h1n1 – the pandemic is here: what clinics, schools, hospitals, and communities need to know george...
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H1N1 – The Pandemic is Here: What Clinics, Schools,
Hospitals, and Communities Need to Know
George C. Mejicano, MD, MSProfessor of Medicine Section of Infectious Diseases
UW School of Medicine and Public Health
George Mejicano has no personal financial relationships with any commercial interests.
Disclosure of Financial Relationships
SubtypesSubtypes
Hemagglutinin (HA, 1-16)Hemagglutinin (HA, 1-16)Neuraminidase (NA, 1-9)Neuraminidase (NA, 1-9)
Matrix (M1 and M2)Matrix (M1 and M2)
Nucleoprotein (NP)Nucleoprotein (NP)
Polymerase proteinsPolymerase proteins(PA, PB1 [PB1-F2], PB2)(PA, PB1 [PB1-F2], PB2)
Nonstructural proteinsNonstructural proteins(NS1, NEP)(NS1, NEP)
Influenza A Virus
H3
Y
YY
YY Y
Y
Y
H3
Y
Y
Y
YY Y Y
Y
Antigenic Drift
Courtesy of Dr. Chris Olsen
United States5-20% attack rate200,000 hospitalizations36,000+ deaths$10 billion
Globally3-5 million severe illnesses250,000-500,000 deaths
Seasonal Influenza
[Bridges et al. 2002. MMWR 51:1-31; Sugaya et al. 1992. JID 165:373-375; Thompson et al. 2003. JAMA 289:179-186; 2004. JAMA 292: 1333-1340]
[http://www.cdc.gov/flu/professionals/acip/clinical.htm#figure1]
Antigenic Shift Y
Y Y
Y Y
YH3
Y
YY
YY Y
Y
Y
H4
Courtesy of Dr. Chris Olsen
Antigenic Drift (Epidemic Influenza)
Antigenic Shift (Pandemic Influenza)
H1N11918
H2N21957
H3N21968
H3N21995
Wuhan
H3N21997
Sydney
H3N21999
Panama
1918 Influenza Pandemic
Influenza Mortality by Age
1918 H1N1 (“Spanish Flu”)675,000 deaths (U.S.)20-50 million deaths (Globally)
[Crosby. 1989. Cambridge University Press; Taubenberger et al. 2000. Virology 274:241-245; 2001. Phil. Trans. R. Soc. Lond. 356:1829-1839]
1957 H2N2 (“Asian Flu”)69,800 deaths (U.S.)2-4,000,000 deaths (Globally)
1968 H3N2 (“Hong Kong Flu”)33,800 deaths (U.S.)1-2,000,000 deaths (Globally)
[Cox and Subbarao. 2000. Annu. Rev. Med. 51:407-421; Klimov et al. 1999. Vaccine 17:S42-S46; Noble. 1982. In: Beare (ed.), Basic and Applied Influenza Research. CRC.; Simonsen et al. 2005]
Influenza Pandemics
Influenza Statistics: USA
From 1979 through 2001, the estimated annual number of hospitalizations due to influenza in the US ranged from 55,000 to 431,000 per annual seasonal epidemic (mean: 226,000)
Approximately 19,000 influenza-associated deaths per year occurred between 1976 and 1990
Approximately 36,000 deaths per influenza season occurred between 1990 and 1999 (thought to be secondary to the aging population in the US)
[http://www.cdc.gov/flu/professionals/acip/clinical.htm#figure1]
Influenza Transmission
Influenza viruses are spread primarily through large-particle respiratory droplets which require close contact (within 3 feet)
Contact with respiratory-droplet contaminated surfaces may also play a role
Incubation period is 1-4 days (mean: 2 days) Adults shed virus for about 8 days starting
from the day before symptoms begin Severely immunocompromised persons can
shed virus for weeks or months
Influenza Symptoms
Influenza like illness (ILI): abrupt onset of fever, headache, myalgia, nonproductive cough, sore throat, malaise, and rhinitis
Otitis media and GI symptoms in children Typically resolves after 3-7 days; cough and
malaise can persist for >2 weeks Influenza virus infections can:
Cause primary influenza viral pneumonia Exacerbate underlying medical conditions Lead to secondary bacterial respiratory
infections
Influenza Movie
[http://www.cdc.gov/h1n1flu/updates/us/#iligraph]
H1N1 Influenza A: USA 2009
From April 15 – July 24, 2009 Total of 43,771 cases Total of 5,011 hospitalizations Total of 302 deaths (0.7% mortality)
Since August 30, 2009 411 deaths out of 8,204
hospitalizations Mortality if hospitalized = 5.0%[http://www.cdc.gov/flu/weekly/ (accessed October 27, 2009)]
[http://pandemic.wisconsin.gov/docview.asp?docid=17469&locid=106 (Accessed August 27, 2009)]
What About Wisconsin?
4583 confirmed cases
1814 probable cases
6397 total cases
H1N1 Influenza A: USA 2009
What is the household attack rate? Acute respiratory illness = 18 - 19% Influenza like illness = 8 - 12%
Percent of the population affected? Approximately 6 – 7% in areas that
have done surveillance
[http://www.cdc.gov/flu/weekly/ (accessed August 27, 2009)]
http://www.cdc.gov/h1n1flu/surveillanceqa.htm
H1N1 Case Rate by Age Group, USA 2009
H1N1 Deaths by Age Group, USA 2009
World Health Organization (WHO) Declares H1N1 Influenza Pandemic on June 11, 2009
[http://www.who.int/csr/disease/avian_influenza/phase/en/ (Accessed August 25, 2009)]
Diagnosing Influenza
In outpatients > 60 years, fever, cough, and acute onset of shortness of breath has a positive predictive value of 30%
Vaccinated older persons with chronic lung disease: cough not predictive of laboratory-confirmed influenza (but fever with myalgia had a positive predictive value of 41%)
Identifying influenza in the absence of laboratory confirmation is challenging!
Differential Diagnosis
Mycoplasma pneumoniae Adenovirus Respiratory syncytial virus Rhinovirus Parainfluenza viruses Legionella pneumophila
Diagnosing Influenza
Best samples for influenza testing include nasopharyngeal swab, nasal wash or aspirate, depending on the type of test
Samples should be collected within the first 4 days of illness
Rapid influenza tests can provide results within 15 minutes or less
Viral culture provides results in 3-10 days Most rapid tests have a sensitivity of 50-
70% & a specificity > 90% (don’t use for novel H1N1)
Rapid Influenza Diagnostic Tests
Diagnosing Novel H1N1 Influenza
Real-time reverse transcriptase polymerase chain reaction (rRT-PCR) is the best test to use to confirm novel influenza A (H1N1) cases
Novel H1N1 virus will test positive for influenza A but negative for influenza B & H3 by rRT-PCR
If reactivity of rRT-PCR for influenza A is strong, this suggests the sample has novel H1N1 virus (as opposed to seasonal H1N1 virus)
Test was originally performed only at CDC, but now available in various labs across the country
[http://www.cdc.gov/h1n1flu/specimencollection.htm (Accessed August 27, 2009)]
Main Prevention Messages
Wash your hands for 20 seconds Cover your mouth and nose when
coughing and sneezing Use tissues and dispose them properly Avoid close contact with sick people Disinfect items people frequently touch Avoid smoking Get vaccinated!
Influenza Vaccine Efficacy in Long-Term Care Facilities
Outcome Gross et al Jefferson et al
Respiratory illness/ILIRespiratory illness/ILI 56% (39%-68%)56% (39%-68%) 23% (6%-36%)23% (6%-36%)
PneumoniaPneumonia 53% (35%-66%)53% (35%-66%) 46% (30%-58%)46% (30%-58%)
HospitalizationHospitalization 48% (28%-65%)48% (28%-65%) 45% (16%-64%)45% (16%-64%)
DeathDeath 68% (56%-76%)68% (56%-76%) 60% (23%-79%)60% (23%-79%)
[Gross P et al. Ann Intern Med. 1995;123:518-527 and Jefferson T et al. Lancet. 2005;366:1165-1174]
Trivalent Inactivated and Live Attenuated Influenza Virus Vaccines
Category TrivalentInactivated (TIV)
Live Attenuated Influenza Virus (LAIV)
Administration &Administration &immune responseimmune response
IM IM Serum antibodiesSerum antibodies
Intranasal Intranasal Mucosal Mucosal immunityimmunity
FormulationFormulation InactivatedInactivated Live attenuatedLive attenuated
Safety (side effects)Safety (side effects) Sore armSore arm CoryzaCoryza
Growth mediumGrowth medium Chick embryosChick embryos Chick cellsChick cells
StorageStorage RefrigeratedRefrigerated FrozenFrozen
IndicationIndication ≥≥6 m (healthy & HR)6 m (healthy & HR) 5–49 y (healthy)5–49 y (healthy)
[MMWR 2005;54(RR-8):1-40]
Vaccine: CDC Recommendations
Recommendation is to give seasonal trivalent influenza vaccine as soon as it is available
H1N1 vaccine targets A/California/07/2009 H1N1 monovalent vaccine will require 1 dose
(two doses for children 6 months – 9 years) Do not give both live vaccines at the same time
(concern for blunting immune response)
[http://www.cdc.gov/h1n1flu/vaccination/clinicians_qa.htm]
Vaccine: High Risk Medical Conditions
Medical conditions that confer a higher risk for influenza-related complications include: Chronic pulmonary (including asthma) illness Cardiovascular (except hypertension) illness Renal illness Hepatic illness Cognitive and neurologic/neuromuscular condition Hematologic illness (including sickle cell disease) Metabolic disorders (including diabetes mellitus) Immunosuppression (whether caused by
medication or condition such as HIV/AIDs)
[MMWR 2009: 58(RR10);1-8 (Released August 28, 2009)]
Vaccine: Initial Target Groups
Advisory Committee on Immunization Practice (ACIP) recommends that vaccine be given to all persons in the following five initial groups as soon as vaccine is available (order does not indicate priority):
Pregnant women Persons who live with or provide care for infants
aged <6 months (e.g., parents, siblings, and daycare providers)
Healthcare and emergency medical service workers
Children & young adults aged 6 months - 24 years Persons aged 25 - 64 years who have medical
conditions that increase their complication risk [MMWR 2009: 58(RR10);1-8 (Released August 28,
2009)]
ACIP recommends that everyone in the following subset of the initial target groups receive priority if vaccine availability is not sufficient to meet demand (order of target groups does not indicate priority):
Pregnant women Persons who live with or provide care for infants aged
<6 months (e.g., parents, siblings, & daycare workers)
Healthcare and emergency medical workers who have direct contact with patients or infectious material
Children aged 6 months - 4 years Children & adolescents aged 5 -18 years who have
increased complication risk
Vaccine: Subset of Initial Target Groups
[MMWR 2009: 58(RR10);1-8 (Released August 28, 2009)]
Outpatient Issues
Good hand hygiene & cough etiquette should be observed by everyone
Patients should be actively screened at entry points to determine if they may have an influenza like illness If so, the patient should immediately
don a surgical mask & be placed in an exam room
Healthcare workers should wear eye protection and either an N-95 mask or a powered air-purifying respirator (PAPR)
No need for gowns or gloves
N-95 Masks and PAPRs
Healthcare Worker Exposure
Face to face contact (within 6 feet) when the patient was not wearing a surgical mask or the healthcare worker was not wearing either an N-95 mask or PAPR
Splashes or sprays or respiratory or oral secretions onto the healthcare worker’s unprotected eyes, nose, or mouth
Sick Healthcare Workers?
Notify supervisor and stay home if healthcare worker has fever and respiratory symptoms
Stay home from work for at least 24 hours after fever resolves (without using antipyretics)
If work area houses patients with severe immunosuppression, temporary reassignment or exclusion from work for 7 days from onset of symptoms or 24 hours after the resolution of symptoms, whichever is longer
Drug Therapy - 1
Both zanamavir and oseltamavir: Effective against Influenza A and B Decrease the duration of symptoms by
approximately 50% (1-2 days) if given within 36 hours of symptom onset
Decrease risk of secondary pneumonia Rimantadine and amantadine only
work against Influenza A; most strains resistant
Drug Therapy - 2
Oseltamavir 75 mg twice daily x 5 days in adults (treatment) Well absorbed but better tolerated with food If renal clearance is < 30 but > 10, give 75 mg daily
Zanamavir Two 5 mg inhalations twice daily x 5 days (treatment) Approximately 10% absorbed Renal excretion of unchanged drug Bronchospasm can occur so use cautiously in persons
with COPD and asthma (i.e., use after inhalers)
Antiviral Resistance: 2009
[http://www.cdc.gov/flu/weekly/ (accessed August 27, 2009)]
[http://www.cdc.gov/h1n1flu/recommendations.htm (Accessed October 27, 2009)]
[http://www.cdc.gov/h1n1flu/recommendations.htm (Accessed October 27, 2009)]
Peramivir
US Food and Drug Administration (FDA) authorized emergency use of this drug on 10/23/09 (600 mg IV daily x 5-10 d)
Only for hospitalized patients with H1N1 Not responding to oral or inhaled drugs Drug delivery by other route is unreliable In adults, when clinician judges IV therapy
is appropriate due to other circumstances[http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
ucm187813.htm]
Who Gets Treated?
Every hospitalized patients with confirmed, probable or suspected 2009 H1N1 influenza
Early empiric treatment now recommended for outpatients who are at higher risk for influenza-related complications (next slide)
Suspected or confirmed influenza with severe illness (i.e., lower respiratory tract infection or clinical deterioration)
[http://www.cdc.gov/h1n1flu/recommendations.htm (Accessed October 27, 2009)]
Conditions That Warrant Early Rx
Children younger than 2 years old Adults 65 years of age or older Pregnant women and women up to 2 weeks
postpartum Persons with chronic pulmonary (including asthma),
cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), or metabolic disorders (including diabetes mellitus)
Disorders that can increase the risk for aspiration (e.g., cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders)
Immunosuppression, including HIV/AIDS
Who Gets Prophylaxis?
Post-exposure prophylaxis recommended for: Close contacts of known or suspected case who are at
high risk for complications (see previous slide) Healthcare workers with an unprotected exposure to
known or suspected case when patient was contagious
Do not give post-exposure prophylaxis: If more than 48 hours have elapsed since last exposure In healthy children or adults simply based on potential
exposures in the community, school, camp, etc.
[http://www.cdc.gov/h1n1flu/recommendations.htm (Accessed October 27, 2009)]
Duration of Prophylaxis?
For typical exposure Duration of chemoprophylaxis is 10 days after the
last known exposure to novel H1N1 influenza For nursing home exposure
Chemoprophylaxis should be administered to all non-ill residents & should continue for a minimum of 2 weeks
If surveillance indicates that new cases continue to occur, prophylaxis should continue until approximately 7 days after illness onset in the last patient
[http://www.cdc.gov/h1n1flu/recommendations.htm#table1 (Accessed August 27, 2009)]
Pregnancy Issues
Pregnant women are at very high risk of severe illness and complications from influenza
Oseltamavir and zanamavir are both Pregnancy Category C medications
Pregnancy is not a contraindication to antiviral therapy with oseltamavir or zanamavir
Oseltamavir is preferred for treatment because it is systemic
Zanamavir is preferred for prophylaxis because it is limited to the respiratory tract[http://www.cdc.gov/h1n1flu/recommendations.htm (Accessed August 27, 2009]
10 Things All Clinics Should Do
Develop a business continuity plan Inform staff of plans to cope with surge Plan to stay open with only 60% staff Demand that sick staff persons stay home Plan for increased demand of your services Care for patients with H1N1 influenza Protect your staff with proper equipment Vaccinate your staff at no charge Know pandemic plans of local hospitals and public
health Know where to find accurate, up-to-date information
[http://www.cdc.gov/h1n1flu/10steps.htm (Accessed August 27, 2009)]
What About Schools?
If conditions are like Spring 2009 Stay home when sick (for at least 24 hours
after fever stops without antipyretics) Separate ill students and staff Hand hygiene and respiratory etiquette Routine cleaning Early treatment of high-risk students/staff Consideration of selective school dismissal
[http://www.cdc.gov/h1n1flu/schools/schoolguidance.htm (Accessed August 27, 2009)]
What About Schools?
If conditions worse than Spring 2009 Active screening (ask each child about suggestive symptoms,
separate those who are ill and send them home ASAP) High-risk students/staff stay home Students with ill household members stay home Increase distance between people at schools
Desks farther apart Cancel events that mix children from different classrooms
Extend the period for ill persons to stay home to at least 7 days, even without symptoms (longer if still symptomatic)
Consider school dismissals Reactive: unable to maintain staffing or sick persons showing up Preemptive: to stop the spread of the virus
[http://www.cdc.gov/h1n1flu/schools/schoolguidance.htm (Accessed August 27, 2009)]
School Screening Questions
Ask about symptoms suggestive of influenza during the past 24 hours, including (send home if 2 or more): Fever >100ºF Cough Runny nose Sore throat
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