A REPORT ON THALASSAEMIA
FOR THE ASSOCIATION OF SOUTH EAST ASIAN NATIONS
[ASEAN]
Prepared by:
Dr Androulla Eleftheriou – TIF Executive Director
Dr Michael Angastiniotis – TIF Medical Advisor
20th AUGUST 2013
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Thalassaemia International Federation
CONTENTS:
About the Thalassaemia International Federation
3
About Thalassaemia: Global Overview
4
Introduction
Haemoglobinopathies in ASEAN countries: KEY FACTS
Current status of Control programmes/Activities:
Services for thalassaemia in ASEAN countries: Some indicators of current
status
The Consequences of not adopting policies for case management and
prevention
The way forward – a summary of needs
Collaboration with other stakeholders: Their potential contribution
5
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Thalassaemia International Federation
7
11
12
13
About the Thalassaemia International Federation
The Thalassaemia International Federation (TIF) is a non-profit, non-governmental
organisation founded in 1986, in official relations with the World Health Organisation (WHO)
since 1996. The Federation is an umbrella organisation, representing national thalassaemia
associations and other members from 62 countries. Our mission is to obtain ‘equal access to
quality care’ for every patient with thalassaemia, across the world. To achieve this, we
undertake a wide range of activities:
• Act as the ‘united’ voice of patients with thalassaemia worldwide, supporting existing
patient/parent associations and encouraging the establishment of new ones;
•
Work with national health authorities (NHAs), supporting efforts to provide all patients
with appropriate, quality health care and to develop effective prevention strategies;
•
Prepare and distribute up-to-date, reliable and unbiased information about thalassaemia,
its prevention and management and research for its cure;
•
Educate patients, parents, health professionals, the general public and policy-makers:
o TIF's internationally recognised Educational Programme includes several
conferences and workshops each year, as well as the preparation, translation and
free-of-charge distribution of an extensive range of books and other informational
material.
o TIF events at the local, national, regional and international levels have benefited
over 22,000 participants since 1989. TIF publications have been translated into
more than 22 languages and distributed to more than 55 countries around the
world.
o The Educational Programme is supported by an ad hoc advisory panel of experts,
as well as an extensive international network of around 200 scientific and medical
collaborators from over 45 countries.
•
Cooperate with health-related organisations and official bodies at national, regional and
international levels to promote control programmes in affected countries:
o TIF's close collaboration with the WHO recently resulted in the adoption of
resolutions EB118.R1 on thalassaemia and WHA59.20 on sickle cell anaemia, with
the focus of attention now shifting to their implementation in all affected countries.
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Thalassaemia International Federation
About Thalassaemia: Global Overview
Thalassaemia is one of a group of genetic blood disorders referred to as
haemoglobinopathies. These disorders, mainly comprising different types of thalassaemia
and sickle cell anaemia, are among the most common hereditary diseases worldwide:
around 7% of the global population carry an abnormal haemoglobin gene, and more than
half a million affected children are born each year.
Patients with β-thalassaemia major—the most severe type of thalassaemia—cannot make
normal red blood cells and do not produce enough haemoglobin. This leads to severe
anaemia, with consequences such as retarded growth, bone deformities and reduced levels
of energy. In the absence of appropriate medical care, affected individuals die at a young
age.
Medical advances in thalassaemia have changed the natural history of the disease, such
that it is now both preventable and treatable—a chronic, rather than fatal, condition. With
appropriate clinical management and health care, patients with thalassaemia can lead a
near-normal life as integrated, productive members of society, a fact well-established in
countries with effective control and treatment programmes in place. Unfortunately, however,
this is not the case for the majority of patients, living in medium- and low-resource countries.
The major challenge, therefore, is to bridge the gap in health service standards and the
quality of life experienced by patients from region to region and country to country, as well as
within individual countries. Improving patient access to quality health care is a key TIF goal.
The treatment of thalassaemia is lifelong, complex and costly, requiring specialised expertise
and a multi-disciplinary approach. The majority of patients, particularly in low-resource
countries, are children. This is because, without treatment, patients die at an early age. In
addition to the struggle faced by patients coping with the disease, thalassaemia has great
emotional, social and financial repercussions for families as a whole. It is in appreciation of
this fact that TIF often refers to “patients/parents” or "patients and their families", rather than
simply "patients".
Births with a Pathological Haemoglobin Disorders per 1,000 live births
Global Distribution of Pathological Haemoglobin Disorders 1996 (WHO)
Source: March of Dimes/Global report on Birth Defects-The hidden toll of dying and disabled children
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Thalassaemia International Federation
INTRODUCTION
Haemoglobinopathies in ASEAN Countries: KEY FACTS
1.1 The thalassaemia syndromes are a group of hereditary blood disorders which are
particularly prevalent in ASEAN countries, where most of the affected children in
the world are born;
1.2 Treatment of these disorders is life-long with considerable economic and social
repercussions and as such these disorders constitute a serious public health
problem, at the national and regional level.
The greatest numbers of affected births occur in this part of the world, with the
majority of patients remaining untreated or sub-optimally managed. In addition, in
the absence of national control strategies and strong awareness programmes, a
significant percentage of the patients remain undiagnosed or misdiagnosed. As a
consequence, there is an in, across the world, leading to very high costs needed
to treat medical complications and to very poor quality of life. In addition, there is
a significant reduction in the life expectancy of these patients who often die
before the first or second decades of their lives.
In certain parts of the world, including the region covered by ASEAN
misdiagnosis can be a frequent observation. Their deaths are often reported as
being caused by infectious diseases (prevalent in many countries of this region),
even before the establishment of the diagnosis, making the true numbers of
patients even more difficult to estimate;
1.3 In most of the ASEAN member states, the true size of the problem is not
accurately known due to lack of updated and upgraded epidemiological
information or patient registries at the national level, and as such, in most cases
the figures used are estimations or repetitions from already published reports
(based on many occasions on old, inappropriately designed studies). In some
countries, however, as a result of more recent work and advances in the
collection and analysis of information, the anticipated or calculated figures may
reflect better the true situation.
In Thailand alone, for example, it is estimated that there are around 600,000
patients with the various forms of thalassaemia needing treatment and almost
10,000 new cases are anticipated to be born every year. In Indonesia around
10,000 new cases are expected each year, in Myanmar 2,400, in Cambodia
1,800, in Laos 1,100, in Malaysia 800, in Vietnam 830, in the Philippines 160, in
Singapore 14, while in Brunei only 1 case, per year;
1.4 Although considerable work is still needed to update and upgrade
epidemiological data, the figures derived from published and unpublished data,
from small-scale studies and individual reports, provide, with the support of
calculations, a picture as near to the reality as possible of the size of the problem,
in each of the countries of the ASEAN ‘umbrella’, as shown below:
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Thalassaemia International Federation
Epid em iolo gy of the thalassaem ias in ASEA N cou ntries
C ou ntry
a - th al
carriers
ß -th al
c arriers
Hb E
carrie rs
An nu al
ex pected
b irths
Kn ow n
patients
trea te d
B run ei
D aru ssalam
?
2%
?
1
179
C am b od ia
35%
3%
35%
17 62
?
L ao s
42%
6%
18%
11 06
?
M a la ysia
23%
4 .5 %
3.4%
72 7
1500
M y anm ar
30%
2 .2 %
22%
23 98
4079
In don esia
0.5% 11%
5%
6%
(1 -3 3% )
93 68
5431
P hilip pines
7%
1 .2 %
0.4%
15 3
600
S inga po re
4%
3%
0.64%
13
154
T ha ilan d
30%
5%
30%
69 83
4000 00
V ietnam
5%
2%
1%
83 0
1000
T otal
~20%
~3.5%
1-30%
~230 00
~4 1300 0
These figures are only an overview of the problem, as in big countries with large
and/or heterogeneous populations in order to plan services effectively micromapping is additionally needed.
In the large countries of the ASEAN family, the population is not homogeneous
and the thalassaemia genes are often more frequent in some tribal groups or
geographical locations. Such micro-mapping is available for example in
Indonesia, Thailand and Malaysia (on a geographical basis), while in some others
such as Myanmar and Vietnam the tribal studies are necessary. At the moment,
only certain tribal groups have been tested, and the overall carrier rate is derived
from this patchy information.
Cambodia and Laos, in more recent years, are producing results from surveys
which are gradually clearing up the picture, while the Philippines have yet to
survey large parts of its territory, before any reliable information becomes
available. Singapore, on the other hand stands out as a small country with more
homogeneous population, and has good and reliable data, due to the
implementation of a national control programme.
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Thalassaemia International Federation
CURRENT STATUS OF CONTROL PROGRAMMES/ACTIVITIES:
Services for thalassaemia in ASEAN countries: some indicators of the current status
Policy/service
Cambodia
Vietnam
Laos
Philippines
Myanmar
Malaysia
Indonesia
Singapore
Thailand
National policy
None
None
No
none
none
Yes
Yes
Yes
Yes
Patient registry
Initiated
2011
None
None
Haematology
Association
none
Hospital
based
Yes
Yes
Hospital
based
none
All
none
All
All
All
All
All
All
Chelation free
no
partial
no
no
no
Yes
Yes
Yes
Partial
support
Specialist
monitoring
(e.g. cardiac
MRI)
no
none
no
no
no
Yes
In major
centres
Yes
Yes
National
Screening
program
no
Pilot
only
no
no
no
yes
no
Yes
Yes
Local Support
association
yes
Yes
since
2011
none
yes
None
Yes
Yes
Yes
Yes
TIF Activities
Yes
Yes
Yes
Yes
none
Yes
Yes
none
Yes
Chelating
agents
registered
Source: TIF Archives
From the above information, recently compiled by TIF through search of published
information and/or delegation visits and joint activities in countries of the ASEAN region, but
also from older information published by regional experts (see table below), conclusions can
be drawn concerning the opportunities for patients to survive.
Thalassemia diagnosis in different ASEAN countries
Country
Blood Cell
Analyzer
OF
Hb Analysis
DNA
Analysis
α
β
Indonesia
(+)
-
+
(+)
(+)
(+)
Myanmar
(+)
-
(+)
-
(+)
(+)
Thailand
+
+
+
+
+
+
Electrophoresis HPLC/LPLC/CE
Thalassemia treatment available in different ASEAN countries
Country
Blood
Transfusion
Iron
Chelation
BM/
Stem cell
Transplant
PND
National
Program
DFO
L1
Exjade
Indonesia
(+)
(+)
(+)
Myanmar
(+)
(+)
+
(+)
-
(+)
-
(+)
-
-
Thailand
+
+
+
-
(+)
+
+
+
Source: Fucharoen, S. 1st Pan-Asian Conference on haemoglobinopathies, February 2012, Bangkok, Thailand.
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Thalassaemia International Federation
For example, it can be seen that in Indonesia over 9,000 new cases are expected to be born
each year, yet only 5,000 patients are known to be receiving treatment. This is an indication
that there are children who die since they may never reach or get access to the appropriate
health services. Even those who do reach health services the level and quality of treatment,
they are provided with is variable, according to location; better quality services are provided
in urban areas and academic centres (in Jakarta), than in rural ones.
However, as the awareness campaign, in Indonesia, reaches more and more families, and
as the new insurance scheme becomes more known, more patients will appear requesting
access to treatment. This will increase the budgetary needs unless an effective prevention
policy is adopted to reduce the new annual affected births.
In Cambodia, Laos, Myanmar and the Philippines there are still many challenges in the
provision of basic care, even in the large centres and cities. Considerable awareness and
education on the disease, and its management are needed, as well as on the great value
and contribution of prevention strategies to the improvement of quality cost-effective care
provision.
In general, the health expenditure per capita which varies considerable in the ASEAN
member states (ranging from ~25 USD in Myanmar to ~2,100 USD in Singapore), reflects to
some level the quality of health care, provided in a country, although, economic
considerations are not the only factors affecting the quality of services.
Focus and prioritization of thalassaemias (haemoglobin disorders) on national health
agendas are clearly related to Governments’ clear recognition of their immense health,
public health, social and economic repercussions.
For example, Thailand and Malaysia, both with moderate expenditure on health have been
interested in thalassaemia over many years and have developed successful, effective
services through national policies, and Indonesia, in more recent years, is following with its
own policies very closely. All countries in the region have much to share and learn from each
other, and there is a need to collaborate closely in policy development.
The magnitude of this health issue introduces a significant economic problem not only at
national but also at family level due to the expense of the treatment, which is multi-faceted
and life-long. There are also indirect costs due to reduced productivity in a significant
proportion of the population and days lost from school or work.
There have been many studies on the costs of care on various Asian countries 7-4.
However, most of these, deal with the cost of treatment and do not consider or include the
cost of no or poor treatment which is in fact much higher. Consequent to sub-optimal or no
treatment, many serious medical complications develop, which must be treated, most of the
time at a high cost. Otherwise, these may sadly lead, in the majority of cases to early death
which further to the immense pain and social distress is a waste of resources.
National Control Policies to reduce the number of affected births have been applied in
various countries, particularly in the South of Europe, with greatsuccess. Such prevention
7
2
3
4
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Ho WL, Lin KH, Wang JD et al. Financial burden of national health insurance for treating
patients transfusion –dependent thalassaemia in Taiwan. Bone Marrow Transplant. 2006
Hadipour Dehshal M, Karimi M, Shah Ahmad Ghasemi MR. A glance at the cost of chelation
therapy with Desferal and Exjade in Iran. Iranian J of Blood and Cancer. 2010; 1:1-5
Luangasanatip N, Chaiyakunapruk N, Upakdee N, Wong P. Iron-chelating therapies in a
transfusion–dependent thalassaemia population in Thailand: a cost effectiveness study. Clin
Drug Investig. 2011; 31(7(: 493-505
Riewpaiboon A, Nuchprayoon, Tocharus K et al. Economic burden of beta thalassaemia major
in Thai children.
Thalassaemia International Federation
programmes include a composite policy of awareness raising, health education, screening to
identify the healthy carriers, preferably before marriage or at or during pregnancy,
counselling the identified at-risk couples and offering them the possibility of prenatal
diagnosis or other way of avoiding the birth of an affected child, if they so wish. The final
informed choice always belongs to the prospective parents. Examples of countries with such
successful prevention policies include Cyprus, Italy and Greece, where over 90% reduction
of affected, anticipated annual births, since the 1990s, has been achieved (as seen in the
figures below for Cyprus and Italy):
Actual vs Expected Births of thalassaemics in Cyprus
70
60
B irths
50
40
Expected
30
Actual
20
10
19
74
19
91
19
92
19
93
19
94
19
95
19
96
19
97
19
98
19
99
20
00
20
01
20
02
0
Year
Source: Data from the WHO collaborating Thalassaemia Centre – Nicosia, Cyprus
Another example is Italy with very similar results:
A ffe c te d p e r 1 .0 0 0 .0 0 0 n e w b o r n s
20
18
Italians
Immigrants
16
14
Reduction of affected births in the Lazio region of Italy
12
10
8
6
4
2
0
Years
75/78 81/82 85/86 89/90 93/94 Source: Amato, A. and Grisanti, P. et al, 2009-Prenatal Diagnosis 29(12):1171-4.
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Thalassaemia International Federation
Of the Eastern Mediterranean – Middle East region, Iran, with a very high carrier and
patients’ prevalence rates, has been the most successful in developing and implementing a
national control strategy for thalassaemia, so far, while a few others have shown similar
success in preventing the birth of patients with sickle cell disease (SCD), e.g. Bahrain. In
most of the ASEAN countries, as in many other countries of the world only some
components (but not holistic) of a prevention strategy have been developed, hence reducing
the numbers of affected births has not yet happened to date.
In the ASEAN region, prevention policies have been, as previously mentioned, adopted by
Thailand and Malaysia, and which both have been successful to a great extend, albeit more
efforts are required to limit, to the minimum, the number of newly affected births. Singapore
is perhaps the only country in the ASEAN region (being smaller and more homogenous in
population) with a complete effective control programme, and one, which includes all the
essential components of a prevention and treatment strategy. The population size and other
factors such as lack of awareness, high birth rates, heterogeneity of the population, other
health priorities will probably result in a slower rate of fall in affected births in many of the
ASEAN countries, but the effort should indeed start as soon as possible.
Adoption of a national prevention policy has proven cost effective where it has been applied
and one that will save considerable resources for the care of existing patients. Studies to
demonstrate this principle are many8-8 and have been published in both western and eastern
world countries.
Ginsberg G, Tulchinsky T, Filon D et al. Cost- benefit analysis of a national thalassaemia prevention
8
6
7
8
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programme in
Israel. J Med Screen. 1998; 5(3): 120-6
Ghotbi N, Tsukatani T. Evaluation of the national health policy of thalassaemia screening in the Islamic Republic of Iran.
East Mediterr Health J. 2005; 11(3): 308-18
Stirling B, Dormandy E, Roberts T et al. Screening for sickle cell and thalassaemia in primary care: a cost-effectiveness
study. Br J Gen Pract. 2011;
Ahmadnezhad E, Sepehrvand N, Jahani FF et al. Evaluation and cost analysis of National Health Policy of thalassaemia
screening in West-Azerbaijian province of Iran. Int J Prev Med. 2012; 3(10): 687-692
Thalassaemia International Federation
2. The consequences of not adopting policies for case management and prevention
2.1 As health systems across the world, including the ASEAN region, improve,
strengthening of public health services occur, and combating and preventing more
effectively communicable and non-communicable diseases improves, more and more
patients, with genetic diseases, including haemoglobin disorders (Hb) will survive,
and through improved, even if not optimal, treatment, will live longer. In the absence
of effective prevention strategies, nationally coordinated, the situation will result in an
increasing number of patients, every year requiring, on a life-long basis, medical and
other care and importantly resources like blood. In addition, in multi-transfused
patients, blood supply should be adequate to maintain Haemoglobin at appropriate
levels to keep barrow marrow expansion sufficiently suppressed, should be readily
available, well matched to the recipient and free from infectious agents. Likewise
drugs for iron chelation, perhaps the most expensive item, must be available and
free-of-charge to all, without interruption.
Careful monitoring of patients to assess iron loading and organ damage is essential
to allow early interventions to prevent serious complications. Such monitoring by
experienced staff requires the availability of technology such as Magnetic Resonance
Imaging (MRI), biochemical and other tests (e.g., serum ferritin measurements).
Such multidisciplinary approach is essential to be nationally coordinated and
sustained financially in a way, so as not to lead patients and their families to financial
ruins, particularly where still today out-of-pocket payment, constitutes the route of
obtaining health services, by a large proportion of patients, in some countries of the
ASEAN region.
Parallel development and implementation by the Government of effective prevention
programmes to address the annual affected births is the recommended way forward.
2.2 Inadequate basic treatment will result in severe complications, mainly but not limited to
iron overload, affecting major organs such as heart, liver and endocrine glands. These
new complications will increase both suffering and costs. Organised patient care with
the provision of free services, to ensure continuity of all treatment modalities, is
ultimately a cheaper option than the prevalent current situation where inadequate
treatment is provided in still many countries of this region. To support these statements
we suggest referral to several review articles9.
2.3 The issue of services for chronic disease is a poignant one for all health systems, and
even in those with low resources the needs of chronic disorders should not be ignored,
especially since affected individuals, with appropriate care can be productive and
socially active.
9
Borgna-Pignatti C, Gamberini MR. Complications of thalassaemia major and their treatment. Expert Rev Hematol. 2011; 4(3):
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Thalassaemia International Federation
3. The way forward – a summary of needs
3.1 Prioritization of Haemoglobin disorders on the national health agenda of every
country in the region.
3.2 Development of a 5-Year plan in the region to support the development of
national plans and support to implement or integrate these into other existing
relevant programmes.
3.3 Identify, strengthen and coordinate services already in place in many countries,
i.e. mapping existing situation.
3.4 Support the creation and/or strengthening of patients’ association.
3.5 Create scientific, medical and patients’ networks, within and across countries of
the ASEAN region and outside, to share experiences and knowledge.
3.6 Establish partnerships and collaborations with other stakeholders, e.g. NGOs and
develop twinning, matching and/or joint projects.
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Thalassaemia International Federation
4. Collaboration with other stakeholders: Their Potential Contribution
4.1 High level awareness:
In order to develop the several policies summarised above, governments which
have many and significant health issues to deal with, need to be made aware of
the seriousness of the hereditary thalassaemia syndromes, in each member
state. ASEAN in this respect should include these disorders in the health priorities
of the council of Ministers, and initiate discussions with the objective of
developing a 3-Year plan of Action. In addition, efforts should focus on
establishing collaboration and partnerships with other stakeholders.
4.2 WHO involvement:
The need for comprehensive policies for thalassaemia control was already
emphasised by the World Health Organisation in resolution EB118.R1, May 2006,
which was circulated to all Ministries of Health. ASEAN should make every effort
to encourage and motivate member states to implement this resolution and to
recommend to utilising the technical knowledge of the regional offices of WHO to
build on and support national efforts.
4.3 Thalassaemia patient support organisations:
Many such organisations, in the ASEAN region, are already registered as NGOs,
and the majority of these are members of TIF. These organisations should be
asked to assist in policy making by informing the ASEAN council on the issues of
most concern to patients and families. Members of these associations are
motivated, extremely knowledgeable and have actively contributed on a voluntary
basis to various public health projects in order to protect their patients. Some of
the ASEAN associations are mentioned in the table below:
JOHOR THALASSAEMIA SOCIETY
PERTUBUHAN THALASAEMIA PULAU PINANG
THALASSAEMIA ASSOCIATION OF MALAYSIA
FEDERATION OF MALAYSIAN THALASSAEMIA SOCIETIES
CLUB RAINBOW (SINGAPORE)
THALASSAEMIA SOCIETY (SINGAPORE)
VIETNAMESE THALASSAEMIA ASSOCIATION
Yayasan Thalassaemia Indonesia
Thalassaemia Foundation of Thailand
BALIKATANG THALASSAEMIA
MINDANAO THALASSEMIA FOUNDATION INC
CAMBODIAN THALASSAEMIA ASSOCIATION
Malaysia
Malaysia
Malaysia
Malaysia
Singapore
Singapore
Vietnam
Indonesia
Thailand
Philippines
Philippines
Cambodia
The Thalassaemia International Federation is a global NGO, which can provide,
through its educational and awareness programme, and international experts’
advisory panel, advice/technical support, education of staff, doctors and patients,
but most importantly assist in formulating a plan of action based on its experience
from many parts of the world. It is advisable to have this organisation as an
advisor and contributor to the ASEAN council’s work on Haemoglobin disorders.
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Thalassaemia International Federation
TIF has a very wide range of publications prepared by international experts,
which today are considered as reference material, particularly with regards to the
prevention and management of the disease.
In addition, TIF has established educational, training and fellowship programmes
for health professionals and the patients/parents communities. Furthermore, TIF
has assisted many countries to develop national policies and create reference
centres through joint projects with national health authorities.
4.4 Medical specialists:
The ASEAN region has a large group of medical specialists in the field who are
both locally, regionally and internationally recognised for their expertise and
research studies. They should be identified and invited to serve as advisors to
ASEAN in terms of the needs of the region in services and on technical matters.
A group of doctors have already formed the Asia Network (established since
2004) for thalassaemia and this includes ASEAN specialists but also doctors from
other Asian countries. This group may be consulted and expanded. TIF can
provide lists of these experts in each member state if this is requested. The
creation of a haemoglobinopathies’ Advisory forum is a very valuable step
forward.
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Thalassaemia International Federation