H1N1 – The Pandemic is Here: What Clinics, Schools, Hospitals, and Communities Need to Know George C. Mejicano, MD, MS Professor of Medicine Section of.

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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