Overview of cytomegalovirus (CMV) infections in children

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).

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

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", section on 'Acquisition and vertical transmission'.)

●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 'Epidemiology of perinatal/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 [1]. 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 [2].

●Blood transfusion and organ transplantation – CMV infection can be acquired through blood transfusion or organ transplantation. Immunosuppressed patients, particularly transplant recipients and those with cancer or HIV infection are commonly infected with CMV and are at risk for developing serious disease. (See 'CMV infections in immunocompromised hosts' below.)

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 [3]. Pregnant health care workers and those contemplating pregnancy are not restricted from caring for CMV-infected patients and should follow universal precautions.

CONGENITAL CMV — 

The epidemiology, clinical features, diagnosis, and treatment of congenital CMV are discussed in detail separately. (See "Congenital cytomegalovirus (cCMV) infection: Clinical features and diagnosis" and "Congenital cytomegalovirus (cCMV) infection: Management and outcome".)

EARLY POSTNATAL INFECTION

Epidemiology of perinatal/postnatal infection — Perinatal and early postnatal infection can arise from any of the following [4]:

●Contact with maternal cervicovaginal secretions during delivery. (See "Cytomegalovirus infection in pregnancy".)

●Ingestion of breast milk containing CMV – This is the most common mode of postnatal CMV transmission from mother to infant. Preterm infants are at the greatest risk of having symptomatic or severe infection [4-11].

●Blood transfusions – Transfusion-related postnatal CMV transmission can be prevented by using CMV-seronegative and leukocyte-reduced blood products ("CMV-safe" blood), as discussed below. (See 'CMV-safe blood products' 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 [7]. 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) [6]. 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 [5]. 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 [4]. 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 [12,13]. (See "Severe combined immunodeficiency (SCID): An overview" and "NK cell deficiency syndromes: Clinical manifestations and diagnosis", section on 'Introduction'.)

Clinical manifestations — Most infants who become infected with CMV perinatally or postnatally are asymptomatic. However, preterm infants and those with primary immune disorders are at risk for severe symptomatic infection (table 1).

●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 [14]. Most patients with liver involvement have improvement in liver function tests by two to three months [14]. 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 [7].

In preterm infants, CMV infection may be serious and even fatal if not diagnosed and treated [8]. 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) [5,15]. CMV infection in preterm neonates has also been associated with necrotizing enterocolitis and increased risk of severe retinopathy of prematurity [10,16]. (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 [17-20]. Studies are conflicting as to whether early postnatal CMV infection adversely impacts long-term neurodevelopmental outcomes [17-21] or increases the risk of bronchopulmonary dysplasia [22,23]; 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 [20]. 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 [21].

●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 [12,13]. (See "Severe combined immunodeficiency (SCID): An overview" and "NK cell deficiency syndromes: Clinical manifestations and diagnosis".)

Diagnosis — The diagnosis of perinatal/postnatal CMV infection is confirmed based upon both of the following:

●Positive urine CMV polymerase chain reaction (PCR) test performed on a sample obtained after onset of symptoms, and

●Negative PCR result on a urine, saliva, or dried blood spot sample obtained earlier in the postnatal course, ideally shortly after birth (thereby excluding congenital CMV infection)

Urine is preferred over saliva for detection of postnatal CMV infection because it is more sensitive than saliva [24]. 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 (cCMV) 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 addition, we may perform testing for CMV in neonates with unexplained thrombocytopenia. (See "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at less than 35 weeks gestation", section on 'Diagnostic tests' and "Neonatal thrombocytopenia: Clinical manifestations, evaluation, and management", section on 'Diagnostic evaluation to identify underlying cause'.)

Neonates with severe CMV infection, such as viral sepsis, necrotizing enterocolitis, hepatitis, pneumonitis, or thrombocytopenia are typically viremic. In these infants, CMV can be detected by CMV quantitative PCR in whole blood or plasma [16].

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.

Treatment — 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 (table 1).

We treat preterm or VLBW infants who have serious CMV disease with antiviral therapy (ganciclovir or valganciclovir, depending on whether the infant can 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 [4].

●Infants able to take oral medication – Thes infants can be treated with oral valganciclovir (15 to 16 mg/kg/dose every 12 hours).

●Infants unable to take oral medication – These infants 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 [15].

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.

CMV INFECTION IN IMMUNOCOMPETENT CHILDREN

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 resource-limited countries, most children are infected by three years of age, whereas in resource-abundant 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 [25].

●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 [26]. 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 [27]. 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 [28,29]. (See "Cytomegalovirus infection in pregnancy" and "Congenital cytomegalovirus (cCMV) infection: Clinical features and diagnosis".)

Clinical manifestations — 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 [15]. Headache, abdominal pain with diarrhea, arthralgias, and rash also may occur. (See "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults", section on 'CMV mononucleosis'.)

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 'Differences between EBV and 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 [25].

Laboratory diagnosis — Diagnosis of primary CMV infection in immunocompetent hosts is usually made with serologic tests. 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'.)

Supportive care and recovery — CMV infections in immunocompetent children are generally self-limited, and treatment is supportive (antipyretics, fluids, rest). Antiviral therapy is generally not indicated. Most patients recover with supportive care alone over a period of days to weeks. (See "Infectious mononucleosis", section on 'Supportive care for most patients'.)

Antiviral therapy may be warranted on rare occasions if the infection is severe or life-threatening (eg, myocarditis, meningoencephalitis, pneumonitis). However, severe manifestations are rarely seen in immunocompetent children. These complications are generally limited to children with immunocompromise. (See 'Treatment of CMV infection in immunocompromised children' below.)

CMV INFECTIONS IN 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.

At-risk populations — Patient populations at risk for CMV disease in this setting include [25,30]:

●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

Clinical manifestations — 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 risk factors, surveillance, and diagnosis", section on 'Nonimmunologic factors'.)

●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: Epidemiology, clinical manifestations, and outcome", section on 'Cytomegalovirus disease'.)

Laboratory diagnosis — Laboratory confirmation of CMV infection 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 tests rarely are helpful in this population because most patients are seropositive and shed the virus. Thus, positive results on these tests is not indicative of active CMV disease. The diagnostic approach is described separately. (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 [32,33]. 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 of CMV infection in immunocompromised children — 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).

The choice of agent depends on the severity of the infection. 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 [25,33-38], as well as indirect evidence from clinical trials in immunocompromised adult patients (eg, solid organ transplant recipients, HIV-infected patients) [39]. (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) [40,41].

●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 ubiquitous, and infection occurs commonly. However, in certain circumstances (eg, during pregnancy, following transplantation), trying to prevent CMV infection is desirable.

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 [42]:

●Use of "CMV-safe" blood products (ie, leukoreduced and/or CMV-seronegative) for all neonates requiring transfusion. This essentially eliminates the risk of transfusion-related CMV infection [4]. (See "Red blood cell (RBC) transfusions in the neonate", section on 'Cytomegalovirus-safe RBCs for all neonates'.)

●Treatment of maternal breast milk by freezing/thawing or pasteurization [43,44]. Freezing/thawing reduces the risk of CMV transmission but does not eliminate it. Pasteurization reduces the risk of CMV transmission; however, it also removes many of the beneficial components. Screening donated breast milk for CMV is important in preventing CMV transmission from this source [45]. 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.

CMV-safe blood products — Transfusions given to newborns (especially preterm infants), pregnant individuals, and immunocompromised patients should use "CMV-safe" blood products (ie, leukoreduced and/or CMV-seronegative). Leukoreduction appears to be comparable with CMV-seronegative blood in preventing CMV transmission. (See "Red blood cell (RBC) transfusions in the neonate", section on 'Cytomegalovirus-safe RBCs for all neonates' and "Red blood cell transfusion in infants and children: Selection of blood products", section on 'Leukoreduced red blood cells'.)

Prevention in transplant recipients — Prevention strategies in transplant recipients include:

●Selection of CMV-seronegative donors for CMV-negative recipients, whenever possible

●Routine frequent monitoring for CMV infection or reactivation in the post-transplant period

●Use of pre-emptive or prophylactic antiviral therapy

These issues are discussed in greater detail separately. (See "Prevention of cytomegalovirus disease in kidney transplant recipients" and "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Cytomegalovirus' and "Prophylaxis of infections in solid organ transplantation", section on 'Cytomegalovirus'.)  

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 5^th to 6^th 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 10^th to 12^th 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 (cCMV) infection: Clinical features and diagnosis", section on 'Epidemiology'.)

●Congenital CMV infection – Congenital CMV infection is discussed separately (see "Congenital cytomegalovirus (cCMV) infection: Clinical features and diagnosis" and "Congenital cytomegalovirus (cCMV) infection: Management and outcome")

●Acquired early postnatal CMV infection

•Transmission – Most early postnatal CMV infections are acquired from ingesting CMV-positive breast milk. Less commonly, the infection may be acquired perinatally from contact with maternal cervicovaginal secretions during delivery or from blood transfusions. (See 'Epidemiology of perinatal/postnatal infection' above.)

•Clinical manifestations – Early postnatal CMV infections in otherwise healthy term infants are usually 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 'Clinical manifestations' above.)

•Diagnosis – The diagnosis of perinatal/postnatal CMV infection is confirmed with a positive urine CMV polymerase chain reaction (PCR) test performed on a sample obtained after onset of symptoms, in conjunction with a negative PCR result on a urine, saliva, or dried blood spot sample obtained earlier in the postnatal course, ideally shortly after birth (thereby excluding congenital CMV infection). (See 'Diagnosis' above.)

•Treatment – Asymptomatic or mildly symptomatic infections do not require treatment. 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 'Treatment' above.)

●Acquired CMV infection in immunocompetent children and adolescents – 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 'Clinical manifestations' above.)

The illness is generally self-limited, and management is supportive (eg, antipyretics, fluids, rest). Patients typically recover over a period of days to weeks. (See 'Supportive care and recovery' above.)

●CMV infections in immunocompromised hosts  

•At-risk populations – Serious CMV-related morbidity can occur in (See 'At-risk populations' above.):

-Transplant recipients

-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

•Clinical manifestations – Clinical manifestations of CMV infection in immunocompromised patients can include fever, leukopenia, and malaise with end-organ involvement (eg, kidney graft loss, hepatitis, pneumonitis, or myocarditis). (See 'CMV infections in immunocompromised hosts' above.)

•Diagnosis – The diagnostic approach is discussed separately. (see "Approach to the diagnosis of cytomegalovirus infection", section on 'Immunocompromised hosts')

•Treatment – 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 'Treatment of CMV infection in immunocompromised children' above.)

●Prevention strategies

•Strategies aimed at reducing the risk of acquiring primary CMV during pregnancy (thereby reducing the risk of congenital CMV infection) are discussed separately. (See "Cytomegalovirus infection in pregnancy", section on 'Behavioral risk reduction interventions'.)

•Strategies aimed at reducing the risk of CMV infection in hospitalized preterm neonates include freezing/thawing or pasteurization of maternal breast milk and using "CMV-safe" blood products (ie, leukoreduced and/or CMV-seronegative). (See 'Prevention of neonatal transmission' above and "Red blood cell (RBC) transfusions in the neonate", section on 'Cytomegalovirus-safe RBCs for all neonates'.)

•Prevention strategies in transplant recipients include selection of CMV-seronegative donors for CMV-negative recipients whenever possible, frequent monitoring for CMV infection or reactivation in the post-transplant period, and use of pre-emptive or prophylactic antiviral therapy. These issues are discussed in greater detail separately. (See "Prevention of cytomegalovirus disease in kidney transplant recipients" and "Prevention of viral infections in hematopoietic cell transplant recipients", section on 'Cytomegalovirus' and "Prophylaxis of infections in solid organ transplantation", section on 'Cytomegalovirus'.)