CMV, EBV, and Rabies Notes

Cytomegalovirus (CMV)

Definition and Overview

Cytomegalovirus (CMV) is a prevalent infection that is generally harmless. Once CMV enters a host's body, it establishes a lifelong presence. Most healthy children and adults infected with CMV remain asymptomatic and may be unaware of their infection. However, some individuals may experience mild illnesses upon initial infection.

Reactivation and Reinfection

When a patient presents with CMV infection later in life, it can be attributed to either reactivation of latent CMV or reinfection from a new exogenous strain.

At-Risk Populations

The populations at a higher risk of CMV infection include:

  • Pregnant Women: Can transmit the virus to the fetus.

  • Children and Young Adults: Specifically, those aged 25-35 years.

  • Immunocompromised Individuals: Such as renal transplant patients or those undergoing chemotherapy; they face severe organ involvement upon reactivation of CMV.

Transmission Routes

CMV is transmitted primarily through contact with the urine of young children infected with the virus or through sexual contact. Many post-childhood infections occur due to exposure to asymptomatic carriers who shed the virus via saliva, urine, and genital secretions.

Congenital CMV

Pregnant women who develop a primary CMV infection have a roughly 40% chance of transmitting CMV to their fetus, which can lead to congenital CMV infection. The clinical features include:

  • Petechial rashes

  • Hepatosplenomegaly

  • Jaundice

Approximately 10% of infected infants may have long-term central nervous system sequelae, including microcephaly, cerebral calcifications, chorioretinitis, and deafness.

Post-Childhood CMV

Most infections in young adults are subclinical. However, some may develop an infectious mononucleosis-like syndrome characterized by:

  • Severe fatigue

  • Fever

  • Inflamed throat

  • Swollen lymph nodes

  • Enlarged spleen and liver

  • Rash.

Complications in Immunocompromised Patients

In severely immunocompromised patients, CMV can cause complications such as:

  • Esophagitis

  • Colitis

  • Pneumonitis

  • Retinitis

  • Encephalitis

Diagnosis

CMV infections are seldom diagnosed due to their subtlety. Blood tests can indicate if a person has ever been infected. Key diagnostic investigations include:

  • CBC: Reveals atypical lymphocytosis

  • Liver Function Tests: Show increased liver enzymes

  • Serological Tests: Focus on detecting CMV-specific IgM antibodies and a four-fold rise or seroconversion of IgG.

In immunocompromised individuals, antibody detection may be unreliable, and diagnosis typically relies on PCR, culture, or histopathology.

Management

For immunocompetent patients, only symptomatic treatment is necessary. Conversely, immunocompromised patients may require antiviral treatment:

  • Ganciclovir: 5 mg/kg IV twice daily or oral valganciclovir 900 mg twice daily for at least 14 days.

  • Alternative Treatments: Foscarnet or cidofovir may be utilized for patients resistant or intolerant to ganciclovir therapy.

Epstein-Barr Virus (EBV)

Overview

EBV, known as human herpes virus 4, is widely disseminated and primarily transmitted through intimate contact. The majority of primary infections are subclinical. Approximately 90-95% of adults worldwide are seropositive for EBV.

Classification of EBV Infection

Primary Infection

  1. Acute Infectious Mononucleosis (IM)

  2. EBV infection in infants and children

  3. Congenital and perinatal infections

  4. Other manifestations

Malignancy

  1. Burkitt lymphoma

  2. Hodgkin and non-Hodgkin lymphoma

  3. Nasopharyngeal carcinoma

  4. Gastric carcinoma

Symptoms of Infectious Mononucleosis

IM typically begins with symptoms like malaise, headache, and low-grade fever, progressing to:

  • Tonsillitis and/or pharyngitis

  • Fever and cervical lymph node tenderness

  • Characteristic symmetric lymphadenopathy, primarily affecting the posterior cervical chain.

Less common findings may include:

  • Palatal petechiae

  • Maculopapular or morbilliform rashes

  • Splenomegaly in 50% of patients

Resolution and Complications

Most individuals recuperate without issue, achieving durable immunity. Acute symptoms usually resolve in one to two weeks, though fatigue may linger for months. Potential complications include rash following antibiotic administration and airway obstruction in severe cases.

Delayed complications may consist of chronic active EBV infections and lymphoproliferative disorders.

Diagnosis of EBV

EBV infections are suspected based on clinical presentation, supported by a blood smear and antibody studies. Confirmation can be achieved via heterophile antibody tests (e.g., Monospot) or detection of specific EBV antibodies.

Peripheral blood typically shows lymphocytosis with atypical lymphocytes, which may also signal other infections.

Treatment

Supportive care is the cornerstone of EBV management, with antipyretics and NSAIDs recommended for managing fever and discomfort. Antiviral therapy with acyclovir may significantly reduce oropharyngeal shedding. Good hygiene is crucial for prevention, and a vaccine is under development.

Rabies

Overview

Rabies is an acute viral infection mostly transmitted through bites from domestic dogs, accounting for over 95% of human rabies deaths. The virus infects central nervous tissue and salivary glands of various mammals, typically through saliva.

The incubation period varies from 9 days to several months, generally spanning 4 to 8 weeks. Higher risk is associated with deep bites, particularly on the head and neck.

Clinical Manifestations

Rabies has two primary forms: furious (classical) and paralytic encephalitis, with furious rabies being more prevalent (approximately 80% of cases).

Early symptoms may include fever and paraesthesia at the bite site. This is followed by a prodromal phase lasting 1-10 days, with developing anxiety and hydrophobia, an inability to drink due to severe muscular contractions. Subsequent manifestations include delusions, hallucinations, and cranial nerve lesions, with death typically occurring within a week of symptom onset.

Diagnosis and Management

Diagnosis is usually clinical but can include rapid immunofluorescent techniques to detect viral antigens. Most established rabies cases cannot be effectively treated, with limited survival documented. Instead, intensive supportive care is necessary, focusing on managing cardiac and respiratory failure.

Prevention

Vaccination is critical for those at high risk, such as animal handlers and laboratory workers. Post-exposure prophylaxis involves thorough wound cleaning, excising damaged tissue, and administering hyperimmune serum and vaccine promptly after exposure. Rabies remains a preventable disease with effective dog vaccination programs.