Outline
• Part 1: Background and epidemiology of avian influenza A
(H5N1) virus infection in humansHuman H5N1 clustersClinical features of human infection with H5N1 virus
• Part 2:Assessing case patients: Collecting clinical and
epidemiologic informationSpecimen collection and diagnosticsTreatment
3
Management of Suspect Cases of Human Infection with
Avian Influenza A (H5N1) Virus
Part 1: Epidemiology and Clinical Features
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
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)
6
*Reported as of March 2, 2009
World Health Organization, Western Pacific Regional OfficeCommunicable Disease Surveillance and Response
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: 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 yearsMale to female ratio = 1:1Median time to hospitalization: 4 daysCase 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)
9
*Update: WHO-confirmed human cases of avian influenza A(H5N1) infection,November 2003–May 2008. Weekly Epidemiological Record, NO. 46, 14 November, 2008WHO Avian Influenza http://www.who.int/csr/disease/avian_influenza/en/
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 poultrySlaughtering, preparing for cooking
• Touching dead wild birds
• Having sick or dead poultry in the household
• Visiting a live poultry market12
Photo: AP/ Bikas Das
Risk Factors:
Culture-Specific Risk
• Eating uncooked duck blood
• Defeathering of swans
• Playing with dead chickens
• Contact with roosters used in cock fighting
13
Photo: TIME Magazine / John Stanmeyer
Avian to Human Transmission of H5N1
• Primary mode of transmission is avian-to-human (zoonotic):Exposure to infected poultryPreparing or consuming uncooked or undercooked H5N1
virus-infected poultry or poultry products
• Indirect transmission may occur through: Inhalation of aerosolized H5N1 virus infected materialContact with surfaces contaminated with infected poultry
feces Contact with infected animals that ate dead poultry
14
Human-to-Human Transmission of H5N1 Virus Infection
• Probable but limited, non-sustained* human-to-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
15*Currently, no evidence of sustained human-to-human H5N1 virus transmission
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 cases7 deaths H5N1 virus was isolated from 7 cases Index case was likely infected by contact with
sick/dead chickensLimited human-to-human-to-human transmission
21
Interpretation of Case Clusters
• Cases with similar illness onset datesSame exposure source, similar incubation
period?
• Cases with illness onset separated in timeSimilar exposure source, different incubation
periods?Different exposure sources? Limited human-to-human transmission?
22
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 peoplePossible increased adaptability of H5N1 viruses to humans
• Signal for:An increased pandemic threat and a change in WHO
Pandemic Alert Period PhasesThe beginning of a pandemicEarly containment measures
• 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
Assessing for Possible Human-to- Human H5N1 Virus Transmission
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. Documented exposure to a confirmed, probable, or suspected human H5N1 case
b. The time interval between contact with a suspected, probable, or confirmed H5N1 case and illness onset is 7 days or less
c. No other apparent source of H5N1 exposure
d. 3 or more cases are reported
e. H5N1 is isolated from common environment of cases
Answer:
a,b, and c
H5N1 Viral Infection in Humans
• Incubation periodGenerally from 2 to 7 days
• Viral shedding period for H5N1 virusStill largely unknownMay be 2 weeks or longer
Longer for children and immune compromised
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H5N1 Clinical Manifestations
• Common signs and symptoms:Fever ≥38C, 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 diseasesCritical to ask about H5N1 exposures
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Possible Complications of H5N1 Infection
• Most common: pneumoniaMay progresses to respiratory failure
May requires mechanical ventilation
Acute respiratory distress syndrome (ARDS)
• Gastrointestinal disease
• Multi-organ failureHeart and kidney dysfunction
• Neurologic symptomsEncephalitis, seizures, altered mental status,
progression to coma 29
30
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”)
Review Question 4
What clinical signs and symptoms are pathognomonic (distinguishing) for Influenza A (H5N1) infection?
a. Fever
b. Cough
c. Shortness of breath
d. Sore throat
e. Pneumonia
f. Gastrointestinal symptoms
g. 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 32
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
33
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 casesClinical specimen collection, diagnostic and laboratory tests
• Know the treatments and interventions for suspected case-patients and their contacts
36
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
37
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
39
Clinical Data to Collect
• Date of illness onset
• Signs and symptoms
• Routine laboratory results
• ComplicationsType and date of onset
• Clinical specimens collected for H5N1 testing
• Precautions used, breaks in precautions
40
Clinical Data
• Common signs and symptoms:FeverCoughShortness of breathDifficulty breathing
• Other signs and symptoms that may occur:Sore throatSputum production (may be bloody)Diarrhea / abdominal painMuscle achesHeadacheRunny nose 41
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
42
Normal lymphocyte count1500 - 4000 / mm3
Normal platelet count 150,000 - 400,000 / mm3
Medical Charts Include:
• Demographic information
• Medical history
• Illness signs and symptoms
• Physical examination findings
• Treatment
• Laboratory testing results
43
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
44Warning! 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
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?
45
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 confirmation47
49
Diagnostic and Laboratory TestingSuspected Human H5N1 Case
• Clinical specimen collection
• Diagnostic tests Laboratory testing
• ImagingChest X-ray
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Clinical Specimens: Lower Respiratory Tract
• H5N1 viruses primarily infect lower respiratory tract tissueDeep 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 tractThroat swabs better for detecting H5N1 virus than other
upper respiratory tract locationsUse for ambulatory patients
• H5N1 virus has also been detected* in:Rectal swab and stool Blood serum and plasmaCerebrospinal fluid (CSF) specimens* These clinical specimens should not be the primary
sources used for H5N1 diagnosis
52
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
53
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
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
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Tests on Respiratory Samples
• Reverse-transcription polymerase chain reaction (RT-PCR)Primary method of confirming H5N1 virus infectionHighly sensitive and specific
• Virus Isolation “Gold standard”Requires BSL-3 laboratoryAllows for characterization of the virus
58
Other Tests
• Serological methodsRequire acute and convalescent sera (serum
obtained >21 days from onset)
• ImmunoflorescenceRequires H5 monoclonal antibodyCan be difficult to interpret
59
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
60
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
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
62Hien TT et al., New England J Med 2004;350:1179-1188
DAY 5 DAY 7 DAY 10
•Fever
•Progressive pulmonary disease
•Death
Severe H5N1 Pneumonia - Vietnam 2004
Review Question 8
What is the most sensitive and specific laboratory test for confirmation of influenza A (H5N1)
infection in humans?a. Real-time PCR
b. Rapid influenza test
c. Chest X-ray
d. Serology
Answer: a. Real-Time RT-PCR
64
A Clinician Should Suspect H5N1 Virus Infection:
• Severe acute respiratory illness
AND
• Exposure 7 days before symptom onsets to:Sick poultry or wild birdsSuspect , 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
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
65* Every country should have access to at least one laboratory capable of H5N1 virus detection by RT-PCR
Treatment for Influenza Viruses
• Neuraminidase InhibitorsOseltamivirZanamivir
• 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
• 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 cells70
Oseltamivir for Seasonal Influenza
• Capsule or suspension administered by mouth
• Approved in the U.S. for treatment of seasonal influenza in children aged ≥1 yearPediatric 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 onsetReduces lower respiratory tract complications,
pneumonia, and hospitalization
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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
• PrecautionsPeople with kidney disease (reduce dose)Pregnant or nursing femalesReports 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 daysPediatric dosing based upon age and weightConsider 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 dosageBased on child’s weightNot approved in children <1 year old
• No aspirin for children <18 years of ageRisk of Reye’s syndrome with aspirinUse 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 nightfor 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 forPeople with chronic respiratory disease Pregnant or nursing females
• ResistanceVery low for human influenza A (H1 and H3)
viruses
80
Zanamirvir for H5N1 Infection
Effectiveness for H5N1 treatment is unknownUsed 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) virusesResistance develops rapidly influenza A viruses
• Adverse effects include gastrointestinal and neurological symptoms
• NOT recommend for H5N1 treatment82
Review Question 9
According to WHO, what drug is the first-line for treatment of Influenza A (H5N1) infection? a. Oseltamivir, 75 mg twice per day, 7-10 daysb. Zanamirvir, 75 mg twice per day, 7-10 daysc. Amandatine, 75 mg twice per day, 7-10 daysd. 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
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 appropriateTreat 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 forHousehold and close contacts of suspected or confirmed
H5N1 casesHealthcare worker with exposure without appropriate PPE
to suspected or confirmed H5N1 patients
• Treatment depends on level of riskWHO recommends oseltamivir
88
WHO. Rapid advice guidelines for pharmacological management of H5N1. 2006
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
89WHO. Rapid advice guidelines for pharmacological management of H5N1. 2006
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 animalsHandlers of sick animals or decontaminating environments while
using appropriate PPE91
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 OxygenMechanical ventilation for respiratory failure in the
intensive care unit
• For the health care provider, PPE and not prophylaxis is the first line of defense!
92
Summary
• Oseltamivir is first line therapy for treatment and prevention of H5N1 virus infectionChemoprophylaxis is recommended depending on
level of risk (low, moderate, high)
• Treatment with antibiotics should be avoided
93
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-RT-
PCR) is the most sensitive and timely method for confirming H5N1.
Rapid influenza tests are not sensitive for detecting H5N194
Part 2 Summary: Clinical Management and Treatment
• Consider all evidence together (epidemiologic, clinical and diagnostic)
• Treatments and interventions for suspected H5N1 patients includeAntiviral treatment with oseltamivirOxygen and mechanical ventilationSupportive care
95
Glossary
• 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 illness96
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 larynx97
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, SARS, Typhus, etc). 98
References and Resources
• 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/EA6D9DF3-688D-43161DF5553E7B1DBCD/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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