Search

The World Health Organization verified that Singapore had eliminated endemic transmission of measles in October 2018. This report summarizes the evidence presented to the Regional Verification Commission for Measles and Rubella Elimination, comprising information about immunization schedules; laboratory testing protocols and the surveillance system; and data on immunization coverage and the epidemiology of cases. Between 2015 and 2017, a total of 246 laboratory confirmed cases of measles were reported. The source or country of infection was unknown for most cases (195; 79.3%). There were 22 clusters, ranging from two to five cases. The most common genotypes detected were D8 and D9. Transmission of B3 was interrupted in 2017, and H1 cases were sporadic and imported. Phylogenetic analyses of the D8 isolates showed the existence of 13 lineages or clusters. Although a few lineages were circulating concurrently, no lineage propagated continuously for a prolonged period, and transmission of each lineage eventually stopped. Although cases and clusters were reported yearly, molecular data showed that none of the lineages resulted in prolonged transmission. There were fewer measles cases in 2017 compared with 2016. The higher number of clusters was likely due to the overall increase in cases because cluster sizes remained small. The occurrence of small clusters is not unexpected since measles is highly infectious. The majority of imported cases did not result in secondary transmission. With the global increase in the number of measles cases, Singapore needs to stay vigilant and continue to promptly test suspected cases; vaccination is the key to preventing infection.

Global travel has led to intermittent importation of multidrug-resistant Salmonella enterica serovar Typhi into industrialized countries. We detected azithromycin-resistant Salmonella Typhi in Singapore, of which 2 isolates were likely locally acquired. Ongoing vigilance and surveillance to minimize the public health risk for this serious pathogen is needed.

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

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.

A total of 1,281 specimens from 1,024 patients were screened. Phylogenetic analysis classified 44 of these isolates as Klebsiella quasipneumoniae subsp. similipneumoniae (44/1,281 [3.4%]) and the remaining three as K. quasipneumoniae subsp. quasipneumoniae. The most common specimen source was urine (21/47 [44.7%]) followed by blood (14/47 [29.8%]). K. quasipneumoniae isolates were nonclonal. Carbapenemase-encoding genes (bla(NDM) and bla(OXA-181)) were detected in only two isolates (2/47 [4.3%]). K. quasipneumoniae appears to cause a spectrum of infections similar to those of K. pneumoniae, although higher rates of susceptibility to many commonly tested antimicrobials and low prevalence of virulence genes were demonstrated.

A measles outbreak involving 19 adults in a home for the intellectually disabled occurred in Singapore in 2019. Further investigation, including a serological survey, was conducted. Mass vaccination and infection control measures were implemented, terminating further secondary transmission. Seropositivity among residents aged 40 to 49 years (90.7%; 95% confidence interval = 78.4%, 96.3%) was lower than among the Singapore adult population (P

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. Published version

We aim to describe a case series of critically and non-critically ill COVID-19 patients in Singapore. This was a multicentered prospective study with clinical and laboratory details. Details for fifty uncomplicated COVID-19 patients and ten who required mechanical ventilation were collected. We compared clinical features between the groups, assessed predictors of intubation, and described ventilatory management in ICU patients. Ventilated patients were significantly older, reported more dyspnea, had elevated C-reactive protein and lactate dehydrogenase. A multivariable logistic regression model identified respiratory rate (aOR 2.83, 95% CI 1.24–6.47) and neutrophil count (aOR 2.39, 95% CI 1.34–4.26) on admission as independent predictors of intubation with area under receiver operating characteristic curve of 0.928 (95% CI 0.828–0.979). Median APACHE II score was 19 (IQR 17–22) and PaO2/FiO2 ratio before intubation was 104 (IQR 89–129). Median peak FiO2 was 0.75 (IQR 0.6–1.0), positive end-expiratory pressure 12 (IQR 10–14) and plateau pressure 22 (IQR 18–26) in the first 24 h of ventilation. Median duration of ventilation was 6.5 days (IQR 5.5–13). There were no fatalities. Most COVID-19 patients in Singapore who required mechanical ventilation because of ARDS were extubated with no mortality.

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.

ObjectivesMDR Pseudomonas aeruginosa is a serious global threat to healthcare institutions. The mechanism by which drug resistance can be acquired is variable, but acquired carbapenemase production has been reported in P. aeruginosa. An investigation was performed to determine the rate and genomic epidemiology of New Delhi MBL (NDM) in β-lactam-non-susceptible isolates.MethodsP. aeruginosa isolates from a tertiary hospital in Singapore between January 2015 and February 2018 were investigated for the presence of NDM genes.ResultsOut of 298 pan-β-lactam-non-susceptible isolates, 31 were found to be NDM positive (10.4%). WGS demonstrated that all 31 NDM-positive isolates were clonal, belonging to ST-308. blaNDM was chromosomally inserted within an integrative and conjugative element (ICE), ICETn43716385. The NDM-P. aeruginosa isolates possessed an extensive repertoire of both cell-associated [flagella, pili, alginate/biofilm, LPS, type III secretion system (T3SS) and type VI secretion system (T6SS)] and secreted virulence factors. Antibiograms revealed higher rates of drug resistance in NDM-positive isolates compared with their non-NDM counterparts. The NDM isolates remained 100% susceptible only to colistin.ConclusionsThe combination of chromosomal mutations, acquired resistance genes and virulence factors likely facilitated the persistent and ongoing spread of the ST-308 clade of P. aeruginosa within the hospital. Our study illustrates the particular threat of NDM-positive P. aeruginosa in a tertiary hospital setting in the era of antimicrobial resistance.

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.

SARS-CoV-2 Infection in Travelers Returning from Wuhan Data on travelers returning from areas with many cases of Covid-19 may be useful in estimating incidence. The authors report follow-up data on...

In May 2019, we investigated monkeypox in a traveler from Nigeria to Singapore. The public health response included rapid identification of contacts, use of quarantine, and postexposure smallpox vaccination. No secondary cases were identified. Countries should develop surveillance systems to detect emerging infectious diseases globally. Published version

Field investigations were conducted after a small cluster of food poisoning involving six cases was reported. While no stool samples were available from the cases for microbiological testing, Salmonella species was found to be present in the stools of food handlers with gastroenteritis symptoms. Four Salmonella isolates recovered from the food handlers were retrospectively investigated at the genome level using whole-genome sequencing (WGS). WGS showed that S. Anfo (antigenic formulae 39:y:1,2), a rarely isolated serovar, caused infections in the food handlers. S. Anfo analysed in this study contained virulence factors required for causing disease. They did not contain any antibiotic resistance genes or plasmid. The epidemiologically related isolates differed to each other by a maximum of one single nucleotide polymorphism. WGS was useful in identifying rare Salmonella serovars and it is potentially more cost-effective than traditional serotyping methods. It can also confidently group epidemiologically related isolates belonging to S. Anfo.

We assessed and found cross-protection between the influenza pandemic and 2 seasonal viruses that circulated in Singapore. Age-related differences in disease severity between the subtypes were investigated, and we demonstrate birth cohort effects consistent with the theory of antigenic sin., Background After 2009, pandemic influenza A(H1N1) [A(H1N1)pdm09] cocirculated with A(H3N2) and B in Singapore. Methods A cohort of 760 participants contributed demographic data and up to 4 blood samples each from October 2009 to September 2010. We compared epidemiology of the 3 subtypes and investigated evidence for heterotypic immunity through multivariable logistic regression using a generalized estimating equation. To examine age-related differences in severity between subtypes, we used LOESS (locally weighted smoothing) plots of hospitalization to infection ratios and explored birth cohort effects referencing the pandemic years (1957; 1968). Results Having more household members aged 5–19 years and frequent public transport use increased risk of infection, while preexisting antibodies against the same subtype (odds ratio [OR], 0.61; P = .002) and previous influenza infection against heterotypic infections (OR, 0.32; P = .045) were protective. A(H1N1)pdm09 severity peaked in those born around 1957, while A(H3N2) severity was least in the youngest individuals and increased until it surpassed A(H1N1)pdm09 in those born in 1952 or earlier. Further analysis showed that severity of A(H1N1)pdm09 was less than that for A(H3N2) in those born in 1956 or earlier (P = .021) and vice versa for those born in 1968 or later (P < .001), with no difference in those born between 1957 and 1967 (P = .632). Conclusions Our findings suggest that childhood exposures had long-term impact on immune responses consistent with the theory of antigenic sin. This, plus observations on short-term cross-protection, have implications for vaccination and influenza epidemic and pandemic mitigation strategies.

An outbreak of invasive group B Streptococcus (GBS) disease occurred in Singapore in mid-2015. We conducted a case–control study of 22 adults with invasive GBS infections during June 21–November 21, 2015. Consumption of raw fish was strongly associated with invasive sequence type 283 infections, but not with non–sequence type 283 infections.

We conducted a retrospective study of 40 case-patients and 58 controls as part of a nationwide investigation of a group B Streptococcus outbreak in Singapore in 2015. Eating a Chinese-style raw fish dish (yusheng) was a major risk factor for bacteremia, particularly caused by serotype III sequence type 283.

Objectives bla OXA-23 is a class D carbapenemase-encoding gene typical of the Acinetobacter genus. However, its occurrence in the Enterobacteriaceae is uncommon. Here we provide the genome characterization of blaOXA-23-positive Proteus mirabilis. Methods In Singapore, a national surveillance of carbapenem non-susceptible clinical Enterobacteriaceae has enabled the collection of OXA-23 bearing isolates. Three clinical P. mirabilis were whole-genome sequenced using Oxford Nanopore MinION and Illumina platforms. The sequence accuracy of MinION long-read contigs was enhanced by polishing with Illumina-derived short-read data. Results In two P. mirabilis genomes, blaOXA-23 was detected as two copies, present on the chromosome and on a 60018 bp plasmid. blaOXA-23 was associated with the classic Acinetobacter composite transposon Tn2006, bounded by two copies of ISAba1 bracketing the carbapenemase gene. The Tn2006 itself was embedded within an Acinetobacter baumannii AbaR4 resistance island. In the chromosome, the AbaR4 was found integrated into the comM gene, which is also the preferred ‘hotspot’ in A. baumannii. In the plasmid, AbaR4 integrated into a putative colicin gene. Conclusions Our description of an A. baumannii AbaR4 encoding blaOXA-23 in P. mirabilis is to our knowledge the first description of an Acinetobacter resistance island in Proteus and suggests that P. mirabilis may be a reservoir for this class D carbapenemase gene.

Objectives To describe the population structure, molecular epidemiology and genetic context of blaKPC-2-bearing Klebsiella pneumoniae. Methods Isolates (n = 157) were retrospective, phenotypically carbapenem-resistant blaKPC-positive K. pneumoniae, collected from public hospitals. WGS was performed on the Illumina platform. Phylogenomic analysis, screening of resistance and virulence genes, and comparison of the genetic environment of blaKPC were carried out. Results Based on core-tree phylogeny, 67.5% of the isolates were K. pneumoniae and the remainder comprised Klebsiella quasipneumoniae. No Klebsiella variicola strains were observed. Only a single K. pneumoniae carbapenemase (KPC) variant type, blaKPC-2, was seen. MLSTs were diverse and did not comprise the ‘traditional’ KPC clonal group (CG) 258. blaKPC-2 was associated with a non-Tn4401 element (NTE) in >99% of genomes. Screening for four key virulence loci: yersiniabactin (ybt), aerobactin (iuc), salmochelin (iro) and colibactin (clb) as well as ICEKp (virulence-associated integrative conjugative element of K. pneumoniae), revealed the lack of virulence factors and ICEKp within K. quasipneumoniae. Amongst the K. pneumoniae, there were 32 ybt+ isolates (32/106, 30.2%) and, of these, 8 isolates were also clb+ (7.5%). K. pneumoniae serotypes K1 and K2, the majority of capsular serotype seen in patients with invasive liver abscess syndrome, were detected at 4.5% (7/157). Conclusions Results suggest that dissemination of blaKPC-2 is driven by NTEKPC in non-ST258 isolates. The detection of blaKPC-2K. pneumoniae serotypes K1/K2 carrying virulence factors, albeit in low numbers, reflects the worrisome convergence of carbapenem resistance and hypervirulence in K. pneumoniae.

The number of salmonellosis cases in Singapore has increased over the years. Salmonella enterica serovar Enteritidis has always been the most predominant serovar in the last five years. The National Public Health Laboratory assisted outbreak investigations by performing multilocus variable number tandem repeat analysis (MLVA) on isolates that were collected at the time of the investigations. Isolates were defined as belonging to a particular cluster if they had identical MLVA patterns. Whilst MLVA has been instrumental in outbreak investigations, it may not be useful when outbreaks are caused by an endemic MLVA type. In this study, we analysed 67 isolates from 12 suspected outbreaks with known epidemiological links to explore the use of next-generation sequencing (NGS) for defining outbreaks. We found that NGS can confidently group isolates into their respective outbreaks. The isolates from each suspected outbreak were closely related and differed by a maximum of 3 single nucleotide polymorphisms (SNPs). They were also clearly separated from isolates that belonged to different suspected outbreaks. This study provides an important insight and further evidence on the value of NGS for routine surveillance and outbreak detection of S. Enteritidis.

Objectives We determined the seroprevalence of chikungunya virus (CHIKV) infection in the adult resident population in Singapore following local outbreaks of chikungunya fever (CHIKF) in 2008–2009. Methods Our cross-sectional study involved residual sera from 3,293 adults aged 18–79 years who had participated in the National Health Survey in 2010. Sera were tested for IgG antibodies against CHIKV and dengue virus (DENV) and neutralizing antibodies against CHIKV. Results The prevalence of CHIKV-neutralizing antibodies among Singapore residents aged 18–79 years was 1.9% (95% confidence interval: 1.4%– 2.3%). The CHIKV seroprevalence was highest in the elderly aged 70–79 years at 11.5%, followed by those aged 30–39 years at 3.1%. Men had significantly higher CHIKV seroprevalence than women (2.5% versus 1.3%, p = 0.01). Among the three main ethnic groups, Indians had the highest seroprevalence (3.5%) compared to Chinese (1.6%) and Malays (0.7%) (p = 0.02 and p = 0.01, respectively). Multivariable logistic regression identified adults aged 30–39 years and 70–79 years, men, those of Indian ethnicity and ethnic minority groups, and residence on ground floor of public and private housing apartments as factors that were significantly associated with a higher likelihood of exposure to CHIKV. The overall prevalence of anti-DENV IgG antibodies was 56.8% (95% CI: 55.1%– 58.5%), while 1.5% (95% CI: 1.1%– 2.0%) of adults possessed both neutralizing antibodies against CHIKV and IgG antibodies against DENV. Conclusions Singapore remains highly susceptible to CHIKV infection. There is a need to maintain a high degree of vigilance through disease surveillance and vector control. Findings from such serological study, when conducted on a regular periodic basis, could supplement surveillance to provide insights on CHIKV circulation in at-risk population., Author summary The prevalence of neutralizing antibodies against chikungunya virus (CHIKV) was low at 1.9% among resident adults in Singapore after local outbreaks in 2008–2009. Adults aged 30–39 years and 70–79 years, men, those of Indian ethnicity and ethnic minority groups, and residence on ground floor of public and private housing apartments were significantly associated with a higher likelihood of exposure to CHIKV.

During November 2012–July 2013, a marked increase of adenovirus type 7 (Ad7) infections associated with severe disease was documented among pediatric patients in Singapore. Phylogenetic analysis revealed close genetic links with severe Ad7 outbreaks in China, Taiwan, and other parts of Asia. Published version

We report a reduction in the vancomycin-resistant enterococci (VRE) rate from a peak of 1.5 cases per 1,000 admissions (95% confidence interval [CI], 1.0−2.1) in August 2012 to 0.5 per 1,000 admissions (95% CI: 0.3−1.0) by January 2015, associated with a bundle of interventions.Infect. Control Hosp. Epidemiol.2015;37(1):107–109

Background Blackwater fever is a complication of malaria infection consisting of a syndrome of febrile intra-vascular haemolysis with severe anaemia and intermittent passage of dark-red to black colour urine. Despite numerous reports and studies of this condition, its pathogenesis remains incompletely understood. Case presentation This report describes a case of classic blackwater fever in a returning traveller, without prior history of malaria infection nor usage of anti-malarial prophylaxis, treated with two courses of oral artemether–lumefantrine combination therapy. Unusual persistence of submicroscopic Plasmodium falciparum parasitaemia was detected by PCR for 18 days after initiation of treatment. Conclusion To the authors’ knowledge this is the first reported occurrence of a case of blackwater fever associated with prolonged submicroscopic parasitaemia. This unusual case challenges the current knowledge of the pathogenesis of this condition and opens questions that may have important diagnostic and treatment implications. Electronic supplementary material The online version of this article (10.1186/s12936-018-2180-1) contains supplementary material, which is available to authorized users.

Increasing rates of Clostridium difficile infection (CDI) among those without traditional risk factors have been reported mainly in Europe and North America. Here we describe the epidemiology, clinical features and ribotypes of CDI at National University Hospital (NUH), a 1000-bed tertiary care hospital in Singapore, from December 2011 to May 2012. All laboratory-confirmed CDI cases ≥21 years old who gave informed consent were included. Clinical data were collected prospectively and participants underwent an interviewer-administered questionnaire. Cases were classified by healthcare facility exposure and severity according to the SHEA guidelines. Included cases were also subjected to PCR and were classified by ribotype. In total, 66 patients participated in the study, of which 33 (50.0%) were healthcare-facility-associated hospital onset (HCFA-HO). Of the 33 community-onset (CO) cases, 14 (42.4%) were HCFA-CO, 10 (30.3%) were indeterminate and 9 (27.3%) were community-associated (CA). Of the CA cases, a majority (90.9%) had prior exposure to a healthcare facility within the last 12 weeks. Clinical characteristics, exposures and outcomes were not different between HO-CDI and CO-CDI. Diagnosis was delayed in CO-CDI compared with HO-CDI (4 days vs. 1 day; P=0.014). There was no difference in distribution of ribotypes between CO-CDI and HO-CDI, with 053 being most prevalent in both groups. CO-CDI increasingly contributes to the burden of CDI in NUH. This may reflect a trend in other parts of Asia. Healthcare professionals should be aware of the possible role of outpatient healthcare environments to CDI risk and thus extend control measures to outpatient settings.

Streptococcus pneumoniae is a major cause of sepsis, meningitis and respiratory disease worldwide. Pneumococcal conjugate vaccines (PCVs) have now been implemented in many countries worldwide, including Singapore. To evaluate the effectiveness of these vaccines, pneumococcal surveillance studies are required. Detailed and unified pneumococcal epidemiology data are currently scarce in South East Asia. Thus, we present data on invasive pneumococcal (IPD) isolates from Singapore that could assist in evaluating the effectiveness of pneumococcal vaccine in Singapore. One hundred and fifty-nine invasive pneumococcal disease isolates were received by the National Public Health Laboratory in Singapore between June 2009 and August 2010. Isolates were characterized using serotyping and multilocus sequence typing. Twenty-four different serotypes were found, the most common of which were 19A, 3, 7F, 23F, 6B, 14, 8 and 19F (in rank order). One hundred and two sequence types were observed, of which 38 were novel due to new alleles or new combinations of already existing alleles. Based on the Simpson’s Index of Diversity, serotypes 3, 6B and 19A were the most genetically diverse. Novel sequence types were more prevalent among conjugate vaccine serotypes 3, 19F and 23F and non-conjugate vaccine serotype 8, serogroup 15 and in non-typable isolates. We have demonstrated considerable genetic diversity among invasive pneumococci before and during the widespread use of conjugate vaccines in Singapore. Approximately half of all novel IPD clones identified in this study were non-conjugate vaccine serotypes. Although PCVs would target the most common serotypes, the high genetic diversity in non-vaccine serotypes would require further surveillance studies.

To investigate the performance of laboratory methods and clinical case definitions in detecting the viral pathogens for acute respiratory infections (ARIs) from a prospective community cohort and hospital inpatients, nasopharyngeal swabs from cohort members reporting ARIs (community-ARI) and inpatients admitted with ARIs (inpatient-ARI) were tested by Singleplex Real Time-Polymerase Chain Reaction (SRT-PCR), multiplex RT-PCR (MRT-PCR) and pathogen-chip system (PathChip) between April 2012 and December 2013. Community-ARI and inpatient-ARI was also combined with mild and severe cases of influenza from a historical prospective study as mild-ARI and severe-ARI respectively to evaluate the performance of clinical case definitions. We analysed 130 community-ARI and 140 inpatient-ARI episodes (5 inpatient-ARI excluded because multiple pathogens were detected), involving 138 and 207 samples respectively. Detection by PCR declined with days post-onset for influenza virus; decrease was faster for community-ARI than for inpatient-ARI. No such patterns were observed for non-influenza respiratory virus infections. PathChip added substantially to viruses detected for community-ARI only. Clinical case definitions discriminated influenza from other mild-ARI but performed poorly for severe-ARI and for older participants. Rational strategies for diagnosis and surveillance of influenza and other respiratory virus must acknowledge the differences between ARIs presenting in community and hospital settings.

Introduction Previous influenza pandemics had second and on occasion third waves in many countries that were at times more severe than the initial pandemic waves. Objective This study aims to determine the seroepidemiology of successive waves of H1N1pdm09 infections in Singapore and the overall risks of infection. Methods We performed a cohort study amongst 838 adults, with blood samples provided upon recruitment and at 5 points from 2009 to 2011 and tested by haemagglutination inhibition (HI) with A/California/7/2009 (H1N1pdm09). Surveys on key demographic and clinical information were conducted at regular intervals, and associations between seroconversion and these variables were investigated. Results After the initial wave from June to September 2009, second and third waves occurred from November 2009 to February 2010 and April to June 2010, respectively. Seroconversion was 13·5% during the first wave and decreased to 6·2% and 6·8% in subsequent waves. Across the three waves, the elderly and those with higher starting HI titres were at lower risk of seroconversion, while those with larger households were at greater risk. Those with higher starting HI titres were also less likely to have an acute respiratory infection. Conclusions The second and third waves in Singapore had lower serological attack rates than the first wave. The elderly and those with higher HI titres had lower risk, while those in larger households had higher risk of seroconversion.

Chikungunya virus (CHIKV) is an alphavirus which causes chronic and incapacitating arthralgia in humans. Although previous studies have shown that antibodies against the virus are produced during and after infection, the fine specificity of the antibody response against CHIKV is not known. Here, using plasma from patients at different times postinfection, we characterized the antibody response against various proteins of the virus. We have shown that the E2 and E3 glycoproteins and the capsid and nsP3 proteins are targets of the anti-CHIKV antibody response. Moreover, we have identified the different regions in these proteins which contain the linear epitopes recognized by the anti-CHIKV antibodies and determined their structural localization. Data also illustrated the effect of a single K 252 Q amino acid change at the E2 glycoprotein that was able to influence antibody binding and interaction between the antibodies and epitope because of the changes of epitope-antibody binding capacity. This study provides important knowledge that will not only aid in the understanding of the immune response to CHIKV infection but also provide new knowledge in the design of modern vaccine development. Furthermore, these pathogen-specific epitopes could be used for future seroepidemiological studies that will unravel the molecular mechanisms of human immunity and protection from CHIKV disease.

Zika virus (ZIKV) is an ongoing global public health emergency with 70 countries and territories reporting evidence of ZIKV transmission since 2015. On 27 August 2016, Singapore reported its first case of local ZIKV transmission and identified an ongoing cluster. Here, we report the genome sequences of ZIKV strains from two cases and find through phylogenetic analysis that these strains form an earlier branch distinct from the recent large outbreak in the Americas.

Objective To investigate the validity of recommendations in treatment guidelines to use higher than approved doses of oseltamivir in patients with severe influenza. Design Double blind randomised trial. Setting Thirteen hospitals in Indonesia, Singapore, Thailand, and Vietnam. Participants Patients aged ≥1 year admitted to hospital with confirmed severe influenza. Interventions Oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent) versus standard dose (75 mg twice a day/paediatric equivalent). Main outcome measure Viral status according to reverse transcriptase polymerase chain reaction (RT-PCR) for influenza RNA in nasal and throat swabs on day five. Results Of 326 patients (including 246 (75.5%) children aged

A sudden increase in invasive infections caused by Bacillus cereus group organisms prompted an investigation at the National University Hospital in Singapore.To describe the investigation and management and subsequent difficulties controlling the outbreak.Clinical case reviews were performed on all patients with B. cereus group recovered from clinical samples. Widespread environmental sampling was performed followed by review of hospital ventilation systems, domestic cleaning and laundry practices.B. cereus was recovered from 171 patients during a six-month period coinciding with large-scale construction work beside the hospital. Most patients presented with bacteraemia (146/171; 85.4%) with 46/171 (26.9%) requiring extended treatment courses with vancomycin or other interventions. Sampling confirmed extensive airborne dispersal inside the hospital, including isolation rooms and air-conditioned wards. Hospital linen was heavily contaminated [7403 cfu/cm(2); 95% confidence interval (CI): 6349-8457; for 30 towels sampled], encouraged by inappropriate storage in airtight plastic bags (4437 cfu/cm(2); CI: 3125-5750) compared with storage in porous canvas bags (166 cfu/cm(2); CI: 76-256; P 0.001). Interventions introduced included revision of laundry practices, transport and storage of hospital linen and towels; bleach-based environmental cleaning; and upgrading of ventilation systems throughout the hospital. Clinical case numbers returned to baseline levels within three months, only to rise again following relaxation of laundry practices.Construction work beside this Singapore hospital encouraged heavy contamination of air and environment with Bacillus spp., assumed to be responsible for the outbreak described. Failure to maintain revised laundry practices allowed resurgence of clinical cases, particularly among immunocompromised patients.

Objectives Owing to gene transposition and plasmid conjugation, New Delhi metallo-β-lactamase (NDM) is typically identified among varied Enterobacteriaceae species and STs. We used WGS to characterize the chromosomal and plasmid molecular epidemiology of NDM transmission involving four institutions in Singapore. Methods Thirty-three Enterobacteriaceae isolates (collection years 2010-14) were sequenced using short-read sequencing-by-synthesis and analysed. Long-read single molecule, real-time sequencing (SMRTS) was used to characterize genetically a novel plasmid pSg1-NDM carried on Klebsiella pneumoniae ST147. Results In 20 (61%) isolates, blaNDM was located on the pNDM-ECS01 plasmid in the background of multiple bacterial STs, including eight K. pneumoniae STs and five Escherichia coli STs. In six (18%) isolates, a novel blaNDM-positive plasmid, pSg1-NDM, was found only in K. pneumoniae ST147. The pSg1-NDM-K. pneumoniae ST147 clone (Sg1-NDM) was fully sequenced using SMRTS. pSg1-NDM, a 90 103 bp IncR plasmid, carried genes responsible for resistance to six classes of antimicrobials. A large portion of pSg1-NDM had no significant homology to any known plasmids in GenBank. pSg1-NDM had no conjugative transfer region. Combined chromosomal-plasmid phylogenetic analysis revealed five clusters of clonal bacterial NDM-positive plasmid transmission, of which two were inter-institution clusters. The largest inter-institution cluster involved six K. pneumoniae ST147-pSg1-NDM isolates. Fifteen patients were involved in transmission clusters, of which four had ward contact, six had hospital contact and five had an unknown transmission link. Conclusions A combined sequencing-by-synthesis and SMRTS approach can determine effectively the transmission clusters of blaNDM and genetically characterize novel plasmids. Plasmid molecular epidemiology is important to understanding NDM spread as blaNDM-positive plasmids can conjugate extensively across species and STs.

Background Plasmodium ovale, considered the rarest of the malaria parasites of humans, consists of two morphologically identical but genetically distinct sympatric species, Plasmodium ovale curtisi and Plasmodium ovale wallikeri. These parasites resemble morphologically to Plasmodium vivax with which they also share a tertian periodicity and the ability to cause relapses, making them easily misidentified as P. vivax. Plasmodium ovale infections are rarely reported, but given the likelihood of misidentification, their prevalence might be underestimated. Methods Morphological and molecular analysis of confirmed malaria cases admitted in Singapore in 2012–2014 detected nine imported P. ovale cases that had been misidentified as P. vivax. Since P. ovale had not been previously officially reported in Singapore, a retrospective analysis of available, frozen, archival blood samples was performed and returned two additional misidentified P. ovale cases in 2003 and 2006. These eleven P. ovale samples were characterized with respect to seven molecular markers (ssrRNA, Potra, Porbp2, Pog3p, dhfr-ts, cytb, cox1) used in recent studies to distinguish between the two sympatric species, and to a further three genes (tufa, clpC and asl). Results The morphological features of P. ovale and the differential diagnosis with P. vivax were reviewed and illustrated by microphotographs. The genetic dimorphism between P. ovale curtisi and P. ovale wallikeri was assessed by ten molecular markers distributed across the three genomes of the parasite (Genbank KP050361-KP050470). The data obtained for seven of these markers were compared with those published and confirmed that both P. ovale species were present. This dimorphism was also confirmed for the first time on: (1) two genes from the apicoplast genome (tufA and clpC genes); and, (2) the asl gene that was used for phylogenetic analyses of other Plasmodium species, and that was found to harbour the highest number of dimorphic loci between the two P. ovale species. Conclusion Misidentified P. ovale infections are reported for the first time among imported malaria cases in Singapore. Genetic dimorphism between P. ovale curtisi and P. ovale wallikeri was confirmed using markers from the parasites’ three genomes. The apparent increase of imported P. ovale since 2012 (with yearly detection of cases) is puzzling. Given decrease in the overall number of malaria cases recorded in Singapore since 2010 the ‘resurgence’ of this neglected species raises public health concerns. Electronic supplementary material The online version of this article (doi:10.1186/s12936-015-0985-8) contains supplementary material, which is available to authorized users.

Summary Background Patients with neutropenic fever after 4–7days of broad-spectrum antibiotics are given antifungals empirically. This strategy may lead to over-treatment. Methods Patients with hematological malignancies undergoing intensive chemotherapy or hematopoietic stem cell transplantation were randomized to two arms. Patients in the ‘preemptive' arm had regular galactomannan (GM) assays, and received caspofungin, amphotericin or voriconazole (CAV) for persistent febrile neutropenia if they had two positive GM results, or a positive GM result and a computed tomography (CT) of the thorax suggestive of invasive pulmonary aspergillosis (IPA). Patients in the ‘empirical' arm received CAV in accordance with established guidelines. Results Of 27 episodes in the preemptive arm, two cases of IPA were picked up by monitoring. In six episodes, CAV was started despite persistently negative GM readings. One additional patient received CAV for a false-positive GM. Of 25 episodes in the empirical arm, CAV was started empirically in 10, one of whom had CT features of IPA. By intent-to-treat and evaluable-episode analyses, respectively, the preemptive approach saved 11% and 14% of patients from empirical antifungals. Twelve-week survival was 85.2% in the preemptive arm and 84% in the empirical arm. Conclusions A preemptive approach may reduce empirical antifungal use without compromising survival in persistently febrile neutropenic patients.

BACKGROUND: Few studies have validated the effectiveness of public health interventions in reducing influenza spread in real‐life settings. We aim to validate these measures used during the 2009 pandemic. METHODS: From 22 June to 9 October 2009, we performed a prospective observational cohort study using paired serum samples and symptom review among 3 groups of Singapore military personnel. "Normal" units were subjected to prevailing pandemic response policies. "Essential" units and health care workers had additional public health interventions (eg, enhanced surveillance with isolation, segregation, personal protective equipment). Samples were tested by hemagglutination inhibition; the principal outcome was seroconversion to 2009 influenza A(H1N1). RESULTS: In total, 1015 individuals in 14 units completed the study, with 29% overall seroconversion. Seroconversion among essential units (17%) and health care workers (11%) was significantly lower than that in normal units (44%) (P = .001). Symptomatic illness attributable to influenza was also lower in essential units (5%) and health care workers (2%) than in normal units (12%) (P = .06). Adjusted for confounders, unit type was the only significant variable influencing overall seroconversion ( P < .05). From multivariate analysis within each unit, age (P < .001) and baseline antibody titer (P = .012 ) were inversely related to seroconversion risk. CONCLUSIONS: Public health measures are effective in limiting influenza transmission in closed environments.

TOC Summary: Infection was associated with occupational and nonoccupational risk factors., We describe incidence and risk factors for pandemic (H1N1) 2009 virus infection in healthcare personnel during the June–September 2009 epidemic in Singapore. Personnel contributed 3 serologic samples during June–October 2009, with seroconversion defined as a >4-fold increase in hemagglutination inhibition titers to pandemic (H1N1) 2009. Of 531 participants, 35 showed evidence of seroconversion. Seroconversion rates were highest in nurses (28/290) and lowest in allied health staff (2/116). Significant risk factors on multivariate analysis were being a nurse (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] 1.0–19.6) and working in pandemic (H1N1) 2009 isolation wards (aOR 4.5, 95% CI 1.3–15.6). Contact with pandemic (H1N1) 2009–infected colleagues (aOR 2.5, 95% CI 0.9–6.6) and larger household size (aOR 1.2, 95% CI 1.0–1.4) were of borderline significance. Our study suggests that seroconversion was associated with occupational and nonoccupational risk factors.

An oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus evolved and emerged from zero to 52% of detectable virus within 48 hours of a patient’s exposure to oseltamivir. Phylogenetic analysis and data gathered by pyrosequencing and cloning directly on clinical samples suggest that the mutant emerged de novo.

Data from longitudinal analyses can be useful in the design and implementation of control strategies., Local transmission of chikungunya, a debilitating mosquito-borne viral disease, was first reported in Singapore in January 2008. After 3 months of absence, locally acquired Chikungunya cases resurfaced in May 2008, causing an outbreak that resulted in a total of 231 cases by September 2008. The circulating viruses were related to East, Central, and South African genotypes that emerged in the Indian Ocean region in 2005. The first local outbreak was due to a wild-type virus (alanine at codon 226 of the envelope 1 gene) and occurred in an area where Aedes aegypti mosquitoes were the primary vector. Strains isolated during subsequent outbreaks showed alanine to valine substitution (A226V) and largely spread in areas predominated by Ae. albopictus mosquitoes. These findings led to a revision of the current vector control strategy in Singapore. This report highlights the use of entomologic and virologic data to assist in the control of chikungunya in disease-endemic areas.

Polymerase chain reaction (PCR) screening of 116 ciprofloxacin-resistant Klebsiella pneumoniae hospital isolates for the presence of qnr genes that mediate plasmid quinolone resistance revealed that none were positive for qnrA or qnrS. However, qnrB was detected in ca. 5.2% of the isolates. Southern hybridisation demonstrated that the qnrB-hybridising plasmids were large (>70 kb) and capable of transferring quinolone resistance by conjugation. Sequence analysis of the qnrB genes detected in this study showed that they were identical to previously identified qnrB1, qnrB4 and qnrB6 genes, although a novel variant designated qnrB20 was also identified. Analysis of the genetic environment around the cloned qnrB genes showed that they were present in diverse plasmid backbones, sometimes within novel genetic contexts, but always associated with mobile or transposable elements.

Influenza-like illness (ILI) case definitions, such as those from the European Centre for Disease Control and Prevention, World Health Organization (WHO) and United States Centers for Disease Control and Prevention, are commonly used for influenza surveillance. We assessed how various case definitions performed during the initial wave of influenza A(H1N1) pdm09 infections in Singapore on a cohort of 727 patients with two to three blood samples and whose symptoms were reviewed fortnightly from June to October 2009. Using seroconversion (≥ 4-fold rise) to A/California/7/2009 (H1N1), we identified 36 presumptive influenza A(H1N1)pdm09 episodes and 664 episodes unrelated to influenza A(H1N1)pdm09. Cough, fever and headache occurred more commonly in presumptive influenza A(H1N1)pdm09. Although the sensitivity was low (36%), the recently revised WHO ILI case definition gave a higher positive predictive value (42%) and positive likelihood ratio (13.3) than the other case definitions. Results including only episodes with primary care consultations were similar. Individuals who worked or had episodes with fever, cough or sore throat were more likely to consult a physician, while episodes with Saturday onset were less likely, with some consultations skipped or postponed. Our analysis supports the use of the revised WHO ILI case definition, which includes only cough in the presence of fever defined as body temperature ≥ 38 °C for influenza surveillance.

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

Vaccination helps reduce disease burden, particularly in the elderly, who are at higher risk for hospitalization and death., Studies of influenza-associated hospitalizations in tropical settings are lacking. To increase understanding of the effect of influenza in Singapore, we estimated the age-specific influenza-associated hospitalizations for pneumonia and influenza during 2004–2008 and 2010–2012. The rate of hospitalization was 28.3/100,000 person-years during 2004–2008 and 29.6/100,000 person-years during 2010–2012. The age-specific influenza-associated hospitalization rates followed a J-shaped pattern: rates in persons >75 years of age and in children 47 times and >26 times higher, respectively, than those for persons 25–44 years of age. Across all ages during these 2 study periods, ≈12% of the hospitalizations for pneumonia and influenza were attributable to influenza. The rates and proportions of hospitalizations for influenza, particularly among the very young and the elderly, are considerable in Singapore and highlight the importance of vaccination in protecting populations at risk.

The emergence of carbapenemase-producing Enterobacteriaceae is a rapidly evolving threat worldwide. Here, we report the molecular characterization of two Klebsiella pneumoniae isolates carrying both bla(OXA -181) and bla(NDM -1) or bla(NDM -5) isolated from epidemiologically unrelated patients in Singapore. The bla(OXA -181) genes were found existing in different genetic environments.

Background The rate of decline of antibody titers to influenza following infection can affect results of serological surveys, and may explain re-infection and recurrent epidemics by the same strain. Methods We followed up a cohort who seroconverted on hemagglutination inhibition (HI) antibody titers (≥4-fold increase) to pandemic influenza A(H1N1)pdm09 during a seroincidence study in 2009. Along with the pre-epidemic sample, and the sample from 2009 with the highest HI titer between August and October 2009 (A), two additional blood samples obtained in April 2010 and September 2010 (B and C) were assayed for antibodies to A(H1N1)pdm09 by both HI and virus microneutralization (MN) assays. We analyzed pair-wise mean-fold change in titers and the proportion with HI titers ≥ 40 and MN ≥ 160 (which correlated with a HI titer of 40 in our assays) at the 3 time-points following seroconversion. Results A total of 67 participants contributed 3 samples each. From the highest HI titer in 2009 to the last sample in 2010, 2 participants showed increase in titers (by HI and MN), while 63 (94%) and 49 (73%) had reduction in HI and MN titers, respectively. Titers by both assays decreased significantly; while 70.8% and 72.3% of subjects had titers of ≥ 40 and ≥ 160 by HI and MN in 2009, these percentages decreased to 13.9% and 36.9% by September 2010. In 6 participants aged 55 years and older, the decrease was significantly greater than in those aged below 55, so that none of the elderly had HI titers ≥ 40 nor MN titers ≥ 160 by the final sample. Due to this decline in titers, only 23 (35%) of the 65 participants who seroconverted on HI in sample A were found to seroconvert between the pre-epidemic sample and sample C, compared to 53 (90%) of the 59 who seroconverted on MN on Sample A. Conclusions We observed marked reduction in titers 1 year after seroconversion by HI, and to a lesser extent by MN. Our findings have implications for re-infections, recurrent epidemics, vaccination strategies, and for cohort studies measuring infection rates by seroconversion. Electronic supplementary material The online version of this article (doi:10.1186/1471-2334-14-414) contains supplementary material, which is available to authorized users.

To the Editor: In the past few years, several publications have reported that Internet search queries may usefully supplement other, traditional surveillance programs for infectious diseases (1–3). The philanthropic arm of Google offers Flu Trends, a site that provides up-to-date estimates of influenza activity in 20 countries of the Pacific Rim and Europe (4) by using data mining techniques to find good predictors of historic influenza indicators (1). This service has yet to be extended to other countries and other diseases because access to official surveillance data is required, among other reasons. However, another Google service, Insights for Search, enables users to find and download time-series data of relative counts of arbitrary searches for a large number of countries (5). Pelat et al. have shown that a few, well-chosen searches on Google Insights provide data that closely correlate with French surveillance data for seasonal influenza, chickenpox, and gastroenteritis (3). Although Internet searches appear to be a promising tool for public health surveillance, our experience from using Google Insights in the context of pandemic (H1N1) 2009 in Singapore suggests it has important limitations. In Singapore, the recent pandemic caused an outbreak that peaked at the start of August 2009; the first confirmed importation was at the end of May and first confirmed unlinked case was at the end of June. However, the number Google searches for “influenza,” “H1N1,” “swine flu,” and similar terms (in English and Chinese), as well as symptoms associated with the disease, peaked much earlier than did the number of cases (Figure). The number of searches surged after newsworthy events but was low during the epidemic itself and had declined to about 20% of maximum search volume by the time of the actual peak, as shown by traditional surveillance. Furthermore, no discernible local maxima were observed that corresponded to the peak in case data. In contrast, alternative traditional measures of influenza incidence—prevalence of the novel strain among viral samples and general practice surveillance (6,7)—provide a consistent description of the outbreak. Figure Number of Google searches conducted for “influenza” (black lines) and “H1N1” (gray lines) compared with number of acute respiratory infections (ARI, gray bars) reported in government clinics, Singapore, 2009. During the ... This finding echoes a major point raised by Carneiro and Mylonakis (2), namely, that without adjusting for spikes driven by disease publicity rather than the disease itself, Internet searches may lose much of their value in supplementing traditional surveillance measures. Our experience is that using Google Insights to survey a disease may not work well for diseases with considerable media exposure, in particular, emerging diseases such as pandemic (H1N1) 2009 or severe acute respiratory syndrome. Such outbreaks may require the more sophisticated approach used by Flu Trends, should it be extended to other diseases and more corners of the globe. We agree with Pelat et al. (3) that Google Insights may work well for less-publicized infectious diseases. The dividing line between well-publicized and unpublicized diseases may, however, remain ambiguous. Thus, to ensure that web search data reflect disease incidence requires validation against traditional surveillance, although in that situation, the availability of corroborating traditional methods of surveillance limits the value of web-query data.