Thomas Tsang

Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong

Summary Background Health authorities worldwide, especially in the Asia Pacific region, are seeking effective public-health interventions in the continuing epidemic of severe acute respiratory syndrome (SARS). We assessed the epidemiology of SARS in Hong Kong. Methods We included 1425 cases reported up to April 28, 2003. An integrated database was constructed from several sources containing information on epidemiological, demographic, and clinical variables. We estimated the key epidemiological distributions: infection to onset, onset to admission, admission to death, and admission to discharge. We measured associations between the estimated case fatality rate and patients’age and the time from onset to admission. Findings After the initial phase of exponential growth, the rate of confirmed cases fell to less than 20 per day by April 28. Public-health interventions included encouragement to report to hospital rapidly after the onset of clinical symptoms, contact tracing for confirmed and suspected cases, and quarantining, monitoring, and restricting the travel of contacts. The mean incubation period of the disease is estimated to be 6.4 days (95% Cl 5.2–7.7). The mean time from onset of clinical symptoms to admission to hospital varied between 3 and 5 days, with longer times earlier in the epidemic. The estimated case fatality rate was 13.2% (9.8–16.8) for patients younger than 60 years and 43.3% (35.2–52.4) for patients aged 60 years or older assuming a parametric γ distribution. A non-parametric method yielded estimates of 6.8% (4.0–9.6) and 55.0% (45.3–64.7), respectively. Case clusters have played an important part in the course of the epidemic. Interpretation Patients’age was strongly associated with outcome. The time between onset of symptoms and admission to hospital did not alter outcome, but shorter intervals will be important to the wider population by restricting the infectious period before patients are placed in quarantine. Published online May 7, 2003 http://image.thelancet.com/extras/03art4453web.pdf

The infection attack rate and severity of 2009 pandemic H1N1 influenza in Hong Kong

BACKGROUND Serial cross-sectional data on antibody levels to the 2009 pandemic H1N1 influenza A virus from a population can be used to estimate the infection attack rates and immunity against future infection in the community. METHODS From April through December 2009, we obtained 12,217 serum specimens from blood donors (aged 16-59 years), 2520 specimens from hospital outpatients (aged 5-59 years), and 917 specimens from subjects involved in a community pediatric cohort study (aged 5-14 years). We estimated infection attack rates by comparing the proportions of specimens with antibody titers ≥ 1:40 by viral microneutralization before and after the first wave of the pandemic. Estimates were validated using paired serum samples from 324 individuals that spanned the first wave. Combining these estimates with epidemiologic surveillance data, we calculated the proportion of infections that led to hospitalization, admission to the intensive care unit (ICU), and death. RESULTS We found that 3.3% and 14% of persons aged 5-59 years had antibody titers ≥ 1:40 before and after the first wave, respectively. The overall attack rate was 10.7%, with age stratification as follows: 43.4% in persons aged 5-14 years, 15.8% in persons aged 15-19 years, 11.8% in persons aged 20-29 years, and 4%-4.6% in persons aged 30-59 years. Case-hospitalization rates were 0.47%-0.87% among persons aged 5-59 years. Case-ICU rates were 7.9 cases per 100,000 infections in persons aged 5-14 years and 75 cases per 100,000 infections in persons aged 50-59 years, respectively. Case-fatality rates were 0.4 cases per 100,000 infections in persons aged 5-14 years and 26.5 cases per 100,000 infections in persons aged 50-59 years, respectively. CONCLUSIONS Almost half of all school-aged children in Hong Kong were infected during the first wave. Compared with school children aged 5-14 years, older adults aged 50-59 years had 9.5 and 66 times higher risks of ICU admission and death if infected, respectively.

Epidemiological Characteristics of 2009 (H1N1) Pandemic Influenza Based on Paired Sera from a Longitudinal Community Cohort Study

Steven Riley and colleagues analyze a community cohort study from the 2009 (H1N1) influenza pandemic in Hong Kong, and found that more children than adults were infected with H1N1, but children were less likely to progress to severe disease than adults.

Lack of Evidence for Human-to-Human Transmission of Avian Influenza A (H9N2) Viruses in Hong Kong, China 1999

In April 1999, isolation of avian influenza A (H9N2) viruses from humans was confirmed for the first time. H9N2 viruses were isolated from nasopharyngeal aspirate specimens collected from two children who were hospitalized with uncomplicated, febrile, upper respiratory tract illnesses in Hong Kong during March 1999. Novel influenza viruses have the potential to initiate global pandemics if they are sufficiently transmissible among humans. We conducted four retrospective cohort studies of persons exposed to these two H9N2 patients to assess whether human-to-human transmission of avian H9N2 viruses had occurred. No serologic evidence of H9N2 infection was found in family members or health-care workers who had close contact with the H9N2-infected children, suggesting that these H9N2 viruses were not easily transmitted from person to person.

Excess Mortality Associated With Influenza A and B Virus in Hong Kong, 1998–2009

BACKGROUND Although deaths associated with laboratory-confirmed influenza virus infections are rare, the excess mortality burden of influenza estimated from statistical models may more reliably quantify the impact of influenza in a population. METHODS We applied age-specific multiple linear regression models to all-cause and cause-specific mortality rates in Hong Kong from 1998 through 2009. The differences between estimated mortality rates in the presence or absence of recorded influenza activity were used to estimate influenza-associated excess mortality. RESULTS The annual influenza-associated all-cause excess mortality rate was 11.1 (95% confidence interval [CI], 7.2-14.6) per 100,000 person-years. We estimated an average of 751 (95% CI, 488-990) excess deaths associated with influenza annually from 1998 through 2009, with 95% of the excess deaths occurring in persons aged ≥65 years. Most of the influenza-associated excess deaths were from respiratory (53%) and cardiovascular (18%) causes. Influenza A(H3N2) epidemics were associated with more excess deaths than influenza A(H1N1) or B during the study period. CONCLUSIONS Influenza was associated with a substantial number of excess deaths each year, mainly among the elderly, in Hong Kong in the past decade. The influenza-associated excess mortality rates were generally similar in Hong Kong and the United States.

Molecular Characterization of the 2011 Hong Kong Scarlet Fever Outbreak

A scarlet fever outbreak occurred in Hong Kong in 2011. The majority of cases resulted in the isolation of Streptococcus pyogenes emm12 with multiple antibiotic resistances. Phylogenetic analysis of 22 emm12 scarlet fever outbreak isolates, 7 temporally and geographically matched emm12 non-scarlet fever isolates, and 18 emm12 strains isolated during 2005-2010 indicated the outbreak was multiclonal. Genome sequencing of 2 nonclonal scarlet fever isolates (HKU16 and HKU30), coupled with diagnostic polymerase chain reaction assays, identified 2 mobile genetic elements distributed across the major lineages: a 64.9-kb integrative and conjugative element encoding tetracycline and macrolide resistance and a 46.4-kb prophage encoding superantigens SSA and SpeC and the DNase Spd1. Phenotypic comparison of HKU16 and HKU30 with the S. pyogenes M1T1 strain 5448 revealed that HKU16 displays increased adherence to HEp-2 human epithelial cells, whereas HKU16, HKU30, and 5448 exhibit equivalent resistance to neutrophils and virulence in a humanized plasminogen murine model. However, in contrast to M1T1, the virulence of HKU16 and HKU30 was not associated with covRS mutation. The multiclonal nature of the emm12 scarlet fever isolates suggests that factors such as mobile genetic elements, environmental factors, and host immune status may have contributed to the 2011 scarlet fever outbreak.

Estimating Infection Attack Rates and Severity in Real Time during an Influenza Pandemic: Analysis of Serial Cross-Sectional Serologic Surveillance Data

This study reports that using serological data coupled with clinical surveillance data can provide real-time estimates of the infection attack rates and severity in an emerging influenza pandemic.

The effective reproduction number of pandemic influenza: Prospective estimation

Background: Timely estimation of the transmissibility of a novel pandemic influenza virus was a public health priority in 2009. Methods: We extended methods for prospective estimation of the effective reproduction number (Rt) over time in an emerging epidemic to allow for reporting delays and repeated importations. We estimated Rt based on case notifications and hospitalizations associated with laboratory-confirmed pandemic (H1N1) 2009 virus infections in Hong Kong from June through October 2009. Results: Rt declined from around 1.4–1.5 at the start of the local epidemic to around 1.1–1.2 later in the summer, suggesting changes in transmissibility perhaps related to school vacations or seasonality. Estimates of Rt based on hospitalizations of confirmed H1N1 cases closely matched estimates based on case notifications. Conclusion: Real-time monitoring of the effective reproduction number is feasible and can provide useful information to public health authorities for situational awareness and calibration of mitigation strategies.

Infection Fatality Risk of the Pandemic A(H1N1)2009 Virus in Hong Kong

One measure of the severity of a pandemic influenza outbreak at the individual level is the risk of death among people infected by the new virus. However, there are complications in estimating both the numerator and denominator. Regarding the numerator, statistical estimates of the excess deaths associated with influenza virus infections tend to exceed the number of deaths associated with laboratory-confirmed infection. Regarding the denominator, few infections are laboratory confirmed, while differences in case definitions and approaches to case ascertainment can lead to wide variation in case fatality risk estimates. Serological surveillance can be used to estimate the cumulative incidence of infection as a denominator that is more comparable across studies. We estimated that the first wave of the influenza A(H1N1)pdm09 virus in 2009 was associated with approximately 232 (95% confidence interval: 136, 328) excess deaths of all ages in Hong Kong, mainly among the elderly. The point estimates of the risk of death on a per-infection basis increased substantially with age, from below 1 per 100,000 infections in children to 1,099 per 100,000 infections in those 60-69 years of age. Substantial variation in the age-specific infection fatality risk complicates comparison of the severity of different influenza strains.

Estimation of the basic reproduction number of enterovirus 71 and coxsackievirus A16 in hand, foot, and mouth disease outbreaks.

Background: Coxsackievirus A16 (Cox A16) and enterovirus 71 (EV71) are common pathogens causing hand, foot, and mouth disease (HFMD) in pediatric population. Little is known about the basic reproductive number (R0) for these enteroviruses. Methods: We estimated the R0 of EV71 and of Cox A16 from laboratory-confirmed HFMD outbreaks reported to the Department of Health, from 2004 to 2009. We derived a mathematical model and calculated R0 based on the cumulative number of cases at the initial growth phase of the outbreaks, as determined by the epidemic curves. We tested the association of R0 with settings and sizes of the institution and total number of persons affected. Results: We analyzed 34 outbreaks, 27 caused by Cox A16 and 7 caused by EV71. Assuming the incubation period to be 5 days, the median R0 of EV71 was 5.48 with an interquartile range of 4.20 to 6.51, whereas the median R0 of Cox A16 was 2.50 with an interquartile range of 1.96 to 3.67. The R0 of EV71 was significantly higher than that of CoxA16, P = 0.002; and sensitivity analysis showed the same results. The R0 was not associated with outbreak settings, sizes of the institutions, or number of persons affected. Conclusions: The R0 for EV71 and for Cox A16 was determined using a model which showed that the R0 for EV71 was higher than that of Cox A16. This finding helps better understand the transmission dynamics of HFMD outbreaks and formulate public health measures for controlling the disease.