Clinical Diagnostic Testing for Human Cytomegalovirus Infections

Abstract

Human cytomegalovirus (HCMV) infections are among the most common complications arising in transplant patients, elevating the risk of various complications including loss of graft and death. HCMV infections are also responsible for more congenital infections worldwide than any other agent. Congenital HCMV (cCMV) infections are the leading nongenetic cause of sensorineural hearing loss and a source of significant neurological disabilities in children. While there is overlap in the clinical and laboratory approaches to diagnosis of HCMV infections in these settings, the management, follow-up, treatment, and diagnostic strategies differ considerably. As yet, no country has implemented a universal screening program for cCMV. Here, we summarize the issues, limitations, and application of diagnostic strategies for transplant recipients and congenital infection, including examples of screening programs for congenital HCMV that have been implemented at several centers in Japan, Italy, and the United States.

Keywords: human cytomegalovirus; congenital infection; diagnosis; pregnancy.

Figure 1.

Algorithms for prevention, diagnosis, and screening for cCMV, as implemented at centers in Japan, Italy, and the United States. A, cCMV screening and diagnosis as implemented in Japan [36, 37]. Optional tests are shown in dotted border boxes. Wide arrows indicate the algorithm employed since an in vitro diagnostic approved NAT became available. B, cCMV screening and diagnosis in Bologna, Italy [35]. C, cCMV screening, diagnosis, and management in Birmingham, Alabama [38]. Abbreviations: AF, amniotic fluid; cCMV, congenital cytomegalovirus; DBS, dried blood spot; GA, gestational age; HCMV, human cytomegalovirus; IVD, in vitro diagnostic; PCR, polymerase chain reaction; NAT, nucleic acid test; UC, umbilical cord; US, ultrasound.

Figure 2.

Saliva PCR identifies more newborns with congenital CMV infection than does a rapid culture assay: data from the CHIMES study [38]. Abbreviations: cCMV, congenital cytomegalovirus; PCR, polymerase chain reaction; RC, rapid culture.