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Infection in Humans
• Defeathering of swans
10
Current Criteria for Suspected Case
H5N1
Unexplained acute lower respiratory illness with documented fever >38°C
with cough, shortness of breath, or difficulty breathing, and 1 or more of
the following exposures within 7 days of symptom onset:
OR
A person meeting the criteria for a suspected case and 1 of the following
criteria:
Evidence of an acute pneumonia on chest radiograph plus evidence of
respiratory failure.
Positive laboratory confirmation of influenza A infection but not
confirmed as H5N1 infection.
Current Criteria for Confirmed Case
H5N1
AND
• Incubation period
– Generally from 2 to 7 days
14
H5N1 Clinical Manifestations
• Common signs and symptoms:
– Fever ≥38C, cough, shortness of breath,
difficulty breathing
• Gastrointestinal disease
• Multi-organ failure
– Heart and kidney dysfunction
• Neurologic symptoms
– Encephalitis, seizures, altered mental status,
progression to coma 16
H5N1 Pathogenesis
• High H5N1 viral levels are associated with an
abnormal inflammatory response
17
Clinical Complications
• Respiratory failure
– Complication from pneumonia within a few days to 2
weeks after illness onset
18
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
20
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
21
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
22
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
23
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
•Fever
•Progressive pulmonary disease
•Death
25
Hien TT et al., New England J Med 2004;350:1179-1188
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
26
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
28
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
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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
31
Neuraminidase Inhibitors
• Two drugs available:
– Oseltamivir (Tamiflu ®); Zanamivir (Relenza ®)
• Resistance
– Can develop with treatment, but frequency
of resistance to oseltamivir is low
34
Oseltamivir for H5N1 Infection
35
Recommended Treatment for
Human H5N1 Infection
WHO recommends Oseltamivir treatment
• Optimal dosage, duration for H5N1 unknown
38
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
39
Zanamivir: Effectiveness
40
Zanamirvir: Considerations
• Resistance
– Very low for human influenza A (H1 and
H3) viruses
41
Zanamirvir for H5N1 Infection
42
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
43
Other Treatments
44
Corticosteroids
47
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
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 49
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
50
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
while using appropriate PPE
51
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! 52