Background Avian influenza A (H5N1) has been circulating around and remains to be one of the major threats to human beings since it first emerged in 1997. Besides vaccines, currently there are two major countermeasures to infection in clinical settings, which are antiviral therapies and immunomodulator treatments. Objectives To summarize evidence on the effectiveness of current treatments against H5N1 infection and to explore the potential benefits of several immunomodulatory agents. Design Systematic review of cross-sectional studies and case series. Data sources Searches of PubMed for articles using the search term “(H5N1[Title]) AND antiviral[Title/Abstract]” and also manual search on PubMed for studies that are cited in some review papers in the first automatic search. Previous search results relating to human H5N1 infection studies are also included. Study selection Included studies that were human H5N1 infection cross-sectional studies or case series in which clinical outcomes were reported, CFR and survival rate were specified or could be easily derived from original data. Results 11 articles met the selection criteria and were included in our analysis. Sample size of the included studies ranged from 8 to 308 lab confirmed cases with median age varied from 10 to 29. Leukopenia, lymphopenia, thrombocytopenia and elevated ALT and AST at admission were strongly associated with worse clinical outcomes with different significance across studies. Oseltmivir treatment was generally initiated earlier among those who survived. Survival benefit of oseltamivir was the most significant if the patient received the treatment within the first two days after symptom onset, and it is still significantly effective when treatment was given up to eight days after symptom onset according to one study we included. Corticosteroid didnot show any beneficial effect or it is associated with a higher risk of death when it is given according to the current treatment protocol and a delayed initiation time. Conclusion Oseltamivir treatment is associated with survival benefit especially when initiated within the first two days after symptom onset, while immunomodulator therapies haven’t shown such benefit so far in clinical setting but some experiments in vitro and in vivo support their use in a manner which is different from the current protocol. / published_or_final_version / Public Health / Master / Master of Public Health

I established the phage antibody library platform for the identification of specific antibodies. In the first part of my study, I tried to identify antibody against SARS-CoV. Two fragments on the spike protein, which is responsible for inducing viral entry, was chosen as target for the selection of antibody. An antibody was identified which can selectively recognize the SARS-CoV infected cells, but not non-infected cells. Although this antibody was found to retain no neutralizing ability, this specific antibody may have potential to develop for diagnostic purpose. / I utilized the phage system-based cloning method as an attractive approach to screen and identify virus-specific antibodies that can be encoded by the human genome. Once a useful phage clone is identified, unlimited amounts of human monoclonal virus-specific antibodies can be manufactured, and potentially applied clinically for prophylactic and therapeutic uses. The study focuses on two of these new infections, both of which cause severe respiratory disease: SARS and avian influenza. / Identification of specific antibodies, either for diagnostic or therapeutic use, was successfully demonstrated in the two infectious disease models. The phage antibody platform offers a fast and cost-effective method to identify phage antibodies, which can easily be converted to human viral specific monoclonal antibodies for clinical use. / In the 21st century, a number of novel infectious diseases emerged suddenly and spread rapidly, endangering the lives and well-being of people around the world. Severe acute respiratory syndrome (SARS) is a life threatening form of atypical pneumonia that ravaged Hong Kong, Taiwan, China, Canada and many cities in 2003. In the same year, novel avian influenza viruses infected human beings on two continents. Both of these diseases originated in animals and crossed over into the human population. These emerging diseases pose significant public health threats while providing a chilling reminder that another influenza pandemic could occur at any time. Thus, the development of effective therapeutics to control the disease is of paramount importance. Although several vaccines against SARS and avian influenza are available nowadays, the poor clinical performance and frequent mutation of viral strains may limit the practical use and value of the vaccines. Moreover, there are no promising antiviral drugs available for the treatment. Therefore, I aimed to develop an immunotherapy as an alternative treatment option against these diseases. / In the second part of my study, the extracellular domain of matrix protein of avian influenza virus was chosen as target for the selection of antibody. I successfully identified an antibody which can neutralize the avian influenza virus infection. This promising result indicated this antibody has potential to develop for therapeutic use and these antibodies can be easily manufactured in unlimited amounts for clinical application. / Leung, Ka Man. / Adviser: Kwok Pui Fung. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0212. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 112-123). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.