Cytomegalovirus

CMV

Clinical Description

Identification

While infection with cytomegalovirus (CMV) is common, it often passes undiagnosed as a febrile illness without specific characteristics. Serious manifestations of infection vary depending on the age and immunocompetence of the individual at the time of infection. The most severe form of the disease develops in 5%–10% of infants infected in utero. These show signs and symptoms of severe generalized infection, especially involving the CNS and liver. Lethargy, convulsions, jaundice, petechiae, purpura, hepatosplenomegaly, chorioretinitis, intracerebral calcifications and pulmonary infiltrates may occur. Survivors show mental retardation, microcephaly, motor disabilities, hearing loss and evidence of chronic liver disease. Death may occur in utero; the neonatal case-fatality rate is high for severely affected infants. Neonatal CMV is the leading cause of congenital viral infection, with an incidence of 0.5–3% of live births worldwide; 90%–95% of these intrauterine infections are inapparent but 15%–25% of these infants eventually manifest some degree of neurosensory disability. Fetal infection may occur during either primary or reactivated maternal infections; primary infections carry a much higher risk for symptomatic disease and sequelae. Seronegative newborns who receive blood transfusions from seropositive donors may also develop severe disease.

Primary infection in an immunocompetent host acquired later in life is generally inapparent, but may cause a syndrome clinically and hematologically similar to Epstein-Barr virus mononucleosis and hepatitis, distinguishable by virological or serological tests and the absence of heterophile antibodies. CMV causes up to 10% of all cases of mononucleosis seen among university students and hospitalized adults aged 25–34. It is the most common cause of mononucleosis following transfusion to non-immune individuals; many post-transfusion infections are clinically inapparent. Disseminated infection, with pneumonitis, retinitis, GI tract disorders (gastritis, enteritis, colitis) and hepatitis, occurs in immunodeficient and immunosuppressed patients—a serious manifestation of AIDS.

CMV is also the most common cause of post-transplant infection, both for solid organ and bone marrow transplants; in the former, this is particularly so with a seronegative recipient and a seropositive (carrier) donor, whereas reactivation is a common cause of disease after bone marrow transplant. In both cases, serious disease occurs in about 1 of 4 cases.

Infectious Agent

Human (beta) herpesvirus 5 (human CMV), a member of the subfamily Betaherpesvirus of the family Herpesviridae; includes 4 major genotypes and many strains, although there often is cross-antigenicity among genotypes and strains.


Diagnosis

Optimal diagnosis in the newborn is through virus isolation or PCR, usually from urine. Positive tests for IgM antibodies to CMV are also helpful. Diagnosis of CMV disease in the adult is made difficult by the high frequency of asymptomatic and relapsing infections. Multiple diagnostic modalities should be used if possible. Virus isolation, CMV antigen detection (which can be done within 24 hours) and CMV DNA detection by PCR or in situ hybridization can be used to demonstrate virus in organs, blood, respiratory secretions, or urine. Serological studies should be done to demonstrate the presence of CMV specific IgM antibody or a 4-fold rise in antibody titer. Interpretation of the results requires knowledge of the patient's clinical and epidemiological background.
 


Epidemiology

Mode of Transmission

Intimate exposure through mucosal contact with infectious tissues, secretions and excretions. CMV is excreted in urine, saliva, breastmilk, cervical secretions and semen during primary and reactivated infections. Persistent excretion may occur in infected newborns and immunosuppressed individuals. The fetus may be infected in utero from either a primary or reactivated maternal infection; serious fetal infection with manifest disease at birth occurs most commonly during a mother's primary infection, but infection (usually without disease) may develop even when maternal antibodies existed prior to conception. Postnatal infection occurs more commonly in infants born to mothers shedding CMV in cervical secretions at delivery; thus, transmission of the virus from the infected cervix at delivery is a common means of neonatal infection. Virus can be transmitted to infants through infected breastmilk, an important source of infection but not of disease, except when milk from a surrogate mother is given to seronegative infants. Viremia may be present in asymptomatic people, so the virus may be transmitted by blood transfusion, probably associated with leukocytes. Many children in day care centers excrete CMV; this may represent a community reservoir. Transmission through sexual intercourse is common and is reflected by the almost universal infection of men who have many male sexual partners.

Incubation Period

Illness following a transplant or transfusion with infected blood begins within 3–8 weeks. Infection acquired during birth is first demonstrable 3–12 weeks after delivery.

Period of Communicability

Virus is excreted in urine and saliva for many months and may persist or be episodic for several years following primary infection. After neonatal infection, virus may be excreted for 5–6 years. Adults appear to excrete virus for shorter periods, but the virus persists as a latent infection. Fewer than 3% of healthy adults are pharyngeal excreters. Excretion recurs with immunodeficiency and immunosuppression.

Reservoir

Humans are the only known reservoir of human CMV; strains found in many animal species are not infectious for humans.

Susceptibility

Infection is ubiquitous. Fetuses, patients with debilitating diseases, those on immunosuppressive drugs and especially organ allograft recipients (kidney, heart, bone marrow) and patients with AIDS are more susceptible to overt and severe disease.

Occurrence

Worldwide. In North America, intrauterine infection occurs in 0.5%–1% of pregnancies, usually as the result of a primary infection. In Europe, intrauterine infection is slightly less common. In Australia, the average annual incidence of children aged 0–14 years admitted to hospital with congenital CMV was 0.4–1.4 per 100 000. The situation in developing countries is not well described, but infection generally occurs early in life and most intrauterine infections are due to reactivation or reinfection of maternal infection. Serum antibody prevalence in young adults varies from 30% in highly industrialized countries to almost 100% in some developing countries; it is higher in women than in men and is inversely related to socioeconomic status within the USA. In the United Kingdom, antibody prevalence is related to ethnic group rather than social class. In various population groups, 8%–60% of infants begin shedding virus in the urine during their first year of life, as a result of infection acquired from the mother's cervix or breastmilk.


Prevention and Control

1)    Preventive measures:

a)    Take care in handling diapers/nappies; wash hands after diaper changes and toilet care of newborns and infants.

b)    Women of childbearing age who work in hospitals (especially delivery and pediatric wards) should use “universal precautions”. Workers in day care centers and preschools (especially those dealing with mentally retarded populations) should observe strict standards of hygiene, including handwashing.

c)    Avoid transfusing neonates of seronegative mothers with blood from CMV-seropositive donors.

d)    Avoid transplanting organs from CMV-seropositive donors to seronegative recipients. If unavoidable, hyperimmune IG or prophylactic administration of antivirals may be helpful. Antivirals are also helpful in seropositive bone-marrow transplant recipients who carry latent CMV.

2)    Control of patient, contacts and the immediate environment:

a)    Report to local health authority: Official report not ordinarily justifiable, Class 5.

b)    Isolation: Secretion precautions may be applied while in hospital for patients known to excrete virus.

c)    Concurrent disinfection: Discharges from hospitalized patients and articles soiled therewith.

d)    Quarantine: Not applicable.

e)    Immunization of contacts: Currently there is no vaccine available.

f)    Investigation of contacts and source of infection: None, because of the high prevalence of asymptomatic shedders in the population.

g)    Specific treatment: The drugs of choice for prophylaxis and treatment of CMV disease are ganciclovir IV or valganciclovir, administered orally. Alternatively, cidofovir IV (together with probenecid), foscarnet IV and fomivirsen have been approved for the treatment of CMV retinitis in immunocompromised persons. Ganciclovir, valganciclovir, cidofovir and foscarnet may also be helpful—especially when combined with anti-CMV immune globulin—for pneumonitis and possibly GI disease in immunocompromised persons; these drugs are licensed for use in CMV infections occurring after organ transplantation. Maribavir is an important candidate currently undergoing phase 3 clinical trials.

3)    Epidemic measures:

None.

4)    Disaster implications:

None.

5)    International measures:

None.

Source: Heymann (Ed.). (2008). Control of Communicable Diseases Manual, 19th edition. Washington, DC: American Public Health Association.
 

Common Disease Taxonomy: