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272  |  Schat

          also decreased in the spleen, but the decrease is often less dra-  of age caused severe respiratory effects especially when the vac-
          matic than in the thymus (Adair et al., 1993; Hu et al., 1993b;   cine was given at one day of age. However, humoral immune
          Bounous et al., 1995). Infection after maternal antibodies waned   responses were not impaired at 6 weeks of age (De Boer et al.,
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          showed similar decreases in CD4  and CD8  T-cells in the spleen   1994). CAV can aggravate bacterial infections probably leading
          and blood (Haridy et al., 2012; Wani et al., 2015). Functional   to enhanced condemnation rates as suggested by Sommer and
          assays have shown that co-infection of REV and CAV causes a   Cardona (2003) (Dermatitis leading to ‘blue-wing disease’ is also
          decrease in REV-specific CD8  cytotoxic T lymphocytes (CTL)   enhanced by CAV infection (Engström et al., 1988).
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          (Markowski-Grimsrud and Schat, 2003). The effect on CD4  Th
          cells was shown by van Ginkel et al. (2008). Co-infection of CAV
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          with infectious bronchitis virus (IBV) reduced the ratio of CD4 /  Epizootiology
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          CD8  in the Harderian gland and caecal tonsils causing a reduc-  CAV infections have been reported in commercial and backyard
          tion in IBV-specific IgA secreting cells and a delayed IgA response   flocks from all continents (reviewed by von Bülow and Schat,
          to IBV. Clearance of IBV was delayed in dually infected birds   1997; Schat, 2009). Publications on isolation of CAV or detec-
          compared with IBV infection alone. Clearly, CAV effects antigen-  tion of CAV antibodies continue to be added to the literature
          specific Th and CTL activity, which provides the explanation for   without adding basic new information. Chickens are the major
          the CAV-induced decrease in vaccine responses and increase in   host as discussed in Host range.
          certain infections.                                      Once maternal antibodies wane in commercial broiler flocks,
                                                                acquired antibodies can be detected as early as 35 days of age
          Interactions with other pathogens and vaccines        (Sommer and Cardona, 2003). A cross-sectional study in Ontario
          Perhaps due to the possibility of injecting CAV-contaminated   showed that 178/231 (77%) of broiler flocks had antibodies to
          MDV vaccines in 1-day-old chicks the interaction between MDV   CAV between 31 and 53 days of age (Eregae et al., 2014). Unfortu-
          and CAV was noted almost as soon as CAV was isolated by Yuasa   nately, there was no information provided on the age brackets for
          et al. (1979) from birds inoculated with a contaminated MDV   the antibody negative flocks. In Georgia (USA), 67 of 68 broiler
          vaccine.                                              flocks were positive for CAV antibodies in 2005. The age of these
            Von Bülow et al. (1983) noted that dual infections of CAV   flocks ranged from 34 to 53 days (L. Dufour-Zavala, unpublished
          and MDV enhanced the anaemia as well early MD lesions.   data quoted by Smith, 2006). These data clearly indicate that the
          HVT-vaccinated chickens dually infected with MDV and CAV   majority of broiler flocks in North America become infected with
          experienced increased mortality with severe thymus and bursal   CAV.
          atrophy and increased MD lesions. Experimental infection with   Most of the breeder and layer flocks also become antibody
          CAV and MDV isolated from the diseased birds confirmed the   positive by natural exposure between 5 and 10 weeks of age. If
          interaction between the two viruses (Otaki et al., 1987). In a   breeder flocks are not seropositive by 8 to 10 weeks of age, vac-
          subsequent study, it was shown that inoculation of HVT plus   cination is recommended to provide maternal immunity to their
          CAV aggravated the depression of mitogen stimulation compared   offspring.
          with CAV alone (Otaaki et al., 1988) suggesting decreased cell-
          mediated immunity, which is of crucial importance for vaccine
          induced protection to MDV (Schat and Xing, 2000). Otaki et   Diagnosis
          al. (1988) suggested that CAV infection can cause MD vaccine   The diagnosis of clinical disease caused by CAV infection can be
          breaks. Fehler and Winter (2001) analysed MDV isolates from 26   problematic because there are no specific lesions associated with
          flocks experiencing MD vaccine breaks and found CAV in 70% of   CAV infection with the exception of eosinophilic refractile intra-
          the isolates. Miles et al. (2001) studied the impact of CAV infec-  nuclear inclusion bodies in thymocytes, which are rarely seen in
          tion on the early pathogenesis of RB-1B, a very virulent (vv) MDV   diagnostic cases (Smyth and Schat, 2013). Severe thymus atrophy
          isolate, and 584A, a vv+ MDV isolate. Co-infection increased the   and pale bone marrow provide some indication that CAV may
          replication of RB-1B to as early as 4 days pi, but the degree of   be involved but these lesions are not specific for CAV-induced
          increase was less severe with 584A. The latter replicated also to a   disease. For example, infection with vv or vv + MDV can also
          higher titre than RB-1B in the absence of CAV. It is likely that the   cause severe thymus atrophy (Calnek et al., 1998). Thus, in addi-
          impact of CAV on the early pathogenesis of MDV depends on the   tion to pathology, the flock history and especially the antibody
          virus dose as suggested by Jeurissen and de Boer (1993) or the   status of the parent flock will provide further evidence that CAV
          degree of MDV replication.                            may be the cause. Detection of viral antigens in affected tissues
            The interactions between IBDV and CAV have been described   by immunohistochemistry or immunofluorescence, preferably
          in the section Pathogenesis in young chickens. CAV infection can   using monoclonal antibodies to VP3, will confirm the involve-
          increase the incidence of inclusion body hepatitis and hydrop-  ment of CAV in clinical disease. Molecular tests, especially qPCR
          ericardium syndrome (Toro et al., 2000). Combined vaccination   and qRT-PCR assays, may be used to further demonstrate the
          with an inactivated fowl adenovirus vaccine and live attenuated   involvement of CAV. Positive results with the qRT-PCR assay is
          CAV vaccine protected against these diseases (Toro et al., 2002).   the most important one because it will indicate that CAV is rep-
          Spray vaccination against NDV using La Sota clone 30 vaccine   licating. Positive qPCR tests only show the presence of CAV and
          at 1 or 10 days of age combined with CAV infection at one day   low copy numbers may reflect the presence of latent viral DNA.
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