published_or_final_version / Clinical Psychology / Master / Master of Social Sciences

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Medicine / Master / Doctor of Medicine

Influenza epidemics have always been a constant public health threat to human populations. Recent societal developments and demographics changes have put us at increased risk of a widespread and potentially deadly influenza epidemic. Antiviral prophylaxis may provide an important epidemic intervention measure especially against influenza epidemic caused by novel influenza viruses where there will be no effective epidemic-specific vaccines available at the initial phase of the epidemic. Antiviral prophylaxis is listed as a fundamental component of the Hong Kong Preparedness Plan for Influenza Pandemics, however the rationale of such plan is not supported by public presentation of scientific evidence and no details of the actual antiviral prophylaxis plan are provided. With a majority of its stockpile set to expire in the very near future, we would like to know if antiviral prophylaxis is an effective intervention strategy against influenza epidemic and should antiviral stockpiling be continued. We identified relevant studies and reviewed the effectiveness of antiviral prophylaxis in preventing influenza infections at the individual, household and population level. We found that prophylactic treatment with Oseltamivir or Zanamivir are both effective in preventing influenza infections at the individual and household level. Both antivirals are well tolerated and neither is associated with major adverse events. Antiviral prophylaxis is effective in mitigating the public health impact of an influenza epidemic such as number of clinical influenza infections, hospitalization and deaths. However, antiviral prophylaxis alone may not be sufficient to contain or avert an influenza epidemic or delay the epidemic progress long enough for public health resources such as epidemic-specific vaccines to be acquired. In addition, the emergence of antiviral resistance and various logistics constraints will hamper the effectiveness of antiviral prophylaxis in containing influenza epidemics. We suggest the use of antiviral prophylaxis as the key intervention to mitigate influenza epidemics, however, with special considerations taken into hedging antiviral resistance and fulfilling the logistics requirements in order to make antiviral prophylaxis effective. In addition, we recommend public health authorities to take a multi-factorial approach in tackling highly transmissible influenza epidemics by incorporating other non-pharmaceutical interventions such as quarantine, school closures and boarder restrictions into the their antiviral prophylaxis-based containment plan. / published_or_final_version / Public Health / Master / Master of Public Health

Throughout history influenzas have consistently qualified as one of the top killers amongst common infectious diseases and it continues today to afflict millions in spite of our vast efforts to curb its effects. The World Health Organization (WHO) notes annual deaths of between 250,000 to 500,000 due to influenza. Alternative medicines have been traditionally used to treat this illness in the past, and have begun to experience an increase in popularity these days as a complementary supplement to improve treatment of influenza’s symptoms. The use of such natural extracts as Echinacea, ascorbic acid, and “Kan Jang” aim to mitigate symptoms and increase the efficiency of the healing process. Their use, however, has been scrutinized and somewhat controversial when looking at their effectiveness. Having such wide-spread use of these treatments, it is important to understand just how beneficial these alternative routes are when treating infectious diseases like influenza. The objective of this literature review is to assess the use of these traditional medicines in the treatment of influenza and influenza-like-illnesses (ILI). In order to do this, randomized controlled trials were studied to establish any benefits these medicines might provide in the treatment of symptoms and the prevention of influenza. Treatment groups with the three different alternative medicines were respectively compared to control groups without any treatment through singular symptoms and duration of these symptoms, as well as prevention of multiple infections. / published_or_final_version / Public Health / Master / Master of Public Health

The evolution and spread of influenza virus impose great impact on the society in the past century. Humans are still facing the zoonotic threat arising from animal influenza viruses; however, the existing knowledge is not sufficient to provide an accurate prediction of the next pandemic strain. My objective is to put forward the preparedness for influenza pandemics in two ways: molecular diagnosis and cross-protective vaccine. Influenza gene reassortment can take place during co-infection and produce novel viruses. While the pig is regarded as the potential mixing vessel for influenza viruses, it is important to develop rapid diagnostic assays to identify reassortment events in swine surveillance. In this study, rapid diagnostic assays were developed for genotyping pandemic H1N1/2009 and closely related swine influenza viruses. Eight real-time SYBR green-based reverse transcription-polymerase chain reactions (RT-PCR) containing locked nuclei acid (LNA) probes differentiated segments derived from pandemic H1N1/2009, Eurasian avian-like (EA), and triple reassortant (TR) swine virus lineages. With the help of these assays, 41 swine isolates collected during January 2009 to January 2010 in an ongoing swine surveillance programme in Hong Kong were successfully genotyped. Ten of these viruses were pandemic H1N1/2009 viruses, suggesting zoonotic transmissions of the virus from humans to pigs. A novel pandemic reassortant was also discovered during the course of surveillance. This study is the first to show pandemic H1N1/2009 virus has reassorted with other endemic swine viruses in the pig population. The genotyping assays provide a rapid and high throughput screening method to select viruses of interesting segment combination for downstream sequencing analysis and characterization. They will be useful for understanding viral reassortment and complex evolutionary dynamics in routine swine surveillance activities. Current influenza vaccines are strain-specific and the production schedule shows significant delay to reach the general population. The study aims at engineering a novel live attenuated virus vaccine which offers cross-subtypic protection. The feasibility for the conserved hemagglutinin (HA) stalk domain to induce broadly neutralizing antibodies was investigated. By manipulating the segment-specific packaging sequences, a nine-segment A/Puerto Rico/8/1934 (H1N1) (PR8) influenza virus carrying the headless HA of a different subtype (A/Hong Kong/1/1968 (H3N2)) (HK68) was generated by reverse genetics. The virus showed attenuated growth in in vitro cell culture and reduced pathogenicity in mice. Although mice vaccinated with this vaccine were better protected in the challenge of HK68 virus in comparison to unvaccinated mice, there is not enough evidence to verify cross-reactive immunity conferred by the HK68 headless HA immunogen, due to the heterosubtypic response induced by live virus administration. The absence of cross-neutralizing antibodies in immune sera may be explained by sub-optimal folding of the HK68 headless HA. Further studies are needed to modify the immunogen into its native conformation and elucidate the underlying vaccine-host interactions. These two studies have resulted in a useful diagnostic tool to increase influenza surveillance capacity at the swine-human interface, and the foundation for better universal vaccine design based on the conserved HA stalk domain. / published_or_final_version / Public Health / Master / Master of Philosophy

Background Large outbreaks of influenza are known to occur at correctional institutions such as prisons. Prisoners are particularly vulnerable due to a combination of environmental and socio-behavioural risk factors. Such outbreaks are also challenging to control because of the unique environmental constraints in these institutions. However, no local guidance is available for the prevention and control of influenza outbreaks in correctional institutions. This paper aims to review and synthesise relevant evidence on the topic so that practical recommendations can be offered to the local public health and correctional services. Methods A literature search was performed using PubMed, Google Scholar and Google to locate all relevant articles in English that examined the control of influenza outbreaks at correctional institutions up to May 2012. Findings Eleven studies describing 16 outbreaks of influenza or influenza-like illness at correctional institutions were included in the review. The studies included ten case reports and one case-control study from four countries. The majority of outbreaks took place at prisons. The number of cases in each outbreak ranged from three to over 500. Attack rates were highly variable between outbreaks, while case-fatality ratios were generally low. Control strategies used included social distancing measures, transmission-based precautions, active surveillance and testing, treatment, chemoprophylaxis and vaccination. Nine studies discussed the risk factors for spread and the challenges encountered in the control of the outbreaks. These included agent, host, socio-behavioural, environmental, staff and infrastructural factors. The limited expertise and capacity of correctional institutions in responding to influenza outbreaks should be acknowledged. Close communication and collaboration with public health agencies is called for. To better prepare these institutions to respond to pandemic influenza, a detailed, multidisciplinary response plan should be set up by the various government agencies involved. Conclusions Correctional institutions require the appropriate guidance and support from public health for the successful control of influenza outbreaks. These institutions should be recognised as serving a vital role in the community, and prisoners deserve the same standards of health care that are available to other members of society. / published_or_final_version / Public Health / Master / Master of Public Health

BACKGROUND Influenza is a potential threat to life, economies and security in our globalized world. However, it is still unclear how efficacious non-pharmaceutical interventions are in reducing the virus’ transmission and how the underlying mechanisms of its transmission modes work. Since 2008, numbers of randomized controlled trials (RCTs) regarding the efficacy of hand hygiene interventions in reducing influenza transmission have been published, yet no metaanalysis has ever been performed. Besides, a guinea pig model in 2009 showed that the efficiency of aerosol transmission is adjusted by the ambient temperature and humidity. Therefore, further evidence is needed to confirm the hypothesis. OBJECTIVES To evaluate the efficacy of hand hygiene interventions alone or combined with facemasks in reducing influenza transmission in the community and to investigate the possible roles of latitude, temperature and humidity in relation to the efficacy of the interventions in controlling the spread of influenza. SEARCH METHODS This meta-analysis followed the PRISMA statement. I searched the MEDLINE, PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Library databases. SELECTION CRITERIA I included all RCTs assessing the effect of hand hygiene interventions in preventing influenza spread in community settings with clear outcome definitions of laboratory confirmed influenza, clinically diagnosed influenza-like illness (ILI) and their related absenteeism. DATA COLLECTION AND ANALYSIS I ranked the methodological quality of each outcome with GRADEprofiler. I also assessed the heterogeneity across RCTs using I2 statistic and publication bias through visual inspection of Begg’s funnel plots and statistical assessment of regression and rank-correlation. I conducted the meta-analysis with random-effect models and further performed separate analyses for developed and developing countries data in case of a significant level of heterogeneity being noted across the studies. I also incorporated meta-regression to assess the association of latitude, temperature and humidity with the efficacy of hand hygiene interventions. RESULTS I identified 1,593 articles in the initial database search, excluded 1,535, included five from reference lists of review articles, retrieved full articles of 33 and included ten for analysis. The quality of evidence of both laboratory confirmed influenza and ILI were high while that of absenteeism was low. The combination of hand hygiene interventions and facemasks contributed to a significant 45% reduced risk of influenza-related absenteeism in the combined country data while it contributed a significant 23% to a reduced risk of both laboratory confirmed influenza and ILI in developed countries subgroup analysis. The metaregression revealed that the efficacy of the combination of hand hygiene interventions with facemasks increased in a less humid environment. CONCLUSIONS The combination of hand hygiene interventions with facemasks is an effective low-cost intervention to prevent influenza. Further studies to assess the association between humidity and mode of influenza transmission are critically important to support the international guideline on hand hygiene interventions and facemask use. / published_or_final_version / Public Health / Master / Master of Public Health

Influenza vaccination is the best preventive measure against influenza virus infection, and antivirals including oseltamivir are effective treatments. From a public health point of view, it is important to evaluate whether vaccination and antiviral treatment reduces transmission of the virus. I analyzed data from a community-based study of influenza virus transmission in households, and identified effectiveness of antiviral treatment in reducing duration of illness and some evidence that treatment reduced transmission to household contacts. I also analyzed data from a community-based placebo-controlled trial of influenza vaccination and confirmed efficacy of vaccination against seasonal influenza but differential efficacy against pandemic influenza possibly because of timing and mediation of seasonal influenza epidemics. In further analyses I found that antibody titers of 1:40 correlated with 50% protection against infection, and repeated vaccination with the same strains tended to be associated with reduced responses to those strains although there was no evidence of reduced efficacy. In the study, one child in each household was randomly allocated to receive vaccine or placebo and I did not identify any evidence of indirect benefits to the household members of vaccinated children. I reviewed vaccine target groups in different countries, and noted that some countries now include school-age children in their target groups based mainly on the principle of herd immunity. My findings did not support the inclusion of school-age children as a target group for vaccination in Hong Kong. Further studies should examine the indirect as well as direct benefits of vaccination in different settings in order to guide optimal influenza vaccination policies. / published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy

Background: Avian influenza is a serious infectious disease attracting great concerns of the world. It not only results in a huge economic loss but also poses a great threat to public health, and poultry production plays a major role of transmission as well as a locus of pathogen evolution, mutation and adaptation of avian influenza virus between wild birds and humans. Therefore, biosecurity measures along the poultry supply chains are important to prevent and control avian influenza. My objective was to summarize the past and present various measures against avian influenza in the industrial, commercial and backyard poultry production systems. Methods: A literature search was performed by PubMed, HKU Scholar Hub and Google. Based on the inclusion criterion and exclusion criterion, the relevant articles were selected with full text in English up to 11st, July 2013. Results: A total of 18 articles were found among the 474 potentially relevant articles. Among these articles, 17articlescame from PubMed and 1 article came from HKU Scholar Hub; 2 articles were closely related to industrial poultry production, 9 articles were closely related to commercial poultry production, 3 articles were closely related to village, rural or backyard poultry production and the rest 4 articles mixed the biosecurity measures in the different poultry production systems. These articles covered various biosecurity measures such as surveillance and monitoring, segregation, cleaning and disinfection, vaccination, training for workers, stamping out, controlling markets and poultry management in the developing and developed countries. Discussion: The common control measures are discussed and the biosecurity is aneffective way to prevent the avian influenza outbreaks in poultry and then to protect the health of all people. However, there were still limitations when implementing biosecurity. Due to local social, cultural, economic, psychological and political factors, it is difficult to prevent and control the avian influenza outbreaks in the poultry supply chains only by one single measure or individual. Therefore, some recommendations referring to cooperation of public and private sectors, comprehensiveness and specifity of measures, improving risk perception and education were discussed. / published_or_final_version / Public Health / Master / Master of Public Health