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Infection in Haematology
Figure 1: Direct and Indirect Effects of without ganciclovir prophylaxis
23
and a reduced risk of bacterial and
Cytomegalovirus Infection
protozoal infections in patients receiving CMV prophylaxis.
7
Latent CMV infection Direct effects: Apart from these complications, CMV infection also promotes the
Nephritis development of non-infectious complications such as diabetes and
Hepatitis
Myocarditis
Guillain-Barré syndrome in SOT recipients.
13,14
Even though
Active CMV infection Pancreatitis
immunosuppressive treatment is the most frequent cause of
Retinitis
Enterocolitis
diabetes in SOT patients, with an incidence of 3–45%, CMV infection
Pneumonia
is another important risk factor for the development of post-
Indirect effects Myelosuppression
transplant diabetes.
14
Guillain-Barré syndrome has also been
associated with CMV. Experimental data proposed immunological
mechanisms for the development of this disease and suggest that
Immunosuppression
infections such as CMV and campylobacter initiate immune
opportunistic infections:
Diabetes
Acute or chronic Candida spp. responses, causing neural damage. A probable causative
Guillain-Barré syndrome
graft rejection Aspergillus spp.
Cardiovascular disease
relationship between viral replication and Guillain-Barré syndrome
Pneumocystis jirovecii
Bacterial infections has been reported after SOT.
13
There is also evidence that CMV
infection is involved in the development of GvHD after alloHSCT.
CMV = cytomegalovirus.
Adapted from Fishman et al., 2007.
41
Our group has demonstrated the induction of syngeneic graft-
versus-host reactivity-like symptoms to be correlated with
replication but by an activation of the immune system as a re-activated viral infections after bone marrow transplantation.
24
consequence of CMV replication. Virus replication takes place in a Söderberg-Naucler et al.
25
have shown the CMV-associated
broad variety of cells, resulting in the initiation of inflammatory autoantigen CD13 to be immunogenic during CMV infection in bone
reactions in the host. This facilitates indirect effects such as graft marrow transplant patients. In their study, all of the 14 patients who
rejection and/or GvHD. Boeckh and Nichols demonstrate a higher had antibodies to CD13 developed either limited or extensive
incidence of acute GvHD in CMV-seropositive recipients after chronic GvHD. The use of pre-emptive CMV therapy was associated
alloHSCT compared with seronegative ones. This is in line with with a reduced risk of extensive or severe chronic GvHD in
activation of the immune system by CMV infection.
18
The multivariate analysis.
26
relationship between CMV infection and graft rejection seems to be
a double-edged sword: CMV is associated with GvHD and rejection, Prophylactic and Pre-emptive Therapy for
yet rejection and GvHD support CMV replication. Cytomegalovirus Infection
There are two main strategies for the management of CMV
Indirect Effects of Cytomegalovirus Infection infection: prophylaxis or pre-emptive therapy. For prophylaxis, all
Some of the indirect effects of CMV occur in transplant recipients patients at risk receive antiviral treatment independent of viral
in general. Increased risks of acute and chronic rejection and acute replication. In the pre-emptive setting, patients receive antiviral
and chronic GvHD have been reported. The development of
cardiovascular disease has been associated with a precedent
CMV infection. Lowance et al. pointed out that CMV infection may
The different courses and manifestations
influence the risk of acute graft rejection after SOT. Valacyclovir
of cytomegalovirus (CMV) disease
was employed for CMV prophylaxis in patients after renal
transplantation. The risk of acute graft rejection was reduced by the
influence the therapeutic approaches to
prophylactic administration of valacyclovir in CMV-seronegative
preventing or treating CMV infections or
recipients receiving a graft from CMV-seropositive donors (26
versus 52%; p=0.001).
19
reactivations and also its direct and
indirect effects.
Epidemiological, pathophysiological and therapeutic results
support the fact that CMV infection also contributes to post-
transplant atherosclerosis in heart transplant recipients.
20–22
To our therapy only when there is evidence of CMV replication detected by
knowledge, no prospective studies have yet been performed that laboratory assays, such as polymerase chain reaction (PCR)-based
explore this clinical phenomenon. The immunomodulatory effects assays or pp65 antigen detection.
of CMV promote the onset of opportunistic infections and other
complications, such as EBV-associated lymphoproliferative The course of CMV disease differs among transplant populations
disease,
6,7,11
leading to strong immunosuppression. such as SOT and HSCT. Recipients of an allogeneic stem cell graft
continue to show a high mortality from CMV disease. CMV-
This effect of CMV infection is supported by the fact that seropositive patients, after kidney transplantation, have an
valacyclovir prophylaxis in renal transplant recipients reduces the increased risk of CMV disease only when receiving intensified
risk of fungal and bacterial infections such as Candida (10% immunosuppressive therapies such as pan T-cell antibodies. The
valacyclovir versus 22% placebo; p=0.04) and staphylococcal different courses and manifestations influence the therapeutic
infections (12 versus 21%; p=0.07).
19
Other groups demonstrated an approaches to preventing or treating CMV infections or
increased risk of fungal infections in heart transplant patients reactivations and also its direct and indirect effects.
27,28
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