Confronting SARS: a view from Hong Kong

Severe acute respiratory syndrome (SARS) emerged as a new disease in Guangdong Province, People's Republic of China in late 2002. Within weeks it had spread to Hong Kong and thence globally to affect over 25 countries across five continents. The disease had the propensity to cause clusters of pneumonia, particularly in healthcare workers or close family contacts. A global effort coordinated by the World Health Organization successfully defined the aetiology, epidemiology and clinical characteristics of the disease, and the implementation of case identification, isolation and infection control measures led to the interruption of the global outbreak by July 2003. The pattern of disease emergence and strategies for control of SARS provides lessons for coping with future emerging infectious disease threats.     

Seroprevalence of pandemic H1N1 antibody among health care workers in Hong Kong following receipt of monovalent 2009 H1N1 influenza vaccine

Background

Healthcare workers in many countries are recommended to receive influenza vaccine to protect themselves as well as patients. A monovalent H1N1 vaccine became available in Hong Kong in December 2009 and around 10% of local healthcare workers had received the vaccine by February 2010.

Methods

We conducted a cross-sectional study of the prevalence of antibody to pandemic (H1N1) 2009 among HCWs in Hong Kong in February–March 2010 following the first pandemic wave and the pH1N1 vaccination campaign. In this study we focus on the subset of healthcare workers who reported receipt of non-adjuvanted monovalent 2009 H1N1 vaccine (Panenza, Sanofi Pasteur). Sera collected from HCWs were tested for antibody against the pH1N1 virus by hemagglutination inhibition (HI) and viral neutralization (VN) assays.

Results

We enrolled 703 HCWs. Among 104 HCWs who reported receipt of pH1N1 vaccine, 54% (95% confidence interval (CI): 44%–63%) had antibody titer ≥1∶40 by HI and 42% (95% CI: 33%–52%) had antibody titer ≥1∶40 by VN. The proportion of HCWs with antibody titer ≥1∶40 by HI and VN significantly decreased with age, and the proportion with antibody titer ≥1∶40 by VN was marginally significantly lower among HCWs who reported prior receipt of 2007–08 seasonal influenza vaccine (odds ratio: 0.43; 95% CI: 0.19–1.00). After adjustment for age, the effect of prior seasonal vaccine receipt was not statistically significant.

Conclusions

Our findings suggest that monovalent H1N1 vaccine may have had suboptimal immunogenicity in HCWs in Hong Kong. Larger studies are required to confirm whether influenza vaccine maintains high efficacy and effectiveness in HCWs.     

Mortality and smoking in Hong Kong: case-control study of all adult deaths in 1998

ObjectiveTo assess the mortality currently associated with smoking in Hong Kong, and, since cigarette consumption reached its peak 20 years earlier in Hong Kong than in mainland China, to predict mortality in China 20 years hence.DesignCase-control study. Past smoking habits of all Chinese adults in Hong Kong who died in 1998 (cases) were sought from those registering the death.SettingAll the death registries in Hong Kong.Participants27 507 dead cases (81% of all registered deaths) and 13 054 live controls aged ⩾35 years.ResultsIn men aged 35-69 the adjusted risk ratios (and 95% confidence intervals) comparing smokers with non-smokers were 1.92 (1.70 to 2.16) for all deaths, 2.22 (1.94 to 2.55) for neoplastic deaths, 2.60 (2.10 to 3.21) for respiratory deaths (including tuberculosis, risk ratio 2.54), and 1.68 (1.43 to 1.97) for vascular deaths (each P<0.0001). In women aged 35-69 the corresponding risk ratios were 1.62 (1.40 to 1.88) for all deaths, 1.60 (1.33 to 1.93) for neoplastic deaths, 3.13 (2.21 to 4.44) for respiratory deaths, and 1.55 (1.20 to 1.99) for vascular deaths (each P<0.001). If these associations with smoking are largely or wholly causal then, among all registered deaths at ages 35-69 in 1998, tobacco caused about 33% (2534/7588) of all male deaths and 5% (169/3341) of all female deaths (hence 25% of all deaths at these ages). At older ages tobacco seemed to be the cause of 15% (3017/20 420) of all deaths.ConclusionsAmong middle aged men the proportion of deaths caused by smoking is more than twice as big in Hong Kong now (33%) as in mainland China 10 years earlier. This supports predictions of a large increase in tobacco attributable mortality in China as a whole.

What is already known on this topic

China, with 20% of the world''s population, smokes 30% of the world''s cigarettes. Men smoke most, and the proportion of male deaths at ages 35-69 attributable to tobacco has been predicted to rise over the next few decades from 13% (in 1988) to about 33%In Hong Kong cigarette consumption reached its peak 20 years earlier than in mainland China, so the epidemic of male deaths from tobacco should now be at a more advanced stage

What this study adds

In the general population of Hong Kong in 1998 tobacco caused about 33% of all male deaths at ages 35-69 plus 5% of all female deaths, and hence 25% of all deaths at these agesIn the male smokers tobacco caused about half of all deaths at ages 35-69The hazards now seen in Hong Kong foreshadow a substantial increase in tobacco deaths among middle aged men in mainland China over the next few decades if current smoking patterns persist     

A cost-effectiveness analysis of "test" versus "treat" patients hospitalized with suspected influenza in Hong Kong

Background

Seasonal and 2009 H1N1 influenza viruses may cause severe diseases and result in excess hospitalization and mortality in the older and younger adults, respectively. Early antiviral treatment may improve clinical outcomes. We examined potential outcomes and costs of test-guided versus empirical treatment in patients hospitalized for suspected influenza in Hong Kong.

Methods

We designed a decision tree to simulate potential outcomes of four management strategies in adults hospitalized for severe respiratory infection suspected of influenza: “immunofluorescence-assay” (IFA) or “polymerase-chain-reaction” (PCR)-guided oseltamivir treatment, “empirical treatment plus PCR” and “empirical treatment alone”. Model inputs were derived from literature. The average prevalence (11%) of influenza in 2010–2011 (58% being 2009 H1N1) among cases of respiratory infections was used in the base-case analysis. Primary outcome simulated was cost per quality-adjusted life-year (QALY) expected (ICER) from the Hong Kong healthcare providers'' perspective.

Results

In base-case analysis, “empirical treatment alone” was shown to be the most cost-effective strategy and dominated the other three options. Sensitivity analyses showed that “PCR-guided treatment” would dominate “empirical treatment alone” when the daily cost of oseltamivir exceeded USD18, or when influenza prevalence was <2.5% and the predominant circulating viruses were not 2009 H1N1. Using USD50,000 as the threshold of willingness-to-pay, “empirical treatment alone” and “PCR-guided treatment” were cost-effective 97% and 3% of time, respectively, in 10,000 Monte-Carlo simulations.

Conclusions

During influenza epidemics, empirical antiviral treatment appears to be a cost-effective strategy in managing patients hospitalized with severe respiratory infection suspected of influenza, from the perspective of healthcare providers in Hong Kong.     

Validation of statistical models for estimating hospitalization associated with influenza and other respiratory viruses

Background

Reliable estimates of disease burden associated with respiratory viruses are keys to deployment of preventive strategies such as vaccination and resource allocation. Such estimates are particularly needed in tropical and subtropical regions where some methods commonly used in temperate regions are not applicable. While a number of alternative approaches to assess the influenza associated disease burden have been recently reported, none of these models have been validated with virologically confirmed data. Even fewer methods have been developed for other common respiratory viruses such as respiratory syncytial virus (RSV), parainfluenza and adenovirus.

Methods and Findings

We had recently conducted a prospective population-based study of virologically confirmed hospitalization for acute respiratory illnesses in persons <18 years residing in Hong Kong Island. Here we used this dataset to validate two commonly used models for estimation of influenza disease burden, namely the rate difference model and Poisson regression model, and also explored the applicability of these models to estimate the disease burden of other respiratory viruses. The Poisson regression models with different link functions all yielded estimates well correlated with the virologically confirmed influenza associated hospitalization, especially in children older than two years. The disease burden estimates for RSV, parainfluenza and adenovirus were less reliable with wide confidence intervals. The rate difference model was not applicable to RSV, parainfluenza and adenovirus and grossly underestimated the true burden of influenza associated hospitalization.

Conclusion

The Poisson regression model generally produced satisfactory estimates in calculating the disease burden of respiratory viruses in a subtropical region such as Hong Kong.     

Curtailing transmission of severe acute respiratory syndrome within a community and its hospital

Severe acute respiratory syndrome (SARS) has been transmitted extensively within hospitals, and healthcare workers (HCWs) have comprised a large proportion of SARS cases worldwide. We present a stochastic model of a SARS outbreak in a community and its hospital. For a range of basic reproductive numbers (R(0)) corresponding to conditions in different cities (but with emphasis on R(0) approximately 3 as reported for Hong Kong and Singapore), we evaluate contact precautions and case management (quarantine and isolation) as containment measures. Hospital-based contact precautions emerge as the most potent measures, with hospital-wide measures being particularly important if screening of HCWs is inadequate. For R(0) = 3, case isolation alone can control a SARS outbreak only if isolation reduces transmission by at least a factor of four and the mean symptom-onset-to-isolation time is less than 3 days. Delays of a few days in contact tracing and case identification severely degrade the utility of quarantine and isolation, particularly in high-transmission settings. Still more detrimental are delays between the onset of an outbreak and the implementation of control measures; for given control scenarios, our model identifies windows of opportunity beyond which the efficacy of containment efforts is reduced greatly. By considering pathways of transmission in our system, we show that if hospital-based transmission is not halted, measures that reduce community-HCW contact are vital to preventing a widespread epidemic. The implications of our results for future emerging pathogens are discussed.     

Socioeconomic Disparity in Breast Cancer Detection in Hong Kong – A High Income City: Retrospective Epidemiological Study Using the Breast Cancer Registry

Background

It is not known whether socioeconomic disparities affect the detection of breast cancer in Asian countries where the incidence of breast cancer is a rising trend. In this study, we explore the socioeconomic profiles of women and the stage of the disease at the time of diagnosis in breast cancer patients aged 40 or over in Hong Kong.

Method

During the period 2008 to 2011, 5393 breast cancer patients registered with the Hong Kong Breast Cancer Registry. Participants and their clinicians were asked to complete standardised questionnaires including patient socio-demographics, health history and risk factors, the course of the disease, post-treatment physical discomfort and psychosocial impact, follow-up recurrence and survival status.

Results

Monthly household incomes, educational levels and the practice of regular screening are independently associated with the stage of the disease at diagnosis. Higher socioeconomic status and a higher educational level were associated with an earlier stage of the disease at the time of diagnosis. Yearly clinical examinations, ultrasound and mammographic screening every 2 to 3 years were significantly associated with the earlier detection of breast cancer.

Conclusion

There were socioeconomic disparities among Hong Kong women who were found to have breast cancer. Population-based screening policies, including raising awareness among women at risk, should be implemented.     

Tuberculosis in Healthcare Workers and Infection Control Measures at Primary Healthcare Facilities in South Africa

Background

Challenges exist regarding TB infection control and TB in hospital-based healthcare workers in South Africa. However, few studies report on TB in non-hospital based healthcare workers such as primary or community healthcare workers. Our objectives were to investigate the implementation of TB infection control measures at primary healthcare facilities, the smear positive TB incidence rate amongst primary healthcare workers and the association between TB infection control measures and all types of TB in healthcare workers.

Methods

One hundred and thirty three primary healthcare facilities were visited in five provinces of South Africa in 2009. At each facility, a TB infection control audit and facility questionnaire were completed. The number of healthcare workers who had had TB during the past three years was obtained.

Results

The standardised incidence ratio of smear positive TB in primary healthcare workers indicated an incidence rate of more than double that of the general population. In a univariable logistic regression, the infection control audit score was significantly associated with reported cases of TB in healthcare workers (OR=1.04, 95%CI 1.01-1.08, p=0.02) as was the number of staff (OR=3.78, 95%CI 1.77-8.08). In the multivariable analysis, the number of staff remained significantly associated with TB in healthcare workers (OR=3.33, 95%CI 1.37-8.08).

Conclusion

The high rate of TB in healthcare workers suggests a substantial nosocomial transmission risk, but the infection control audit tool which was used did not perform adequately as a measure of this risk. Infection control measures should be monitored by validated tools developed and tested locally. Different strategies, such as routine surveillance systems, could be used to evaluate the burden of TB in healthcare workers in order to calculate TB incidence, monitor trends and implement interventions to decrease occupational TB.     

A possible geographic origin of endemic hepatitis C virus 6a in Hong Kong: evidences for the association with Vietnamese immigration

Background

Hepatitis C virus (HCV) 6a accounts for 23.6% of all HCV infections of the general population and 58.5% of intravenous drug users in Hong Kong. However, the geographical origin of this highly predominant HCV subgenotype is largely unknown. This study explores a hypothesis for one possible transmission route of HCV 6a to Hong Kong.

Methods

NS5A sequences derived from 26 HCV 6a samples were chosen from a five year period (1999–2004) from epidemiologically unrelated patients from Hong Kong. Partial-NS5A sequences (513-bp from nt 6728 to 7240) were adopted for Bayesian coalescent analysis to reconstruct the evolutionary history of HCV infections in Hong Kong using the BEAST v1.3 program. A rooted phylogenetic tree was drawn for these sequences by alignment with reference Vietnamese sequences. Demographic data were accessed from “The Statistic Yearbooks of Hong Kong”.

Results

Bayesian coalescent analysis showed that the rapid increase in 6a infections, which had increased more than 90-fold in Hong Kong from 1986 to 1994 correlated to two peaks of Vietnamese immigration to Hong Kong from 1978 to 1997. The second peak, which occurred from 1987 through 1997, overlapped with the rapid increase of HCV 6a occurrence in Hong Kong. Phylogenetic analyses have further revealed that HCV 6a strains from Vietnam may be ancestral to Hong Kong counterparts.

Conclusions

The high predominance of HCV 6a infections in Hong Kong was possibly associated with Vietnamese immigration during 1987–1997.     

A Comparison of Functional Outcome in Patients Sustaining Major Trauma: A Multicentre,Prospective, International Study

Objectives

To compare 6 month and 12 month health status and functional outcomes between regional major trauma registries in Hong Kong and Victoria, Australia.

Summary Background Data

Multicentres from trauma registries in Hong Kong and the Victorian State Trauma Registry (VSTR).

Methods

Multicentre, prospective cohort study. Major trauma patients and aged ≥18 years were included. The main outcome measures were Extended Glasgow Outcome Scale (GOSE) functional outcome and risk-adjusted Short-Form 12 (SF-12) health status at 6 and 12 months after injury.

Results

261 cases from Hong Kong and 1955 cases from VSTR were included. Adjusting for age, sex, ISS, comorbid status, injury mechanism and GCS group, the odds of a better functional outcome for Hong Kong patients relative to Victorian patients at six months was 0.88 (95% CI: 0.66, 1.17), and at 12 months was 0.83 (95% CI: 0.60, 1.12). Adjusting for age, gender, ISS, GCS, injury mechanism and comorbid status, Hong Kong patients demonstrated comparable mean PCS-12 scores at 6-months (adjusted mean difference: 1.2, 95% CI: −1.2, 3.6) and 12-months (adjusted mean difference: −0.4, 95% CI: −3.2, 2.4) compared to Victorian patients. Keeping age, gender, ISS, GCS, injury mechanism and comorbid status, there was no difference in the MCS-12 scores of Hong Kong patients compared to Victorian patients at 6-months (adjusted mean difference: 0.4, 95% CI: −2.1, 2.8) or 12-months (adjusted mean difference: 1.8, 95% CI: −0.8, 4.5).

Conclusion

The unadjusted analyses showed better outcomes for Victorian cases compared to Hong Kong but after adjusting for key confounders, there was no difference in 6-month or 12-month functional outcomes between the jurisdictions.     

Timely identification of optimal control strategies for emerging infectious diseases

Background

Health authorities must rely on quarantine, isolation, and other non-pharmaceutical interventions to contain outbreaks of newly emerging human diseases.

Methods

We modeled a generic disease caused by a pathogen apparently transmitted by close interpersonal contact, but about which little else is known. In our model, people may be infectious while incubating or during their prodrome or acute illness. We derived an expression for ℜ, the reproduction number, took its partial derivatives with respect to control parameters, and encoded these analytical results in a user-friendly Mathematica™ notebook. With biological parameters for SARS estimated from the initial case series in Hong Kong and infection rates from hospitalizations in Singapore, we determined ℜ's sensitivity to control parameters.

Results

Stage-specific infection rate estimates from cases hospitalized before quarantine began exceed those from the entire outbreak, but are qualitatively similar: infectiousness was negligible until symptom onset, and increased 10-fold from prodrome to acute illness. Given such information, authorities might instead have emphasized a strategy whose efficiency more than compensates for any possible reduction in efficacy.

Conclusions

In future outbreaks of new human diseases transmitted via close interpersonal contact, it should be possible to identify the optimal intervention early enough to facilitate effective decision-making.     

Psychometric Assessment of the Chinese Version of the Supportive Care Needs Survey Short-Form (SCNS-SF34-C) among Hong Kong and Taiwanese Chinese Colorectal Cancer Patients

Background

Accurate assessment of unmet supportive care needs is essential for optimal cancer patient care. This study used confirmatory factor analysis (CFA) to test the known factor structures of the short form of Supportive Care Need Survey (SCNS-34) in Hong Kong and Taiwan Chinese patients diagnosed with colorectal cancer (CRC).

Methods

360 Hong Kong and 263 Taiwanese Chinese CRC patients completed the Chinese version of SCNS-SF34. Comparative measures (patient satisfaction, anxiety, depression, and symptom distress) tested convergent validity while known group differences were examined to test discriminant validity.

Results

The original 5-factor and recent 4-factor models of the SCNS demonstrated poor data fit using CFA in both Hong Kong and Taiwan samples. Subsequently a modified five-factor model with correlated residuals demonstrated acceptable fit in both samples. Correlations demonstrated convergent and divergent validity and known group differences were observed.

Conclusions

While the five-factor model demonstrated a better fit for data from Chinese colorectal cancer patients, some of the items within its domain overlapped, suggesting item redundancy. The five-factor model showed good psychometric properties in these samples but also suggests conceptualization of unmet supportive care needs are currently inadequate.     

Modelling strategies for controlling SARS outbreaks

Severe acute respiratory syndrome (SARS), a new, highly contagious, viral disease, emerged in China late in 2002 and quickly spread to 32 countries and regions causing in excess of 774 deaths and 8098 infections worldwide. In the absence of a rapid diagnostic test, therapy or vaccine, isolation of individuals diagnosed with SARS and quarantine of individuals feared exposed to SARS virus were used to control the spread of infection. We examine mathematically the impact of isolation and quarantine on the control of SARS during the outbreaks in Toronto, Hong Kong, Singapore and Beijing using a deterministic model that closely mimics the data for cumulative infected cases and SARS-related deaths in the first three regions but not in Beijing until mid-April, when China started to report data more accurately. The results reveal that achieving a reduction in the contact rate between susceptible and diseased individuals by isolating the latter is a critically important strategy that can control SARS outbreaks with or without quarantine. An optimal isolation programme entails timely implementation under stringent hygienic precautions defined by a critical threshold value. Values below this threshold lead to control, but those above are associated with the incidence of new community outbreaks or nosocomial infections, a known cause for the spread of SARS in each region. Allocation of resources to implement optimal isolation is more effective than to implement sub-optimal isolation and quarantine together. A community-wide eradication of SARS is feasible if optimal isolation is combined with a highly effective screening programme at the points of entry.     

Comparing Quality of Public Primary Care between Hong Kong and Shanghai Using Validated Patient Assessment Tools

Objectives

Primary care is the key element of health reform in China. The objective of this study was to compare patient assessed quality of public primary care between Hong Kong, a city with established primary care environment influenced by its colonial history, and Shanghai, a city leading primary care reform in Mainland China; and to measure the equity of care in the two cities.

Methods

Cross sectional stratified random sampling surveys were conducted in 2011. Data were collected from 1,994 respondents in Hong Kong and 811 respondents in Shanghai. A validated Chinese version of the primary care assessment tool was employed to assess perceived quality of primary care with respect to socioeconomic characteristics and health status.

Results

We analyzed 391 and 725 respondents in Hong Kong and Shanghai, respectively, who were regular public primary care users. Respondents in Hong Kong reported significant lower scores in first contact accessibility (1.59 vs. 2.15), continuity of care (2.33 vs. 3.10), coordination of information (2.84 vs. 3.64), comprehensiveness service availability (2.43 vs. 3.31), comprehensiveness service provided (2.11 vs. 2.40), and the total score (23.40 vs. 27.40), but higher scores in first contact utilization (3.15 vs. 2.54) and coordination of services (2.67 vs. 2.40) when compared with those in Shanghai. Respondents with higher income reported a significantly higher total primary care score in Hong Kong, but not in Shanghai.

Conclusions

Respondents in Shanghai reported better quality of public primary care than those in Hong Kong, while quality of public primary care tended to be more equitable in Shanghai.     

Noise Exposure and Hearing Impairment among Chinese Restaurant Workers and Entertainment Employees in Hong Kong

Background

Noise-induced hearing loss (NIHL) is a major concern in the non-manufacturing industries. This study aimed to investigate the occupational noise exposure and the NIHL among Chinese restaurant workers and entertainment employees working in the service industry in Hong Kong.

Methods

This cross-sectional survey involved a total of 1,670 participants. Among them, 937 were randomly selected from the workers of Chinese restaurants and 733 were selected from workers in three entertainment sectors: radio and television stations; cultural performance halls or auditoria of the Leisure and Cultural Services Department (LCSD); and karaoke bars. Noise exposure levels were measured in the sampled restaurants and entertainment sectors. Each participant received an audiometric screening test. Those who were found to have abnormalities were required to take another diagnostic test in the health center. The “Klockhoff digit” method was used to classify NIHL in the present study.

Results

The main source of noise inside restaurants was the stoves. The mean hearing thresholds showed a typical dip at 3 to 6 KHz and a substantial proportion (23.7%) of the workers fulfilled the criteria for presumptive NIHL. For entertainment sectors, employees in radio and television stations generally had higher exposure levels than those in the halls or auditoria of the LCSD and karaoke bars. The mean hearing thresholds showed a typical dip at 6 KHz and a substantial proportion of the employees fulfilled the criteria for presumptive NIHL (38.6%, 95%CI: 35.1–42.1%). Being male, older, and having longer service and daily alcohol consumption were associated with noise-induced hearing impairment both in restaurant workers and entertainment employees.

Conclusion

Excessive noise exposure is common in the Chinese restaurant and entertainment industries and a substantial proportion of restaurant workers and entertainment employees suffer from NIHL. Comprehensive hearing conservation programs should be introduced to the service industry in Hong Kong.     

Economic Evaluation of Individual School Closure Strategies: The Hong Kong 2009 H1N1 Pandemic

Background

School closures as a means of containing the spread of disease have received considerable attention from the public health community. Although they have been implemented during previous pandemics, the epidemiological and economic effects of the closure of individual schools remain unclear.

Methodology

This study used data from the 2009 H1N1 pandemic in Hong Kong to develop a simulation model of an influenza pandemic with a localised population structure to provide scientific justifications for and economic evaluations of individual-level school closure strategies.

Findings

The estimated cost of the study’s baseline scenario was USD330 million. We found that the individual school closure strategies that involved all types of schools and those that used a lower threshold to trigger school closures had the best performance. The best scenario resulted in an 80% decrease in the number of cases (i.e., prevention of about 830,000 cases), and the cost per case prevented by this intervention was USD1,145; thus, the total cost was USD1.28 billion.

Conclusion

This study predicts the effects of individual school closure strategies on the 2009 H1N1 pandemic in Hong Kong. Further research could determine optimal strategies that combine various system-wide and district-wide school closures with individual school triggers across types of schools. The effects of different closure triggers at different phases of a pandemic should also be examined.     

Conservation evaluation of nine Hong Kong mangals

A comparative analysis of the conservation value of nine Hong Kong mangals spread across Hong Kong has been undertaken. The analysis is based on both biological and socio-economic attributes. Biological attributes used in the analysis include plant species richness, benthic and arboreal gastropod species richness, occurrence of rare species within each site, and site representativeness. A review of the past and present development and development plans around and within each site has been undertaken to assess the comparative degree of hazard to each mangal. The drastic decline of mangal habitats throughout Hong Kong highlights the need for conservation of what remains today. Priorities and strategies for conservation of these nine mangals are discussed with particular emphasis on the preservation of biodiversity and the management of these habitats as education and research sites.Department of Applied Biology & Chemical Technology, Hong Kong Polytechnic     

Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells

Background

Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells.

Methods

We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro.

Results

We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus.

Conclusion

The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.