The symptoms following infection with low pathogenic AIV may be as discrete as rufßed feathers, transient reductions in egg production or weight loss combined with a slight respiratory disease (Capua and Mutinelli 2001). Some LP strains such as certain Asian H9N2 lineages, adapted to efÞcient replication in poultry, may cause more prominent signs and also significant mortality (Bano 2003, Li 2005). In its highly pathogenic form, the illness in chickens and turkeys is characterised by a sudden onset of severe symptoms and a mortality that can approach 100 % within 48 hours (Swayne and Suarez 2000). Spread within an affected ßock depends on the form of rearing: in herds which are litter-reared and where direct contact and mixing of animals is possible, spread of the infection is faster than in caged holdings but would still require several days for complete contagion (Capua 2000). Often, only a section of a stable is affected. Many birds die without premonitory signs so that sometimes poisoning is suspected in the beginning (Nakatami 2005). It is worth noting, that a particular HPAI virus isolate may provoke severe disease in one avian species but not in another: in live poultry markets in Hong Kong prior to a complete depopulation in 1997, 20 % of the chickens but only 2.5 % of ducks and geese harboured H5N1 HPAIV while all other galliforme, passerine and psittacine species tested virus-negative and only the chickens actually showed clinical disease (Shortridge 1998). In industrialised poultry holdings, a sharp rise followed by a progressive decline in water and food consumption can signal the presence of a systemic disease in a ßock. In laying ßocks, a cessation of egg production is apparent. Individual birds affected by HPAI often reveal little more than severe apathy and immobility (Kwon 2005). Oedema, visible at feather-free parts of the head, cyanosis of comb, wattles and legs, greenish diarrhoea and laboured breathing may be inconsistently present. In layers, soft-shelled eggs are seen initially, but any laying activities cease rapidly with progression of the disease (Elbers 2005). Nervous symptoms including tremor, unusual postures (torticollis), and problems with co-ordination (ataxia) dominate the picture in less vulnerable species such as ducks, geese, and ratites (Kwon 2005). During an outbreak of HPAI in Saxonia, Germany, in 1979, geese compulsively swimming in narrow circles on a pond were among the Þrst conspicuous signs leading to a preliminary suspicion of HPAI. The clinical presentation of avian influenza infection in humans is discussed in detail in the chapter entitled .Clinical Presentation of Human Influenza.. Pathology: LPAI: Lesions vary with the viral strain and the species and age of the host. In general, only turkeys and chickens reveal any gross and microscopic alterations especially with strains adapted to these hosts (Capua and Mutinelli 2001). In turkeys, sinusitis, tracheitis and airsacculitis have been detected, although secondary bacterial infections may have contributed as well. Pancreatitis in turkeys has been described. In chickens, mild involvement of the respiratory tract is most commonly seen. In addition, lesions concentrate on the reproductive organs of layers (ovaries, oviduct, yolk peritonitis). 58 Avian Influenza HPAI: Gross pathological and histopathological alterations of HPAI reveal similar dependencies to those listed for the clinical presentation. Four classes of pathological alterations have been tentatively postulated (Perkins and Swayne 2003): (i) Peracute (death within 24.36 hours post infection, mainly seen in some galliforme species) and acute forms of disease reveal no characteristic gross pathological alterations: a discrete hydropericardium, mild intestinal congestion and occasionally petechial bleedings of the mesenterical and pericardial serosa have been inconsistently described (Mutinelli 2003a, Jones and Swayne 2004). Chickens infected with the Asian lineage H5N1 sometimes reveal haemorrhagic patches and significant amounts of mucus in the trachea (Elbers 2004). Serous exudates in body cavities and pulmonary oedema may be seen as well. Pinpoint bleedings in the mucosa of the proventriculus, which were often described in text books in the past, have only exceptionally been encountered in poultry infected with the Asian lineage H5N1 (Elbers 2004). Various histological lesions together with the viral antigen can be detected throughout different organs (Mo 1997). The virus is Þrst seen in endothelial cells. Later on virus-infected cells are detected in the myocardium, adrenal glands and pancreas. Neurons as well as the glial cells of the brain also become infected. Pathogenetically, a course similar to other endotheliotropic viruses may be assumed, where endothelial and leukocyte activation leads to a systemic and uncoordinated cytokine release predisposing to cardiopulmonary or multi-organ failure (Feldmann 2000, Klenk 2005). (ii) In animals which show a protracted onset of symptoms and a prolonged course of disease, neurological symptoms and, histologically, non-suppurative brain lesions predominate the picture (Perkins and Swayne 2002a, Kwon 2005). However, virus can also be isolated from other organs. This course has been described in geese, ducks, emus and other species experimentally infected with an Asian lineage HPAI H5N1 strain. In laying birds, inßammation of the ovaries and oviducts, and, after follicle rupture, so-called yolk peritonitis, can be seen. (iii) In ducks, gulls and house sparrows, only restricted viral replication was found. These birds showed mild interstitial pneumonia, airsacculitis and occasionally lymphocytic and histiocytic myocarditis (Perkins and Swayne 2002a, 2003). (iv) In the experiments described by Perkins and Swayne (2003), pigeons and starlings proved to be resistant against H5N1 infection. However, Werner et al. (to be published) were able to induce protracted neurological disease, due to nonsuppurative encephalitis (Klopßeisch 2006), in 5/16 pigeons using a recent Indonesian HPAI H5N1 isolate. Differential Diagnosis: The following diseases must be considered in the differential diagnosis of HPAI because of their ability to cause a sudden onset of disease accompanied by high mortality or haemostasis in wattles and combs: Laboratory Diagnosis 59 a) velogenic Newcastle disease b) infectious laryngotracheitis (chickens) c) duck plague d) acute poisonings e) acute fowl cholera (Pasteurellosis) and other septicaemic diseases f) bacterial cellulitis of the comb and wattles Less severe forms of HPAI can be clinically even more confusing. Rapid laboratory