1. 1 Case Management of Suspect Human Avian Influenza Infection Part 1: Background information on clinical features and management of avian influenza

2. 2 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

3. 3 Part 1 Session Overview Clinical features Epidemiologic information –Risk for infection –Transmission Current antiviral medications Group exercise

4. 4 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?

5. 5 Clinical Features

6. 6 General Information Human influenza Avian influenza Vulnerable Age Groups All ages affected Highest rates in children < 5 years Most complications in elderly >60 years Children < 5 years Healthy young adults Adolescents Time from exposure to illness Mean 2 days Range: 1 – 5 days Mean 2 – 3 days Range: 2 – 10 days

7. 7 Signs and Symptoms Human InfluenzaAvian Influenza (H5N1) Type of infectionUpper respiratoryLower respiratory FeverYes HeadacheYes CoughYes Respiratory symptoms Varies; sore throat to difficulty breathing Difficulty breathing, crackles, increased respiratory rate Gastrointestinal symptoms Rare: Children, elderlyRare: Variable, watery diarrhea, vomiting, abdominal pain Recovery2-7 daysLonger

8. 8 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

9. 9 Complications Seasonal Influenza Ear infection, sinusitis Bronchitis, bronchiolitis Pneumonia –viral or secondary bacterial Exacerbation of chronic conditions Muscle inflammation Neurologic Disease –Seizures –Brain inflammation –Reye’s syndrome Avian Influenza Almost all develop pneumonia Acute Respiratory Distress Syndrome (ARDS) Multiorgan failure Encephalitis

10. 10 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)

11. 11 Alak and Darin Question: Do you think Darin has signs and symptoms of avian influenza? Why or why not?

12. 12 Epidemiologic Information

13. 13 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

14. 14 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

15. 15 Alak and Darin Question: Do you think Darin is at risk for avian influenza H5N1 infection? Why or why not?

16. 16 Routes of Transmission

17. 17 Risk Factors Direct contact with birds Risk Factors: –Playing with birds –Working with birds –Preparing birds for meals Contaminated water

18. 18 Routes of Transmission Indirect contact –Infected materials, surfaces Person-to-person rare at present Eating undercooked or raw bird products –Meat, eggs, blood

19. 19 Alak and Darin Question: Has Darin had an exposure that could lead to transmission?

20. 20 Using All of The Information

21. 21 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

22. 22 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

23. 23 Alak and Darin Question: Would you suspect avian influenza H5N1 infection? Why or why not?

24. 24 Current Antiviral Treatment

25. 25 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

26. 26 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

27. 27 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

28. 28 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

29. 29 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

30. 30 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

31. 31 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

32. 32 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

33. 33 Alak and Darin Question: What would you tell Dr. Sarasin to do?

34. 34 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

35. 35 Questions?

36. 36 Case Study Exercise Background information on clinical features and management of avian influenza

37. 37 Case Management of Suspect Human Avian Influenza Infection Part 2: Case Management of Suspected Avian Influenza Cases

38. 38 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 case- patients and their contacts

39. 39 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

40. 40 Assess Suspected Avian Influenza Patients

41. 41 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

42. 42 Clinical Data to Collect Date of illness onset Symptoms Clinical measurements Complications –Date of onset Any clinical specimens collected for laboratory testing

43. 43 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

44. 44 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 / mm 3 Normal platelet count 150,000 - 400,000 / mm 3

45. 45 Medical Charts Include: Demographic information Medical history Current medical complaint / symptom history Physical examination findings Recommended treatment Laboratory or other test results

46. 46 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 _______________________________________________________

47. 47 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________________ _______________________________________________________

48. 48 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

49. 49 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) ___________________________________________

50. 50 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

51. 51 Role Playing Activity

52. 52 Advise on Testing Needs for a Suspected Case

53. 53 Suspect Case Diagnosis Influenza diagnostics General laboratory testing Imaging

54. 54 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

55. 55 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

56. 56 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

57. 57 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

58. 58 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

59. 59 Avian Influenza Chest X-Ray Chest x-ray of an avian influenza patient, 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.

60. 60 Advise on Treatments and Interventions for Suspected Cases and their Contacts

61. 61 Treatment Options Antivirals –Consider age group Antibiotics Supportive care

62. 62 Antivirals Early treatment is best Suspected cases should receive a neuraminidase inhibitor –Oseltamivir –Zanamivir Last choice –Amantadine –Rimantadine Not been studied –Ribavirin

63. 63 Antiviral Side Effects Oseltamivir –Nausea –Vomiting –Rash Zanamivir –Wheezing and breathing problems –Other suspected side effects not proven

64. 64 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

65. 65 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

66. 66 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

67. 67 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

68. 68 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

69. 69 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

70. 70 Advising on Case Management Role Playing Exercise

71. 71 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.

72. 72 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 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 http://www.who.int/csr/disease/avian_influenza/guide lines/vietnamclinical/en/index.html