Validation of an automated immunoglobulin G–only cytomegalovirus (CMV) antibody screening assay and an assessment of the risk of transfusion transmitted CMV from seronegative blood

Abstract

BACKGROUND:Cytomegalovirus (CMV) antibody donor screening assays have predominantly included both immunoglobulin G (IgG) and immunoglobulin M (IgM) detection. However, since in the majority of cases both CMV IgG and IgM are detected concomitantly during early seroconversion, CMV assays based only on IgG are now widely applied for donor screening. STUDY DESIGN AND METHODS:The performance of an automated microparticle CMV IgG assay (Abbott AxSYM CMV IgG microparticle enzyme immunoassay [MEIA]) was compared with an established total antibody blood screening assay (Abbott CMV Total AB EIA). Sensitivity and specificity were assessed using 5050 random blood donors and 13 seroconversion panels. A risk analysis was undertaken to estimate the residual risk of transfusion-transmitted CMV (TT-CMV) from presumptive seronegative blood components. RESULTS: The EIA achieved marginally (but not significantly) better resolved sensitivity (100%) than the AxSYM IgG assay (99.93%). The AxSYM IgG resolved specificity (99.34%) was superior to the EIA (96.4%). This superiority was maintained (98.61%) when a modified cutoff was applied to the AxSYM IgG assay to achieve 100 percent resolved sensitivity. The seroconversion sensitivities of the EIA and the AxSYM IgG were equivalent, detecting the same bleed as positive in the majority of the seroconversion panels tested. The median TT-CMV residual risk estimate for the two assays was approximately 1 in 66,000 (range, 42,000-165,000). CONCLUSION: The AxSYM IgG MEIA is suitable for blood donor screening and was optimized by applying a modified cutoff of 9 AU per mL. The modeling predicts that implementing the AxSYM IgG assay would not negatively impact the already very low risk of TT-CMV associated with seronegative blood components in Australia.H uman cytomegalovirus (CMV) is a ubiquitous betaherpesvirus that generally causes asymptomatic infection in the 40 to 90 percent of individuals it infects.1 However, transfusiontransmitted CMV (TT-CMV) can cause serious morbidity and mortality in susceptible patients particularly when immunocompromised. At-risk patient populations include preterm CMV-seronegative neonates, seronegative recipients of autologous or allogeneic marrow or peripheral blood stem cell transplantation, solid organ transplant recipients, and CMV-seronegative AIDS patients. [2][3][4] The primary mechanism for TT-CMV is thought to be the infusion of latently infected mononuclear cells; however, reinfection or reactivation in seropositive recipients has also been reported. 5,6 The detection of CMV DNA in the plasma of some newly infected blood donors suggests the possibility that plasma viremia might also contribute to the incidence of TT-CMV. 7 The incidence of TT-CMV in susceptible patients, which was reported in the range of 10 to 40 percent in the 1970s and 1980s, has declined substantially to 1 to 4 percent as a result of CMV antibody screening and more recently leukodepletion of donated blood. 8,9 There has been substantial debate about the value of maintaining CMV antibo...

The residual risk of transfusion‐transmitted cytomegalovirus infection associated with leucodepleted blood components

“…Notwithstanding this, the estimates are well below the threshold of 1 in 1 million, generally considered negligible when contextualizing transfusion risks and substantially lower than our published estimate for the risk per non‐leucodepleted, sero‐negative unit of approximately 1 in 66 000 (range, 1 in 165 000–1 in 42 000) . Importantly though, the LD‐only and serological testing risk estimates cannot be compared because of the differing methods of derivation and cannot be deemed additive because there is likely significant overlap.…”

“…Even with this substantial risk reduction, the limitations of both major strategies (sero‐negative or leucodepleted) result in reported breakthrough infections at a rate of 1–7% per transfused recipient . Modelling performed prior to the 2008 implementation of universal leucodepletion for platelets and red cell concentrates (red cells) in Australia estimated the residual risk per sero‐negative (non‐leucodepleted) unit was approximately 1 in 66 000 (range, 42 000–165 000) . Interestingly, this modelled estimate is substantially lower than the rate of up to 0·23% (1 in 2300) per unit reported for non‐CMV antibody screened, leucodepleted cellular products in prospective clinical follow‐up of transfusion recipients in the USA .…”

Cytomegalovirus (CMV) seroprevalence in Japanese blood donors and high detection frequency of CMV DNA in elderly donors

“…The same authors showed that CMV DNA levels peak during the late phase of primary infection in newly seropositive donors. 8 Although whether a rationale exists for introducing screening for specific IgM in addition to IgG remains to be determined, 18 the chemiluminescence tests for CMV currently applied by the Japanese Red Cross detect only IgG. Although we have discussed seroprevalence and its relationship with the presence of DNA by interpreting IgM positivity as representing primary infection, reactivity for CMV-specific IgM measured by EIAs must be considered with caution.…”

CMV: Prevention, Diagnosis and Therapy

“…Prior to transplant, CMV serology should be performed on all donors and recipients. Tests for anti-CMV IgG are recommended, as they have better specificity than IgM or combination IgG and IgM tests, neither of which should be used for pretransplant screening, as false positive tests for IgM may significantly decrease test specificity (54)(55)(56). If the initial result was negative and there was a significant lapse in time after testing, serology should be repeated at the time of SOT, in order to not overlook those donors or recipients who are now seropositive.…”