Cytomegalovirus
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Direct answer
Cytomegalovirus is a beta herpesvirus that establishes latency in monocytes and progenitor cells and is the leading non-genetic cause of congenital infection. Infected cells enlarge and show owl's-eye intranuclear inclusions surrounded by a clear halo, which is the classic histological clue. Ganciclovir and valganciclovir treat serious disease, and foscarnet is the alternative when resistance or marrow toxicity limits ganciclovir.
What you must remember
- Classification: Human betaherpesvirus 5, a double-stranded DNA virus that stays latent in monocytes and CD34-positive progenitors.
- Owl's-eye cell: An enlarged cell with a large basophilic intranuclear inclusion and a clear halo, seen in salivary gland, kidney and lung tissue.
- Congenital CMV: Sensorineural hearing loss is the commonest sequela, and features include microcephaly, periventricular calcification, chorioretinitis and blueberry-muffin petechiae.
- Newborn testing: Urine or saliva PCR within the first three weeks of life is the reliable test, because IgM is insensitive in the neonate.
- Transplant disease: Fever, leukopenia, pneumonitis and hepatitis appear mostly in the first few months after solid organ or stem cell transplantation.
- AIDS retinitis: Typically appears when CD4 counts fall below about 50 cells per microlitre, with a haemorrhagic, necrotising retinal lesion.
- Drug resistance: Ganciclovir resistance arises through mutations in the viral UL97 kinase, and cidofovir or foscarnet are used when this happens.
- Transmission: Saliva, urine, breast milk, blood, transplanted organs and sexual contact all carry the virus.
A graded pathway from suspicion to treatment
A transplant recipient with fever and a falling white cell count is the classic setting for CMV disease. The diagnostic route moves from blood to tissue as the picture becomes clearer.
- Clinical suspicion: Fever, leukopenia or hepatitis in a transplant recipient or a patient with low CD4 counts raises the question of CMV.
- Quantitative PCR: Blood CMV DNA load in plasma or whole blood confirms infection and guides monitoring, since a rising load predicts tissue disease.
- Tissue confirmation: Biopsy with immunohistochemistry for CMV antigen or owl's-eye inclusions proves end-organ disease, as in colitis or pneumonitis.
- Antigenaemia test: The older pp65 antigen assay on neutrophils has largely given way to PCR in current practice.
- Choosing treatment: Ganciclovir or valganciclovir is first line, while foscarnet or cidofovir is chosen when ganciclovir causes marrow suppression or resistance develops.
- Monitoring: Repeat the viral load at intervals during induction, because a falling load confirms that treatment is working.
Where the exam tries to catch you
CMV questions usually test whether the candidate knows which test is reliable in which patient.
- Trap: Using IgM to rule out congenital CMV in a newborn. Correct: IgM is insensitive in the neonate and maternal IgG can confound results, so urine or saliva PCR within three weeks of birth is the reliable test.
- Trap: Treating CMV retinitis with acyclovir. Correct: Acyclovir has poor activity against CMV, so ganciclovir or foscarnet is needed.
- Trap: Assuming CMV spreads only through sexual contact. Correct: Saliva, urine, breast milk, transfusion and transplanted organs are equally important routes, especially for newborns and transplant recipients.
Frequently asked questions
What is the histological hallmark of cytomegalovirus infection?
Owl's-eye cells are the histological hallmark of cytomegalovirus infection. They are enlarged cells with a large basophilic intranuclear inclusion surrounded by a clear halo, and they are seen in tissue biopsies and in urine sediment.
Which drug treats CMV retinitis in AIDS patients?
Ganciclovir, given intravenously or as oral valganciclovir, is the standard drug for CMV retinitis in AIDS patients. Foscarnet or cidofovir are alternatives when ganciclovir resistance or marrow suppression limits its use.
What are the classic congenital features of cytomegalovirus infection?
Congenital cytomegalovirus infection causes sensorineural hearing loss, microcephaly, periventricular calcification, chorioretinitis and petechiae resembling a blueberry-muffin rash. Hearing loss can appear late, so infants with congenital CMV need follow-up beyond the newborn period.
Why is cytomegalovirus the leading congenital infection?
Cytomegalovirus crosses the placenta during primary or non-primary maternal infection and is the commonest non-genetic cause of congenital infection. Most congenitally infected infants look normal at birth, which is why newborn screening matters.
How does CMV mononucleosis differ from Epstein-Barr virus mononucleosis?
Cytomegalovirus causes a mononucleosis-like illness in which the heterophile test is usually negative, so the Monospot cannot make the diagnosis. CMV IgM or viral PCR confirms the cause, and the absence of marked pharyngitis is a common clinical clue.