Links to articles on clinical and pharmacological management of Influenza A (H5N1) [2004-2010]

WHO, February 20, 2004

WHO interim guidelines on clinical management of humans infected by influenza A (H5N1).
These guidelines are based on current knowledge of human influenza A(H5N1) infections deriving from experience during the 1997 outbreak in Hong Kong Special Administrative Region of China (Hong Kong SAR) 1, 2 and from preliminary reports of recent cases in Thailand and Viet Nam (see Annex 1, Summary of preliminary clinical features of humans infected by influenza A(H5N1)). As more case data become available, these guidelines will be modified as appropriate. . . .
WHO, May 2006

WHO Rapid Advice Guidelines on pharmacological management of humans infected with avian influenza A (H5N1) virus
Human cases of avian influenza A(H5N1) infection have remained rare and sporadic, but the disease is very severe and the case fatality is high. With the H5N1 virus now confirmed in birds in more than 50 countries, additional sporadic human cases should be anticipated. Using innovative guideline development methods based on the best available evidence, the WHO assembled an international panel of experts in March 2006 to develop rapid advice for the pharmacological management of patients with H5N1 infection. The recommendations are classified as strong or weak and cover several specific patient and exposure groups for the treatment and chemoprophylaxis of H5N1 virus infection. All recommendations are specific to the current pre-pandemic situation and are based on careful consideration of the current evidence about benefits, harms, burdens and cost of interventions. As there are currently no clinical trials in patients with avian influenza H5N1 disease, the overall quality of evidence on which to base judgments is very low. . . .

full text:
WHO January 2007 (Lancet)

WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus
Holger J Schünemann, Suzanne R Hill, Meetali Kakad, Richard Bellamy, Timothy M Uyeki, Frederick G Hayden, Yazdan Yazdanpanah, John Beigel, Tawee Chotpitayasunondh, Chris Del Mar, Jeremy Farrar, Tran Tinh Hien, Bülent Özbay, Norio Sugaya, Keiji Fukuda, Nikki Shindo, Lauren Stockman, Gunn E Vist, Alice Croisier, Azim Nagjdaliyev, Cathy Roth, Gail Thomson, Howard Zucker, Andrew D Oxman, for the WHO Rapid Advice Guideline Panel on Avian Influenza
Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has increased the threat of human infections with H5N1 virus worldwide. Despite international agreement to stockpile antivirals, evidence-based guidelines for their use do not exist. WHO assembled an international multidisciplinary panel to develop rapid advice for the pharmacological management of human H5N1 virus infection in the current pandemic alert period. A transparent methodological guideline process on the basis of the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to develop evidence-based guidelines. Our development of specific recommendations for treatment and chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms, burden, and cost of interventions in several patient and exposure groups. Overall, the quality of the underlying evidence for all recommendations was rated as very low because it was based on small case series of H5N1 patients, on extrapolation from preclinical studies, and high quality studies of seasonal influenza. A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease. Similarly, strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations. Emergence of other novel influenza A viral subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus strains, will require an update of these guidelines and WHO will be monitoring this closely. . . .
WHO August 15, 2007

Clinical management of human infection with avian influenza A (H5N1) virus
Updated advice 15 August 2007
Since late 2003 the widespread occurrence across several continents of infection among poultry and birds with the highly pathogenic avian influenza A(H5N1) virus has increased the risk of human exposure to the virus and resulted in growing numbers of A(H5N1) virus-infected persons (1). In June 2006 WHO published recommendations on the pharmacological management of A(H5N1) virus infections (2, 3). The current document reviews both commonly used pharmacological and supportive treatment modalities and provides advice on case management based on current knowledge of human influenza A(H5N1) virus infections. This guidance is based on information collected from publications as well as reports on A(H5N1) cases in affected countries that were presented at the first WHO Consultation on Human H5N1 Infections, Hanoi, Viet Nam, May 2005 (4) and at the Second WHO Consultation on clinical aspects of human infection with avian influenza (H5N1) virus in Antalya, Turkey, March 2007 (5).
This document replaces the WHO interim guidelines on clinical management of humans infected by influenza A(H5N1) published in 2004 and serves as a supplement to the WHO pharmacological management guidelines (2 , 3). . . .
WHO, January 17, 2008

Update on Avian Influenza A (H5N1) Virus Infection in Humans
Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus, N Engl J Med 2008; 358:261-273 January 17, 2008
(see also - link)
The unprecedented epizootic of avian influenza A (H5N1) viruses among birds continues to cause human disease with high mortality and to pose the threat of a pandemic. This review updates a 2005 report1 and incorporates information recently published or presented at the Second World Health Organization (WHO) Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus. . . .
CDC, 2009

Human Infection with Highly Pathogenic Avian Influenza A (H5N1) Virus: Review of Clinical Issues
Timothy M. Uyeki
Epidemiology and Prevention Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control, Prevention, Atlanta, Georgia
This article provides an updated review of the clinical issues related to human infection with highly pathogenic avian influenza A (H5N1) virus. The clinical data available to date are presented, as well as recent findings on the pathogenesis of and antiviral treatment and immunotherapy for H5N1 virus infection in humans and animal models. . . .
J Infect Dis., 2010

Effectiveness of Antiviral Treatment in Human Influenza A(H5N1) Infections: Analysis of a Global Patient Registry
Wiku Adisasmito, Paul K. S Chan, Nelson Lee, Ahmet Faik Oner, Viktor Gasimov, Faik Aghayev, Mukhtiar Zaman Ebun Bamgboye, Nazim Dogan, Richard Coker, Kathryn Starzyk, Nancy A. Dreyer, and Stephen Toovey

Background. Influenza A (H5N1) continues to cause infections and possesses pandemic potential. Methods. Data sources were primarily clinical records, published case series, and governmental agency reports. Cox proportional hazards regression was used to estimate the effect of treatment on survival, with adjustment using propensity scores (a composite measure of baseline variables predicting use of treatment).
Results. In total, 308 cases were identified from 12 countries: 41 from Azerbaijan, Hong Kong SAR, Nigeria, Pakistan, and Turkey (from clinical records); 175 from Egypt and Indonesia (from various sources); and 92 from Bangladesh, Cambodia, China, Thailand, and Vietnam (from various publications). Overall crude survival was 43.5%; 60% of patients who received ⩾1 dose of oseltamivir alone (OS+) survived versus 24% of patients who had no evidence of anti-influenza antiviral treatment (OS−) ( P < .001). Survival rates of OS+ groups were significantly higher than those of OS− groups; benefit persisted with oseltamivir treatment initiation ⩽6–8 days after symptom onset. Multivariate modeling showed 49% mortality reduction from oseltamivir treatment.
Conclusions. H5N1 causes high mortality, especially when untreated. Oseltamivir significantly reducesmortality when started up to 6–8 days after symptom onset and appears to benefit all age groups. Prompt diagnosis and early therapeutic intervention should be considered for H5N1 disease. . . .
Full article: nglish-US%2FJID_H5N1.pdf&rct=j&q=Effectiveness%20of%20ant iviral%20treatment%20in%20human%20influenza%20A(H5 N1)%20infections%3A%20analysis%20of%20a%20Global%2 0Patient%20Registry&ei=dDQVTsCXG6GvsQKkrLkp&usg=AF QjCNHe-PhCEP-IYwHmLcK81jPj373T3A&cad=rja