Table of contents
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Epstein-Barr Virus (EBV)
Introduction
- Ubiquitous (90-95% of pop'n have evidence of infection).
- 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)
- Common: (due to T cell and NK cell poliferation and cytokine response)
- Characteristic: Giving ampicillin during early EBV mononucleosis --> Maculopapular rash.
- After intial infection, EBV persists for life in B-cells and oropharyngeal cells (lytic infection)
- 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)
- 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).
- Mononucleosis (heterophil (Monospot) - negative mononucleosis)
- Immunocompromised:
- Severe disease in many organ systems:
- Retinitis
- Hepatitis
- Pneumonitis
- GI disease (gastric/esophageal ulcers, colitis)
- Enteritis
- Esophagitis
- Colitis
- Gastritis
- Meningoencephalitis
- Polyradiculopathy
- Severe disease in many organ systems:
- Pregnant
- Primary infection of pregnant woman causes neonatal disease:
- jaundice, petechiae, microcephaly, chorioretinitis, cerebral calcifications, mental retardation, neonatal death, deafness.
- Primary infection of pregnant woman causes neonatal disease:
- 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.
- Normal host: Almost never required
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.
- Influenza A - many hosts, subdivided based on surface proteins (Hemaglutinin and Neuraminidase)
- 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.
- Pneumonia (esp if underlying chronic illnesses) - primary viral pneumonia, secondarily bacterial can occur (or both).
- Fever, headache, myalgia, non-productive cough, sore throat, nasal discharge.
- 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.
- Trivalent (inactivated) - injected.
- 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
- Both - neuraminidase inhibitors for Influenza A and B.
- 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.
- In patients >13yo not immunized and no evidence of immunity, give two doses 4-8w apart.
- 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.
- Useful in preventing and lessening symptomatic varicella in high risk patients (after exposure)
- 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.
- Varicella immunization routinely recommended in children 12-15mo with second dose at ages 4-6yo.
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)
- Acute symmetric small joint polyarthritis - Symmetric Swelling & Stiffness.
- Diagnosis:
- Presence of IgM to Pavrovirus B19 establishes diagnosis
- Management:
- NSAIDs (i.e. ibuprophen)
- Self limited!
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