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Overview of cytomegalovirus infections in children

Overview of cytomegalovirus infections in children
Literature review current through: Jan 2024.
This topic last updated: Feb 16, 2023.

INTRODUCTION — Cytomegalovirus (CMV) is a ubiquitous virus that commonly infects people of all ages throughout the world. In children, the spectrum of disease caused by CMV infection ranges from asymptomatic or mild disease in immunologically normal hosts to severe and potentially life-threatening disease in newborns and immunocompromised children (table 1) [1].

Postnatally acquired CMV infection in infants, children, and adolescents will be reviewed here. Congenital CMV infection is discussed separately. (See "Congenital cytomegalovirus infection: Clinical features and diagnosis" and "Congenital cytomegalovirus infection: Management and outcome".)

VIROLOGY — CMV is a member of the Herpesvirus family, along with Epstein-Barr virus; herpes simplex viruses 1 and 2; varicella-zoster virus; and human herpesviruses 6, 7, and 8. These viruses all share properties, including a genome of double-stranded linear DNA, a virus capsid of icosahedral symmetry, and a viral envelope [2]. They also share the biologic properties of latency and reactivation, which cause recurrent infections in the host.

CMV replicates slowly, often taking as long as 24 hours to produce virus progeny in infected cells and several days to weeks to produce visible cytopathic effect in laboratory cell lines (picture 1). No distinct serotypes of CMV exist; however, strain differences can be detected by molecular analysis of DNA, providing a classification of genotypes [3].

MODES OF TRANSMISSION — CMV can be transmitted by:

In utero infection – Vertical transmission from mother to fetus during pregnancy is discussed separately. (See "Cytomegalovirus infection in pregnancy".)

Perinatal infection – Transmission can occur from contact with maternal cervicovaginal secretions during delivery. (See "Cytomegalovirus infection in pregnancy".)

Breast milk – CMV can be acquired postnatally from breast milk. As discussed below, preterm infants appear to be at greatest risk of having symptomatic infection from early postnatal CMV infection through breast milk. (See 'Early postnatal infection' below.)

Close contact – CMV can be transmitted among family members; a young child most frequently is the index case. CMV infection during pregnancy most often occurs from maternal exposure to saliva or urine from an infected toddler in the household, especially if the child attends a group childcare setting on a regular basis [4]. Transmission can occur between siblings, from child to parent, and between parents.

Sexual transmission – The sexual transmission of CMV also is well documented with shedding of the virus in cervicovaginal secretions and semen. CMV antibody is associated with other indices of sexual activity, such as a history of sexually transmitted disease, and CMV primary infection has been observed in young women with a recent first sexual experience [5].

Blood transfusion and organ transplantation – Blood products and organ transplantation are sources of CMV infection in hospitals. Post-perfusion syndrome caused by CMV can be seen in newborns, especially preterm infants, as well as in infants, older children, and adolescents. Immunosuppressed patients, particularly those with HIV infection, cancer, or receipt of a solid organ or bone marrow transplant, are commonly infected with CMV and are at risk for developing serious disease [1,6].

Nosocomial transmission of CMV from person to person has not been documented. Universal precautions appear adequate to prevent transmission of CMV within hospitals, and isolation of patients known to be CMV-infected is not routinely recommended [6]. Pregnant health care workers and those contemplating pregnancy are not restricted from caring for CMV-infected patients and should follow universal precautions.

EPIDEMIOLOGY — Infection with CMV occurs commonly; seroepidemiologic studies have shown the prevalence of antibody to CMV is influenced by age, geography, cultural and socioeconomic status, and child-rearing practices. In developing countries, most children are infected by three years of age, whereas in developed countries, such as the United States or the United Kingdom, infection occurs throughout childhood and adolescence, with as many as 60 to 80 percent of the population infected with CMV by adulthood [1].

Congenital infection — The epidemiology of congenital CMV infection and CMV infection in pregnancy are discussed in separate topic reviews. (See "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Epidemiology' and "Cytomegalovirus infection in pregnancy".)

Early postnatal infection — Perinatal and early postnatal infection can arise from any of the following:

Via contact with maternal cervicovaginal secretions during delivery (see "Cytomegalovirus infection in pregnancy")

From breast milk ingestion after delivery – This is a common mode of CMV transmission from mother to infant. Preterm infants appear to be at greatest risk [7-13]

From blood transfusions – Transfusion-related postnatal CMV transmission can be prevented by using CMV-seronegative and leukocyte-reduced blood products [11] (see 'Prevention' below)

The risk of symptomatic and severe neonatal CMV infection is greatest in the following settings:

Preterm infants – Low birth weight and early transmission of virus in the postnatal period are risk factors for acquiring symptomatic disease [9]. CMV infection in very low birth weight (VLBW; birth weight <1500 grams) infants appears to result from reactivation of the virus in the mother. Seropositive mothers who are breastfeeding have a high rate of CMV reactivation (96 percent) [8]. The rate of transmission to the newborn depends upon whether the infant is fed untreated or frozen/thawed breast milk (higher transmission rates occur with untreated breast milk). This was demonstrated in a meta-analysis of 13 studies including 480 VLBW infants, among whom the rate of CMV transmission from breast milk was 15 percent and the rate of symptomatic CMV infection was 7 percent [7]. The rate of transmission was higher in studies of infants fed untreated breast milk compared with studies of infants fed frozen/thawed breast milk (18 versus 10 percent).

In a multicenter, prospective study of 539 VLBW infants, the cumulative incidence of postnatal CMV infection at 12 weeks postnatal age was 7 percent [11]. Transmission occurred from CMV-positive breast milk in nearly all (96 percent) of the cases in this cohort, and there were no transfusion-related infections. Five of the 29 (17 percent) CMV-infected infants developed symptomatic CMV disease, and three infants (10 percent) died.

Primary immunodeficiency – Infants with a primary immune disorder of cellular function (eg, severe combined immune deficiency, natural killer [NK] cell disorders; acquired immune disorders such as HIV) may also manifest severe or fatal postnatally acquired CMV infection [14,15]. (See "Severe combined immunodeficiency (SCID): An overview" and "NK cell deficiency syndromes: Clinical manifestations and diagnosis", section on 'Introduction'.)

Out-of-home childcare — Children not congenitally or perinatally infected with CMV may acquire the virus during the toddler years or preschool years, especially if they are in contact with other children in a group childcare setting. The prevalence of active CMV shedding in the saliva and urine in children in out-of-home childcare in the United States ranges from 10 to >80 percent [16]. This high prevalence, coupled with the active and often less-than-hygienic daily practices of toddlers, frequently results in horizontal transmission of the virus to both children and adult daycare center workers [17]. Toddlers who are actively shedding CMV may also transmit the virus to their mothers and family members.

Adolescence — Adolescence is another period of rapid acquisition of CMV. CMV infection can be acquired through kissing and sexual activity. Congenital CMV infection can occur in infants born to teenage mothers [18,19]. (See "Cytomegalovirus infection in pregnancy" and "Congenital cytomegalovirus infection: Clinical features and diagnosis".)

CLINICAL MANIFESTATIONS — The clinical manifestations of CMV infection in infants and children depend upon the age and immune status of the patient (table 1).

Congenital infection — Clinical manifestations of congenital CMV infection are summarized in the table and are discussed in greater detail separately (table 1). (See "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Clinical manifestations'.)

Early postnatal infection — Most infants who are infected perinatally or postnatally are asymptomatic. However, preterm infants and those with primary immune disorders are at risk for severe symptomatic infection.

Term infants – In term infants, symptoms, when present, are usually transient and include fever, gastrointestinal symptoms (eg, vomiting, diarrhea, abdominal distension), hepatosplenomegaly, hepatitis, mild pneumonitis, and abnormalities of blood counts [20]. Most patients with liver involvement have improvement in liver function tests by two to three months [20]. However, some affected patients may have persistent cholestasis.

Preterm infants – Preterm infants, especially very low birth weight (VLBW; birth weight <1500 grams) infants, are vulnerable to severe CMV disease. Infection may become apparent as early as three weeks and as late as three to six months of age. Early transmission of the virus is a risk factor for symptomatic disease [9].

In preterm infants, CMV infection may be serious and even fatal if not diagnosed and treated [10]. A sepsis-like syndrome occurs in approximately 15 percent of infected VLBW infants and is associated with hepatosplenomegaly, hepatitis, pneumonitis, and abnormalities of blood counts (including lymphopenia, neutropenia, and/or thrombocytopenia) [7,21]. CMV infection in preterm neonates has also been associated with necrotizing enterocolitis and increased risk of severe retinopathy of prematurity [13,22]. (See "Neonatal necrotizing enterocolitis: Clinical features and diagnosis" and "Retinopathy of prematurity (ROP): Risk factors, classification, and screening".)

It is unclear if there are long-term consequences of early postnatal CMV infection in preterm infants. Based on data from follow-up studies comparing CMV-infected infants with noninfected infants matched for gestational age and birth weight, there appear to be no differences in growth, hearing, or cerebral palsy [23-26]. Studies are conflicting as to whether early postnatal CMV infection adversely impacts long-term neurodevelopmental outcomes [23-27] or increases the risk of bronchopulmonary dysplasia [28,29]; if there is an effect, it appears to be small.

In a study of 356 preterm infants who were prospectively screened for postnatal CMV infection, infected infants (n = 49) and uninfected infants (n = 307) had similar scores on neurodevelopmental tests performed at 24 to 30 months corrected age [26]. Among children in this cohort who underwent repeat testing at approximately six years of age, mean scores were in the normal range for infected and uninfected children, but infected children had slightly lower verbal intelligence quotient (IQ) scores (96±16 versus 103±15). After adjusting for maternal education status and presence of respiratory distress syndrome, postnatal CMV infection was not independently associated with risk of low verbal IQ. No children with postnatally acquired CMV developed sensorineural hearing loss. In another study of 42 adolescents born very preterm, those with early postnatal CMV infection (n = 19) scored lower than those without (n = 23) for overall IQ (93±15 versus 103±14), though mean scores were in the normal range in both groups [27].

Infants with primary immune disorders – Infants with severe combined immune disorder or other primary immune disorders of T cell or natural killer (NK) cell function also may experience severe, even fatal, symptoms associated with postnatally acquired CMV infection [14,15]. (See "Severe combined immunodeficiency (SCID): An overview" and "NK cell deficiency syndromes: Clinical manifestations and diagnosis".)

Immunocompetent children — Acquired CMV infection in healthy children and adolescents is most often asymptomatic. However, approximately 10 percent of acquired CMV infections produce symptoms. CMV can cause a mononucleosis-like syndrome; the most common manifestations are fever, fatigue, pharyngitis, adenopathy (especially cervical adenopathy), and hepatitis [21]. Headache, abdominal pain with diarrhea, arthralgias, and rash also may occur. Laboratory abnormalities can include abnormal lymphocyte count (lymphocytosis or lymphopenia), neutropenia, thrombocytopenia, and elevated transaminases. Unlike mononucleosis caused by Ebstein-Barr virus, the heterophile antibody (Monospot) test is negative in CMV-associated mononucleosis-like illness. (See "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults", section on 'CMV mononucleosis'.)

Unusual manifestations or complications of acquired CMV infections in healthy individuals include rare reports of pneumonitis, myopericarditis, hemolytic anemia, viral hemophagocytic syndrome, granulomatous hepatitis, Guillain-Barré syndrome, and meningoencephalitis [1].

Immunocompromised hosts — Immunocompromised children and adolescents are at risk for acquiring serious CMV disease. Infection may result from reactivation of endogenous virus, infection from the transplanted organ, or from blood product transfusion. An imbalance of increased viral activation and lack of immune surveillance commonly produces CMV disease in these patients.

Patient populations at risk for CMV disease in this setting include [1,30]:

Transplant recipients, especially if any of the following apply:

Donor is CMV-seropositive and recipient is CMV-seronegative

Donor has CMV viremia or high CMV viral load

Recipient had high pretransplant CMV viral load

Recipient has evidence of decreased T cell function (eg, from the immunosuppressive regimen)

Patients with primary or acquired immune disorders that affect T lymphocytes or NK cells

Patients with hematologic malignancies (eg, acute lymphocytic and acute myeloid leukemias)

Patients receiving immunosuppressive therapy for Crohn's disease or ulcerative colitis

The consequences of acquired CMV infections in immunocompromised hosts include significant morbidity and increased risk of mortality.

The most common manifestations of CMV infection in immunocompromised children include fever, malaise, and leukopenia. Other signs and symptoms include colitis, retinitis, pneumonitis, and meningoencephalitis. Manifestations in transplant recipients may include (see "Infection in the solid organ transplant recipient", section on 'CMV and EBV'):

Hematopoietic stem cell transplant recipients – CMV typically causes fever leukopenia syndrome or pneumonitis in this setting. (See "Overview of infections following hematopoietic cell transplantation".)

Renal transplant recipients – CMV infection in renal transplant recipients can be associated with graft loss. (See "Clinical manifestations, diagnosis, and management of cytomegalovirus disease in kidney transplant patients".)

Liver transplant recipients – CMV may cause hepatitis and colitis in liver transplant recipients. (See "Infectious complications in liver transplantation", section on 'Cytomegalovirus'.)

Heart transplant recipients – CMV can cause myocarditis in heart transplant recipients, and it can contribute to allograft vasculopathy. (See "Heart transplantation in adults: Cardiac allograft vasculopathy pathogenesis and risk factors", section on 'Cytomegalovirus infection'.)

Lung transplant recipients – CMV typically causes pneumonitis in lung transplant recipients. (See "Clinical manifestations, diagnosis, and treatment of cytomegalovirus infection in lung transplant recipients".)

Children with HIV and CMV coinfection may experience retinitis, colitis, pneumonitis, and encephalitis/encephalopathy; a rapid progression of HIV infection frequently occurs during infancy in these patients if they are untreated [31]. (See "Pediatric HIV infection: Classification, clinical manifestations, and outcome", section on 'Cytomegalovirus disease'.)

LABORATORY DIAGNOSIS — The laboratory diagnosis of CMV infection depends upon the specific setting in which CMV disease is under consideration.

Congenital infection — Laboratory tests for diagnosis of congenital CMV infection are summarized in the table and are discussed in detail separately (table 2). (See "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Diagnostic approach'.)

Early postnatal infection — The diagnosis of perinatal/postnatal CMV infection is confirmed with positive urine CMV testing (with culture or polymerase chain reaction [PCR]) performed after the first three weeks of life, in conjunction with negative testing performed within the first three weeks (thereby excluding congenital CMV infection).

Urine is preferred over saliva for detection of postnatal CMV infection because it is more sensitive than saliva [32]. In addition, false positives may occur due to contamination of the saliva sample with retained breast milk in the mouth of the newborn if collected within an hour of breast milk feeding. If a CMV urine or saliva detection test was not performed at birth, retrospective analysis can be performed using a newborn dried blood spot obtained for the purposes of universal newborn screening. (See "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Birth to three weeks'.)

At the author's institution, urine CMV testing is performed in preterm infants who present with clinical sepsis if the work-up for bacterial, fungal, and other viral causes (eg, herpes simplex virus) is negative in patients with unexplained thrombocytopenia. (See "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Evaluation'.)

Neonates with severe CMV infection, such as viral sepsis, necrotizing enterocolitis, hepatitis, pneumonitis, or thrombocytopenia are typically viremic, and CMV virus can be detected by CMV quantitative PCR in whole blood or plasma [22].

Serology for CMV immunoglobulin G (IgG) antibody determination is not helpful in diagnosing early postnatal infection, because a positive result may only reflect passive transfer of maternal antibody to the infant.

Children and adolescents — Diagnosis of primary CMV infection in immunocompetent hosts is usually made using serologic studies. The detection of CMV-specific immunoglobulin M (IgM) and/or a fourfold rise in CMV-specific IgG establish a presumptive diagnosis in the appropriate clinical setting. (See "Approach to the diagnosis of cytomegalovirus infection", section on 'Immunocompetent hosts'.)

Immunocompromised hosts — Laboratory confirmation that a CMV infection is causing disease in an immunocompromised host is difficult and frequently requires demonstration of CMV in the end organ involved, in combination with a positive or rising quantitative PCR for CMV in the blood. Serology and urine or saliva cultures rarely are helpful in this population because most patients are seropositive and shed virus and the presence of these positive tests is not specific for the development of disease. (See "Approach to the diagnosis of cytomegalovirus infection", section on 'Immunocompromised hosts'.)

At some centers, transplant recipients are monitored by routine (eg, weekly) laboratory viral surveillance using quantitative whole blood or plasma CMV PCR [33,34]. If the PCR is positive or rising, antiviral therapy is initiated even if overt disease has not yet developed. This strategy, referred to as "preemptive" therapy, is discussed in greater detail separately. (See "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'CMV prevention' and "Prevention of cytomegalovirus disease in kidney transplant recipients", section on 'Preemptive therapy (low risk)'.)

TREATMENT

Congenital infection — Treatment of congenital CMV infection is discussed separately. (See "Congenital cytomegalovirus infection: Management and outcome", section on 'Antiviral treatment'.)

Early postnatal infection — Most early postnatal infections in term infants are asymptomatic and do not require treatment; however, treatment may be warranted in preterm or very low birth weight (VLBW) infants with severe infection. We treat preterm or VLBW infants who have serious CMV disease with antiviral therapy (ganciclovir or valganciclovir, depending on whether or not the infant is able to take oral medication). Although clinical trial data are lacking, case series of VLBW infants with serious life-threatening CMV disease have suggested that treatment with antiviral medication is associated with improved survival [11].

Infants who are able to take oral medication can be treated with oral valganciclovir (15 to 16 mg/kg/dose every 12 hours). Infants unable to take oral medication are treated with intravenous (IV) ganciclovir (6 mg/kg/dose every 12 hours) and are transitioned to valganciclovir once they are stable and tolerating oral feeds [21]. The duration of therapy is typically three weeks, though some infants may require longer therapy to resolve end-organ disease and CMV viremia. Consultation with an infectious disease specialist is recommended for these challenging situations.

Monitoring during ganciclovir treatment includes assessment of clinical response and measurement of virologic response with weekly quantitative CMV polymerase chain reaction (PCR). In addition, monitoring for bone marrow and hepatic toxicity includes twice-weekly measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and complete blood count with differential and platelet count.

Immunocompetent children — Antiviral therapy is not usually indicated for CMV infections in immunocompetent children. In these patients, the illness is generally self-limited, with complete recovery over a period of days to weeks. Patients with mononucleosis-like symptoms can generally be managed with supportive care alone (eg, antipyretics, fluids, rest). (See "Infectious mononucleosis", section on 'Symptomatic treatment'.)

Immunocompromised hosts — For immunocompromised children with active CMV disease, we recommend antiviral therapy. We also suggest antiviral therapy for immunocompromised children who lack signs or symptoms of end-organ disease but have evidence of CMV viremia (eg, positive or rising quantitative PCR). Serious infections are treated with IV ganciclovir; mild CMV disease can be treated with oral valganciclovir.

Our recommendations are based on observational studies demonstrating a substantial risk of morbidity and mortality associated with CMV disease in immunocompromised children [1,34-39], as well as indirect evidence from clinical trials in immunocompromised adult patients (eg, solid organ transplant recipients, HIV-infected patients) [40]. (See "Clinical manifestations, diagnosis, and management of cytomegalovirus disease in kidney transplant patients", section on 'Treatment' and "Treatment of AIDS-related cytomegalovirus retinitis", section on 'Systemic therapy'.)

Treatment of CMV disease in immunocompromised pediatric patients is similar to that in adults. Treatment is usually divided into an induction phase and a maintenance phase (also called secondary prophylaxis).

Induction phase – The induction phase consists of ganciclovir 5 mg/kg/dose IV every 12 hours for two to three weeks, depending upon the clinical and virologic response. This is followed by a maintenance phase for high-risk patients (eg, hematopoietic stem cell transplant recipients, patients with HIV infection, or those in whom prolonged immunosuppression is anticipated) [41,42].

Maintenance therapy – Maintenance therapy usually consists of a single daily dose of ganciclovir IV at 5 mg/kg administered every other day or five days a week, skipping the weekend. Oral valganciclovir, at 15 mg/kg/dose every 12 hours, may be used for maintenance therapy in patients who are able to tolerate and absorb oral medication. For transplant recipients with active CMV disease, management may also include reducing immunosuppression. Such decisions should be made by the child's transplant team.

Ganciclovir and valganciclovir both produce a reversible, dose-dependent bone marrow suppression that may manifest as leukopenia, neutropenia, anemia, or thrombocytopenia. The incidence of neutropenia associated with oral valganciclovir may be lower than with IV ganciclovir. In addition, elevation of liver transaminases may be observed but rarely to the level requiring cessation of the medication. Patients receiving ganciclovir or valganciclovir should have complete blood counts, AST, and ALT monitored regularly. Ganciclovir and valganciclovir are excreted renally, and the dose should be adjusted if renal insufficiency or renal failure is present. Local infiltration of the IV ganciclovir solution also may produce local reaction, ulcers, and even scarring.

If clinical or virologic response is not observed within several weeks of treatment with ganciclovir or valganciclovir, then foscarnet may be added to the regimen if renal function allows. Cidofovir is another antiviral with specific anti-CMV activity that may be used in children with careful monitoring of renal function and metabolic condition. Some experts add hyperimmune CMV globulin to the treatment regimen in high-risk patients, but the efficacy of this approach is uncertain. Testing for CMV antiviral resistance may be indicated, especially in immune-compromised patients who fail to respond to treatment with ganciclovir or valganciclovir.

PREVENTION — Preventing CMV infection is challenging because the virus is so ubiquitous and infection occurs so commonly. However, in certain circumstances (eg, pregnancy), trying to prevent CMV infection is desirable. The Centers for Disease Control and Prevention provides additional resources for prevention of CMV infection.

Prevention during pregnancy — Prevention strategies aimed at reducing the risk of acquisition of primary CMV during pregnancy are discussed separately. (See "Cytomegalovirus infection in pregnancy", section on 'Behavioral risk reduction interventions'.)

Prevention of neonatal transmission — Preventive measures to reduce transmission of CMV to newborns include [43]:

Use of CMV-seronegative or leukocyte-reduced blood for extremely preterm infants, which essentially eliminates the risk of transfusion-related CMV infection [11]. (See 'Blood products and organ donors' below.)

Treatment of maternal breast milk by freezing/thawing or pasteurization. Freezing/thawing appears to reduce the risk of transmission but does not eliminate it [9]. Pasteurization may reduce or even prevent transmission of CMV but removes many of the beneficial components. Screening donated breast milk for CMV is important in preventing CMV transmission from this source [44]. Methods to reduce the risk of transmission through human milk are the subject of active research in the attempt to inactivate the virus yet retain the nutritional and immunologic benefits of human milk.

Blood products and organ donors — Blood products given to newborns (especially preterm infants), pregnant individuals, and immunocompromised patients should be from CMV-seronegative donors or leukoreduced. Leukoreduction appears to be comparable with CMV seronegative blood in preventing CMV transmission. Selection of CMV-seronegative donors for organ and hematopoietic stem cell transplantation, when appropriate and available, also will reduce the risk of CMV infection and disease in CMV-negative recipients. (See "Red blood cell transfusion in infants and children: Selection of blood products", section on 'Leukoreduced red blood cells'.)

Prophylaxis — Passive immunoprophylaxis with intravenous immune globulin (IVIG) or CMV hyperimmune globulin may prevent acquisition of serious CMV disease in hematopoietic stem cell and solid organ transplant recipients at high risk for acquiring CMV disease [30,45].

Antiviral prophylaxis with ganciclovir and valganciclovir administered pre-transplant and immediately post-transplant to recipients at high risk for CMV disease also may reduce the risk of serious CMV disease in the early post-transplant period. However, CMV infection and disease may still develop or may be delayed. (See "Prevention of viral infections in hematopoietic cell transplant recipients" and "Prevention of cytomegalovirus disease in kidney transplant recipients".)

Vaccines — A variety of experimental CMV vaccines have been evaluated in clinical trials; however, none are licensed. Experts are hopeful that a CMV vaccine someday will be available for prevention of CMV disease in newborns and immunocompromised patients [46-48]. (See "Cytomegalovirus infection in pregnancy", section on 'Development of a vaccine'.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Cytomegalovirus (The Basics)")

SUMMARY AND RECOMMENDATIONS

Virology and epidemiology – Cytomegalovirus (CMV), a member of the Herpesvirus family, is a ubiquitous virus that infects people of all ages throughout the world. Although most CMV infections are asymptomatic or cause mild disease, the virus can cause serious disease in preterm and very low birth weight (VLBW) newborns and immunocompromised children (table 1). CMV can be transmitted perinatally from maternal breast milk or cervical vaginal secretions, through contact with toddlers in the childcare setting, among family members and close contacts, between partners through intimate or sexual contact, and through transfusion of blood products or organ transplantation. (See 'Epidemiology' above and 'Modes of transmission' above and "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Epidemiology'.)

Acquired CMV in infancy and childhood

Early postnatal infection – Perinatal and early postnatal infection can arise from maternal secretions, ingestion of breast milk, or blood product transfusions. Most early postnatal infections in term infants are asymptomatic or cause a mild illness. In preterm and VLBW infants, CMV can cause a variety of clinical symptoms, most commonly sepsis-like syndrome, pneumonitis, hepatitis, and necrotizing enterocolitis. Preterm infants are at higher risk for developing severe life-threatening disease. (See 'Early postnatal infection' above.)

Immunocompetent children – Acquired CMV infection in healthy children and adolescents is most often asymptomatic. Approximately 10 percent of infected children develop a mononucleosis-like illness, including fever, fatigue, pharyngitis, adenopathy (especially cervical adenopathy), and hepatitis. (See 'Immunocompetent children' above.)

Immunocompromised hosts – Risk factors for CMV infections in immunocompromised hosts include transplantation of an organ from a CMV-seropositive donor into a CMV-seronegative recipient, depressed T cell function, natural killer (NK) cell disorders, and transplantation of a CMV-infected organ. Clinical manifestations of infection in immunocompromised infants, children, and adolescents include fever, leukopenia, and malaise with end-organ involvement (such as kidney graft loss, hepatitis, pneumonitis, or myocarditis). (See 'Immunocompromised hosts' above.)

Diagnosis – Laboratory tools for the diagnosis of CMV include virus isolation in culture, detection of CMV DNA using polymerase chain reaction (PCR), and serology. The approach depends on the setting (see 'Laboratory diagnosis' above):

Congenital CMV infection is discussed separately (see "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Approach to testing')

Perinatal and early postnatal CMV infection is diagnosed by isolation or PCR after the first three weeks of life, in conjunction with negative testing performed within the first three weeks (thereby excluding congenital CMV infection) (see 'Early postnatal infection' above)

In children and adolescents, diagnosis of CMV infection in immunocompetent hosts is usually made using serologic studies (see "Approach to the diagnosis of cytomegalovirus infection", section on 'Immunocompetent hosts')

In immunocompromised hosts, confirmation of CMV infection is challenging and may require demonstration of infection in blood and an end organ (see "Approach to the diagnosis of cytomegalovirus infection", section on 'Immunocompromised hosts')

Treatment – Treatment of acquired CMV infections in infants and children depends on the clinical circumstances (see 'Treatment' above):

Preterm infants with postnatal infection – For preterm or VLBW infants who have serious early postnatal CMV disease (eg, sepsis syndrome, pneumonitis, hepatitis, necrotizing enterocolitis), we suggest antiviral treatment with ganciclovir or valganciclovir (Grade 2C). (See 'Early postnatal infection' above.)

Immunocompetent children – Antiviral therapy is not usually indicated for CMV infections in immunocompetent children. (See 'Immunocompetent children' above.)

Immunocompromised children – For immunocompromised children with active CMV disease, we recommend antiviral therapy with ganciclovir (Grade 1B). We also suggest antiviral therapy with ganciclovir or valganciclovir for immunocompromised children who lack signs or symptoms of CMV disease but have laboratory evidence of CMV viremia (Grade 2C). (See 'Immunocompromised hosts' above.)

Prevention – Strategies for preventing CMV infection include personal hygienic precautions and use of CMV-seronegative or leukocyte-reduced blood products for at-risk patients (eg, preterm infants and immunocompromised children). In preterm infants, treatment of maternal breast milk by freezing/thawing or pasteurization may reduce transmission. Use of intravenous immune globulin (IVIG) or CMV hyperimmune globulin in combination with antiviral drugs can reduce the risk of CMV infection in organ transplant patients. (See 'Prevention' above.)

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Topic 5965 Version 28.0

References

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