INFECTIOUS DISEASES: Diagnosis of CMV

Recognition of the importance of diagnosing and treating congenital cytomegalovirus (CMV) infection early in children is fueling the development of faster diagnostic techniques, perhaps most notably, real-time polymerase chain reaction (PCR) analysis.

Because children with congenital CMV often have normal hearing at birth, newborn hearing screenings fail to identify many children who will develop CMV-related sensorineural hearing loss. To appropriately target monitoring and interventions, said Shannon A. Ross, MD, FAAP, in her presentation “Diagnosis and Treatment of Neonates With Congenital CMV,” identifying congenitally infected infants early-using rapid, reliable and relatively inexpensive techniques-is crucial.

Whereas traditional culture techniques required 2 to 3 weeks to provide reliable results, the shell vial assay (a modified viral culture that involves centrifugation of a urine specimen onto a fibroblast monolayer) does so in 2 to 3 days, with comparable sensitivity and specificity. As such, rapid-culture techniques represent the gold standard for diagnosing congenital CMV infection.

The dried blood spots (DBS) collected from all US-born infants for metabolic screening may provide a ready sample source for CMV testing. Potential advantages of using PCR for this purpose include the fact that PCR requires no tissue culture facilities and is amenable to automation. However, a multicenter study involving more than 20,000 newborns showed that DBS PCR detected less than 40% of congenitally infected infants.¹

Previous studies-mostly small and lacking comparisons to standard rapid culture methods-have shown promise in analyzing saliva samples with PCR-based methods. More recently, an ongoing multicenter newborn screening study showed that real-time PCR of saliva samples provides 100% sensitivity and 99.9% specificity.² Because the PCR assay used in this study eliminates the need to extract DNA from saliva, this method could prove useful for screening large numbers of newborns more efficiently than current methods.

Additionally, a recent trial showed that real-time PCR analysis of saliva and urine performs as well as rapid culture techniques.³

Shannon A. Ross, MD, FAAP, is associate professor, pediatrics infectious disease, University of Alabama at Birmingham.

REFERENCES

1. Boppana S, Ross SA, Novak Z, et al; National Institute on Deafness and Other Communication Disorders CMV and Hearing Multicenter Screening (CHIMES) Study. Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection. JAMA. 2010;303(14):1375-1382.

2. Boppana S, Ross SA, Shimamura M; National Institute on Deafness and Other Communication Disorders CHIMES Study. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N Engl J Med. 2011;364(22):2111-2118.

3. Ross SA, Ahmed A, Palmer AL; National Institute on Deafness and Other Communication Disorders CHIMES Study. Detection of congenital cytomegalovirus infection by real-time polymerase chain reaction analysis of saliva or urine specimens. J Infect Dis. 2014;210(9):1415-1418.

Cytomegalovirus is the most common infectious cause of fetal abnormalities. Even though it's not very common, it's devastating when it happens. Pregnant women or women considering pregnancy should be screened for CMV because if they acquire it during pregnancy, it can cause everything from fetal abnormalities to fetal death as well as pulmonary, gastrointestinal, cardiac, neurological, and other malformations. Thus, CMV should be feared more than herpes, Ebola, or anything else because it's by far the most frequent cause of fetal abnormalities in this country.

In dermatology, we see CMV in the neonatal nursery, where we may be consulted regarding the manifestations of CMV on the skin-the so-called blueberry muffin baby. This is not a technical term, but it's been around for probably a century. That's where a congenital infection causes growth of blood vessels that appear blue under the skin. Notably, CMV is by far the most common cause of this syndrome.

Like most infectious diseases, it's always better to prevent CMV than treat it. By the time a child is born with fetal abnormalities, giving an antiviral drug might prevent progression of those problems, but not necessarily reverse them.

Blood testing is the best way to test for susceptibility to the virus. If a woman has immunoglobulin G antibodies, she's already been exposed to the virus and has immunity, and therefore won't pass the virus through the placenta. However, if she has no antibodies, and if her male partner is CMV-positive, then she is at risk. If she develops immunoglobulin M antibodies during the pregnancy, that reflects a recent exposure. Such patients need very frequent monitoring to make sure that any signs of fetal distress can be handled appropriately.

To test for the actual virus, PCR screening is not universally available, but it's very sensitive and specific, and the results can be obtained within hours, not days. Because of the devastating nature of CMV in pregnancy or the newborn, PCR will become more widely used. We standardly use it to detect HIV, herpes simplex viruses 1 and 2, papillomaviruses, and, increasingly, hepatitis A, B, and C. The PCR assay is also being used increasingly to detect bacteria that are difficult to culture, such as Mycobacterium tuberculosis.

With PCR becoming available in almost any large laboratory, it's just a question of adding the appropriate "primers" to find the virus, or any infectious agent. Although we don't standardly test for every infectious agent, there's really no infectious agent that couldn't be found with PCR.

Stephen K. Tyring, MD, PhD, MBA, FAAD, is clinical professor of dermatology, microbiology/molecular genetics, and internal medicine at the University of Texas Health Science Center, Houston, and medical director of the Center for Clinical Studies, Houston.

Mr Jesitus is a medical writer based in Colorado. He has nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.