Infections In Pregnancy /

Cytomegalovirus CMV

01 In Brief

Cytomegalovirus is a common infection  that causes a glandular fever like illness. Infection for the first time pregnancy results in transmission to the fetus in 1 in 3 cases. Congenital CMV syndrome is associated with severe sequelae such as central nervous system abnormalities, growth retardation, microcephaly (small head), visual and hearing problems. Symptoms are present at birth in 10% of cases and the greatest risk is when the infant is infected between 4-22 weeks gestation. Young children who acquire the infection excrete the virus is their saliva and urine for many months and they are usually the source of infection in the mother.

02 What Do I Need To Know?

• Cytomegalovirus (CMV) is  Human Herpes virus 5. Other viruses of the Herpes family include Herpes simplex types1 2, Varicella Zoster virus (chicken pox) and Epstein Barr virus (infectious mononucleosis or glandular fever). They all have in common the ability to remain in the body after the first infection in a dormant state. In Australia the prevalence rate is 54% compared to parts of Africa where it is close to 100%. 

TYPES OF CMV INFECTION 

• Primary infection: the first infection in a previously uninfected or sero negative person.  Many primary infections with CMV are asymptomatic and rarely cause serious illness particularly in younger children. In children and adults it causes a glandular fever like illness with flu like symptoms, fever, enlarged lymph glands and hepatitis. The incubation period is not clear but can range from 4 weeks to 4 months. 
• Latency: after primary infection and the virus remains dormant in the body. It may be reactivated by immunosuppression or other factors.
• Non Primary infection: a previously infected person has a reactivation of dormant CMV or is infected with a new strain.

SORCES OF INFECTION

• CMV is excreted from urine, saliva, tears, breast milk and from the genital tract (cervical and vaginal secretions and semen) and is spread by close contact with body fluids that contain the virus.
• Infants and young children shed the virus in their saliva and urine for many months. 
• Sources of infection
  • Intrauterine: primary infection occurs either immediately prior to or during pregnancy. Between 1-5% of healthy women develop primary infection during pregnancy and it is usually the result of infection from a child in the family or from a day care setting. Women are either asymptomatic or have a mild from of the disease. There is a 1 in 3 chance of infecting the fetus. Congenital infection can also occur in non primary infections however it is rare for the fetus to develop the severe form of congenital CMV.
  • During Birth: CMV may be present in cervical secretions in the birth canal and can be transmitted from mother to baby during birth. These infections do not cause disease in the baby unless the baby s very small, premature or sick.
  • Day care: children in day care are in close daily contact and often spread it to each other through saliva on hands and toys.
  • Breastfeeding: CMV is excreted in breast milk and is commonly spread from mother to baby through breastfeeding. This can only occur if the mother has been infected with CMV and in most instances the baby is asymptomatic;
  • Blood transfusion and organ transplantation. 

• At highest risk for primary infection 
  • Seronegative pregnant women who work in high risk settings e.g. childcare or have younger children attending child care; 
  • Younger mothers who have not been exposed previously; 
  • Parents of children who are shedding CMV virus. 

CONGENITAL CMV

• Congenital CMV is the most common cause of serious congenital birth defects in the world. The severity and sequelae are related to when in pregnancy the infection occurs. The most severe affected are those who are infected between 4-22 weeks gestation. Only 10% of newborns with congenital CMV have symptoms at birth and although they have a better outcome than symptomatic newborns they are at risk for hearing loss.

Incidence of Severe Sequelae and Handicaps Following Primary Maternal Infection 

Source: Stagno et al., JAMA,1986 

• Symptoms of Congenital CMV atbirth include 
  • Growth retardation 
  • Central nervous system abnormalities with evidence of intracranial calcification.enlarged ventricles,cerebral atrophy and white matter abnormalities
  • Microcephaly;
  • Sensorineural hearing loss;
  • Visual problems with chorioretinitis and optic atrophy;
  • Dental defects;
  • Generalised infection:
  • Enlargement of the liver and spleen and jaundice, 
  • Fluid around the heart and lungs, 
  • Low platelet count with bleeding in to the skin,
  • inguinal hernia. 

•  Asymptomatic at birth:  5-10% develop  sequelae:
  • Hearing defects: 8% develop hearing loss and in 50% it is bilateral and in 50% it is progressive.18% have a delayed onset with a median age of detection at around 2-21/2 years age. Newborn screening does not detect all cases
  • Intellectual disability.

TESTING

• As the symptoms of primary infection are non specific testing for specific antibodies to CMV can  help determine if the infection is primary or if there is evidence of previous infection.The Immunoglobulin M and G (IgM and IgG)  determine if the infection is recent or has occurred previously.
  • IgG: Detection of CMV-specific IgG is used as a marker of past CMV infection. 
  • IgM: Detection of CMV-specific IgM is used as a marker of active or recent CMV infection. These are produced during the acute and late phases of a primary CMV infection and may persist for months or years. 
• A CMV IgM-positive result alone does not accurately predict the risk of fetal infection; a positive IgM test should therefore be considered only as a starting point and a more further  evaluation and specialist infectious disease input is necessary to determine whether there is a risk of fetal infection

TREATMENT

• In specialist centres various antiviral drugs are used particularly with immunosuppressed persons with HIV with lung or eye infections.
• Recent trials in the US using antiviral agents have shown promising results with improvement in hearing  outcomes but the drug is toxic and would be limited to thiose with severe disease. see ref below Nassetta et al

PREVENTION  

• There is no vaccine available to protect against CMV. 
• The following preventative measures have been recommended fro women who are pregnant or planning pregnancy

•  
  • Wash hands with soap and water often and thoroughly, especially when in contact with young children (nappy changes, etc).
  • Avoid kissing young children on the mouth.
  • Do not share food or eating utensils with young children.
  • If you are employed in a childcare setting, you can reduce your risk by working with children who are older than 2 ½, especially if you do not know your CMV status.

03 What Others Say

• Victorian Government Blue Book infectious disease.

The Blue book Cytomegalovirus infection

• Gov of South Australia: Maternity care in SA

 CMV in pregnancy 

• New York State department Communicable Disease fact Sheet

Cytomegalovirus: CMV

04 I Want To Know More

•  J Antimicrob Chemother. 2009 May; 63(5): 862–867
  
  

Treatment of congenital cytomegalovirus infection: implications for future therapeutic strategies:

• Queensland Health: Comprehensive guidelines for prevention of infection in childcare facilities using a risk management approach

Prevention of CMV infection in childcare

05 Clinicians Tools and Resources

• In depth e learning guide for congenital infections with flow diagrams for treatment and interpretation  of tests 

http://www.abbottdiagnostics.com.au/viewFile.cfm?file=congenital_learning_guide.pdf

perinatal infection ASID

• Paediatrics and Child Health: 2005 Jul-Aug; 10(60: 361 

Congenital cytomegalovirus infection; What is the best way to make the diagnosis

Last updated: 28/11/2010

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