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181 Cards in this Set
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- Back
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efficacy of flu vaccine in immunocompetent patients?
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- 70-90% efficacy in healthy (> 6 years of age)
- Variable antibody response among high risk children |
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efficacy of flu vaccine in elderly patients? >65 yo
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- 58% efficacy vs. respiratory illness, but may be less
- 50-60% effective in preventing hospitalization for P/I among LTC residents and 80% effective in preventing death |
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adverse effects of flu vaccine
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Injection site soreness
-suggest premedication to reduce incidence Systemic febrile reaction Hypersensitivity reaction to egg protein Guillain-Barre syndrome (1/1,000,000) |
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desc. association between Guillian Barre and Flu vaccine?
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*rare
1976 swine influenza vaccine associated with 1 additional case of GBS per 100,000 persons No consistent evidence for causal relation between subsequent vaccines and GBS Influenza virus infection is a known trigger of GBS Frequency of influenza-related GBS is ~4-7 times higher than vaccine-associated GBS Persons with prior GBS have a greater likelihood of subsequent GBS Persons not at high risk for severe influenza and known to have had GBS within 6 weeks should not be vaccinated |
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characteristics of the Flumist intranasal vaccine
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Live vaccine
Antigenically representative viruses A/H1N1, A/H3N2, B Cold-adapted Temperature-sensitive Attenuated Intranasal administration induces protective mucosal and serum antibodies Efficacy 85-100% |
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Who is Flumist indicated for?
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Healthy children and adolescents 2-17 years of age
Healthy adults 18-49 years of age ** >2, <50 |
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who is Flumist contraindicated in?
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Children <2 and adults 50 years of age
Children <5 with possible reactive airways disease Children or adults with significant risk factors for influenza illness & complications Immunocompromised patients or those receiving immunosuppressive drugs Children receiving aspirin or aspirin-containing therapy History of allergy to eggs or egg products |
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most common side effects of Flumist?
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runny nose/congestion, headache, cough
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Dosage schedule for Flumist
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Children age 5-8 years, not previously vaccinated with FluMist = 0.5 mL x 2 doses at least 6 weeks apart
Children age 5-8 years, previously vaccinated with Flumist = 0.5 mL x 1 dose/season Children and adults age 9-49 years = 0.5 mL x 1 dose/season |
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Desc. high dose Fluzone flu vaccine
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Covers same viral strains as standard vaccines but contains four time the quantity of antigenic viral proteins (hemagglutinin)
Intended to produce more vigorous immune response in older patients Elicits significantly greater antibody titer, but no data concerning whether more effective than standard-dose vaccines |
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who is the high dose flu vaccine indicated for?
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people 65 years and older
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what are the 2 drug classes for for flu?
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M2 protein inhibitors (adamantanes)
neuramidase inhibitors |
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what are the M2 inhibitors?
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amantadine
rimantadine |
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what are the neuramidase inhibitors?
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zanamivir
osltamivir |
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benefits to pharmacologic treatment for flu?
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None definitely proven to prevent influenza-related complications in adults
Must be administered within 2 days of onset of flu-like symptoms Preferably <36 hours after onset of symptoms Reduces symptom duration by ~ 1-1.5 day Duration of treatment is 5 days To reduce resistance, M2 inhibitors should be discontinued appropriately |
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what is the duration of treatment for pharmacologic flu agents?
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5 days
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MOA M2 protein inhibitors
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Interferes with uncoating of influenza A through
inhibition of viral M2 protein; may also interfere with viral assembly after replication |
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features of amantadine
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MOA: Interferes with uncoating of influenza A through inhibition of viral M2 protein; may also interfere with viral assembly after replication
Renal excretion GI and CNS adverse Effects (5-10%) Cost: $11 per 5 day course |
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features of rimantadine
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Similar MOA to amantadine
Hepatic excretion, minimal renal excretion GI and CNS adverse effects less frequent (3-5%) & milder Cost: $21 per 5 day course |
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amantadine vs. rimantidine:
indications |
A:Children & Adults:
Treatment & prophylaxis R: Adults: Treatment & prophylaxis Children: Prophylaxis only |
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amantadine vs. rimantidine:
adult dose |
A:Based on CrCl:
If >80 ml/min, 100 mg BID R: 100mg BID in healthy; 100mg QD if CrCl <10 or severe hepatic dysfunction |
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amantadine vs. rimantidine:
renal excretion |
A: Excreted unchanged in urine
R:Partially excreted in urin |
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amantadine vs. rimantidine:
hepatic excretion |
A: None
R:Mostly metabolized in liver |
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amantadine vs. rimantidine:
Adverse effects (CNS, incidence increased in elderly) |
A:Confusion, lightheadedness, nervousness, insomnia; urinary retention; dry mouth, nausea, constipation, diarhea
R: Same, but less than amantadine |
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features of zanamivir
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Treatment of influenza A & B for patients >7 years old
Prophylaxis of influenza A & B for patients >5 years old Dosage form: Inhaler Dose: 2 puffs (10 mg) BID for 5 days AE: H/A, cough, bronchospasms Caution in patients with asthma or COPD Advantage: Non-systemic, good for pregnant females Cost: $48/5-day course |
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features of oseltamivir
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Treatment and prophylaxis of influenza A & B for patients >1 y.o.
Dosage form: 75 mg capsule Dose: 75 mg BID for 5 days. (If CrCl < 30ml/min, 75 mg QD for 5 days) AE: N/V; Administer with food to Advantage: Ease of use, safe for high risk pulmonary patients Cost: $60/5-day course |
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study: benefits of oseltamivir therapy vs. placebo for reduction in flu duration?
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statistically significant reduction in flu duration vs. placebo:
1.3 day reduction |
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Flu in children
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High infection rates
Frequent complications Otitis media Sinusitis Late-onset bacterial pneumonia Progressive primary viral pneumonia Excess hospitalizations Increased outpatient visits Increased antibiotic use |
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benefits to oseltamivir in children
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36% reduction in median time to alleviation of symptoms
-- 18 symptoms, parentally assessed 40% reduction in physician-diagnosed complications 28% (65/235) placebo vs 17% (36/217) oseltamivir (P=0.005) 40% reduction in the risk of otitis media 27% (53/200) placebo vs 16% (29/183) oseltamivir 24% reduction in patients receiving antibiotic prescriptions 41% (97/235) placebo vs 31% (68/217) oseltamivir phosphate (P=0.03)* |
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chemoprophylaxis for the flu?
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Not a substitute for vaccination
Provides protection against variant strains not covered by vaccine Critical adjunct in prevention and control of influenza during peak season. Amantadine and rimatadine are 70-90% effective in preventing illness from Influenza A. Oseltamivir – Protective efficacy estimated to be 74% Although no formal FDA indication, prophylactic zanamivir has demonstrated a 79 percent rate of protection in unvaccinated patients. |
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resistance of flu to antiviral drugs
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In 2007-08:
Resistance to adamantanes = 99.8% of influenza A (H3N2) viruses tested 10.7% of A (H1N1) Resistance to oseltamivir = 10.9% of influenza A (H1N1) viruses tested Increased from 0.7% in 2006-07 Represents about 2% of all influenza viruses in 2007-08 No cross-resistance with adamantane-resistant viruses 0% in A (H3N2) and influenza B Resistance to zanamivir = 0% in all viruses tested |
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what flu strains is oseltamivir resistant to?
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seasonal A/H1N1
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what flu strains are amantadine/rimantadin resistant to?
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novel H1N1, seasonal A/H3N2, Influenza B
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what flu strains is zanamivir resistant to?
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none, it works against all strains:
novel H1N1, seasonal A/H1N1, seaonsal A/H3N2, influenza B |
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what are CDC advisory recommendations for immunization practices 2009-10?
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The adamantanes (amantadine, rimantadine) were NOT recommended for treatment or prophylaxis of influenza during the 2009-2010 season
Expected circulating strain of influenza A (H3N2) exhibited high resistance to these drugs Only oseltamivir and zanamivir were recommended Most resistance was in seasonal influenza A (H1N1), which was rarely seen last year Recommendations for the 2010-11 season not yet available but should be similar |
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recommendations for antiviral treatment for 2009 H1N1?
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All patients requiring hospitalization
Patients at increased risk of complications Children <2 years* Adults 65 years and older Pregnant women Persons with immune suppression, chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), neurologic, neuromuscular, or metabolic disorders (including diabetes mellitus) or > 65 years Children <19 on chronic aspirin therapy Early treatment with either oseltamivir or zanamivir Clinicians should not wait for confirmatory tests to treat |
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who should receive flu pharmacologic agent prophylaxis?
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All to LTC residents and unvaccinated staff during an institutional outbreak.
Priority Patients vaccinated after influenza activity has begun and until immunity has developed. Unvaccinated persons in frequent contact with priority patients. Persons who have immune deficiencies. Persons who have a contraindication to the vaccine and wish to avoid influenza illness. |
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Avian influenza
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it's all FYI, so no study cards
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ticks as vectors for disease
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Vectors of bacterial, viral, and protozoal diseases
2nd only to mosquitoes worldwide 1st in North America |
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list some tick borne illnesses in N. america
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lyme dx
rocky mtn spotted fever ehrlichiosis(HME, HGE) babesiosis STARI relapsing fever tick paralysis |
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what is tick paralysis?
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Pathogenesis
Occurs with prolonged attachment (5-7 days) Caused by a neurotoxin in tick saliva Acute, ascending, flaccid motor paralysis Treatment Removal of the tick |
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how to treat tick paralysis?
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remove the tick
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tick borne illnesses cause by bacterial spirochetes?
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tick borne relapsing fever
southern tick assorted rash illness(STARI) *lyme disease |
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what is tick borne relapsing fever?
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Areas affected
Mostly midwest and mountainous regions of western U.S Rare disease; Soft tick - bites and detaches so difficult to detect Presentation Fever and chills Headache, myalgia, arthralgia, N/V, abdominal pain Acute symptomatic period lasts approximately 3 days, then relapse occurs ~ 1 week later |
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treatment for tick borne relapsing fever?
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doxycycline, tetracycline, chloramphenicol, penicillin, or erythromycin
5-10 days of therapy |
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what is STARI?
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Southern Tick-Associated Rash Illness
Eruption develops 2-12 days after discovery and removal of tick Fever, mild systemic symptoms |
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treatment for STARI?
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Treatment
Doxycycline 100 mg BID x 10 days |
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what is lyme disease causing bacterium?
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(Spirochete)
Borrelia burgdorferi |
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what is the tick vector for lyme disease?
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deer tick
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affected areas for lyme disease?
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Most cases reported from Northeast, Mid-Atlantic and North-Central U.S.
Some cases in South and West Coast |
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clinical manifestations of lyme disease?
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Stage 1: Early Infection
Malaise, fatigue, headache, fever, chills Erythemic skin lesion at site of tick bite Stage 2: Disseminated Infection Several days to weeks after initial onset Multiple secondary skin lesions Usually fades within 3-4 weeks (range 1 day-14 months) Stage 3: Late Persistent Infection Months to years after first infection Intermittent attacks of joint swelling and pain Primarily large joints, especially the knee 5% of untreated patients develop chronic neurologic manifestations Polyneuropathy, ataxia, cognitive impairment, etc |
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clinical manifestations of lyme disease:
stage 1 |
Stage 1: Early Infection
Malaise, fatigue, headache, fever, chills Erythemic skin lesion at site of tick bite |
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clinical manifestations of lyme disease:
stage 2 |
Stage 2: Disseminated Infection
Several days to weeks after initial onset Multiple secondary skin lesions Usually fades within 3-4 weeks (range 1 day-14 months) |
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clinical manifestations of lyme disease:
stage 3 |
Stage 3: Late Persistent Infection
Months to years after first infection Intermittent attacks of joint swelling and pain Primarily large joints, especially the knee 5% of untreated patients develop chronic neurologic manifestations Polyneuropathy, ataxia, cognitive impairment, etc. |
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lyme disease treatment?
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Preferred:
Doxycycline 100 mg BID x 14-21 days Also: Amoxicillin 500 mg TID x 14-21 days Alternatives Cefuroxime Erythromycin Penicillin G |
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patient case:
FJ is a 26 year old male who presents to the emergency department after 24 hours of flu-like symptoms and joint pain. PMH: Tick bite back in July, had a rash for about 1 month, but it gradually got better SH: Park ranger, spends most of his time in the outdoors Meds: none Allergies: NKDA How would you treat this patient? |
doxycycline
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patient case:
FJ is a 26 year old male who presents to the emergency department after 24 hours of flu-like symptoms and joint pain. PMH: Tick bite back in July, had a rash for about 1 month, but it gradually got better SH: Park ranger, spends most of his time in the outdoors Meds: none Allergies: NKDA How long would you treat FJ? |
14-21 days, then assess for symptom resolution
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tick borne illness caused by protozoa
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babesiosis
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what is babesiosis?
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Reservoirs
Wild and Domestic animals (cattle) Northeast and upper Midwest Presentation Most infections are asymptomatic Appear 1-4 weeks after tick bite Malaise, fatigue, anorexia, chills, fever Hemolytic anemia, thrombocytopenia Potentially fatal disease in asplenic or immunocompromised |
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in which patient populations migh babesioisis be fatal?
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asplenic or immunocompromised patients
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tick born illnesses cause by ehrlichioses?
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Ehrlichiosis chaffeensis
Human monocytic ehrlichiosis (HME) Anaplasma phagocytophilum Human granulocytic ehrlichiosis (HGE) |
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what is ehrlichioses?
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Reservoirs
Dogs, Deer Disease Ehrlichiosis chaffeensis Human monocytic ehrlichiosis (HME) Anaplasma phagocytophilum Human granulocytic ehrlichiosis (HGE) Areas most affected Missouri, Tennessee, Oklahoma, Texas, Arkansas, Virginia Timing Symptoms occur approximately 1 month after bite Peak incidence between May and July |
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incubation/presentation of ehrlichioses?
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Incubation
Median 7 days Presentation Fever, myalgia, headache, nausea Rash (36%) Leukopenia, thrombocytopenia, increased LFTs Acute Respiratory failure, renal failure, coagulopathy, shock, death Symptom duration Median ~ 23 days |
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traetment for ehrlichioses?
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Doxycycline 100 mg po BID or tetracycline
Pregnancy – rifampin may be an option |
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where is rocky mtn spotted fever most prevalent?
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southeast
(1st case in idaho = "rocky mtn") |
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pathogen causing rocky mtn spotted fever?
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rickettsia ricketsii
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vector tick for rocky mtn spotted fever?
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*dog tick
also rocky mtn wood tick |
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incubation period and clinical manifestations rocky mtn spotted fever
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Incubation period
2-14 days (median 7 days) Clinical Manifestations Fever, headache, myalgia Due to release of inflammatory cytokines N/V, abdominal pain, diarrhea Rash Mortality ~ 3% |
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treatment rocky mtn spotted fever
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Doxycycline 100 mg q12h x 7 days
Tetracycline Chloramphenicol (if can't use a tetracycline-pregnant, allergy) |
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Pt. case:
DP is a 32 year old female who presents to a North Carolina emergency department with a diffuse red spotty rash on her extremities. PMH: Non-contributory SH: Trail runner All: Tetracycline how would you treat DP for rickettsia infection? |
chloramphenicol
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tick borne illness infection prevention?
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Avoid tick-infested areas
Insecticides DEET (N,N-diethylmetatoluamide) Avoid applying excessive amounts directly to skin Permethrin Can only be applied to clothing, not skin Check for ticks 24-72 hours of attachment is usually necessary to transmit infection Vaccine? Available for lyme disease in 1999, but withdrawn because of poor sales |
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key points from tick borne illness lecutre?
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Ticks are vectors for many diseases in the US
Specific ticks can be linked to diseases Dog Tick – Rickettsia; Deer Tick – Lyme disease Infecting pathogens discussed were spirochetes, protozoa, and rickettsia Treatment regimens and duration depends on infecting pathogen Prevention is key! |
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Defn of acute HIV 1 infection
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“Interval during which HIV can be detected in blood, serum and plasma before the formation of antibodies routinely used to diagnose infection.”
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clinical features of acute HIV infection?
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2/3 of patients symptomatic
Incubation period 10 to 14 days Fever present in 80-90% Rash, pharyngitis, lymphadenopathy common Radiculopathy, meningitis, encephalopathy, Guillain-Barré syndrome rarely occur |
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what is the problem with acute HIV symptoms?
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symptoms are so nonspecific that there is almost no indication that it is acute HIV infection unless there is a suspicion
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labratory findings of acute HIV 1 infection?
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Leukopenia with CD4+ lymphopenia (may persist for months)
Atypical lymphocytosis Thrombocytopenia Liver function test abnormalities CSF pleocytosis |
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treatment options: potential benefits of early HIV treatment
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Relief of symptoms of acute retroviral syndrome
Reduction in viral load: decreases transmission risk (important public health perspective) Limiting HIV-1 viral reservoir, HIV-1 diversification Indirectly preventing infection of HIV-1 specific CD4+ T cells Preservation of host immune function, CTL response |
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treatment optoins: potential pitfalls to acute HIV infection treatment?
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Adverse reactions from medication
Short term Long term Adherence issues and development of resistance Duration of therapy unknown and whether treatment interruptions are indicated To date no study has documented a benefit in treating acute HIV-1 infection Treatment when pursued is undertaken as with treatment of chronic HIV-1 infection |
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clinical presentations of syphilis?
primary |
Primary syphilis
Incubation period averages 2 – 3 weeks Painless (typically) ulcer or chancre develops Lymphadenopathy is common Heals spontaneously, 3 – 6 weeks |
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clinical presentations of syphilis?
secondary |
Secondary syphilis – develops in 25% of untreated patients
Onset from a few weeks to 6 months after exposure Rash with systemic symptoms is typical Symptoms resolve without therapy but may relapse |
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clinical presentations of syphilis?
latent |
Latent syphilis
Asymptomatic Early < 1 year Late > 1 year Undetermined (treated as if late latent) |
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clinical presentations of syphilis?
tertiary |
Tertiary syphilis
Neurosyphilis Cardiovascular syphilis |
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syphilis treatment:
primary, secondary, early latent |
***Recommended regimen
Benzathine Penicillin G, 2.4 million units IM x 1 Penicillin Allergy Doxycycline 100 mg po bid x 14 days or Ceftriaxone 1 gm IM/IV daily x 8-10 days Cautions: Azithromycin no longer routinely recommended High rates of resistance noted in some U.S. cities (up to 50%) |
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syphilis treatment:
late latent syphilis |
Recommended regimen
Benzathine penicillin G 2.4 million units IM weekly x 3 doses Penicillin allergy* Doxycycline 100 mg po bid x 28 days or Tetracycline 500 mg po qid x 28 days *Close clinical and serologic follow-up; data to support alternatives to PCN are limited |
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tertiary syphilis treatment?
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Recommended Regimen
Penicillin G 12 – 24 million units IV daily for 10 - 14 days Alternative Regimen Procaine penicillin G, 2.4 million units IM daily + Probenecid 500mg po qid both for 10 days Penicillin Allergic - Desensitize everyone gets a PCN w/ teriary |
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what is neurocysticercosis caused by?
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pork tapeworm
(Taenia solium) |
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clinical presentation of neurocysticercosis?
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Presenting signs and symptoms depend on the location, stage, and number of cysts
However, most disease is asymptomatic With intraparenchymal disease, seizures are the most common presentation With extraparenchymal disease, headache secondary to hydrocephalus is common Focal neurologic deficits are usually mild and/or transient Retinal disease commonly exists with neurologic disease, it can present with blurred vision |
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antiparasitic agent options for neurocysticercosis?
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Albendazole 15mg/kg/day divided bid
Mechanism – microtubule degeneration and decreased ATP production in helminths Preferred agent, excellent bioavailability, no drug interactions with seizure meds, levels not decreased by steroids Praziquantel 50mg/kg/day divided tid Mechanism – increases cellular permeability to calcium in helminths Drug levels decreased by steroids and many antiepileptic medications |
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albendazole for antiparasites for neurocysticercosis?
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preferred b/c less drug interactions
15mg/kg/day divided bid Mechanism – microtubule degeneration and decreased ATP production in helminths Preferred agent, excellent bioavailability, no drug interactions with seizure meds, levels not decreased by steroids |
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praziquantal for antiparasites neurocystocercosis?
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50mg/kg/day divided tid
Mechanism – increases cellular permeability to calcium in helminths Drug levels decreased by steroids and many antiepileptic medications |
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concomitant tx for neurocysticercosis?
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Antiepileptics
Start for anyone with seizure activity, therapy may be lifelong Administer prior to treatment with antiparasitic agents, continue for 6 – 12 months Corticosteroids Should be used in all individuals with parenchymal disease to decrease inflammation caused by dying organisms |
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when to use antiepileptics for neurocysticercosis?
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Antiepileptics
Start for anyone with seizure activity, therapy may be lifelong Administer prior to treatment with antiparasitic agents, continue for 6 – 12 months |
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when to use corticosteroids for neurocysticercosis?
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Corticosteroids
Should be used in all individuals with parenchymal disease to decrease inflammation caused by dying organisms |
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treatment for neurocysticercosis?
intraperenchymal lesions |
Intraparenchymal lesions - Viable Cysts:
Single lesion – antiparasitic x 7 days + steroids Multiple lesions – antiparasitic x 10 -14 days + steroids Heavy (>100 lesions) antiparasitic with high dose steroids, or just steroids |
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treatment for neurocysticercosis?
cysticercal encephalitis |
Cysticercal encephalitis – diffuse cerebral edema with multiple inflamed cysticerci – treat with steroids alone, duration based on response, consider antiparasitic after edema resolved
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treatment for neurocysticercosis?
calcified cyticerci |
Calcified cyticerci – any number, no antiparasitic agent, antiepileptics only
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treatment for neurocysticercosis?
extrapyramidal lesions |
Extraparenchymal lesions
Ventricular cysts - neuro-endoscopic removal if available or VP shunt followed by antiparasitic + steroids Subarachnoid cysticercosis – antiparasitic x 28 days + steroids, VP shunt if hydrocephalus present Hydrocephalus without visible cysts – VP shunt, no antiparasitic or steroids Spinal: surgical removal Ophthalmic: surgical removal |
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key points from emerging infectious dx lecture
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Acute HIV is hard to diagnose, appears very similar to other viral infections, the utility of antiretroviral therapy is unknown
Syphilis is back, and is predominantly circulating in MSM in the U.S., diagnostic testing can be confusing, penicillin is the drug of choice Neurocysticercosis is relatively common, albendazole (when indicated) is the drug of choice, steroids are always used with albendazole, antiepileptics are commonly required |
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hepatitis virus with fecal-oral transmision
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HAV
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hepatitis virus with blood borne transmission
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HBV HCV
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hepatitis virus with chronic infection
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HBV
HCV |
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hepatitis with vaccine available
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HAV
HBV |
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HAV genome, enveloped?
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ssRNA
non-enveloped |
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HBV genome, enveloped?
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partially dsDNA
enveloped |
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HCV genome, enveloped?
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ssRNA
enveloped |
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HAV characteristics
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ssRNA
Classification: Picornaviridae One serotype and multiple genotypes Nonenveloped, acid and heat stable Does not cause chronic disease |
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HAV routes of transmission
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Close Personal Contact
Household or sexual Day care center Fecal-oral contamination of food and water Food handlers Raw or undercooked seafood Travel to endemic areas Blood-borne (rare) Injection drug users |
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HAV infection and replication
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Since HAV is acid resistant, it passes through the stomach and replicates in the lower intestine
Transported to the liver (major site of replication) Taken up by hepatocytes Once in hepatocyte, viral RNA is uncoated and genome is copied Assembled virions are shed into the biliary tree and excreted in the feces |
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lab tests for identifying HAV?
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IgM (acute HAV)
clinical illness occurs ~4 wks after infection IgG (pt. had and cleared HAV or is immune b/c of vaccine) |
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sympotoms of HAV
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Fever
Malaise Anorexia Nausea Abdominal Discomfort Dark Urine Pale Stools Jaundice |
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clinical features of HAV
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jaundice (increase with age, esp >14 yo)
rare complications in immunocompromised or other liver dx pts (Fulminant hepatic failure, Cholestatic hepatitis, Relapsing hepatitis, Autoimmune extrahepatic disease) |
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rare complications of HAV
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Fulminant hepatic failure
Cholestatichepatitis Relapsing hepatitis autoimmune extrahepatic disease |
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things for diagnosis of HAV
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IgM in serum
clinical symptoms (jaundice) LFT (increase ALT, billirubin) |
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treatment for HAV
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SUPPORTIVE CARE
Antivirals don’t work Hospitalization is only necessary for those who have severe symptoms or complications PREVENTION is best! |
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prevention of HAV
preexposure |
Hygiene (e.g., hand wasing)
Sanitation (e.g., clean water sources) Hepatitis A vaccine Immune globulin |
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prevention of HAV
postexposure |
Hepatitis A vaccine
Immune globulin |
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HAV vaccines features
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First licensed in 1995
Inactivated 94-100% effective in preventing HAV infection in clinical trials |
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what is twinrix?
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combined hep a and b vaccine
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Twinrix
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Contains 720 EL.U. hepatitis A antigen and 20 μg. HBsAg
Vaccination schedule: 0, 1, 6 months (like Hep B) Accelerated Dosing Schedule: If travel will occur in < 28 days from 1st dose 0, 1, and 3-4 weeks and a booster at 12 months |
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side effects/safety of HAV vaccines
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Most common side effects
Soreness / tenderness at the injection site ~50% Headache 15% Malaise 7% No severe adverse reactions attributed to the vaccine Safety in pregnancy not determined – risk likely low |
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duration of protection for HAV vaccine
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Persistence of antibody
At least 5-8 years among adults and children Mathematical models of antibody decline suggest protective antibody levels persist for at least 20 years |
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administration of HAV vaccine?
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Can be given at the same time as other vaccines without compromising efficacy
Diphtheria, tetanus, live or inactivated polio, oral and injectable typhoid, cholera, Japanese encephalitis, rabies, yellow fever, and hepatitis B Products can be interchanged, protective antibody levels will not differ As with other inactivated vaccines, it can be safely given to immunocompromised persons |
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HAV vaccine recommendations in children?
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Administer to all children > 12 months of age.
Administer the 2 doses in the series at least 6 months apart. Children not fully vaccinated by age 2 years can be vaccinated at subsequent visits. |
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who should get the HAV vaccine?
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Children
Ages 12-23 months Catch up for older children in selected areas Those for whom immunity is desired Those traveling to countries with high or intermediate rates of infection MSM Persons who use illegal drugs Persons who work with HAV in research laboratories Persons with clotting-factor disorders Those with chronic liver disease Those with close contact with an international adoptee from a country of high or intermediate endemicity in first 60 days of their arrival in US |
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preexposure prophylaxis for HAV?
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For travel to countries with high or intermediate endemicity
Vaccination preferred If just 1 shot, use Hep A alone (not A/B combo) Ig can be considered in addition to vaccine for those > 40 years, immunocompromised, and persons with chronic liver disease or other chronic medical conditions who are traveling to an area within 2 weeks |
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when should Ig be considered for HAV prevention?
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in addition to vaccine for those > 40 years, immunocompromised, and persons with chronic liver disease or other chronic medical conditions who are traveling to an area within 2 weeks
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preexposure Ig prophylaxis for HAV?
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Immunoglobulin (Ig) provides protection against HAV by passive transfer of concentrated antibodies (immunoglobulins) against HAV (anti-HAV).
85% effective when used within 2 weeks of exposure Ok to give to pregnant or lactating women, but when Ig is given to pregnant women or infants use thimerosal-free preparations Both IV and IM Ig contain anti-HAV, but only the IM formulation is used for prevention of HAV infection |
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timing of Ig and vaccine admin. for HAV?
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Hep A vaccine can be given concomitantly with Ig,
the antibody titer obtained is lower (but still protective) compared to when the vaccine is given alone Give in a separate anatomic site than vaccine |
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timing of Ig and live vaccine admin?
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Ig can interfere with MMR and varicella vaccine responses, thus these vaccines should be delayed for 3 and 5 months, respectively after Ig administration
If Ig is administered within 2 and 3 weeks of the MMR and varicella vaccines, the MMR and varicella vaccines the person will likely require revaccination |
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patient case:
HM is a 52 yo WM who presents to the University of Colorado Infectious Diseases Group Practice Travel Clinic. He is going to Thailand and wants to know if he needs Hepatitis A prophylaxis? what would you recommend for trip to thaliand? (has HIV, going in Jan, no HAV vaccine or dx ever) |
hep. a vaccine
no need for Ig b/c no traveling within 2 weekds (but he is >40, immunocompromised w/ chronic med condition) |
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who requires intervention after HAV exposure?
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Those with close personal contact with a person who has Hep A (e.g., household or shared illicit drugs)
Staff and attendees of day care centers where Hep A is documented Common-source exposures Patrons and other food handlers at locations where a food handler has Hep A Schools, hospitals, and work settings with several cases of Hep A transmission |
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should vaccine or Ig be used for post exposure HAV prophylaxis?
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Limited data comparing vaccine vs. Ig in this setting, but available data suggests vaccine is 86% effective vs. 90% for Ig
Vaccine: ages 12 mos. – 40 years otherwise healthy Not the combo vaccine, Hep A only Ig: ages < 12 mos. or >40 years or other underlying medical conditions (e.g., HIV or chronic liver disease) Can give vaccine too if indication for it |
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post exposure Ig prophylaxis for HAV?
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same as pre exposure
those given vaccine at least 1 month before exposure dont need Ig |
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patient case:
FJ is a 30 yo AAM who presents to the local ED after hearing on the news that a food handler at the restaurant where he dined last week was diagnosed with Hep A FJ does not have any signs or symptoms of Hep A at this time FJ doesn’t think he has ever had the Hep A vaccine FJ says he does not have any underlying liver disease or HIV infection what should we do? |
give hep A vaccine
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features of HCV
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ssRNA
50 nm in diameter Enveloped 6 genotypes (1-6) (1-3 in US) |
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HCV genotypes
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Little evidence that genotype affects
Transmissibility Level of replication Rate of progression to liver disease BUT there are marked differences in response to treatment GT 1 is hardest to treat 70% of patients in US have GT 1 |
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HCV statistics in US
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HCV is the most common blood-borne infection
40% of chronic liver disease is related to HCV 4.1 million Americans have anti-HCV 2.7 of those had chronic HCV 10,000 – 12,000 HCV-related deaths each year |
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exposures assoc. with HCV infection
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Injection drug use
Transfusion, transplant from infected donor Occupational exposure to blood Mostly needle sticks Birth in infants born to HCV-infected mother Iatrogenic Dirty needles / equipment Sex with infected partner |
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why can HCV be cured?
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b/c all viral replication occurs in the cytoplasm, never in the nucleus, never integrated with host DNA
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lab info we test for to determine HCV
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HCV RNA (viral load)
HCV antibody |
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recommendations for HCV routine testing?
high risk |
Ever injected illegal drugs
Received clotting factors made before 1987 Received blood/organs before July 1992 Ever on chronic hemodialysis Evidence of liver disease People in settings with demonstrated high HCV prevalence where risk factor attainment may be poor (e.g., inmates) |
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recommendations for HCV routine testing?
exposure management |
Healthcare, emergency, public safety workers after needle stick/mucosal exposures to HCV-positive blood
Children born to HCV-positive women Sexual partners of HCV infected persons |
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interpretation:
+anti-HCV +HCV RNA |
infected, unsure if acute/chronic
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interpretation:
+anti-HCV -HCV RNA |
cleared virus/immune
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interpretation:
-anti-HCV +HCV RNA |
acute HCV infectino
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interpretation:
-anti-HCV -HCV RNA |
not infected
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considerations for initiating HCV treatment
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For genotype 1 patients, degree of liver damage
Eligibility Ability to Tolerate Adverse Effects |
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treatment for HCV
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Interferon and Pegylated Interferon
Can be used as monotherapy Ribavirin Cannot be used as monotherapy Best therapy is the combination |
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pegylated INF for HCV treatment
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Pegasys® (pegylated interferon alpha 2a)
Peg Intron® (pegylated interferon alpha 2b) |
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Pegasys® (pegylated interferon alpha 2a)
dosing/duration for HCV treatment |
180 mcg SQ weekly x 48 weeks
Hepatically metabolized and renally cleared Ready to use: 1-mL single dose vial containing 180 mcg / vial Refrigerated |
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Peg Intron® (pegylated interferon alpha 2b)
dosing/duration for HCV treatmen |
1.5 mcg/kg SQ weekly x 48 weeks
Renally cleared Requires reconstitution: Single dose vials with lyophylized powder and 5 mL vials of sterile water diluent Room temp until reconstituted then can be refrigerated for 24 hours prior to use |
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ribavirin for HCV treatment
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Oral, guanosine nucleoside analogue
Available as tablets, capsules, liquid For patients with genotype 1 dose is 400 mg in am and 600 mg in pm for those <75 kg 600 mg BID for those ≥75 kg For patients with genotype 2 or 3 dose is 400 mg BID |
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ribavirin dosing for HCV
genotype 1 |
400 mg in am and 600 mg in pm for those <75 kg
600 mg BID for those ≥75 kg |
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ribavirin dosing for HCV
genotype 2,3 |
400 mg BID
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proposed MOA ribavirin
(4) |
1. change Th phenotype from Th2 to Th1 for increase virus CL
2. RMP inhibits IMPDH, makes less GTP, drug more likely to be incorporated 3. integrate triphosphate drug form into RdRp(RNA dependednt RNA polymerase) 4. direct RNA mutagen, decrease successful virus replication |
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what is RVR
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rapid virologic response, a 2-log drop or loss of HCV RNA at 4 weeks into therapy
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what is EVR
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early virologic response, a 2-log drop or loss of HCV RNA at 12 weeks into therapy
when treatment decisions are made |
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what is SVR
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(cure) sustained virologic response, an undetectable HCV RNA 24 weeks after cessation of therapy
PRIMARY GOAL |
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what is biologic reponse?
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live enzymes normalize
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what is histologic response?
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improvement in biopsy findings
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IL28B genetics
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Single nucleotide polymorphism upstream of the gene IL-28B on chromosome 19, coding for IFN-λ-3
INFλ enhances and sustains effects of INFα on HCV replication IL28B genetics accounts for 50% of lower SVR rates in black vs. nonblack patients A commercial test is available to determine IL28B genotype CC genotype increases rates of cure compared to TT, CT genotype |
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contraindications for IFN in HCV
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Cirrhosis (decompensated)
Coronary or cerebrovascular disease Organ transplant (other than liver) Current or history of psychosis Severe depression Neutropenia Thrombocytopenia Uncontrolled Seizures Autoimmune disorders Uncontrolled diabetes |
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contraindications to ribavirin
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Pregnancy category X
2 contraceptive measures during and 6 months after treatment CrCl < 50 mL/min Hgb < 11 g/dL |
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adverse effects of IFN
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Flu-like symptoms
Insomnia Psychiatric Disorders Depression, irritability Rash and Pruritis Anorexia Neutropenia Thrombocytopenia Thinning of hair Thyroid dysfunction |
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ribavirin adverse effects
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***Hemolytic anemia
Teratogenicity Cough Dyspnea Rash Insomnia Anorexia |
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ITPA genetics used to predict hemolytic anemia
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ITPA makes the enzyme inosine triphosphatase (ITPase)
Single nucleotide polymorphisms (SNPs) in ITPA have been associated with reduced ITPase Less ITPase = more ITP protect from ribavirin-induced anemia Mechanism of protection of high levels of ITP is unclear May relate to maintaining ATP levels in red cells |
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monitoring parameters while on HCV therapy
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CBC and LFTs at weeks 1, 2, 4, and at 4-8 week intervals thereafter
HCV RNA at weeks 4, 12, 24, and 48 (at a minimum) Thyroid-stimulating hormone levels every 3-6 months Serum creatinine Determine adherence Assess for clinical adverse effects and recommend management |
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management of IFN adverse effects
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Flu-like symptoms
Bedtime / weekend dosing Pre-treatment with OTC analgesics Psychiatric Dose reductions Antidepressants (SSRIs) ± antipsychotics Bone Marrow Dose reductions Neutropenia: GCSF 300 mcg SQ 1-3 times per week when ANC < 750 cells/mm3 Thrombocytopenia: oprelvekin 50 mcg/kg SQ 3 times per week for platelets < 100,000 cells/mm3 |
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management of flu like sx from adverse effects from IFN
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Bedtime / weekend dosing
Pre-treatment with OTC analgesics |
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management of psychiatric adverse effects from IFN
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Dose reductions
Antidepressants (SSRIs) ± antipsychotics |
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management ofbone marrow effects from IFN
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Dose reductions
Neutropenia: GCSF 300 mcg SQ 1-3 times per week when ANC < 750 cells/mm3 Thrombocytopenia: oprelvekin 50 mcg/kg SQ 3 times per week for platelets < 100,000 cells/mm3 |
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managing ribavrin adverse effects:
hemolytic anemia |
Hemolytic anemia
Dose reductions D/C if Hgb < 8.5 g/dL Erythropoeitin 40,000 IU SQ once weekly Hgb < 12 g/dL or ≥ 3 g decrease from baseline |
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HCV PIs
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Telaprevir and boceprevir – used in combination with PegINF and ribavirin
Approval expected in summer 2011 Thrice daily dosing Adverse effects Telaprevir – rash Boceprevir – anemia, dysgeusia Both drugs are metabolized by CYP3A drug interactions |
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triple therapy for HCV
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cure rates found to be higher with triple therapy for 12 wks, then continue on w/ PEG IFN/RBV
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telaprevir in previous failures?
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40% non-responders and 76% relapsers achieved SVR on telaprevir/PegINF/RBV x 12 wks + PegINF/RBV for an additional 24 wks
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boceprevir in previous failures?
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52% non-responders and 75% relapsers boceprevir/PegINF/RBV for 48 weeks vs. 21% SOC
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HCV prevention: why no vaccines?
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Difficulty studying vaccine response
Chimpanzee only animal model Mutability Multiple genotypes, can’t make a vaccine that works against them all |
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methods to reduce risks for aquiring HCV
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Screen and test donors
Virus inactivation of plasma-derived products Risk-reduction counseling and services Obtain history of high-risk drug and sex behaviors Provide information on minimizing risky behavior, including referral to other services Vaccinate against hepatitis A and/or hepatitis B Safe injection and infection control practices |
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HCV postexposure management
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Follow-up after needlesticks, sharps, or mucosal exposures to HCV-positive blood
Test source for anti-HCV Test worker if source anti-HCV positive HCV RNA, ALT HCV Ab+ can be delayed in ~30% Confirm all anti-HCV results with RIBA Refer infected worker to specialist for medical evaluation and management |
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acute treatment for HCV
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Peginterferon monotherapy for 24 weeks, SVR up to 98%
Meta-analysis suggest best time to treat is between 2-6 months post-exposure At 1 year post-exposure, chance to clear the virus is the same as someone infected 10 years |
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key points to HCV lecutre
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Hepatitis remains a significant global health concern, especially Hepatitis B and C
Current therapies have low efficacy rates and are associated with adverse effects and high costs Pharmacists can decrease the disease burden by Identifying patients who need prophylaxis and/or testing Determining who is eligible for treatment, what therapeutic options may be best for that particular patient, and monitoring patients on antiviral therapies for therapeutic success and tolerability |
