Biology Reference
In-Depth Information
1986; Schmidt et al. 1991). Although HCMV remains the most common posttrans-
plantation infection, mortality rates have fallen dramatically even in the most
severely immunocompromised patients.
Of more recent concern has been the role of HCMV in infections in late times
after transplantation and perhaps more importantly, chronic graft dysfunction.
Infection can follow one of several routes, including:
1. Infection from the transplanted organ
2. Reactivation or dissemination of existing host infection
3. Through blood products required in the posttransplantation period
4. Hospital or community exposure to infectious virus
Replicating virus amplifies and disseminates in the absence of effective host
immune responses and multiple organ systems become infected. Clinical symptoms
are dependent on end-organ dysfunction such as hepatocellular damage, colitis, or
interstitial pneumonitis.
A well-described febrile syndrome associated with laboratory abnormalities in
peripheral hematological values and liver functions is a well-recognized clinical
presentation of CMV infection (CMV syndrome) in the posttransplantation period
is perhaps the most common clinical presentation of CMV infection in these
populations. In contrast to patients with HIV infections and AIDS (see Sect. 3.3),
HCMV infection of structures within the eye are uncommon in allograft recipients
and occur at a very low rate of less than 1% (Chung et al. 2007).
In addition to the clinical manifestations of disseminated HCMV infection,
HCMV infection in the donor or recipient has been associated with acute rejection
episodes in up to 35% of renal allograft recipients, a finding that is consistent with
the association between acute rejection events and the chronic graft rejection (Sola
et al. 2003; Chen et al. 2005; Reischig et al. 2006).
Early studies documented the onset of virus replication in the posttransplantation
period utilizing techniques of virus isolation. These studies indicated that patients at
risk from infection from the transplanted organ or from reactivation/recurrence of
persistent infection usually began excreting virus between 4 and 8 weeks after trans-
plantation (Meyers et al. 1982; Rubin 1986). Studies using PCR have demonstrated
virus replication as detected by viral DNA in blood within the first few weeks after
transplantation, suggesting that infection in these patients likely results in virus rep-
lication, amplification and dissemination, a course similar to that seen in primary
infection in normal hosts. It is important to note that these studies were done before
the widespread use of antiviral agents as prophylaxis in the posttransplantation
period to limit viral replication during the period of intensive immunosuppression.
In many centers in North America, solid organ allograft recipients receive antiviral
prophylaxis for up 100 days after transplantation. Thus, the kinetics of virus reactiva-
tion and replication has been modified such that HCMV infections more frequently
occur late in the course of transplantation (late infections). Currently, it is estimated
that late infections occur in approximately 20-30% of patients at risk for CMV infec-
tions, and up to 50% of these infections can be severe and invasive (Rubin 1986). In
contrast to these rates of late infections, a recent study reported that 62% of renal
