Influenza-associated mortality in Hong Kong

Background. The impact of influenza on mortality in countries in subtropical and tropical regions is poorly quantified. Estimation of influenza-related illness in warm-climate regions is more difficult, because the seasonality of virus circulation is less well-defined. Partly as a result of these factors, influenza vaccine is grossly underutilized in the tropics, even for individuals ≥65 years of age. Methods. Weekly numbers of deaths were modeled by Poisson regression, and excess deaths attributable to influenza in Hong Kong were estimated for 1996-1999. Comparison of weekly mortality during periods of influenza predominance and periods of low influenza activity was used to derive an alternative estimate of influenza-associated mortality. Results. Estimates derived from the Poisson model indicated that influenza resulted in 7.3 deaths per 100,000 population per year (95% confidence interval [CI], 3.1-11.4) from cardiorespiratory disease among individuals aged 40-65 years and 102.0 deaths per 100,000 per population per year (95% CI, 61.2-142.7) among individuals aged ≥65 years. Although respiratory diseases accounted for the majority of influenza-related deaths, influenza also contributed to 13.8% (95% CI, 4.8%- 22.7%) and 5.3% (95% CI, 1.2%-9.3%) of deaths related to ischemic heart disease. Conclusion. Influenza is associated with deaths due to ischemic heart disease as well from respiratory diseases. Overall influenza-associated mortality in a region with a warm climate, such as Hong Kong, is comparable with that documented in temperate regions. The need for influenza vaccination in tropical regions needs to be reassessed.published_or_final_versio

Age-Matched comparison of children hospitalized for 2009 pandemic H1N1 influenza with those hospitalized for seasonal H1N1 and H3N2

Background: A wide spectrum of clinical manifestation ranging from deaths to a mild course of disease has been reported in children infected with the 2009 pandemic H1N1 (pH1N1) influenza. Methodology/Major Findings: We conducted an age-matched control study comparing children hospitalized for pH1N1 with historic controls infected with seasonal H1N1 and H3N2 influenza to correct for the effect of age on disease susceptibility and clinical manifestations. We also compared children with pH1N1 to children concurrently admitted for seasonal influenza during the pandemic period to adjust for differences in health-seeking behavior during the pandemic or other potential bias associated with historic controls. There was no death or intensive care admission. Children with pH1N1 were more likely to have at least one risk condition for influenza, an underlying chronic pulmonary condition, more likely to have asthma exacerbation and to be treated with oseltamivir. There was no difference in other aspects of the clinical course or outcome. Conclusion: Disease manifestation of children hospitalized for pH1N1 infection was mild in our patient population. © 2011 Chiu et al.published_or_final_versio

Screening for retinopathy of prematurity and treatment outcome in a tertiary hospital in Hong Kong

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Influenza-related hospitalizations among children in Hong Kong

Background: It has been difficult to define the burden of influenza in children because of confounding by the cocirculation of respiratory syncytial virus (RSV). In Hong Kong, China, the influenza and RSV infection seasons sometimes do not overlap, thus providing an opportunity to estimate the rate of influenza-related hospitalization in a defined population, free from the effects of RSV. Methods: In a retrospective, population-based study, we estimated the influenza-associated excess rate of hospitalization among children 15 years old or younger in the Hong Kong Special Administrative Region from 1997 to 1999. Data from a single hospital with intensive use of virologic analyses for diagnosis were obtained to define and adjust for underestimation of the model. Results: Peaks of influenza and RSV infection activity were well separated in 1998 and 1999 but overlapped in 1997. The adjusted rates of excess hospitalization for acute respiratory disease that were attributable to influenza were 278.5 and 288.2 per 10,000 children less than 1 year of age in 1998 and 1999, respectively; 218.4 and 209.3 per 10,000 children 1 to less than 2 years of age; 125.6 and 77.3 per 10,000 children 2 to less than 5 years of age; 57.3 and 20.9 per 10,000 children 5 to less than 10 years of age; and 16.4 and 8.1 per 10,000 children 10 to 15 years of age. Conclusions: In the subtropics, influenza is an important cause of hospitalization among children, with rates exceeding those reported for temperate regions. Copyright © 2002 Massachusetts Medical Society.published_or_final_versio

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. © 2008 Yang et al.published_or_final_versio

Generation of recombinant influenza A virus without M2 ion-channel protein by introduction of a point mutation at the 5′ end of the viral intron

The aim of this study was to inhibit influenza virus M2 protein expression by mutating the splicing signal of the M gene. Mutations were introduced into the GU dinucleotide sequence at the 5′-proximal splicing site of the M gene (corresponding to nt 52-53 of M cRNA). Transfected cells expressing mutated M viral ribonucleoproteins failed to generate M2 mRNA. Interestingly, recombinant viruses with mutations at the dinucleotide sequence were viable, albeit attenuated, in cell culture. These recombinants failed to express M2 mRNA and M2 protein. These observations demonstrated that the GU invariant dinucleotide sequence at the 5′-proximal splicing site of M gene is essential for M2 mRNA synthesis. These results also indicated that the M2 ion-channel protein is critical, but not essential, for virus replication in cell culture. This approach may provide a new way of producing attenuated influenza A virus. © 2005 SGM.postprin

Environmental factors and mortality risks associated influenza

BACKGROUND AND AIMS: The subtropical and tropical regions exhibit a distinct seasonality of influenza incidence from the temperate regions, and the mechanism behind it remains unclear. Environmental factors have been related to the transmission and survival of influenza viruses but no studies have ever explored the role of environmental factors on regulating severity of influenza infection. METHODS: We applied a Poisson regression model to the mortality data of two Asian metropolitan cities located at the subtropical zone, Guangzhou and Hong Kong. Interaction between …postprin

Inpatient emergencies encountered by an infectious disease consultative service

The spectrum of infections disease (ID) emergencies in hospitalized patients was assessed in a prospective study of 3,626 inpatient ID consultations in a 1,350-bed teaching hospital. ID emergencies, defined by a need or anticipated need for advanced life support or by irreversible organ damage leading to permanent functional loss, were encountered in 175 patients. Infections of the central nervous system (26.3%), cardiovascular system (14.9%), alimentary system (13.1%), and lower respiratory tract (7.4%) and adverse reactions to antimicrobial agents (7.4%) were most common. In 18.9% of the cases, the referring clinicians were unaware of the emergency at the time of referral. Drug reactions (46.1%), severe alimentary and peritoneal infections (32.0%), upper respiratory tract infections (28.6%), and skin and soft-tissue infections (27.3%) were most frequently missed. The emergency ID conditions were not recognized because they had an atypical presentation (51.5%), were not commonly seen in the referring specialty (24.2%), were due to rare organisms (15.2%), or had unusual anatomical sites of involvement (9.1%). A close liaison between clinicians and the ID team is crucial for recognition of ID emergencies at their early stages so that appropriate investigations and management can be instituted expediently, before the occurrence of irreversible damage.published_or_final_versio

Viral genetic determinants of h5n1 influenza viruses that contribute to cytokine dysregulation

Human disease caused by highly pathogenic avian influenza (H5N1) is associated with fulminant viral pneumonia and mortality rates in excess of 60%. Cytokine dysregulation is thought to contribute to its pathogenesis. In comparison with human seasonal influenza (H1N1) viruses, clade 1, 2.1, and 2.2 H5N1 viruses induced higher levels of tumor necrosis factor-α in primary human macrophages. To understand viral genetic determinants responsible for this hyperinduction of cytokines, we constructed recombinant viruses containing different combinations of genes from high-cytokine (A/Vietnam/1203/04) and low-cytokine (A/WSN/33) phenotype HlNl viruses and tested their cytokine-inducing phenotype in human macrophages. Our results suggest that the H5N1 polymerase gene segments, and to a lesser extent the NS gene segment, contribute to cytokine hyperinduction in human macrophages and that a putative H5 pandemic virus that may arise through genetic reassortment between H5N1 and one of the current seasonal influenza viruses may have a markedly altered cytokine phenotype. © 2009 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Disease burden of influenza in three tropic and sub-tropic cities in Asia

Powerpoint PresentationSession 2 - Disease burden and transmission dynamics of inter-pandemic influenzaThe impact of influenza on mortality in sub-tropical and tropical countries is poorly quantified. The obstacle is mainly from assessing the disease burden among irregular seasonality of influenza activities in the warm climates. In this study we applied statistical modeling methods to three metropolitan cities in East and Southeast Asia: Guangzhou, Hong Kong, and Singapore, all of which have standardized influenza surveillance networks for years 2004-2006. We applied the method of Generalized Additive Modeling (GAM) to evaluate the effect of influenza circulation in the community on all-cause mortality and on mortality with an underlying cause of cardio-respiratory diseases. The strength of GAM lies on its capability in adjusting for the seasonality of health outcomes in the investigation for their association with influenza activity, particularly in the subtropics and tropics. Our findings indicated that influenza was associated with 12.4 (95% confidence interval (CI): 1.2, 23.0), 13.9 (95% CI: 6.4, 20.9) and 8.7 (95% CI: 3.0, 13.9) deaths for all causes per 100,000 population in Guangzhou, Hong Kong, and Singapore, respectively. For the cardio-respiratory mortality, influenza was associated with 11.2 (95% CI: 2.4, 19.6), 9.1 (95% CI: 4.3, 13.6) and 5.5 (95% CI: 1.6, 9.4) deaths per 100,000 population in the three cites. These results showed that the disease burdens in the two subtropical cities Guangzhou and Hong Kong were similar and slightly higher than those in the tropical city, Singapore. In the future, a cross region study involving temperate, subtropical, and tropical climates could provide more information about the health effects of influenza in Asia.postprin