Cytomegalovirus infection in liver-transplanted children

Table 2 Cytomegalovirus assays and clinical use

Investigation	Sample	Uses	Properties
Cell culture
Traditional cell culture (human fibroblast cells)	Tissue or non-tissue (blood, urine, oral secretion) sample	Not widely available	Highly specific
Shell vial assay (centrifugation-amplification technique)			Can be tested for phenotypic susceptibility; Takes a long time (2 to 21 d), more rapid with the shell vial assay (16 h)
Histopathology of organ-specific tissues
Plain histological microscopy	Tissue sample	Gold standard for diagnosis of tissue-invasive CMV disease	Low sensitivity but very high specificity
Immunohistochemistry		Used for reference of endpoint of treatment of tissue-invasive CMV disease
Molecular diagnosis (detection of viral genome)
Plasma quantitative nucleic acid testing (plasma QNAT)	Blood (plasma or whole blood)	Used to detect CMV DNAemia with high sensitivity; used in diagnosis, surveillance to guide pre-emptive antiviral treatment, and therapeutic monitoring	Generally high sensitivity but less sensitivity in R+ patients
Tissue QNAT	Tissue sample	Need more clinical trial studies	Better specificity but a lack of studies
Real-time PCR	Blood	Alternative to conventional plasma QNAT	More rapid and precise
NASBA assay	Blood	Under study as an alternative to conventional quantitative antigenaemia as a guide for starting pre-emptive therapy	Increased sensitivity for detection of CMV viraemia
Direct viral pp65 antigen detection	Whole blood or plasma	Diagnosis of CMV infection by detecting antigenaemia; Quantitative result, can guide initiation of pre-emptive therapy	After the blood collection, the sample must be processed within 6 h; False-negatives in patients with neutropenia
Serological analysis (viral antibody detection)
CMV IgG antibody testing	Plasma	Diagnosis of CMV infection	Better sensitivity and specificity; also positive in past infection
CMV IgM antibody testing		Pre-transplant assessment for serostatus of the donor and the recipient	Low sensitivity and specificity for diagnosis
Viral cellular response detection
QuantiFERON-CMV assay: IFN-γ released measurement	Plasma	Prognostic marker for risk of developing CMV disease: a positive result is associated with a lower incidenceMonitoring during prophylaxis or pre-emptive therapy	High positive predictive value but low negative value

CMV: Cytomegalovirus; D: Donor; IFN-γ; Interferon-gamma; NASBA: Nucleic acid sequence-based amplification; QNAT: Quantitative nucleic acid testing; R: Recipient; PCR: Polymerase chain reaction; Ig: Immunoglobulin.