Enhancing Awareness and Prevention of Cytomegalovirus (CMV) During CMV Awareness Month

June is Cytomegalovirus (CMV) Awareness Month,¹ a crucial period for infection preventionists (IPs) to enhance their knowledge and strategies regarding this pervasive viral infection, one of the most common congenital infections worldwide. Yet, it often flies under the radar, even within the health care community. In the United States, nearly 1 in 3 children is already infected with CMV by age 5, and over half of adults have been infected with CMV by age 40.¹ This gap in awareness can result in missed opportunities for early diagnosis and intervention, particularly among high-risk groups such as pregnant women, newborns, and immunocompromised individuals.

During CMV Awareness Month, IPs are called to focus on the transmission pathways, clinical manifestations, and effective prevention measures for CMV. By increasing understanding and vigilance, IPs can play a pivotal role in reducing the spread of CMV, implementing robust infection control practices, and ultimately improving health outcomes for those impacted by this significant pathogen.

In healthy individuals, CMV infection can sometimes manifest as mild illnesses characterized by fever, sore throat, fatigue, and swollen glands. In some instances, CMV can cause more significant conditions like mononucleosis or hepatitis, which involves liver inflammation.^1,2

“Human cytomegalovirus infections commonly are associated with the salivary glands. CMV infection may be asymptomatic in healthy people, but it can be life-threatening in an immunocompromised patient. Congenital cytomegalovirus infection can cause morbidity and even death. After infection, CMV often remains latent, but it can reactivate at any time. Eventually, it causes mucoepidermoid carcinoma, and it may be responsible for prostate cancer,” wrote Mohit Gupta Cleveland Clinic Foundation; Mahmoud Shorman in their book Cytomegalovirus.²

In immunocompromised patients, CMV infection can affect various organs, including the eyes, lungs, liver, esophagus, stomach, and intestines, resulting in severe symptoms.

Babies born with CMV can experience a range of health issues affecting the brain, liver, spleen, lungs, and growth. The most prevalent long-term health complication for infants with CMV infection is hearing loss, which can be identified shortly after birth or develop later in childhood.¹

Despite the possibility of lifelong challenges from the disease, “Congenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to neurodevelopmental disabilities. Universal newborn infant screening of cCMV has been increasingly advocated. In the absence of a high-throughput screening test which can identify all infected newborn infants, the development of an accurate and efficient testing strategy has remained an ongoing challenge, “according to the CDC.¹

While a vaccine³ is being developed, much more, such as better tests, must be done to protect people of all ages against CMV. “CMV testing is very significant for healthcare personnel due to its communicability. CMV testing can help determine whether a patient should be placed in a monitoring situation. Additionally, it is crucial for making preoperative or postoperative diagnoses. It is particularly important for environmental services (EVS) personnel in the cleaning and decontamination process, as they must ensure the use of a virucidal agent to eliminate the respective pathogens in the environment as they encounter bodily fluids during daily cleanings of occupied and unoccupied patient rooms,” said Tommy Davis, PhD, ACHE, CEPHP, BLS, CSSWB, the CEO, president, and principal officer at High Distinction Consulting, LLC. He is also an Infection Control Today^® (ICT^®)2023 Editorial Advisory Board member.

ICT spoke with Dana Wolf, MD, the Ted and Frances Chanock Chair in Virology and the Head of the Clinical Virology Unit Department of Clinical Microbiology & Infectious Diseases at Hadassah University Hospital in Jerusalem, Israel, to learn more about CMV and the tests currently available.

ICT: Why is there so little awareness of CMV, especially when people know about rare viruses like Zika?

Dana Wolf, MD: I believe it is mostly because CMV infection is often invisible, unlike some other viral infections presenting with acute symptoms (such as polio or measles) and is not routinely screened; it is often asymptomatic and goes unnoticed in pregnant women (if they are not routinely screened by antibody tests) and in congenitally infected children (if they are not routinely universally screened).

As we stressed in our attached paper,⁴ the majority (~90%) of neonates born with congenital CMV infection are initially asymptomatic at birth. The second potential reason why public awareness is so low is because congenital CMV is not a “terrifying” emerging pandemic like Zika or COVID-19. But it is still a silent, ongoing worldwide epidemic.

ICT: Why are most people not harmed by it, while some—like newborns and the immunocompromised—are?

DW: Most of the human population lives with CMV. After the primary (first) infection, the virus remains in our body for the rest of our lives in a state of latency, or dormancy, with occasional reactivations and reinfections, which are primarily asymptomatic and well-controlled by the immune system in healthy individuals. There is an ongoing balance maintained between the virus and our immune system.

In healthy individuals, antibodies and cell-mediated immunity effectively control the virus (keeping it in the latent state). In immunocompromised patients (ie, transplant patients or hemato-oncology patients with suppressed cellular immunity) or immunologically immature individuals (fetuses), the virus replication, spread, and associated tissue damage are uncontrolled due to the lack of effective immune responses.

ICT: Which test is more accurate—the pooled saliva test or the blood spot?

DW: The pooled saliva test is more accurate. It is very sensitive (99.5% sensitivity compared to individual-patient saliva tests, which are the most sensitive tests), whereas the blood spot test has limited sensitivity—approximately 75% sensitivity (at the most) compared to individual-patient saliva tests.

ICT: Is it possible to say whether the pooled saliva test or the blood spot is easier to implement, or are there too many variables to make that statement? Which one is easier to implement?

DW: It may be dependent on the specific setting of the medical center or on the specific state’s/country’s routinely implemented diagnostic system. For example, the states in the US/Canada that have implemented the blood spot tests have chosen this approach because it relies on routinely collected dried blood spots (sparing the need to collect de-novo saliva and urine samples). However, processing the blood spots for CMV detection has remained technically challenging (and, as indicated above, associated with compromised sensitivity). Overall, from our perspective and experience in both tests, I believe the pooled saliva test would be easier to implement, as detailed in our published work.

ICT: Can you give me more details about how the pooled saliva method would be implemented? What makes it a good fit for most medium and large hospitals?

DW: It is detailed in the [our] paper (Methods) and in Figure 1b of the paper.⁵

[Quoted from the study. “This prospective, population-based cohort study was conducted at the two hospitals of Hadassah Medical Center (including seven newborn nurseries, intermediate care neonatal units, and neonatal intensive care units) from April 2022 through April 2023. After prior design and validation of pooled saliva RT–PCR testing for the detection of cCMV,… and a 3-month pilot implementation period…all newborn infants whose parents provided written informed consent were screened for cCMV using pooled saliva RT–PCR testing as part of a routinely implemented newborn screening policy. Infants with positive saliva tests (identified by the initial pooled testing with subsequent retesting of all samples in the positive pool; see below) had confirmatory urine testing (Fig. 1). Urine samples were tested for CMV using RT–PCR. All saliva specimens and most urine specimens were collected during the first 1–3 days of life. All specimens were collected no later than 10 days after birth. The study was approved by the Hadassah Medical Center institutional review board (no. 0272-22-HMO).”]⁴

ICT: Can you give me the CMV vaccine’s latest “state of play”? What are the remaining challenges, and how far are you and your colleagues from success?

DW: In 2024, there are multiple CMV vaccine candidates and platforms (ie, mRNA vaccines, live attenuated or replication-defective virus vaccines, and more). Two have reached phase 2 (MSD replication-defective vaccine) and phase 3 (Moderna mRNA) clinical trials. There are still significant knowledge gaps regarding (and need to better understand) our immune correlates of protection and natural immunity.

To sum up her concern about CMV, Wolf said, “It is surprising and frustrating how little public awareness there is about CMV despite its immense impact on women’s and children’s health. In this regard, please also note the last sentence of our paper: “Beyond the direct clinical implications toward early diagnosis, monitoring band treatment of cCMV, data derived from the implemented universal screening will serve to define the burden, risk factors and clinical outcomes of cCMV over time and to increase awareness of this underrecognized congenital infection.“4

About cytomegalovirus. Cytomegalovirus (CMV) and Congenital CMV Infection. CDC. May 30, 2024. Accessed June 28, 2024. https://www.cdc.gov/cytomegalovirus/about/index.html#:~:text=In%202011%2C%20Congress%20passed%20a,infectious%20cause%20of%20birth%20defects

Gupta M, Shorman, M. Cytomegalovirus. In: StatPearls. StatPearls Publishing; 2023. Accessed June 28, 2024. https://www.ncbi.nlm.nih.gov/books/NBK459185/