DHF (adjusted Relative Risk [aRR] = 1.74) and SD (aRR = 2.1) whereas DENV-2 had a lower risk of DHF (aRR = 0.5). DENV-1 genotype 1 and DENV-2 cosmopolitan were the predominant genotypes identified. Infecting dengue serotype and possibly genotype may play an important role in disease severity among adult dengue patients in Singapore., (© The American Society of Tropical Medicine and Hygiene.)

Introduction: From 2011 to 2012, we received an unexpectedly high number of reports of suppurative lymphadenitis following administration of a BCG vaccine used in our childhood vaccination programme in Singapore. We sought to determine the local incidence rates of BCG-associated suppurative lymphadenitis across the 2009 to 2012 vaccinated cohorts, and to analyse the potential factors contributing to this outbreak., Methods: Reports of lymphadenitis following BCG vaccination from an AEFI active surveillance system at the KK Women's and Children's Hospital (KKH) and passive surveillance data from other healthcare institutions were reviewed. All valid reports received from January 2009 to December 2013 involving neonates vaccinated with the BCG vaccine in 2009 to 2012 that met case definitions were included in our analysis. Details of the demographics and vaccination history of the child, and statistics from the local vaccination programme were also obtained. Potential contributory factors were selected for further investigation based on a literature review of similar outbreaks overseas., Results: We identified 283 cases of lymphadenitis, of which 76% were suppurative. A spike in suppurative lymphadenitis cases was seen in the 2011 vaccinated cohort, with an incidence rate of 3.16 per 1000 vaccinees, as compared to 0.71 to 0.85 per 1000 in the 2009, 2010 and 2012 cohorts. Our investigations identified the likely cause of the outbreak to be batch-related, arising from manufacturing issues encountered by the manufacturer, after ruling out vaccine administration-related and host-related factors., Conclusions: The three-fold spike in BCG-associated suppurative lymphadenitis cases observed in the 2011 vaccinated cohort, possibly due to batch-to-batch variation of the vaccine, highlights that manufacturing controls can continue to be a challenge. Development of a more sensitive assay to test the reactogenicity of the BCG vaccine may help reduce the occurrence of such outbreaks and improve public confidence in the nation's vaccination programme., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: In Singapore, reporting of adverse events following immunization (AEFI) was historically passive. In 2009, Health Sciences Authority collaborated with KK Women's and Children's Hospital to perform active surveillance for AEFI. We report the methodology and initial findings of this surveillance following childhood vaccines., Methods: From April 2010 to March 2012, we screened all paediatric admissions for possible relationships to vaccination, excluding elective admissions, and performed causality assessment for each case using standardized definitions for certain, probable, possible and unlikely. Baseline demographics, data on implicated vaccines and clinical details including severity and outcomes were collected. Total hospital admissions were used to calculate rates of AEFI., Results: We screened 45,571 (80%) of 56,526 admissions, and evaluated 1988 (4.4%) children. Median age at presentation was 3.1 months, while median interval from vaccination to symptom onset was 6 days. There were 311 (15.6%) children with AEFI that were considered possibly, probably or certainly associated with vaccines. However, 98.8% recovered without any long-term sequelae. The hospital-based active surveillance of AEFI enabled the detection of a 5-fold increase (95% CI 1.2-33.1) in BCG-associated regional lymphadenitis in April 2010, which triggered follow-up safety analysis to guide public health advice., Conclusions: Hospital-based active surveillance can enhance signal detection and follow-up investigations of AEFI. Subsequently, public health bodies are better equipped to maintain public confidence in vaccination programmes and physicians are able to provide relevant advice to parents. It also allows for a better understanding of risk-benefit ratios of specific vaccines and aids the generation of public health vaccination policy., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: In 2009, the World Health Organization (WHO) proposed seven warning signs (WS) as criteria for hospitalization and predictors of severe dengue (SD). We assessed their performance for predicting dengue hemorrhagic fever (DHF) and SD in adult dengue., Method: DHF, WS and SD were defined according to the WHO 1997 and 2009 dengue guidelines. We analyzed the prevalence, sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of WS before DHF and SD onset., Results: Of 1507 cases, median age was 35 years (5(th)-95(th) percentile, 17-60), illness duration on admission 4 days (5(th)-95(th) percentile, 2-6) and length of hospitalization 5 days (5(th)-95(th) percentile, 3-7). DHF occurred in 298 (19.5%) and SD in 248 (16.5%). Of these, WS occurred before DHF in 124 and SD in 65 at median of two days before DHF or SD. Three commonest warning signs were lethargy, abdominal pain/tenderness and mucosal bleeding. No single WS alone or combined had Sn >64% in predicting severe disease. Specificity was >90% for both DHF and SD with persistent vomiting, hepatomegaly, hematocrit rise and rapid platelet drop, clinical fluid accumulation, and any 3 or 4 WS. Any one of seven WS had 96% Sn but only 18% Sp for SD., Conclusions: No WS was highly sensitive in predicting subsequent DHF or SD in our confirmed adult dengue cohort. Persistent vomiting, hepatomegaly, hematocrit rise and rapid platelet drop, and clinical fluid accumulation, as well as any 3 or 4 WS were highly specific for DHF or SD.

In England, during pandemic 2009 H1N1, vaccine efficacy and immunogenicity population studies in priority groups were rolled out in parallel to evaluate the pandemic vaccination programme. This provided a unique opportunity to compare immunogenicity and clinical protection in the same population and thus provide insights into the correlates of protection for the pandemic H1N1 2009 vaccine in risk groups. While clinical protection from AS03-adjuvanted pandemic 2009 H1N1 vaccine was high in those aged <25 years and pregnant women, effectiveness in older adults with chronic conditions has been found to be surprisingly poor. Here we present results from the immunogenicity study derived from the same population. Individuals from priority groups eligible for pandemic vaccination attending participating general practices were recruited. Pre and post-vaccination blood samples were collected and HI antibody testing to assess immune response to vaccination performed. The final cohort consisted of 610 individuals: 60 healthy children aged <5 years; 32 healthy pregnant women; 518 individuals from risk groups. Seroconversion rate in healthy children aged <5 years (87%, 95% CI: 75% to 94%) was higher than that of risk groups combined (65%, 95% CI: 61% to 69%) (p<0.001). Multivariable analysis of risk groups showed that the size of response in those who did seroconvert was lower in those who received the 2009/10 seasonal TIV (Fold effect: 0.52, 0.35 to 0.78). Predicted immunological boosting from higher pre-vaccine titres after 2009 pandemic H1N1 vaccination only occurred in children (seroconversion rate = 92%) and not in individuals aged 10 to 39 from risk groups (seroconversion rate = 74%). The lack of clinical protection identified in the same population in older adults from risk groups could be attributed to these lower seroresponses. Current immunogenicity licensing criteria for pandemic influenza vaccine may not correlate with clinical protection in individuals with chronic disease or immunocompromised.

This report describes the chikungunya cases and local transmission detected in Brunei Darussalam for the first time, despite the country being situated in a region that has experienced a multitude of outbreaks over the years. A combined strategy of active case detection, patient isolation and vector control measures was deployed in an attempt to avert further transmission. The findings have important public health implications for international surveillance and control strategies for this re-emerging disease.

We analyzed data from hospital admissions and enhanced mumps surveillance to assess mumps complications during the largest mumps outbreak in England and Wales, 2004-2005, and their association with mumps vaccination. When compared with nonoutbreak periods, the outbreak was associated with a clear increase in hospitalized patients with orchitis, meningitis, and pancreatitis. Routine mumps surveillance and hospital data showed that 6.1% of estimated mumps patients were hospitalized, 4.4% had orchitis, 0.35% meningitis, and 0.33% pancreatitis. Enhanced surveillance data showed 2.9% of mumps patients were hospitalized, 6.1% had orchitis, 0.3% had meningitis, and 0.25% had pancreatitis. Risk was reduced for hospitalization (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.43-0.68), mumps orchitis (OR 0.72, 95% CI 0.56-0.93) and mumps meningitis (OR 0.28, 95% CI 0.14-0.56) when patient had received 1 dose of measles, mumps, and rubella vaccine. The protective effect of vaccination on disease severity is critical in assessing the total effects of current and future mumps control strategies.

Background: Children with cancer have an increased susceptibility to influenza infection. The objective of this study was to assess the immunogenicity of pandemic (H1N1) 2009 vaccine in children with cancer., Methods: Children were recruited from the Royal Marsden Hospital, England, during November 2009. The vaccination schedule consisted of 2 doses of an AS03(B)-adjuvanted vaccine given at days 0 and 21. Serological analysis was performed on blood samples obtained at day 0 and day 42. The primary immunological end point was the seroconversion rate, which was defined as the proportion of subjects with an individual 4-fold increase in hemagglutination inhibition titer and a postvaccination hemagglutination inhibition titer ≥1:32., Results: Fifty-four children with a median age of 6.3 years (range, 1.4-16.6 years) were vaccinated and had samples taken for serological analysis. Twenty-four (44.4%) of 54 children demonstrated seroconversion. Seroconversion rates were 33.3% (9 of 27) among children with acute lymphoblastic leukemia, 36.4% (4 of 11) among those with lymphoma or other leukemias, 66.7% (6 of 9) among those with brain tumors, and 71.4% (5 of 7) among those with other solid tumors. Seroconversion occurred in 4 (28.6%) of 14 children receiving acute lymphoblastic leukemia maintenance therapy. Univariate analysis showed significantly higher responses among children with solid tumors, compared with those with hematological malignancies (11 [68.8%] of 16 vs 13 [34.2%] of 38; P = .03), and among those not receiving treatment, compared with those receiving treatment (7 [87.5%] of 8 vs 17 [37.0%] of 46; P = .02). Multivariable analysis showed that age, cancer type, and lymphopenia did not influence seroconversion rates., Conclusion: These data suggest that this AS03(B)-adjuvanted pandemic (H1N1) 2009 vaccine can induce limited but useful protective immune responses in children with cancer.