Pandemic Influenza Overview
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Transcript of Pandemic Influenza Overview
Pandemic InfluenzaOverview
衛福部 疾病管制署中區傳染病防治醫療網
王任賢 指揮官
Outline
• What is influenza?
• What is an influenza pandemic?
• History of influenza pandemics
• Control measures
Influenza
• Respiratory infection• Transmission: contact with respiratory secretions
from an infected person who is coughing and sneezing
• Incubation period: 1 to 5 days from exposure to onset of symptoms
• Communicability: Maximum 1-2 days before to 4-5 days after onset of symptoms
• Timing: Peak usually occurs December through March in North America
Clinical Presentation of Influenza
Influenza Symptoms
• Rapid onset of:– Fever– Chills– Body aches– Sore throat– Non-productive cough– Runny nose– Headache
Adapted from the National Institute of Allergy and Infectious Diseases.
Signs & Symptoms Influenza ColdOnset Sudden GradualFever Characteristic, high (over Rare
101F); lasting 3 to 4 daysCough Nonproductive; can Hacking
become severeHeadache Prominent Rare Myalgia (aches and pains) Usual; often severe Slight Fatigue; weakness Can last up to 2 to 3 weeks Very mildExtreme exhaustion Early and prominent NeverChest discomfort Common Mild to
moderateStuffy nose Sometimes CommonSneezing Sometimes UsualSore throat Sometimes Common
Influenza vs Cold Symptoms
Cox NJ, Fukuda K. Infect Dis Clin North Am. 1998;12:28.
Classic Signs & Symptoms of Influenza• Rapid onset of symptoms
• Fever, usually over 100F• Nonproductive cough
• Headache
• Myalgia
• Chills and/or sweats
• Sore throat
• Potentially severe, persistent malaise
• Substernal soreness, photophobia & ocular problems
Adapted from Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Disease. 5th ed. 2000:1831.
Onset of Influenza A in Volunteer
Days After Inoculation
Temp °F
Illness
Headache, Malaise, Myalgia
Nasal Obstruction and Discharge,Throat Pain, Cough
-1-1 00 11 22 33 44 55 66 77 88 2323
100100
9999
9797
Shedding of Influenza A in Volunteer
Adapted from Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett’s Principles andPractice of Infectious Disease. 4th ed. 1995:1554.
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Influenza is a serious illness
• Annual deaths: 36,000*• Hospitalizations: >200,000** Average annual estimates during the 1990’s
• Who is at greatest risk for serious complications?– persons 65 and older– persons with chronic diseases– infants– pregnant women– nursing home residents
Complications of influenza
• Viral and bacterial pneumonia
• Myositis/myoglobulinemia & renal failure
• Myocarditis
• CNS manifestations
Respiratory complications of influenza
• Primary viral pneumonia• Secondary bacterial pneumonia• Combined viral-bacterial pneumonia• Exacerbation of COPD• Exacerbation of asthma
Viral Pneumonia Bacterial Pneumonia 2nd to Flu
Patients more at risk – Children and adults with – Age >65 yrscardiovascular disease, chronic – Patients with chronic pulmonary,pulmonary and metabolic disease cardiac and metabolic or other and hemoglobinopathies disease
– Pregnant women– Young adults (H1N1)– Immunosuppressed patients, such
as those with cancer, HIV/AIDS ororgan transplants
Clinical history Rapid progression from classic flu Improvement after classic flu symptoms symptoms, then worsening
Sputum Gram stain Predominantly normal flora – no Pneumococcussignificant evidence of Staphylococcus pathogenic bacteria Haemophilus influenzae
Moraxella catarrhalis
Chest x-ray Bilateral findings Consolidation
WBC Leukocytosis with shift to left Leukocytosis with shift to left
Adapted from Treanor JJ. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 5th ed. 2000:1834-1835; Piedra PA. Semin Respir Infect. 1995;10:218.
DDx of Viral vs Bacterial Pneumonia
Patients with Indicated Bacterial Etiology (%)
0 10 20 30 40 50 60 70 80 90 100
Other Gram-NegativeOrganisms
Haemophilusinfluenzae
Mixed, IncludingStaphylococcus
Staphylococcus
Pneumococcus
Preceding Year (no influenza) During Influenza Outbreak(1968-69)
Bac
teria
l Etio
logy
The marked changes that may occur in the etiology of bacterial pneumonia during an influenza outbreak are shown in the graph above. Note that the percentage of patients with staphylococcal pneumonia more than doubles during an influenza outbreak (and is more than 2.5 times as high if staphylococci found with other organisms are included), while the proportion attributable to pneumococcal infection decreases.
Hospital Practice December 1976
Influenza Types
• Type A– Epidemics and pandemics– Animals and humans– All ages
• Type B– Milder epidemics– Humans only– Primarily affects children
Influenza Virus Composition
Type of nuclear material
Virus type
Geographic origin
Strain number
Year of Isolation
Virus subtype
A/Beijing/32/92 (H3N2)
HemagglutininNeuraminidase
Structure of hemagglutinin (H) and neuraminidase (N) periodically change:
• Drift: Minor change, same subtype– In 1997, A/Wuhan/359/95 (H3N2) virus was dominant– A/Sydney/5/97 (H3N2) appeared in late 1997 and became the
dominant virus in 1998
• Shift: Major change, new subtype– H2N2 circulated in 1957-67– H3N2 appeared in 1968 and replaced H2N2– Pandemic potential
Influenza Antigenic Changes
Timeline of Emergence of Timeline of Emergence of Influenza A Viruses in HumansInfluenza A Viruses in Humans
1918 1957 1968 1977 19971998/9
2003
H1
H1
H3H2
H7H5H5
H9
SpanishInfluenza
AsianInfluenza
RussianInfluenza
AvianInfluenza
Hong KongInfluenza
Pandemic influenza: definition
• Global outbreak with:
– Novel virus, all or most susceptible– Transmissible from person to person– Wide geographic spread
Impact of Past Influenza Pandemics/Antigenic Shifts
Pandemic, or Antigenic Shift
Excess Mortality Populations Affected
1918-19(A/H1N1)
500,000 Persons <65 years
1957-58(A/H2N2)
70,000 Infants, elderly
1968-69(A/H3N2)
36,000 Infants, elderly
1977-78(A/H1N1)
8,300 Young (persons <20)
Pandemic influenza: 2nd waves
• 1957: second wave began 3 months after peak of the first wave
• 1968: second wave began 12 months after peak of the first wave
Next pandemic: impact
Attack rate ranging from 15% to 35%:
• Deaths: 89,000 - 207,000
• Hospitalizations: 314,000 - 733,000
Source: Meltzer et al. EID 1999;5:659-71
Estimated hospitalizations due to influenza pandemic
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15% 20% 25% 30% 35%
National, 1 year gross attack rate
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spit
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5th percentile
Source: Meltzer et al. EID 1999;5:659-71
Mean
Estimated deaths due to influenza pandemic
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15% 20% 25% 30% 35%
National, 1 year gross attack rate
Dea
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('00
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95th percentile
5th percentile
Source: Meltzer et al. EID 1999;5:659-71
Mean
The 1918 Influenza Pandemic
America’s Forgotten Pandemicby Alfred Crosby
“The social and medical importance of the 1918-1919 influenza pandemic cannot be overemphasized. It is generally believed that about half of the 2 billion people living on earth in 1918 became infected. At least 20 million people died. In the Unites states, 20 million flu cases were counted and about half a million people died. It is impossible to imagine the social misery and dislocation implicit in these dry statistics.”
America’s deaths from influenza were greater than the number of U.S. servicemen
killed in any war
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Civil WWI 1918-19 WWII Korean Vietnam
War Influenza War War
Thousands
Spanish Influenza
• Slowed to a trickle the delivery of American
troops on the Western front.
• 43,000 deaths in US armed forces.
• Slow down and eventual failure of the last German offensive (spring and summer 1918) attributed to influenza.
Infectious Disease Mortality, United States--20th Century
Armstrong, et al. JAMA 1999;281:61-66.
Worldwide Spread in 6 MonthsWorldwide Spread in 6 Months
69,800 deaths (U.S.)69,800 deaths (U.S.)
Spread of H2N2 Influenza in 1957“Asian Flu”
Spread of H2N2 Influenza in 1957“Asian Flu”
Feb-Mar 1957Apr-May 1957Jun-Jul-Aug 1957
February 1957 – Outbreak in Guizhou Province, China
April-May 1957– Worldwide alert– Vaccine production begins
October 1957– Peak epidemic, follows school openings
December 1957– 34 million vaccine doses delivered – Much vaccine unused
January-February 1958 – Second wave (mostly elderly)
“Asian Flu” Timeline
Close calls: avian influenza transmitted to humans
• 1997: H5N1 in Hong Kong 18 hospitalizations and 6 deaths
• 1999: H9N2 in Hong Kong 2 hospitalizations• 2003:
» H5N1 in China 2 hospitalizations, 1 death
» H7N7 in the Netherlands 80 cases, 1 death (eye infections, some resp. symptoms)
Avian Influenza Poultry Outbreaks, Asia, 2003-04
Avian Influenza Poultry Outbreaks, Asia, 2003-04
• Historically unprecedented scale of outbreak in poultry
• Human cases reported from Vietnam and Thailand (as of 1/21/05: 52 cases; 39 deaths)
• No sustained person-to-person transmission identified
• Duration of the outbreak creates potential for genetic change that could result in person-to-person transmission
“The pandemic clock is ticking, we just don’t know what time it is”
E. Marcuse
Influenza Control: vaccine
– Cornerstone of prevention
– Annual production cycle ensures availability by late summer/early summer
surveillance
select strains
prepare reassortants
standardize antigen
assign potency
review/license
formulate/test/package
vaccinate
WHO/CDC)
WHO/CDC/FDA
CDC/FDA
FDA
FDA
FDA
manufacturers
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
clinic
Vaccine Development
Pandemic Vaccine
• Annual vaccine is trivalent (3 strains), pandemic vaccine will be monovalent.
• Production using current technologies would likely take 4-5 months may not be available before 1st pandemic wave
• There will be vaccine shortages initially
• 2 doses may be necessary to ensure immunity
Influenza control: antiviral medications
• Uses– Prophylaxis– Treatment
• Issues– Limited supply– Need for prioritization (among risk groups and
prophylaxis versus treatment)– Unlikely to markedly affect course of
pandemic
Influenza control: infection control
• influenza isolation precautions*– Private room or with other influenza patient– Negative air pressure room, or placed with
other suspected influenza cases in area of hospital with independent air supply
– Masks for HCW entering room– Standard droplet precautions (hand washing,
gloves, gown and eye protection)
* 1994 Guidelines for Prevention of Nosocomial Pneumonia
Infection control, cont’d
• Feasibility of these measures in a pandemic setting is questionable, priorities should include:– Droplet transmission precautions (use of
masks and hand hygiene) – Cohorting of influenza-infected patients
Influenza control: other control measures
• Education to encourage prompt self-diagnosis
• Public health information (risks, risk avoidance, advice on universal hygiene behavior)
• Hand hygiene• Face masks for symptomatic persons• School closures (?)• Deferring travel to involved areas
Influenza control: quarantine• Challenges
– short incubation period for influenza– a large proportion of infections are
asymptomatic– clinical illness from influenza infection is non
specific
• Not used during annual epidemics
• Could potentially slow onset of a pandemic before sustained person-to-person transmission has been established
Medical care during an influenza pandemic
• Surge capacity of the hospital system is limited.
• Challenges:– Magnitude and duration– Staff shortages– Limited ability to call in external resources
Despite . . . – Expanded global and national surveillance – Better healthcare, medicines, diagnostics– Greater vaccine manufacturing capacity
New risks:– Increased global travel and commerce– Greater population density– More elderly and immunosuppressed– More daycare and nursing homes– Bioterrorism
Pandemic Flu Today
抗病毒藥物
Oseltamivir Treatment: Effect on Hospitalizations
Hospitalizations % Reduction
Placebo Oseltamivir
Healthy adults 5/662 (0.8%) 3/982 (0.3%) 60%
High-risk + elderly
13/401 (3.2%) 6/368 (1.6%) 50%
Total 18/1063 (1.7%)
9/1350 (0.7%) 59% (P=0.019)
Kaiser et al. Arch Intern Med 163:1667, 2003
Oseltamivir and Complications: Retrospective Cohort Study, USA
Outcome Exposed Unexposed Adj. Hazard Ratio (95% CI)
Age 1-12
Pneumonia
Hosp.
(n=586)
4 (0.7%)
1 (0.2%)
(n=17,886)
453 (2.5%)
120 (0.7%)
0.34 (0.13, 0.90)
0.29 (0.04, 2.07)
Age 13-59
Pneumonia
Hosp.
(n=10,649)
138 (1.3%)
99 (0.9%)
(n=41,007)
885 (2.1%)
510 (1.2%)
0.81 (0.68, 0.97)
0.75 (0.60, 0.93)
Age 60+
Pneumonia
Hosp.
(n=463)
8 (1.7%)
10 (2.2%)
(n=3,298)
290 (8.8%)
163 (4.9%)
0.41 (0.20, 0.82)
0.55 (0.29, 1.05)
Nordstrom et al. 44th ICAAC, abst no. V-1260, 2004
INHALED ZANAMIVIR TREATMENT: Effect on Complications and Antibiotic Use
Respiratory events leading to antibiotics
Any event
Upper respiratory
Lower respiratory
Acute bronchitis
Pneumonia
Hospitalizations
Placebo(n=765)
18%
8%
9%
7%
2%
0.4%
Zanamivir (n=807)
13%
7%
5%
5%
1%
0.4%
RiskReduction
28%*
10%
40%*
Kaiser et al. Arch Intern Med 160: 3234, 2000 *p<0.05
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