CMV Infection
Risk of CMV infection post transplant Cytomegalovirus
(CMV) is a γ-herpes virus and is one of the most common infections encountered
post-transplant. The likelihood of infection post-transplant is dependent on
whether the recipient has had previous CMV infection and therefore has
immunological memory of the virus. Immune memory is detected by looking for the
presence of CMV-specific antibody (IgG).
Around 50% of adults in the UK are CMV immune (seropositive) and
50% seronegative. Seronegative transplant recipients (R–) who receive an
allograft from a CMV seropositive donor (D+) are at risk of developing primary
infection; in the absence of prophylaxis, 60% will develop symptomatic CMV
infection post-transplant. Thus, most transplant
centres would give CMV prophylaxis to this high-risk group of recipients in the
form of oral valganciclovir. Many centres also offer ‘universal prophylaxis’ to
all at risk patients (D+R–, D–R+, D+R+).
Clinical features of CMV infection
The presentation of post-transplant CMV is very variable;
infection can be relatively asymptomatic in patients with immunological memory
to the virus and is diagnosed only by routine screening by polymerase chain
reaction (PCR). In others, particularly those who develop primary infection
while immunosuppressed, it can be life-threatening. Systemic symptoms
associated with CMV include fever, sweats, lethargy and weight loss. Abdominal
pain may accompany gastrointestinal (GI) infection or pancreatitis. CMV can
also present with organ-specific disease, including:
· colitis
– symptoms include diarrhoea and weight loss
· retinitis
– typical retinal appearance is of a ‘brush fire’
· pneumonitis
– patients present with breathlessness, widespread alveolar infiltrates visible
on chest radiograph or CT
· allograft
– viral inclusions can be observed on renal transplant biopsy, and are usually
associated with a decline in allograft function, even in the absence of
rejection.
Diagnosis
CMV is diagnosed by the detection of virus particles in the blood
(viraemia) or in urine. PCR performed on blood/urine samples allows the identification of viral
DNA. Alternatively, classical ‘owl eye’ inclusion bodies may be observed within
the nuclei of infected cells isolated by biopsy or bronchi alveolar lavage by
histology or cytology. CMV-specific antibodies can also be used in
immunohistochemical staining of biopsy material.
Treatment
CMV should be treated in the following ways.
· Reduction
in immunosuppression – the development of a CMV infection
suggests that the patient is relatively over-immunosuppressed. Usually the
target trough level of calcineurin inhibitor (CNI) is reduced and the
antiproliferative agent (azathioprine or mycophenolate) stopped.
· Specific
treatment for CMV – intravenous ganciclovir is the treatment of
choice for patients with life-threatening disease. Patients with low viral
titres or with reactivation rather than primary disease can be treated with
high-dose oral valganciclovir. Valganciclovir is a pro-drug which is converted
in the liver to ganciclovir. Ganciclovir must be phosphorylated in order to
generate its active metabolite ganciclovir triphosphate. Phosphorylation is
dependent in part on a CMV-synthesised enzyme UL97 phos-photransferase. Thus,
the virus may become resistant to ganciclovir if it mutates to produce a
non-functional enzyme.
· Other
agents used include foscarnet, cidofovir and intravenous CMV immune globulin,
although these are usually reserved for patients with refractory or ganciclovir
resistant disease.
Complications of CMV infection
Studies suggest that CMV infection (either symptomatic or
asymptomatic) can have an adverse effect on both patient and allograft
survival. CMV infection has been associated with:
· acute
rejection
· chronic
allograft nephropathy (CMV infection induces fibrosis and vascular thickening
in animal models of transplantation). Such chronic changes together with an
increase in acute rejection reduce long-term allograft survival
· cardiovascular
complications, thus a reduced patient survival
· post-transplant
diabetes mellitus.
