From SARS to Avian Influenza Preparedness in Hong Kong.

The first human H5N1 case was diagnosed in Hong Kong in 1997. Since then, experience in effective preparedness strategies that target novel influenza viruses has expanded. Here, we report on avian influenza preparedness in public hospitals in Hong Kong to illustrate policies and practices associated with control of emerging infectious diseases. The Hong Kong government's risk-based preparedness plan for influenza pandemics includes 3 response levels for command, control, and coordination frameworks for territory-wide responses. The tiered levels of alert, serious, and emergency response enable early detection based on epidemiological exposure followed by initiation of a care bundle. Information technology, laboratory preparedness, clinical and public health management, and infection control preparedness provide a comprehensive and generalizable preparedness plan for emerging infectious diseases.

Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection.

BACKGROUND: Experience from treating patients with Spanish influenza and influenza A(H5N1) suggested that convalescent plasma therapy might be beneficial. However, its efficacy in patients with severe pandemic influenza A(H1N1) 2009 virus (H1N1 2009) infection remained unknown. METHODS: During the period from 1 September 2009 through 30 June 2010, we conducted a prospective cohort study by recruiting patients aged ≥ 18 years with severe H1N1 2009 infection requiring intensive care. Patients were offered treatment with convalescent plasma with a neutralizing antibody titer of ≥ 1:160, harvested by apheresis from patients recovering from H1N1 2009 infection. Clinical outcome was compared with that of patients who declined plasma treatment as the untreated controls. RESULTS: Ninety-three patients with severe H1N1 2009 infection requiring intensive care were recruited. Twenty patients (21.5%) received plasma treatment. The treatment and control groups were matched by age, sex, and disease severity scores. Mortality in the treatment group was significantly lower than in the nontreatment group (20.0% vs 54.8%; P = .01). Multivariate analysis showed that plasma treatment reduced mortality (odds ratio [OR], .20; 95% confidence interval [CI], .06-.69; P = .011), whereas complication of acute renal failure was independently associated with death (OR, 3.79; 95% CI, 1.15-12.4; P = .028). Subgroup analysis of 44 patients with serial respiratory tract viral load and cytokine level demonstrated that plasma treatment was associated with significantly lower day 3, 5, and 7 viral load, compared with the control group (P < .05). The corresponding temporal levels of interleukin 6, interleukin 10, and tumor necrosis factor α (P < .05) were also lower in the treatment group. CONCLUSIONS: Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.

Prevention of acute myocardial infarction and stroke among elderly persons by dual pneumococcal and influenza vaccination: a prospective cohort study.

BACKGROUND: Despite World Health Organization recommendations, the rate of 23-valent pneumococcal (PPV) and influenza (TIV) vaccination among elderly persons in Hong Kong, China, is exceptionally low because of doubts about effectiveness of vaccination. The efficacy of dual vaccination remains unknown. METHODS: From 3 December 2007 to 30 June 2008, we conducted a prospective cohort study by recruiting outpatients aged ≥65 years with chronic illness to participate in a PPV and TIV vaccination program. All were observed until 31 March 2009. The outcome of subjects, including the rates of death, hospitalization, pneumonia, ischemic stroke, acute myocardial infarction, and coronary and intensive care admissions, were determined. RESULTS: Of the 36,636 subjects recruited, 7292 received both PPV and TIV, 2076 received TIV vaccine alone, 1875 received PPV alone, and 25,393 were unvaccinated, with a duration of follow-up of 45,834 person-years. Baseline characteristics were well matched between the groups, except that there were fewer male patients in the PPV and TIV group and fewer cases of comorbid chronic obstructive pulmonary disease among unvaccinated persons. At week 64 from commencement of the study, dual-vaccinees experienced fewer deaths (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.55-0.77]; P<.001) and fewer cases of pneumonia (HR, 0.57; 95% CI, 0.51-0.64; P<.001), ischemic stroke (HR, 0.67; 95% CI, 0.54-0.83; P<.001), and acute myocardial infarction (HR, 0.52; 95% CI, 0.38-0.71; P<.001), compared with unvaccinated subjects. Dual vaccination resulted in fewer coronary (HR, 0.59; 95% CI, 0.44-0.79; P<.001) and intensive care admissions (HR, 0.45; 95% CI, 0.22-0.94; P=.03), compared with among unvaccinated subjects. CONCLUSIONS: Dual vaccination with PPV and TIV is effective in protecting elderly persons with chronic illness from developing complications from respiratory, cardiovascular, and cerebrovascular diseases, thereby reducing hospitalization, coronary or intensive care admissions, and death.

School closure and mitigation of pandemic (H1N1) 2009, Hong Kong.

In Hong Kong, kindergartens and primary schools were closed when local transmission of pandemic (H1N1) 2009 was identified. Secondary schools closed for summer vacation shortly afterwards. By fitting a model of reporting and transmission to case data, we estimated that transmission was reduced approximately 25% when secondary schools closed.

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.

A nurse-delivered brief health education intervention to improve pneumococcal vaccination rate among older patients with chronic diseases: a cluster randomized controlled trial.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine is recommended for elders, especially those with chronic conditions. OBJECTIVE: The aim of this study was to determine if an additional multi-component health education intervention increases the uptake rate of the pneumococcal vaccination among older patients with chronic diseases. METHODS: A cluster randomized controlled trial was conducted from 3 December 2007 to 7 March 2008. The clusters were the individual weeks within five Hong Kong outpatient clinics over a 10-week period. A sample of 2517 patients aged 65 or above with chronic diseases was recruited. Intervention group received a 3-min brief telephone education intervention before and a 3-min face-to-face intervention during scheduled medical appointments at the respective clinics. All subjects received standard care including health education leaflets and/or a video show at the clinics. Pneumococcal vaccination rate and awareness of the vaccination at 3-month follow up were measured. RESULTS: The vaccination rate was higher in the intervention group compared to the control group (57% vs 48%; relative risk=1.20, 95% CI=1.06-1.37), but the two groups did not differ significantly in their awareness of the vaccination at 3-month follow up (65% vs 59%, relative risk=0.86, 95% CI=0.69-1.07). DISCUSSION: A nurse-delivered brief health education intervention was effective in increasing uptake of pneumococcal vaccination among older patients with chronic diseases.

Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection.

BACKGROUND: Experience from influenza pandemics suggested that convalescent plasma treatment given within 4 to 5 days of symptom onset might be beneficial. However, robust treatment data are lacking. METHODS: This is a multicenter, prospective, double-blind, randomized controlled trial. Convalescent plasma from patients who recovered from the 2009 pandemic influenza A(H1N1) (A[H1N1]) infection was fractionated to hyperimmune IV immunoglobulin (H-IVIG) by CSL Biotherapies (now BioCSL). Patients with severe A(H1N1) infection on standard antiviral treatment requiring intensive care and ventilatory support were randomized to receive H-IVIG or normal IV immunoglobulin manufactured before 2009 as control. Clinical outcome and adverse effects were compared. RESULTS: Between 2010 and 2011, 35 patients were randomized to receive H-IVIG (17 patients) or IV immunoglobulin (18 patients). One defaulted patient was excluded from analysis. No adverse events related to treatment were reported. Baseline demographics and viral load before treatment were similar between the two groups. Serial respiratory viral load demonstrated that H-IVIG treatment was associated with significantly lower day 5 and 7 posttreatment viral load when compared with the control (P = .04 and P = .02, respectively). The initial serum cytokine level was significantly higher in the H-IVIG group but fell to a similar level 3 days after treatment. Subgroup multivariate analysis of the 22 patients who received treatment within 5 days of symptom onset demonstrated that H-IVIG treatment was the only factor that independently reduced mortality (OR, 0.14; 95% CI, 0.02-0.92; P = .04). CONCLUSIONS: Treatment of severe A(H1N1) infection with H-IVIG within 5 days of symptom onset was associated with a lower viral load and reduced mortality. TRIAL REGISTRY: ClinialTrials.gov; No.: NCT01617317; URL: www.clinicaltrials.gov.

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

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% CI 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 gamma 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.