Epidemiology
- worldwide distribution
- once infected an individual probably carries virus for life. Usually these
infections remain latent. However if cell mediated immunity becomes impaired CMV
reactivation syndromes may develop
- most primary CMV infections in organ transplant recipients result from
transmission of the virus in the graft itself. In CMV seropositive transplant
recipients infection results from reactivation of latent virus or, less
commonly, from reinfections by a new strain of CMV
- about 25% of bone marrow and organ transplant recipients develop CMV
pneumonitis. Infection may be primary/reactivation/superinfection
- incidence of clinical disease differs in 3 forms of infection: 60%, <20%
and 20-50% respectively
- type of immunosuppression has important effect on incidence and severity of
infection. Antilymphocyte antibodies have greatest effect in inducing CMV
disease; cyclosporin, azathioprine, cyclophosphamide have intermediate effect;
steroid minimal effect
- tends to cause infection 1-6 months post transplant
- transplanted organ particularly vulnerable as a target for CMV infection (ie
CMV hepatitis follows liver transplantation)
Clinical features
In immunosuppressed patients CMV induces a variety of syndromes including:
- fever and leucopaenia
- hepatitis
- pneumonitis
- oesophagitis
- gastritis
- colitis
- retinitis
Often begin with prolonged fever, malaise, anorexia, fatigue, night sweats,
myalgia and arthralgia. Liver function abnormalities, leucopaenia,
thrombocytopaenia and atypical lymphocytosis may be observed during these
episodes
- dry cough, dyspnoea and hypoxia in pneumonitis. CXR: bilateral interstitial or
reticulonodular infiltrates beginning in the periphery of the lower lobes and
spreading centrally and superiorly. Localized segmental, nodular or alveolar
patterns less commonly involved. Diagnosis requires lung biopsy or BAL. Most
cases associated with bacterial, fungal or protozoal superinfection so it can be
difficult to assess the clinical relevance of CMV isolation from respiratory
secretions or positive serology.
- GI involvement may be localized or extensive
- fatal CMV infections often associated with persistent viraemia and multiple
organ involvement. Progressive pulmonary infiltrates, pancytopaenia,
hyperamylasaemia and hypotension are characteristic. Superinfection with
bacterial, protozoa and fungi common.
- other early manifestations (1-6 months post transplant) of CMV infection
include:
- encephalitis
- transverse myelitis
- cutaneous vasculitis
Investigations
Diagnosis cannot usually be made reliably on clinical grounds alone.
Virus isolation from appropriate clinical specimens, together with
demonstration of a fourfold or greater rise in antibody titre or persistently
elevated titres is preferred diagnostic approach
Shell vial assay may expedite diagnosis when virus titres are too low to
produce rapid diagnosis from tissue culture
CMV in blood more clinically significant than in oropharyngeal
secretions/urine as excretion from the latter sites may continue for months to
years following illness
Detection of CMV immediate-early antigens or DNA in peripheral WBCs may
hasten diagnosis of disease in certain populations (eg organ transplant
recipients). Positivity in such assays may antedate culture positivity by
several days
Rises in Ab titres may not be detectable for up to 4 weeks after primary
infection and titres often remain high for years after infection. Detection of
CMV-specific IgM sometimes useful in the diagnosis of recent or active
infection
Treatment
- ganciclovir (2-3 week course) and hyperimmune globulin to CMV or (pooled
immunoglobulin). Latter thought to act as a modulator of the immune response as
pneumonitis is mainly mediated by immunopathological mechanisms rather than the
viral infection that causes damage in other tissues
- foscarnet is an alternative. Also inhibits viral DNA polymerase but because it
does not phosphorylation to an active form it is effective against ganciclovir-resistant
CMV. Adverse effects include renal dysfunction, hypomagnesaemia, hypokalaemia,
hypocalcaemia, fits, fever and rash. All occur in >5% of patients
Prevention
- use of seronegative donors and blood products for seronegative recipients
- acyclovir in high dose from time of transplantation decreases risk of CMV
disease significantly in BMT recipients and patients receiving kidney
transplants from seropositive donors
- acyclovir does not prevent CMV disease in HIV positive patients
- conflicting results regarding effectiveness of ganciclovir, interferon and
immune globulin in prophylaxis
Further reading
Ong ELC. Viral infections in the immunocompromised host. Hospital Update Apr
'95
http://www.cdc.gov/ncidod/diseases/cmv.htm
© Charles Gomersall November 1999
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