Question 11

College answer

Syllabus topic/section:

2.1.3    Sepsis and Infections: Rarer infections with specific ICU considerations: L1

Discussion: 

Many candidates were able to score at standard and above. Candidates who did well outlined the specific clinical features and discussed the features of both a CMV syndrome and tissue-invasive CMV disease, although this distinction and terminology was not required to be at standard.
Part b) required the diagnostic tests (for example serology, PCR and tissue biopsy) along with the expected findings. Some candidates wrote a more generic list of investigations (for example CT scan, blood smear) which did not attract marks as the question required diagnostic tests.
Part c) was well answered by those who have an understanding and knowledge of the disease.
Those with a knowledge gap about the topic tended to have incomplete answers across all 3 the sections.

Discussion

Clinical features: CMV "syndrome"

• Fever ≥38°C for at least 2 days.
• New or increased malaise or  fatigue 
• Leukopenia or neutropenia 
• >5% atypical lymphocytes
• Thrombocytopenia 
• Elevation of aminotransferases

CMV end organ disease:

• Pneumonia
• Colitis
• Oesophagitis
• Retinitis and uveitis
• Encephalitis
• Meningitis
• Pericarditis and myocarditis
• Hepatitis
• Guillain-Barre syndrome

Diagnostic tests and expected findings:

• Positive CMV antibodies (IgM or IgG) - sensitive for recent or acute infection
• Antigen assay (for pp65 antigen) 
• Qualitative PCR for CMV DNA- very sensitive for the presence of CMV, but they do not distinguish between active and latent infection.
• Quantitative PCR for CMV DNA - ideal test, as it provides a quantitative assessment of viral load, and allows the monitoring of therapy. The WHO have set up an international standard for this technique.
• Tissue histology: one cannot always have access to the tissue, but it does allow the identification of these characteristic cytomegalic cells with "owl's eye" inclusion bodies. Immunohistochemistry for the virus is the gold standard.
• Viral cultures: These take some time; in vivo CMV is cultured in fibroblasts.

Initial antiviral management:

• Ganciclovir is first-line: a selective inhibitor of CMV DNA polymerase. Much more activity against CMV than aciclovir.
  • Valganciclovir usually follows: it is the orally bioavailable pro-drug.
• Foscarnet is second-line: it is sodium phosphonoformate, and it also inhibits CMV DNA polymerase.
• Cidofovir is an alternative second-line: a nucleotide analogue, it also selectively inhibits CMV DNA polymerase.
• CMV immunoglobulin is specific antibodies to CMV from immune hosts.