The Fourth Horseman:thoughts on influenza, pandemics and medicineJon Temte, MD/PhD12 November 2009

Professor of Family MedicineUniversity of Wisconsin School of Medicine and Public HealthVice Chair, CDC Advisory Committee on Immunization Practices

The Fourth HorsemenI looked and there before me was a pale horse! Its rider was named Death to kill by sword, famine and plague, and by the wild beasts of the earth. Revelations 6:3-4

Katharine Anne Porter (1890-1980)Her mind tottered and slithered again, broke from its foundation and spun like a cast wheel in a ditch... She sank easily through deeps and deeps of darkness until she lay like a stone at the farthest bottom of life

Pale Horse, Pale Rider, 1939Personal experience withSpanish flu (H1N1) in 1918

The Fourth HorsemanThe night air is cool and damp. My initial irritation at being awake at 2:15 AM is tempered by my familiarity with the patient I am driving in to admit to the hospital; well-known, pleasant, but defeated by life, and now hemorrhaging. As usual, while making my early morning on-call drive, I catch the BBC World Service on my public radio affiliate. The story deals with the World Health Organizations efforts to discover the origins of the latest emergence: influenza A(H1N1) (S-OIV).

(May 1, 2009)

I know that the tranquility of a Wisconsin spring, and of my life are in the process of shattering. I have been in cross training for the last 15 years a family doctor with an interest in community patterns of infectious disease. I have been a watcher of influenza, studying its recurrent seasonal spread across my state. My skills have been in surveillance and communication. Ive participated over the years with local, state and national pandemic planning and disaster response. Ive climbed the ladders of professional society leadership and appointments to national advisory panels. Influenza is an old familiar friend. I know all this cold. And I am not ready.

The cases will mount. The calls and emails will grow beyond hope. There will be too much coordination in too many directions.

Life goes on. I admit my patient, drive home and settle into a brief and fitful sleep.

an overviewbasic epidemiologyswine influenzalessons learnedbasic rules of influenzaresponse

Basic Influenza Epidemiology

Necessary Conditionsfor Epidemicsexposure to pathogenssusceptible populationsappropriate environmentenhanced person-to-person contact

Exposure to pathogen (spark)immigrant effectremote communitiesglobal nature of influenzahemispheric oscillationseasonalityZoonoses (antigenic gift)prevalence in numerous speciesoccasional interspecific transmission

Susceptible populations (fuel)role of antigenic driftminor year-to-year change in antigensrole of antigenic shiftmajor change in antigenshemaglutinin and neuraminidaseimmunizationbased upon strains likely to circulatehigh risk population prophylaxis

NeuraminidaseHemaglutininSource: Dr. Timothy Paustian www.bact.wisc.edu/ microtextbook

Environment (condition)climatictemperaturehumidity monsoonanthropogeniclong-term trends

Seasonal Correlates of Influenza A in Wisconsin( Wisconsin Influenza Isolates: 7/1/80 through 6/30/05 )

Enhanced contact (catalyst)cultural / economicschool contactsemployment contactsthe commutephysicalconfined spaces (e.g., air travel)socialholidays

Vectors of Respiratory VirusesChildhood illnessschool-aged children age 5 through 18high attack ratesup to 40%variable symptomstransmission parents, grandparentssiblingswere vectorsMonday, December 13, 2004Mom DadVirus culture on December 20, 2006 positive for Influenza A H3N2 California

Influenza in the Community

The role of schoolSeasonality - the year starting in SeptemberWisconsin: 9/2007 to 8/2008UW Family Medicine Clinical Data Warehouse

1957 Pandemic Kansas Cityattack rate and mortalityInformation taken from: Serfling et al., Am J Epidemiol 1967;86:433-41Chin et al., J Public Health Rep 1960; 75:149-58

Basic Epidemic Math

Nt = NoertNt = the number of cases at time tNo = the number of cases at time 0 e = the natural exponentialt = the number of generations

A word about rr is the intrinsic rate of growthcan be considered in terms of how many new cases are caused by each existing case equal to the natural logarithm of the number of new cases per existing caser = ln(N1/N0)If 2 cases caused by current case: r = 0.693If 3 cases caused by current case: r = 1.099

Example: effect of r

This would lead to exponential growth ...

... except that r rapidly declines after a period of relative stabilitySusceptible individualsbecome less prevalent In general population

because r declines, a classic epidemic curve emerges

This is reflected in the average epidemic curve for WisconsinFirst CasesTransitionPeakLast Cases

Modeling Annual Influenza A Epidemics in Wisconsinr = 0.693; pre-season immunity = 30%

Effect of pre-season immunityon shape and timing of epidemic curveTime

Effect of pre-season immunityon total percent of population infected

Swine Flu and PoohImage: CDC/ C. S. Goldsmith and A. Balish As the two friends wandered through the snow on their way home, Piglet grinned to himself, thinking how lucky he was to have a best friend like PoohPooh thought to himself: If the pig sneezes, hes dead.

Novel Influenza A (H1N1)swine-originated influenza virusGenes fromNA pigsEA pigsHumansTurkeysChickens Rapidly evolving situationApril 21 case report -2 cases in California Children

Doubling Time Global: 1.8 days US: 2.1 days

Chart1

111

222

333

8254

555

6386

40667

81058

651489

10925710

14133111

1606153

2268983

27910853

40314905

64215165

171717

181818

191919

202020

US - CDC

Global - WHO

Day Number

Cases

Sheet1

ProbableConfirmed Cases

DateWisconsinWisconsinUSWORLDDay #

4/20/051

3/21/052

4/22/053

4/23/058254

4/24/055

4/25/05386

4/26/0540667

4/27/051058

4/28/05651489

4/29/05310925710

4/30/0514133111

5/1/05316061512

5/2/0565322689813

5/3/051023279108514

5/4/051195403149015

5/5/051195642151616

5/6/0517

5/7/0518

5/8/0519

5/9/0520

Nt=Noert

Generation Time =2.5days

Global e =0.3988from chart

USA e =0.3359from chart

r (global) =0.997

r (USA) =0.83975

secondary cases (g) =2.71

secondaty cases (u) =2.32

doubling time (g)1.7

doubling time (u)2.1

Sheet1

US - CDC

Global - WHO

Wisconsin

Day Number

Cases

Sheet2

US - CDC

Global - WHO

Day Number

Cases

Sheet3

Current Status ReportGlobal (November 1, 2009)482,300 cases 6,071 deaths (case fatality rate = 1.26%)

U.S. (November 6, 2009)17,838 hospitalizations672 deaths

Wisconsin (November 6, 2009)10,685 confirmed or probable cases 20 deaths (case fatality rate = 0.094%)My best guess for case fatality rate = 0.002 to 0.010%

Cumulative Cases of novel H1N1 August 30 - November 6Wisconsin, by county

Cumulative Rates of novel H1N1 August 30 - November 6Wisconsin, by county

Outpatient influenza-like illness visits

Pneumonia and influenza death percent

Pediatric DeathsHigh Risk Condition Any 67% Neurodevelopmental 61% Multiple ND 36% Chronic Pulmonary28% ND with CPD25% Congenital Heart 8% Metabolic/Endocrine 6% Immunosuppression 6%

H1N1 and pregnancyPregnancy is a significant risk factorWomen of childbearing age have increased exposureCase rate = 1/100,000 pregnancies four-fold increased rate of hospitalizationCase series: 11 admissions out of 34 cases (32.4%)0.32/100,000 in pregnancy 0.076/100,000 for general population6 deaths (antivirals started 8-15 days post-onset)5 in 3rd trimester (C-section); 1 in first trimester

Signs and Symptoms

Basic DemographicsSex Ratiofemale = male Median AgeAll cases = 12 yearsHospitalized cases = 20 yearsDeaths = 37 years

1957 Pandemic Kansas Cityattack rate and mortalityInformation taken from: Serfling et al., Am J Epidemiol 1967;86:433-41Chin et al., J Public Health Rep 1960; 75:149-58

Louie, J. K. et al. JAMA 2009;302:1896-1902.Hospitalization and Fatality Rates and Case-Fatality Proportion Among Reported Hospitalized Cases California, April 23 Through August 11, 2009

Age Distribution of Hospitalizations

Hospitalization Rates (per 100,000)

*Based on confirmed cases for whom these data are available at time of report

Percent of Hospitalized Patientswith underlying medical conditions

Lessons learned: Imagine an iceberg

Seasonal Influenza36,000 deaths200,000 hospitalizations

Pandemic influenza672 deaths 17,838 hospitalizations

Influenza Isolates WisconsinApril 26 October 3, 2009

Influenza Isolates Wisconsin(excluding 2009 H1N1) April 26 October 3, 2009

Chart1

2.30094959822.3009495982

1.64504903511.6450490351

0.52417006410.5241700641

0.78902229850.7890222985

0.49941245590.4994124559

1.61943319841.6194331984

1.58394931361.5839493136

1.06082036781.0608203678

1.74757281551.7475728155

0.46701692940.4670169294

0.40816326530.4081632653

1.06382978721.0638297872

0.09643201540.0964320154

0.36496350360.3649635036

1.03519668741.0351966874

0.95419847330.9541984733

0.52219321150.5221932115

0.21067415730.2106741573

0.4477611940.447761194

1.04166666671.0416666667

0.61162079510.6116207951

0.45045045050.4504504505

0.34364261170.3436426117

1.31578947371.3157894737

0.31948881790.3194888179

0.53191489360.5319148936

0.52910052910.5291005291

0.35335689050.3533568905

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

all states

staes with at least 1 death

State by State Incidence (cases/100,000)

Case Fatality Rate (%)

y = -0.0018x + 0.4794R2 = 0.0049

y = -3E-05x + 0.8518R2 = 0.0053

Sheet1

StatecasespopulationdeathsCFR%incidence/100,000deaths/100,000

New York273819306000632.3014.180.33

California316136458000521.658.670.14

Texas515123508000270.5221.910.11

Florida291518090000230.7916.110.13

Illinois340412832000170.5026.530.13

Utah9882550000161.6238.750.63

Arizona9476166000151.5815.360.24

New Jersey14148725000151.0616.210.17

Michigan5151009600091.755.100.09

Connecticut1713350500080.4748.870.23

Pennsylvania19601244100080.4115.750.06

Washington658639600071.0610.290.11

Wisconsin6222555700060.10111.970.11

Massachusetts1370643700050.3621.280.08

North Carolina483885700051.045.450.06

Oregon524370100050.9514.160.14

Maryland766561600040.5213.640.07

Hawaii1424128500030.21110.820.23

Minnesota670516700030.4512.970.06

Rhode Island192106800021.0417.980.19

Virginia327764300020.614.280.03

Georgia222936400010.452.370.01

Indiana291631400010.344.610.02

Missouri76584300011.321.300.02

Nebraska313176800010.3217.700.06

Ohio1881147800010.531.640.01

Oklahoma189357900010.535.280.03

Tennessee283603900010.354.690.02

Alabama477459900000.0010.370.00

Alaska27267000000.0040.600.00

Arkansas131281100000.004.660.00

Colorado171475300000.003.600.00

Delaware38185300000.0044.670.00

Idaho166146600000.0011.320.00

Iowa165298200000.005.530.00

Kansas204276400000.007.380.00

Kentucky143420600000.003.400.00

Louisiana232428800000.005.410.00

Maine145132200000.0010.970.00

Mississippi252291100000.008.660.00

Montana9494500000.009.950.00

Nevada467249600000.0018.710.00

New Hampshire247131500000.0018.780.00

New Mexico232195500000.0011.870.00

North Dakota6363600000.009.910.00

South Carolina244432100000.005.650.00

South Dakota4578200000.005.750.00

Vermont5962400000.009.460.00

Washington, D.C.4558200000.007.730.00

West Virginia243181800000.0013.370.00

Wyoming11151500000.0021.550.00

total436932994030003020.0714.590.10

estimated10000000.03334.00

Sheet1

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all states

staes with at least 1 death

State by State Incidence (cases/100,000)

Case Fatality Rate (%)

y = -0.0018x + 0.4794R2 = 0.0049

y = -3E-05x + 0.8518R2 = 0.0053

Sheet2

Sheet3

Telephone Call VolumeSep 7Sep 14Sep 21Sep 28Oct 5Oct 12

Basic Rules of Influenza(1) Human influenza viruses are transmitted person-to-person

Children are effective vectors. Social distancingmaintaining distance between susceptible persons and casesis a uniformly effective measure that will prevent transmission.

Basic Rules of Influenza(2) Influenza viruses are primarily transmitted by respiratory droplets formed from respiratory secretions and propelled forth by a cough or sneeze.

Deflecting or containing respiratory droplets will prevent transmission. Face masks, used by infected or susceptible persons, can be effective in preventing transmission.

Basic Rules of Influenza(3) Influenza viruses prefer cool, dry air. Influenza is a highly seasonal virus with most transmission limited to late fall and winter across temperate latitudes.

Transmission can occur at other times, but is far less efficient. When novel viruses (such as H1N1 influenza) emerge, transmission can occur at unusual times because of the absence of immunity.

Basic Rules of Influenza(4) Influenza viruses target respiratory mucosa. The potentially "exposed" respiratory mucosa covers the nasal passages, nasopharynx, conjunctiva, pharynx, larynx, trachea, bronchi, bronchioles, and alveoli.

Protection of respiratory mucosa from droplets and/or direct contact will prevent transmission. Contaminated hands can provide direct contact. Hand-washing reduces direct contact.

Basic Rules of Influenza(5) Once exposed, there is a fairly predictable incubation period for influenza viruses. Clinical illness will appear within 24 to 72 hours following infection.

The lack of clinical illness following exposure signifies no infection, adequate immunity, or subclinical infection.

Basic Rules of Influenza(6) Once infected, there is a fairly predictable period of virus shedding and transmissibility. Peak shedding of the virus occurs during day two to three of clinical illness, generally corresponding to the period of peak symptoms.

Sick persons are less likely to move through the community. Medical systems, however, often require sick persons to present to the community. After five to six days of illness, an individual is unlikely to transmit influenza.

Basic Rules of Influenza(7) Once infected, a pathway leading to immunity is triggered within the influenza host. The immune response leads to some of influenza's symptoms.

Infection and recovery produce lasting immunity to that particular strain of influenza, provided that the host's immune system is intact. People who successfully avoid H1N1 influenza will be susceptible in the future and should be vaccinated.

Basic Rules of Influenza(8) Infection leads to recovery and immunity, or death.

The propensity towards host death depends on strain and host factors. In general, influenza mortality is highest in very young and very old, and in the most immunocompromised persons.

Basic Rules of Influenza(9) Immunity may be acquired via infection or via immunization.

Previous infection with other strains and/or immunization does not guarantee immunity. Host factors and poor vaccine match can significantly reduce immunity. As an H1N1 influenza vaccine becomes available, physicians will need to immunize patients according to recommendations.

Basic Rules of Influenza(10) Influenza epidemics follow predictable patterns over time. This general behavior can be modeled using estimates of immunity, transmissibility, and generation time.

Many of the parameters needed to model epidemics are difficult to obtain; models work best in retrospect. Many excellent regional and national surveillance systems exist which can guide appropriate practice.

Basic Rules of Influenza(11) There is a delicate interplay between the infectivity of a virus and the population's level of pre-existing immunity. For transmission to occur, susceptible persons in the exposed population are needed. Reducing the likelihood of contact with a susceptible person reduces the infectivity of a virus.

Novel influenza viruses are unconstrained by factors of immunity and achieve high infectivity potential. As late fall and winter return, H1N1 influenza may become significantly worse.

Basic Rules of Influenza(12) "All living things contain a measure of madness that moves them in strange, sometimes inexplicable ways.*" Any of these rules may be broken at any time; influenza viruses have a high potential for mutation, genomes may be recombined, and population patterns are not fixed.

Whereas basic rules can set the conversation for planning activities, ongoing surveillance and modification of response are necessary for influenza prevention and control efforts. *Yann Martel, Life of Pi 2003

responding toinfluenza

HandwashingRespiratory Protective Equipment

6/06

Faculty Documentation Form for Evidence-Based CME Clinical Content

Complete this form for each topic seeking AAFP EB CME designation and submit with the CME application. Please print supporting evidence for each practice recommendation from the approved source web site. Submit only the page(s) where the evidence is cited. This page must show the specific web page address. No more than three recommendations are needed for each credit.

Learners must be informed in writing of 1) the approved practice recommendation, 2) the AAFP-approved EBM source used, 3) the specific URL where that information can be found, and 4) the strength of the sited evidence.

Date of Submission: July 14, 2006

Activity Title: 2006 AAFP Scientific Assembly, Annual Lecture Series

Topic Title: Pandemic Influenza: What You Need to Know Now

Date (if applicable): September 27 - October 1, 2006 Author/Speaker: Jonathan L. Temte, MD, PhD

Number of EB CME credits requested: 1

In the past year, has this topic been approved for AAFP EB CME designation? FORMCHECKBOX Yes FORMCHECKBOX No

________________________________________________________________________________________________

Handwritten recommendations cannot be accepted for review. A sample practice recommendation can be found at the end of this form.

# 1 PRACTICE RECOMMENDATION (a statement of clinical guidance, supported by evidence, that learners can use within their practice.)

Handwashing can reduce trasmission or respiratory viruses, including (potentially) influenza H5N1

Name of AAFP-approved source of systematic evidence review: Bandolier

Specific webpage address citing the evidence supporting the recommendation from the approved source (not the sources home page):

http://www.jr2.ox.ac.uk/bandolier/band91/b91-4.html

Strength of evidence (narrative and/or grade with explanation of what the grade means as provided by the approved source):

Frequent handwashers have fewer self-reported respiratory illness than infrequent handwashers [OR = 1.5 (95% CI: 1.2 to 2.8)]

Infrequent handwashers have significantly more hospital admissions [OR = 11 (95% CI: 2.7 to 46 )]

________________________________________________________________________________________________

# 2 PRACTICE RECOMMENDATION (a statement of clinical guidance, supported by evidence, that learners can use within their practice.)

The use of respiratory protective equipment, for example a particulate filter mask, is indicated when exposure to a significant respiratory pathogen is possible.

Name of AAFP-approved source of systematic evidence review: National Guideline Clearinghouse (NGC)

Specific webpage address citing the evidence supporting the recommendation from the approved source (not the sources home page):

http://www.guideline.gov/summary/summary.aspx?doc_id=5069

Strength of evidence (narrative and/or grade with explanation of what the grade means as provided by the approved source):

Grade D - Directly based on category IV evidence, or extrapolated recommendation from category I, II or III evidence

_______________________________________________________________________________________________________________________________________

# 3 PRACTICE RECOMMENDATION (a statement of clinical guidance, supported by evidence, that learners can use within their practice.)

Neuraminidase inhibitors are recommended for treatment of influenza, and can possibly be of benefit for influenza A (H5N1). Recommendations are provided for adults and children

Name of AAFP-approved source of systematic evidence review: Cochrane Database of Systematic Reviews

Specific webpage address citing the evidence supporting the recommendation from the approved source (not the sources home page):

http://www.cochrane.org/reviews/en/ab001265.html http://www.cochrane.org/reviews/en/ab002744.html

Strength of evidence (narrative and/or grade with explanation of what the grade means as provided by the approved source):

For Adults:

NIs were 74% effective (95% CI: 50%-87%) in preventing clinically defined influenza

NIs were 60% effective (95% CI: 76%-33%) in preventing cases of laboratory confirmed influenza

NIs shorten the duration of symptoms by one day (95% CI: 1.3 to -0.6).

For Children:

Oseltamivir reduced the median duration of illness by 26% (36 hours) in previously healthy children with laboratory confirmed influenza (p < 0.0001) and by 17% (21 hours) for intention-to-treat population (p = 0.0002).

Zanamivir reduced the median duration of illness by 24% (1.25 days) in previously healthy children with laboratory confirmed influenza (p < 0.001) and by 10% (0.5 days) for intention-to-treat population (p = 0.011).

________________________________________________________________________________________________

# 4 PRACTICE RECOMMENDATION (a statement of clinical guidance, supported by evidence, that learners can use within their practice.)

Influenza vaccine--if availble--is recommended to prevent influenza A (H5N1). Recommendations are provided for both adults and children.

Name of AAFP-approved source of systematic evidence review: Cochrane Database of Systematic Reviews

Specific webpage address citing the evidence supporting the recommendation from the approved source (not the sources home page):

http://www.cochrane.org/reviews/en/ab001269.html http://www.cochrane.org/reviews/en/ab004879.html

Strength of evidence (narrative and/or grade with explanation of what the grade means as provided by the approved source):

For Adults: LAIV reduced cases of serologically confirmed influenza by 48% (95% CI: 24% to 64%) and clinical influenza cases by 15% (95% CI: 8% to 21%). TIV had a vaccine efficacy of 70% (95% CI: 56% to 80%) for of serologically confirmed influenza and of 25% (95% CI: 13% to 35%) for clinical I influenza cases.

For Children: LAIV showed an efficacy of 79% (95% CI: 48% to 92%) and an effectiveness of 33% (95% CI: 28% to 38%). TIV had a vaccine efficacy of 59% (95% CI: 41% to 71%) and an effectiveness of 36% (95% CI: 24% to 46%)

________________________________________________________________________________________________

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Oops... evidence encounters dogma

Antiviral MedicationVaccine

# 3 PRACTICE RECOMMENDATION (a statement of clinical guidance, supported by evidence, that learners can use within their practice.)

Neuraminidase inhibitors are recommended for treatment of influenza, and can possibly be of benefit for influenza A (H5N1). Recommendations are provided for adults and children

Name of AAFP-approved source of systematic evidence review: Cochrane Database of Systematic Reviews

Specific webpage address citing the evidence supporting the recommendation from the approved source (not the sources home page):

http://www.cochrane.org/reviews/en/ab001265.html http://www.cochrane.org/reviews/en/ab002744.html

Strength of evidence (narrative and/or grade with explanation of what the grade means as provided by the approved source):

For Adults:

NIs were 74% effective (95% CI: 50%-87%) in preventing clinically defined influenza

NIs were 60% effective (95% CI: 76%-33%) in preventing cases of laboratory confirmed influenza

NIs shorten the duration of symptoms by one day (95% CI: 1.3 to -0.6).

For Children:

Oseltamivir reduced the median duration of illness by 26% (36 hours) in previously healthy children with laboratory confirmed influenza (p < 0.0001) and by 17% (21 hours) for intention-to-treat population (p = 0.0002).

Zanamivir reduced the median duration of illness by 24% (1.25 days) in previously healthy children with laboratory confirmed influenza (p < 0.001) and by 10% (0.5 days) for intention-to-treat population (p = 0.011).

________________________________________________________________________________________________

# 4 PRACTICE RECOMMENDATION (a statement of clinical guidance, supported by evidence, that learners can use within their practice.)

Influenza vaccine--if availble--is recommended to prevent influenza A (H5N1). Recommendations are provided for both adults and children.

Name of AAFP-approved source of systematic evidence review: Cochrane Database of Systematic Reviews

Specific webpage address citing the evidence supporting the recommendation from the approved source (not the sources home page):

http://www.cochrane.org/reviews/en/ab001269.html http://www.cochrane.org/reviews/en/ab004879.html

Strength of evidence (narrative and/or grade with explanation of what the grade means as provided by the approved source):

For Adults: LAIV reduced cases of serologically confirmed influenza by 48% (95% CI: 24% to 64%) and clinical influenza cases by 15% (95% CI: 8% to 21%). TIV had a vaccine efficacy of 70% (95% CI: 56% to 80%) for of serologically confirmed influenza and of 25% (95% CI: 13% to 35%) for clinical I influenza cases.

For Children: LAIV showed an efficacy of 79% (95% CI: 48% to 92%) and an effectiveness of 33% (95% CI: 28% to 38%). TIV had a vaccine efficacy of 59% (95% CI: 41% to 71%) and an effectiveness of 36% (95% CI: 24% to 46%)

________________________________________________________________________________________________

Influenza H1N1Priority Group 1Pregnant women Household contacts/caregivers of infants younger than 6 months Healthcare personnel and EMS Children and adolescents6 months to 18 years 78 millionhigh incidence of infection & potent influenza spreadersYoung adults age 19-24 years Adults aged 25-64 years with certain medical conditionsImage: CDC/ C. S. Goldsmith and A. Balish Image: CDC/ Dr. Terrence Tumpey

Aggregate doses H1N1 vaccine shipped as of 11/04/09: 26,248,100 (10.5%)

Parents Efforts to Get H1N1 Flu VaccineHarvard Opinion Research Program, Harvard School of Public Health, October 30-November 1, 2009.% Among ParentsTried to get H1N1 vaccine for childrenGot H1N1 vaccine for childrenCould NOT Get H1N1 vaccine for children% Among Parents who Tried to Get VaccineDid NOT try to get H1N1 vaccine for children

High Priority Adults* Efforts to Get H1N1 Flu VaccineHarvard Opinion Research Program, Harvard School of Public Health, October 30-November 1, 2009.% Among High Priority AdultsTried to get H1N1 vaccineGot H1N1 vaccineCould NOT Get H1N1 vaccine% Among High Priority Adults who Tried to Get VaccineDid NOT try to get H1N1 vaccine*High priority adults include: pregnant women, health care or emergency health personnel, adults who live with/care for child

Personal Reactions in Trying to Get H1N1 Flu Vaccine% Among Those Who Tried but Could Not Get H1N1 VaccineVery frustratedSomewhat frustratedWill try again this yearWill not try again this yearHarvard Opinion Research Program, Harvard School of Public Health, October 30- November 1, 2009.Not Very frustratedNot frustrated

Other concerns

Other VaccinesSeasonal Influenza Vaccine (TIV or LAIV)Pneumococcal VaccineAge over 65AsthmaCigarette SmokersChronic lung disease Chronic cardiovascular diseasesDiabetes mellitusChronic liver diseasesChronic renal failure or nephrotic syndromeFunctional or anatomic asplenia Immunocompromising conditionsCochlear implants Cerebrospinal fluid leaks

Diagnosing InfluenzaClinical SymptomsPPV for fever and (cough or sore throat) = 80%Seasonal influenza When influenza is circulatingOver the age of 4 yearsRapid antigen tests for influenzaSensitivity for H1N1 from 40% to 69%Dependent on viral titerSpecificity is goodPCRGold standard, but too slow for ambulatory care

Targets for Antiviral Medicationany severe Lower Respiratory Infection hospitalized patientschildren younger than 5 years of ageadults 65 and older people with chronic pulmonary, cardiovascular, renal, hepatic, hematological, neurologic, neuromuscular, or metabolic disorders people with immunosuppressionpregnant womenpeople < 19 years on long-term aspirin therapy

Treatment of Influenza H1N1Neuraminidase inhibitors Oseltamivir Oral Treatment from age 1Chemoprophylaxis from age 1ZanamivirInhaled powerTreatment from age 7Chemoprophylaxis from age 5Start within 48 hours of symptomsLate initiation may benefit hospitalized patients

Early use of antiviral enhances benefitAoki FY, et al. J Antimicrob Chemother. 2003;51:123-129.Reduction in duration (days)Time to treatment (hours)Impaired activityImpaired healthFever612243602468

Antiviral Resistance

When all else failsyou can count on the legislatureA member of the State Legislature in Wisconsin has introduced a resolution to stop state agencies and their employees from using the term Swine Flu.

When all else fails novel approaches for novel influenzahttp://www.youtube.com/watch?v=CVTFxYMhwiA

The fourth horseman revisited The night air has warmed with the advance of spring. The baby robins in the nest built in our castaway Christmas tree, propped against the garage, are nearly fledged. It has been 29 days since a previous call night; I am finally returning home after again admitting a number of patients, including one from last time who is still defeated by life, and now suffers from a bout of severe nausea and vomiting. To my dismay, the admission requires a gown, a pair of gloves, a respirator and eye protection, as she had a cough influenza A(H1N1). (May 21, 2009)

As I drive through the Wisconsin night I again catch the BBC World Service. This time the story is on the Chelsea Flower Show and the banning of gnomes from garden displays. I am bemused.

The tranquility of our springtime was indeed shattered. I witnessed a very prompted and vigorous response to a newly emerged threat. Practitioners, however, were buried in a sea of emails, webcasts, clinical guidances, and updates that were mostly uncoordinated, often conflicting, and poorly presented for the busy clinician.

The value of the primary care in the ambulatory practice was largely ignored. Early on came the chorus of infectious disease end-timers, predicting the millions of casualties. As the relatively benign influenza virus emerged, we seemed powerless to accept this, unwilling to stand down. On a brief trip to New York for CDC business, I exerted myself to note that the air grid was still under an orange threat level. Seeing this, I got a cup of coffee and read the paper.

Influenza is an old familiar friend. After a month, I recognize its patterns and settle in for the coming months. I am ready.

Life goes on. As I drive home for a brief sleep I wonder if garden gnomes need droplet precaution.

AcknowledgementsWisconsin Division of Public HealthBureau of Communicable DiseasesWisconsin State Laboratory of HygieneCenters for Disease Control World Health Organization