Viral Illnesses

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    Epstein-Barr Virus (EBV)

    Introduction

    • Ubiquitous (90-95% of pop'n have evidence of infection).EBVpath.png
    • In US 50% of kids seropositive at 5 yrs, and the rest seroconvert in early adulthood.
    • Transmission: via oropharyngeal secretions of asymptomatic shedding ("Kissing disease").
    • Infects B-cells.

     

     

    Symptoms/Diagnosis

    • Symptoms:
      • Common:   (due to T cell and NK cell poliferation and cytokine response)
        • fever
        • Sore throat/tonsillitis (can be exudative)
        • malaise
        • lymphadenopathy (non-tender)
        • nasal congestion
        • Very difficult to distinguish from Group A Strep throat infection.  A hint of mono (EBV) is that it doesn't improve after 1 week of sx (strep throat should 
      • Decreasing frequency:
        • Splenomegaly (LUQ pain)
        • hepatitis
        • palatal petechiae
        • jaundice
        • rash (non specific)
      • Some patients develop chronic active infection (ongoing lytic EBV replication).  Can involve multiple organs such as pneumonitis, hepatitis, pancytopenia, and iritis.
        • High risk is inherited X-linked immunodeficiency (Duncan syndrome)
    • Characteristic: Giving ampicillin during early EBV mononucleosis --> Maculopapular rash.
    • After intial infection, EBV persists for life in B-cells and oropharyngeal cells (lytic infection)
      • However if pt is immunosuppressed or immunodeficient: uncontrolled oligoclonal and monoclonal B cell proliferation of latently infected cells.  Uncontrolled pharynx infection manifested by oral hairy leukoplakia

                            hairyLeukoplakia.jpg
                                                                 (Hairy Leukoplakia)
    • Persistent Infection also associated with:
      • Burkitt's lymphoma
      • Nasopharyngeal carcinoma
      • Types of Hodgkin's disease
      • Gastric adenocarcinoma
      • Leiomyosarcoma in HIV host.
    • Investigations:
      • Heterophile antibodies (a monospot test)

    Cytomegalovirus (CMV)

    • CMV.jpg
    • 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!
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