**4. Diagnosis**

The diagnosis of congenital CMV infections should be considered when it is detected in the newborns with signs and symptoms consistent with congenital CMV disease or with abnormal neuroimaging consistent with CMV or newborns who have documented sensorineural hearing loss (SNHL). Newborns who are possessed by a mother with seroconversion positivity or with positive CMV immunoglobulin G (IgG) and CMV immunoglobulin M (IgM) antibody or with mononucleosis-like illness during pregnancy should also be evaluated for congenital CMV infections. Infants with an abnormal T-cell receptor in newborn screening should be suspected for congenital CMV infections. The reliable diagnosis of congenital CMV infections must be detected through sources of virus and viral nucleic acids from urine, saliva, and blood within the first 3 weeks of life in infants. The newborns with suspected congenital CMV infection should be analyzed by viral culture, modified culture (also called rapid culture or shell vial assay), and polymerase chain reaction (PCR) for diagnosis. Detection of CMV by PCR in blood or plasma samples is more accurate than other diagnostic tests [15]. Due to the fact that the polymerase chain reaction provides quantitative results, urine and saliva that include high levels of CMV DNA are generally evaluated in newborns suspected with CMV.

Primary infection of CMV in nonimmunocompromised individuals requires evidence of an IgM reactivity for CMV in blood. It can persist for months depending on the sensitivity of the particular assay. Due to the fact that the infected

**88**

**Table 2.**

cephalitis [7].

Early postnatal CMV infection

*Human Herpesvirus Infection - Biological Features, Transmission, Symptoms, Diagnosis...*

premature infants or infants born to nonimmune women.

have the risk of mortality as high as 30% caused by a fulminant course. Death is usually caused by viral-associated hemophagocytic syndrome or severe end-organ disease of the liver, lungs, bone marrow, or central nervous system. Even if the infants with a life-threatening disease associated with congenital CMV are able to live, neurological sequelae might persist for a lifetime (e.g., microcephaly, intellectual disability, cerebral palsy, and hearing disorders) [10, 11]. Pneumonitis, signs of viral sepsis, thrombocytopenia, and coinfections are more likely to have existed in premature infants than term neonates [7]. Additionally, preterm infants can also present with a classical triad of apneas, bradycardia, and gray pallor describing CMV sepsis-like syndrome [12]. The cases with perinatal infections which are generally not associated with any clinical manifestations can be acquired during birth or ingestion of CMV-containing breast milk. Disseminated infections associated with end-organ disease and death might be seen in extremely

The vast majority of healthy children and adolescents infected with CMV infections (acquired CMV infection) are most often asymptomatic (**Tables 2** and **3**). However, the remaining patients (approximately 10%) could present with several mild or moderate symptoms. A clinical entity named mononucleosis-like syndrome with no heterophile antibody titers or positive monospot tests is characterized by fever, fatigue, pharyngitis, adenopathy (especially cervical adenopathy), and hepatitis. A headache, abdominal pain with diarrhea, arthralgias, and rash can also be observed in mononucleosis-like syndrome in acquired CMV infection. Laboratory findings mimic to EBV-related mononucleosis syndrome like lymphocytosis or lymphopenia with thrombocytopenia and elevated transaminases [13]. Unusual manifestations or complications of acquired CMV infections in healthy individuals consist of pneumonitis, myopericarditis, hemolytic anemia, viral hemophagocytic syndrome, granulomatous hepatitis, Guillain-Barré syndrome, and meningoen-

When a reactivation of the endogenous virus and infection from the transplanted organ or from blood product transfusion take place in immunocompromised children and adolescents, serious CMV disease can be observed which is linked to the underlying disease process responsible for the immunosuppression (**Table 4**). Non-specific symptoms such as fever, malaise, and leukopenia might be seen in all types of patients. Patients with renal transplant are at graft loss; the liver recipients are most likely to be associated with hepatitis and colitis. Early myocarditis followed by late atherosclerosis is seen in heart transplant recipients. Recipients

**Clinical manifestations Treatment Outcome**

Most term infants and asymptomatic preterm infants do not require antiviral treatment Ganciclovir or valganciclovir for severe symptomatic infections in premature infants

Term infants: no permanent sequelae. Premature and VLBW infants: mortality rate with symptomatic infection is 5–10% There does not appear to be increased risk of hearing loss, cerebral palsy, or other neurodevelopmental disabilities; however, long-term outcomes are not clearly understood

**Term infants: Most infants are** 

Fever, hepatosplenomegaly, mild pneumonitis, abnormal blood counts, abnormal liver function

**Premature and VLBW infants: Infection can be severe and** 

*Clinical manifestations, treatment, and outcome of early-postnatal CMV infection.*

**asymptomatic**

**life-threatening** Sepsis-like syndrome, hepatosplenomegaly, pneumonitis, hepatitis, NEC, abnormal blood counts

tests

individuals can intermittently shed virus, body fluids such as saliva or urine do not provide the diagnosis of CMV infection. Polymerase chain reaction-based methods are also utilized for diagnosis of urine, saliva, and blood and in tissue specimens obtained at biopsy. A combination with immunofluorescence detection of CMV-encoded and conventional culture of CMV using human dermal fibroblasts remains standard in many institutions. Characteristic nuclear (and cytoplasmic) inclusions (owl's eye inclusions) can be detected by histologic stains in tissue specimens.

#### **5. Treatment**

Treatment is recommended to be initiated to the infants who have a symptomatic infection or primary immunodeficiency or asymptomatic infection with an isolated hearing loss for congenital CMV infection within the first month of life. At the first line, ganciclovir through intravenous route and its orally available prodrug, valganciclovir, for treatment of congenital CMV disease are indicated. Randomized clinical trials of the Collaborative Antiviral Study Group suggested that 6 weeks of ganciclovir treatment could confine hearing loss and improve developmental outcome in infants infected symptomatically. In addition, infants with severe perinatal CMV infection caused by breast milk could be treated with ganciclovir [7, 16].

In the normal host and early-postnatal infections in term asymptomatic infants, treatment of acquired CMV infections is not recommended. However, treatment must be implemented in preterm or very-low-birth-weight (VLBW) infants with severe infection.

Immunocompromised hosts are recommended with antiviral therapy with ganciclovir in children with active CMV disease. Even if there are no signs or symptoms of end-organ disease in immunocompromised children, it is also suggested to apply the antiviral therapy due to CMV viremia (e.g., positive or rising quantitative PCR). Treatment of CMV disease in immunocompromised pediatric patients consists of ganciclovir and oral valganciclovir similar to that in adults. Treatment is usually given in the form of intravenous ganciclovir or oral valganciclovir for 4–6 weeks on average [17]. Patients are recommended to seek for antiviral treatment monitorization with white blood cell count, AST, and ALT regularly. In some cases, when the antiviral therapy cannot improve clinical or virologic response within several weeks of treatment with ganciclovir or valganciclovir, foscarnet might be integrated to the treatment. Another specific anti-CMV treatment is cidofovir that may be used in children with careful monitoring of renal function and metabolic condition when antiviral resistance occurs.

#### **6. Prevention**

#### **6.1 Passive immunoprophylaxis**

Intrauterine disease could be prevented from infection through passive transfer of anti-CMV antibodies. However, this transfer is not successful in allograft recipients. A neonatal transfer is prevented from CMV infection using CMV-seronegative or leukocyte-reduced blood for extremely preterm infants. Freezing/thawing or pasteurization eliminates the risk of transfusion-related CMV infection in breast milk contaminated with CMV, however; it might not be complete. The passive transfer of anti-CMV antibodies is recommended to limit transmission and disease in pregnant women with primary CMV infection.

**91**

**Author details**

Unit, Ege University, Izmir, Turkey

provided the original work is properly cited.

\*Address all correspondence to: sule.gokce@ege.edu.tr

Şule Gökçe

*Human Cytomegalovirus Infection: Biological Features, Transmission, Symptoms, Diagnosis...*

Cytomegalovirus is a common agent that can be seen all over the world. Although CMV is generally asymptomatic in healthy individuals, it can lead to severe infection in individuals with immune deficiency. During pregnancy, CMV also cause significant disabilities in babies whose mother has CMV. After its primary infection, the virus remains as an inactive form in the host throughout the life. Recurrent CMV infections may occur with the reactivation of the silent virus. Due to the fact that congenital CMV infections are asymptomatic, a hearing test is

Ege University Faculty of Medicine, Department of Pediatrics, General Pediatrics

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

A number of different vaccine platforms that will be available for prevention of CMV disease in newborns and immunocompromised patients have been evaluated

*DOI: http://dx.doi.org/10.5772/intechopen.81833*

in clinical trials. However, none are licensed.

strongly recommended to the newborns.

**6.2 Active immunoprophylaxis**

**7. Final considerations**

*Human Cytomegalovirus Infection: Biological Features, Transmission, Symptoms, Diagnosis... DOI: http://dx.doi.org/10.5772/intechopen.81833*
