Eric H. Y. Lau

Synchrony of clinical and laboratory surveillance for influenza in Hong Kong.

Background Consultation rates of influenza-like illness (ILI) in an outpatient setting have been regarded as a good indicator of influenza virus activity in the community. As ILI-like symptoms may be caused by etiologies other than influenza, and influenza virus activity in the tropics and subtropics is less predictable than in temperate regions, the correlation between of ILI and influenza virus activity in tropical and subtropical regions is less well defined. Methodology and Principal Findings In this study, we used wavelet analysis to investigate the relationship between seasonality of influenza virus activity and consultation rates of ILI reported separately by General Out-patient Clinics (GOPC) and General Practitioners (GP). During the periods 1998–2000 and 2002–2003, influenza virus activity exhibited both annual and semiannual cycles, with one peak in the winter and another in late spring or early summer. But during 2001 and 2004–2006, only annual cycles could be clearly identified. ILI consultation rates in both GOPC and GP settings share a similar non-stationary seasonal pattern. We found high coherence between ILI in GOPC and influenza virus activity for the annual cycle, but this was only significant (p<0.05) during the periods 1998–1999 and 2002–2006. For the semiannual cycle high coherence (p<0.05) was also found significant during the period 1998–1999 and year 2003 when two peaks of influenza were evident. Similarly, ILI in GP setting is also associated with influenza virus activity for both the annual and semiannual cycles. On average, oscillation of ILI in GP and of ILI in GOPC preceded influenza virus isolation by approximately four and two weeks, respectively. Conclusions Our findings suggest that consultation rates of ILI precede the oscillations of laboratory surveillance by at least two weeks and can be used as a predictor for influenza epidemics in Hong Kong. The validity of our model for other tropical regions needs to be explored.

Vancomycin MIC creep in MRSA isolates from 1997 to 2008 in a healthcare region in Hong Kong.

OBJECTIVES To assess whether vancomycin MIC creeps among blood methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from 5 hospitals in Hong Kong from 1997 to 2008. METHODS Blood cultures MRSA isolates from 1997 to 1999 (period 1), 2004 (period 2) and 2006-2008 (period 3) were retrieved. Etest method was used to determine their vancomycin MIC. The genotypic features were determined by PCR and sequencing. RESULTS 247 blood MRSA isolates were studied. The vancomycin MIC were 0.375, 0.5, 0.75 and 1 mg/L for 15 (6.1%), 68 (27.5%), 89 (36%) and 75 (30.4%) isolates, respectively. There was an increase in the percentage of isolates with an MIC=1mg/L from 10.4% (5/48) during period 1 to 21.6% (8/37) during period 2 and 38.3% (62/162) during period 3 (period 1 vs. period 3, P<0.001). Molecular typing showed that this was due to increased percentages of clonal cluster (CC) 8/SCCmec III/IIIA (agr group I), CC45/SCCmec IV/V (agr group IV) and other minor clones with elevated MIC over time. CONCLUSION This study found vancomycin MIC creep among blood MRSA isolates over time. As elevated MIC within the susceptible range may reduce vancomycin efficacy, clinical laboratories should adopt methods with the required precision to accurately determine MICs.

Sequential introduction of single room isolation and hand hygiene campaign in the control of methicillin-resistant Staphylococcus aureus in intensive care unit

BackgroundAfter renovation of the adult intensive care unit (ICU) with installation of ten single rooms, an enhanced infection control program was conducted to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) in our hospital.MethodsSince the ICU renovation, all patients colonized or infected with MRSA were nursed in single rooms with contact precautions. The incidence of MRSA infection in the ICU was monitored during 3 different phases: the baseline period (phase 1); after ICU renovation (phase 2) and after implementation of a hand hygiene campaign with alcohol-based hand rub (phase 3). Patients infected with extended spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella species were chosen as controls because they were managed in open cubicles with standard precautions.ResultsWithout a major change in bed occupancy rate, nursing workforce, or the protocol of environmental cleansing throughout the study period, a stepwise reduction in ICU onset nonbacteraemic MRSA infection was observed: from 3.54 (phase 1) to 2.26 (phase 2, p = 0.042) and 1.02 (phase 3, p = 0.006) per 1000-patient-days. ICU onset bacteraemic MRSA infection was significantly reduced from 1.94 (phase 1) to 0.9 (phase 2, p = 0.005) and 0.28 (phase 3, p = 0.021) per 1000-patient-days. Infection due to ESBL-producing organisms did not show a corresponding reduction. The usage density of broad-spectrum antibiotics and fluoroquinolones increased from phase 1 to 3. However a significant trend improvement of ICU onset MRSA infection by segmented regression analysis can only be demonstrated when comparison was made before and after the severe acute respiratory syndrome (SARS) epidemic. This suggests that the deaths of fellow healthcare workers from an occupational acquired infection had an overwhelming effect on their compliance with infection control measures.ConclusionProvision of single room isolation facilities and promotion of hand hygiene practice are important. However compliance with infection control measures relies largely on a personal commitment, which may increase when personal safety is threatened.

Using Social Media for Actionable Disease Surveillance and Outbreak Management: A Systematic Literature Review

Objective Research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals’ ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: Can social media be integrated into disease surveillance practice and outbreak management to support and improve public health? Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes? Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n = 15), Infectious Diseases (n = 6), Non-infectious Diseases (n = 4), Medication and Vaccines (n = 3), and Other (n = 5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n = 10), Infectious Diseases (n = 3), Non-infectious Diseases (n = 9), and Other (n = 10). Conclusions The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review is to identify opportunities that enable public health professionals to integrate social media analytics into disease surveillance and outbreak management practice.

A profile of the online dissemination of national influenza surveillance data

BackgroundInfluenza surveillance systems provide important and timely information to health service providers on trends in the circulation of influenza virus and other upper respiratory tract infections. Online dissemination of surveillance data is useful for risk communication to health care professionals, the media and the general public. We reviewed national influenza surveillance websites from around the world to describe the main features of surveillance data dissemination.MethodsWe searched for national influenza surveillance websites for every country and reviewed the resulting sites where available during the period from November 2008 through February 2009. Literature about influenza surveillance was searched at MEDLINE for relevant hyperlinks to related websites. Non-English websites were translated into English using human translators or Google language tools.ResultsA total of 70 national influenza surveillance websites were identified. The percentage of developing countries with surveillance websites was lower than that of developed countries (22% versus 57% respectively). Most of the websites (74%) were in English or provided an English version. The most common surveillance methods included influenza-like illness consultation rates in primary care settings (89%) and laboratory surveillance (44%). Most websites (70%) provided data within a static report format and 66% of the websites provided data with at least weekly resolution.ConclusionAppropriate dissemination of surveillance data is important to maximize the utility of collected data. There may be room for improvement in the style and content of the dissemination of influenza data to health care professionals and the general public.

Kinetics of serological responses in influenza A(H7N9)-infected patients correlate with clinical outcome in China, 2013

The novel avian influenza A(H7N9) infection has recently emerged to cause severe respiratory illness in China. The objectives of this study were to define the kinetics of the antibody responses in patients with influenza A(H7N9) disease and to correlate these kinetics with clinical outcome. Serial serum samples were obtained at intervals of three to four days from 18 patients with virologically confirmed A(H7N9) disease in Shanghai. We determined the kinetics of the haemagglutination inhibition (HI) and A(H7H9) pseudotype neutralisation antibody (Nab) responses and correlated these with clinical outcomes. Most patients had robust serological responses by both HI and Nab tests. Taking into account censoring due to time of testing and death, the median time from onset of illness to Nab titre ≥1:40 was 14 days (95% confidence interval (CI): 11–18 days) in the fatal cases and 10.5 days (95% CI: 7–12) in the survivors (p=0.003). The two groups did not differ in initial Nab titres, but the rate of increase in Nab titres was significantly faster for survivors by approximately 10-fold per 15 days (p=0.007). Early and rapid induction of Nab was correlated significantly with better clinical outcome.

Comparison of serological assays in human Middle East respiratory syndrome (MERS)-coronavirus infection.

Plaque reduction neutralisation tests (PRNT), microneutralisation (MN), Middle East respiratory syndrome (MERS)-spike pseudoparticle neutralisation (ppNT) and MERS S1-enzyme-linked immunosorbent assay (ELISA) antibody titres were compared using 95 sera from 17 patients with MERS, collected two to 46 days after symptom onset. Neutralisation tests correlated well with each other and moderately well with S1 ELISA. Moreover to compare antigenic similarity of genetically diverse MERS-CoV clades, the response of four sera from two patients sampled at two time periods during the course of illness were tested by 90% PRNT. Genetically diverse MERS-CoV clades were antigenically homogenous.

A comparative epidemiologic analysis of SARS in Hong Kong, Beijing and Taiwan

BackgroundThe 2002-2003 Severe Acute Respiratory Syndrome (SARS) outbreak infected 8,422 individuals leading to 916 deaths around the world. However, there have been few epidemiological studies of SARS comparing epidemiologic features across regions. The aim of this study is to identify similarities and differences in SARS epidemiology in three populations with similar host and viral genotype.MethodsWe present a comparative epidemiologic analysis of SARS, based on an integrated dataset with 3,336 SARS patients from Hong Kong, Beijing and Taiwan, epidemiological and clinical characteristics such as incubation, onset-to-admission, onset-to-discharge and onset-to-death periods, case fatality ratios (CFRs) and presenting symptoms are described and compared between regions. We further explored the influence of demographic and clinical variables on the apparently large differences in CFRs between the three regions.ResultsAll three regions showed similar incubation periods and progressive shortening of the onset-to-admission interval through the epidemic. Adjusted for sex, health care worker status and nosocomial setting, older age was associated with a higher fatality, with adjusted odds ratio (AOR): 2.10 (95% confidence interval: 1.45, 3.04) for those aged 51-60; AOR: 4.57 (95% confidence interval: 3.32, 7.30) for those aged above 60 compared to those aged 41-50 years. Presence of pre-existing comorbid conditions was also associated with greater mortality (AOR: 1.74; 95% confidence interval: 1.36, 2.21).ConclusionThe large discrepancy in crude fatality ratios across the three regions can only be partly explained by epidemiological and clinical heterogeneities. Our findings underline the importance of a common data collection platform, especially in an emerging epidemic, in order to identify and explain consistencies and differences in the eventual clinical and public health outcomes of infectious disease outbreaks, which is becoming increasingly important in our highly interconnected world.

Hepatitis B reactivation in occult viral carriers undergoing hematopoietic stem cell transplantation: A prospective study

Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)–negative, antibody to hepatitis B core antigen (anti‐HBc)–positive patients after allogeneic hematopoietic stem cell transplantation (HSCT) has not been prospectively studied. HBsAg‐negative, anti‐HBc–positive patients with undetectable HBV DNA undergoing allogeneic HSCT were prospectively monitored every 4 weeks. The primary endpoint was HBV reactivation, defined as detectable HBV DNA (≥10 IU/mL). Secondary endpoints included overall survival, HBsAg positivity, and changes in liver biochemistry and antibody to HBsAg levels. Among 297 allogeneic HSCT recipients, 85 (28.7%) were HBsAg‐negative, anti‐HBc–positive, of whom 62 were recruited and monitored for a median of 48 (4‐104) weeks. The 2‐year cumulative HBV DNA detectability rate was 40.8%, occurring at a median of 44 (8‐100) weeks. Multivariate analysis showed that age ≥50 years (P = 0.004, hazard ratio = 8.2) and chronic graft‐versus‐host disease (P = 0.010, hazard ratio = 5.3) were significantly associated with HBV reactivation. Other clinical parameters, including baseline antibody to HBsAg status, serial changes in antibody to HBsAg levels, and donor serology, were not associated with HBV reactivation. Patients <50 years old and without chronic graft‐versus‐host disease, compared with the remaining patient cohort, had a significantly lower 2‐year cumulative HBV reactivation rate (5.6% versus 65.0%, P = 0.004). Entecavir successfully suppressed HBV DNA to undetectable levels, with no cases developing biochemical hepatitis. Conclusion: HBsAg‐negative, anti‐HBc–positive patients had a high rate of HBV reactivation after allogeneic HSCT, with determinants of HBV reactivation including age ≥50 years and chronic graft‐versus‐host disease; treatment strategies based on these parameters may prevent HBV reactivation and subsequent complications. (ClinicalTrials.gov identifier NCT01481649.) (Hepatology 2017;65:1451‐1461).

A comparison study of realtime fatality rates: severe acute respiratory syndrome in Hong Kong, Singapore, Taiwan, Toronto and Beijing, China

Summary.  In an outbreak of a completely new infectious disease like severe acute respiratory syndrome (SARS), estimation of the fatality rate over the course of the epidemic is of clinical and epidemiological importance. In contrast with the constant case fatality rate, a new measure, termed the ‘realtime’ fatality rate, is proposed for monitoring the new emerging epidemic at a population level. A competing risk model implemented via a counting process is used to estimate the realtime fatality rate in an epidemic of SARS. It can capture and reflect the time‐varying nature of the fatality rate over the course of the outbreak in a timely and accurate manner. More importantly, it can provide information on the efficacy of a certain treatment and management policy for the disease. The method has been applied to the SARS data from the regions affected, namely Hong Kong, Singapore, Toronto, Taiwan and Beijing. The magnitudes and patterns of the estimated fatalities are virtually the same except in Beijing, which has a lower rate. It is speculated that the effect is linked to the different treatment protocols that were used. The standard estimate of the case fatality rate that was used by the World Health Organization has been shown to be unable to provide useful information to monitor the time‐varying fatalities that are caused by the epidemic.