1. Thalassemia is a major health issue in Indonesia due to its large population and ethnic diversity which results in a high frequency of thalassemia mutations. 2. The government has begun pilot prevention programs and provides some financial support for diagnosis and treatment, but challenges remain due to limited resources and the country's demographics. 3. Non-government organizations and health professionals are working to increase awareness and screening, but many affected individuals still go undiagnosed or do not receive adequate care due to the costs and complexities of managing the disease.

1. Pustika Amalia Wahidiyat
P ik A li W hidi
Thalassaemia Centre
Department of Child Health
p
Cipto Mangunkusumo Hospital Jakarta, Indonesia

2. Indonesian Archipelago
 13.670 islands
6 i l d
 2 millions square km
q
 224 millions populations
 ± 200 ethnics groups
 Birth rate ± 20‰
Birth rate ±

3. The distribution and frequency (%) of β‐thalassemia carriers
in Indonesia

4.  Indonesia:
 Health budget: < 2% Budget Revenues and Expenditures
 Income per capita (2010): USD 2,970 / person (IMF)
 Government insurance: NOT all, but for government
employed only
 Unemployment : 8,12 million people
 Government special insurance for poor people: Gakin,
Jamkesmas, Jamkesda (limited budget)
 Mostly low social economic status, uneducated

5. Carrier frequency of OGD α-Thalassemia in Indonesian Population
Karo
O.15
3
0.3
Mandar Kajang
TBSS Malay Makasarese
0.3 Java 0.6 0.65 Toraja
0.6 0.3 0.1 0.7 O.2
Sumba
0.3 0.1
(Kodi+Waingapu)
3.7 kb
4.2 kb 12.89
3.7
Ita Nainggolan, Eijkman Institute, 2003

6. Spectrum of β‐Thalassemia mutations & hemoglobinopathies
p β g p
in Indonesia
ACEH BATAK SOUTH CELEBES
IVS1‐nt1 HbMalay HbE
HbD Los‐Angeles IVS1‐nt5
Poly‐A (Black’s) Hb Lepore
PADANG
Codon 35
IVS1‐nt5
Filipino deletion
Codon 35
Poly‐A (Malay)
Codon 41‐42
Initiation Codon
Codon 17
HbS
Poly‐A
y
MALAY
IVS1‐nt5 JAVANESE
HbMalay BETAWI SUNDANESE
IVS1‐nt5
5 IVS1‐nt5
5 HbE Codon 30
HbE IVS1‐nt5 Codon 41‐42
d
Codon 26 IVS1‐nt1 IVS1‐nt1
Codon 17 HbE IVS1‐nt1 IVS2‐nt654
Codon 41‐42 Codon 35 IVS1‐nt2
Codon 15 Codon 15
25bp deletion Codon C d 8‐9
C d 17 Codon 8
IVS1‐nt1 Codon 26 HbG Makassar
HbS HbG Sirriraj

7. Distribution of ‐thalassemia mutations in population
and  thalassemia major patients
and ‐thalassemia major patients
Mutation distribution (%)
Type of mutations
Population Patient
MILD MUTATION
HbE 60 41
HbMalay 16 8.7
HbD Los Angeles 1.8 0
Poly A (Malay)
Poly‐A (Malay) 0.9 0.9
Poly‐A (Black) 0.9 0
SEVERE MUTATION
IVS1‐nt5 3.6 26
IVS1‐nt1 0 1.7
Cd26 stop 1.8
18 1.3
13
Cd 35 0 10
Cd 41/42 0.9 0.9
Filipino deletion 2.7 3
HbLepore 0.9 6
Eijkman Institute

8. Distribution of SAO in Indonesia
Kimura et al (1998), Yuwono (2002), Kimura et al (2003), Syafruddin (2006), Syafruddin (2007), Megawati (2008)

9. Estimation of affected population
 There will be 2,500 affected children will born/year
 Until October
U il O b 2011, 5,000 patients registered patients i all over I d
i i d i in ll Indonesia
i
 The number of patients were quite large but far below the real number in
population because:
 Mild mutations  asymptomatic  under diagnosed
 Undetected patients by health workers  lack of knowledge

10. Problems
P bl
 Increased number of new patients every year
 Di
Diagnosis: Limited number of established laboratory
i Li it d b f t bli h d l b t
• Established lab only in 6 big cities: Jakarta, Bandung, Semarang,
Surabaya, Yogyakarta, Makasar
 Treatment :
• High cost: USD 20.000‐30.000/patient/year
• Inadequate quantity and quality of blood
q q y q y
• NAT screening not widely used
• High incidence rate (33.3%) of hepatitis B/C virus infection, HIV in 2 patients
 Iron overload only measured by:
 Serum ferritin and transferrin saturation every 3‐6 months
 Cardiac iron overload: Echo (Government hospital), T2* MRI available only in
1 private hospital, price quite expensive (USD 230)
i t h it l i it i (USD )
• Under dose of iron chelations: Uncontrolled complications
• Limited number of pediatric hematologist
• No transplantation program yet

11. N b f ti t i
Number of new patients in
Thalassaemia Centre Jakarta
(1994-September 2011)
Distribution
Di t ib ti
according to age
(N=1,569)
• Mean age 14 years old
• Range: 9 months – 43 years old

12. Prevention programs
 Prevention program
 Indonesian Ministry of Health launch Health Technology Assesstment
on thalassemia screening protocol and prevention program in 2009
 Pilot project in 10 big cities in Indonesia with high gene frequency
 G l reduce th number of b t th l
Goal: d the b f beta thalassemia major and b t
i j d beta
thalassemia/HbE patients
 Methods:
 A t
Antenatal screening and f il screening of th th l
t l i d family i f the thalassemia
i
patients and by co‐incidence
 Red blood cell indices
 Hb analysis
l i
 PND

13. Prevention program
 Other activities:
 Professionals:
 Indonesian Pediatrics Associations (IDAI): Seminar and
workshop to GP and pediatrician outside Jakarta
 Indonesian Obstetric‐Gynecology Associations (POGI):
Screening the pregnant women and high risk couple, PND
g p g g p ,
 Obstetricians in Jakarta and some provinces have started to
routinely screened for thalassemia during ANC.
 Eijkman Institute: Genetic counseling, DNA analysis
j g, y
 Indonesian Thalassemia foundation with NGO (Rotary)
 Mass screening at the thalassemia center for students, office
staffs women activities  5 9% carrier beta and HbE
staffs, 5.9%
 Medical students organization (Center of Medical
Students’ Association/CIMSA) with 17 medical faculty from all
over Indonesia  4 76% carrier beta and HbE
4.76%

14. Prevention program
P i
I
Increased thalassemia awarness to:
d h l i
 Students especially Medical students
• Included thalassemia in the curriculum for medical students
• Seminar and free / low prices to thalassemia screening  4.76%
carrier beta and HbE
• “Thalassemia Awareness Projects”
Thalassemia Projects
 Public / Layman:
• First lady  Thalassemia icon
• Mass media (TV, newspaper, radio, magazines);
• Thalassemia foundation: Thalassaemia bulletin start in March 2010,
p
publish every 3 months distributed to 23 POPTI branch, hospitals,
y 3 , p ,
and layman.
• Make social events: fund rising, fun bike
• Seminar and screening thalassemia on the spot (low prices)

15. Financial support
 Government:
 Most of patients covered by
p y
government insurance namely
Gakin, Jamkesmas, Jamkesda,
SKTM, Askes PNS
k
 October 2011: Jampelthas:
ll ti t hi h
covers all patients which not t
included in any insurance
 Only cover treatment (blood
transfusion and iron chelation
therapy), without monitoring  USD
750/patient/month

16. Management
 September 2011: Thalassemia Diagnosis & Management
Guidelines by Indonesian Hematology and Blood Transfusion
Association
 Oral iron chelators
 Available since 2007 (DFP caplet)
 followed by DFX (2008)
 DFP oral solution (2011)

17. Management
 Price of blood: USD 30/bag, leucodepleted (ELISA) 
high infection
 NAT screening not widely used  plus USD 50/bag

18. Prenatal Diagnosis
l i i
 Total PND 2000 2010: 84
2000‐2010:
 17% ‐ couples whom detected as thalassemia carriers during
routine ANC
 67 % ‐ history of thalassemia major in the family
 Results:
 Compound heterozygotes or homozygote: 20 %
 all (except 1) affected fetus were terminated
 Two PNDs were misdiagnosed. Both were β‐thalassemia
compound heterozygotes but were prenatally diagnosed as
heterozygotes.
h t t
Problem: Government Act: Abortion ONLY 6 weeks of gestation

19. Summary
 Thalassemia prevention program in Indonesia has been done
as pilot projects starting 1998 government involvement in
1998,
2009
 Government start to support national thalassemia campaign
campaign,
funding for diagnostic and treatment and pilot project for
p
prevention program
p g
 There are many obstacles to bring this issue as a national
p g
program such as demographic, ethnicity, and diversity of
g p , y, y
mutations and phenotypes