Influenza and Other Infections of Public Health Significance

Influenza viruses pose constant threats to global public and animal health. Its control requires a multidisciplinary "One Health" approach. Hong Kong, a densely populated city situated at an epicenter pandemic influenza emergence provides an ideal location to study influenza ecology, transmission, and public health interventions. The research cluster has four areas of research focus: (1) understanding the ecology and the origin of pandemic and zoonotic influenza viruses; (2) understanding the mode of influenza transmission in between humans and from animals to humans; (3) understanding influenza pathogenesis; and (4) identifying efficient public health interventions for the control of influenza in human and animals. These same research strategies are applied to other emerging viral pathogens, for example MERS coronavirus.

 

(1) Ecology and the origin of pandemic and zoonotic influenza viruses

A diverse gene pool of influenza virus resides in multiple reservoirs and interspecies transmission is a known contributing factor for the emergence of pandemic influenza viruses in human populations. It is therefore critical to understand the ecological factors favoring interspecies transmission and the drivers of the emergence of pandemic influenza viruses. Many of the past pandemic influenza viruses emerged from Southeastern China, which has been proposed as the "epicentre" of influenza due to the unique human-animal interactions and ecology in this region. The research group here at the University of Hong Kong has been conducting surveillance on animal influenza viruses since the 1970s and has made important contributions in identifying the genetic origin of pandemic and zoonotic influenza viruses. This includes characterizing the evolution and origin of the influenza A(H5N1) virus which caused an outbreak in Hong Kong in 1997, determining the genetic origin of the 2009 pandemic influenza A(H1N1) virus from its swine influenza precursors, and more recently, identifying the genetic origin of the avian influenza A(H7N9) virus that has caused human infections in Eastern China since 2013. We are continuing to investigate how integrated analysis of the viral genetic information together with the viral functionality studies can allow recognition of critical molecular signatures and identification of field isolates with greater pandemic potential.

 

(2) Modes of influenza virus transmission and transmission dynamics

Human influenza viruses spread between people via respiratory secretions, and there continues to be major controversy over the importance of small particle "aerosols" in influenza transmission. We have contributed to the literature on aerosol transmission through a series of large community-based studies, primarily in households, and we are one of the few groups worldwide running such studies. We are also one of the few research groups carrying out experimental transmission of influenza in ferrets (the best animal model as surrogate for influenza transmission in humans) together with aero-biological studies on airborne particles and virus viability within particles of different sizes. We are continuing to collect data on contact patterns between and within different population subgroups such as age groups, schools and households. We will then use this information together with large-scale seroepidemiological studies to parameterize mathematical models of influenza transmission dynamics in the community, and infer the impact of control measures such as school closures or vaccination of school-age children.

 

(3) Influenza pathogenesis

Influenza infections in humans may lead to self-limited respiratory symptoms, pneumonia, acute respiratory distress, or death. Influenza pathogenesis is driven by multiple viral and host factors. To better approximate human response after influenza infection, we adopted different human primary and ex vivo cultures of to study viral tropism and innate immune responses. Host responses elicited after infection of influenza virus of different pathogenicity will be analyzed and compared using transcriptomic or proteomic analysis. To address the viral determinants critical for host adaptation and pathogenicity, we adopt the plasmid-based reverse genetics system to identify critical viral gene segments and amino acid residues that confer to the pathogenic phenotype. The long term goal is to understand the critical functionality associated with the molecular changes in virus genome; which will help to identify novel therapeutic options.

 

(4) Efficient public health interventions for the control of influenza

Because influenza virus infections generally cause mild and self-limiting disease, transmission largely occurs in the community, control of transmission to mitigate epidemics and pandemics is challenging. In recent years we have evaluated the effectiveness of a range of interventions used to control epidemics of human influenza, including randomized controlled trials and observational studies of influenza vaccination, antiviral treatment, hand hygiene and surgical face masks. We have published modeling studies on the effectiveness of school closures, the feasibility of convalescent plasma treatment, and the optimal distribution of influenza vaccines and other interventions. In 2013 the influenza A(H7N9) epidemic in China raised new concerns about the risk of human infections with avian influenza viruses, while highly pathogenic influenza A(H5N1) viruses have continued to circulate in the region since the first human cases were identified in Hong Kong in 1997. We have made major contributions to the evidence base on the epidemiology and control of avian influenza viruses.

 

Future perspectives

Our unique geographic location in the epicenter of influenza activity, and within a 5-hour flight of 50% of the global population, places us in a vital position for surveillance of, and response to, newly emergent and re-emergent viruses. Our integrated multidisciplinary research programme includes internationally recognized expertise, and has grown in recent years with support from a number of large infrastructure grants. In the coming years, we aim to broaden our perspective to respiratory viruses, informing control of these pathogens that are responsible for a major morbidity and mortality burden every year, and improving our capacity to respond to newly emerging and re-emerging diseases.

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