Sorasak Lochindarat, M.D.

1
Experiences of Services Response to Avian Flu
in Thailand
Sorasak Lochindarat, M.D.
2
Poultry outbreaks and human cases of AI
(H5N1) in Thailand, 2004-2005
Country Situation

• Three waves of poultry outbreaks since early Jan
  2004
• Each wave accompanied with human cases, total 22
  cases with 14 deaths
• Characters of cases
• Male Female 13 9
• Case fatality by age
• under 5 years 1 / 3 (33)
• 5-14 years 8 / 9 (88)
• 15 yr over 5 / 10 (50)
• Risk factors
• Contact with sick/dead birds 12 cases
• Living in village having sick/dead birds 8
  cases
• Close contact with cases 2 cases

(Diagrammatic)
First wave
Poultry outbreaks
Second wave
Thirdwave
Human cases
2004
2005
3
Spot maps of human cases and poultry outbreaks in
Thailand
Third round (Oct05-Jan06)
Second round (Jun-Oct 2004)
First round (Jan-May 2004)
Source BOE, MOPH
4
Monthly Influenza Isolates 2004-2005
Pranee Thawatsupha, National Institute of
Health, Department of Medical Sciences
5
Reservoir Sources

• Backyard farm
• Free range duck
• Fighting cock

6
Clinical Description of Influenza(H5N1) in
Thailand (31 Oct 04) (1)
Number 17 case (9 children, 8 adult) Age -
median 14 y. (2-58 y.) M F 9
8 Confirmed diagnosis by culture or PCR for
H5 and / or virus isolation Fatality rate
Children (lt 14 y.) 89 Adult (gt 14 y.)
50
7
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
8
Result of Confirmatory Diagnosis of17 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)
9
Rapid Test For Flu A in Confirmed H5N1 Patients
Total H5N1 patients tested 11 cases Rapid test
use - Quick Vue, Directigen A,
Bianax Results of 11 cases - positive 4/11
(36), median 13 d. (6-18 d.) - negative
7/11 (64), median 7 d. (4-18 d.) - notdone
6/17 Mostly Directigen A
10
Viral Isolation of 16 H5N1 Patients in Thailand
(2)

• viral culture N No. of Day P
• range median
• Positive 11 3-12 7 0.211
• Negative 5 6-16 10

Number of day from onset of illness to culture
11
Laboratory Results of 17-H5N1 Patients, Thailand,
2004 (1)
Laboratory finding Survived Died
p-value (n 5) (n 12)
WBC median (/cumm) 5,400
2,450 0.008 Lymphocyte median
(/cumm) 2,429 663.5
0.096 Platlet count median (/cumm) 203,000
137,500 0.496
12
Laboratory Results of 17-H5N1 Patients, Thailand,
2004 (2)
Laboratory finding Survived Died
p-value (n 5) (n 12)
No. Tested 4 10 - SGOT
median (IU) 101.5 202.5
0.282 SGPT median (IU) 49 51
0.325
13
Radiologic Findings of 17-H5N1 Patients,Thailand,
2004
Radiologic Survived Died
P findings (N5) (N12)
CXR (early) - interstitial 1 1
0.51 - lobar, patchy 4 11 CXR
(late) - ARDS (diffuse bilateral) 1 12
0.02 - No ARDS 4 0
14
CXR Finding of Patient 8 YO
D 4 of Illness
D 8 of Illness
15
(No Transcript)
16
Antibiotics Therapy in 17 H5N1 Patients 2004,
Thailand
Antibiotics use 2 - 5 kinds (65 of cases use 3-4
kinds) 3rd gen. cephalosporin 11/17 (65) Macrol
ides 10/17 (59) Aminoglycosides
8/17 (47) Carbapenem 7/17 (41) Doxycyline
3/17 (18) Other - Co-trimoxazole,
piperacillin, quinolones
17
Corticosteriod Therapy in 17 H5N1 Patients 2004,
Thailand
Corticosteriod therapy in 8/17 (47) methyl
prednisolone 5/8 hydrocortisone 2/8 dexametha
sone 1/8
Number of day from onset of illness to start
corticosteroid medium 7.5 d. (Range 4-13 d.)
18
Oseltamivir Treatment of 10 H5N1 Patients
Thailand, 2004
Rx N mean duration mean
duration from onset to Rx
of Rx Survived 5 3 5.3 d.
6.7 d. (4-7 d.) (5-10
d.) Died 12 7 10.9 d.
3.5 d. (5-22 d.)
(1-5 d.) Total 17 10
- -
N
19
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)
20
Multi-sectoral coordination for avian influenza
control
CABINET
Private Sectors
Other Agencies
MOPH
National Avian Influenza Committee
Dept. of Livestock Development
National Operation Center
MOPH Operation Center
DLD Operation Center
27 Jan 05
21
1. New influenza virus in animals low risk for
human
Phases in development of influenza pandemic
(WHO 2005)
Prevent
Contain
Respond
A new pandemic is certain and
imminent,
only the matter of when!
11 Aug 05
22
Estimated impact of new influenza pandemic in
Thailand
Deaths 260,000
Extensive social and economic impacts
deaths 65,000
16 Apr 05
23
Cabinet approved 25 January 2005
The Cabinet
Strategic plans on Avian Influenza and Influenza
Pandemic Preparedness
National Committee on Avian Influenza Response
Thailand is prepared for the prevention of and
response to influenza pandemic
27 Jan 05
24
Objectives of Pandemic Flu Prepareness
- prevention and surveillance of pandemic flu -
reduce morbidity / mortality - appropriate
management - set up commanding network of health
care systems - reduce economic and
bio-psycho-social effects
25
Aims of Pandemic Flu Prepareness
- Appropriate organization in the situation of
pandemic flu - Conduct lab tests - NIH,
University lab at Bangkok viral study - 13
regional lab centers RT-PCR - Stockpile
Oseltamivir for 325,000 cases (0.5 of
population) - Hospital capacity for severe flu
10,000 beds and field hospital 5,000
beds - Mechanical ventilator 2 for each
district hospital
High frequency oscillator in
25 regional
hospitals
26
Strategies of Pandemic Flu Prepareness
- Prevention and control of epidemic in human
and animal - Prepareness of rapid test, stock
pile, PPE, ventilator, respiratory isolation
room and vaccine - Prepareness for pandemic
threat in - health care
system - community - Mass
communication for community awareness -
Organization neworks in health care system
27
SRRT Surveillance and Rapid Response Team
Central Regional SRRTs

• Surveillance
• Outbreak investigation
• control
• Information
• knowledge exchange

Provincial SRRTs
District SRRTs
Sub-district Health Centers
Village Health Volunteers Community Leaders
Over 1000 SRRTs have been established
3 Mar 06
28
Case Management Hospital Infection Control
Case management - CPG - training course
for HCWS - triage system - rational use
of rapid test oseltamivir - prepared
ventilator, pulse oximeter Infection control in
hospital - PPE - airborne infection
isolation room (regional/ university
hospital), respiratory isolation room
(provincial/district hospital)
29
Risk communication

• Dissemination of risk communication messages
  through various media, including call centers
• Centralized media releases with daily update of
  situation and public advices

3 Mar 06
30
Stockpiling and logistics

• Vaccine
• Antiviral drug
• Diagnostic test kits
• Respirators
• PPE

3 Mar 06
31
Administration of viral study supphy
19 Regional CDC centers
- Organized supply - Seasonal flu vaccine
for HCWS, Culler, surveillance team, lab
personnel - Rapid test - Oseltamivir
- PPE
13 Regional Lab centers
- RT-PCR - send specimens to NIH (WHO National
Influenza Center) in Bangkok
32
Draft CPG for avian flu/pandemic flu
Pilot table-top exercise Drills
Scenarios
Modification of CPG
CPG implementation
Evaluation
33
Guideline for avian flu/pandemic flu
prepareness Patients with suspecious of avian
flu/pandemic flu
Moderate to severe ARI and - Hx contact with
sicked/dead poultry - Hx contact with unexplained
pneumonia patient - Travel to/residence in area
affected by avian flu outbreak
Group 1
Unexplained severe pneumonia Cluster of
pneumonia Pneumonia in HCWS
Group 2
Group 3
Cluster of ILI
ARI acute respiratory illness ILI
influenza like illness
34
Group 1 Algorithm for avian flu
Persons with unexplained mod to severe ARI and
- Hx contact with sicked/dead poultry - Hx
contact with unexplained pneumonia patient -
Travel to/residence in area affected by avian
flu outbreak
CXR Rapid test (for Flu AB) Viral study
Rapid test neg CXR normal
Rapid test neg CXR pneumonia
Rapid test Flu A CXR normal/
pneumonia
Rapid test Flu B CXR normal/
pneumonia
35
Group 1 Algorithm for avian flu (Cont)
- Isolation room, PPE - Oseltamivir - waiting for
RT-PCR
Rapid test Flu A CXR normal/pneumonia
Severe Rx as above Mod supportive Rx
waiting for RT-PCR
Rapid test neg CXR pneumonia
Rapid test neg CXR normal
- OPD case/F.U. in 48 hr - Viral study
- Isolation room - Oseltamivir - waiting for
RT-PCR
Rapid test Flu B CXR normal/pneumonia
36
Group 2 Algorithm for pandemic flu prepareness
- persons with unexplained severe pneumonia -
Cluster of pneumonia - Pneumonia in HCWS
Rapid test for Flu AB Viral study
Rapid test neg - Supportive RX - Waiting for
RT-PCR
Rapid test Flu A - Isolation room, PPE -
Oseltamivir - Waiting for RT-PCR
Rapid test Flu B - Isolation room -
Oseltamivir - Waiting for RT-PCR
37
Group 3 Algorithm for surveillance of pandemic
flu
Cluster of ILI in community
Surveillance and rapid response team
Randomized viral study Closed observation for
pandemic flu
38
Lab investigation
Lab
Frequency of checking
Remark
1. CBC 2. UA 3. Hemo C/S, BUN, Cr, LFT,
BS 4. Quantitative PCR for H5 in blood 5.
Freeze serum
Baseline then as need Baseline then as
need Baseline then as need Day 0, day 1-
4 then as need Day 0, day 1, 3, 5, 7 then as need
For viral load For cytokine study
39
Lab investigation (cont)
Lab
Frequency of checking
Remark
6. Nasal swab, throat swab Tracheal
suction for viral study 7. Rectal swab
esp. diarrhea for viral study 8.
Urine for viral study 9. CSF for viral
study 10. CXR
OD until discharge OD for 5 days D
0 Baseline then as need Baseline then as need
PCR, IFA PCR, IFA Case neuro involvement
40
Severity of avian flu and referral system
Severity of AI
Level of hospital
No pneumonia Mild pneumonia Severe
pneumonia ARDS, sepsis/septic shock Multi-organ
failures
District hospital Provincial hospital Provincial
hospital Regional hospital University hospital
41
True numbers remain elusive in bird flu outbreak

• Mostly seriously ill patients get tested for H5N1
• Milder cases are likely to slip through the
  cracks
• Ducks can carry H5N1 without symptoms
• H5N1 can present with diarrhea and brain
  inflammation
• Family clusters of H5N1 in Vietnam and Thailand
  humantohuman transmission
• Seriously ill patients from the process of
  cytokines or drug resistant or delay treatment

42
Thank You
43
Oseltamivir stockpiling initiative

• Purchase from Roche
• 100,000 treatment courses in 2005
• to secure 100,000 treatment courses in 2006
• Effort for local production by GPO
• pilot production (from imported API) underway,
  bio-equivalent test pending, expecting to acquire
  FDA in 2006
• Proposal for government support to establish a
  production plant submitted in Mega-project
  package, approved in principal by the Cabinet
• Advocacy for establishment of regional stockpiles

3 Mar 06
44
Exposure of 17 H5N1 Patients, 2004
Direct contact with ill/dead chicken(n9)

• Living in village with dead poultry
• 15 (backyard chickens
• /fighting cocks)
• 1 (Duck)

No direct contact (7)
17 case (half are children under 15)
Male Female 11
Not living in village With dead poultry
Provide bedside care Of a probable case
( Dr. K Ungchusak, BOE, MoPH)
45
Strengthening Laboratory Capacity Networking

• Establish Lab Network NIH, NAIH, University,
  Military, etc.
• Equip and train 13 regional labs nationwide for
  molecular technique testing
• Enhance laboratory biosafety and biosecurity

3 Mar 06
46
National Strategic Plan on Avian Influenza
Control, 2005-2007Approved by the Cabinet, 25
January 2005

• Strengthening disease surveillance control
  (animal health, public health, wildlife)
• Improving animal husbandry
• Empowering the community for active roles in
  disease prevention and control
• Supporting RD/ knowledge management
• Promoting integrated management of disaster
• Strengthening organization and manpower capacity

16 Apr 05
47
Progress of the implementation of pandemic
preparedness plan

• Influenza surveillance Strengthened
• laboratories improved
• SRRTs established in all districts

• National antiviral stockpile initiated
• Logistic system under improvement
• Clinical trials of pandemic vaccine to be
  initiated

• ?Surveillancein man animals
• ?Stockpiling and logistics
• ? Emergency responses
• Public health
• Community
• ?Public communication
• ?Coordination and command

• Case management guidelines revised
• Training supervision underway
• Isolation rooms under improvement/construction

• Master operation plan prepared
• Pandemic preparedness plan to be integrated in
  national disaster preparedness plan
• To initiate table-top exercise on PPP at
  provincial level

7 Nov 05
48
Cabinet approved 25 January 2005
The Cabinet
Strategic plans on Avian Influenza and Influenza
Pandemic Preparedness
National Committee on Avian Influenza Response
Thailand is prepared for the prevention of and
response to influenza pandemic
27 Jan 05
49
Strategic plans on Avian Influenza and Influenza
Pandemic Preparedness (2005-2007)
25 July 05
50
Pandemic Influenza Preparedness Strategies

• Surveillance in man animals
• Stockpiling and logistics
• Emergency responses
• Public health
• Community
• Public communication
• Coordination and command

1 Aug 05
51
Avian Influenza Control Measure,Thailand 2004

• Influenza Vaccine - Culler
  - HCWs esp. assigned medical
• and nursing team
• - Laboratory personnels
• - Surveillance team
• (medical, livestock)
• Antiviral prophylaxis - Household
  contact
• (oseltamivir) - Culler
• (in case of improper PPE)
• - HCWs
• (in
  case of improper PPE)

52
Histologic Examination in H5N1 Patients
Thailand, 2004
Full postmortem autopsy was done on 2 patients
one child one adult (formalined) Necropsy was
done on 3 patients lung, liver, spleen
53
If pandemic flu happened in Thailand
Death 260,000
Death 65,000
Cases 6,500,000
Cases 26,000,000
Sick 10 of population (65 million) Mortality
1 Minimum expectation
Sick 40 of population Mortality 1 Maximum
expectation
54
Flu strain analysis 2004-2005
Pranee Thawatsupha, National Institute of
Health, Department of Medical Sciences