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Case Management of Suspect
Human Avian Influenza Infection
Part 1: Background information on
clinical features and management of
avian influenza
1
Learning Objectives
• Recognize clinical features of H5N1 in
humans
• Understand how information about the
patient before onset of illness can help you
suspect infection
• Know the types of treatment options
available
2
Part 1 Session Overview
• Clinical features
• Epidemiologic information
– Risk for infection
– Transmission
• Current antiviral medications
• Group exercise
3
Illness Scenario
• 5-year-old Darin sick for three days
–
–
–
–
–
Fever
Watery diarrhea
Headache
Cough
Short of breath
• No one else sick
• Darin and a friend play with chickens
Question: Is this avian influenza?
What should Dr. Sarasin do?
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Clinical Features
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General Information
Human
influenza
Vulnerable • All ages affected
Age Groups • Highest rates in
children < 5 years
• Most complications
in elderly >60 years
Time from
• Mean 2 days
exposure to
• Range: 1 – 5 days
illness
Avian
influenza
• Children < 5
years
• Healthy young
adults
• Adolescents
• Mean 2 – 3 days
• Range: 2 – 10
days
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Signs and Symptoms
Human Influenza
Avian Influenza (H5N1)
Upper respiratory
Lower respiratory
Fever
Yes
Yes
Headache
Yes
Yes
Cough
Yes
Yes
Varies; sore throat to
difficulty breathing
Difficulty breathing,
crackles, increased
respiratory rate
Rare: Children, elderly
Rare: Variable, watery
diarrhea, vomiting,
abdominal pain
Type of infection
Respiratory
symptoms
Gastrointestinal
symptoms
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Recovery
2-7 days
Longer
Unusual Presentations
• Knowledge of avian influenza infection
in humans changes as we learn more
• Unusual symptoms
– Absence of respiratory symptoms
– Severe watery diarrhea
– Loss of consciousness
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Complications
Seasonal Influenza
• Ear infection, sinusitis
• Bronchitis, bronchiolitis
• Pneumonia
– viral or secondary
bacterial
• Exacerbation of chronic
conditions
• Muscle inflammation
• Neurologic Disease
Avian Influenza
• Almost all develop
pneumonia
• Acute Respiratory
Distress Syndrome
(ARDS)
• Multiorgan failure
• Encephalitis
– Seizures
– Brain inflammation
– Reye’s syndrome
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Laboratory Findings
Commonly associated with avian
influenza:
• Drop in white blood cell count (lymphocytes)
• Mild to moderate drop in blood platelet count
• Increased aminotransferases (Liver
enzymes)
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Alak and Darin
Question:
Do you think Darin has signs and
symptoms of avian influenza? Why or
why not?
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Epidemiologic Information
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Risk for Infection
from Animals
Within 10 days before
symptoms begin:
• Close contact with live, sick, or
dead birds
• In setting with confined birds
• Contact with contaminated
surfaces
• Ingestion of uncooked infectious
poultry
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Risk for Infection
from Humans
• Uncertain risk of person-to-person spread
• Within 10 days before symptoms begin:
– Face-to-face contact
– Touching or within 1 meter of suspected or
diagnosed H5N1 patient without proper precautions
– Touching or being within 1 meter of a person who
has severe pneumonia or dies from an acute
respiratory illness without proper precautions
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Alak and Darin
Question:
Do you think Darin is at risk for avian
influenza H5N1 infection?
Why or why not?
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Routes of Transmission
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Risk Factors
• Direct contact with
birds
Risk Factors:
– Playing with birds
– Working with birds
– Preparing birds for
meals
• Contaminated water
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Routes of Transmission
• Indirect contact
– Infected materials,
surfaces
• Person-to-person rare
at present
• Eating undercooked or
raw bird products
– Meat, eggs, blood
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Alak and Darin
Question:
Has Darin had an exposure that could
lead to transmission?
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Using All of The Information
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A Clinician Should Suspect H5N1
Infection if a Patient Has:
• Severe acute respiratory illness
• Exposure 10 days before symptoms to:
– Suspect / diagnosed avian H5N1 patient
– Poultry or Wild Birds
• Residence in an area with known H5N1
activity in poultry
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Darin’s Situation
• 5-year-old Darin sick for three days
– Fever
– Watery diarrhea
– Headache
– Cough
• No one else sick
• Darin and a friend play with and hold
chickens
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Alak and Darin
Question:
Would you suspect avian influenza
H5N1 infection? Why or why not?
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Current Antiviral Treatment
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Neuraminidase Inhibitor
• Neuraminidase enzyme breaks bond
between infected cell and newly formed
virus
• Inhibitor prevents enzyme from
breaking bond and releasing virus
• Virus particles cannot infect other cells
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Neuraminidase Inhibitor
• Two drugs available
– Oseltamivir (Tamiflu®) and
Zanamivir (Relenza ®)
– Should be given as soon as possible
– Effective for treatment and prevention
– Used for seasonal or avian
influenza
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Oseltamivir
Dosage for seasonal influenza
Adults:
75 mg twice a day for 5 days
Children:
<1 year, not studied adequately
< 15 kg - 30 mg twice a day for 5 day
>15 kg to <23 kg - 45 mg twice a day for 5 days
>23 kg to <40 kg - 60 mg twice a day for 5 days
>40 kg - 75 mg twice a day for 5 days
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Oseltamivir
Dosage for avian influenza
• Best dosage for H5N1 unknown
– Longer treatment (7 to 10 days) OR
– Higher doses (150 mg)
• Dosage for prevention
– Once daily for 7 to 10 days after last exposure
• Side Effects
– Nausea and vomiting
– Skin rash
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Oseltamivir
• Effectiveness in seasonal influenza
– Reduces influenza symptoms 1 - 3 days
– Reduces lower respiratory tract complications,
pneumonia, and hospitalization
• Cautions- Consider Risk versus Benefits
– People with kidney disease (adjust dose)
– Pregnant or nursing females
• Resistance
– Detected in several avian influenza H5N1 patients
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Zanamivir
• Inhaled by mouth via special device
• May be used for > 5 years of age
• Treatment dosage
– Once in morning and night, 5 days
• Side effects
– Wheezing, and breathing problems
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Zanamivir
• Effectiveness in seasonal influenza
– Reduces influenza symptoms 1 - 3 days
– Reduces lower respiratory tract
complications
• Consider Risk vs. Benefit
– People with chronic respiratory disease
– Pregnant or nursing females
• Resistance
– Not identified in human H5N1 infections
– Active against Oseltamivir resistant H5N1
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Other Treatments?
• Amantadine and Rimantadine
– H5N1 resistant in some isolates
– Not as effective as
neuraminidase inhibitors
• Corticosteroids
– Low dose for sepsis
– Unclear if high dose useful
– Risk of side effects
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Alak and Darin
Question:
What would you tell Dr. Sarasin to do?
33
Part 1 Summary
• Ask about recent exposure and contact with
humans or animals that may have had avian
influenza H5N1 infection
• Laboratory can confirm H5N1, but you
should not wait
• Individuals with avian influenza H5N1
infection may not have respiratory symptoms
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Questions?
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Case Study Exercise
Background information on
clinical features and
management of avian influenza
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Case Management of Suspect
Human Avian Influenza Infection
Part 2: Case Management of
Suspected Avian Influenza Cases
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Learning Objectives
• Collect appropriate clinical and
exposure information
• Recognize laboratory tests used for a
suspected case patient
• Know how to advise on treatments and
interventions for suspected casepatients and their contacts
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Session Outline
• Data to use in managing a suspect case
– Clinical data
– Information from medical charts
– Epidemiologic context (exposures)
• Clinical specimens, types of laboratory
tests and imaging (x-rays)
• Administration of medical care
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Assess Suspected Avian
Influenza Patients
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Assess Suspected Avian
Influenza Patients
Does the patient have avian influenza?
1. Confirm and / or collect clinical history
and physical exam data
2. Evaluate the epidemiologic context
3. Consider clinical, laboratory, and
epidemiologic information together
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Clinical Data to Collect
• Date of illness
onset
• Complications
– Date of onset
• Symptoms
• Any clinical
specimens collected
for laboratory
testing
• Clinical
measurements
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Clinical Data
• Common symptoms:
– Fever
– Cough
– Shortness of breath
• Other symptoms that may occur:
–
–
–
–
–
Sore throat
Sputum (may be bloody)
Diarrhea / abdominal pain
Vomiting
Muscle aches
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Clinical Complications
• Acute Respiratory Distress
Syndrome
• Respiratory failure
– May occur within a few days to
2 weeks after illness onset
• Multiple organ failure
– Renal dysfunction
– Cardiac problems
– Bone marrow depression
(lymphocytes and platelets)
– Hypotension
– Arrhythmia
Normal lymphocytes
1500 - 4000 / mm3
Normal platelet count
150,000 - 400,000 / mm3
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Medical Charts Include:
• Demographic information
• Medical history
• Current medical complaint / symptom history
• Physical examination findings
• Recommended treatment
• Laboratory or other test results
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Sample Patient Chart:
Clinical Information
Demographic Information
Date: _____
Name __________
Age ____
Gender ___
Occupation_______
Address______________________________________________________
History of Illness
Chief Complaint_____________________
Date of Illness Onset _________________
Other Symptoms and symptom onset date:
_______________________________________________________
_______________________________________________________
Physical Exam Findings
_______________________________________________________
_______________________________________________________
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Sample Patient Chart:
Clinical Information
Demographic Information
Date: _Nov 1, 2006
Name _Sok Phhoung_
Age __21_
Gender:_F_
Occupation______
Address___Patang village, Rattanakiri, Cambodia_____________
History of Illness
Chief Complaint___Dyspnea_________
Date of Illness Onset ___Oct 27, 2006______
Other Symptoms and symptom onset date:
__Fever – onset Oct 25_________________________________
__Cough – onset Oct 25 ________________________________
Physical Exam Findings
_Current fever – 39.4°C, Pulse 123 beats/min________________
_______________________________________________________
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Epidemiologic Context
• Potential exposure to H5N1
– Occupational exposure
– Travel or residence in area
affected by avian influenza
outbreaks in animals
– Direct contact with dead or
diseased birds or other
animals in affected area
– Close contact with a person
with unexplained moderate or
severe acute respiratory illness
Warning! Even if NO reports of ill poultry in a province, there could be
disease in that area, especially if poultry influenza vaccines are used 48
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)
___________________________________________
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Use All Information
• Clinical signs compatible with avian
influenza
• History compatible with exposure to
avian influenza
• 3 or more cases could indicate an
emergency
• Send samples for laboratory
confirmation
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Role Playing Activity
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Advise on Testing Needs for a
Suspected Case
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Suspect Case Diagnosis
• Influenza diagnostics
• General laboratory testing
• Imaging
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Diagnostics
• Every country should have access to at
least one lab capable of rapid H5N1
detection
• Commercial kits may be used for
outbreak investigations, but not for
patient diagnosis
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Clinical Specimens
• Respiratory
– Throat swabs and nasal swabs
– Collect as soon as possible
– Collect tracheal specimens from intubated patients
• Blood
– Useful for detection of virus and antibodies
• Stool
– Can detect presence of virus
• Collect all possible specimens, repeat
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Lab Tests for Influenza A
• Rapid tests
– Several methods
– Commercial kits
– Results in 15 – 30
minutes
• Virus culture
– Results in 2 – 10
days
– Must be done in a
special lab
• PCR
– Detects viral genes
– Results in a few
hours
– Uses respiratory
sample, serum or
culture
– Can be specific for
H5N1
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Diagnosing Avian Influenza
If:
• Specimen is positive for Influenza A; AND
• Patient is suspected of avian influenza
infection
Then:
• Send the specimen to a WHO H5 reference
laboratory for further testing and verification
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Imaging
X-ray changes are
common in the lungs of
avian influenza patients
• Non-specific changes
• Diffuse or patchy infiltrates
• Fluid in the space
surrounding the lungs
• Cavities forming in the lung
tissue
BBC News. http://bbb.co.uk
Saturday, 3 December 2005
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Avian Influenza Chest X-Ray
Day 5
Day 7
Day 10
Chest x-ray of an avian influenza patient,
shown by day of illness
Tran Tinh Hien, Nguyen Thanh Liem, Nguyen Thi Dung, et al. New England 59
Journal of Medicine. 18 March, 2004. vol. 350 no. 12. pp 1179-1188.
Advise on Treatments and
Interventions for Suspected
Cases and their Contacts
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Treatment Options
• Antivirals
– Consider age group
• Antibiotics
• Supportive care
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Antivirals
• Early treatment is best
• Suspected cases should
receive a neuraminidase
inhibitor
– Oseltamivir
– Zanamivir
• Last choice
– Amantadine
– Rimantadine
• Not been studied
– Ribavirin
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Antiviral Side Effects
• Oseltamivir
– Nausea
– Vomiting
– Rash
• Zanamivir
– Wheezing and breathing problems
– Other suspected side effects not proven
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Treating Children
• Different Oseltamivir dosage
– Based on child’s weight
– Not approved in children <1 year
• No aspirin for children < 18 years of age
– Use Paracetemol or Ibuprofen
• Children infectious for 21 days after illness
– If child cannot remain hospitalized, educate family
about infection control
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Antibiotics
• Broad-spectrum
– Do not use as a prophylactic
– Give empiric therapy for suspected
bacterial pneumonia
• Secondary bacterial infection therapy
– Treat with intravenous antibiotics as
recommended
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Supportive Care
Hospital care for proven or suspected avian
influenza cases should include the capacity to:
• Isolate the patient
• Provide supplemental oxygen and ventilation
• Provide intensive care support for organ failure
• Provide low dose corticosteroids for sepsis
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Infection Control Measures
• Few cases
– Hospitalize and isolate all patients
– Monitor, test, and treat patients in hospitals
– Provide infection control education to discharged
patients and their families
• Many cases
– May not be possible to hospitalize less severe cases
– Educate patients and families on influenza
transmission prevention
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Serum Specimen
Collection Protocol
• Collect two serologic (blood) samples:
– Early sample: <7 days after illness onset
– Follow-up sample: 21 - 28 days after illness onset
• Follow up with the patient to assure that the
final diagnosis is made
– Positive early test alone cannot confirm infection
– Positive follow-up test strongly suggests infection
– Increase in immune response indicates infection
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Part 2 Summary
• The most common symptoms of avian influenza are
fever, cough, and shortness of breath
• Laboratory and clinical information in the patient’s
medical chart can be used to look for characteristics
of avian influenza
– Multiple clinical samples should be collected
• Laboratory and clinical information should be
examined in context of whether the person could
have been exposed to avian influenza
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Advising on Case Management
Role Playing Exercise
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Glossary
Seasonal Influenza
Expected rise in influenza occurrence among humans
living in temperate climates; occurs during the winter
season with strains of influenza that have minor
changes from season to season.
Avian Influenza
A subspecies of the influenza A virus that causes
influenza among fowl and poultry.
Contraindication
A specific circumstance when the use of a certain
treatment could be harmful.
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References and Resources
• WHO interim guidelines on clinical management of
humans infected by influenza A(H5N1), 2 March
2004.
http://www.who.int/csr/disease/avian_influenza/guide
lines/clinicalmanage/en/index.html
• Tran Tinh Hien, et al. Avian Influenza A (H5N1) in 10
Patients in Vietnam. N Engl J Med March 18, 2004:
350(12), p 1179-1181.
• Preliminary clinical and epidemiological description
of influenza A (H5N1) in Viet Nam
12 February 2004.
http://www.who.int/csr/disease/avian_influenza/guide
lines/vietnamclinical/en/index.html
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