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Cytomegalovirus


OVERVIEW OF Cytomegalovirus :

Cytomegalovirus (CMV) is the common virus that causes the infection in humans. The patient might not show any symptoms if he/she has any higher level of immune responses.


CAUSES :

When the virus is active in your body, you can pass the virus to other people. The virus is spread through body fluids — including blood, urine, saliva, breast milk, tears, semen and vaginal fluids.

The cytomegalovirus causes the following disease:

 

Primary cytomegalovirus infection and viraemia:

The replication of the CMV DNA and morphogenesis of the virion capsid take place in the nucleus. Following maturation of the capsid, newly synthesized, viral DNA is cleaved by an enzyme that results in packaging of linear genomic DNA. The viral DNA which contains the capsids acquires an inner layer of the tegument proteins from the nucleus including essential interactions between proteins and capsid protein which helps in the stabilization of the virion.

Congenital cytomegalovirus disease:

The clinical manifestation includes thrombocytopenia, petechiae, hepatomegaly, splenomegaly, hepatitis, intrauterine growth restriction, CNS involvement (microcephaly, ventriculomegaly, intracerebral calcifications, white matter changes with seizures and abnormal tone), ophthalmologic abnormalities (chorioretinitis, optic atrophy), and sensorineural hearing loss, among others. Mortality due to congenital CMV infection is low (approximately 4% of infants). Symptomatic disease can be classified as moderate to severe (multiple manifestations with or without CNS involvement) or mild disease (1-2 manifestations with no CNS involvement).  Some complications include cognitive impairement, chorioretinitis and cerebral palsy.

 

Cytomegalovirus pneumonia:

This is seen in immunocompromised individuals. Pneumonitis is the most common manifestations of the CMV.  In neonates it can lead to chronic lung disease and fibrosis. Symptoms might include dry cough, shortness of breath and fever.

Cytomegalovirus hepatitis:

This causes elevated levels of bilirubin or liver enzymes levels in combination with the detection of the CMV.  The first described case of CMV hepatitis involved a child with chorioretinitis, hepatosplenomegaly, and cerebral calcifications.

Hepatitis has been commonly observed in patients with primary CMV infection and mononucleosis. levels of hepatocellular enzymes may be mildly and transiently increased, and, in rare cases, jaundice may develop. Sometimes it can lead to death of the patient.

Cytomegalovirus gastritis and colitis:

The clinical presentation includes abdominal pian, diarrhoea and hematochezia which is termed as vomiting of blood.

Cytomegalovirus CNS disease:

The CNS symptoms include the detection of CMV in the Cerebrospinal fluid( CSF) culture or brain biopsy.

Cytomegalovirus syndrome:

it takes place in the solid organ transplantation recipients, CMV syndrome is better defines ad the fever which is greater than 38 degree celsius for at least 2 days within a 4 day period and either neutropenia or thrombocytopenia might occur.

 


PATHOPHYSIOLOGY :

Cytomegalovirus is a cytolytic virus. The histological hallmark of the CMV infection is an enlarged call with viral inclusion bodies.  The microscopic description to these cells is most commonly called as a owl’s eye appearance. This characteristic feature is minimal or absent in the infected persons.when the cytomegalovirus infects the host it can be detected with polymerase chain reactions (PCR) in all the different call lineages and organ systems in the body. With initial infection the cytomegalovirus infects the epithelial cells of the salivary gland which results in persistent infection and viral shedding. Infection in the genitourinary tract causes inconsequent viruria. Inspite of viral replication that takes place in the kidney, the damage to the kidney is very minimal.

Immunology:

Primary CMV infection is defined as an infection in an individual who shows previousy CMV seronegative. The initial infection with the IgM antibodies may be found as early as 4-7 weeks after the initial infection and it can persists as long as 16-20 weeks.  The presence of CMV DNA in the blood and viruria is present in some women. Cell mediated immunity is found to be considered as the most important factor in controlling the disease. Patient who are deprived of cell mediated immunity are at greater risk of contracting the infection. CMV specific CD 4+ and CD8+ lymphocytes plays a vital role in primary infection or reactivation of the viruses.

 


ROUTES OF TRANSMISSION :

Casual contact doesn't transmit CMV.

Ways the virus can be transmitted include:

  • Touching your eyes or the inside of your nose or mouth after coming into contact with the body fluids of an infected person.
  • Sexual contact with an infected person.
  • The breast milk of an infected mother.
  • Organ, bone marrow or stem cell transplantation or blood transfusions.
  • Birth. An infected mother can pass the virus to her baby before or during birth. The risk of transmitting the virus to your baby is higher if you become infected for the first time during pregnancy.


COMMON CLINICAL SIGNS AND SYMPTOMS :

These are the common symptoms with the babies:

  • Premature birth
  • Low birth weight
  • Yellow skin and eyes (jaundice)
  • Enlarged and poorly functioning liver
  • Purple skin splotches or a rash or both
  • Abnormally small head (microencephaly)
  • Enlarged spleen
  • Pneumonia
  • Seizures

The symptoms in people with the weakened immunity:

If your immune system is weakened, you might experience serious problems that affect your:

  • Eyes
  • Lungs
  • Liver
  • Esophagus
  • Stomach
  • Intestines
  • Brain

The symptoms in the healthy adults:

Most people who are infected with CMV who are otherwise healthy experience few if any symptoms. When first infected, some adults may have symptoms similar to infectious mononucleosis, including:

  • Fatigue
  • Fever
  • Sore throat
  • Muscle aches


DIAGNOSTIC :

Histopathology:

The characteristic feature of CMV is inclusion of the viral bodies which reveals the owl eye appearances.

Chest Xray:

The chest x ray predicts any abnormal area in the lungs

Computed tomography:

It reveals the slice of the lung. It uses both the combination of x ray and computer aided device.

It helps to analyse the size, shape and position of any lung tumour and also it helps in the detection of enlarged lymph nodes.

It also looks for any masses in the adrenal gland, liver, brain and other organs.

 CT guided needle Biopsy:

CT scan might be used to guide a biopsy needle into this  area to get the tissue for lung and further investigations are made. Ground glass opacities is seen in Computed Tomography.

MRI scan:

It uses the soft tissue image of the organ. It uses the both the magnet and radiowaves and aids in the view of soft tissues of the internal organs.

Immunosorbent assay- detect the virus specific IgM or IgG antibodies.

Greater than fourfold rise in titer between acute and convalescent sera  and  cerebo spinal fluid containing virus specific IgG or IgM or both are the diagnostic features.

 

Real-time polymerase chain reaction (RT-PCR)- is valuable in the early confirmation of arbovirus infections, particularly chikungunya. However, the value of RT-PCR is limited to diagnosis in the viraemic phase, with later infection requiring serology.

 

Direct immunofluorescence assay – it shows a high sensitivity and specificity and is used in the latter stages. However, the use of these tests in the tropics may be limited by financial constraints.

 

A normal erythrocyte sedimentation rate-  it is defined as the rate of red blood cell which are termed as erythrocytes and their deposition or sedimentation rate. The normal erythrocyte sedimentation rate is 0-22mm/hr.

 Echocardiogram:

It is used to find the movements of the heart.

Electrocardiogram:

It is used to find the electrical impulses of the heart.

Lumbar puncture or spinal tap:

 The fluid is drawn from the spinal cord and further investigations are made.

 


TREATMENT AND PROGNOSIS :

Ganciclovir is the drug of choice for the treatment of CMV virus. It inhibits the DNA synthesis like similar manner to the acyclovir.

Valganciclovir is also used in the treatment which shows similar treatment to the Ganciclovir.

Lentermovir prophylaxis:

Letermovir is an anti-CMV drug that was approved by the FDA in November 2017. It inhibits the CMV DNA terminase complex (pUL51, pUL56, and pUL89), which is required for viral DNA processing and packaging by affecting the production of proper unit length genomes and interfering with virion maturation

Foscarnet

Foscarnet is a DNA chain inhibitor of phosphorylation. It has been used to treat resistant HSV and ganciclovir-resistant viruses. It is an effective antiviral.

Meticulous attention must be paid to the patient's renal function. Small changes in creatinine levels require new calculations for renal clearance. Foscarnet is nephrotoxic.

 Acyclovir prophylaxis:

High doses of antivirals such as acyclovir, valacyclovir, famciclovir can be used in the treatment .

 Cytomegalovirus immunoglobulin:

    CMV immunoglobulin is used in combination with gamciclovir in the treatment of the pneumonia.

 


PROGNOSIS :

Prognosis:

The prognosis is good with the CMV patients. The patient might show some sort of tiredness and fatigue for weeks to months.

 


PREVENTION :

A recombinant CMV vaccines has been developed which shown to reduce the congenital CMV.

Regular follow up after the treatment is necessary.

Avoid contaminated objects

Main a distance with the infected persons.


Medicines used in the Treatment :

Valgancyclovir

Gancicyclovir

Acyclovir

Foscarnet