CONTINUING EDUCATION :: CYTOMEGALOVIRUS INFECTION Serology Population


Pregnant woman


Fetus Newborn Transplant donor/recipient Molecular testing Detection of active infection


Not possible to differentiate primary infection from reactivation/reinfection.


Amniocentesis: Detection of active infection


Detection cCMV transmitted by mother within the first 2–3 weeks after birth.


Detection of active infection before and after transplantation


Not relevant Table 2: Relevant laboratory testing for different at-risk populations for CMV infection.


(amniocentesis) has been established as the gold standard due to its high sensitivity and specificity. However, amniocentesis has risks for the pregnant woman and fetus.30


On the other


hand, when fetal abnormalities are detected by ultrasound and the pregnant woman has low IgG avidity antibodies, the fetus has a higher risk of being infected. Therefore, the newborn will need to be monitored to confirm or rule out cCMV infection.22


Newborn testing Molecular testing, such as quantitative polymerase chain reac- tion (qPCR), is the gold standard for cCMV detection in new- borns within the first 2–3 weeks of life to distinguish congenital from a postnatal infection acquired during or after delivery (Tables 1 and 2).22,31


Saliva and urine are the preferred sample


types for testing because they contain high viral loads of CMV. However, blood can also be used. The CDC recommends first testing saliva and then confirming positive samples with urine because CMV is also shed in breast milk. Therefore, confirmation with urine will help to rule-out false positives from breast milk.17 If the newborn is negative, the baby is considered uninfected,


and no further tests are warranted. If a newborn is infected as indicated through a positive result from molecular testing, the newborn will be monitored for hearing loss or other sequela, thus increasing opportunities for early intervention.32 Serological testing for newborns within the first 2–3 weeks is not recommended because IgM antibodies are only present in 70% of infected newborns.16


Additionally, newborn IgG anti-


bodies mainly come from the mother and transfer through the placenta to the fetus.33


As with molecular testing, serological


tests will not distinguish prenatal from perinatal CMV infection after 2–3 weeks of life.16 As mentioned above, a large percentage of infected newborns are asymptomatic at birth but develop symptoms later.7,8


Therefore, it


can be helpful to screen newborns at birth. Several studies support the need of neonatal screening to identify earlier infected infants at risk to develop neurological sequelae and provide the appropriate treatment to reduce and treat CMV diseases.34


This is important because DBS are collected from all newborns for metabolic screening and sometimes for detection of newborn disorders.22,35


In the United States,


universal screening is not included in routine newborn screening. The CDC is investigating dried blood spot (DBS) to be used for this purpose.17


In fact, there are already commercially


available assays to detect cCMV in newborns through DBS.36 Interestingly, some states have already implemented universal screening. In February 2022, Minnesota become the first state in the nation to screen every newborn for cCMV.37


10 DECEMBER 2022 MLO-ONLINE.COM


Transplantation population testing Another population that is at risk of developing complications from CMV infection are recipients of organ or hematopoietic stem cell transplantation. Direct detection of CMV by molecular testing is suggested for


detecting and monitoring current infections in transplant recipi- ents (Table 2). Transplant donors must be also tested for CMV active infection prior to donation.22,38


Conclusion


CMV is a common virus that can infect people of all ages. As does herpes virus, CMV remains latent in the human body. Therefore, the virus can be reactivated after primary infection and induce an active infection. Immunocompro- mised individuals are the main population at risk to develop complications from CMV primary infection, reactivation, and reinfection. These include pregnant women, newborns, and transplant recipients. Depending on the at-risk population, either serology or molecular testing are performed to detect an active infection or differentiate a primary infection from reactivation or reinfection.


A combination of molecular testing and serology provides the most accurate diagnosis of CMV infection. Due to the complications associated with a primary infection in pregnant women, it is important to raise awareness about CMV infection and implement initiatives to reduce the risk of transmitting the virus to the fetus. Furthermore, monitoring newborns is essential for identifying the infection quickly and administer- ing the appropriate treatment. However, in some countries, prenatal or universal newborn screening is not recommended. One of the factors influencing that decision is the cost as- sociated with testing. Nonetheless, it would be interesting to investigate the long-term consequences and costs of not screening these two populations. Vaccine candidates are now being evaluated in clinical The approval of a vaccine to prevent CMV infec-


studies.40


tion will have a significant impact on the groups at risk. In addition, there may be a shift in the role of serology in terms of monitoring the immune system’s response to vaccines. While waiting for a vaccine, those at risk should adopt proper hygiene practices to avoid CMV infection. For instance, fre- quent handwashing and avoiding touch with another person’s saliva, especially avoiding contact with the saliva and urine of small children.


On the other hand, serologi-


cal testing is recommended for transplant donors and recipients to reduce the risk of a primary infection and reactivation.38,39


IgM IgG Seroconversion Avidity


The combination of all serology parameters will aid in determining if the infection is primary, secondary, or reinfection.


Not relevant Not relevant


IgG detection important for risk assessment


Not relevant Not relevant


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