Current Situation in Control Strategies and Health Systems in Malaysia by Hishamshah Ibrahim MD, Ministry of Health, Malaysia

1. ‘Current situation in control
strategies and Health
Systems in Asia – Malaysia’
Hishamshah Ibrahim, MD
Ministry of Health, MALAYSIA
Thursday, 9 February 2012,12:25 – 12:35 AM

2. National Programme in Malaysia
(Designated: THALASSAEMIA PREVENTION & CONTROL PROGRAMME)
1. Public awareness & health education
 TV advertorials/Radio adverts/Mass media
2. Population Screening & laboratory diagnosis
 Screening of focus groups
 Adolescents, Pre-marital age group, High risk families, cascade screening
 Improved laboratory diagnosis at all levels
 + Pre-natal diagnosis
3. Comprehensive management of patients
 Setting a National KPI for quality of care
4. Thalassaemia registry
5. Cost Implications

3. Monday, 10 May 2004
Dr Chua: Registry proposed to track thalassaemia cases
THE HEALTH MINISTRY WANTS TO SET UP
A NATIONAL THALASSAEMIA REGISTRY TO FIND OUT
THE LEVEL OF INCIDENCE ON THE DISORDER.
Health Minister Datuk Dr Chua Soi Lek said a report on the registry was in its final stage
of preparation by a task force headed by the ministry’s Family And Health
Development Division director Datuk Dr Narimah Awin.
“I expect to table it to the Cabinet in two months,” he said after launching the first
National Thalassaemia seminar in Kuala Lumpur on Sunday. Thalassaemia is a
genetic disorder, which disrupts red blood cell-formation. The red blood cells are
easily destroyed and have a short lifespan, resulting in anaemia, causing patients to
become pale and easily tired.
Dr Chua said: “The problem starts when both parents are carriers. This has a
multiplying effect as they will produce children with thalassaemia major, who
generally require blood transfusion and iron therapy treatment.” Between 3% and 5%
of Malaysians are carriers of this genetic disorder.

5. National Programme in Malaysia
(THALASSAEMIA PREVENTION & CONTROL PROGRAMME)
1. Public awareness & health education
 TV advertorials/Radio adverts/Mass media
2. Population Screening & laboratory diagnosis
 Screening of focus groups
 Adolescents, Pre-marital age group, High risk families, cascade screening
 Improved laboratory diagnosis at all levels
 + Pre-natal diagnosis
3. Comprehensive management of patients
 Setting a National KPI for quality of care
4. Thalassaemia registry updates
5. Cost Implications
 Cabinet memorandum

6. The Strategy & Policy of Prevention (Source: WHO)
Strategy & Policy
% of baseline number of
new cases of
thalassaemia
Policy 1: No prevention programme (baseline situation) 100%
Policy 2: Best possible care (BPC) + Retrospective genetic 60%
counseling (RGC) after the 1st affected child is diagnosed
Policy 3: BPC + RGC + Prenatal diagnosis (PND) & abortion in 50%
subsequent affected pregnancies
Policy 4: BPC + RGC + Prospective pre-marital carrier screening 25-50% - slow
and counseling (PPMC) and no PND (+abortion) (over 20 years)
In Malaysia: BPC + RGC + some PPMC +
Policy 25-50% - slow
‘Voluntary’ population based screening + Family
4.5 screening. Minimal PND + abortion. (?years)
Policy 5: BPC + RGC + PPMC + Population based screening + Approximately 25%
Family screening of index cases and no PND (+abortion)
Policy 6: BPC + RGC + PPMC + PND (+abortion) + antenatal <10%
screening

7. ALGORITHM FOR VOLUNTARY AND CASCADE SCREENING
Index Case – Thalassaemia
Walk-in for voluntary Major /Carriers
screening
Pre-test counselling Offer pre-test counselling and screening for family Offer pre-test counselling and screening for
members immediate family members
(Uncles, aunts and cousins of the index case) (Parents + siblings of the index case)
FBC Send FBC result & unstained PPBF slide with
remaining blood to Hospital for Hb analysis
Hb-normal YES
Hb – normal Hb-low MCH < 27
MCH >27 MCH < 27 All can be performed on one 2.5cc EDTA sample
Post-test Check & treat for iron
counselling deficiency anaemia Definitive
diagnosis Normal
UNCERTAIN
YES
NO
Response to Consult Haematologist/Paediatrician/Physician Thalassaemia carrier
treatment
YES
Continue
treatment Consider DNA analysis
NO Definitive YES Counselling
Further investigation as
appropriate diagnosis
List of clinics that conduct thalassaemia screening is available at
http://fh.moh.gov.my/uploads/pend_kes/kk_talasemia.pdf

8. Would Malaysian couples accept this option?
Non-Directed Counselling
Thalassaemia counsellors
 
Would Malaysian thalassaemia carriers accept this?

9. Assessment of Prevention programme
– Secondary Indicator
Birth of new thalassaemia
patients
 Prevention programme
Population screening
Have not reached targets
1 birth cohort annually
All target groups

10. Birth of new Thalassaemia patients
- surrogate index for good control programme
2002
2003
2004
2005
2006
2007
2008
2009
Year
2010
2011
New
226 177 192 184 175 167 137 82 14 1
Births
? Policy 4.5
(Malaysian Thalassaemia Registry 2009 – unpublished data)

11. National Programme in Malaysia
(THALASSAEMIA PREVENTION & CONTROL PROGRAMME)
1. Public awareness & health education
 TV advertorials/Radio adverts/Mass media
2. Population Screening & laboratory diagnosis
 Screening of focus groups
 Adolescents, Pre-marital age group, High risk families, cascade screening
 Improved laboratory diagnosis at all levels
 + Pre-natal diagnosis
3. Comprehensive management of patients
 Setting a National KPI for quality of care
4. Thalassaemia registry
5. Cost Implications

12. Iron Chelation Therapy
Launched in
2010 by
YBMK during
the WORLD
THALASSAEMIA
DAY
12

13. CLINICAL INDICATORS
FOR QUALITY MANAGEMENT
Indicators Significance
Percentage of leucoreduced Packed Good blood transfusion service
Red Blood Cell (PRBC) units issued  Leucoreduction better done at Blood bank
 Provision of adequate budget
to transfusion dependent
thalassaemia patients
Percentage of transfusion Prompt treatment
dependent patients with serum
ferritin > 1000 µ/L receiving iron
chelation therapy
Percentage of patients with mean Quality of chelation therapy
annual serum ferritin < 2500 µg/L National KPI
Mortality rate per annum Mortality trend

14. Other Indicators to measure quality of
clinical management
• Percentage of patients with SF >5000 mcg/L
• Percentage of patients with SF >10000 mcg/L
• Percentage of leucoreduced pRBC used
• Percentage of patients with pre-transfusion Hb < 9 gm%
• Percentage of patients with Hepatitis B/C positivity
• Percentage of patients with short stature
• Percentage of patients with delayed puberty
• Percentage of patients with Diabetes/Impaired GTT
• Percentage of patients with hypothyroidism or other
endocrinopathies
• Percentage of patients with osteopaenia/osteoporosis
• Percentage of patients with T2* value < 20 ms
• Percentage of patients with Liver iron > 7 mg/gm DW

15. Quality of care indicators
1. Mortality
Survival curves
Causes of death
Role of Compliance
2. Morbidity
Multi-organ toxicities
Serum Ferritin levels

16. Causes of Death in Thalassaemia,
Malaysia, 2006 – 2009 (n=124)
TOTAL
Causes
No %
Cardiac 47 38
Infections 20 16
Liver Disease 3 2
Endocrine 15 12
Thrombosis 1 1
Tumours 3 3
*Others 5 4
Unknown/Unspecified 30 24
TOTAL 124 100
(Malaysian Thalassemia Registry 2010 – unpublished data)

17. Quality of care indicators
1. Mortality
Survival curves
Causes of death
Role of Compliance
2. Morbidity
Multi-organ toxicities
Serum Ferritin levels

18. Multi-organ toxicities in Thalassaemia
patients: HUKM (2003) & IPHKL (2004)
Complications Prevalence
Growth impairment 54.5%*
Pubertal delay 21.2%*
Lung dysfunction 33.3%*
Hypothyroidism (subclinical) 5.6%#
Osteoporosis 84.2%*
Impaired GTT 44.4%*, 22.2%#
Diabetes mellitus 1.9%#
Cardiac dysfunction 70%*
Hepatitis C seropositive 22.4%*, 9.3%#
(HUKM- 2003*, IPHKL-2004# >10 years (n=54))

19. Percentage (%) of thalassaemia patients by States
grouped by Serum Ferritin levels
(<2500, 2501 – 10000, >10000) µg/L, Malaysia 2009
Many states have incomplete data for serum ferritin level levels of their patients
(Malaysian Thalassaemia Registry 2009 – unpublished data)

20. How high should we set KPI?
80%
70%
PERCENTAGE (%)
60%
50% 50%
40%
Serum Ferritin level of transfusion dependent patients by Age groups, Malaysia, 2010 (n=1594) – unpublished data

21. Serum Ferritin (µg/L), < 10 years old, transfusion
dependent thalassaemia patients, IPHKL, 2009 - 2010
 National targeted KPI is 60% of transfusion dependent Thalassaemia
patients below 10 years old to have serum ferritin levels < 2500 µg/L
2009 2010
Serum Ferritin
No. (%) (%) No. (%) (%)
(µg/L)
< 1000 5 11.4 10 16.9
50.0 64.4
1000-2499 17 38.6 28 47.5
2500-4999 17 38.6 15 25.4
5000-9999 5 11.4 50.0 6 10.2 35.6
> 10,000 0 0.0 0 0.0
TOTAL 44 100 100 59 100 100

22. Therapeutic goals
Parameter Normal Mild Moderate Severe
Liver Iron <1–2 3–7 7 – 15 > 15
Concentration
(mg Fe/g dw)
T2* (ms) > 20 15 - 20 10 – 15 <10
Serum Ferritin < 300 <1000 1000- >2500
(µg/ml) 2500
NTBI/LPI/LCI To be kept within normal limits

23. Optimal chelation
Start Iron Chelation therapy if serum ferritin > 1,000 µg/L
MONOTHERAPY
•DFO 20 – 40 mg/kg/day (children)/50 - 60 mg/kg/day (adults)
•DFX 20-30 mg/kg/day in young children more than 2 years old
•DFP 75-100 mg/kg/day in older children
Adequate chelation: Inadequate chelation:
•Serum ferritin <2,500 µg/L •Serum ferritin >2,500 µg/L
•T2*heart >20ms •T2*heart <20ms
•LIC < 7mg Fe/gm DW •LIC > 7 mg Fe/gm DW
(If MRI is available, T2* MRI for those >10)
(If MRI is available, T2* MRI for those>10)
•Check compliance
•Optimise monotherapy
Continue current iron chelator & aim for
serum ferritin < 1,000 µg/L •Consider combination therapy

24. Management strategy by stratifying
patients by risk groups
 Assess iron load
Low/Good  Stratify patients by
Risk risk group
 Adopt appropriate iron
chelation strategies
National cohort of thalassaemia patients in Malaysia – Dec 2009

25. National Programme in Malaysia
(THALASSAEMIA PREVENTION & CONTROL PROGRAMME)
1. Public awareness & health education
 TV advertorials/Radio adverts/Mass media
2. Population Screening & laboratory diagnosis
 Screening of focus groups
 Adolescents, Pre-marital age group, High risk families, cascade screening
 Improved laboratory diagnosis at all levels
 + Pre-natal diagnosis
3. Comprehensive management of patients
 Setting a National KPI for quality of care
4. Thalassaemia registry
5. Cost Implications

26. 04 March 2005
RM40mil to treat 600,000 victims of thalassaemia
PUTRAJAYA
……………………………………………………..
“WE WILL ALSO START
A CENSUS TO REGISTER
ALL THALASSAEMIA PATIENTS
AND CARRIERS IN THE COUNTRY
BEGINNING WITH SECONDARY SCHOOL
STUDENTS”
……………………….Datuk Chua Soi Lek

27. Epidemiology – Malaysia
Number of Patients
Distribution Pattern
Changing trend - patients surviving & living longer
Geographical distribution
 Borneo
 Bordering Thailand
Age groups
Clinical Diagnoses
Ethnicity

28. Number of Thalassaemia patients
(by States, Malaysia, 2006 – 2010)
Increasing Trend  Old cases + New cases
Better reporting + New births + Less mortality
+ Increasing number of survivors because of better treatment

29. Prevalance rate of thalassaemia patients per
100,000 population by states, Malaysia 2009
(Malaysian Thalassemia Registry 2009 – unpublished data)

30. Changing Thalassaemia Demographic Pattern
Comparing Italy with Malaysia
Malaysia is @20 years behind.
Developed countries
• Less young patients
• More older patients
Developing countries
• More young patients
• Less older patients
University of Turin, Italy

31. We have more patients surviving
Patient population cohort, Malaysia 2002  2006  2010
• More children are surviving  adolescents  young adults
• Presence of more older patients
• Patient population cohort shifting to the right
2002 2006 2010
Median Age group: 5 – 9 yrs Median Age group: 5 – 10 yrs Median Age group: 10 – 15 yrs
35.6 %
27.6 %
18.2 %
12.6 %
6%
0-4 5-9 10-14 15-19 > 20
Age (years)
(n = 1683(@30 hospitals)

32. Thalassaemia by Clinical diagnoses, Malaysia, 2009
Clinical Diagnosis N (%)
Beta thalassaemia major 2109 44.7
Hb E-Beta thalassaemia 1489 31.6
Beta thalassaemia
465 9.8
intermedia
HbH Disease 476 10
*Others 176 3.7
TOTAL 4715 100
(Malaysian Thalassemia Registry 2009 – unpublished data)

33. Thalassemia by Ethnicity, Malaysia 2009
Malaysian
Ethnic (%)
population
Malay 62 % 50.4 %
Kadazan-Dusun 14 % 3.6%*
Chinese 13 % 23.7%
Other Indigenous
ethnic groups (minus 7.4%
10 %
Kadazan Dusun)
Others 7.8%
Indian 1% 7.1%
TOTAL 100 100 %
(Malaysian Thalassemia Registry 2009 – unpublished data). * estimates for Kadazan-Dusun

34. Diagnoses by ethnic groups, 2010
Various ethnic groups exhibit different thalassaemia phenotypes
(Malaysian Thalassemia Registry 2010 – unpublished data)

35. Distribution of Patients by Iron
Chelation, Malaysia, 2009
Patients
Chelators
No. %
Desferrioxamine (DFO) 1479 65.7
Currently on regular Iron
Deferiprone (DFP) 222 9.9
Chelation
Deferasirox (DFX) 217 9.6
Desferrioxamine (DFO) +
332 14.8
Deferiprone (DFP)
Total 2250 100 %
(Malaysian Thalassemia Registry 2009 – unpublished data)

36. National Programme in Malaysia
(THALASSAEMIA PREVENTION & CONTROL PROGRAMME)
1. Public awareness & health education
 TV advertorials/Radio adverts/Mass media
2. Population Screening & laboratory diagnosis
 Screening of focus groups
 Adolescents, Pre-marital age group, High risk families, cascade screening
 Improved laboratory diagnosis at all levels
 + Pre-natal diagnosis
3. Comprehensive management of patients
 Setting a National KPI for quality of care
4. Thalassaemia registry
5. Cost Implications
 Commitment of additional funding from the Government 2012

37. Summary – Thalassaemia update
1. The Malaysian National Thalassaemia Prevention &
Control Programme started in 2005
2. United stakeholders & strong political will
3. Changing epidemiology in Malaysia
 Total number of registered patients are increasing
 Total number of birth is declining
 Unique Geographical & Ethnic distribution
4. Patient management & outcomes are improving
 Monitoring of clinical outcome parameters
5. More resources required to improve the programme

38. TEriKMa
kAsiH.....
Thalassaemia
patients
Tawan Kinabalu
2007