What we need to know about influenza

What we need to know about influenza

Family Medicine Forum

October 28, 2009

Speakers

Jim Dickinson MBBS CCFP PhD FRACGP

Professor of Family Medicine, U Calgary

Director Tarrant Viral Watch

Kevin Fonseca PhD D(ABMM)

Clinical Virologist, Provincial Laboratory

Andre Corriveau MD MBA FRCPC

Chief Medical Officer of Health Alberta.

Outline

Where are we now? Laboratory issues: What is this virus?Clinical responseProtection and preventionVaccines and antivaccine arguments

Current best available science– Observing & Inventing as we go along

Outline

Where are we now? Laboratory issues: What is this virus?Clinical responseProtection and preventionVaccines and antivaccine arguments

Alberta’s Response toPandemic (H1N1) 2009

Influenza– André Corriveau, MD, MBA, FRCPC– Chief Medical Officer of Health– Alberta Health and Wellness

– October 29, 2009

6

Influenza Affects Us Every Year

Fever and cough (1 week)Sore throat, malaise, muscle aches, headaches

Pneumonia, exacerbation of underlying chronic illnesses, encephalitis

1 - 4 out of 10 persons ill with flu each year Globally, +/- 0.5million deaths / year

+/- 4,000 in Canada More severe illness typically seen in the very old and the very

young, although other risk factors also recognized (pregnancy, lung disease, smoking, etc.)

7

Flu pandemics in history

1918/19: Spanish Flu(H1N1)

40-50 million deaths

1957: Asian flu(H2N2)

1 million deaths

1968: Hong Kong flu(H3N2)

1 million deaths

Pandemic (H1N1) 2009 Influenza Virus

Pandemic (H1N1) 2009 virus – new strain

Subtype of influenza A virus Re-assortment of human, swine, and

avian influenza A viruses Limited population immunity Viral replication occurs more readily in

lung tissue than seen with other influenza strains

Virus does not appear to be changing

Pandemic (H1N1) 2009 Influenza – Clinical Characteristics

Generally mild symptoms, similar to seasonal influenza

Acute onset of respiratory symptoms

Fever and cough and one or more of: sore throat, muscle aches, joint pain, or weakness

Gastrointestinal symptoms may also be present, more often in children

Small subset of people develop severe respiratory infection requiring support in intensive care unit

Pandemic (H1N1) 2009 Influenza – Transmission

Similarly to seasonal influenza:Predominantly through droplets

dispersed by coughing or sneezing Indirect transmission through self-

inoculation after contact with surfaces and objects contaminated with the virus from infected persons

11

The World Health Organization (WHO) Issues the Declaration

– Was done on June 11, 2009

The Declaration triggers:– Vaccine development– Enhanced surveillance– Planning of immunization strategy – Planning for release of antiviral & other stockpiles– Enhanced communication activities

Declaration of a pandemicDeclaration of a pandemic

Pandemic H1N1 Summary in Alberta(as of October 26, 2009)

3,052 laboratory confirmed cases– 190 hospitalized– 12 deaths– 53% female– Median age is 19 years– Vast majority of respiratory

outbreaks this fall have occurred in schools

Pandemic H1N1 Summarycontinued…

Younger Population AffectedAll Confirmed Cases

Age range: 1 month - 99 years

Median Age: 19 years

HospitalizedAge Range: 1 month - 89

yearsMedian Age: 32 years

DeathsAge Range: 25 – 90 yearsMedian Age: 48.5 years

0

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<2 2-4 5-9 10-14 15-19 20-44 45-64 65+

Age Groups

Num

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Epi Curve of Cases in Alberta by Date Specimen Collected

Epi-Curve of Confirmed Pandemic (H1N1) 2009 Cases in Alberta, by Date Specimen Collected, by Week (ending October 17, 2009)

0

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2009

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Aboriginal Summary(as of October 26, 2009)

Total Confirmed 31 cases (out of 3,052) or 1%

– Age range: 4 months to 66 years

– Median age is 25 years

Hospitalized 20 cases (out of 190) or 10.5%

– Age range: 4 months to 50 years

– Median age is 25.5 years

Deaths 3 cases (out of 12) or 25%

– Age range: 25 years to 43 years

– Median age is 39 years

– 5 cases ICU

– 2 cases Ventilated

– 12 cases Diagnosed with Pneumonia

12 cases with underlying conditions– 9 Asthma or Chronic lung disease

– 3 immune-suppressed

– 3 diabetes or heart disease

– 2 pregnant

* Some cases have more than one underlying condition

Underlying Conditions(as of October 26, 2009)

Underlying Conditions

– Hospitalized – 150 out of 190 cases had

one or more conditions

– Deaths – 11 out of 12 deaths had one

or more conditions

Percentage of Cases with Underlying

Conditions

Condition Deaths Hospitalized Cases

Chronic Heart Disease 17% 9%

Diabetes 33% 12%

Kidney Disease 25% 6%

Immune Suppressed 25% 13%

Asthma 17% 22%

Chronic Lung Disease 25% 19%

Pregnant 0% 6%

Other Conditions 67% 45%

* Totals due not add to 100% due to some cases having more than one condition

Pandemic H1N1 Cases Admitted to ICU

Severe CasesAbout 22% or 42/190 hospitalized cases were admitted to ICU

Age range: 5 years - 79 yearsMedian Age: 39 yearsGender split equally (50/50)5 cases were Aboriginal

Underlying Conditions63% had at least one

underlying condition, with 56% of those cases having either asthma or another chronic lung disease

40% had diabetesDeaths

8 cases admitted to ICU died

ICU H1N1 Cases by Month Admitted to Hospital

0 5 10 15

April

May

June

July

August

September

October

As of October 27, 2009 n=42

Reporting Week

1 2 3 4 5 6 7 8 91

01

11

21

31

41

51

61

71

81

92

02

12

22

32

42

52

62

72

82

93

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13

23

33

43

53

63

73

83

94

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1.5

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2.5

3.0

Influenza Like IllnessLower Respiratory Tract Infection

Influenza Like Illness seen through TARRANT Sentinel Sites, 2009, Alberta

Outline

Where are we now?

Laboratory issues: What is this virus?Clinical responseProtection and preventionVaccines and antivaccine arguments

See separate presentation:

Fonseca

Outline

Where are we now. Laboratory issues: What is this virus?

Clinical responseProtection and preventionVaccines and antivaccine arguments

How should we respond clinically?

How accurate are physicians at diagnosing a patient with influenza-like illness?

How should we treat?

How do we protect our staff and ourselves?

Case Example

Early May, 24 year old girlHigh fever, cough, very unwellNo recent travelSwab taken, Oseltamivir prescribedToo ill to live on own, cared for at parents house.Slept 20hrs/day for 2 days then slowly recovered

Swab was negative for all viruses

How do we know it is Influenza?

Diagnostic testing: delay, ? availableEpidemiological information

Surveillance Program

Goal of Tarrant Viral Watch:

Detect Influenza-Like Illness (ILI) as it occurs in the community, and measure influenza virologically in the lab

Influenza Surveillance: Alberta

ProvLab tests for: – Influenza A (including pH1N1)– Influenza B – Respiratory syncytial virus– Adenovirus– Enterovirus/rhinovirus– Coronavirus– Parainfluenza virus– Human metapneumovirus


Tarrant Viral Watch:Recruits sentinel physicians and nurse

practitioners from Family Medicine practices in Alberta

Currently has 77 sentinel sites in the network representing all former health regions of the province. Some gaps.


Fundamental step in developing a surveillance system:– CASE DEFINITION

Classical definition of influenza-like illness:

FEVER AND COUGH AND ONE OF:

sore throat, myalgia, arthralgia, prostration


Every week, sentinels take a nasopharyngeal swab from at least 2 patients with ILI

Currently doing heightened surveillance: swab all ILI patients!


Lab results are sent to the physician for patient care, and to Tarrant Viral Watch for surveillance purposes.

Data is compiled by Tarrant Viral Watch prior to being forwarded to:– Alberta Health and Wellness;– The Public Health Agency of Canada; and– The World Health Organization.

Influenza Surveillance: Canada

FluWatch: network of sentinel labs, primary care practices, ministries of health, and pediatric hospitals. Reports on:– Sentinel ILI consultation rates – Regional influenza activity levels– Work/school absenteeism– Lab-based virus detections– Strain identification and antiviral resistance– Pediatric influenza-related hospital

admissions/mortality

1. Influenza Surveillance: Canada

FluWatch animated maps:

Diagnostic Accuracy

How accurate are physicians at diagnosing a patient with influenza-like illness?

Physician Diagnostic Accuracy

Challenges:– Vague ILI definition

– Compared with seasonal influenza, pH1N1 causes different symptomsMore diarrhoea/GI upsetsLess fever

Seasonal and Pandemic Influenza Cases Reported by Tarrant and FluWatch, by Month (2008-09)

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Nov Dec Jan Feb Mar Apr May Jun Jul Aug

Month

# o

f C

ases

Alberta seasonal cases

Alberta pH1N1 cases

Tarrant seasonal cases

Tarrant pH1N1 cases

759

Laboratory Results by Month 2008-09

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Nov Dec Jan Feb Mar Apr May Jun Jul Aug

Month

Per

cen

tag

e (%

)

Negative

Other respviruses

Entero/rhino

FluB

FluA H3

FluA H1(untyped)

FluA H1(seasonal)

FluA H1(swine)

105 158 132 132 172 122 123 74 85 54N=

How should we treat?

Oseltamivir (Tamiflu) tabletsZanamivir (Relenza) inhalationBest during replication phase: <72 hrs

– Severe cases, LRTI, replication continues

Caution about prophylactic treatment– Development of drug resistance.

Details: Rx Files– Drug side effects: at least 10%– High risk, high probability

www.RxFiles.cawww.RxFiles.ca

Who is at risk?: Usual suspects

Elderly: but those over 60 may be immune– Pre 1957 viruses

Young children: under age 2yrsHealthy pregnant women: 2nd & 3rd trimesterChronic Health conditions

– Cardiac, pulm., diabetes & metabolic diseases, ,Immune deficiency &immune suppression, cancer, renal disease, anemia or hemoglobinopathy.

Poor living conditions: – Some First Nations, immigrants, street people

Who is at high risk?

ICU cases across Canada

Young adults: mean age 32.4

Females: 67%

Children: 30%

Aboriginal: 25.6%

4 days from onset to ICU admission

(Inter-Quartile Range 2-7days)

Kumar et al. JAMA 2009;302(17)1496

Acute Resp Illness Hospitalisation rates in Hunter/New England region during 2009 influenza outbreak

compared with peak months in 2007 & 2008

3 winter months: June – August

Hospitalisations:

2007 1736 9.7/10,000

2008 1267 5.8/10,000

2009 2378 11.4/10,000

Dawood et al Med J Aust 2009 26 Oct

Acute Resp Illness Hospitalisation rates in Hunter/New England region during 2009 influenza outbreak, compared with peak months in 2007 & 2008

Dawood et al Med J Aust 2009 26 Oct

Who should be treated?

Patients want treatmentGuidelines suggest only severe cases, or

high risk be treatedDrug most useful if given early

– Not so useful if wait till severe

??? Clinical judgment in face of uncertainty

Prescribing for pneumonia

Suggest add antibiotics in patients with:Resp rate >25Pulse >100

Outline

Where are we now. Laboratory issues: What is this virus?Clinical response

Protection and preventionVaccines and antivaccine arguments

Sequence of care

Patient phones with symptoms– Receptionist triage

Patient arrives– Mask and hygeine– Immediate transfer to isolation room

Assessment– ? Protection level

Diagnosis & treatmentFollow-up

How should we protect ourselves?

Science of infection control: probabilitiesHow spread occurs

– Respiratory secretions– Mostly droplets: range 1 meter– Aerosols: longer, penetrate into resp tract

Surgical masks stop droplets: exitN95 masks reduce aerosols: inhalation

– Difficult to use, hard to work in.

Council of Canadian Academies:2008

How should we protect ourselves?

Ocular mucosa: unclear– Visors or goggles

Most important – Hand transmission– From patient, to people and surfaces– Gloves and hand-washing– Destroyed by soap and water

Science of protection by masks

RCT, Nurses in Ontario hospitalsN95 vs surgical masksInfluenza measured by pcr or rise in titresSurgical masks N=225: 50 infections (23.6%)N95 masks N=221: 48 infections (22.9%)P=0.86: no effective difference.

Loeb M et al JAMA 2009 302 (17);1466

Who should we protect specially?

Staff who are at risk?– Pregnant, Immune Deficiencies

Previously infected and recovered– Precious resource– Should diagnose in acute illness– NP swabs

Outline

Where are we now. Laboratory issues: What is this virus?Clinical responseProtection and prevention

Vaccines and anti-vaccine arguments

Vaccines and Anti-Vaccine arguments

Science of vaccines– Composition– Effectiveness– Balance of benefit vs harm

Anti vaccine arguments– Semi-science– Non-science

How well do flu vaccines work?

Cochrane reviews: Tom JeffersonTrials show low efficacy: 30-60%Works best in healthy adultsNot effective in those at greatest risk

– Children under 2, Young children, elderly– Adults with chronic disease

Problems with trials of Vaccines

Wrong endpoints: ILI, culture of virus“Rare” disease Difficult to culture at right time. Three epidemics:

– 3 components - mismatches

Overall efficacyDelay in results: too late

Vaccine effectiveness

Observational designs can offer an alternative way to estimate VE annually.

VE can be estimated by a case-control “test negative” study design– Cases: patients with influenza– Controls: patients without influenza– Cases and controls need to come from the same

source population– Confounders need to be addressed

Sample lab req

J Infect Dis. 2009 Jan 15;199(2):168-79

Surveillance & case-control studies

Methods– Sentinel surveillance network (BC, AB, QC)– Patients ≥9years present with influenza-like illness

(within 7 days of symptom onset)– Informed about the study and asked for consent– Swabbed and asked questions about their vaccine use– Laboratory-confirmed outcomes– VE estimated as

1-[OR vaccinated/nonvaccinated]


Any influenza

TotalYes No

Vaccinated 39 127 166

Not Vaccinated 298 377 675

Total 337 504 841

Odds Ratio: 0.39 (95% CI: 0.26, 0.57)

Risk Ratio: 0.53 (95%CI: 0.4, 0.71)


FindingsOverall VE: 47% (95%CI: 18, 65%)H1N1 component well matched, age-adjusted VE

was high– 92% (95%CI: 40, 99%)

H3N2 component half-mismatched, reduced VE– 41% (95%CI: 6, 63%)

B component poorly-matched, lowest VE:– 19% (95%CI: -112, 69%)


Assumptions/Limitations– Vaccinated and unvaccinated individuals have

same likelihood of influenza exposure and presentation to physician

– Healthcare-seeking behaviour addressed– Vaccine status is self-reported– VE will generally be underestimated using this

design (Orenstein et al., 2007)

Vaccine effectiveness

High provided there is no drift of the virus.H1 types are generally stable (cf. H3) Current pandemic H1N1 has not changed

since vaccine seed sample taken. Therefore likely to be 95%+ effectiveMay have lower effectiveness in high risk

groups: but will work in young adults

Outline

Where are we now. Laboratory issues: What is this virus?Clinical responseProtection and prevention

Vaccines and anti-vaccine argumentsConclusions

Pandemic (H1N1) 2009 - Antivirals

Little viral resistance to neuraminidase inhibitors (oseltamivir and zanamivir) detected so far

No instances of onward transmission of drug-resistant virus

However, the use of antivirals is: not recommended for prophylaxis (pre, or post-exposure), as most

patients have mild to moderate illness and recover on their own. important for early treatment in selected patients at risk of more

severe disease. To be considered for those providing direct care to at-risk patients

(decreased viral shedding and shorter duration of illness)

Pandemic (H1N1) 2009 - Vaccine

Pandemic (H1N1) 2009 vaccine is available to all who want and need it.

Those at highest-risk must be given priority. Front-line health care workers also a priority

group. Seasonal influenza immunization will not

protect against pandemic influenza, but still important.

Alberta’s Response to Pandemic (H1N1) 2009 – Governance

Provincial Deputy Ministers’ Committee on Pandemic Influenza

– Coordinates Government of Alberta, municipal, and industry response

Alberta Health & Wellness Pandemic (H1N1) 2009 Planning Task Force– Provides strategic leadership and decision-making

Alberta Health Services’ Pandemic H1N1 Steering Committee– Focus on health system response

Alberta Health and Wellness/Alberta Health Services Joint Pandemic (H1N1) 2009 Governance Committee

Declaration of Public Health Emergency

Made by: the Alberta Government’s Cabinet, on advice of the CMOH, for a

province-wide state of public health emergencyor by the Board of Alberta Health Services, in consultation with the

CMOH, for a local state of public health emergency

Purposes: In response to serious social disruptions &/or health care system

dysfunctions Provides additional authority to the Minister or to Alberta Health

Services (and their delegates) to access critical resources (financial, human and infrastructure) as required to combat or alleviate the emergency and protect public health.

Alberta’s Pandemic (H1N1) 2009 Influenza Response – Further Information

Alberta Health and Wellnesswww.health.alberta.ca/professionals/health-professionals.html

Alberta Health Serviceswww.albertahealthservices.ca/

Public Health Agency of Canadawww.phac-aspc.gc.ca/alert-alerte/h1n1/index-eng.php

Health Link AlbertaToll-free 1-866-408-5465 In Edmonton, call 780-408-5465 In Calgary, call 403-943-5465 www.healthlinkalberta.ca/default.htm

Documents

What we need to know about influenza