Clin Med II Infectious Disease

1. Clin Med II Infectious Disease Lecture II—Viral Diseases, part 3/3

2. Measles

3. Measles • Acute systemic paramyxovirus • Inhalation of infective droplets • Major worldwide cause of morbidity and mortality • 750,000 deaths in 2000  197,000 deaths in 2007 • Rising rates of intentional undervaccination—sporadic outbreaks • Highly contagious

4. Measles • Fever (40-40.6 C or 104-105 F) • Malaise, coryza, cough, conjunctivitis • Koplik spots • Rash appears about 4 days after oonset • Pinhead-sized papules  brick-red, irregular, blochymaculopapular rash  may become uniform erythema • Face and behind ears  trunk  extremities • Erythematous pharynx with yellowish tonsillar exudate • Coated tongue • Generalized lymphadenopathy • Splenomegaly

5. Measles

6. Measles

7. Measles • Labs—Leukopenia, thrombodytopenia, proteinuria • Can culture virus from nasopharyngeal washings and blood • IgM measles bodies or 4x rise in serum hemagglutination inhibition, fluorescent antibody staining of respiratory or urinary epithelial cells • Complications • CNS—postinfectious encephalomyelitis—multiple forms—read in text • Bronchopneumonia, bronchiolitis, bronchiectasis • Secondary bacterial infections • Immune reactivity • Gastroenteritis • Conjunctivitis, keratitis, otosclerosis

8. Measles—Treatment • General—isolation until week following rash onset; bed rest until afebrile • Antipyretics and fluids • High dose vitamin A—maintains GI and respiratory mucosa • Treatment of secondary bacterial infections • Encephalitis—symptomatic treatment only

9. Measles • Prevention—immunization (12-15 mo, 4-6 yrs) • Do not give in pregnancy or immunosuppression • Report all cases to public health. Refer in cases of HIV and pregnancy • Admit: • Meningitis, encephalitis, myelitis • Severe pneumonia • Diarrhea that compromises fluid balance

10. Mumps

11. Mumps • Spread by respiratory droplets • Children are most commonly affected • Incidence highest in spring • Incubation 14-21 days • Up to 1/3 of infection--asymptomatic

12. Mumps • Parotid tenderness, swelling • Trismus • Glands usually normal within 1 wk • Fever and malaise • Meningitis • Orchitis—most common extrasalivary site in adults • Pancreatitis—most common cause of pancreatitis in children

13. Mumps • Labs—mild leukopenia, amylasemia (from salivary glands), mild kidney function abnormalities • CSF—pleiocytosis, hypoglorrhachia • Diagnosis—usually characteristic clinical picture • Isolate of virus from swab of the duct of the parotid or other affected salivary gland • Can isolate virus from CSF early in aseptic meningitis • Nucleic acid amplification—more sensitive than viral culture but limited availability • Elevated IgM--diagnostic

14. Mumps • Treatment—isolate till swelling subsides, bed rest till afebrile; symptomatic relief • Topical compresses • IVIG—can try for complicated disease but no consensus • Meningitis—symptomatic; manage cerebral edema, airway, vital functions • Epididymoorchitis—scrotal support, ice bags, pain relief • Pancreatitis—symptomatic, hydration • Usually lasts no longer than 2 weeks • Prevention—live virus vaccine; routine immunization • Often in combination with measles, rubella and VZV

15. Rubella

16. Rubella • Systemic disase—togavirus transmitted by inhalation of infective droplets • One attack usually confers permanent immunity • Difficult to distinguish from mono, measles, other viral illnesses—arthritis is more prominent in rubella • Principal importance—devastating effects on fetus in utero

17. Rubella • Fetal—devastating • Postnatally acquired—innocuous—up to 50% asymptomatic • Fever, malaise, tender suboccipital adenitis, coryza • Arthritis—fingers, wrists, knees • Early posterior cervical and postauricular lymphadenopathy • Erythema of palate and throat • Fine pink maculopapular rash on face, trunk and extremities in rapid progression (2-3 days) and fades quickly1 day in each area

18. Rubella

19. Rubella • Labs—leukopenia • Diagnosis—elevated IgM antibody, isolation of virus, 4x or greater rise in IgG • False positive IgM—Epstein-Barr, CMV, parvovirus, RF • Exposure during pregnancy—immediate hemagglutination-binding rubella antibody level • Infection during 1st trimester—congenital rubella in 80% • Evaluate immunization—titers fall to seronegativity in 10% of patients after about 12 yrs

20. Rubella • Congenital rubella—usually have wide variety of manifestations—eye disease, microphthatlmia, hearing deficits, psychomotor retardation, heart defects, organomegaly, maculopapular rash • Younger fetus at infection—more severe illness • Second trimester—deafness • Specific test for IgM rubella antibody • Postinfectious encephalopathy—mortality rate 20%

21. Rubella • Treatment—symptomatic (acetaminophen) • Prognosis—mild—rarely lasts more than 3-4 days • Congenital—high mortality rate and permanent defects • Prevention—live attenuated rubella virus vaccine—often in combination with measles, mumps, and varicella • Try to immunize girls prior to menarche • Do not give immunization during pregnancy • In US—80% of 20-year-old women are immune to rubella

22. Roseola

23. Roseola • Human herpesvirus 6—principal cause of exanthema subitum • Primary HHV6—children under 2 years; major cause of infantile febrile seizures • May also see encephalitis and acute liver failure • HHV6 encephalitis—hippocampus, amygdala, limbus • Symptomatic HHV6 is rare in immunocompetent adults—mono-like illness (primary) or encephalitis (reactivated) • Can see infection during pregnancy / congenital transmission • Reactivated disease—mainly in immunocompromised adults—associated with graft rejection, graft-versus-host disease • May cause fulminant hepatic failure and acute decompensation of chronic liver disease in children

24. Roseola

25. Influenza

26. Influenza • Highly contagious—respiratory droplets • 3 types of viruses—Type A infects many mammals and birds, Types B and C infect humans almost exclusively • Type A—subtypes from hemagglutinin (H) and neuraminidase (N) • Annual epidemics in fall and winter—10-20% of global population each year • Pandemics—longer intervals (decades)—major genetic reassortment of virus or mutation of animal virus • Main current viruses—H1N1 and H3N2 subtypes and type B.

27. Influenza • Types A and B—clinically indistinguishable infections • Type C—minor • Abrupt onset—Fever, chills, malaise, myalgias, cough substernal soreness, headache, nasal stuffiness, nausea • Elderly—may present with only lassitude, confusion • Mild pharyngeal infection, flushed face, conjunctival redness, cervical lymphadenopathy • Labs—leukopenia, may see leukocytosis; proteinuria; isolate virus from throat swasbs, nasal washings, cell cultures • Rapid assays—nasal or throat swabs—60-80% sensitivity

28. Influenza • Complications—necrosis of respiratory epithelium—secondary bacterial infections • Bacterial enzymes activate influenza viruses • Frequent complications—sinusitis, otitis media, purulent bronchitis, pneumonia • Young children, pregnant women, elderly, LTC facility patients, patients with comorbidities—higher risk of complications • Read—Reye Syndrome

29. Influenza • Treatment—bed rest, analgesics, cough medicine • Treat - suggestive clinical infection or laboratory confirmed influenza and high risk for complications • No proven benefit of antivirals after 48 hrs, but should consider if patient is hospitalized • Neuraminidase inhibitors—inhaled zanamivir or oral oseltamivir—equally effective in treatment • reduce duration of symptoms and secondary complications • do not reduce hospitalizations or mortality • Adamantanes—amantadine and rimantadine—high levels of resistance and not recommended for treatment • Prognosis—uncomplicated lasts 1-7 days; excellent prognosis in healthy, nonelderly adults • Prevention—annual administration of influenza vaccine • Read—information on flu vaccine including contraindications

30. HPV

31. Human Papilloma Virus • Skin Warts—flat (superficial) or plantar (deep growths)—typically regress over time—HPV 1-4 • Benign Head and Neck Tumors— • single oral papillomas—pedunculated with stalk and rough papillary appearance • Laryngeal papillomas—most often caused by HPV-11—most common benign epithelial tumors of larynx; can cause airway obstruction in children • CondylomaAcuminata—almost exclusively on squamous epithelium of external genitalia and perianal areas • 90% due to HPV 6 and HPV 11

32. Human Papilloma Virus—Skin Warts

33. Human Papilloma Virus—Oral papilloma

34. Human Papilloma Virus—CondylomaAcuminata

35. Human Papilloma Virus—CondylomaAcuminata

36. Human Papilloma Virus • Cervical dysplasia—koilocyotic cells—HPV 16-18 (70%) • Dysplasia—40-70% of lesions spontaneously regress • Progressive changes from mild (CIN I) to moderate (CIN II) to severe (CIN III) dysplasia, carcinoma in situ, or both

37. HPV Diagnosis • wart can be confirmed microscopically by histologic appearance—hyperplasia of prickle cells and excess keratin • HPV infection—koilocytoctic (vaculolated) squamous epithelia cells that are rounded and occur in clumps • HPV virions on electron microscopy • Molecular probes for HPV DNA—establish in cervical swab and tissue • HPV does not gro in cell cultures • HPV antibodies—rarely used

38. Human Papilloma Virus • Treatment—spontaneous disappearance of warts is the rule; may take months to years • Cryotherapy, Electrocautery, Chemical • Recurrences are common • See guidelines for follow-up on cervical dysplasia • Prevention—HPV quadrivalent vaccine (Gardasil) • Types 6,11,16,18

39. HIV

40. HIV Whole chapter of its own—I suggest you read!  You should know: • Major risk factors/Modes of transmission • Presenting symptoms (Hallmark of symptomatic HIV?) and major complications • Prevention measures • HIV risk for health care professionals • Major pathogens that need prophylaxis • Indications for antiretroviral therapy

41. Questions?