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Updated 13 February 2013

Cytomegalovirus

Cytomegalovirus (CMV) is a common virus that affects almost all adults.

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Definition

Cytomegalovirus (CMV) is a member of the herpes virus family, and almost all adults are silently infected with it, usually during childhood. CMV is found in various body fluids including saliva, blood, urine, semen, vaginal secretions and breast milk. The virus is most commonly transmitted through sexual or close personal contact, while it can also be spread through breastfeeding, via the placenta from mother to infant and by blood transfusions.

In a healthy person who is infected with CMV, the immune system prevents the virus from replicating and causing disease. Although never completely eradicated from the body, the virus lies dormant. It is only when the immune system is severely weakened that CMV results in significant disease.

A large proportion of people with HIV infection have been infected with CMV. It is usually in the very late stages of Aids, when the CD4 cell count falls below 100, that CMV is reactivated and can attack a number of organs. CMV disease in AIDS patients from South Africa is relatively rare, even with low CD4 counts. This is very unusual given that almost all adults have previously been infected with CMV.

Symptoms

CMV primary infection in healthy individuals can cause an illness called “mononucleosis” very similar to “glandular fever” or “infectious mononucleosis” that is caused by another type of human herpes virus called Epstein Barr Virus (or EBV). CMV is responsible for about 10% of mononucleosis cases.

Mononucleosis due to CMV is characterised by fever, malaise, fatigue, sore throat, swollen glands and fever. But as a rule, CMV infection in a healthy individual is clinically silent causing no symptoms at all. About 5% of pregnant women who acquire CMV during their pregnancy will have similar symptoms.

CMV infection is frequently spread from mother to infant through the placenta, during birth or via breast milk. If a mother becomes infected early during pregnancy, there is a chance that her infant will get severe brain damage from CMV, including deafness. Clinical evidence of infection in a full term healthy infant is rare. Occasionally mild liver and lung infections may occur that quickly get better on their own. However, in low birth weight infants with a birth weight <1500grams, the risk for CMV disease is much higher with high fevers, abnormal blood profiles, liver and bleeding disorders.

CMV infection in immune compromised hosts are extremely common and difficult to diagnose and treat. These infections can occur by reactivation of a person’s latent virus when they get immune suppressed, by reinfection with CMV from an outside source or a new or primary infection. Procedures like blood transfusions, organ transplants, medications that cause immune suppression as part of a transplant treatment, all enhance the chances of a CMV infection. Also Aids due to HIV infection can increase an individual’s chances for CMV infection. CMV disease in immune suppressed individuals can manifest in a variety of different ways including:

  • Cytomegalovirus retinitis: The eye is vulnerable to CMV – specifically the retina, the layer of special light-detecting cells at the back of the eye. Cytomegalovirus retinitis causes failing vision in one or both eyes. If untreated it will eventually cause blindness. The condition is painless.
  • Cytomegalovirus oesophagitis: CMV can attack the oesophagus (the passage between the mouth and the stomach), causing pain in the mid-chest area when food is swallowed.
  • Cytomegalovirus colitis: Cytomegalovirus colitis affects the colon, frequently causing diarrhoea, abdominal discomfort, fever and decreased appetite.

Many of the symptoms of CMV are similar to those of other diseases and conditions, which is why a correct diagnosis may initially be difficult. When a person is first infected with CMV they may suffer from a sore throat, swollen glands, tiredness and fever, all of which may be confused with symptoms of other illnesses.

People with CMV may show signs of jaundice, where the skin and eyes appear yellow. Less frequently, CMV can affect the nervous system (neuropathy), causing numbness, pain, or a tingling sensation in the limbs. CMV can also affect the lungs, resulting in pneumonia.

Diagnosis

CMV retinitis can be diagnosed by examination of the retina using a hand-held opthalmoscope. The doctor will see tell-tale haemorrhages (bleeding) and exudates (fluffy spots) on the retina.

In order to diagnose CMV in other organs, it is necessary to perform a biopsy (take a tissue sample). While a simple blood test may show the presence of CMV, it is not evidence enough to conclude that there is active disease. The sample of tissue that is removed is sent to the laboratory where it is studied under a microscope for signs of active CMV disease.

Treatment of CMV-related disease

There are currently three drugs available for treating CMV infections.

  • Ganciclovir can be given intravenously or orally, but in the case of retinitis it is best given as a slow-release implant placed directly in the eye under local anaesthetic. Treatment for CMV retinitis must usually be life-long or the disease will relapse.
  • Foscarnet can be used to treat retinitis and other CMV infections, but is only available as an intravenous preparation.

When ganciclovir and foscarnet are given intravenously, the drug is infused through a small tube (catheter) that goes directly into the chest or arm. Both of these drugs must be infused on a daily basis and the procedure can take up to two hours. The catheter remains in place and must be kept covered, clean and dry to prevent infection.

  • Cidofovir can also be used to treat retinitis and other CMV infections, and is also given intravenously. Cidofovir is administered less frequently, but does have more serious side-effects.

There is no cure for CMV disease, but the drugs can alleviate symptoms and stop further injury to the affected parts of the body. However, these drugs have several side effects.

Side-effects of anti-CMV drugs

  • Ganciclovir use can result in a low white cell count (neutropenia). This condition is usually without symptoms, but can cause problems when ganciclovir is taken in combination with certain antiretrovirals that also cause a low white cell count. Other side- effects may include nausea, vomiting, diarrhoea, fever, rash, anaemia and abnormal liver function. Complications when placing the retinal implant can result in inflammation of the inside of the eye or retinal detachment.
  • Foscarnet can cause metabolic disturbances, skin ulcers, and kidney damage.
  • Cidofovir can cause severe kidney damage.

Prevention

The only way to prevent CMV-related illnesses is to keep as healthy as possible. Ensuring that you get the best care for your HIV infection and taking your antiretroviral medication consistently will help prevent a drop in your CD4 cell count and keep CMV infection at bay.

Reviewed by Dr Eftyhia Vardas, University of the Witwatersrand

 
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