Biology Reference
In-Depth Information
allograft recipients who did not receive routine antiviral prophylaxis were infected
with HCMV in the first 100 days after transplantation (Sagedal et al. 2004). This
incidence of infection is significantly different than rates of less than 10% in patients
receiving routine antiviral prophylaxis in the immediate posttransplantation period
and has been used as evidence supporting the routine use of antiviral prophylaxis to
limit HCMV disease in the early posttransplantation period and possibly decreasing
chronic graft rejection that is associated with HCMV infection (Sagedal et al. 2004;
Potena et al. 2006; Stoica et al. 2006; Fishman et al. 2007). The incidence of late
infections with CMV in patients receiving antiviral prophylaxis has remained rela-
tively steady and is a significant cause of morbidity and mortality in the transplant
recipient, suggesting that antiviral prophylaxis does not eliminate the clinical impact
of HCMV in allograft recipients (Singh 2005). Furthermore, quantitation of viral
load in patients with late HCMV disease has been reported to be less predictive of
disease susceptibility, suggesting that differences in the biology of the virus infec-
tion could exist between early and late infections (La Rosa et al. 2007). In hemat-
opoietic allograft recipients, the most severe disease is associated with pulmonary
infection, a site of disease that is observed less frequently in solid organ allograft
recipients, with the exception of heart-lung transplant recipients (Wreghitt et al.
1988; Smyth et al. 1991; Sharples et al. 1996; Wreghitt et al. 1999). The mechanism
for the severe lung disease seen in recipients of an allogenic bone marrow transplant
is unclear but may involve concomitant graft-vs-host disease (host-vs-graft in heart-
lung recipients), preexisting lung disease, or damage associated with pretransplant
conditioning (Horak et al. 1992; Barry et al. 2000). In the mouse model of MCMV
infection in the immunocompromised host, reactivation of MCMV following suble-
thal irradiation also involves the lung, and in this experimental model it has been
argued that lung disease develops secondary to the lung being an important site of
viral latency (Kurz et al. 1997; Reddehase et al. 2002).
Regardless of the exact mechanism of disease, HCMV infection is a necessary
prerequisite for disease and effective therapy for this virus has reduced the mortality
and morbidity of this posttransplantation complication. Finally, although lung
disease observed in hematopoietic marrow allograft recipients is widely disseminated
based on clinical parameters such as radiographic studies and clinical findings, early
studies demonstrated only focal areas of virus infection (Myerson et al. 1984). This
finding raised the possibility that HCMV may cause disease in this group of
patients by a mechanism other than direct lytic infection, possibly by altering
regulation of the inflammatory response in the infected host (Grundy et al. 1987).
Infection in solid organ allograft recipients is nearly universal if either the donor
or the host has had a previous infection with HCMV. Epidemiological studies have
consistently shown that transplantation of an organ from a previously infected donor
(D
+
) into an noninfected recipient (R
-
), a D
+
/R
-
mismatch, can result in a primary and
often severe infection in both the early and late posttransplantation period in the
immunocompromised host. These individuals are at greatest risk for severe disease
secondary to uncontrolled virus replication and have about a two- to threefold higher
incidence of late disease following antiviral prophylaxis as compared to D
-
/R
+
, or D
+
/
R
-
transplant recipients (Bonatti et al. 2004; Murray and Subramaniam 2004; Carstens
