Computer virus may be amplified in embryonated chicken eggs or mammalian cell culture, and then subjected to further testing for identification. Viruses (ISIRV) and the Foundation for Innovative New Diagnostics (FIND). This marked the first time public and private sectors met at length to discuss this important issue. An open forum meeting style was adopted, and substantial time was allotted for discussion. Overall, the consultation addressed: ?? The state of the art for H5N1 diagnostics in humans. ?? Considerations and gaps related to H5N1 diagnostic?capacity. ?? Collaborative ways forward and Olesoxime the roles of WHO,?private industry and other stakeholders. Olesoxime This meeting summary will present the discussions and recommendations generally agreed by the consultation participants. Background Influenza diagnostics in humans (and animals) Diagnostic tests (to identify influenza virus in clinical material, containing cells and secretions and tissues) are based either on growth of virus in culture or by direct detection of virus antigen or RNA. Virus may be amplified in embryonated chicken eggs or mammalian cell culture, and then subjected to further testing for identification. Serological techniques [e.g. haemagglutination inhibition (HI) or microneutralization (MN)] may also be used to identify the presence of antibody in the serum of exposed individuals, providing indirect evidence of infection. These basic techniques can be used for diagnosing infections both in humans and in animals. In general, antigenic Olesoxime or molecular screening is used to first identify influenza virus type (A or B). Then the specific subtype is identified based on either serological reactivity of two viral surface glycoproteins, haemagglutinin (HA) and neuraminidase (NA), or on molecular characterization of the genes coding for these two proteins. There are 16 recognized HA and nine recognized NA subtypes of influenza A viruses. Wild waterfowl are considered the natural reservoir for influenza FEN-1 A viruses, and all HA and NA subtypes of influenza A have been identified in birds. Currently, only two influenza A subtypes (H1N1 and H3N2) are circulating or appearing in humans, causing recurring human seasonal influenza epidemics. H5N1 HPAI and new challenges Since the start of the current H5N1 HPAI epizootic in 2003, the virus has caused disease in poultry and wild birds in at least 59 countries in Asia, Africa, and Europe (http://www.oie.int). Although to date H5N1 remains an avian virus, it can cross the species barrier, and human infections with the avian H5N1 virus have now been confirmed in 12 countries. ? In addition to global concern about disease and deaths in humans, there is also concern that the virus will mutate into a form easily transmitted between humans, initiating a pandemic. The ongoing exposure of humans in countries experiencing disease in animals and ensuing global pandemic concern have highlighted some gaps and challenges in human influenza diagnostics. Appropriate clinical management, including timely treatment of human H5N1 cases ? , as well as plans for containing an emerging influenza pandemic, rely on the ability to rapidly and accurately diagnose the virus in humans. Ensuring that effective influenza diagnostic systems are in place globally could be extremely cost effective. For example, it has been shown that although laboratory diagnosis represents a small percentage of medical centre costs, it leverages 60C70% of all critical decisions, e.g. admission, discharge and drug therapy. 1 Diagnosis of H5N1 in humans is not yet Olesoxime achievable in the vast majority of diagnostic laboratories. One challenge to rapid and accurate diagnosis is the continual evolution of influenza viruses. 2 The eight RNA gene segments of influenza Olesoxime A viruses mutate at different rates. 3 Specifically, the HA and NA genes, on which diagnostics depend, have high mutation rates compared to the other genes. This rapid evolution in the H5N1 viruses isolated since 1997 has resulted in the emergence of genetically and antigenically distinct lineages (http://www.WHOweblink.org). The circulating H5N1 viruses can currently be grouped into many different clades with four clades including viruses that have infected humans in the following countries: 4 ?? Clade 1 Thailand, Vietnam, Cambodia, China ?? Clade 2.1 Indonesia ?? Clade 2.2 China, Iraq, Azerbaijan, Turkey, Egypt,????Nigeria, Djibouti ?? Clade 2.3 China, Laos, Vietnam A second major challenge to global diagnostic capability is the availability of healthcare infrastructure to rapidly diagnose H5N1 infection at the initial point of care (POC), as the virus is circulating in many regions that lack existing diagnostic capacity, even for seasonal influenza. In practice, diagnosis of viral infections is conducted in several.