Antiviral therapyAntiviral therapy

Practical PointsPractical Points

No treatment for most viral diseaseNo treatment for most viral disease Prevention is the mainstayPrevention is the mainstay

VaccinationsVaccinations Social distancingSocial distancing Hand hygieneHand hygiene

Antibiotic stewardshipAntibiotic stewardship

OverviewOverview

Identify the few situations where Identify the few situations where viral infections are treatableviral infections are treatable

Understand BASIC mechanism of Understand BASIC mechanism of action (when known) of appropriate action (when known) of appropriate antiviral, window when intervention antiviral, window when intervention is meaningful, resistance patterns is meaningful, resistance patterns and toxicity of treatmentand toxicity of treatment

N.B. Viral hepatitis will be discussed later this week and will not be covered

Case 1Case 1

35 year old male with 4 days of 35 year old male with 4 days of rhinorrhea, nasal congestion and rhinorrhea, nasal congestion and pharyngitis; he mentions this pharyngitis; he mentions this incidentally during his routine follow incidentally during his routine follow up for HLP.up for HLP. 4 children at home, 2 of them are under 4 children at home, 2 of them are under

5 and in day care 5 and in day care

Case 1Case 1

What is the likely pathogen?What is the likely pathogen? What is the only intervention shown What is the only intervention shown

to have efficacy in this situation? to have efficacy in this situation? (despite numerous trials)(despite numerous trials)

When is the therapeutic window?When is the therapeutic window? When do we start worrying this might When do we start worrying this might

not be a virus and feel inclined to not be a virus and feel inclined to treat (i.e. acute bacterial sinusitis)?treat (i.e. acute bacterial sinusitis)?

RhinovirusRhinovirus

What is the only intervention shown What is the only intervention shown to have efficacy in this situation? to have efficacy in this situation? (despite numerous trials)(despite numerous trials) Zinc (nasal gel better than lozenge) Zinc (nasal gel better than lozenge)

Inhibits RNA polymeraseInhibits RNA polymerase – – not echinacea, Vit Cnot echinacea, Vit C

When is the therapeutic window?When is the therapeutic window? First 24 hrs, and only decreases time to First 24 hrs, and only decreases time to

resolution by 1-2 daysresolution by 1-2 days

Case 2Case 2

You are on your geriatric rotation in You are on your geriatric rotation in February and while on rounds the February and while on rounds the charge nurse informs you of 6 charge nurse informs you of 6 residents with myalgias, respiratory residents with myalgias, respiratory illness and fever, 2 of whom were illness and fever, 2 of whom were hospitalized yesterdayhospitalized yesterday

The remaining 4 have become symptomatic The remaining 4 have become symptomatic over the last dayover the last day

Case 2Case 2

What is the viral likely pathogen?What is the viral likely pathogen? What is the significance of the month and What is the significance of the month and

setting of infection?setting of infection? What is your intervention?What is your intervention?

What info would be helpful in making your What info would be helpful in making your decision?decision?

What aspects of drug toxicity and tx spectrum What aspects of drug toxicity and tx spectrum are important to consider? are important to consider?

What could have prevented this outbreak? What could have prevented this outbreak? (possibly) – think broadly (i.e. introduction and (possibly) – think broadly (i.e. introduction and propagation)propagation)

InfluenzaInfluenza

What is the significance of the month and What is the significance of the month and setting of infection?setting of infection? Waning immunity in nursing home residents from Waning immunity in nursing home residents from

initial vaccination (and overall poor response)initial vaccination (and overall poor response) What is your intervention?What is your intervention?

Neuraminidase inhib +/- rimantidine*Neuraminidase inhib +/- rimantidine* (w/i 48 hrs sx)(w/i 48 hrs sx)

What info would be helpful in making your What info would be helpful in making your decision?decision?

Current influenza activity in the communityCurrent influenza activity in the community http://www.cdc.gov/flu/weekly

*http://www2a.cdc.gov/HAN/ArchiveSys/ViewMsgV.asp?AlertNum=00279

InfluenzaInfluenza

What aspects of drug toxicity and tx What aspects of drug toxicity and tx spectrum are important to consider?spectrum are important to consider? Oseltamavir – NA/particle cleavage and Oseltamavir – NA/particle cleavage and

release; GI sxrelease; GI sx Zanamavir – NA/particle cleavage and Zanamavir – NA/particle cleavage and

release; asthma exacerbation, requires release; asthma exacerbation, requires cooperative patientcooperative patient

Rimantidine – ? Viral Uncoating; (only good Rimantidine – ? Viral Uncoating; (only good for flu A)for flu A)

Ribavirin – guanosine analogue; not FDA Ribavirin – guanosine analogue; not FDA approved for flu, off-label for combo with approved for flu, off-label for combo with oseltoselt

InfluenzaInfluenza

What could have prevented this What could have prevented this outbreak? (possibly) – think broadly outbreak? (possibly) – think broadly (i.e. introduction and propagation)(i.e. introduction and propagation) Revaccination of residents (?) – Revaccination of residents (?) –

probably notprobably not Compliance with vaccination of HCPsCompliance with vaccination of HCPs

(usu <50%) - YES(usu <50%) - YES

50K die and 350K are hospitalized each year from SEASONAL influenza in the US

Avian Influenza – 1997 and Avian Influenza – 1997 and forwardforward

Total # of human deaths = 254 (63% case Total # of human deaths = 254 (63% case fatality)fatality)

# countries = 15, leading: Indonesia, Viet # countries = 15, leading: Indonesia, Viet NamNam

Animal control (vaccination and culling) Animal control (vaccination and culling) controls the infectioncontrols the infection Government compensation is keyGovernment compensation is key

Use of PPE, avoidance of bird markets, Use of PPE, avoidance of bird markets, thorough cooking of potentially infected meat thorough cooking of potentially infected meat

Neuraminidase inhibitors work, theoreticallyNeuraminidase inhibitors work, theoretically Increasing resistanceIncreasing resistance

Human vaccine in the worksHuman vaccine in the workshttp://www.who.int/csr/disease/avian_influenza/country/cases_table_2009_02_09/en/index.html

Case 3Case 3

22 yo active duty male presents to 22 yo active duty male presents to sick call with this eruptionsick call with this eruption

Case 3Case 3

What two viruses is he infected What two viruses is he infected with? (at a minimum)with? (at a minimum)

Describe the treatment options for Describe the treatment options for bothboth What additional information would be What additional information would be

helpful in making a decisionhelpful in making a decision ClinicalClinical laboratorylaboratory

HIVHIV

Antiretroviral treatment is:Antiretroviral treatment is: Complex (and evolving)*Complex (and evolving)* Requires extreme dedicationRequires extreme dedication Selection guided by genotype/phenotypeSelection guided by genotype/phenotype Ideally at least 3 active agentsIdeally at least 3 active agents Response should be monitoredResponse should be monitored Toxicity monitored and offset (?more Toxicity monitored and offset (?more

meds)meds) No vaccine in the foreseeable futureNo vaccine in the foreseeable future

*http://www.aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=7

HIVHIV

Monitor toxicityMonitor toxicity Allergy / hypersensitivityAllergy / hypersensitivity

Genetic screening for abacavirGenetic screening for abacavir Long term effectsLong term effects

Protease inhibitors (PIs) – lipids, glucoseProtease inhibitors (PIs) – lipids, glucose Non-nucleoside reverse transcriptase inhibitors Non-nucleoside reverse transcriptase inhibitors

(NNRTIs) – lipids (TG), hepatic(NNRTIs) – lipids (TG), hepatic nucleoside reverse transcriptase inhibitors (NRTIs) – nucleoside reverse transcriptase inhibitors (NRTIs) –

renal, marrow, neuropathyrenal, marrow, neuropathy Integrase inhibitors – myositisIntegrase inhibitors – myositis CCR5 receptor blocker - hepatitisCCR5 receptor blocker - hepatitis

HerpesviridaeHerpesviridae

Acyclovir and its derivatives Acyclovir and its derivatives fam, valfam, val

Increased bioavailability (and cost), same Increased bioavailability (and cost), same spectrumspectrum

Inhibits viral DNA polymeraseInhibits viral DNA polymerase Thymidine kinase mutants Thymidine kinase mutants resistance resistance HSV>VZV>>EBV≠CMV (intrinsically HSV>VZV>>EBV≠CMV (intrinsically

resistant)resistant) Iv form --? Crystalluria/stonesIv form --? Crystalluria/stones

HerpesviridaeHerpesviridae

Foscarnet or ganciclovir:Foscarnet or ganciclovir: CMV and acyclovir resistant HSVCMV and acyclovir resistant HSV Toxicity: Toxicity:

foscarnet: renal tox, sz, foscarnet: renal tox, sz, gancyclovir: marrow suppressiongancyclovir: marrow suppression

Case 4Case 4

30 yo unmarried active duty male 30 yo unmarried active duty male presents with the following lesions presents with the following lesions which have developed over several which have developed over several monthsmonths He reports unprotected sex with 3 He reports unprotected sex with 3

partners over the last yearpartners over the last year

Case 4Case 4

What virus is responsible for these What virus is responsible for these lesions?lesions?

What cancers has it been associated with?What cancers has it been associated with? What methods of treatment exist?What methods of treatment exist?

Major side effects from each?Major side effects from each? What further work up should ensue?What further work up should ensue? What surgical intervention would What surgical intervention would

decrease STD transmission to his female decrease STD transmission to his female partners and decrease his risk of cancer?partners and decrease his risk of cancer?

HPVHPV

What cancers has it been associated with?What cancers has it been associated with? CervicalCervical PenilePenile AnalAnal

What methods of treatment exist?What methods of treatment exist? Physical destruction / removalPhysical destruction / removal

Cryo, laser, surgery (pain, scarring)Cryo, laser, surgery (pain, scarring) Local Immune enhancementLocal Immune enhancement

Imiquimod (irritation)Imiquimod (irritation)

HPVHPV

What further work up should ensue?What further work up should ensue? Full STD evaluation – HIV, RPR, Full STD evaluation – HIV, RPR,

gc/chlam, Hep B, Hep Cgc/chlam, Hep B, Hep C What surgical intervention would What surgical intervention would

decrease STD transmission and decrease STD transmission and cancer risk to the patient and cancer risk to the patient and partners?partners? circumcisioncircumcision

http://www.who.int/hiv/topics/malecircumcision/en/index.htmlhttp://www.cdc.gov/hiv/resources/factsheets/circumcision.htm

Case 5Case 5

28 yo female presents to her primary 28 yo female presents to her primary care doctor after developing a painful care doctor after developing a painful and itchy blisters on her face 1 week and itchy blisters on her face 1 week after seeing her boyfriend who has after seeing her boyfriend who has since deployed to Iraqsince deployed to Iraq

Case 5Case 5

What pre-deployment vaccination is What pre-deployment vaccination is the source for this infection?the source for this infection?

What drugs/biologics are available What drugs/biologics are available for intervention?for intervention?

What are indications for treatment?What are indications for treatment? What are the potential side effects?What are the potential side effects?

PoxviridaePoxviridae

Orthopoxviruses (Monkeypox, Orthopoxviruses (Monkeypox, vaccinia) – potentially life threateningvaccinia) – potentially life threatening VIG-IV (allergic reaxn-rigors, fever)VIG-IV (allergic reaxn-rigors, fever) Cidofovir: targets DNA polymeraseCidofovir: targets DNA polymerase

nephrotoxic – needs to be given with nephrotoxic – needs to be given with hydration and probenecidhydration and probenecid

ST-246: targets viral maturationST-246: targets viral maturation ORALORAL placebo-likeplacebo-like Works against CDF-resistant strainsWorks against CDF-resistant strains

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5204a1.htm

PoxviridaePoxviridae

Parapoxviruses and molluscum Parapoxviruses and molluscum contagiosum – localized, only serious contagiosum – localized, only serious in immunocompromised in immunocompromised Imiquimod, intralesional cidofovirImiquimod, intralesional cidofovir

Orf virus infection

Case 6Case 6

8 year old Filipina girl BIB parents 2 8 year old Filipina girl BIB parents 2 weeks after sustaining a bite to the weeks after sustaining a bite to the face from a local dog. She is face from a local dog. She is currently exhibiting tremors, slurred currently exhibiting tremors, slurred speech and she is refusing to speech and she is refusing to eat/drink eat/drink

Case 6Case 6

What virus is responsible for her What virus is responsible for her condition?condition?

What interventions are recommended in What interventions are recommended in the acute setting of such a dog bite the acute setting of such a dog bite (asymptomatic patients)?(asymptomatic patients)?

What recent protocol has saved the What recent protocol has saved the lives of at least 2 symptomatic patients?lives of at least 2 symptomatic patients?

What is the risk to close contacts/health What is the risk to close contacts/health care providers of this girl?care providers of this girl?

RabiesRabies

What interventions are recommended What interventions are recommended in the acute setting of such a dog bite in the acute setting of such a dog bite (asymptomatic patients)?(asymptomatic patients)? RIG (not needed if pre-exposure vax given)RIG (not needed if pre-exposure vax given) Rabies vaccineRabies vaccine

What recent protocol has saved the What recent protocol has saved the lives of at least 2 symptomatic lives of at least 2 symptomatic patients?patients?

RabiesRabies

Milwaukee protocolMilwaukee protocol Ketamine, midazolam, ribavirin, Ketamine, midazolam, ribavirin,

amantadineamantadine No vaccine/biologic (fear of potentiating No vaccine/biologic (fear of potentiating

immune response)immune response) Potential risk to HCPsPotential risk to HCPs

Never been documentedNever been documented At least 2 non-lab confirmed human-to-At least 2 non-lab confirmed human-to-

human via salivahuman via salivaRabies in a dog imported from Iraq--New Jersey, June 2008.Centers for Disease Control and Prevention (CDC).MMWR Morb Mortal Wkly Rep. 2008 Oct 3;57(39):1076-8. No abstract available.

Case 7Case 7

30 yo female missionary returns 30 yo female missionary returns from Nigeria with facial/neck edema, from Nigeria with facial/neck edema, fever, conjunctivitis and one bout of fever, conjunctivitis and one bout of bloody emesis. She reports living in bloody emesis. She reports living in a rural village for 1 month and did a rural village for 1 month and did indulge in the local delicacy of indulge in the local delicacy of grilled rodent which she helped her grilled rodent which she helped her host family to prepare.host family to prepare.

Case 7Case 7

What is the likely viral etiology?What is the likely viral etiology? What is the reservoir?What is the reservoir? Are healthcare workers at risk for Are healthcare workers at risk for

infection?infection? What drug may be of benefit?What drug may be of benefit?

Lassa FeverLassa Fever

What is the reservoir?What is the reservoir? mastomysmastomys

Are healthcare workers at risk for Are healthcare workers at risk for infection?infection? Yes, contact precautionsYes, contact precautions

What drug may be of benefit?What drug may be of benefit? RibavirinRibavirin

Hemolytic anemia, teratogenHemolytic anemia, teratogen Activity against arenaviridae (LF) and bunyaviridae Activity against arenaviridae (LF) and bunyaviridae

(CCHF)(CCHF)

ReferencesReferences

Survival after treatment of rabies with induction of coma. Willoughby RE et al. Willoughby RE et al.

N Engl J Med. 2005 Jun N Engl J Med. 2005 Jun 16;352(24):2508-14.16;352(24):2508-14.

Combinatorial ribavirin and interferon alfacon-1 therapy of acute arenaviral disease in hamsters.

Gowen BB et al. Antivir Chem Gowen BB et al. Antivir Chem Chemother. 2006;17(4):175-83.Chemother. 2006;17(4):175-83.

http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/lassaf.htm

References cont.References cont.

Efficacy of zinc against common cold viruses: an overview. J Am Pharm Assoc (2003) J Am Pharm Assoc (2003). 2004 Sep-. 2004 Sep-Oct;44(5):594-603Oct;44(5):594-603

Clinical practice. Prevention and treatment of seasonal influenza. N Engl J Med N Engl J Med. 2008 Dec 11;359(24):2579-85. 2008 Dec 11;359(24):2579-85

Successful Treatment in the Monkeypox Successful Treatment in the Monkeypox and Variola Primate Models of Smallpox and Variola Primate Models of Smallpox by the Oral Drug ST-246by the Oral Drug ST-246 Antiviral ResearchVolume 74, Issue 3, June 2007, Page A35 , June 2007, Page A35

References cont.References cont.

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e507a1.htm (human rabies prevention, 2008 (human rabies prevention, 2008 recommendations)recommendations)