WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus

Abstract

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.

What is the evidence for giving chemoprophylaxis to children or students attending the same preschool, school or college as a case of meningococcal disease?

“…Therefore, the European Centre for Disease Prevention and Control (ECDC) launched the development of guidance on the public health management of sporadic cases of meningococcal disease. This involved systematic literature reviews and the application of GRADE methodology [40][41][42][43] to grade the evidence and strength of recommendations [44]. In this paper, we present the results of a systematic literature search performed as part of this project to search for direct and indirect evidence on the effectiveness of chemoprophylaxis in educational settings.…”

A screening assay for neuraminidase inhibitors using neuraminidases N1 and N3 from a baculovirus expression system

“…Although the cumulative number of confirmed patients remains relatively small, the scientific community agrees in considering the emergence of a new highly pathogenic H5N1 influenza pandemic as a real concern [1][2][3] . So far, the only drugs approved to treat avian flu infected patients are the neuraminidase inhibitors Tamiflu (oseltamivir) and Zanamivir (relenza) 4 . These drugs target the enzyme neuraminidase that is responsible for allowing budding progeny virus to be released from the surface of infected cells by cleaving the terminal neuraminic acid residues from the glycan structures on the cell surface.…”

Human Infection with Highly Pathogenic Avian Influenza Virus (H5N1) in Northern Vietnam, 2004–2005

“…Therefore, this issue can only be addressed through observational studies. Despite limited empirical evidence, the World Health Organization (WHO) reported that oseltamivir improved survival (14) and recommended treatment with oseltamivir because of high mortality rates associated with infl uenza A virus (14,15). Patients from northern Vietnam are described in detail.…”