Overview of Hemorrhagic Enteritis/Marble Spleen Disease in Poultry
Hemorrhagic enteritis is an acute GI disorder affecting young turkeys ≥4 wk old. In its most severe form, it is characterized by depression and hemorrhagic droppings. Mortality may be increased; however, this is rare because of extensive use of vaccines. Marble spleen disease is an acute respiratory disease of pheasants characterized by depression, enlarged mottled spleens, pulmonary congestion, and death. Both diseases are caused by similar viruses. Species-specific differences in clinical response are thought to be related to differences in the target organs for anaphylaxis and variation in viral pathotype. Infection with less virulent pathotypes in either host often may go undetected until secondary bacterial infections begin to develop as a result of viral-induced immunosuppression.
Similar diseases have been seen sporadically in other species of birds such as chickens (splenomegaly), guinea fowl, peafowl, and chukar partridges.
The etiologic agent is a nonenveloped, icosahedral DNA virus, 70–90 nm in diameter. It is a member of the family Adenoviridae and the genus Siadenovirus. Based on differences in presentation within host species, numerous viral pathotypes appear to exist. These differ slightly at the DNA level but are indistinguishable serologically.
Both hemorrhagic enteritis and marble spleen disease are geographically widespread and considered endemic in areas where turkeys and pheasants are raised commercially. The usual route of infection is oral, and virus is often introduced onto previously uninfected premises via personnel or equipment contaminated with infectious feces. Turkey poults and pheasants 3–4 wk old are resistant to infection because of age-related resistance or, more commonly, the presence of maternal antibody. The virus may survive under moist conditions (ie, in litter) well beyond the refractory period. As infection begins to cycle through a flock, large quantities of virus are shed in the feces, which facilitates rapid spread through susceptible birds. Morbidity usually approaches 100% for both hemorrhagic enteritis and marble spleen disease.
In commercial operations, hemorrhagic enteritis typically affects turkeys 6–12 wk old but is most common between 7–9 wk of age. In outbreaks involving highly virulent pathotypes, clinical signs can include depression, pallor, and bloody droppings. Acute mortality can range from 1%–60%, with an average of 10%–15% throughout a 2-wk period. Birds that survive the acute phase experience a transient immunosuppression related to the lymphotrophic, lymphocytopathic nature of the virus. This often manifests itself in the form of secondary bacterial infections, eg, colibacillosis (see Colibacillosis) ~10–14 days after exposure to the virus. Thus, a second peak in mortality, potentially overlapping the first, may be seen and, in less virulent outbreaks, may actually dominate the clinical picture. The second wave of mortality often lasts 2–4 wk and is characterized by lesions commonly associated with bacterial respiratory disease or septicemia, eg, fibrinopurulent pneumonia, airsacculitis, pericarditis, peritonitis, perihepatitis, hepatomegaly, and splenomegaly. Concomitant or prior exposure to necrotic enteritis (see Necrotic Enteritis), coccidiosis (see Coccidiosis), Newcastle disease virus (see Newcastle Disease in Poultry), Bordetella avium (see Bordetellosis), or Mycoplasma gallisepticum and M synoviae (see Mycoplasmosis) can exacerbate the problem. Similar multiple agent interactions have been implicated in mortality associated with the use of vaccines for hemorrhagic enteritis.
Marble spleen disease typically affects pheasants 3–8 mo old. Onset is acute, with dyspnea, asphyxiation, and sudden death occurring as a result of pulmonary congestion and edema. Mortality is commonly 2%–3% but can reach 15%. Secondary bacterial infections as a result of immunosuppression have also been noted.
Necropsy of moribund or dead birds infected with hemorrhagic enteritis virus reveals gross congestion and occasional intraluminal hemorrhage in the proximal small intestine. The spleen is usually enlarged, friable, and mottled white, except in birds that have hemorrhaged extensively. Hemorrhage in the intestine is not common in field cases. Histopathologic changes in the duodenum include congestion, hemorrhage, and necrosis of the intestinal epithelium. This lesion in particular is thought to be the result of a virally induced, cytokine-mediated anaphylactic reaction, with the GI tract being considered the target shock organ in turkeys. Basophilic intranuclear inclusions can be found in lymphocytes and macrophages in a variety of tissues (eg, intestine, liver, and lungs) but predominantly in the spleen, where lymphoreticular hyperplasia and lymphoid necrosis are noted. Intranuclear inclusions in the renal tubular epithelial cells of the kidneys can be seen in turkeys that have recovered from hemorrhagic enteritis.
On histopathologic evaluation of pheasants with marble spleen disease, flooding of the atria and tertiary bronchi with fibrin and RBCs, as well as generalized vascular congestion and focal necrosis, are often seen in the lung. As with hemorrhagic enteritis, this response may be anaphylactic in nature, with the lung being considered the target shock organ in the pheasant. Splenomegaly with lymphoreticular hyperplasia and lymphoid necrosis also occur and are the characteristic lesions for which marble spleen disease is named. Basophilic or magenta-colored intranuclear inclusions may be found in a variety of tissues excluding the GI tract, with the highest concentration of virus found in the spleen.
Diagnosis of virulent outbreaks of hemorrhagic enteritis or marble spleen disease can often be made based on clinical signs and gross lesions. Confirmation is by histopathology and the presence of seroprecipitating virus in the spleen as determined by agar gel immunodiffusion. PCR techniques to detect hemorrhagic enteritis viral DNA in tissue have also been described and are in regular use in select laboratories. To determine whether hemorrhagic enteritis or marble spleen disease is a predisposing factor in cases of bacterial respiratory disease or septicemia, or to verify a primary diagnosis, acute and convalescent sera (3 wk apart) can be tested using either agar gel immunodiffusion or ELISA. In turkeys, differential diagnoses include colibacillosis, pasteurellosis, paratyphoid, and erysipelas. Reticuloendotheliosis or lymphoproliferative disease should be considered when lymphoreticular hyperplasia is the predominant lesion. GI lesions without splenic involvement should evoke consideration of other viral, bacterial, parasitic, and toxic enteritides of turkeys. In pheasants with acute respiratory disease, differential diagnoses include Newcastle disease, avian influenza, and in the case of birds reared in confinement, gaseous toxins.
Virulent outbreaks of hemorrhagic enteritis have been successfully treated and controlled by SC injection of exposed birds with 0.5–1 mL of antiserum obtained from recovered flocks. It is presumed that a similar approach may be effective for pheasants. In anticipation of secondary bacterial complications, antibiotics may be used, but if possible, an informed choice should be made based on current antibiotic susceptibility profiles for locally obtained Escherichia coli isolates. In addition to good biosecurity, prevention hinges on the use of vaccines administered in the water at ~4–5 wk of age. Commercially available tissue culture products and crude splenic preparations containing avirulent isolates produce lifelong protection. Quality control on crude splenic preparations, such as examining them for bacteria, Mycoplasma, and other viruses, should be done before they are prepared. A subunit vaccine to prevent hemorrhagic enteritis in turkeys has been described in Europe.
Vaccines intended for use in turkeys should not be used in pheasants, and vice versa, because the avirulent isolates used for vaccinating one species are typically virulent in the other. Because of the potential for interaction with other agents, including live vaccines, regular disease monitoring and careful integration of hemorrhagic enteritis and marble spleen disease vaccines into flock vaccination protocols is encouraged. Intuitively, vaccines should not be administered to birds exhibiting signs of illness or within 2 wk of any other vaccination.