Chicken anemia virus (CAV) has a worldwide distribution. Infection of young chickens causes anemia, decreased weight gain, transient immunosuppression, and increased mortality rate. Infection of chickens older than 3 or 4 weeks usually does not cause clinical signs. However, it can cause immunosuppression, resulting in secondary infections, and it can result in economic losses even when no disease is evident. Diagnosis in live birds is based on decreased hematocrit and detection of CAV nucleic acids in blood lymphocytes by PCR assay. Postmortem diagnosis is based on thymic atrophy, lymphoblast depletion of the thymic cortex, pale bone marrow, and detection of CAV DNA or antigens in tissues. There is no specific treatment, and the disease is controlled through vaccination or natural exposure of breeders.
Etiology and Pathogenesis of Chicken Anemia Virus Infection
Chicken anemia virus (CAV) is a 25-nm-diameter, nonenveloped, icosahedral virus with a 2.3-kb single-stranded, negative-sense, circular DNA genome.
CAV belongs to the genus Gyrovirus of the family Anelloviridae together with 8 other species, including 2 viruses isolated from chickens (Gyrovirus galga 1 and Gyrovirus galga 2). CAV isolates have been grouped into 5 genotypes, but thus far all isolates belong to one serotype.
When day-old susceptible chicks are inoculated intramuscularly with CAV, viremia occurs within 24 hours. Virus can be recovered from most organs and rectal contents up to 35 days after inoculation.
The principal sites of CAV replication are hemocytoblasts in the bone marrow, precursor T cells in the cortex of the thymus, and dividing CD4 and CD8 T cells in the spleen and other organs. Replication in and destruction of the hemocytoblasts decreases the precursor populations for RBCs, thrombocytes, and heterophils, causing anemia, hemorrhages, and increased susceptibility to bacterial infections. Replication in and destruction of dividing T cells causes immunosuppression.
Virus-neutralizing (VN) antibodies are detectable 21 days after infection, and clinical, hematologic, and pathological parameters return to normal approximately 35 days after infection. However, virus or viral DNA can remain in the gonads in the presence of VN antibodies, suggesting that CAV can establish a latent infection. CAV can be reactivated when hens become sexually mature through the activation of an estrogen-responsive promoter region in the viral genome.
Chicken anemia virus infection can cause a marked decrease in the generation of antigen-specific cytotoxic T cells and helper T cells directed against other pathogens. Because of decreased helper T cells, antibody production can decrease after vaccination against other pathogens. In addition to T-cell defects, macrophage functions such as Fc-receptor expression, phagocytosis, and antimicrobial activity may be impaired. CAV infection also has adverse effects on proliferative responses of spleen lymphocytes and on the production of IL-2 and interferons by splenocytes.
Subclinical horizontally acquired infection with CAV in broiler progeny of seropositive parent flocks may be associated with impaired economic performance. In addition, subclinical infection of chickens older than 4 weeks, after maternal antibody has waned, can cause immunosuppression resulting in secondary infections and result in economic losses even in the absence of evidence of any disease.
Syndromes involving CAV infection along with other pathogens include hemorrhagic aplastic anemia syndrome, gangrenous dermatitis, inclusion body hepatitis (IBH), and IBH and hydropericardium syndrome.
Epidemiology and Transmission of Chicken Anemia Virus Infection
Horizontal transmission of chicken anemia virus infection is by the fecal-oral route, through infected feather follicle epithelium, and perhaps by the respiratory route. Contaminated litter is a common source of introduction.
Vertical transmission occurs when seronegative hens become infected and continues until adequate levels of VN antibodies develop in the hens. Chicks hatched from these eggs are viremic, and CAV can rapidly spread horizontally from the chicks to susceptible maternal antibody–negative hatchmates. Roosters shedding CAV in semen are another source of vertical transmission.
Vaccination of seronegative flocks before the onset of egg production is recommended to prevent vertical transmission.
Many SPF flocks develop antibodies against CAV during or after the onset of sexual development, most likely as a consequence of activation of latent virus by estrogen, which may result in the production of CAV-positive embryos. As a consequence, cell culture- or embryo-derived vaccines may be contaminated with CAV and become a source of infection.
Maternal antibody–negative chicks are susceptible to infection and disease until they are 1–2 weeks old. In contrast, maternal antibody–positive chicks are protected from disease and probably from infection. Age resistance to clinical disease, but not infection, begins at approximately 1 week old and is closely associated with the ability of chickens to generate VN antibodies after infection. The age resistance can be overcome by coinfection with viruses causing immunosuppression such as infectious bursal disease virus (IBDV), Marek's disease virus, and reticuloendotheliosis virus.
Live, attenuated vaccines against IBDV can be categorized by attenuation level as mild, intermediate, or intermediate-plus (or "hot"), with each subsequent category also resulting in increasing levels of immunosuppression. Hot IBDV vaccine strains can cause enough immunosuppression to negatively affect age resistance to CAV.
Chicken anemia virus poses no known zoonotic risk to humans.
Clinical Signs of Chicken Anemia Virus Infection
Clinical signs of illness or adverse effects on egg production from chicken anemia virus infection do not occur when seronegative adult chickens become infected. However, vertical transmission or infection of maternal antibody–negative chicks < 1 week old can cause clinical disease 12–17 days after hatching or infection. In this young population, high mortality rates (generally 10%-20% but up to 60%) are caused by anemia or secondary infections.
Clinical signs include the following:
paleness as a consequence of anemia (PCV < 27%)
anorexia
lethargy
listlessness
hemorrhages in the skin often combined with bacterial skin infections (see blue wing disease image)
decreased weight gain
Gross Lesions
Organs are pale; the thymus is generally atrophied, and the cloacal bursa (bursa of Fabricius) may be small. Bone marrow is pale or yellow. Hemorrhages may be present in or under the skin and in muscle and other organs. Lesions associated with secondary infections may also be present.
Gangrenous dermatitis of the skin (known as "blue wing") under the wings of a bird infected by chicken anemia virus.
Courtesy of Dr. Mohamed M. El-Gazzar.
A. Thymus from a 14-day-old broiler chicken suspected of infection with chicken anemia virus. Note the loss of thymocytes in the cortex and the presence of hemorrhage. Scale bar = 500 mcm. B. Normal thymus from an unaffected hatchmate. Scale bar = 500 mcm.
Courtesy of Dr. Oscar J. Fletcher.
A. Bone marrow from a 14-day-old broiler chicken suspected of infection with chicken anemia virus. Note the loss of cellularity and replacement by adipose. Scale bar = 200 mcm. B. Normal bone marrow from an unaffected hatchmate. Scale bar = 200 mcm.
Courtesy of Dr. Oscar J. Fletcher.
Gangrenous dermatitis of the skin (known as "blue wing") under the wings of a bird infected by chicken anemia virus.
Courtesy of Dr. Mohamed M. El-Gazzar.
A. Thymus from a 14-day-old broiler chicken suspected of infection with chicken anemia virus. Note the loss of thymocytes in the cortex and the presence of hemorrhage. Scale bar = 500 mcm. B. Normal thymus from an unaffected hatchmate. Scale bar = 500 mcm.
Courtesy of Dr. Oscar J. Fletcher.
A. Bone marrow from a 14-day-old broiler chicken suspected of infection with chicken anemia virus. Note the loss of cellularity and replacement by adipose. Scale bar = 200 mcm. B. Normal bone marrow from an unaffected hatchmate. Scale bar = 200 mcm.
Courtesy of Dr. Oscar J. Fletcher.
Histopathological Lesions
Lymphoid cell populations are depleted in primary and secondary lymphoid organs. Most notable is severe lymphocytic depletion of the thymic cortex (see thymus images).
Granulocytic and erythrocytic compartments in the bone marrow are atrophic or hypoplastic (see bone marrow images). If blood smears are made, leukopenia and pancytopenia are often noticed.
Diagnosis of Chicken Anemia Virus Infection
Decreased hematocrit and PCR assay for detection of CAV nucleic acids in blood, thymus, or spleen lymphocytes
Immunohistochemistry or immunofluorescence
A tentative diagnosis of chicken anemia virus infection is based on history, clinical signs, and gross and histopathological lesions. Confirmation requires detection of virus or viral DNA in the thymus, spleen, or bone marrow.
PCR assay and quantitative PCR techniques are commonly used to demonstrate the presence of CAV DNA. Highly conserved portions of the CAV genome enable design of PCR assays that reliably detect most CAV strains. Detection of viral RNA by RT-qPCR assay can be used to show active viral replication.
Alternatively, viral antigens in the thymus can be detected by immunohistochemistry or immunofluorescence.
Viral isolation is generally not used in the course of diagnosis because it is slow and expensive. In addition, it is difficult because of the limited number of cell lines supporting CAV replication. Only a limited number of chicken lymphoblastoid cell lines are available, some of which can become resistant to CAV infection with cell passage. Furthermore, these cell lines grow in suspension, so the cytopathic effect of CAV infection is difficult to recognize.
To isolate CAV, chloroform-treated extracts of tissues are inoculated in MDCC-MSB1 (a lymphoblastoid cell line derived from Marek's disease tumors) or into maternal antibody–negative day-old chicks.
The presence of CAV DNA or proteins in culture or in tissues can be verified by PCR or antibody assays (eg, immunohistochemistry or immunofluorescence). Commercial ELISA kits are available to detect serum antibodies against CAV and can be used to identify breeder flocks that are seronegative before egg production and to monitor the efficacy of vaccination.
Treatment, Control, and Prevention of Chicken Anemia Virus Infection
No specific treatment available
Control best achieved by vaccination
There is no specific treatment for chicken anemia virus infection. Secondary bacterial infections can be treated with antimicrobials.
One strategy to control CAV infection is vaccination of breeder flocks with commercially available live vaccines before the start of egg production. Because only a single serotype of CAV has been identified, the vaccine does not need to be matched to regional variants.
Vaccine administration is by injection or by addition to the drinking water, depending on the type of vaccine available in individual countries. For example, the USDA allows vaccination by injection around 10 weeks by the wing-web method, which is almost always done in combination with avian pox and avian encephalomyelitis vaccines.
Pearls & Pitfalls
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Many operations rely instead on natural exposure of breeders to CAV before the onset of egg production, with serological monitoring to confirm that seroconversion has occurred. However, variability in seroconversion can lead to vertical transmission and infection of progeny with suboptimal maternal antibody levels via horizontal transmission or vaccination with CAV-contaminated vaccines.
Because of the synergism between CAV and other immunosuppressive viruses, control of the latter is also important, especially to prevent disease in chickens infected after the decline of maternal antibodies.
Eradication of CAV from premises is not a feasible strategy for control because the virus is extremely resistant to chemical disinfectants and heat.
Key Points
CAV infection causes anemia and transient immunosuppression in chicks 2–3 weeks old in the absence of maternal antibodies.
In adult chickens, CAV can cause transient immunosuppression and economic losses.
CAV is ubiquitous in poultry operations worldwide and is highly resistant in the environment.
The diagnosis of CAV infection is based on detection of CAV DNA in thymus, spleen, or blood lymphocytes.
CAV infection is controlled by vaccination or natural exposure of breeders before the start of egg production.
For More Information
Schat KA, van Santen VL. Chicken infectious anemia and circovirus infections in commercial flocks. In: Swayne DE, ed. Boulianne M, Logue CM, McDougald LR, Nair V, Suarez DL, associate eds. Diseases of Poultry. 14th ed. Wiley-Blackwell; 2020:284-321.
Cardona C, Shivaprasad HL. Chicken infectious anemia. In: Brugère-Picoux J, Vaillancourt J-P, Bouzouaia M, Shivaprasad HL, Venne D, Association française pour l'avancement des sciences, eds. Manual of Poultry Diseases. AFAS; 2015:204-207.
Smyth JA, Schat KA. Chicken anemia virus. In: Williams SM, Dufour-Zavala L, Jackwood MJ, et al, eds. A Laboratory Manual for the Isolation, Identification and Characterization of Avian Pathogens. 6th ed. American Association of Avian Pathologists; 2016:183-188
Schat KA. Chicken infectious anemia. In: Samal SK, ed. Avian Virology: Current Research and Future Trends. Caister Academic Press; 2019:241-287.
Varsani A, Kraberger S, Opriessnig T, et al. Anelloviridae taxonomy update 2023. Arch Virol. 2023;168(11):277. doi:10.1007/s00705-023-05903-6
