Case Management of Suspect Avian Influenza A

(H5N1) Virus Infection in Humans

Part 1: Background information on clinical features of human infection with avian

influenza A (H5N1) virusesMay, 2007

Learning Objectives

• Recognize clinical features of avian Influenza A (H5N1) virus infection in humans

• Understand how information about the patient before onset of illness can help you suspect H5N1 virus infection

Part 1 Session Outline

• Clinical features

• Epidemiological Context– Exposure

Illness Scenario

• Alex sick for three days– Fever– Headache– Cough– Shortness of breath– Muscle aches– Watery diarrhea

• No one else sick• Works at poultry farm and handles poultry

Question: Is avian Influenza A (H5N1) the most likely cause of Alex’s symptoms?

Clinical Features

General InformationHuman

influenza

Avian Influenza A (H5N1)

Affected

Age Groups

• All ages affected

• Highest attack rate in children <5 years

• Most complications in elderly >65 years and persons with chronic medical conditions

• Children of all ages

• Healthy young adults

• Highest CFR in adolescents.

Estimated Incubation Period

• Mean: 2 days

• Range: 1 – 4 days

• Mean: 2 – 5 days

• ≤7 days

Signs and Symptoms

Avian Influenza A (H5N1)Type of infection Lower respiratory

Symptoms Fever, Cough, Headache

Shortness of breath, difficulty breathing

Diarrhea in some cases

Hospitalized Patients Pneumonia

Hypoxia requiring oxygen and respiratory failure requiring intubation and mechanical ventilation

Acute Respiratory Distress Syndrome (ARDS)

Laboratory Findings

Commonly associated with human infection with avian influenza A (H5N1) viruses:

– Drop in white blood cell count (leukopenia)• Drop in lymphocytes, a kind of white blood cells

(lymphopenia)

– Mild to moderate drop in blood platelet count

– Increased aminotransferases (liver enzymes)

Unusual Clinical Manifestations and Outcomes

• Knowledge of avian influenza A (H5N1) virus infection in humans is still evolving

• Unusual symptoms– Southern Vietnam – encephalitis and diarrhea– Fever and diarrhea can be the only early signs

and symptoms before pneumonia occurs later with H5N1 virus infection

Complications

Seasonal Influenza • Ear infections, sinusitis• Bronchitis, bronchiolitis• Pneumonia

– viral or secondary bacterial• Exacerbation of chronic

conditions• Muscle inflammation• Neurologic Disease

– Seizures– Encephalopathy and

encephalitis– Reye syndrome

H5N1 Virus Infection in Humans • Most cases develop

pneumonia• Acute Respiratory Distress

Syndrome (ARDS)• Multiorgan failure• Encephalitis• Cytokine storm

Alex

Question:

Do you think Alex has signs and symptoms of H5N1? Why or why not?

Epidemiological Context

Exposure to Avian Influenza (H5N1) Virus

1. Infected poultry, particularly coming in contact with respiratory secretions

2. Infected wild or pet birds

3. Other infected animals (e.g., pigs, cats, dogs)

4. Wild bird feces, poultry manure and litter containing high concentrations of virus

5. Fecally contaminated surfaces

H5N1 Virus Exposures Continued

6. Under- or uncooked poultry meat or eggs from infected birds

7. Contaminated vehicles, equipment, clothing, and footwear at affected sites, such as poultry farms with outbreaks

8. Contaminated air space (e.g., a barn, hen-house, or the air space proximal to barn exhaust fans)

9. Bodies of water with infected bird carcasses

10. Close contact with (within 3 feet of) confirmed human cases

 

Local Customs - Unique Exposures 

• Cock fighting

• Swan defeathering

• Playing with dead chickens

• Duck blood pudding, local customs

• Hunting practices

Alex

Question:

Do you think Alex could have been exposed to highly pathogenic avian influenza A (H5N1) virus?

Using All of The Information

Alex’s Situation

• 24 year old Alex sick for three days– Fever– Headache– Cough– Shortness of breath– Muscle aches– Watery diarrhea

• No one else sick

• Alex works on poultry farm where he handles poultry

Alex

Question:

Would you suspect avian influenza A (H5N1) virus infection? Why or why not?

Part 1 Summary

• Individuals with avian influenza A (H5N1) virus infection may have non-specific lower respiratory symptoms, or (rarely) none at all

• Ask about recent exposure and contact with humans or animals that may have had avian influenza A (H5N1) virus infection

Case Management of Suspect Avian Influenza A (H5N1) Virus Infection in

Humans

Part 2: Case Management of Suspected Human Cases of Avian Influenza A

(H5N1) Virus Infection

Learning Objectives

• Testing available for diagnosing– Clinical specimens

• Current treatment options

• Infection control measures

Part 2 Session Overview

• Laboratory Testing

• Treating Suspected Patients

• Infection Control in the Healthcare Setting

Laboratory Testing

Diagnostics

• Avian Influenza A (H5N1) Virus– Specimens for testing

• Influenza A

• Imaging

Avian Influenza A (H5N1) VirusLaboratory Tests

• RT-PCR– Detects viral RNA– Diagnose H5N1 in

humans– BSL-2 conditions– Results within hours

• Viral culture – Only in enhanced

BSL-3 laboratory– Results in 2-10 days

• Serologic Testing– Rise in H5N1 specific

antibodies – Testing only in

enhanced BSL-3 laboratory

Clinical Specimens for Detecting Avian Influenza A (H5N1)

• Lower Respiratory Tract* – Broncheoalveolar lavage fluid– Endotracheal aspirate – Pleural fluid – Sputum

• Upper Respiratory Tract– Oropharyngeal swabs* – Nasal Swab

• Collect multiple specimens from the same suspect H5N1 patient on different days for RT-PCR testing * Preferred specimens

Clinical Specimens for Testing

• Serology– Acute and convalescent serum specimens

• Acute collected within 1 week of symptom onset• Convalescent collected 2-4 weeks after

symptom onset

– Other infections or concurrent illness

• Collect all possible specimens, serial collection

Clinical Specimens for Testing

• Autopsy Specimens– Eight blocks or fixed-tissue specimens from each

of the following sites• Central (hilar) lung with segmental bronchi• Right and left primary bronchi• Trachea (proximal and distal)• Pulmonary parenchyma from both right and left lung

– Major organs• Myocardium (right and left ventricle)• CNS (cerebral cortex, basal ganglia, pons, medulla, and

cerebellum)• Organ with significant gross or microscopic pathology)

Rapid Influenza Diagnostic Tests

• NOT RECOMMENDED TO DETECT AND DIAGNOSE H5N1 VIRUS INFECTION– Many commercial kits available– Results in 15-30 minutes– Low sensitivity (FALSE NEGATIVES LIKELY)– Positive result cannot differentiate seasonal

influenza A from avian influenza A (H5N1) virus infection

– Negative result does not rule out avian influenza A (H5N1) virus infection as diagnosis

Laboratory Diagnostics

• CDC’s influenza laboratory is nation’s influenza reference laboratory

• Capable of performing additional tests– Immunohistochemical testing on autopsy

specimens

• CDC’s Emergency Response Hotline– 770.488.7100

Imaging

Chest X-ray changes of pneumonia are common in the lungs of H5N1 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.ukSaturday, 3 December 2005

Avian Influenza A (H5N1) Virus Patient’s Chest X-Rays

Chest x-ray of a patient with avian influenza A (H5N1) virus infection, shown by day of illness

Day 5 Day 7 Day 10

Tran Tinh Hien, Nguyen Thanh Liem, Nguyen Thi Dung, et al. New England Journal of Medicine. 18 March, 2004. vol. 350 no. 12. pp 1179-1188.

Treating Suspected Cases

Treatment Options

• Antivirals

• Supportive care

Neuraminidase Inhibitors

• Two drugs available– Oseltamivir (Tamiflu®) and

Zanamivir (Relenza ®)

– Should be given as soon as possible

– Effective for treatment and prevention

– Used for seasonal influenza and infection with avian influenza A (H5N1) viruses

OseltamivirDosage for seasonal influenza

Adults: 75 mg twice a day for 5 days

Children:

• <1 year, not recommended

• If < 15 kg: the dose should be 30 mg twice a day for 5 days

• If >15 kg to <23 kg: the dose should be 45 mg twice a day for 5 days

• If >23 kg to <40 kg: the dose should be 60 mg twice a day for 5 days

• If >40 kg: the dose should be 75 mg twice a day for 5 days

OseltamivirTreatment for H5N1 patients

• Best dosage for H5N1 patients unknown– Consider longer treatment (7 to 10 days) OR– Higher doses (150 mg)– Begin as soon as possible

• Dosage for prevention– Once daily for 7 to 10 days after last exposure

• Side Effects– Nausea and vomiting– Skin rash– Neurological problems

Oseltamivir• Effectiveness in seasonal influenza

– Reduces influenza symptoms by 1 day– Reduces some complications of influenza

• Cautions- Consider Risk versus Benefits– People with kidney disease (adjust dose)– Pregnant or nursing females

• Contraindication– <1 year of age– Hypersensitivity to any component of product

• Resistance – Detected in some H5N1 patients

Zanamivir

• Inhaled by mouth via special device

• May be used for treatment of influenza >7 years of age

• Treatment dosage– Once in morning and night, 5 days

• Side effects– Wheezing, and breathing problems

Zanamivir• Effectiveness in seasonal influenza

– Reduces influenza symptoms by one day– Reduces lower respiratory tract complications

• Consider Risk vs. Benefit– People with chronic respiratory disease – Pregnant or nursing females

• Resistance– Very rare in human cases of avian influenza A

(H5N1) virus infections– Active against Oseltamivir resistant H5N1 viruses

Other Treatments?

• Amantadine and Rimantadine– Some H5N1 viruses are resistant

• Corticosteroids– Not recommended– Only for worsening sepsis with adrenal

insufficiency

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 Acetaminophen or Ibuprofen

• Children potentially infectious for longer periods than adults– If child cannot remain hospitalized, educate family about

infection control

– Source: WHO Writing Group, Emerging Infectious Diseases, Vol. 12, No. 1, January 2006.

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

Supportive Care

Hospital care for suspected or confirmed avian influenza A (H5N1) cases should include:

• Isolating the patient

• Supplemental oxygen and ventilation

• Intensive care support for organ failure

Infection Control in Health Care Setting

Infection Control Measures

• Patients hospitalized for clinical monitoring, diagnostic testing, and antiviral therapy

• Droplet/airborne precautions – Isolation– N95 respirators or more protective

• Eye protection (within 3 feet)– Goggles or face shields

Infection Control Measures

• Standard Precautions– Hand washing before and after contact with patient

or potentially contaminated items

• Contact Precautions– Gloves and gown worn– Dedicated equipment used

• CDC recommendations http://www.cdc.gov/flu/avian/professional/infect-control.htm

Managing Corpses

• No known risk of transmission from dead bodies

• Autopsy procedures could result in transmission– Use appropriate protective equipment

• You should know– Where corpses may be sent for disposal– Cultural or religious beliefs to respect when handling

corpses

Part 2 Summary

1. Important appropriate clinical specimens are collected and tested

2. Begin treatment with neuraminidase inhibitor (oseltamivir) immediately! Do not wait!

Case Management of Suspect Avian Influenza A

(H5N1) Virus Infection in Humans

Part 3: Public Health Action

Learning Objectives

• Understand case management from public health perspective

• Recognize opportunities for public health authorities to effectively communicate avian influenza A (H5N1) information

Part 3 Session Overview

1. Collect Case Information • Classify case according to case definition for

surveillance2. Facilitate specimen collection and

laboratory testing3. Information on avian influenza A (H5N1)

illness4. Infection control measures in the home5. Active case follow up 6. Identify close contacts and recommend

antiviral chemoprophylaxis (oseltamivir)7. Enhance surveillance

Pandemic Influenza Plan

• Know your role and responsibilities as outlined in your health department’s plan

• Identify key collaborators before and during investigation

Collecting Case Information

Case Information

Name and contact Information

Unique IdentifierOccupation (address)DemographicSymptoms Test Results

TreatmentOutcomeTravel history Potential exposures Close contacts

• Name of person reporting• Healthcare facility name and location

• Patient information:

Updated Interim Guidance for Laboratory Testing

of Persons with Suspected Infection with Avian

Influenza A (H5N1) Virus in the United States

Testing for avian influenza A (H5N1) virus infection is recommended for

a patient who has an illness that:

• requires hospitalization or is fatal; AND

• has or had a documented temperature of ≥100.4° F; AND

• has radiographically confirmed pneumonia, acute respiratory distress syndrome (ARDS), or other severe respiratory illness for which an alternate diagnosis has not been established; AND

• has at least one of the following potential exposures within 10 days of symptom onset:

A) History of travel to a country with influenza H5N1 documented in poultry, wild birds, and/or humans, AND had at least one of the following potential exposures during travel:• direct contact with (e.g., touching) sick or dead domestic poultry;

• direct contact with surfaces contaminated with poultry feces;

• consumption of raw or incompletely cooked poultry or poultry products;

• direct contact with sick or dead wild birds suspected or confirmed to have influenza H5N1;

• close contact (approach within 1 meter [approx. 3 feet]) of a person who was hospitalized or died due to a severe unexplained respiratory illness;

B) Close contact (approach within 1 meter [approx. 3 feet]) of an ill patient who was confirmed or suspected to have H5N1;

or

C) Worked with live influenza H5N1 virus in

a laboratory.

Case by Case Considerations!

• Mild or atypical disease (hospitalized or ambulatory) with one of the exposures listed above

• Severe or fatal respiratory disease whose epidemiological information is uncertain, unavailable, or otherwise suspicious but does not meet the criteria above

Proposed Influenza Division/CDC Case Definitions

• Confirmed• Suspect• Report under investigation• Non-case

• To be used for reporting purposes• A separate CDC Health Alert Network was

released that includes criteria for who should be tested for Influenza A (H5N1)

Confirmed Case (symptoms, exposure, laboratory confirmation)– Documented temperature >38 C (>100.4 F) and one of the

following: cough, sore throat, and/or respiratory distress

AND

– One of the following exposures within 10 days of onset• Direct exposure to sick or dead domestic poultry• Direct exposure to surfaces contaminated with poultry feces• Consumption of raw or partially cooked poultry or poultry

products• Close contact (within 3 feet) of an ill patient with confirmed or

suspected avian influenza A (H5N1) infection• Works with live HPAI (H5N1) virus in a laboratory

AND…

Proposed Influenza Division/CDC Case Definitions

Confirmed Case (Continued)

– Positive for avian influenza A (H5N1) virus by one of the following methods

• Isolation of H5N1 from viral culture• Positive RT-PCR for H5N1• 4 fold rise in H5N1 specific antibody titer by

microneutralization assay in paired sera• Positive IFA for H5 antigen using H5N1

monoclonal antibodies

Proposed Influenza Division/CDC Case Definitions

Suspect Case– Documented temperature >38 C (>100.4 F) and one of the

following: cough, sore throat, and/or respiratory distress AND

– One of the following exposures within 10 days of onset• Direct exposure to sick or dead domestic poultry• Direct exposure to surfaces contaminated with poultry feces• Consumption of raw or partially cooked poultry or poultry

products• Close contact (within 3 feet) of an ill patient with confirmed or

suspected avian influenza A (H5N1) virus infection• Works with live HPAI (H5N1) virus in a laboratory

– Laboratory test for avian influenza A (H5N1) is pending, inadequate or unavailable

Proposed Influenza Division/CDC Case Definitions

• Report Under Investigation– Additional information needed on clinical

and exposure information

• Not a Case– Negative avian influenza A (H5N1) virus

testing result from a sensitive laboratory testing method using adequate and appropriately timed clinical specimens

Proposed Influenza Division/CDC Case Definitions

Reporting

• Report through normal channels

• Information shared with WHO—probable and confirmed cases according to WHO case definition

• Help determine pandemic phase in US

Local PH

State PH

CDC

Facilitate Specimen Collection and Laboratory

Testing

Specimen Collection

• Best specimens– Lower respiratory tract

• Broncheoalveolar lavage fluid• Endotracheal aspirate • Pleural fluid

– Upper respiratory tract• Oropharyngeal swabs

• Have supplies stocked for timely collection of appropriate specimens

Laboratory Testing

• Be familiar with testing available in your area

• Know which laboratories can perform which tests

• Know tests available at CDC

Provide Information on Avian Influenza A (H5N1)

Illness

Avian Influenza A (H5N1) Virus Infection

• Emerging disease with evolving knowledge

• Empathy with public concerns

• Provide consistent and up to date literature to healthcare providers– Appropriate reading level– Translation for non-English speaking community

members

• Information such as clinical features, exposure, and treatment options

Educate on Infection Control Measures in the

Home

Infection Control Measures• Give consistent and up to date

literature to healthcare providers

• Hand washing – Soap and water for 15-20 seconds– Alcohol based sanitizer, >60%

alcohol

• Limit close contact with patient

• CDC Guidance on Community Mask Use During a Pandemic. www.pandemicflu.gov

Infection Control Measures• Seek medical care if condition

worsens

• Stay home for 24 hours after symptoms resolve

• CDC’s recommendation for in-home isolation– http://

www.cdc.gov/ncidod/sars/guidance/i/pdf/i.pdf

Conduct Active Case Follow Up

Active Follow Up

• Reasons for follow up– Specimens for testing– Timely notification of results– Monitor delivery of antiviral therapy– Secure antivirals if shortage– Note unusual clinical presentations

or complications

• Follow up by telephone– Patient– Healthcare provider (when available)– Surrogate (e.g. spouse)

Identify Close Contacts

Definition of Close ContactsThe definition of close contact is household and other

contacts in work, school, and community settings who had close unprotected (i.e., not wearing PPE) contact in the 1

day before through 14 days after the case patient’s symptom onset. Examples of close contact (within 1 meter)

with a person include providing care, speaking with, or touching. *

http://www.who.int/csr/resources/publications/influenza/WHO_CDS_EPR_GIP_2006_4r1.pdf

* Depending on the specific circumstances suspect or confirmed cases that have completed isolation for at least 7 days, and who are no longer

symptomatic, may not be considered a source of exposure to others.

Identifying Close Contacts

• List of contacts from patient’s case report form

• Close contact = within 3 feet or 1 meter– Sharing utensils, close conversation, direct contact

• Follow Up– Characterize exposure – Identify signs and symptoms

• Those with symptoms treated as potential case of infection with avian Influenza A (H5N1) virus

Recommendations to Contacts

No symptoms• Post-exposure prophylaxis for close

contacts of a strongly suspected or confirmed human case of avian influenza A (H5N1) virus infection – WHO “high” and “moderate” risk

categories, poultry depopulators, and responders who have been on infected premises should receive post exposure prophylaxis

Instruction to Contacts

No symptoms (continued)• Self monitor for 10 days after last

exposure– Fever, respiratory symptoms, diarrhea,

and/or conjunctivitis– Seek medical care if symptoms present– Notify public health authorities

• Follow infection control measures in the home

Enhance Surveillance

Enhance Surveillance during an Animal or Human Outbreak of Avian Influenza A

(H5N1) Virus Infections• Active case finding among occupationally

exposed• Sensitization of community to report illness• Expand SARI and/or ILI surveillance to local

hospitals, private practice etc... – Screening in hospitals

• Training on procedures and reporting• Door-to-door community surveillance • Telephone hotlines for reporting

Part 3 Summary

• Public health authorities serve as protectors of their community’s health

• Important that public health authorities provide clear and consistent messages to patients and contacts

• Case management also means identifying contacts

GlossaryAvian Influenza A VirusesInfluenza A viruses that cause infection of wild birds and poultry.

ContraindicationA specific circumstance when the use of a certain treatment could be harmful.

Seasonal InfluenzaExpected rise in influenza occurrence among humans living in temperate climates; occurs during the winter season with strains of human influenza viruses that have minor changes from season to season.

References and Resources• CDC Guidance for State and Local Health Departments for Conducting

Investigations of Human Illness Associated with Domestic Highly pathogenic Avian Influenza Outbreaks in Animals (Draft).

• Preliminary clinical and epidemiological description of influenza A (H5N1) in Viet Nam. 12 February 2004. http://www.who.int/csr/disease/avian_influenza/guidelines/vietnamclinical/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.

• WHO interim guidelines on clinical management of humans infected by influenza A(H5N1), 2 March 2004. http://www.who.int/csr/disease/avian_influenza/guidelines/clinicalmanage/en/index.html

• WHO pandemic influenza draft protocol for rapid response and containment. Updated draft 30 May 2006. http://www.who.int/csr/disease/avian_influenza/guidelines/protocolfinal30_05_06a.pdf