Queen Sirikit National Institute of Child Health 9 August 2006

Transcription

1 By Queen Sirikit National Institute of Child Health 9 August 2006

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3 Influenza Virus Family Orthomyxoviridae Genus Influenzavirus A, B, C Avian influenza H1 16 N1 9 All highly pathogenic avian influenza is Influenza A; Subtype H5, H7 Human influenza H 1, 2, 3 N 1, 2

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5 Avian influenza situation in the region ( ) 2006) H5N1 in Poultry H5N1 in Human South Korea Romania Azerbaijan 8/5 Japan MIDDLE Cambodia 6/6 Vietnam EAST ASIA China 19/12 Thailand AFRICA Cambodia AFRICA Djibouti 1/0 China Egypt 14/6 Indonesia Indonesia 53/41 Laos Iraq 2/2 Malaysia Thailand 24/16 Russia Turkey 12/4 Kazakstan Vietnam 93/42 Mongolia Tibet Burma Bulgaria (7 August 2006) 233/135

6 Epidemic curve of confirm H5 human cases in Thailand from 2004 to August 2006 (24 cases with 16 dead in 4 waves) cases 8 จ านวน (ราย) Acknowledge AI in poultry and human dead survive Declared AI free mobilize village health volunteers Nov-03 Jan-04 Mar-04 May-04 July-04 Sep-04 Nov-04 Jan-05 Mar May-05 July-05 Sep-05 Nov-05 Jan-06 Mar-06 May-o6 Jul J A Sep Remark: 3097 Notification and investigation in Notification and investigation in Notification and investigation in 2006

7 Exposure of 24 H5N1 Patients, Thailand, patients had history of sick/dead poultry contact 16 direct contact 7 indirect contact 1 patient probable contact from human-to-human transmission

8 Transmission of Avian-Flu 1. Direct contact with secretion esp. feces of poultry 2. Indirect contact from feed, water, equipment clothing 3. Human-to-human :- possible but low risk (CID 2002; 34: )

9 Clinical Manifestation

10 Guideline for Human Avian Influenza in Thailand (1) 1. Fever + RT symptom AND 2. History of contact* with sick/dead poultry within 7 day OR OPD (Triage) Isolate Exam. Room Doctor :- Hx, PE 3. Contact with pneumonia patient within 10 d. OR 4. Living in village with sick/dead poultry within 14 d. Cause identified Rx others Cause unidentified Portable CXR F/U, if remain sick > 48 h.

11 Bird Flu Screening เอ ก อ เอ ก เอ ก If you have fever, cough, dyspnea and contact chicken Please tell us VERSION1 VERSION2 ( Kamphangphet Hospital )

12 Clinical Forms of Human Avian-Flu 1. Asymptomatic 2. Mild URI 3. Severe pneumonia 4. Multiple organ failure (CID 2002; 34: )

13 Clinical Features of Human Avian-Flu Fever Headache Conjunetivitis Diarrhea Malaise Myalgia Sorethroat Cough Severe Pneumonia ARDS Organ failure Runny rose

14 Clinical Description of Influenza (H5N1) in Thailand ( ) 06) (1) Number 24 case (12 children, 12 adult) Age :- median 14 y. ( y.) M : F = 14 : 10 Confirmed diagnosis by culture or PCR for H5 and / or virus isolation Fatality rate (overall 67%) Children (< 14 y.) 75% Adult (> 14 y.) 58%

15 Clinical Description of Influenza (H5N1) in Thailand (31 Oct 04) (2) Presentation at hospital Fever, cough and dyspnea 100% Sore throat 71% Myalgia 53% Diarrhea 41% Rhinorrhea 53% Vomiting 24% Abdominal pain 24%

16 Clinical Features among Patients with H5N1 (2) Presentation (%) HK Thai VT HCM Cam (N=18) (N=17) (N=10) (N=10) (N=4) Fever Cough Dyspnea NA Diarrhea NA 50 Myalgia NA Pulm. Infiltrate ( N Engl J Med 2005;353: )

17 Clinical Features among Patients with H5N1 (3) Outcomes (%) HK Thai VT HCM Cam (N=18) (N=17) (N=10) (N=10) (N=4) Respiratory failure Renal dysfunction Time from onset of NA illness to death (d) (8-29) (9-30) (4-17) (4-21) (6-10) Oseltamivir Death ( N Engl J Med 2005;353: )

18 Are there any asymptomatic or mild illness of H5N1 infected patient? 351 residents of a Cambodian village where poultry and one patient die from H5N1 Significant exposure to poultry and infected people HCW s had no PPE 2 veterinarians who had autopsied H5N1 infected birds No one have asymptomatic or mild illness during H5N1 Outbreak in Cambodia

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20 Lab. Diagnosis of Human Avian-Flu Flu 1. Culture (Madin-Darby canine kidney cells) - Cytopathic effect prelim. using H5 specific RT-PCR or immunostaining with monoclonal antibody 2. H5 specific RT-PCR 3. Rapid test :- IFA from NP, endotracheal :- antigen detection 4. Serodiagnosis :- NT in paired serum

21 Result of Confirmatory Diagnosis of 17 H5N1 Patients in Thailand Positive RT-PCR for H5 17/17 (100%) Virus isolation for H5N1 11/16 (69%) IFA 11/16 (69%) Positive Rapid test for Flu A 4/11 (36%)

22 Laboratory Results of 17-H5N1 Patients, Thailand, 2004 (1) Laboratory finding Survived Died p-value (n = 5) (n = 12) WBC median (/cumm) 5,400 2, Lymphocyte median (/cumm) 2, Platlet count median (/cumm) 203, ,

23 Laboratory Results of 17-H5N1 Patients, Thailand, 2004 (2) Laboratory finding Survived Died p-value (n = 5) (n = 12) No. Tested SGOT median (IU) SGPT median (IU)

24 Radiologic Findings of 17-H5N1 Patients, Thailand, 2004 Radiologic Survived Died P findings (N=5) (N=12) CXR (early) -interstitial lobar, patchy 4 11 CXR (late) -ARDS(diffuse bilateral) No ARDS 4 0

25 CXR Finding of Patient 8 YO D 4 of Illness D 8 of Illness

26 Treatment and Care

27 Inpatients Isolation 1. isolate patient to a single room (negative pressure if available) 2. cohort patients separately in designated multi-bed rooms or wards 3. bed should be placed > 1 metre with curtain or partition ( WHO interim guidelines on clinical management of humans infected by influenza A (H5N1) : 20 Feb 2004)

28 Treatment of Avian-Flu 1. Supportive care :- Ventilator support when needed 2. Antiviral agents eg. Amantadine, Rimantadine, Zanamivir, Oseltamivir etc (Antiviral agents is the most effective when given within 2 days of onset, but don t know in Avian Flu)

29 Supportive Care of H5N1 Patient 1. IV fluid 2. monitor oxygen saturation 3. nebulizer and high-air-flow oxygen mask should be avoided (except under strict infection control airborne transmission precaution) ( WHO interim guidelines on clinical management of humans infected by influenza A (H5N1) : 20 Feb 2004)

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31 Antibiotics Therapy in 17 H5N1 Patients 2004, Thailand Antibiotics use 2-5 kinds (65% of cases use 3-4 kinds) 3 rd gen. cephalosporin 11/17 (65%) Macrolides 10/17 (59%) Aminoglycosides 8/17 (47%) Carbapenem 7/17 (41%) Doxycyline 3/17 (18%) Other :- Co-trimoxazole, piperacillin, quinolones

32 Corticosteriod Therapy in 17 H5N1 Patients 2004, Thailand Corticosteriod therapy in 8/17 (47%) methyl prednisolone 5/8 hydrocortisone 2/8 dexamethasone 1/8

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34 Limitation of Antiviral Agents 1. effective within 48 hr. of onset 2. decreased duration of symptoms by 1-2 d. 3. decreased viral population (data from human influenza) (no data for avian influenza) (Red Book 2003 : 384-5)

35 Daily Dosage Oseltamivir (Tamiflu ) Treatment in Adult and Children Weight < 15 kg ; Oseltamivir 30 mg, bid x 5d kg ; Oseltamivir 45 mg, bid x 5d kg ; Oseltamivir 60 mg, bid x 5d. > 40 kg ; Oseltamivir 75 mg, bid x 5d. Adult ; Oseltamivir 75 mg, bid x 5d.

36 Non-Specific Treatment of 17-H5N1 Patients Thailand, 2004 all patient whom developed ARDS require ventilator (mostly high frequency) inotropic drugs therapy in 8 of 17 patients Bronchodilator nembulizer in 8 of 17 patients Diuretic therapy in 7 of 17 patients

37 Oseltamivir Treatment of 10 H5N1 Patients Thailand, 2004 N Rx N mean duration mean duration from onset to Rx of Rx Survived d. 6.7 d. (4-7 d.) (5-10 d.) Died d. 3.5 d. (5-22 d.) (1-5 d.) Total

38 Antiviral Agents Treatment Recommendation in Thailand 1. patient whom influenza A positive (rapid test) 2. patient whom influenza A negative in severe viral pneumonia 3. culler with Flu-liked symptom whom had history of culling the poultry within 7 days 4. HCW s with Flu-liked symptom whom had history of contact with H5N1 patient within 7 days

39 Outcome of 17 H5N1 Patients, Thailand, 2004 Total number (as of October 2004) 17 cases Respiratory failure 13 (76%) Cardiac failure 7 (41%) Renal failure 5 (29%) Liver failure 3 (18%) Bone marrow failure 1 (6%) Dead 12 (71%)

40 Home care of H5N1 Patient Adult :- infection control measure for 7 days after resolution of fever Children :- younger than 12 y. can shed virus for 21 days Measure home quarantine for this period surgical mask hand-washing, hand-washing

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42 Prevention of Avian-Flu for Health Care Worker Same as SARS measure 1. Isolation room 2. PPE (as SARS is more than enough) 3. disinfectants of material

43 Appropriate PPE consists of 1. high efficiency mask (eg. N 95) if available or surgical mask 2. gown 3. goggles or face shield 4. gloves ( WHO interim guidelines on clinical management of humans infected by influenza A (H5N1) : 20 Feb 2004)

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46 Benefit of Influenza Vaccine for HCW s and Culler 1. Prevent reassortment of virus 2. Prevent human influenza 3. Strengthen the vaccination systems

47 Chemoprophylaxis

48 Use of Oseltamivir to Prevent Influenza Oseltamivir administered daily for six weeks by the oral route is safe and effective (~ 75-92%) for the prevention of influenza. (Frederick HC. N Engl J Med 1999; 341:1336.)

49 Chemoprophylaxis in Pre-Exposure To H5N1 infection NO (recommend appropriate PPE for HCW s and culler while working all the time)

50 Chemoprophylaxis in Post-Exposure To H5N1 infection (1) Definition :- anyone whom contact with 1. Proven case of H5N1 infection (including H5N1 poultry) AND 2. Working within 1 metre from index patient AND 3. Without or inappropriate wearing of PPE while working all the time

51 Chemoprophylaxis in Post-Exposure To H5N1 infection (2) 1. Household or close contact with index case 2. HCW s who do not or inappropriate wearing of PPE while working with index patient (confirmed H5N1 later) 3. Culler who do not or inappropriate wearing of PPE while working with H5N1 infected poultry within 7 days after their last exposure (Oseltamivir 75 mg/d,orally,7-10 days)

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53 Influenza Pandemics in 20th Century Credit: US National Museum of Health and Medicine 1918: Spanish Flu 1957: Asian Flu 1968: Hong Kong Flu million deaths 1-4 million deaths 1-4 million deaths A(H1N1) A(H2N2) A(H3N2) Source: Meslin / WHO 5 Oct 04

54 H5N1 Mutations from Indonesian Cluster (1) Total of 32 mutations in 6 patients 21 mutation from one patient (father) 1-4 mutations were found in 5 of 6 patients 1 mutation confer resistance to Amantadine

55 H5N1 Mutations from Indonesian Cluster (2) No genetic reassortment with human or pig influenza virus Mutations didn t make virus more transmissable or virulent No change in receptor binding site

56 Criteria to Meeting for Pandemic Flu 1. New virus (people do not have immunity) 2. Can cause human illness (~ 200 cases) 3. Can be transmitted from human to human easily (some evidence starting?) ( World is currently in phase 3/6 )

57 1. New influenza virus in animals low risk for human 2. High risk for human Phases in development of influenza pandemic (WHO 2005) 3. Human infections, no or only inefficient man-to-man Tx Current situation? 4. Increased man-to-man Tx, limited outbreak 5. Significant increase in man-to-man Tx, extended outbreak 6. Pandemic 11 Aug 05

58 Strategy in Fighting Pandemic Flu 1. Early detection :- most important - HCW s all level ready for fighting - laboratory facilities - PPE & stockpiling 2. Early treatment and prevention - HCW s all level ready for fighting. -Ward, hospital - antiviral drug 3. Early containment - Pandemic vaccine

59 Guideline for Pandemic Influenza Screening in Thailand, Screening for AI OPD (Triage) unidentified causes of severe pneumonia > 1 case cluster of pneumonia > 2 cases pneumonia in HCW Isolate Exam. Room Doctor :- Hx, PE Cause identified Rx others F/U, if remain sick > 48 h. Cause unidentified Portable CXR

60 Preparedness of HCW s Dr. Tawee Chotpitayasunondh as a guest speaker (Kumphangphet Hospital)

61 Antiviral drug

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63 Thank you