1. Common Viral Infections: Influenzaviruses and Herpesviruses
Tintinalli: Chapter 143
Dave Piatt

2. Influenza A & B Antigenic drift Antigenic shift
Minor mutations of the H or N molecule
Antigenicity changes with mutations
Causes annual epidemics (usually type A)
Antigenic shift
New virus produced by genetic reassortment within a host infected by two different influenzaviruses
Population lacks immunity against new virus
Causes major flu pandemics (such as in 1918)

3. Influenza Epidemiology Spread via droplets produced during cough
Occurs Nov. thru April in the U.S.
Occurs year-round in the tropics
Spread via droplets produced during cough
Incubation period is 2 days
Viral shedding (contagiousness) starts 24 hours before onset of symptoms

4. Influenza Clinical features (onset is usually rapid)
Fever (38.6o – 39.8o) for 2-4 days
Chills/rigor
Headache
Myalgias
Malaise
Cough
Rhinorrhea
Sore throat
Elderly often do not have classic symptoms and may have only fever, malaise, confusion, and congestion

5. Influenza
Diagnosis
Clinical diagnosis during outbreak has an accuracy of about 85%
Rapid antigen tests
Decrease empirical antibiotics
Sensitivity 57-81%
Specificity %

6. Influenza Complications Pneumonitis Secondary Pneumonia
Flu symptoms progressing to cough and dyspnea
Hypoxia
Bilateral infiltrates on CXR similar to ARDS
Supportive treatment
Secondary Pneumonia
Occurs 1-2 weeks after flu
Treat with broad spectrum antibiotics and pulmonary support
COPD, Reye syndrome (with aspirin use), croup, myocarditis are also complications

7. Influenza Treatment Amantadine and rimantadine (100 mg BID X 5 days)
Approved for type A only; not active against type B
If started within 48 hours of onset of symptoms, it can reduce duration of symptoms by 1-2 days
Avoid in pregnancy
Approved for children over 1 year of age
Oseltamivir and zanamivir (Tamiflu and Relenza)
Active against types A & B
Reduces duration of symptoms by 1 day if started within 48 hours of onset of symptoms

8. Influenza Prophylaxis
Annual formulation contains 2 strains of type A and 1 strain of type B
70-90% effective in those under age 65
Recommended for all persons over age 65, residents of chronic care facilities, patients with chronic cardiopulmonary disease, diabetes, metabolic disease, or renal disease; immunosuppressed patients, and healthcare workers
Safe for pregnant/lactating women
Anti-influenza medicines are 75-90% effective in preventing influenza if given as a 6-8 week course during peak flu season

9. Herpesviruses Dwell in host as a lifelong latent infection
May cause clinical disease at a time distant from the primary infection
Some are carcinogenic
Varicella-zoster virus (VZV) is spread via aerosolized particles and close contact
Herpes simplex virus (HSV) and Epstein-Barr virus (EBV) transmission occurs during asymptomatic shedding

10. Herpes Simplex 1 & 2 Epidemiology
Transmitted via infected secretions on mucous membranes or open skin
HSV-2 is primarily transmitted sexually

11. Herpes Simplex 1 & 2 Oral HSV Primarily HSV-1, but can be HSV-2
Primary lesion lasts 1-2 weeks
Lesions recur in 60-90% of infected people
Recurrences triggered by local trauma, illness, or stress
Treatment: acyclovir 400 mg PO 5 times/day (topical acyclovir is ineffective)
Prophylaxis: oral acyclovir reduces outbreaks by % in those with frequent/severe outbreaks

12. Herpes Simplex 1 & 2 Genital HSV Ocular HSV Majority caused by HSV-2
Covered in chapter 141 (STDs)
Ocular HSV
Usually HSV-1
Ulcerative keratitis is most common manifestation. May lead to corneal blindness
Vesicles may be seen on the conjunctiva or lid
Fluorescein stain may show corneal dendritic ulcers
Ophthalmologic consultation is imperative, and patient may need to be admitted for IV acyclovir

13. Herpes Simplex 1 & 2 Encephalitis Usually HSV-1
Temporal lobes are the major target and lesions may be seen on CT and MRI
Presents as headache, fever, and altered mental status with preceding viral-like illness. Patients may have olfactory hallucinations
CSF findings: elevated WBCs with mononuclear predominance
Empirical treatment with IV acyclovir at 10 mg/kg every 8 hours should be initiated if suspicion exists
If untreated, mortality rate is 70%

14. Herpes Simplex 1 & 2 Bell Palsy Usually HSV-1
Causes palsy of the peripheral branch of CN VII
Presents as facial hemiplegia or hemiparesis, taste disturbance, decreased blinking, dry eyes, facial numbness, and jaw/face pain
Central CN VII lesions spare the forehead but cause unilateral lower facial weakness. Peripheral lesions result in forehead paralysis. Attempting to close the eye on the affected side results in an upward gaze (Bell phenomenon)

15. Herpes Simplex 1 & 2 Bell Palsy
Examination of the ear, tympanic membrane, mastoid, and parotid gland should be normal
Bell palsy with otitis media, mastoiditis, or parotitis is an ENT emergency
Vesicles on the TM or canal is diagnostic of Ramsay Hunt syndrome
Differential includes stroke, tumor, atypical Guillain-Barre, and Lyme disease
Treatment: prednisone 60 mg PO X 5 days with acyclovir 400 mg 5 times/day for 10 days
Eye care with artificial tears is the most important therapeutic intervention made by the ED physician

16. Herpes Simplex 1 & 2 Herpetic Whitlow
HSV infection of the finger (usually one digit)
HSV-1 is seen in children who self-inoculate during an episode of oral herpes and in health care workers (dentists)
HSV-2 more common if digital/genital contact
Very painful and accompanied by axillary adenopathy
Vesicles contain necrotic epithelial cells, not pus. If confused with paronychia and the finger is incised, delayed healing and secondary infection may occur
Spontaneously heals in 2-3 weeks, may use acyclovir

17. Herpes Zoster: Chickenpox
HZV is human herpesvirus 3
Primary infection is chickenpox
Reactivates later as zoster (shingles)
Epidemics occur late winter/early spring
Spread via respiratory droplets
Patients are infectious 48 hours before rash appears until the vesicles have crusted over
Rash appears 14 days after exposure. The virus becomes latent in a dorsal root ganglion

18. Herpes Zoster: Chickenpox
Clinical features
Prodrome of 1-2 days of fever, malaise
Clear vesicles on an erythematous base appear on the face and trunk, then spread centripetally to the extremities. New lesions will appear and the old ones will become turbid and scab over. The hallmark of chickenpox is vesicular lesions in various stages
Complications can include encephalitis, cerebellar ataxia, pneumonitis, and Reye syndrome
Mortality rate among adults is 15 times higher than in children
Chickenpox during pregnancy can cause fetal abnormalities

19. Herpes Zoster: Chickenpox
Treatment
Over age 12
Acyclovir 800 mg PO QID X 5 days started within 24 hours of onset of rash
Neonates of mothers who developed chickenpox 5 days before delivery or within 48 hours postpartum
Varicella-zoster immune globulin (VZIG) to confer passive immunity
Patients with varicella encephalitis, pneumonitis, or who are immunocompromised should be admitted for IV acyclovir
Varicella vaccine recommended for children over age 1 year. It is a live vaccine and is contraindicated in immunocompromised patients and in pregnant/lactating women

20. Herpes Zoster: Shingles
Is a reactivation of latent VZV infection
Lifetime incidence of 20%, usually in elderly
Lesions limited to a single dermatome, usually thoracic or lumbar
Begins as a prodrome of pain for 1-3 days in the affected area, followed by a maculopapular rash that progesses to vesicles
Disease course is 2-4 weeks
Disseminated disease can cause pneumonitis, hepatitis, or meningoencephalitis

21. Herpes Zoster: Shingles
Complications:
Herpes zoster ophthalmicus (HZO)
Involves the ophthalmic branch of CN V
Vision-threatening
Hutchinson sign (lesion of tip of nose) may be seen before ocular involvement
May also see a dendriform corneal ulcer with fluorescein staining
Mandatory ophthalmologic consult

22. Herpes Zoster: Shingles
Complications:
Ramsay Hunt syndrome
Involves the geniculate ganglion of CN VII
Presents with facial palsy, unilateral weakness, loss of taste, and ear canal or TM vesicles
May also see intraoral lesions
May be a cause of mental status change in elderly
Presentation and treatment are similar to Bell palsy
Admit immunocompromised patients for IV acyclovir

23. Herpes Zoster: Shingles
Complications:
Postherpetic neuralgia
Most common complication
Occurs in 10-20% of all shingles cases, and in 70% of patients over age 70
Resolves in 1-2 months
First-line treatment is systemic analgesics; second-line treatment is amitriptyline or carbamazepine
Corticosteroids improve quality-of-life in elderly
Start 21-day taper at 60 mg PO daily

24. Epstein-Barr Virus: Infectious Mononucleosis
Human herpesvirus 4
Spread by close contact, such as kissing
Incubation period of 1-2 months, followed by prodrome of malaise, fatigue, and fever
Classic symptoms include fever, sore throat (exudative pharyngitis), lymphadenopathy, splenomegally, and atypical lymphocytosis. Bilateral tender cervical adenopathy is universal
Hepatomegally and jaundice is common in adults

25. EBV: Infectious Mononucleosis
Palpable splenomegally occurs in ½ of patients, most prominent during week 2 of the illness
The incidence of splenic rupture is % and is generally at week 2-3 of the illness. Patients should be instructed to avoid contact sports and strenuous activity for 4 weeks
Complications of mono include hemolytic anemia, thrombocytopenia, encephalitis, meningitis, obstructive tonsillitis, and lymphoma

26. EBV: Infectious Mononucleosis
Lab analysis may show elevated WBC with increased atypical lymphocytes and monocytes
Commercial tests (monospot) are 78-83% sensitive and % specific. Patients with classic EBV symptoms and a negative monospot should have a repeat monospot in 1 week
Treatment is supportive. If penicillin is given to treat a suspected strep pharyngitis, 95% of patients will develop a rash

27. Cytomegalovirus Human herpesvirus 5
Causes a primary illness and then exists in a latent state in the host until reactivation
Found in milk, saliva, urine, semen, and cervical secretions
Also transmitted during blood transfusions and bone marrow and organ transplantations
One of the TORCH agents known to cause intrauterine infections

28. Cytomegalovirus
Infection is usually asymptomatic, but symptoms can include fever, chills, myalgias, and headache. Fever may last for 1-5 weeks
May see atypical lymphocytosis, splenomegally, lymphadenopathy, and increased LFTs
Consider CMV in patients with mono-like symptoms but who are monospot negative

29. Cytomegalovirus
10% of AIDS patients develop CMV retinitis, which causes floaters or decreased vision. Fundoscopic exam may show retinal hemorrhages or exudates. Without treatment, this will progress to blindness
Treat with IV ganciclovir or foscarnet

30. Cytomegalovirus
CMV causes significant morbidity and mortality in post-transplant patients
Pneumonia is the most common infection
Most common in bone marrow transplant patients
CMV should be considered for a fever within 3 months of a transplant

31. Cytomegalovirus Treat CMV with ganciclovir or foscarnet
Ganciclovir is approved for CMV retinitis in AIDS patients and for CMV prevention in transplant patients
Foscarnet is used for resistant CMV infections or for patients unable to take ganciclovir
Neither medication cures patients of CMV, but they suppress the acute disease process

32. Questions 1. Bell palsy involves which cranial nerve? A. CN IV B. CN V
C. CN VI
D. CN VII
E. CN VIII
2. Which is false regarding influenza?
A. The vaccine is unsafe in pregnancy
B. Amantadine is effective against types A and B
C. Complications of influenza include pneumonia, pneumonitis, and COPD exacerbation
D. The vaccine is 70-90% effective
E. Antigenic drift causes annual epidemics
3. Incision of a herpetic whitlow vesicle will produce pus
T or F?

33. 4. Which of the following is false regarding EBV?
A. Splenomegally is palpable in % of all patients with infectious mononucleosis
B. Bilateral cervical adenopathy is nearly universal
C. Virus is spread by close contact, such as kissing
D. Atypical lymphocytosis is a common finding
E. Treatment is primarily supportive
5. Retinitis in AIDS patients is usually caused by which virus?
A. VZV
B. EBV
C. CMV
D. HSV-1
E. HSV-2

34. Answers
1. D
2. B
3. False
4. A
5. C