Cytomegalovirus Infection(CMV)

Cytomegalovirus (CMV) is a very common but mild viral illness. It belongs to the herpes virus family and hardly causes symptoms in people with good health. Whereas people with low and weakened immune systems and pregnant women must see a doctor if they have flu-like symptoms or any condition associated with the risk of CMV. Women who get this infection during pregnancy can transmit the virus to their babies, who can present with symptoms. This virus is highly contagious and remains the point of concern that once it infects or enters the body, it remains throughout the whole life. It can be a seriously debilitating disease in individuals who have previous organ transplants and bone marrow or stem cells transplant.

Cmv is transmitted through body fluids, like blood, saliva, urine, semen, and breast milk. There is no permanent cure, but symptoms can be controlled relatively through medications. CMV can only be transmitted if it is in the active virulent stage. This could be due to reinfection with another strain of CMV or weak immunity, or kids catch it when they start their early childhood education. Transmission can also occur through sexual contact or from breast milk to nursing infants. It can affect the intestines, eyes, lungs, liver, esophagus, and stomach. Reactivation of the virus may not necessarily result in severe cases.

1.       Congenital cytomegalovirus disease

2.       Cytomegalovirus Pneumonia

3.       Cytomegalovirus hepatitis

4.       Cytomegalovirus gastritis and colitis

5.       Cytomegalovirus  CNS disease

6.       Cytomegalovirus retinitis

7.       Cytomegalovirus nephritis

8.       Cytomegalovirus syndrome

9.       Cytomegalovirus Graft versus host disease

Congenital CMV

Congenital (at birth) cytomegalovirus is a condition that can occur when an infant is infected with CMV before birth. Congenital CMV occurs when an infected mother passes the virus to the fetus through the placenta, called vertical transmission. The mother may be completely unaware that she has CMV as it was maybe asymptomatic. Most babies with CMV appear healthy. Symptoms may sometimes not appear for months or years after birth. Some signs are hearing loss and developmental delay. Some babies may also develop vision problems. Babies who have congenital CMV and who are sick at birth may have these findings concomitantly; Premature birth, low birth weight, Yellow skin, and eyes (jaundice).

Some common risk factors include:

·         People using immunosuppressing medications for diseases like Systemic lupus erythematosus, Crohn’s disease, rheumatoid arthritis, psoriasis.

·         Underlying HIV infection.

·         Individuals working in daycares.

·         Patients undergoing frequent blood transfusions.

·         Multiple sex partners.

·         Mismatched organ transplants.

·         Intercourse with an infected person.

·         Increasing age.

·         Transplant population.

In the United States, one in three children is almost infected with CMV by age five. More than half are infected with CMV by age 40. Most people with CMV infection are symptom-free and aren’t aware that they have been infected. Almost 60% of the US population has been exposed to CMV,  being prevalent among high-risk groups like male homosexuals. Occurrence is more in developing countries, and most infections are acquired during childhood. However, in developed countries, up to half of the young adults are CMV seronegative. The incidence of CMV seropositivity rises with age, and in a US-based study was reported to increase from 36% in children aged 6-11 years to 91% in individuals older than 80 years. Association with CMV seropositivity include ethnicity, commonest in Mexican Americans, then black Americans, female sex, foreign-born status, and low socioeconomic conditions.

Some common signs and symptoms include

• Fever of unknown origin
• Fatigue
• Muscle aches
• Enlarged glands
• Sore throat
• Enlarged spleen and liver
• Headache           

Some common life-threatening associated clinical features include:

• Anemia (hemolytic anemia)
• Fever
• Pneumonia
• Inflammation of the retina in the eye (retinitis) is the commonest presentation in HIV patients.
• Inflammation of the brain (encephalitis) 
• Inflammation of the large intestine (colitis)
• Inflammation of the liver (hepatitis). 
• Mononucleosis syndrome
• Fine crackles initially in the lungs

After acquiring history and physical examination, diagnosis is further supplemented by the following Tests;

1.      Laboratory Studies

Ø  Qualitative polymerase chain reaction.

It is Qualitative PCR to detect cytomegalovirus in blood and tissue samples. It is a highly sensitive test as it can detect the activity of the disease.

Ø  Quantitative polymerase chain reaction.

It is quantitative PCR to detect cytomegalovirus in plasma. It detects the number of cytomegalovirus genomes present in plasma.

Ø  Shell vial assay

It is performed by the addition of a clinical specimen to a vial that contains an activated cell line of cytomegalovirus. It is as sensitive as traditional tissue culture tests performed through fluorescent microscopy.

Ø  Cytopathology

This appears as Owls eye due to intracellular inclusions with clear halo and various stains.

Ø  Antigen testing

High antigen tire in blood shows detection of CMV p65 in white blood cells. It is only detected during active replication. People with reduced immunity show low or moderate CMV antigenemia, indicating reactivation or infection.

2.      Imaging studies

Ø  Chest radiograph.

Ø  CT scanning.

3.      Cytomegalovirus resistance testing

If resistant CMV infection is suspected, alternative therapy should be used based on Mutation or genetic resistance. Ganciclovir is used in high doses in mildly resistant cases.

4.      Histological findings

Histologically the hallmark of CMV infection is the presence of intranuclear inclusions consistent with herpesvirus infection. CMV infection is confirmed using in situ hybridization or direct or indirect staining of intranuclear inclusions using CMV-specific antibodies linked to an indicator system (e.g., horseradish peroxidase, fluorescein).

Some medical conditions that can be confused as Cytomegalovirus infection include.

·         Viral hepatitis

·         Autoimmune hepatitis.

·         Toxoplasmosis.

·         Early symptomatic HIV infection.

·         Enteroviruses

·         Fever of unknown origin.

·         HIV infection and AIDS.

·         Human herpesvirus 6 infections.

·         Epstein Barr virus, infectious mononucleosis.

·         Aseptic meningitis

·         Encephalitis

·         Polyneuritis

·         Guillain-Barré syndrome.

·        Chorioretinitis

Medications to treat or prevent CMV are:

·         Ganciclovir: It’s the drug of choice. It is used intravenously. It’s effective against CMV, HSV, VZV, HHV-6, HHV-7, and HHV-8. Common side effects of this therapy include fever rash, diarrhea, neutropenia, anemia, thrombocytopenia. Oral ganciclovir is far less effective than intravenous ganciclovir.

·         Valganciclovir: Its prodrug of ganciclovir that is activated in the liver and gut. It is used in certain CMV cases, such as CMV retinitis orn aids patients.

·         Letermovir prophylaxis

·         Foscarnet

·         Acyclovir prophylaxis

·         Cidofovir prophylaxis: It is used for refractory CMV retinitis in HIV patients.

·         Marina: It works on CMV and EBV.

·         Leflunomide

·         Cytomegalovirus immune globulin: CMV immune globulin has been approved for the prophylaxis of CMV disease in high-risk lung transplant recipients when given in addition to ganciclovir. In cardiothoracic transplant recipients, those who received CMV immune globulin plus ganciclovir had a higher infection-free period, less rejection, higher survival rate, and reduced coronary intimal thickening compared with patients who received ganciclovir alone. These observations need further research.

·         CMV pneumonia is treated by a combination of CMV immune globulin and ganciclovir.

The prognosis of CMV hepatitis is remarkably praising. Some primary symptoms can stay longer for several months after primary infection, For example, fatigue. Recovery in some patients is effectively reversible.CMV pneumonia in marrow transplant recipients has the highest mortality. The use of ganciclovir plus high-dose immune globulin for the treatment of CMV pneumonia in allogeneic marrow transplant recipients has reduced the mortality rate Up to 60%. Because patients who develop CMV disease have low immunity, their prognosis may be determined by their underlying medical condition. Mechanical ventilation requirement is a poor prognostic sign.

Good hygiene is the best prevention against CMV. Some precautions include;

·         Frequently washing hands  Use soap and water for 15 to 20 seconds, significantly if you have contact with young children or their diapers, saliva, or other oral secretions. It is crucial for children attending daycare.

·         Avoid contact with body secretions when you kiss a child. Avoid kissing a child on the lips, for instance, kiss on the forehead. This is especially important if the woman is pregnant.

·         Avoid sharing food or drinking in the same utensils. Sharing glasses and kitchen utensils with infected individuals can spread CMV.

·         Be careful with disposable items. When disposing of materials like diapers, tissues, and other things that have been contaminated with bodily secretions, wash your hands thoroughly before touching your face.

·         Clean toys and countertops. Extensive Cleaning of all the surfaces that come in contact with children's urine or saliva.

·         Practice safe sex. Wear a condom during sexual intercourse to prevent the spread of CMV through fluids (vaginal and semen).

If you have a weaker immune system, antiviral treatment may help you prevent CMV infection. Experiments on vaccines are being held for women of childbearing age. These vaccines might help prevent vertical transmission of CMV infection in mothers and infants, and reduce the chance that babies born to women who are infected while pregnant will bypass any disabilities.

Our clinical experts continually monitor the health and medical content posted on CURA4U, and we update our blogs and articles when new information becomes available. Last reviewed by Dr.Saad Zia on May 16, 2023.

References

Cytomegalovirus (CMV) Infection: Causes & Symptoms (clevelandclinic.org)

https://my.clevelandclinic.org/health/diseases/21166-cytomegalovirus

Cytomegalovirus (CMV) and Congenital CMV Infection | CDC

https://www.cdc.gov/cmv/index.html#:~:text=Cytomegalovirus%20(pronounced%20sy%2Dtoe%2D,it%20is%20called%20congenital%20CMV.