Transcript Slide 1

Management of Suspect Cases of
Human Infection with
Avian Influenza A (H5N1) Virus
1
Outline
• Part 1:
 Background and epidemiology of avian influenza A
(H5N1) virus infection in humans
 Human H5N1 clusters
 Clinical features of human infection with H5N1 virus
• Part 2:
 Assessing case patients: Collecting clinical and
epidemiologic information
 Specimen collection and diagnostics
 Treatment
Management of Suspect Cases of
Human Infection with
Avian Influenza A (H5N1) Virus
Part 1: Epidemiology and Clinical Features
3
Part 1: Learning Objectives
• Understand the epidemiology of known human H5N1
cases and risk factors
• Importance of clusters
• Recognize clinical features of H5N1 in humans
4
Epidemiology of Influenza A(H5N1)
Virus Infection of Humans
Photo: T. Uyeki, CDC
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Global Epidemiology
• 409 cases have been reported to WHO from 15
countries*
• Case fatality proportion = 256/409: ~ 63%
• Human surveillance has focused upon severe
respiratory disease (pneumonia)
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*Reported as of March 2, 2009
Progression of Human Cases
Human Avian Influenza A (H5N1) Cases by Onset Date and Country
(as of 23 November 2009)
As of 23 March 2009, total of 412 cases were reported officially to WHO
* Cases missing
onset date
are excluded:
World Health
Organization,
Western Pacific Regional Office
Communicable
Disease
Surveillance
and Response
1 Viet
Nam, 13 Indonesia,
3 Azerbaijan,
20 Egypt,
1 Turkey, 1 Iraq, 1 Nigeria
** CFR Trend: computed based on cumulative dead & total number of cases
WHO Summary of H5N1 cases
• Epidemiologic summary of H5N1*
 Median age: 18 years (range 3 months - 75 years)
 90% of cases were aged <40 years
 Male to female ratio = 1:1
 Median time to hospitalization: 4 days
 Case fatality proportion: ~60%
 Highest case fatality: 10-19 years (76%)
 Lowest case fatality: ≥50 years (40%)
 Median time to death: 9 days (range 2 – 31 days)
*Update: WHO-confirmed human cases of avian influenza A(H5N1) infection,
November 2003–May 2008. Weekly Epidemiological Record, NO. 46, 14 November, 2008
WHO Avian Influenza http://www.who.int/csr/disease/avian_influenza/en/
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Review Question 1
Which two countries have reported the most cases Influenza A
(H5N1) to WHO to date?
a. Indonesia and Vietnam
b. Egypt and Thailand
c. China and Cambodia
d. India and China
Answer: a. Indonesia and Vietnam
Review Question 2
What age group has the highest reported case fatality rate from
H5N1 virus infection?
a. 0-9 years old
b. 10-19 years old
c. 20-29 years old
d. > 50 years old
Answer: 10 – 19 years old
Risk Factors: Exposures in the Week
Before Illness
• Touching sick or dead poultry
 Slaughtering, preparing for cooking
• Touching dead wild birds
Photo: AP/ Bikas Das
• Having sick or dead poultry in the household
• Visiting a live poultry market
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Risk Factors:
Culture-Specific Risk
• Eating uncooked duck blood
• Defeathering of swans
• Playing with dead chickens
Photo: TIME Magazine / John Stanmeyer
• Contact with roosters used in cock fighting
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Avian to Human Transmission of H5N1
• Primary mode of transmission is avian-to-human
(zoonotic):
 Exposure to infected poultry
 Preparing or consuming uncooked or undercooked H5N1
virus-infected poultry or poultry products
• Indirect transmission may occur through:
 Inhalation of aerosolized H5N1 virus infected material
 Contact with surfaces contaminated with infected poultry
feces
 Contact with infected animals that ate dead poultry
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Human-to-Human Transmission of H5N1
Virus Infection
• Probable but limited, non-sustained* humanto-human transmission
Very rare, but documented
Occurred during close, prolonged, unprotected
contact with a human H5N1 case
Mostly in family members
Transmission in hospital setting reported
*Currently, no evidence of sustained human-to-human H5N1 virus transmission
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Human Influenza A(H5N1)
Case Clusters
Occurrence of H5N1 Clusters
• >25% of all cases have occurred in clusters
• Clusters are 2 or more H5N1 cases that are
epidemiologically-linked
Occurred in several countries
Hong Kong (2003)
Thailand (2004)
Indonesia (2006)
Human Case Cluster, Hong Kong 2003
• Family of five Hong Kong residents visited Fujian
Province, southern China in late January 2003
• 7-year old girl developed pneumonia and died, was
buried, but not tested
• Four survivors returned to Hong Kong
• Father and son were hospitalized with pneumonia;
both confirmed with H5N1, father died
• No direct link between cases and avian flu infection
in poultry was found
Human Case Cluster, Thailand 2004
•
11-year old girl who lived in a rural village with her aunt
where poultry deaths occurred
 Mother lived near Bangkok (no poultry exposure)
•
The girl developed fever and lower respiratory tract disease,
hospitalized with pneumonia
 Mother and aunt traveled to hospital to provide care
•
•
•
The girl died 24 hours later
Mother and aunt became sick, were confirmed with H5N1
virus infection; mother died
Probable human-to-human transmission of H5N1 virus from
girl to her mother and aunt
Human Case Cluster, Indonesia 2006
• A large H5N1 family cluster occurred in North
Sumatra
1 probable + 7 confirmed H5N1 cases
7 deaths
H5N1 virus was isolated from 7 cases
Index case was likely infected by contact with
sick/dead chickens
Limited human-to-human-to-human transmission
Interpretation of Case Clusters
• Cases with similar illness onset dates
Same exposure source, similar incubation
period?
• Cases with illness onset separated in time
Similar exposure source, different incubation
periods?
Different exposure sources?
Limited human-to-human transmission?
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Significance of Case Clusters
• Increase in number and size of clusters, or increase in
number of mild cases can indicate:
 That H5N1 viruses are spreading to more people
 Possible increased adaptability of H5N1 viruses to humans
• Signal for:
 An increased pandemic threat and a change in WHO
Pandemic Alert Period Phases
 The beginning of a pandemic
 Early containment measures
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Assessing for Possible
Human-to- Human H5N1 Virus Transmission
•
•
•
Documented exposure to a confirmed, probable, or
suspected human H5N1 case,
AND
The time interval between contact with a suspected,
probable, or confirmed H5N1 case and illness onset is 7
days or less,
AND
No other sources of H5N1 exposures
Such as: birds, other animals, feathers, droppings, fertilizers made of fresh
bird droppings, live poultry markets, contaminated environments, or
laboratory specimens
H5N1 Cluster Summary
•
~25% of confirmed H5N1 cases have occurred in clusters
worldwide
 Mostly among blood related family members
 Most cluster cases had contact with sick birds
•
•
•
•
Evidence of limited, non-sustained, human-to-human contact
has occurred
Clinically mild pediatric H5N1 cases identified during
investigations of severely ill index cases
Changes in size, number or epidemiology of clusters could
signal important viral changes/adaptability, or pandemic
Epidemiologic evidence that H5N1 virus can be transmitted
from patients to healthcare workers
Review Question 3
If you recognize a cluster of human H5N1 cases, what would
cause you to suspect that human-to-human transmission of H5N1
virus has occurred?
a.
b.
c.
d.
e.
Documented exposure to a confirmed, probable, or suspected human
H5N1 case
The time interval between contact with a suspected, probable, or
confirmed H5N1 case and illness onset is 7 days or less
No other apparent source of H5N1 exposure
3 or more cases are reported
H5N1 is isolated from common environment of cases
Answer:
a,b, and c
Clinical Features of
Human Infection with H5N1 Virus
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H5N1 Viral Infection in Humans
• Incubation period
 Generally from 2 to 7 days
• Viral shedding period for H5N1 virus
 Still largely unknown
 May be 2 weeks or longer
 Longer for children and immune compromised
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H5N1 Clinical Manifestations
• Common signs and symptoms:
 Fever ≥38C, cough, shortness of breath, difficulty
breathing
• Other findings (less common):
 Sore throat, headache, muscle aches, diarrhea
• Clinical findings are non-specific, and are
similar to other common acute respiratory
diseases
 Critical to ask about H5N1 exposures
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Possible Complications of H5N1
Infection
•
Most common: pneumonia
 May progresses to respiratory failure
 May requires mechanical ventilation
 Acute respiratory distress syndrome (ARDS)
•
•
Gastrointestinal disease
Multi-organ failure
 Heart and kidney dysfunction
•
Neurologic symptoms
 Encephalitis, seizures, altered mental status,
progression to coma
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H5N1 Pathogenesis
•
•
High H5N1 viral levels are associated with an abnormal
inflammatory response
Other blood changes
 Decreased white blood cell count
 Low lymphocyte count
 Mild to moderately decreased platelet count
•
Infection and inflammation contribute to respiratory
failure and multi-organ failure
 Cytokine dysregulation (cytokine “storm”)
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Review Question 4
a.
b.
c.
d.
e.
f.
g.
What clinical signs and symptoms are pathognomonic
(distinguishing) for Influenza A (H5N1) infection?
Fever
Cough
Shortness of breath
Sore throat
Pneumonia
Gastrointestinal symptoms
None of the above
Answer: g. These symptoms may typically occur, but they are
non-specific and similar to other acute respiratory diseases.
Part 1 Summary: Epidemiology
• Most human H5N1 cases have been healthy children
and young adults
• Epidemiology and exposure sources critical to
suspecting a case
• Most H5N1 cases had direct contact with sick or dead
poultry or birds in the week prior to illness onset
• Limited, non-sustained human-to-human transmission
of H5N1 virus is rare, but has occurred
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Part 1 Summary: Clinical
Manifestation
• Signs and symptoms of H5N1 infection are
non-specific and are observed in other
respiratory diseases:
Fever, cough, shortness of breath, difficulty
breathing
• Pneumonia
• Peripheral blood changes may occur but are
non-specific
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Management of Suspect Cases of
Human Infection with Avian
Influenza A (H5N1) Virus
Part 2: Diagnosis, Management, and Treatment
Part 2: Overview
• Clinically assessing suspected patients:
•
•
Collecting clinical and epidemiologic
information
Diagnostic and laboratory tests
Current recommendations for clinical
treatment
Part 2: Learning Objectives
• Identify important sources of clinical and
epidemiologic information
• Recognize laboratory tests used for
identification of new cases
 Clinical specimen collection, diagnostic and laboratory tests
• Know the treatments and interventions for
suspected case-patients and their contacts
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Part 2: Learning Objectives, cont
• Know what pharmaceutical treatments are
available for seasonal and pandemic influenza
• Understand the difference in the
recommendations between seasonal vs.
pandemic flu treatment
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Assessing Suspected
H5N1 Patients
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Assessing Suspected H5N1 Patients
Does the patient have findings consistent with H5N1
virus infection?
1. Collect clinical history and data on clinical
findings
2. Evaluate epidemiological data
3. Consider clinical, laboratory, and epidemiologic
information together
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Clinical Data to Collect
• Date of illness onset • Complications
 Type and date of onset
• Signs and symptoms • Clinical specimens
collected for H5N1 testing
• Routine laboratory
results
• Precautions used, breaks
in precautions
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Clinical Data
• Common signs and symptoms:
 Fever
 Cough
 Shortness of breath
 Difficulty breathing
• Other signs and symptoms that may occur:
 Sore throat
 Sputum production (may be bloody)
 Diarrhea / abdominal pain
 Muscle aches
 Headache
 Runny nose
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Clinical Complications
•
Respiratory failure
 Complication from pneumonia within a few days to 2 weeks after
illness onset
•
•
Acute Respiratory Distress Syndrome
Multiple organ failure
 Renal dysfunction
 Cardiac dysfunction
•
Abnormal lab values
 Low lymphocytes: <1500 / mm3
 Low platelets: < 150,000 / mm3
Normal lymphocyte count
1500 - 4000 / mm3
Normal platelet count
150,000 - 400,000 / mm3
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Medical Charts Include:
• Demographic information
• Medical history
• Illness signs and symptoms
• Physical examination findings
• Treatment
• Laboratory testing results
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Epidemiologic Context
Potential exposure to H5N1
• Occupational exposure
Animal culler, veterinarian, health care workers
• Residence or travel in area affected by H5N1
outbreaks in birds or animals (e.g., poultry market)
• Direct contact with dead or diseased birds or other
animals in affected area
• Close contact with a person with H5N1 virus
infection, unexplained moderate or severe acute
respiratory illness
Warning! Even if NO reports of ill poultry in a location, there could be disease in
that area, especially if poultry influenza vaccines are used or reporting is poor
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Sample Patient Chart:
Exposure History
Contact with ill people? (If yes, date and name, relationship to patient)
___________________________________________
___________________________________________
Contact with diseased poultry (Live or dead)? (If yes, date and location)
___________________________________________
___________________________________________
Recent travel? (If yes, date and location)
___________________________________________
___________________________________________
Other close patient contacts (Household members, close coworkers)
___________________________________________
Are any of these contacts ill?
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Review Question 5
What are the critical pieces of epidemiologic information that
must be collected from a patient with illness that is clinically
compatible with Influenza A (H5N1) infection?
Answer:
 Occupational exposure - Animal culler, veterinarian, health care
workers
 Residence or travel in area affected by H5N1 outbreaks in birds or
animals (e.g., poultry market)
 Direct contact with dead or diseased birds or other animals in affected
area
 Close contact with a person with H5N1 virus infection, unexplained
moderate or severe acute respiratory illness
Use All Information
• Clinical signs compatible with H5N1 virus infection
• History suggests exposure to H5N1 virus 7 days prior
to symptom onset
• Are there multiple cases or respiratory deaths in the
same family or in contacts?
• Send samples for laboratory confirmation
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Specimen Collection and
Diagnostics
Diagnostic and Laboratory Testing
Suspected Human H5N1 Case
• Clinical specimen collection
• Diagnostic tests
 Laboratory testing
• Imaging
Chest X-ray
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Clinical Specimens:
Lower Respiratory Tract
• H5N1 viruses primarily infect lower respiratory tract
tissue
 Deep lung tissues
• Best specimens for detecting H5N1 viruses:
Lower respiratory tract
Endotracheal aspirates from intubated, mechanically
ventilated patients
Bronchioalveolar lavage (BAL)
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Other Clinical Specimens for H5N1
Testing
• Upper respiratory tract has worse virus yield than lower
respiratory tract
 Throat swabs better for detecting H5N1 virus than other
upper respiratory tract locations
 Use for ambulatory patients
• H5N1 virus has also been detected* in:
 Rectal swab and stool
 Blood serum and plasma
*Cerebrospinal
(CSF) specimens
These clinicalfluid
specimens
should not be the primary
sources used for H5N1 diagnosis
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Collecting Specimens for H5N1
Testing
• All respiratory secretions and bodily fluids of H5N1
patients should be considered potentially infected
with H5N1 virus!
• Collect specimens from different respiratory sites
from the same patient on multiple days
• Collect oropharyngeal and nasal/nasopharyngeal
swabs from both ventilated and non- ventilated
patients
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Collecting Specimens, cont.
• Respiratory
 Collect endotracheal specimens from mechanically ventilated
patients
 Collect throat and nasal swabs from all patients
 Collect specimens as soon as possible
• Blood
 May be useful for detection of H5N1 antibodies three weeks
after infection
 Not useful for rapid detection of H5N1 virus infection for rapid
detection of outbreaks
 Need to collect paired sample: acute and convalescent
• Rectal swab or diarrheal stool
•
Not primary specimen for confirming H5N1 virus infection
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Review Question 6
What are the optimal specimens to collect from a
non-ambulatory suspected case of Influenza
A(H5N1) infection?
Answer: Lower respiratory tract; endotracheal
aspirates from intubated, mechanically
ventilated patients
Review Question 7
What are the optimal specimens to collect from
an ambulatory suspected case of Influenza
A(H5N1) infection?
Answer: Throat swabs
Diagnosis
Tests on respiratory samples (most common):
•
•
•
•
PCR-based techniques
Virus isolation
Immunofluorescence
Rapid antigen detection (Flu A or B)
Tests on serum:
•
•
Measurement of specific antibodies
PCR-based techniques
Other tools:
•
Chest X-Ray
Tests on Respiratory Samples
• Reverse-transcription polymerase chain reaction
(RT-PCR)
 Primary method of confirming H5N1 virus infection
 Highly sensitive and specific
• Virus Isolation
 “Gold standard”
 Requires BSL-3 laboratory
 Allows for characterization of the virus
57
Other Tests
• Serological methods
Require acute and convalescent sera (serum
obtained >21 days from onset)
• Immunoflorescence
Requires H5 monoclonal antibody
Can be difficult to interpret
58
Rapid Influenza Test
• Commercially available
• Results in 15 - 30 minutes
• Detect human influenza A and B viruses
• Very low accuracy to detect H5N1 virus and
seasonal influenza
 Not sensitive or specific for detecting H5N1 virus
 May result in false negatives and false positives
• NOT RECOMMENDED for DETECTION of H5N1
virus
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Other Diagnostic Tools
Peripheral blood
• Decrease in the white blood cell count
(WBC)
Decrease in lymphocyte count (one type of white
blood cell)
• Mild to moderate decrease in the blood
platelet count
60
Imaging
Radiologic Imaging (X-ray)
• Non-specific evidence of pneumonia on
admission
• Often progresses to bilateral, multi-lobar
pneumonia
• Diffuse or patchy infiltrates
• Fluid in the space surrounding the lungs
• Cavities may form in the lung tissue
Severe H5N1 Pneumonia - Vietnam 2004
DAY 5
DAY 7
DAY 10
•Fever
•Progressive pulmonary disease
•Death
Hien TT et al., New England J Med 2004;350:1179-1188
62
Review Question 8
What is the most sensitive and specific
laboratory test for confirmation of influenza A
(H5N1) infection in humans?
a.
b.
c.
d.
Real-time PCR
Rapid influenza test
Chest X-ray
Serology
Answer: a. Real-Time RT-PCR
A Clinician Should Suspect H5N1
Virus Infection:
• Severe acute respiratory illness
AND
• Exposure 7 days before symptom onsets to:
 Sick poultry or wild birds
 Suspect , probable, confirmed H5N1 case
OR
• Residence in an area with known H5N1 virus
infections of poultry or other animals
OR
• Occupational risk factors, or reported cases of
severe respiratory illness among close contacts and
household members
64
Diagnostic Tests
•
•
If
Patient is suspected human H5N1 case or meets other
trigger criteria (link to trigger criteria)
Then
Patient’s specimen should be sent to a WHO H5
Reference Laboratory* for further influenza testing
and confirmation
* Every country should have access to at least one laboratory capable of
H5N1 virus detection by RT-PCR
65
Clinical Treatment for Seasonal
and Pandemic Influenza
66
Treatment for Influenza Viruses
• Neuraminidase Inhibitors
 Oseltamivir
 Zanamivir
• Other Treatments
• Chemoprophylaxis
• Clinical Management
Top image located at: http://www.biota.com.au/?page=1021001&subpage=1021019.
Bottom image located at: http://www.free-rx-drugstore.com/gb/.
Antivirals
68
Antivirals
• Used for the treatment and
prevention of seasonal
influenza A and B virus infections
• Effectiveness against H5N1 virus infection is
unknown
• WHO recommended first line therapy for
treatment and prevention of H5N1 virus infection
• Treatment should be given as soon as possible
• May be given as chemoprophylaxis to prevent
H5N1 disease in exposed persons
69
Neuraminidase Inhibitors
• Two drugs available:
 Oseltamivir (Tamiflu ®); Zanamivir (Relenza ®)
• Inhibit the Neuraminidase enzyme which
provides the bond between infected cell and new
virus particles
• Prevents the release of new virus particles from
the infected cell
• Virus particles cannot go on to infect other cells
70
Oseltamivir for Seasonal Influenza
•
•
•
•
•
Capsule or suspension administered by mouth
Approved in the U.S. for treatment of seasonal
influenza in children aged ≥1 year
 Pediatric dosage depends on age and weight
Administered twice a day for 5 days
Side effects: nausea, vomiting
Effectiveness
Reduces influenza symptoms by 1 day when
administered within 2 days of illness onset
Reduces lower respiratory tract complications,
pneumonia, and hospitalization
71
H1N1 Oseltamivir Resistance
•
Seasonal H1N1 resistance
observed EU in 2008
 Prevalence varies: 0-60+%
•
H1N1 resistance elsewhere
 8% in the U.S.
 None reported elsewhere
•
Implications for avian
influenza H5N1
 Need to know more about
why H1N1 resistance
occurred
 Theoretically viruses could
swap genes, but evidence does
not support this possibility
European Center for Disease Prevention and Control
Oseltamivir: Considerations
• Precautions
People with kidney disease (reduce dose)
Pregnant or nursing females
Reports of delirium in pediatric patients (mostly
from Japan)
• Resistance
Can develop with treatment, but frequency of
resistance to oseltamivir is low
73
Oseltamivir for H5N1 Infection
Effectiveness for H5N1 treatment is unknown
However is first line therapy for H5N1
infections
74
Recommended Treatment for
Human H5N1 Infection
WHO recommends Oseltamivir treatment
• Optimal dosage, duration for H5N1 unknown
• WHO recommends similar dosage to seasonal
influenza (capsule and oral suspension)
75 mg twice per day, 7-10 days
 Pediatric dosing based upon age and weight
 Consider longer treatment, and higher doses (150 mg) on
case by case basis, especially in patient with progressive
disease
75
OseltamivirTreatment for
Human H5N1 Infection
• Should be started as early as possible in suspected
H5N1 patients
• Warranted even with late presentation
• Resistance has been reported during treatment of a
small number of H5N1 patients
Zanamivir can treat oseltamivir resistant viruses
76
Treatment of Children
• Different oseltamivir dosage
 Based on child’s weight
 Not approved in children <1 year old
• No aspirin
for children <18 years of age
 Risk of Reye’s syndrome with aspirin
 Use paracetemol or ibuprofen
• Children potentially infectious for longer periods than
adults after illness onset
77
Zanamivir
•
•
•
•
Orally inhaled powder – administered by mouth
via special device
Approved in the U.S. for treatment of seasonal
influenza in patients aged 7 years and older and
for chemoprophylaxis in persons older than 5
years of age
Treatment dosage for seasonal influenza is one
puff in the morning and one at night
for 5 days
Side effects
 Wheezing, and breathing problems
78
Zanamivir: Effectiveness
• Effectiveness in seasonal influenza
Can reduce influenza symptoms by 1 day if
administered within 48 hours
Reduces lower respiratory tract complications
Oseltamivir-resistant influenza A(H1N1) viruses
remain sensitive to zanamivir
79
Zanamirvir: Considerations
• Not recommended for
People with chronic respiratory disease
Pregnant or nursing females
• Resistance
Very low for human influenza A (H1 and H3)
viruses
80
Zanamirvir for H5N1 Infection
Effectiveness for H5N1 treatment is unknown
Used as second line therapy for H5N1 infections
when virus is resistant to oseltamivir
81
Adamantanes
Amantadine and Rimantadine
• Chemically related, orally administered drugs
• Reduce viral replication of Influenza A viruses
• No activity against Influenza B viruses
• High frequency of resistance among circulating
human influenza A (H3) viruses
 Resistance develops rapidly influenza A viruses
• Adverse effects include gastrointestinal and
neurological symptoms
• NOT recommend for H5N1 treatment
82
Review Question 9
According to WHO, what drug is the first-line
for treatment of Influenza A (H5N1) infection?
a.
b.
c.
d.
Oseltamivir, 75 mg twice per day, 7-10 days
Zanamirvir, 75 mg twice per day, 7-10 days
Amandatine, 75 mg twice per day, 7-10 days
Rimantadine, 75 mg twice per day, 7-10 days
Answer: a.
• Consider longer treatment, and higher doses (150 mg) on
case by case basis
• Pediatric dosing is based on age and weight
Other Treatments
84
Corticosteroids
• No proven effectiveness on clinical H5N1
infection
• Risk of side effects, including opportunistic
infections
• May be considered on case by case basis for
persistent septic shock with adrenal insufficiency
85
Recommended Treatment with
Antibiotics
• Antibiotic prophylaxis should be avoided
• When pneumonia is present:
Antibiotic treatment is appropriate
Treat according to published evidence-based
guidelines
86
Treatment for the
Acute Respiratory Distress Syndrome
(ARDS)
• Therapy for H5N1 virus infection associated ARDS
should be based upon published guidelines for
ARDS
Lung protective mechanical ventilation with low
tidal volume
87
WHO Recommnedations:
Antiviral Chemoprophylaxis for
Human Infections with H5N1 Virus
• Pre-exposure prophylaxis may be considered for
 Those involved in culling or disposing of infected poultry
• Post-exposure prophylaxis should be considered for
 Household and close contacts of suspected or confirmed
H5N1 cases
 Healthcare worker with exposure without appropriate PPE
to suspected or confirmed H5N1 patients
• Treatment depends on level of risk
 WHO recommends oseltamivir
WHO. Rapid advice guidelines for pharmacological management of H5N1. 2006
88
Antiviral Chemoprophylaxis:
High Risk
WHO recommends Oseltamivir for chemoprophylaxis
of high-risk groups:
75 mg / day for 7-10 days after the last known exposure
High-risk:
Household or family members and close contacts, including
pregnant women, of a strongly suspected or confirmed H5N1
patient
WHO. Rapid advice guidelines for pharmacological management of H5N1. 2006
89
Chemoprophylaxis: Moderate Risk
Antiviral chemoprophylaxis may be considered in persons
defined by WHO as having moderate risk
Moderate Risk:
 Persons handling sick animals, decontaminating environments,
without the appropriate use of PPE or without using PPE 100%
of the time
 Unprotected and very close direct exposure to sick or dead
animals infected with H5N1 virus or birds implicated in human
cases
 Healthcare workers in close contact with strongly suspected or
confirmed H5N1 patients (performing intubation, tracheal
suctioning, delivering nebulized drugs, handling body fluids)
without the appropriate use of PPE
90
Chemoprophylaxis: Low Risk
Antiviral chemoprophylaxis is generally not recommended
for low risk persons
Low Risk:
 Healthcare workers not in close contact with a strongly
suspected or confirmed H5N1 patient and having no direct
contact with infectious material
 Healthcare workers in contact with H5N1 cases wearing
appropriate PPE
 Culling of non-infected or likely non-infected animals
 Handlers of sick animals or decontaminating environments
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while using appropriate PPE
Clinical Management
• Infection control:

Isolate patient
 Implement infection control precautions
–
–
All bodily fluids, secretions, clinical specimens should be
considered potentially infectious
Proper personal protective equipment (PPE) for caregivers
• Supportive care:
 Supplemental Oxygen
 Mechanical ventilation for respiratory failure in the
intensive care unit
• For the health care provider, PPE and not
prophylaxis is the first line of defense!
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Summary
• Oseltamivir is first line therapy for treatment and
prevention of H5N1 virus infection
Chemoprophylaxis is recommended depending on
level of risk (low, moderate, high)
• Treatment with antibiotics should be avoided
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Part 2 Summary: Epidemiology and
Diagnosis
• Collect clinical and epidemiologic data from multiple
sources
• Identify and collect appropriate specimens for
diagnostic testing
 Lower respiratory tract
 Multiple respiratory samples should be collected for H5N1 testing
• Diagnostic Tests:
 Real-time reverse-transcription polymerase chain reaction (RT-RTPCR) is the most sensitive and timely method for confirming
H5N1.
 Rapid influenza tests are not sensitive for detecting H5N1
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Part 2 Summary: Clinical Management
and Treatment
• Consider all evidence together (epidemiologic,
clinical and diagnostic)
• Treatments and interventions for suspected H5N1
patients include
 Antiviral treatment with oseltamivir
 Oxygen and mechanical ventilation
 Supportive care
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Glossary
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•
•
•
•
•
•
•
•
•
Case fatality proportion:
The proportion (percentage) of all the cases of disease who died within a specific
time period. Also know as the case fatality rate
Incubation period
The period of time between the exposure to a virus or disease causing pathogen and
when the actual infection or disease onset begins.
Viral shedding
process that occurs when a virus is present in bodily secretions and can thereby be
transmitted to another persons.
Encephalitis
Inflammation in the brain usually caused by a virus (viral encephalitis).
Pathogenesis
The origination and development of a disease or the mechanism through which the
disease causes illness
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Glossary
•
•
•
•
•
•
Cytokine dysregulation (“cytokine storm”)
A complicated and uncontrolled immune response caused by severe
infections. This exaggerated and damaging immune response can lead to
organ damage, multi-organ failure, and death. Symptoms include:
hypotension, tachycardia, dyspnea, fever, ischemia, or insufficient tissue
perfusion (especially involving the major organs), uncontrollable
hemorrhage, and multisystem organ failure (caused primarily by hypoxia,
tissue acidosis, and severe metabolism dysregulation
Lower respiratory tract:
Portion of the respiratory system that refers to the Trachea, Primary bonchi
and lungs
Upper respiratory tract
Portion of the respiratory system that refers to the nasal cavity, pharynx and
larynx
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Glossary
•
•
•
•
Sensitive
Used to describe a test that is “accurate” or “sensitive” to cases of true disease The
proportion of specimens that are infected with the Influenza A(H5N1) virus that test
positive based on diagnostic criteria.
Specificity
Proportion of true negatives among specimens that are not infected with Influenza
A(H5N1) virus.
•
•
False negatives
A case that tests negative for disease although they are actually infected
•
•
False positive
A person who tests positive for disease but are not actually infected
•
•
Biosafety Level 3 (BSL3)
The level of biocontainment and safety practices for facilities that work on
potentially dangerous agents (biological or environmental). Level three is
applicable for agents which cause serious or potentially lethal disease (e.g., anthrax,
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SARS, Typhus, etc).
References and Resources
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WHO. Update: WHO-confirmed human cases of avian influenza A(H5N1) infection, 25
November 2003 – 24 November 2006. Weekly Epidemiological Record 2007;82:41-48.
Recommendations and laboratory procedures for detection of avian influenza A(H5N1) virus in
specimens from suspected human cases, August 2007.
http://www.who.int/csr/disease/avian_influenza/guidelines/RecAIlabtestsAug07.pdf
WHO. WHO Rapid Advice Guidelines for pharmacological management of human infection
with avian influenza A (H5N1) virus. 2006
http://www.who.int/medicines/publications/WHO_PSM_PAR_2006.6.pdf
WHO. Avian influenza, including influenza A (H5N1), in humans: WHO interim infection
control guideline for health care facilities. 24 April 2006.
http://www.wpro.who.int/NR/rdonlyres/EA6D9DF3-688D43161DF5553E7B1DBCD/0/InfectionControlAIinhumansWHOInterimGuidelinesfor2b_0628.
pdf
Clinical management of human infection with avian influenza A (H5N1) virus. 15 August
2007. http://www.who.int/csr/disease/avian_influenza/guidelines/ClinicalManagement07.pdf
Risk of Influenza A (H5N1) Infection among Health Care Workers Exposed to Patients with
Influenza A (H5N1), Hong Kong
Carolyn Buxton Bridges, Katz JM, Seto WH, Chan PKS, Tsang D, Ho W, Mak KH, Lim W,
Tam JS, Clarke M, Williams SG, Mounts AW, Bresee JS, Conn LA, Rowe T, Hu‐Primmer J,
Abernathy RA, Lu X, Cox NJ, and Fukuda K. The Journal of Infectious Diseases 2000 181:1,
344-348
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