Cytomegalovirus infection overview

# Overview
CMV infection is caused by cytomegalovirus which belongs to the family Herpesviridae. Transmission of CMV occurs from person to person and results in activation of the immune system. Patients often present with a mononucleosis-like presentation with particularly severe complications in immunocompromised individuals and rarely in immunocompetent individuals. Reactivation can occur in response to inflammatory stimuli, physiologic stress and immunosuppressionrwhicheleasinevirions that can infect new cells causing CMV end organ infection. CMV infection can affect the eye, gastrointestinal tract and the central nervous system. Common complications of CMV infection in immunocompromised patients include CMV retinitis, CMV colitis, CMV encephalitis and CMV pneumonia. CMV is associated with increased risk of graft versus host disease, myelosuppression, and invasive bacterial and fungal infections increasing morbidity and mortality of the patients. Antiviral therapy is the primary treatment of choice. The duration of therapy and the antiviral agents are selected based on the severity of the disease, location of the disease and the level of immunosuppression of the patient. Ganciclovir and valganciclovir are the most commonly used antiviral drugs for the treatment of CMV infection.

# Historical Perspective
In 1881, Ribbert described the presence of inclusion bodies in the cells in sections of kidney of a still born. In 1960, Thomas H.Weller from Harvard University, coined the term "cytomegalovirus" and isolated the virus from the urine sample of an infant with generalized disease.

# Classification
Cytomegalovirus infection may be classified based on the organ system involved into the following: CMV retinitis, CMV colitis, CMV esophagitis, CMV pneumonitis, and CMV encephalitis.

# Pathophysiology
Transmission of CMV occurs from person to person and primary CMV infection causes activation of the immune system and resulting in a mononucleosis like presentation and its complications in immunocompromised individuals and few immunocompetent individuals. Reactivation can occur in response to inflammatory stimuli, physiologic stress and immunosuppression releasing new virions that can infect new cells causing CMV end organ infection.

# Causes
CMV infection is caused by cytomegalovirus. It belongs to order Herpesvirales, in the family Herpesviridae, in the subfamily Betaherpesvirinae.

# Differential Diagnosis of Cytomegalovirus infection
CMV infection can affect the eye, gastrointestinal tract, and the central nervous system. Diagnosis of CMV requires differentiation of infections and diseases presenting with similar features. The majority of patients with CMV end organ infection are immunosuppressed. Therefore CMV infection must be suspected in all the patients presenting with immunosuppression and differentiated from other conditions known to affect immunocompromised patients.

# Epidemiology and Demographics
Cytomegalovirus infection is seen approximately 40-90% of the world population, however, only manifests in serious complications in immunocompromised patients.

# Risk Factors
Patients with the following conditions or undergoing the following procedures are at a higher risk for developing symptomatic cytomegalovirus infection: solid organ transplant, hematological stem cell transplant, AIDS, and existing T-cell deficiency.

# Screening
There is no standard screening recommended for cytomegalovirus infection due to the high seroprevalence.

# Natural History, Complications and Prognosis
Primary CMV infection takes place in childhood and early adolescence is asymptomatic. After the resolution of the primary infection CMV is latent in the mononuclear leukocytes. Reactivation in immunocompetent patients presents with mononucleosis like syndrome, but severe infection can occur in elderly and critically ill patients. Common complications of CMV infection in immunocompromised patients include CMV retinitis, CMV colitis, CMV encephalitis, CMV pneumonia and CMV myocarditis. CMV is associated with increased risk of graft versus host disease, myelosuppression, and invasive bacterial and fungal infections increasing morbidity and mortality of the patients.

# Diagnosis

## History and Symptoms
Primary infection in majority of patients have a mononucleosis like presentation. Patients with immunosuppression have symptoms related to the affected organ system. Retinitis presents with blurred vision and floaters. Colitis presents with abdominal pain and bloody diarrhea. Pneumonitis is usually asymptomatic. Neurologic infection presents with altered mental status and focal neurological deficits.

## Physical Examination
The appearance of the patient depends on the stage of the disease. The patient may look very healthy or be ill-looking and cachectic. On fundus examination fluffy yellow-white retinal lesions, with or without intraretinal hemorrhages can be demonstrated in patients with CMV retinitis. Abdominal distension and tenderness can be present on examination in patients with CMV colitis. In patients with CMV encephalitis altered mental status and focal neurological deficits are present.

## Laboratory Findings
There are no specific laboratory findings associated with CMV infection. Elevated ESR and a low lymphocyte count may be present in patients with complications. Diagnosis is usually done by demonstration of the inclusion bodies from the tissue biopsies or by a positive PCR for CMV DNA.

## Electrocardiogram
There are no EKG changes associated with cytomegalovirus infection.

## Chest X-Ray
Chest X-Ray in cytomegalovirus pneumonitis demonstrates diffuse pulmonary interstitial infiltrates.

## CT Scan
CT scan of the abdomen in patients with CMV colitis demonstrates colonic thickening.  On brain CT, the presence of periventricular enhancement is suggestive of ventriculoencephalitis which is a common (but non-specific) finding in CMV encephalitis.

## MRI
Periventricular enhancement is present in patients with ventriculoencephalitis on brain MRI.

## Echocardiography
There are no echocardiography findings associated with CMV infection.

## Other imaging findings
CMV infection is diagnosed by demonstration of intranuclear inclusion bodies and a positive PCR, therefore there are no other specific imaging findings for CMV infection.

## Other Diagnostic Tests
Other diagnostic studies helpful for the diagnosis of CMV infection include upper GI endoscopy, colonoscopy, serology and PCR.

# Treatment

## Medical Therapy
Antiviral therapy is the primary modality of treatment. Duration of therapy and the antiviral agents are selected based on the severity of the disease, location of the disease and the level of immunosuppression. Ganciclovir and valganciclovir are the commonly used antiviral drugs for the treatment of CMV infection.

## Surgery
Surgical intervention is not recommended for the management of cytomegalovirus infection.

# Prevention

## Primary Prevention
Primary prevention measures for CMV infection include regular hand washing to reduce the spread of infections. Healthcare providers should follow standard precautions to prevent nosocomial transmission particularly to immune compromised individuals.

## Secondary Prevention
Secondary prevention of CMV infection includes preemptive treatment with antiviral agents in asymptomatic patients with positive blood PCR for CMV DNA.