1. Case Management of Suspect Avian Influenza A (H5N1) Virus Infection in Humans May, 2007

2. Learning Objectives Recognize clinical features of avian influenza A (H5N1) virus infection in humans Treatment of cases Public health action

3. Clinical Features

4. General Information Human 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

5. Signs and Symptoms Avian Influenza A (H5N1) Type of infectionLower respiratory SymptomsFever, Cough, Headache Shortness of breath, difficulty breathing Diarrhea in some cases Hospitalized PatientsPneumonia Hypoxia requiring oxygen and respiratory failure requiring intubation and mechanical ventilation Acute Respiratory Distress Syndrome (ARDS)

6. 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)

7. Epidemiological Context

8. 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

9. 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

10. Local Customs - Unique Exposures Cock fighting Swan defeathering Playing with dead chickens Duck blood pudding, local customs Hunting practices

11. Specimen Testing

12. 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

13. 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

14. Avian Influenza A (H5N1) Chest X-Ray Chest x-ray of a patient infected with avian influenza A (H5N1) virus, 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.

15. Treating Suspected Cases

16. Treatment Options Antivirals Supportive care

17. 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

18. Other Treatments? Amantadine and Rimantadine –Some H5N1 viruses are resistant Corticosteroids –Not recommended –Only for worsening sepsis with adrenal insufficiency

19. Public Health Action

20. Response Overview 1.Collect Case Information Classify case according to case definition for surveillance 2.Facilitate specimen collection and laboratory testing 3.Information on H5N1 illness 4.Infection control measures in the home 5.Active case follow up 6.Identify close contacts and recommend oseltamivir chemoprophylaxis—monitor for symptoms 7.Enhance surveillance

21. 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:

22. 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;

23. 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.

24. 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

25. Proposed Influenza Division/CDC Case Definitions Confirmed Suspect Report under investigation Non-case To be used for reporting purposes A separate CDC HAN was released that includes criteria for who should be tested for Influenza A (H5N1)

26. 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)

27. Identify Close Contacts

28. Definition of Close Contacts The 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/i nfluenza/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.

29. Identifying Close Contacts List of contacts from patient’s case report form Close contact = Within 3 feet –Sharing utensils, close conversation, direct contact Follow Up –Characterize exposure –Identify signs and symptoms Those with symptoms treated as person under investigation or suspected case

30. Recommendations to Contacts No symptoms Post-exposure oseltamivir chemoprophylaxis for close contacts of a strongly suspected or confirmed case of H5N1 –WHO “high” and “moderate” risk categories, and poultry depopulators and responders who have been on infected premises should receive post exposure prophylaxis

31. Instruction to Contacts No symptoms (continued) Self monitor for 7-10 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

32. Summary Ask about any recent exposure to humans or animals that may have had suspected or known avian influenza A (H5N1) virus infection Clinical features of highly pathogenic avian influenza A (H5N1) virus infection in people can be non-specific, especially early in the illness. Appropriate clinical specimens need to be collected and tested Begin treatment with neuraminidase inhibitor immediately! Do not wait! Contacts must also be followed for possible illness.

33. Breakout Groups