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Author

C W Leung

Bio: C W Leung is an academic researcher. The author has contributed to research in topics: Transmission and infection of H5N1 & Virus. The author has an hindex of 1, co-authored 1 publications receiving 783 citations.

Papers
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Journal ArticleDOI
TL;DR: Findings suggest that cytokine dysfunction contributes to the pathogenesis of H5N1 disease and development of vaccines against influenza A (H5N 1) virus should be made a priority.

809 citations


Cited by
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Journal ArticleDOI
TL;DR: This Article contains typographical errors in Table 2 where ‘Week 2 (N = 32)’ was incorrectly given as ‘week (n’=‬2’.
Abstract: Scientific Reports 5: Article number: 10942; published online: 01 June 2015; updated: 23 February 2016 This Article contains typographical errors in Table 2 where ‘Week 2 (N = 32)’ was incorrectly given as ‘Week (N = 2)’.

2,328 citations

Journal ArticleDOI
TL;DR: The concerted and coordinated response that contained SARS is a triumph for global public health and provides a new paradigm for the detection and control of future emerging infectious disease threats.
Abstract: The severe acute respiratory syndrome (SARS) is responsible for the first pandemic of the 21st century. Within months after its emergence in Guangdong Province in mainland China, it had affected more than 8000 patients and caused 774 deaths in 26 countries on five continents. It illustrated dramatically the potential of air travel and globalization for the dissemination of an emerging infectious disease and highlighted the need for a coordinated global response to contain such disease threats. We review the cause, epidemiology, and clinical features of the disease.

2,167 citations

Journal ArticleDOI
TL;DR: The observations indicate that high viral load, and the resulting intense inflammatory responses, are central to influenza H5N1 pathogenesis and the focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment.
Abstract: Avian influenza A (H5N1) viruses cause severe disease in humans, but the basis for their virulence remains unclear. In vitro and animal studies indicate that high and disseminated viral replication is important for disease pathogenesis. Laboratory experiments suggest that virus-induced cytokine dysregulation may contribute to disease severity. To assess the relevance of these findings for human disease, we performed virological and immunological studies in 18 individuals with H5N1 and 8 individuals infected with human influenza virus subtypes. Influenza H5N1 infection in humans is characterized by high pharyngeal virus loads and frequent detection of viral RNA in rectum and blood. Viral RNA in blood was present only in fatal H5N1 cases and was associated with higher pharyngeal viral loads. We observed low peripheral blood T-lymphocyte counts and high chemokine and cytokine levels in H5N1-infected individuals, particularly in those who died, and these correlated with pharyngeal viral loads. Genetic characterization of H5N1 viruses revealed mutations in the viral polymerase complex associated with mammalian adaptation and virulence. Our observations indicate that high viral load, and the resulting intense inflammatory responses, are central to influenza H5N1 pathogenesis. The focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment.

1,773 citations

Journal ArticleDOI
TL;DR: In this paper, the authors discuss the public health implications of the Spanish influenza pandemic of 1918-1919, which caused ≈50 million deaths worldwide and remains an ominous warning to public health.
Abstract: The “Spanish” influenza pandemic of 1918–1919, which caused ≈50 million deaths worldwide, remains an ominous warning to public health. Many questions about its origins, its unusual epidemiologic features, and the basis of its pathogenicity remain unanswered. The public health implications of the pandemic therefore remain in doubt even as we now grapple with the feared emergence of a pandemic caused by H5N1 or other virus. However, new information about the 1918 virus is emerging, for example, sequencing of the entire genome from archival autopsy tissues. But, the viral genome alone is unlikely to provide answers to some critical questions. Understanding the 1918 pandemic and its implications for future pandemics requires careful experimentation and in-depth historical analysis.

1,657 citations

Journal ArticleDOI
TL;DR: How high-throughput genomic methods are revealing the importance of the kinetics of cytokine gene expression and the remarkable degree of redundancy and overlap in cytokine signaling is highlighted.
Abstract: The cytokine storm has captured the attention of the public and the scientific community alike, and while the general notion of an excessive or uncontrolled release of proinflammatory cytokines is well known, the concept of a cytokine storm and the biological consequences of cytokine overproduction are not clearly defined. Cytokine storms are associated with a wide variety of infectious and noninfectious diseases. The term was popularized largely in the context of avian H5N1 influenza virus infection, bringing the term into popular media. In this review, we focus on the cytokine storm in the context of virus infection, and we highlight how high-throughput genomic methods are revealing the importance of the kinetics of cytokine gene expression and the remarkable degree of redundancy and overlap in cytokine signaling. We also address evidence for and against the role of the cytokine storm in the pathology of clinical and infectious disease and discuss why it has been so difficult to use knowledge of the cytokine storm and immunomodulatory therapies to improve the clinical outcomes for patients with severe acute infections.

1,501 citations