Viral Illnesses

Epstein-Barr Virus (EBV)

Cytomegalovirus (CMV)

• 
• Very common infection (40-80% of children are infected by puberty)
• Transmission: Person-to-Person ANY body fluid
  • blood, urine, saliva, cervical secretions, feces, breast milk, semen.  
  • Includes: sexual spread, blood transfusion, organ donation.
• Symptoms:
  • Most subclinical (80-90%)
  • In normal host:
    • Mononucleosis (heterophil (Monospot) - negative mononucleosis)
      • Difficult to distinguish from EBV mononucleosis.
      • Pharyngitis and cervical LAD less common than EBV.
      • Fever >3w (but can persist >32w if obtained from blood transfusion).
      • Mild liver enzyme elevation (hepatitis/jaundice RARE)
      • Rash (30% of pts) (Ampicillin provocation noted).
  • Immunocompromised:
    • Severe disease in many organ systems:
      • Retinitis
      • Hepatitis
      • Pneumonitis
      • GI disease (gastric/esophageal ulcers, colitis)
        • Enteritis
        • Esophagitis
        • Colitis
        • Gastritis
      • Meningoencephalitis
      • Polyradiculopathy 
  • Pregnant
    • Primary infection of pregnant woman causes neonatal disease:
      • jaundice, petechiae, microcephaly, chorioretinitis, cerebral calcifications, mental retardation, neonatal death, deafness.
• Complications:
  • Hepatitis
  • Pneumonitis
  • Guillain-Barre Syndrome (12% of CMV)
• Diagnosis:
  • Quantative PCR of CMV DNA (useful for reactivation)
  • Biopsy affected site with viral tissue culture (i.e. colonoscopy with biopsy for CMV colitis)
  • CMV IgG - rise in titer to 4x baseline value.  (Most Reliable)
  • CMV IgM (also indicates acute infection, but also seen in reactivation)
• Treatment:
  • Normal host: Almost never required
    • SELF LIMITING, WAIT!
    • Steroids for autoimmune or hematologic complications.
    • Ganciclovir (Or PO form Valganciclovir) or Foscarnet if causing organ disease (i.e. esophagitis)
    • Liposomal form of cidofovir - strong antiviral activity with minimal renal toxicity.
    • Vaccine: (in trials as of 2014) , in pregnant women: 50% efficacy in prevent CMV infection.
  • Resistance:
    • Rapidly rising in transplant population to: Ganciclovir: mutation in UL97 kinase or CMV DNA polymerase.  Foscarnet resistance also on the rise.

Influenza

• High contagenous acute febrile respiratory illness.
• 36,000 deaths/year.
• In northern + summer hemispheres: almost exclusively  in winter months.
  • In tropics: occur throughout the year.
• Rates of infection are highest among children, risk of death <2y and >65y.
• Influenza A, B, and C are human pathogens
  • Influenza A - many hosts, subdivided based on surface proteins (Hemaglutinin and Neuraminidase)
    • "antigenic drifts" - cause small changes by point mutations and recombinations. (local outbreaks)
    • "antigenic shifts" - major changes (epidemics/pandemics).
    • Sprint 2009 - novel influenza A virus (H1N1) - antigenic shifts.
  • Influenza B
    • Less severe outbreaks.
    • Clinically impossible to distinguish A from B.
  • Influenza C infection is rare.
• Symptoms:
  • Fever, headache, myalgia, non-productive cough, sore throat, nasal discharge.
    • GI sx can occur in children.
  • Incubation: 1-4 days.
  • Complications:
    • Pneumonia (esp if underlying chronic illnesses) - primary viral pneumonia, secondarily bacterial can occur (or both).
      • Primary pathogens: Strep pneumo (most common), Staph aureus, H. influenza.
    • Other (less common): Myocarditis, pericarditis, myositis, rhabdomyolysis, encephalitis, aseptic meningitis, transverse myelitis, GBS.
• Diagnosis:
  • Mostly clinical.
  • Can confirm with RT-PCR or viral culture.
  • Rapid influenza diagnostic tests - immunoassays Influenza A+B - fast results 15min.
    • (poor sensitivity, good specificity, negative results do not exclude dx).
    • helpful in public health (fast detection of outbreaks).
• Treatment:
  • Influenza Vaccination - best method to prevent.
  • Vaccines:
    • Trivalent (inactivated) - injected.
      • Used in >6mo, including health, chronic disease, pregnant women.
    • Live -  intranasal vaccine.
      • Used in healthy 2-49, not pregnant, not immunocompromized.
    • in 2010 - CDC recommend annual influenza vaccine for everyone >6months.
  • For treatment:
  • Two FDA-approved antivirals: (for treatment or chemoprophylaxis)
    • Both - neuraminidase inhibitors for Influenza A and B.
      • Amantadine and Rimantadine (Adamantine class - no longer used, high rate of resistance, not active against influenza B).
      • Oseltamivir (Tamiflu) and Zenavimir   (Peramivir is IV)
        • Both indicated for Influenza A H1N1, Influenza A H3N2, Influenza B or non-typed.
        • Oseltamivir 75mg po BID for treatment (OD for prophylaxis) x5 days
        • Zenavimir - delivered by inhalation, not recommended for underlying airway disease (asthma, COPD) - can induce bronchospasm
        • Peramivir - IV formulation only
    • Antiviral Indicated for:    (Advisory committee for immunization practices)  
      • Hospitalized patients.
      • Severe complicated/progressive illness
      • High risk for influenza complications
    • Low-risk patients - avoid treatment.
    • When treatment is indicated, must be started in first 2 days of symptom onset.
      • Reduces duration of illness or reduce serious complications.
    • Start treatment in first 2 days promptly (before confirmation of influenza) of symptom onset
      • Shown to reduce treatment complications and duration
  • Pregnant women or severe/progressive illness:
    • Starting 3-4 days after onset may be beneficial.

Herpes Simplex Virus (HSV)

• HSV infection can occur at any skin location.
• Lesions on abraided skin (herpetic whitlow) - common among healthcare workers, but rare due to better hand hygeine.
• Recurrent HSV-1 keratitis - #1 cause of blindness in developed countries. - Dendritic ulcers on fluorescein.
• Most common cause of sporatic encephalitis in US.
• Being unilateral in temporal lobes, spreads contralateral --> hemorrhagic.
• Symptoms
  • Mucocutaneous: Genital and labial lesions.
  • Encephalitis: Personality/behavioural changes, headache, fever, decreased LOC, abnormal speech.
    • Focal seizures.
  • Immunocompromized (can cause pneumonia, aspetic meningitis, esophagitis, colitis, colitis, disseminated cutaneous disease.  Oral/genital lesions can be extensive).
• Investigations:
  • Focal lesions on imaging.
  • CSF - pleocytosis sometimes erythrocytes.  Normal glucose.
    • HSV-DNA by PCR
• Treatment
  • Prompt as soon as dx suspected
  • Acyclovir, Valacyclovir, Famcyclovir for mucocutaneous and visceral HSV infection, preventing HSV infection, and reactivation.
    • Resistance to acyclovir (common in immunocompromised): foscarnet or cidofovir
  • Long-term Suppressive therapy indiations:
    • frequent (>6x/year) recurrences, or severe recurrences of genital HSV, or immuncompromize.
  • HSV Encephalitis, life threatening infections, cannot tolerate oral therapy.
    • IV acyclovir.
  • Topical agents (i.e. trifluorothymidine) - avilable for ocular infections. 
  • Topical corticosteroids contraindicated for ocular HSV infections!!
  • Valacyclovir in high doses associated with TTP after extended use in patients with AIDs

Varicella Zoster Virus (VZV)

• Two distinct forms of the clinical disease:
  • 1. Varicella (Chicken Pox)
  • 2. Herpes Zoster (Shingles).
• Varicella
  • Primary infection by Herpes Zoster virus
  • Highly contageous - generalized vesicular rash. (face + extremities towards the trunk - centrifugal rash?)
    • Macules, papules, vesicles, scab lesions can be present simultaneously.
  • Adults: Systemic symptoms more common.
  • Airborne
  Immunocompromised and Pregnant women: Disseminated diComplications
  • Diagnosis:
    • Clinically
    • Viral culture and immunohistochemistry can be done.
• Herpes Zoster
  • Reactivation of prior infection with varicella zoster virus.
  • Vesicular rash in dermatomal distribution.
  • Consider inpatients with pain along a dermatome, followed in 2-3 days by vesicular eruption
• Treatment
  • Varicella immunization routinely recommended in children 12-15mo with second dose at ages 4-6yo.
    • In patients >13yo not immunized and no evidence of immunity, give two doses 4-8w apart.
      • A second "catch up dose" given >13 yo if only got one dose as child.
  • Zoster vaccine:
    • recommended for prevention in >60yo
    • Reduces incidence of zoster infection, and incidence and severity of post-herpetic neuralgia.
      • ~50% reduction of shingles risk, and reduces post-shingles pain by ~90%.
      • If had zoster episode, controversial, but many recommend delay vaccine by 3 years (protected from infection)
  • Post-Exposure Prophylaxis: VZV IgG (if available) or VZV Immunoglobulin (VariZig)
    • Useful in preventing and lessening symptomatic varicella in high risk patients (after exposure)
      • Immunocomromised, negative or unkonwn chicken pox history,  not been vaccinated.
      • Pregnant women who are seronegative for VZV and have had exposure to virus.
      • Newborn infants if <5d before delivery or 48hrs postpartum.
  • Acyclovir
    • Approved for Varicella and Zoster infection.
    • Reduces duration of lesion formation and number of new lesions (decreases systemic sx).
    • Treatment recommended for:
      • Adolescents
      • Adults
      • Pts w/ high risk of complications.
    • Initiate within 24hrs of lesion onset.
  • Valacyclovir and Famcyclovir both approved as oral.
    • Better oral bioavailability than oral acyclovir, and better for hastening healing of skin lesions, and reducing risk of post-herpetic neuralgia.
  • NOTE: Varicella Zoster Ophthalmicus -> Zoster reactivation in the ophthalmic division of trigeminal nerve
    • High risk of loss of vision and debilitating pain. 
  • Corticosteroids as part of management is controversial.

Pavrovirus B19

• Risk Factors:
  • Day Care & Kids exposure (usually pediatric illness - "Slapcheeck").
• Symptoms:
  • Acute symmetric small joint polyarthritis - Symmetric Swelling & Stiffness.
    • Often similar joint distribuish as Rheumatoid Arthritis
  • Flu-like symptoms
  • Classic "Slap Cheek" rash  (rash can be absent or atypical in adults)
• Diagnosis:
  • Presence of IgM to Pavrovirus B19 establishes diagnosis
• Management:
  • NSAIDs (i.e. ibuprophen)
  • Self limited!