what we need to know about influenza
DESCRIPTION
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 - PowerPoint PPT PresentationTRANSCRIPT
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
200
400
600
800
1000
1200
<2 2-4 5-9 10-14 15-19 20-44 45-64 65+
Age Groups
Num
ber o
f Cas
es
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
50
100
150
200
250
300
350
19A
PR
2009
26A
PR
2009
03M
AY
2009
10M
AY
2009
17M
AY
2009
24M
AY
2009
31M
AY
2009
07JU
N20
09
14JU
N20
09
21JU
N20
09
28JU
N20
09
05JU
L200
9
12JU
L200
9
19JU
L200
9
26JU
L200
9
02A
UG
2009
09A
UG
2009
16A
UG
2009
23A
UG
2009
30A
UG
2009
06S
EP
2009
13S
EP
2009
20S
EP
2009
27S
EP
2009
04O
CT
2009
11O
CT
2009
Nu
mb
er
of C
ase
s
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
03
13
23
33
43
53
63
73
83
94
04
14
2
Pe
rce
nt
of
Pa
tie
nts
Se
en
0.0
0.5
1.0
1.5
2.0
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
Influenza Surveillance: Alberta
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.
Influenza Surveillance: Alberta
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
Influenza Surveillance: Alberta
Every week, sentinels take a nasopharyngeal swab from at least 2 patients with ILI
Currently doing heightened surveillance: swab all ILI patients!
Influenza Surveillance: Alberta
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)
0
50
100
150
200
250
300
350
400
450
500
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]
Surveillance & case-control studies
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)
Surveillance & case-control studies
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%)
Surveillance & case-control studies
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