Clin Med II Infectious Disease

Clin Med II Infectious DiseaseLecture IIViral Diseases, part 2/3Herpes Simplex VirusWhats with all the numbers?Human HerpesvirusesHHV 1Herpes Simplex Virus type 1HHV 2Herpes Simplex Virus type 2HHV 3Varicella Zoster VirusHHV 4Epstein-Barr VirusHHV 5CytomegalovirusHHV 6Roseola InfantumHHV 7The MultitaskerRoseola, Seizures, Encephalitis, helps CMV in renal transplantsHHV 8Kaposi sarcoma/primary effusion lymphomaHerpes Simplex VirusHSV-1oral HSV-2genitalRisksin textblack race, female gender, lower socioeconomic status, and high-risk sexual historyAsymptomatic shedding HSV-2 and HIVlinkedHSV-2 increases risk of HIV HSV-2 reactivates more often in advanced HIVHSV-2 suppression can decrease HIV-1 plasma level and genital tract shedding

Mucocutaneous HSV-1HSV-1mouth and oral cavityherpes labialis or gingivostomatitisHerpetic whitlowpainful digital lesionsHerpes gladiatorumpainful rash transmitted classically by sports contactFrequent asymptomatic sheddingmonthly or moreVesiclesulcers (1-2 days)epithelialization (1-2 wks)Recurrences--fewer lesions, labial, heal fasterTriggersstress, fever, infection, sunlight, chemo, ???Mucocutaneous HSV-1

Mucocutaneous HSV-1

Mucocutaneous HSV-1

Mucocutaneous HSV-2Primarily involves genital tractMay affect perianal region, buttocks, upper thighsMultiple, painful, small, grouped, vesicular lesionsDysuria, cervicitis, urinary retentionIncreased HSV-2 lesion ratespostpartum period and among women who have sex with womenHIV patientsproctitis and sacral lesionsextensive, ulcerating, weeping lesions Drug-resistant isolateslarge ulcerations, atypical lesionsMucocutaneous HSV-2

Mucocutaneous HSV-2

Mucocutaneous HSV-2

Mucocutaneous HSV DiagnosisClinicalStandardviral cultures of vesicular fluid or direct immunofluorescent antibody staining of lesionsIntranuclear inclusion bodiesMultinucleated giant cells on Tzanck smear or Calcofluor prep

Mucocutaneous HSV Treatment often not necessary in immunocompetent ptsGenital infectionoral agentsacyclovir, valacycloivr, famiciclovirPrimary7-10 days and higher doses; Recurrent1-3 daysPrimary herpes labialisoral antivirals as for primary genitalRecurrent herpes labialistopical acyclovir and hyrocortisone, topical penciclovir, or oral antiviralsImmunocompromisedconsider IV antiviralsAtypical isolates, large ulcerations, new lesions, poor responseSecondary prophylaxisrecurrent infectionsdaily oral antiviralsOcular HSVKeratitis, Blepharitis, KeratoconjuncitvitsIf epithelialheal without vision impairmentIf stroma involveduveitis, scarring, blindnessFrequent recurrenceSecond most common cause of acute retinal necrosis

Ocular HSVBranching (dendritic) ulcers on fluorescein stainTreat with topical antiviralsAcute retinal necrosisIV acyclovir or oral famciclovirTopical steroidsmay exacerbateLong term treatment can reduce recurrences

Congenital/Neonatal HSVHSV-1 and HSV-2Congenitalorganomegaly, bleeding, CNS abnormalitiesNeonatal is more common than congenitalHighest riskmaternal infection in 3rd trimester70% of infections are asymptomatic or unrecognized

Congenital/Neonatal HSVTreat disseminated lesions with IV acyclovir for 2-3 weeksCounseling with serologic screening should be offered to pregnant mothersMaternal antenatal suppressive therapy with acyclovir at 36 weeks gestationC-section for pregnant women with active genital lesions or prodromal symptomsHSV and CNS DiseaseHSV-1: HSV Encephalitis, may enhance Alzheimer diseaseEncephalitis symptoms: flu-like prodrome, headache, fever, behavioral or speech disturbances, seizuresHigh mortality rateuntreated, presentation with comaDoes not occur disproportionately among immunocompromised

HSV-2: Meningitis (primary or recurrent)

Both HSV-1 and HSV-2: benign recurrent lymphocytic meningitis; mild, nonspecific neurologic symptoms

HSV Encephalitis and Recurrent MeningitisCSF Pleocytosis commonHSV DNA PCR of CSFrapid, sensitive, specific but can have up to 25% false negativesMRI scanningincreased signal in temporal and frontal lobesIV acyclovir q 8 hours for 10+ days if suspected HSV encephalitisLong term neurologic sequelae are common

HSV Encephalitis

Other HSV ManifestationsDisseminatedimmunosuppression, pregnancyBells Palsyassociated with HSV-1EsophagitisHSV-1; immunocompromisedProctitisprimarily in men who have sex with menErythema multiformeleading association with EM and SJS (along with medications)Acute liver failure1% of cases but 75% mortalityLower respiratory tractmechanically ventilated ptsHSV-1perinephric abscess, febrile neutropenia, chronic urticaria, SLE-related esophagitis and enteritis, H. pylori-negative upper GI ulcers, atrial myxomaHSV PreventionAntiviral suppressive therapyCounselingBarrier precautionsDisclosure of partner status50% decrease in HSV-2 transmissionHand washing and glove/gown precautionsHSV-2 glycoprotein D vaccine is under developmentVaricella Zoster VirusVaricella Zoster VirusManifests as chickenpox (varicella) and shingles (zoster)Varicellatypically in childhood; incubates 10-20 daysHighly contagiousdroplet inhalation or lesion contactZosterup to 25% of population; increases with age

VaricellaFever and malaisePruritic rashMaculopapulesvesiclespustulescrustsMultiple stages of eruption usually present simultaneouslydew drop on rose petalComplicationssecondary bacterial infection, pneumonitis, encephalitisin 1%More severe in older pts and immunocompromised

ZosterMostly among adultsPainsevereoften precedes rashVaricella-like lesionsusually in dermatomal distributionHerpes Zoster Ophthalmicuslesions on tip of nose, inner corner of eye, and root and side of the nose (Hutchinson sign)Herpes Zoster Oticusfacial palsy, lesions of ear +/- TM involvement, vertigo, tinnitus, deafness (Ramsay Hunt syndrome)Contact with varicella patientsnot a risk factorHerpes Zoster Ophthalmicus

Herpes Zoster Oticus

Varicella Zoster VirusDiagnosisusually clinical Confirm with direct immunofluorescent antibody staining or PCR of scrapings from lesionsMultinucleated giant cells on Tzanck smearLeukopenia and subclinical AST/ALT elevationThrombocytopeniaVaricella skin test and ELISPOTVZV susceptibilityVaricella ComplicationsSecondary bacterial skin superinfectionsInterstital VZV pneumoniaNeurocerebellar ataxia, encephalitisPurpura fulminansextremely rareLiverhepatitis, Reyes syndromePregnancy1st or 2nd trimesters, small risk of congenital malformations3rd trimester, risk of disseminated disease 31Zoster ComplicationsPostherpetic neuralgia60-70% of pts >60 years oldBacterial skin superinfectionsHerpes zoster ophthalmicus or unilateral ophthalmoplegiaCranial nerve involvement Aseptic meningitisPeripheral motor neuropathyTransverse myelitisEncephalitisAcute cerebellitisStroke or vasculopathyAcute retinal necrosis or progressive outer retinal necrosis32VZV Encephalitis

33VZVTreatment General treatment measuresinitial isolation; bed rest till afebrile; control of pruritisAntiviralsAcyclovir within 24 hours after rash onsetConsiderpatients over 12 years old, secondary contacts, patients with chronic cutaneous and cardiopulmonary disease, and children on long-term salicylate therapyHigh dose IV antiviralsfor immunocompromised patients, pregnancy (3rd trimester), extracutaneous diseaseProphylaxis for profoundly immunosuppresed patientsPostherpetic neuralgiagabapentin, lidocaine patchesTricyclic antidepressants, opioids, capsaicin creamEpidural injection of steroids and anestheticsVZVPrognosis and PreventionVaricelladuration usually 2 weeks or less; fatalites rareZoster2-6 weeks; greater antibody responseOphthalmic involvementperiodic exams

Screen healthcare workers and vaccinate if negativeWorkers with zoster should receive antiviral agents during 1st 72 hours of disease and stay away from work until lesions are crustedIsolate patients with active VZV from negative contactsVaricella VaccinationUniversal childhood vaccination against varicella98.1% effective when given after 13 months of age1st dose 12-15 months, 2nd dose 4-6 yearsAvoid aspirin for at least 6 weeksSeronegative individuals over 13 years old2 doses of varicella vaccine 4-8 weeks apartConsider vaccination for HIV + adolescents and adults with CD4 200 cells/mcL or higherAlso other selected immunocompromised pts (see text)Varicella incidence decreased 67%-87% due to vaccinationPostexposure vaccination recommended for unvaccinated persons without other evidence of immunityVaricella Zoster immunoglobulinconsider for susceptible pts who cannot receive vaccine

Zoster VaccinationLive attenuated VZV vaccinefor patients 60 and olderReduces incidence of postherpetic neuralgia by 67%Reduces incidence of herpes zoster by 51%Should not co-administer with pneumonia vaccine Rabies RabiesViral encephalitis transmitted by infected saliva50,000-100,000 deaths/year globallyIn USdog rabies has almost disappeared, but wildlife rabies has greatly increasedIncubation10 days to years (usually 3-7 weeks)Inoculation site nerves brain efferent nerves salivary glandsForms cytoplasmic inclusion bodiesAlmost uniformly fatal

Rabies SymptomsHistory of animal bite (may not notice bat bite)Pain (at bite location), fever, malaise, headache, nausea, vomitingAerophobia and sensitivity to temperature changePercussion myoedema10 days after prodromeCNS stageEncephaliticfurious80%--classic rabies symptomsParalyticdumb20%--acute ascending paralysisProgresses to coma, ANS dysfunction, and deathRabies DiagnosisBitten animals that appear wellquarantine 10 daysIll or dead animalstest for rabiesIf animal cannot be examinedpresume that raccoons, skunks, bats, foxes, bats and foxes are rabidDirect fluoroscent antibody testingskin material from posterior neck60-80% sensitivityDefinitive diagnostic assaysRT-PCRnucleic acid sequence-based amplificationdirect rapid immunohistochemical testviral isolation from CSF or salivaRabies TreatmentIntensive careairway, oxygenation, seizure controlUniversal precautionsPostexposure prophlaxis given prior to symptomsnearly 100% successful in disease preventionOnce symptoms have appeared, death almost inevitably occurs after 7 days, usually from respiratory failure

RabiesPreventionImmunization of household dogs, cats, and patients with significant animal exposureCleansing, debridement, and flushing of woundsDo not suture animal bite woundsDecision to treat with immune globulin or antiserumvaries with circumstances of biteConsult with state and local health departmentsGive treatment as promptly as possible if indicatedReadwhen to admit, when to referQuestions?