TIF Global Thalassaemia Review 2021

ISBN [978-9963-717-21-7]
ISBN [978-9963-717-20-0]
©Thalassaemia International Federation 2021
All rights reserved.
The publication may not be reproduced nor copied for
distribution, in whole or in part, without the prior written
permission of TIF.
CITATION: Eleftheriou, A. & Angastiniotis M. (2021). Global
Thalassaemia Review 2021, Thalassaemia International
Federation.
All reasonable efforts have been made to verify the
information contained in this publication. Information is
correct at the time of publication. Any updates are closely
monitored and included in updated versions accordingly.
The material in this publication do not imply the expression
of any opinion by the authors or publishers concerning the
legal status of any country, territory, city or area. The mention
of specific manufacturers does not imply their endorsement
in preference to others of a similar nature that are not
mentioned.
Published in Nicosia, Cyprus
PUBLISHERS
THALASSAEMIA INTERNATIONAL FEDERATION
PO BOX 28807, 2083 STROVOLOS, CYPRUS
Tel: +357 22 319 129
Fax: +357 22 314 552
Email: thalassaemia@cytanet.com.cy
Website: www.thalassaemia.org.cy

AUTHORS
Androulla Eleftheriou, B.Sc., M.Sc., Ph.D.
Michael Angastiniotis, MD.
EDITOR
Lily Cannon, B.Sc., M.A., M.Sc.
COORDINATOR OF OPERATIONS
Eleni Antoniou, B.A., M.A., Ph.D Cand.
CONTRIBUTORS
Dimitris Farmakis, MD
Eleni Antoniou, B.A., M.A., Ph.D Cand.
Lily Cannon, BSc, M.A., MSc
Josep Darbà, Ph.D.
Sotiris Soteriades, Ph.D.
Meritxell Ascanio, M. Sc.
THE THALASSAEMIA INTERNATIONAL FEDERATION BOARD OF
DIRECTORS:
 HH Sheikha Sheikha Bint Seif Al-Nahyan
 Panos Englezos
 Shobha Tuli
 Elena Mylona
 George Constantinou
 Riyard Elbard
 Saeed Jaafar Al-Awadhi
 Abdul Baset Mohd Merdas
 Michele Maalouli Abi Saad
 Robert Ficarra
 Roanna Maharaj
 Odysoulla Stavrou-Cooper
 Eleni Michalaki
 Anton Skafi
 Loris Angelo Brunetta
 Fatemeh Hashemi
DESIGN & LAYOUT:
Stella Eleftheriou, B.A.
PHOTO CREDITS:
All photos included are submissions received in the
International Thalassaemia Day 2015 - 2019 Photography
Contests and taken during TIF Delegation visits.
SPECIAL ACKNOWLEDGEMENT
The Board of Directors of the Thalassaemia International
Federation (TIF), and executive office staff, express their
gratefulness and sincere appreciation to every single patient
and parent, within or outside a national association, for their
support, participation and invaluable contribution, without
which the preparation and completion of this Global
Thalassaemia Review (2021) would not have been possible.
SPECIAL APPRECIATION
The Board of TIF expresses its deepest and most sincere
appreciation to Mr. Junping Yu, the responsible Technical
Officer for the official relations of TIF with the World Health
Organization (WHO).
Deep appreciation is expressed by the Board of Directors of
TIF to the invaluable work of many decades performed by the
WHO through a number of projects, programmes and
recommendations promoted, and in particular, through
diseases-specific decisions and resolutions.
The TIF Board of Directors is most grateful to the global
Healthcare Professional community and more specifically for
the invaluable work of Dr Dimitris Farmakis, Dr Josep Darbà,
Dr Soteris Soteriades and Ms. Meritxell Ascanio.

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GLOBAL THALASSAEMIA REVIEW: TIF'S PERSPECTIVE 8
EXECUTIVE SUMMARY 10
GLOBAL EPIDEMIOLOGY OF Β-THALASSAEMIA 26
THE PREVENTION OF THALASSAEMIA REVISITED BY THALASSAEMIA INTERNATIONAL FEDERATION:
A HISTORICAL AND ETHICAL PERSPECTIVE 124
REVIEWING THE EFFECTIVENESS OF THALASSAEMIA PREVENTION PROGRAMMES:
TIF’S PERSPECTIVE IN A GLOBAL SNAPSHOT 144
BLOOD – THE GLOBAL SCENE TIF’S PERSPECTIVE 178
IRON OVERLOAD IN THALASSAEMIA:
ITS MONITORING AND TREATMENT TIF’S PERSPECTIVE 238
GLOBAL REVIEW OF MRI SERVICES FOR THALASSAEMIA:
TIF’S PERSPECTIVE 264
MULTIDISCIPLINARY CARE AND REFERENCE CENTRES IN ADDRESSING HAEMOGLOBIN DISORDERS 292
SOCIAL HEALTH PROTECTION AND THALASSAEMIA:
ADDRESSING THE SOCIAL DETERMINANTS OF HEALTH FOR IMPROVED HEALTH OUTCOMES
TIF’S PERSPECTIVE 314
ESTIMATING THE COST OF THALASSAEMIA CARE:
TIF’S GLOBAL CONTRIBUTION 344
DISEASE BURDEN OF TRANSFUSION DEPENDENT THALASSAEMIA TIF’S PERSPECTIVE 398
THALASSAEMIA REGISTRIES:
A CALL FOR ACTION A REPORT OF THE THALASSAEMIA INTERNATIONAL FEDERATION 422
THE VALUE OF PATIENTS’ ENGAGEMENT 442
UNMET NEEDS OF PATIENTS WITH THALASSAEMIA: TIF’S PERSPECTIVE 474
TABLE OF CONTENTS

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8 | F o r e w o r d
FOREWORD
THIS GLOBAL THALASSAEMIA REVIEW is dedicated to the work and collaboration of the
Thalassaemia International Federation (TIF) with the World Health Organisation (WHO)
in its status as an NGO in official relations since 1996.
TIF, in fulfilling its mission, has been guided and supported by the principles and vast
experience of the WHO in the context of both disease specific decisions, resolutions
and programmes including public health programmes and policies that are related to
the control and management of a genetic, hereditary, multiorgan disease like
thalassaemia. For such a disease there is today ample knowledge and experience on
how to effectively prevent and appropriately manage it at the clinical level. Moreover in
recent years, research advances have been impressive both in the area of management
but also in the area of cure giving great hope to the patients for their future.
TIF, in its early efforts was guided by the Hereditary Disease Programme of the WHO
headed by close and invaluable collaborators including Professors Anver Kuliev and
Victor Boulyjenkov, who have supported and guided our work in a number of ways. In
addition, and as TIF achieved the status of an “NGO in official relations with the WHO”
a number of other eminent health care professionals and relevant programmes’ leaders
have supported our work including amongst others, Dr Neelam Dhingra, and Dr Junping
Yu as well as the different Directors and officials of WHO Regional and country offices
and Collaborating Centres.
TIF continues its efforts with an undivided commitment to continue through its work and
partnerships with the global patient/parent associations and the large network of heath
care professionals across the world, to fight for the rights of patients for equal access to
quality health, social and other care.
GLOBAL THALASSAEMIA REVIEW:
TIF'S PERSPECTIVE

9
On behalf of the Board of Directors of TIF, which I have the privilege and the honour to
represent through this message, I would also like to express my wholehearted gratitude
and respect, to every single health care professional who has been with us from the
beginning and without the support of whom the work of TIF would not have progressed
positively towards achieving its mission. Special and particular gratitude goes to every
single parent and patient that has been with us through the years and continues to be
with us sharing with us challenges, concerns, successes, strengths but most importantly
providing confidence and trust to the work of TIF.
I hope that this Global Review which is a dynamic activity of TIF to be updated on a
continual basis as reliable and new information becomes available, will give some, even
gross, insights into the naked truth with regards to the provision of services for this
disease across the globe aiming to sensitize governments and competent authorities to
revisit and implement the recommendations offered by WHO’s Resolution WHO
EB118.R1 Thalassaemia and Other Heamoglobinopathies (2006).
On behalf of the Board of Directors of Thalassaemia International Federation,
Mr Panos Englezos
President
10 | E x e c u t i v e S u m m a r y
THE THALASSAEMIA INTERNATIONAL FEDERATION (TIF) was born because of the realization
that there are gross inequalities in the provision of disease specific services around the
world and the belief that ‘we can do better’ for all patients if collective advocacy on behalf
of the global patient community is presented to service providers and decision makers
at national and international level.
Beta thalassaemia, which is the condition which was, historically, the first concern of the
founding members of the Federation, is an inherited inability of the organism to form
beta globin chains, necessary to complete the haemoglobin molecule. The chain
imbalance in the molecule is the basis of the pathophysiology [1, 2] resulting in
ineffective erythropoiesis, severe anaemia, the need for blood transfusions and iron
accumulation in vital organs of the body requiring chelation on a daily, lifelong basis. As
patients grow, various co-morbidities to different extent based on the quality and level
of disease specific services provided to them, make their appearance, requiring, a well-
coordinated and expert multidisciplinary care approach. Although there is a spectrum
of severity, ranging from transfusion dependency from infancy to relative non-
dependency (NTDT), the severe form (TDT) is more common in most populations. TDT,
depending on the quality of services, or lack of services, has the following possibilities:
EXECUTIVE SUMMARY

11
 No treatment including no blood transfusion– death in early childhood,
generally before the age of 5 years
 Treatment based only on blood transfusion therapy - early death before
reaching the second decade of their lives
 Inadequate management – i.e. suboptimal transfusion therapy and
ineffective iron load monitoring and treatment can only result in the
postponement of death and poor quality of life. Survival is usually into the
late teens or young adulthood. This is the experience of the majority of
the global patient population, as this publication aims to demonstrate [3,
4]. Progress towards optimal patient care is slowly benefitting more
patients but there is much ground to be covered yet
 Optimal care (Table 1) is available to a minority of patients across the
world who are being cared for in reference centres. These are mostly found
in countries in which high disease prevalence is coupled with strong health
infrastructures and relative prosperity. Long patient survival has been
achieved in these countries but even so, this is still not equivalent to that
of the general population. Quality of life is also greatly improved with
optimal care, with patients achieving educational, career and social
goals, at least in their majority
 Curative treatments which at present include haemopoietic red cell
transplantation (HRCT) but also gene based approaches which at the
time of writing this review and despite the authorization of one such
curative therapy by EMA and currently under review by FDA, these have
reached a tiny minority of patients with their future uncertain but which
nevertheless hold great hope for the years to come[5, 6, 7].
1 Adequate and safe blood donation for regular lifelong transfusions
2
Maintaining a pre-transfusion Hb of not less than 9g/dl to correct anaemia and minimise endogenous,
ineffective erythropoiesis, and so marrow expansion.
3 Regular and specialised monitoring of iron load in vital organs
4 Daily iron chelation therapy with expert individual (personalised) management of iron overload
5
Coordinated, well-structured disease expert multidisciplinary approach to both monitoring, prevention and
managing organ involvement
6
Psychological support for the timely response to stress factors including special focus on self-management
and adherence to treatment
7 Social and financial support minimising or even eliminating out of pocket expenses
Table 1. Necessary services for optimal management of TDT
The provision of such services is not available equally and to the same quality standards
to affected patients within and across countries. In fact only a minority of patient
benefits from the truly huge medical and scientific advances achieved in the
management of haemoglobin disorders in the last 2-3 decades and this is evident in the
outcomes which are observed across all regions of the world. Thalassaemia is not unique
in experiencing such inequalities. All chronic and rare disorders are the poor relatives in
the stratification of what are considered priorities on the national healthcare and
budgetary agendas [8]. Inequity is a global phenomenon which affects all aspects of life
and is not confined to healthcare.
TIF is dedicated to promoting equal access to appropriate care for all patients. It may be
arguable whether a patient driven organization can have an impact in changing the
situation or whether this is a Don Quixote complex by a group of interested and
passionate protectors of doomed patients. Certainly, addressing global inequity in
health is not a matter of simply exerting political pressure. Many economic, social, racial
and political factors influence policy making and health related decisions [9, 10]. Nor is
it a simple matter of affordability of services, even though economic prosperity does play
a major role. Even within high resource countries health inequities and social gradients
are found which are known to affect health outcomes [11].
THE ECONOMIC DETERMINANTS OF HEALTH:
The question that has to be discussed is whether these inequalities in health outcomes
are avoidable. One position is that since health service provision depends on
socioeconomic circumstances which have such a wide variation globally, it is the socio-
economic conditions that must be addressed first to allow for progress in quality of
services. Faced with limited resources, spending should be prioritized to health threats
which affect the majority, thus safeguarding an adequate level of community wellbeing.
This logical approach has been the basis of the investment in primary care, of aiming for

13
‘maximum health gain for the money spent’ [8], which has led to the Alma Ata declaration
of 1978 by the WHO. This approach has had a positive impact health services globally.
The basis of the empirical observation by Modell & Kuliev some decades ago, that ‘the
importance of genetic disorders tend to be recognized when infant mortality falls below
40/1000 live births’, is related to the fact that before health authorities can consider and
acknowledge the needs to adress congenital and lifelong conditions as ‘other’ priorities,
reduction of infant mortality must be first effectively addressed [12]. It is the philosophy
on which cost-benefit has become the motto of health planners and certainly, the
application of evidence based costing. The comparison of cost to the benefits gained is
a pragmatic approach to health economic thinking. Wise spending will benefit the
community but the definition of benefit becomes unclear when the outcomes of service
interventions are examined more closely. If avoidance of disability and premature death
are the true expected outcomes, then the focus of health systems must also turn to the
individual.
THE RIGHT OF EACH INDIVIDUAL TO HEALTH:
The individual facing disability and premature death cannot be viewed simply as a health
or financial burden. Any civilized society must protect its most vulnerable members
based on the universal acceptance that health is a fundamental human right.
Recognizing health as a right means recognizing the individual’s need to achieve the best
possible in life. This need can only be visible if the affected individual speaks out and
presents experiences and suffering – the patient’s voice. This is very rarely heard where
and when it is needed most and which is mainly at the level of services planing. Patient
experience is not just the experience of ill health. It includes discrimination, poor access
to medications, to proactive monitoring, to social integration, education, relations,
friendships, networking, marriage and so many aspects and values of life. Reducing
patients to a number (YYL, DALYs, QALYs) may be helpful in addressing and managing
public health issues. But no indicator can adequately reflect on the experience of
individual lives. So should the focus then be on the individual or on the wider social
good? This dilemma is not just a philosophical query but must be seen in the context of
practical health planning and balanced decisions taken. It moves the economists’ view
of health to an ethical and philosophical realm that few have attempted to visit let alone
try to tackle.
THE ROLE OF TIF:
The creation of Thalassaemia International Federation (TIF) in 1987, was considered as
a continuation of the successful effort made in the 1960s and 1970s in the control of
heamoglobin disorders in, mainly and primarily, the Southern Mediterranean countries,
including Greece, Italy and Cyprus. Devoted parents mainly, but also young, then,
patients shared the vision that through a global umbrella organization health authorities
across the world can be better influenced to strengthen the provision of essential
services in the context of national disease specific plans. . This was, and still is the vision
of TIF that mandates its mission, work and activities. The influence of united social
groups was a real experience in some high prevalence countries and transferring their
experience to other countries was based mainly on successful advocacy, which indeed
changed the fortunes of patients wherever this was applied. The idea of sharing
experiences in advocacy across borders, of transferring knowledge and presenting a
united voice to local health authorities in individual countries through an international
consortium with medical back up, became a practical reality in 1987 in an international
meeting in Milano, Italy where TIF was born. Since then TIF has grown both
geographically and in membership – at the time of writing representing over 200 support
associations in 62 countries.
The difficulty and multiple challenges in providing adequate care was faced in low &
middle income countries (LIMC) as well as in countries in which the haemoglobin
disorders are very rare and/or not prevalent in the indigenous populations, irrespective
of economic or social development. Despite some improvements over the decades,
gross inequalities which seem to be related to these two main factors, country income
and the rarity of these disorders, continue so that the majority of thalassaemia patients
are still poorly managed in the same environments that were identified in the 1980s
when TIF was formed. The reasons are complex and cannot be ascribed to economic
reasons alone.

15
LOW & MIDDLE INCOME COUNTRIES (LMIC):
There can be no doubt that resource restrictions play a major role in the inability of LIMC
countries to reduce amenable mortality in chronic non-communicable diseases like
thalassaemia, which are indeed resource demanding. If the objective is to reach the
individual patient with evidence based clinical interventions aiming to reduce not only
the possibility of early death but also to reduce complications through monitoring and
secondary prevention, then examining resource availability must be supplemented by
an enquiry into reasons why resources are not reaching our patient. This implies a need
to examine factors that affect implementation. Where resources are limited certainly
competition with other health needs is a factor that most of TIF’s national associations
have to face. This means persuading health planners to provide thalassaemia patients
with a larger slice of a pie that is already limited in size compared to the mouths that it
is meant to feed. Advocacy in such a competitive situation is forced on support
groups as a sad reality which results inevitably in winners and losers, a very unfair
state for families and patients to have to work in. Yet survival of the most vocal,
and the most politically connected is a reality within which TIF and its associations
have been working for decades. Raising awareness, educating the public (an active
participant in hereditary disease services), educating healthcare professionals and
above all sensitizing health planners are all part of the same strategy to gain attention
and support. Through such actions, patient driven associations endeavor to increase
resources but support is often given in half measures in the effort of providers to satisfy
as many of the pressure groups as possible. Even when support is gained
implementation of services requires planning which in turn requires in depth
knowledge of the total needs of a multi-organ disease, affecting different age
groups differently and requiring a comprehensive approach for best outcomes.
The clinical expertise required is often lacking even among medical professionals and
poorly understood by health planners. The outcome of these deficits in both knowledge
and resources, results in wasting money and poor patient outcomes. It must not be
forgotten that well treated patients with thalassaemia are active tax paying
citizens, while those not benefitting from adequate care eventually become
chronic invalids requiring attention and care from many specialists throughout
their lives in order to address organ(s) damage while at the same time risks for
premature mortality are increased.
In addition to these challenges the social determinants of health and their role in service
implementation must be understood and addressed. Housing, employment, family
income, education, culture and religion (both so influential in disease prevention). In
chronic disease, the availability or lack of health coverage and thus the threat of financial
hardship, even bankruptcy, is an additional, very importantfactor threatening both social
and mental health. There is no doubt that economic hardship is correlated to poor
health, poverty once said is the biggest enemy of health.
As an umbrella organization TIF provides its members with the tools to promote their
needs including:
 Advocacy through capacity building workshops, but also supports
national groups by partaking in visits to health authorities when
requested.
 Education to both professionals and patients through publications,
organization of events and in more current years through tele-medicine,
webinars and electronic platforms. An educational programme supported
by a number of international and national experts in the field.
 The formation of expert patient groups and patient advocacy groups, to
address issues like patient rights and clinical trials
 The creation of national and international advisory panels
 Developing and maintaining epidemiological tools such as registries,
electronic medical records and keeping its own epidemiological
database with information both from the published literature and its
contact with countries and member groups
 Promoting self-management for patients, including the development of
Mobile Apps
 Working with WHO at both central, regional and country levels to influence
governments and their policies
 Encouraging research into more affordable and sustainable monitoring
and other interventions. An example is the early detection of organ iron
toxicity with alternative measures where MRI is not available.
 Finding new ways to generate resources, such as the more efficient use of
manpower, encouraging cross-border collaborations, so that
technologies and medical and scientific knowledge and expertise may be
shared.

17
HIGH RESOURCE COUNTRIES WHERE THE THALASSAEMIAS ARE RARE IN THE
INDIGENOUS POPULATION:
It is easy to assume that robust and well-financed health systems necessarily provide
optimal care. When a chronic condition is rare and even more when a hereditary
condition is not part of the local population’s pattern of disease, then weaknesses are
experienced. In the countries of the Americas and of Europe north of the Mediterranean
coast, migrations both historical and recent have introduced haemoglobin disorders to
a varying extent, even though they are still rare. Even though population movements
have been a phenomenon known throughout history, the recent increase of population
shifts from South to North and East to West, have brought with them an increase in these
chronic diseases which are over above the general acute health issues that are expected.
Migrations from Iraq, Thailand, Syria, Afghanistan and Turkey, for example are
entering Europe from the Eastern borders of Greece and the Balkans are carriers
of thalassaemia genes and HbE. One example is that of Germany, where in 2014
only about 1,000-1,500 sickle cell patients were recorded [13], while in 2016 a
neonatal screening study revealed a frequency of SCD in one in 2385 newborns,
probably of Sub-Saharan ancestry [14].
The clinical experience is lacking and even diagnosis is often delayed or inadequate.
Specialised clinical care may be provided in selected centres, but most migrants are
scattered and often do know where to seek expert help, while local physicians provide
basic blood transfusions and no expertise in management. Language and cultural
difficulties, the concerns about housing and employment all lead to the patient taking
place even within the family. There is absence of national registries so that the issue may
not be ‘visible’ to health authorities and since patient numbers and location are not
known, planning of services is absent or insufficient to meet the needs.
REFUGEES TO OTHER HIGH PREVALENCE AREAS:
The flow of refugees from war zones to neighbouring countries, which have also a high
burden of these disorders, remains of utmost concern for TIF. These protracted
emergencies have created, a great humanitarian crisis. Many patients from Syria have
gone to Lebanon, which hosts around 1-1.5 million Syrian refugees while Jordan
has received around 700,000 and Egypt over 100,000. These are countries, which have
an indigenous haemoglobinopathy problem, a burden with which they are hardly coping
for their own population. Yet no knowledge exists about the fate of the refugee patients
in these countries. Who is responsible for their care is not really known.
THE GLOBAL THALASSAEMIA REVIEW 2021
The Global Thalassaemia Review was put together by TIF as a collection of independent
reports , to document the existing situation across the world in the context of the various
components of public health, clinical and social services which are deemed essential for
patient wellbeing. The main concern in the Review is the transfusion dependent patient
who demands the most services in terms of quantity and quality. All patients with
haemoglobin disorders and congenital anaemias are expected to benefit and their well-
being and quality of life are considered in the daily agenda of TIF. The focus is on the
historical conventional treatments for thalassaemia in the dawn of an era when
 The preparation of the individual chapters in this Review, by different authors,
means that it is anticipated that there will be overlap in subject matter and
information. However, this is accepted since the message of inequality and the
need for more efforts to overcome deficiencies is the same and at the core of
this Global Review. It was also necessary for each author to provide some form
of introduction and basis for his/her comments in the content, part of which may
appear in a similar way and style in other chapters.
 The way the chapters were written is quite descriptive and each one of them
can form a separate, complete topic on its own. Due to severe lack of published
information, statistical analysis of data is very limited in this Review. The
objective however was to bring to light deficiencies which are documented and
easily discernable in terms of poor patient outcomes.

19
innovative therapies are emerging. If conventional therapy is not reaching the majority,
innovative therapies, however successful, will only increase inequalities.
The main components that contribute to the effective control of this disorder have been
almost exhaustively covered including: prevention, blood transfusion services, iron load
monitoring and iron chelation treatment services, the value of multidisciplinary care and
expert centres in the management of haemoglobin disorders, social and disability needs,
very importantly the cost of disease and disease burden and last but not least, the value
and role of national registries and patient engagement.
This Global Review was completed by a compilation and analysis of the available
information at TIF and/or from published information in the literature and focused on
the description of disease related services and other related significant components
mainly drawn from demographic data. There was an attempt by the authors to describe
the services not only at Regional level, but also at country level.
Heterogeneity and inequality in patients accessing appropriate services for their needs
are what this Review, for which TIF has meticulously worked over 2 years has captured
and brought to the surface.
For most chapters, attempts were made by the authors to provide even a gross
assessment of the availability of disease specific services and to grade their effectiveness
Acknowledging the fact that TIF’s intentions are to publish each chapter separately in a
later point in time, it is anticipated as previously mentioned that the reader will
encounter some degree of content overlap particularly in the introduction, discussions
and conclusions sections of some of the chapters.
TIF deeply and sincerely apologizes in advance if an omission or a
misinterpretation has occurred with regards to assessing individual country’s
services. Lack of nationwide registries, patient health records and published
information in literature may have contributed to such issues. Apart from the very
valuable insights regarding services, this Review brings also to the forefront the
substantial value of publishing information and sharing experiences and best practices
amongst involved stakeholders – governments, competent authorities, heath care
professionals, patients, academia, industry and indeed this is an element significantly
lacking in the field of heamoglobin disorders.
THIS REVIEW IS CONSIDERED BY TIF AS A DYNAMIC ACTIVITY AIMING TO BE UPDATED ANNUALLY, AS
NEW AND RELIABLE INFORMATION BECOMES AVAILABLE TO TIF OR TO THE PUBLISHED LITERATURE.
CONCLUSION:
The problem of inequality in healthcare provision is almost universal and well known,
but TIF has decided to focus and record its experience with thalassaemia patients across
the world. The data gathered, even from peer reviewed publications is often of
questionable accuracy. Yet, the attempt to give as clear a picture as possible, not only of
the global situation but also of each country, may offer some insights into the priorities
that need to be tackled and policies to pursue. Passively accepting morbidity and
mortality in young people cannot be acceptable particularly when regarding a
condition/disorder, for which there is ample knowledge and documented expertise for
decades now on how to effectively prevent and appropriately treat.. Authorities and
decision makers must be sensitized and made aware that survival of the fittest or the
richest cannot remain silent realities which no one wishes to acknowledge.
Above all this collection of facts and approximations is meant to guide TIF in its own
pursuit of answers and guidance as to what can be practically done to allow a section of
the community who can benefit from what medical science has to offer, and live a life
that is guaranteed by international proclamations. The whole philosophy is that ‘we can
do better’. TIF is a firm believer in this philosophy and passionately fights for the patient
voice to be heard and the despair of many to become an element of the past; And in this
effort, one organisation cannot change the world. Iinternational bodies like WHO,
governments, health planners, economists, the academia, the industry, the patient
support organizations at local, national and regional level must all join hands and minds
to bring about change.
TIF is very grateful to the WHO for its long term invaluable guidance and productive
collaboration in the context of its work as ‘an NGO in official relations’ with the WHO.
This Global Review is indeed a deliverable of its last 3 years plan of collaboration 2018-
2020.
The findings of this Review will support TIF in sensitizing governments and competent
authorities on their responsibility towards adopting and implementing the
recommendations provided in the context of the WHO decisions on thalassaemia and
other heamoglobin disorders with regards to the control of these disorders and seek for
their collaboration and support in transforming these to a disease specific Resolution
(WHO EB118.R1 Thalassaemia and Other Heamoglobinopathies (2006).

21
TIF in addition, acknowledges and is greatly indebted to the scientists/health care
professionals at country and international level who have been working and
collaborating for decades with TIF on a totally voluntary basis through its educational
programme across the six WHO Regions of the world. TIF also expresses through this
Review, its deep appreciation to the medical societies for their close and productive
collaboration in relevant projects including the European Hematology Association (EHA)
and to other than thalassaemia disease oriented NGOs with which TIF is sharing
experiences and best practices. Last but not least TIF is grateful to every individual
patient and parent who mainly through their national patient organizations’ support the
work, and share with TIF their challenges, concerns, successes, weaknesses and
strengths making it possible through their trust, confidence to TIF and to their active and
meaningful involvement and engagement, for TIF to continually advocate and fight for
the improvements of its own services towards the patients it represents all over the
world.
“We do not live to be treated.
We are treated to live”
G. Constantinou
Expert Patient
“Violating human and
patients’ rights for
equal access of
patients to quality
health and other care is
not acceptable”
Thalassaemia International
Federation
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10.1038/gim.2016.173. PMID: 27811859.
2. Origa R in 2021 Guidelines for the Management of Transfusion Dependent
Thalassaemia (TDT), Cappellini, M.D. Porter, J. Taher, A. Editors. Chapter 1. Thalassaemia
International Federation. 4th edition.
3. Weatherall DJ. The challenge of haemoglobinopathies in resource-poor countries.
Br J Haematol. 2011; 154(6):736-44. doi: 10.1111/j.1365-2141.2011.08742.x. PMID:
21726207.
4. Viprakasit V, Gattermann N, Lee JW, Porter JB, Taher AT, Habr D, Martin N,
Domokos G, Cappellini MD. Geographical variations in current clinical practice on
transfusions and iron chelation therapy across various transfusion-dependent
anaemias. Blood Transfus. 2013 Jan;11(1):108-22. doi: 10.2450/2012.0012-12. PMID:
22871821.
5. Strocchio L, Locatelli F. Hematopoietic Stem Cell Transplantation in Thalassemia.
Hematol Oncol Clin North Am. 2018 Apr;32(2):317-328. doi: 10.1016/j.hoc.2017.11.011.
PMID: 29458734.
6. Cappellini MD, Motta I. New therapeutic targets in transfusion-dependent and -
independent thalassemia. Hematology Am Soc Hematol Educ Program. 2017 Dec
8;2017(1):278-283. doi: 10.1182/asheducation-2017.1.278. PMID: 29222267; PMCID:
PMC6142569.
7. Cappellini MD, Porter JB, Viprakasit V, Taher AT. A paradigm shift on beta-
thalassaemia treatment: How will we manage this old disease with new therapies? Blood
Rev. 2018 Jul;32(4):300-311. doi: 10.1016/j.blre.2018.02.001.PMID: 29455932.
8. World Development Report 1993: Investing in Health.
https://openknowledge.worldbank.org/handle/10986/5976
9. Arcaya MC, Arcaya AL, Subramanian SV. Inequalities in health: definitions,
concepts, and theories. Glob Health Action. 2015 Jun 24;8:27106. doi:
10.3402/gha.v8.27106. PMID: 26112142.

23
10. Marmot M. Social justice, epidemiology and health inequalities. Eur J Epidemiol.
2017 Jul;32(7):537-546. doi: 10.1007/s10654-017-0286-3. PMID: 28776115.
11. Pearce A, Dundas R, Whitehead M, Taylor-Robinson D. Pathways to inequalities in
child health. Arch Dis Child. 2019 Oct;104(10):998-1003. doi: 10.1136/archdischild-2018-
314808. PMID: 30798258.
12. Modell B, Kuliev A. The history of community genetics: the contribution of the
haemoglobin disorders. Community Genet. 1998; 1(1):3-11. doi: 10.1159/000016129.
PMID: 15178981.
13. Eber S, Dickeroff R. Anemia and haemoglobin diseases in patients with migration
background.Dtsch Med Wochenschr. 2014; 139(9): 434-40
14. Grosse R, Lukacs Z, Cobos PN, Oyen F, ET AL. The prevalence of Sickle cell disease
and its implication for newborn screening in Germany (Hamburg Metropolitan Area).
Pediatr Blood Cancer. 2016; 63(1): 168-70

25 26 | G l o b a l E p i d e m i o l o g y o f β - T h a l a s s a e m i a
INTRODUCTION
According to Lilienfeld1
, epidemiology is the study of the distribution of a disease or a
physiological condition in the human population and the factors that influence that
distribution. An inherited disorder like β-thalassaemia has its own distinct geographical
distribution, affecting certain populations more than others. Environmental factors have
influenced the landscape of this genetic condition. To this interplay of genetic and
environmental factors other confounding factors, such as customary consanguineous
marriages, prevention programmes, and population migrations, have influenced the
prevalence of both carriers and actual clinically affected individuals globally. The most
important environmental factor that has affected thalassaemia epidemiology is the
protective effect of the carriers when infected by Plasmodium falciparum2,3
. This
selective advantage has contributed to the survival of carriers with the mutated β globin
gene, allowing them to increase in numbers, in areas where the malarial parasite is or
was most active. This correlation has been more strongly supported where the sickle cell
gene and α-thalassaemia are concerned, but the geographical coexistence between β-
thalassaemia and the malaria belt seems to confirm the same relationship. The well-
known thalassaemia belt has been mapped through epidemiological studies:
It has been estimated that 5 – 7% of the world’s population carries a mutated gene
affecting the production or function of the haemoglobin molecule4
. This suggests that
over 330,000 affected infants are born annually of which 83% are sickle cell disorders
and 17% thalassaemias (around 56,000). These numbers, and country specific figures,
are based on data collected by individuals and groups who maintain databases based
on literature reports. These include Modell's Haemoglobinopathologist's Almanac
(www.Modell-Almanac.net) and the IthaMaps database maintained by the Ithanet
project (www.ithanet.eu › ithamaps). The Thalassaemia International Federation (TIF)
keeps its own database, based not only on published surveys, but also on information
GLOBAL EPIDEMIOLOGY OF Β-THALASSAEMIA
AUTHORS: Angastiniotis M, Cannon L, Soteriades S, Antoniou E, Eleftheriou A

27
gathered through country visits and discussion with local experts. In this report the
discussion is about β-thalassaemia, even though the geographical distribution of this
condition coincides with other haemoglobin disorders, mainly α-thalassaemia and sickle
cell syndromes. There is no attempt in this report to [provide data on the whole global
picture. Countries were selected because of high birth incidence of beta thalassaemia or
in order to study current population movements and their possible effect on services to
the patient community.
WHY ARE EPIDEMIOLOGICAL DATA IMPORTANT?
The importance of collecting data and supporting databases lies in the role that accurate
epidemiological facts have in the development of health policies. Epidemiology is the
basis of public health and policymaking and not an academic exercise; to quote an
eminent epidemiologist and ex-director of the CDC, William H Foege5
who emphasized
that ‘epidemiology is no better than the information on which it is based’. Indeed complex
chronic disorders, such as β-thalassaemia, require policies and strategies to provide a
strong diagnostic infrastructure, day transfusion services, multidisciplinary care, cost-
effective treatment modalities, centres of expertise and screening services that offer the
possibility of preventing affected births6
. In view of the economic pressures that such
policies imply, providing policymakers with convincing information is a major step in
advocating for change and service improvement for the benefit of the patient. In
addition, such data enable further understanding of the social implications of disease.
Epidemiological data provide invaluable information for the monitoring and evaluation
of policies, as well as for the study of the natural history and prognosis of syndromes
allowing the observation of changes over time and place.
The collection of accurate figures (using surveys and registries) is therefore imperative,
as is their correct interpretation (using probability and other statistical methods).
However, the data collected by various databases are in fact not always of the quality
that can assure accuracy or even approximation in many locations. Additionally, patient
registries that are regularly updated are hard to come by. Survey data are often based
on small projects, which cannot be representative of the whole population. In fact,
approximations have become an accepted norm since the task of carefully conducted
surveys seems impossible. The question arises whether approximations are adequate
to establish a health policy and plan adequate quality services.
28 | G l o b a l E p i d e m i o l o g y o f β - T h a l a s s a e m i a
The Thalassaemia International Federation (TIF), collects such epidemiological
information to support its advocacy efforts for the promotion of national health service
development for haemoglobin disorders. This role is fulfilled through the provision of
tailored, evidence-based recommendations to national competent authorities for the
development of policies and services that will improve the lives of patients. In addition,
TIF develops and provides tools and resources that will assist national patient
associations better influence their local governments thus constituting productive and
active partners in the decision-making process. TIF is fully aware of the limitations of the
data collected, which are explained below. However, the best approximations are
calculated based on the information collected from the literature and from local experts.
The need to regularly review data is recognized, and the effort to reach as near to the
truth as possible cannot be abandoned since the unmet needs of patients must be
brought to the attention of policymakers to ensure the appropriate resource allocation
is provided for the development of new, or the refinement of existing policies for
patients with β-thalassaemia.
METHODOLOGY
The data which are collected for the TIF epidemiological database are listed in Table 1.
The collective interpretation of these indicators provides a meaningful picture of the
national landscape regarding α- and β-thalassaemia.
Information describing each country’s development profile varies from year to year and
is regularly updated, based on international databases, such as the World Bank and the
CIA Factbook, as well as WHO sources.

29
COUNTRY INDICATORS FOR MAJOR
HEMOGLOBIN DISORDERS
SUBGROUPS
OVERALL CARRIER RATES
Alpha thalassaemia (overall)
β-thalassaemia
HbE
HbS
HbC
ANNUAL EXPECTED BIRTHS/1000 LIVE BIRTHS
β-thalassaemia homozygotes
HbE/β-thalassaemia
HbS homozygotes
HbS/β-thalassaemia
TOTAL AFFECTED BIRTHS EXPECTED ANNUALLY
β-thalassaemia homozygotes
HbE/β-thalassaemia patients
Total β-thalassaemia syndromes (1+2)
Sickle cell disease (SS+SC)
HbS/β-thalassaemia
Total sickle c ell syndromes (4+5)
TOTAL NUMBER OF KNOWN PATIENTS
β-thalassaemia syndromes
Sickle cell syndromes
COUNTRY PROFILE
POPULATION CHARACTERISTICS
Total population
Crude birth rate
Total annual births
RELEVANT HEALTH INDICES
Infant Mortality Rate/1000 livebirths (lbs)
Under-5 mortality rate/1000 livebirths (lbs)
Consanguinity rate/coefficient
COUNTRY HEALTH DEVELOPMENT
Human Development Index (HDI)
Income per capita
Health expenditure per capita
Universal Health coverage
Table 1. Data collected for each country in the TIF database
In addition, a more detailed literature review was undertaken concerning the global
epidemiology of both α- and β- thalassaemia, with the objective to both update data, but
also to review the accuracy of the methods used in various studies. This was assigned to
the Epidemiology Department of the University of Larissa (Greece). The research group
conducted an overview of the research efforts made over the last decade (2009-2019),
with the aim of establishing the prevalence and incidence of thalassaemia as a disease
or of thalassaemia-related genes around the world. Three research databases were
searched (namely PubMed, Scopus and Web of Science) for studies whose methodology
involved sampling and screening of the following conditions: thalassaemia, α-
thalassaemia trait (α+
-thalassaemia and α0
-thalassaemia), Haemoglobin H disease, Hb
Barts hydrops fetalis, β-thalassaemia heterozygotes and β-thalassaemia homozygotes.
A total of 6,373 research articles were identified by the initial search. Their abstracts were
then screened to decide if they contained relevant information. 432 articles were
selected which then underwent a more thorough process of evaluation, by reading the
full text of the articles, in order to compose a final list. In the end, 116 studies were
identified.
RESULTS
LITERATURE REVIEW (2009 – 2019)
The Epidemiology Department of the University of Larissa (Greece) which undertook a
targeted literature review as described in the Methodology section of this Chapter,
identified a total of 116 studies in 31 countries that fulfilled the search criteria. However,
about two thirds of studies occurred in only four countries, namely China, India, Thailand
and Turkey. Only three studies were nationwide (Brazil, Malawi and Saudi Arabia).
One of the first objectives is to establish the proportion of the population at a given
location that carries a thalassaemia gene. The elements for accurate estimation of
carrier frequency include the following:
For thalassaemia, relatively simple techniques, suitable
for testing large numbers of individuals exist and in fact
these have been used extensively in screening
programmes as well as in surveys7
. Extensive
heterogeneity existed among the studies about the way
in which carriers or cases were ascertained. For
example, in the case of β-thalassaemia minor, the
commonest diagnostic method was measuring the
levels of HbA2. However, different thresholds were
applied. Although most studies used >3.5%, some studies used 3.4, 3.6, 3.9 or 4.0% as
the cut-off point. Furthermore, some studies used the naked-eye single-tube red-cell
osmotic fragility (NESTROF) test, others used capillary electrophoresis to measure HbA2,
while others still used high-performance liquid chromatography or reverse dot-blot
hybridisation. Furthermore, other studies checked for specific β-globin gene mutations
using DNA sequencing. Some studies had two stages of screening, in which they would
check the levels of HbA2 and then perform DNA sequencing on those who were positive
in the first stage. This diversity of methodology is understandable since each diagnostic
test has a different cost and each research team in the each of the studies did not have
Having simple and
adequate laboratory
methods to identify
carriers in the target
population, with minimal
error rates.

31
the same amount of funding or resources available to them. However, this precludes an
accurate comparison of different studies. Therefore, any comparisons that do occur
should be made with caution.
In the literature review the sample size varied from 120 participants to 4.6 million. The
median sample size was 1,272 participants.
CARE NOT TO INTRODUCE BIAS. The way population
samples are selected is variable and a variety of
methodologies were employed. The vast majority were
cross-sectional (over a period of a few months) or
prospective studies (lasting more than one year).
Recurring themes included (a) screening camps in
specific rural/tribal communities, (b) blood donors, (c)
pregnant women visiting antenatal clinics, (d) couples
seeking premarital screening (mandatory or voluntary),
(e) healthy subjects receiving routine health checks, and (f) newborn screening and
students. Very few studies applied multi-stage clustered or stratified sampling, which
would be the most reliable way to minimise the risk of bias. Furthermore, many studies
were not very clear as to how they selected their participants and the sampling
methodology was only implied or omitted completely. This means that an assessment
of the risk of bias cannot be made with confidence and thus there is significant
uncertainty about the external validity (generalisability) of the results. It is important to
mention that studies were excluded if they involved participants that were referred for
thalassaemia screening specifically because of anaemia or clinical suspicion of
thalassaemia or known family history. Such a sample would be heavily biased and would
not allow for an estimation of thalassaemia prevalence that is representative of the
general population.
STATISTICAL ANALYSIS. In this recent review of the literature, the most striking finding was
that only three studies reported 95% confidence intervals along with their point
estimates. Considering that science is the study of uncertainty, the application of well-
established methods to quantify this uncertainty should be pursued. Another
observation was that since most samples were non-probabilistic, weighting could not be
applied to the individual measurements. In the case of probabilistic sampling, it was not
always clear if and how weighting was applied.
The sample size is
adequate and
unselected to reflect
the defined population.
MICROMAPPING. The importance of micromapping cannot be overemphasised, since even
in relatively small countries the distribution of thalassaemia is uneven, with some areas
or tribal groups being more affected than others. This observation was recognized many
years ago and has been related to a possible relationship with the historical malaria
prevalence in a specified region8
. For a more accurate estimate of the number of
carriers, the number of at-risk couples and the need for service planning, the local data
for a country are good indicators of where to locate services and the size of services to
meet real needs. Micromapping is an essential exercise9
that is rarely found in practice.
Examples of such efforts are given below, including those of Iran and Azerbaijan.
Micromapping provides information about geographic variations and should provide
more accurate prevalence data on which to base calculations concerning birth incidence
and other indicators of the burden of disease.
Figure 1. β-Thalassaemia carrier rates across the World, based on data gathered by TIF.

33
Figure 3. HbS (SCD) carrier
rates across the World,
based on data gathered by
TIF.
Figure 4. World distribution
of Malaria, from mid-19th
century to 2010.
Figure 2. HbE carrier rates
across the World, based on
data gathered by TIF.
The following portray results from selected countries with a significant birth incidence
of β- thalassaemia patients, and for which data has been collected. In addition, European
countries affected by the recent migrations have also been included. Data are derived
from published literature, TIF country visits and reports (including those obtained in the
course of conferences). Countries have been grouped in regions as defined by the World
Health Organisation.
EASTERN MEDITERRANEAN REGION
BAHRAIN: This is a small country of around 1.5 million people. It has a very high HDI and
a health expenditure/ cap of over 11,000$. IMR is 5.9/1000lbs and under-5 mortality rate
of 6.9/1000lbs. These are indicators of a well-developed health system and there is
universal health coverage. Sickle cell syndromes are predominant, but the β-
thalassaemia carrier rate is also significant. The Hereditary Disease Programme started
in Bahrain in 1984; in 1991 a National Committee for Prevention of Genetic Disease was
formed to plan the control programme of these diseases in the country. The prevention
strategy consisted of health education, screening and counseling programmes. A law
(Government Gazette: Issue 2640, 23rd June 2004) was passed which made premarital
counselling mandatory (implemented in 2005). Premarital counselling is provided by
physicians supported by trained health nurses at all health centres and is based on
clearly defined protocols and guidelines laid down by the Ministry of Health.
The sickle cell trait in a sample of 60,424 students was found to be 13.3%10
. This rate was
confirmed in an unpublished survey of 82,000 pupils in 2012 (13.05%) (reported by Al
Arrayed and Al Mahdi). The β-thalassaemia carrier rate was reported as 2.9% in a survey
of 5,685 pupils11
. For this reason β-thalassaemia is a significant contributor to the
disease burden in Bahrain.
PART 1
THE EPIDEMIOLOGY OF Β-THALASSAEMIA AND SICKLE CELL ANAEMIA

35
The total consanguinity rate and the first cousin marriages rate in 1990 were 39% and
24% respectively, while the rate was reduced to 11% and 7.8% respectively in 2007;
denoting a 66% decline (from an unpublished report by Al Arrayed). Based on these data,
the expected homozygote β-thalassaemia annual affected births would be 4, while 117
would have sickle cell syndromes including S/S and S/β thalassaemia. It is noted that in
this calculation we have ignored the quoted coefficient of consanguinity due to the
expected continued reduction in cousin marriages.
Hence, Bahrain has a very high burden of haemoglobin disorders, but a well-structured
service led by the Ministry of Health, which deals successfully with these syndromes,
both in terms of prevention and clinical care.
EGYPT: A populous country of over 100 million people. The large population makes health
issues difficult to manage. Its health expenditure/ cap is 112$. IMR is 17/1000lbs and
under-5 mortality 24/1000lbs. Income /cap is low at 3,020$ and even though financial
support for a chronic condition like thalassaemia is free-of-charge for patients under the
age of 18, older patients are still not fully covered. All elements of prevention, screening,
prenatal diagnosis and preimplantation genetic testing are available, but not as a
nationally coordinated policy; since the population is poorly informed, uptake of these
services in order to make an impact on the health burden, is limited.
The national response is running behind the real needs, which are quite high given the
carrier rate for β-thalassaemia which has been estimated to vary between 5.3% - 9% in
various surveys12
. Sickle cell trait is confined to specific oasis, so that in the general
population the rate is about 0.3%. Based on these figures it is expected that
0.702/1000lbs will have homozygous β-thalassaemia and 0.082/1000lbs will suffer from
sickle cell syndromes. On the basis of the current population, this adds up to just under
2,000 thalassaemia births per year and around 230 sickle cell births. If all expected β-
thalassaemia births were to survive to 10 years then there should be at least 20,000
living patients receiving treatment. Current reports from physicians and clinics (there is
no national register) indicate around 10,000 patients of all ages are receiving treatment.
This suggests a considerable loss of children due to haemoglobin disorders.
Alpha thalassamia is less common in Egypt since in one study based on neonatal
samples and molecular analysis, 3.1% had one α-globin gene deleted and 4.2% had two
(see section on alpha thalassaemia further down).
Thus, Egypt is a country with a rapidly increasing population with scarce resources
allocated to chronic diseases as a result of its many other health priorities. Expertise in
thalassaemia management is not lacking and bibliography from academic centres is
prolific on the subject. National prioritization of haemoglobin disorders, including
prevention, should be promoted.. Full insurance coverage is provided for young patients
but this is partial for adults, resulting in severe out-of-pocket expenses.
IRAN (ISLAMIC REPUBLIC OF): Another large country of 85 million people with a large burden
of thalassaemia and sickle cell disease that has resulted in much effort being applied by
the authorities to address the issue. All health indices are improving with the IMR
12.4/1000lbs (17.7 in 2009) and under-5 mortality of 14.4/1000lbs in 2018. Health
expenditure/capita is 1,372$ but development is severely limited by difficulties in foreign
trade due to political embargo13
.
Assessing the disease burden has been an ongoing exercise in Iran and the carrier rates
of each administrative district have been calculated (Fig 2)14
. Calculating from the
reported population of each region, the population who are carriers amount to 4.56% of
the total population. To have an accurate a picture as possible of the expected births,
the actual births of each region should be known so that an estimate of affected births
can be calculated according to the Hardy Weinberg rule. Even so, high carrier rates in
some nomadic groups are not included in the micromapping exercise15
. Taking the
overall rate of consanguineous marriage into account, reported as 38.6% with a mean
inbreeding coefficient of 0.018516
, the expected thalassaemia births is 700 per year. The
overall sickle cell carrier rate is 1%, with the highest prevalence in south west Iran, mainly
in Khuzestan province, where the rate reaches 7%17
. Micromappingof the whole country
is not reported, therefore it is difficult to estimate birth incidence of sickle cell disease
(SS + S/β thalassaemia), which could be as high as 300 per year.
Iran, with these estimates, has a high prevalence of haemoglobin disorders in its
population. According to current reports, there are 18,777 transfusion dependent
patients and 2,000 non-transfusion dependent patients, along with 2,000 sickle cell
patients living in the country. In 201618
the annual cost to treat each patient with major
thalassaemia was estimated to be 8,321.8$ according to World Bank data GDP/capita in
2017 was 5,520.3$. Average family income would be less and so universal health
coverage supports patients, even though access to some services (such as MRI) is limited.
A national prevention policy has been implemented over the last 25 years and has
limited new births (for more information see Chapter on Prevention).

37
Figure 5. Micromapping of β-thalassaemia in Iran (from Miri M. et al 2013)
IRAQ: This is a country which has suffered much political and civil upheaval in the last few
decades that has made it difficult to take advantage of its oil revenue to support its
health service19
. Health indicators have been improving steadily over the years. IMR is
still high at 21.8/1000lbs and an under-5 mortality rate of 25.9/1000lbs. Health
expenditure per capita is low at $210.3.
The haemoglobinopathy burden is considerable; the overall carrier rate for β-
thalassaemia is quoted to be 4.8%, even though data on all provinces is not available.
The highest carrier rate is reported from Erbil province20
at 6.94% (with a total population
of almost 3 million), while most provinces report around 4% carriers. Sickle cell carriers
are prominent in the southern governorates, mainly Basrah21
where 6.5% carry the S-
gene compared to less than 1% in the northern Kurdish populations. It is expected that
at least 600 new births with β-thalassaemia syndromes will be born each year and
around 200 with sickle cell syndromes.
The latest information received by TIF from Ministry of Health officials is that there are
17,000 β-thalassaemia patients and 6,075 sickle cell patients receiving treatment.
Management of these patients according to published reports is suboptimal compared
to western standards, with a median age of 13 years (1-35)22
. A more recent report at
the 2019 Arab Thalassaemia Forum (unpublished) the following emerged:
 Pre-transfusion haemoglobin is <7g/dl in 35% of patients, 7-9g/dl in 50%, and
only in 15% of patients is it kept over 10g/dl.
 47% of patients experience various transfusion reactions.
 1% are infected by transfusion transmitted infections (TTI).
 MRI is available in Baghdad only.
 Complications recorded are in the heart (30%), hypoparathyroidism (13%) and
osteoporosis (14%).
 Poor compliance to iron chelation is witnessed generally.
 Peak age of patients is between 16-25 years.
 Secondary education in patients over the age of 16 years is completed by 6.6%
and university by 2.8%.
 Causes of death are due to infections (38%), cardiac complications (74.5%) and
severe anaemia (4.2%).
A policy and action plan for haemoglobin disorders is underway by the Ministry’s
Advisory Committee on Haemoglobin Disorders in an effort to address these issues.
Insurance coverage is universal but not all services are available.
JORDAN: The β-thalassaemia carrier rate in Jordan reflects those in much of the
neighbouring Arab populations with a variable rate across the country23
, ranging from
3.04% to 3.5%. General health parameters are improving with IMR now at 12.8/1000lbs
and under-5 mortality rate of 16.2/1000lbs. Health expenditure per capita is low at
340.66$ and income / capita 4,330$. First-cousin marriages have declined from 28.5%
(marriages contracted between 1950 – 1979) to 19.5% (marriages contracted after
1980)24
. Sickle cell carriers are 3.17% according to a newborn screening sample from
north Jordan25
, while in a sample 1,000 subjects 1% were identified to be carriers26
. These
were studies by the same group in the north of the country, while other regions of the
country have no published data. It is assumed that in Jordan at least 1.5% of the total
population are carriers of AS until a nationwide survey is carried out. With these
assumptions, there should be 80-100 new β-thalassaemia births annually and about 80
new cases with sickle cell syndromes.
The number of known patients recorded by TIF’s contacts is 1,300 thalassaemia patients
and 150 sickle cell patients. In a country of 10.8 million this is a significant burden on the
health services (exactly half of the total for Greece in both carrier rates and number of
patients – see more information below).

39
Jordan has implemented a premarital screening programme supported by the choice of
prenatal diagnosis. In the 2019 Arab Thalassaemia Forum, the effect of Jordan’s ongoing
prevention programme was estimated at around 50% prevention of new affected births,
but with no formal figures to confirm. Patient care is supported by the health service,
but it is unclear whether quality of care meets high standards. In a 2018 publication the
most reported clinical complication was facial deformity in 86.9%, which suggests under-
transfusion of patients27
.
SAUDI ARABIA: This is a high income country with a GDP/capita of 23,139$. This has
allowed the development of treatment centres of high quality and the provision of
universal health coverage, at least for the indigenous population. The major
haemoglobin disorder in this country is sickle cell disease. The Saudi Premarital
Screening Programme estimated the prevalence of the sickle cell gene in the adult
population at 4.2% for sickle-cell trait and 0.26% for SCD, with the highest prevalence
noted in the eastern provinces (approximately 17% for sickle-cell trait and 1.2% for
SCD)28
. In the eastern provinces there is also a high β-thalassaemia rate estimated at
3.4%29
. The distribution of the major haemoglobinopathy syndromes is accurately
pictured by the premarital screening programme30
, that has been active in the country
for many years now as depicted in Table 2 below (borrowed from Alsaeed, 2017)31
.
Table 2. Prevalence rate for β-thalassaemia and Sickle Cell disorders by region, in Saudi Arabia, 2011 –
2015.
Based on this information and population figures from each province (2017), then the
total carrier prevalence for β-thalassaemia is 1.2% and for AS 4.66%. These figures are
derived mainly from the Saudi population, while non-Saudi residents affect these totals
mainly in so far as β-thalassaemia is concerned; but also introducing HbE (at a rate
potentially reaching 1.9%). The expected births for thalassaemia is expected to be 130
per year while for SCD the figure is much higher, at 420.
In 2004, the Health Ministry issued a Royal Decree, that made premarital screening
compulsory for potential partners. This programme has met variable success since
marriage cancellation has not been fully accepted (for more information see Chapter on
Prevention).
In the absence of a national patient registry, it is not possible to have accurate data on
the number of patients. However, it is estimated that there are around 9,000
thalassaemia patients and 26,000 sickle cell patients in the country. The National
Guidelines for Blood Safety and Transfusion Services are based on international
standards and all three iron chelation drugs are available. However, only a small number
of hospitals offer a multidisciplinary monitoring service.
National health insurance covers all of the indigenous population while expatriates,
which represent around 30% of the total population, have a mandatory health
insurance. The majority of expats (around 90%) are from high prevalence countries.
Figures 6 & 7 Carrier rate for β-thalassaemia and Sickle Cell disorders of provinces, in Saudi Arabia.
KUWAIT: Kuwait is a petroleum based economy and one of the richest countries in the
world – 4th richest in per capita income. Universal health coverage is available to all
Kuwait nationals. A public health insurance scheme allows non-citizens to utilise these
services at the cost of 50 KWD per year. Expats, however, make up around almost 70%
of the population. Since they originate mainly from Arab and Asian countries with a high

41
haemoglobinopathy prevalence, there are many patients with these disorders in the
expat community and many have actually been born in Kuwait. The quality of health care
in Kuwait is generally high. Infant mortality ratio is currently reported as 6.8/1000lbs and
under-5 mortality rate of 8.1/1000lbs.
Concerning the epidemiology of haemoglobin disorders, much reliance is put on the
data accumulated by the premarital screening programme, which was initiated in 2014
as an obligatory programme aiming to reduce ‘un-safe’ marriages. From the first 130,000
tests (unpublished data) the results indicate the following:
 β- thalassaemia carriers: 2.2%
 Sickle cell carriers: 1.99%
 Other variants: 0.5%
These findings are in contrast to the findings of a study published in 2002 on 2,386 cases
where the β-thalassaemia carrier rate was reported as 14% and HbS as 6%. This may not
have been a random sample32
. The results of the population screening are regarded as
more accurate because of the large sample and with selection bias less likely. Based on
these figures and according to the Hardy-Weinberg rule, the birth incidence based on an
annual birth rate of 13.77 (2019) and a total of 63,737 reported births in 2018 is as
follows.
CLINICAL CATEGORY
EXPECTED NO. AFFECTED PER 1000 LIVE
BIRTHS /YEAR
ANNUAL TOTAL NO. OF EXPECTED
AFFECTED BIRTHS
Β-THALASSAEMIA 0.121 8
HBS/S 0.099 6
HBS/Β-THALASSAEMIA 0.219 14
This calculation has not included the consanguinity coefficient, which for Kuwait is
reported to be 0.02.
The premarital screening has now exceeded 300,000 tests and 218 at-risk marriages
were prevented, but the current birth incidence birth incidence is not known. A national
patient registry is an urgent requirement. The estimated patient population is 475
thalassaemia patients and over 600 sickle cell patients. As far as patient care is
concerned, a national reference centre is under consideration with a multidisciplinary
team, to be housed in new hospital premises currently under construction. A newborn
screening policy has been decided and at the time of writing, is about to start.
LEBANON: A country with developed health services and satisfactory health indicators,
despite political upheaval. IMR is currently at 6.8/1000lbs and under-5 mortality rate of
7.4/1000. Health expenditure per capita is 901$ and income per capita 19,500$.
However, it is a middle-income country (HDI 0.730 which ranks high) with a healthcare
system that provides limited social protection for its citizens (for more information see
Chapter on Social Protection). The creation of the Chronic Care Centre (CCC), supported
by both private funds and government funding, has enabled the provision of free care
to patients, and the effective management of the national prevention programme, based
on mandatory premarital screening (for more information see Chapter on Prevention).
Screening programmes showed a carrier rate of 2.3% for β-thalassaemia in the general
population33
. Neonatal screening of 10,095 neonates indicated 1.8% carriers of HbS, and
0.04% HbC. Geographical clustering of sickle cell was noted in 2 regions: North Lebanon
(50. 66%) and South Lebanon (30. 26%)34
. Apart from regional variations, there are
marked differences in the various religious groups, which are important since marriages
are likely to be within each group; and cultural differences will affect the response to the
prevention programme. These differences are identified in a study based on the
population of thalassaemia patients, where 42% of patients were from the Shia
community (27% of the total national population), 36.2% from the Sunni (27% of the total
national population), 11.9% from the Maronite community (21% of the national
population), 5% Orthodox Christians (8% of the national population) and 2.3% Druze
(5.6% of the national population)35
.
The latest figures from the CCC report 375 thalassaemia patients and 387 sickle cell
patients, who benefit from high level clinical care and take part in clinical trials.
OMAN: This is a very high HDI ranking country with well organised health services.
Current health indices indicate an infant mortality rate of 6.8/1000lbs and an under-5
mortality rate of 11.4/1000lbs. Haemoglobin disorders are in this population as
demonstrate by a neonatal survey of 7,837 babies, where 5.46% were found to carry a
HbS gene36
. Micromapping of the country was conducted in 200337
by screening 6,342
children under 5 years of age, with overall findings: S-trait 6%, β-thalassaemia 2.1%, HbD
0.6%, HbE 0.3%, HbC 0.02%, G6PD 25% (M) and 10% (F)
REGION/ POPULATION
IN 2017
SICKLE CELL TRAIT % Β-THALASSAEMIA TRAIT %
NORTH SHARQIYA
(279,223)
10
(27,922 carriers)
1.1
(3,071 carriers)
SOUTH SHARQIYA
(312,822)
3.9
(12,200 carriers)
1.2
(3,754 carriers)

43
DAKHILIYA
(490,900)
9
(44,181 carriers)
2
(9,818 carriers)
MUSCAT
(1,380,509)
8
(110,440 carriers)
2.8
(38,654 carriers)
SOUTH BATINAH
(2019 - 316,491)
7.9
(25,003 carriers)
1.5
(4,747 carriers)
NORTH BATINAH
(519,660)
2.9
(15,070 carriers)
3.9
(20,267 carriers)
MUSANDAM
(31,425)
4.7
(1,477 carriers)
1.6
(503 carriers)
DHOFAR
(458,734)
0.2
(918 carriers)
0.2
(918 carriers)
DHAHIRA
(224,225 IN 2019)
3.9
(8,745 carriers)
1.7
(3,812 carriers)
AL WOUSTA
(42,111)
0 0
TOTAL POP = 4,056,100
6.06%
(245,956)
2.1%
(85,544)
Table 3. Regional Micromapping in Oman
With these carrier rates, it is expected that 0.205/1000lbs (18 – 20 new cases /year) on
current birth rate) new births of β-thalassaemia syndromes are expected yearly, and
1.53/1000lbs of sickle cell syndromes (about 134/year on current birth rate). This
calculation does not include the effect of consanguinity (coefficient 0.018)
From a TIF visit in 2019, it was noted that 591 β-thalassaemia patients were being
followed in 2 central thalassaemia centres and some smaller centres in the periphery.
These are regularly followed according to guidelines in the University centre, while in the
general hospital there was a lack of multidisciplinary teamwork. The peak age is 20-30
years, with older patients increasing. Sickle cell patients are less regularly followed, and
their numbers are estimated to be about 8,000.
Like all Gulf States around 2 million (45% of entire population) expatriates live in Oman,
most of whom are workers from India, Pakistan, Bangladesh, Morocco, Jordan, and the
Philippines, all high prevalence countries. These expatriates are not covered by the
national health insurance scheme and so are expected to hold private insurance. The
real numbers of haemoglobinnopathy patients in the expat community is not known.
Figure 8 β-Thalassaemia
carrier rates of provinces in
Oman based on data
gathered by TIF.
PAKISTAN: A country with a very large population of 233 million, of which 60% live in the
province of Punjab, where there are also the most organised services. Much of the
population, around 60%, live in underdeveloped rural areas and health expenditure per
capita is very low (22.56$) while income per capita is also low at 2,500$. This means that
Figure 9. SCD carrier rates of
provinces in Oman based on
data gathered by TIF.

45
as far haemoglobin disorders are concerned the prevalence and chronicity of these
conditions has led charity organisations to take over the creation of treatment centres;
many of which have developed their own blood banks and laboratories to support
clinical care. The quality of the services offered by these centres varies considerably, as
does the level of out-of-pocket expenses expected from families38
. Some patients pay
for blood transfusion and most pay for blood filtration. Laboratory tests are almost
always paid out-of-pocket. A charity organisation at national level, Bait-ul-Mal, has also
created treatment centres and provides financial support to many families. Regional
governments support screening programmes, especially in Punjab and Sindh. Prenatal
diagnosis is available in major urban centres (acceptance of termination of pregnancy is
based on fatwas1, expressed at various times and locations39
).
Concerning the epidemiology of β-thalassaemia, there are regional and tribal
differences in the prevalence of carriers. Some data (from Dr Suhaib Ahmed40
) are
available concerning these differences (based on this there are 10-11 million carriers or
4.5% of the total population):
REGION REGION POPULATION CARRIER RATE (%) EST. NO. OF CARRIERS
Punjab 100 million 4.6% 4.63million
Pathan 25 million 5.2% 1.3million
Sindhi 49.8 million 4.3% 2.1 million
Beluchi 12.3 8.0% 1 million
Urdu speaking 30 million 5.3% 1.6 million
In one study in Karachi in the province of Sindh, involving 202,600 subjects, the carrier
rate was 5.2%.
Based on this data, it expected that 0.9-1.0/1000lbs will be affected by β-thalassaemia
and 0.077/1000lbs by sickle cell disease. With 6.4 million births per year in Pakistan, this
means an estimated annual 6,334 affected births with thalassaemia and 490 annual
affected births with sickle cell.
It is difficult to estimate the actual number of patients. Quality of care is variable, and for
the majority poor, so mortality in the early years is expected to be high. If all patients
survive to 10 years then at least 60,000 patients should be living, and this is the figure
quoted by local experts. In a recent study41
from 4 centres, approximately half (52%) of
the patients demonstrated severe myocardial iron overload (T2* <10 ms) and the
1 A ruling on a point of Islamic law given by a recognized authority.
majority (58%) were not on adequate chelation therapy. Another characteristic study,
reflecting not only Pakistan but most of Asia, refers to patient outcomes who are
seriously undertreated42
.
In large countries with limited resources, keeping up with chronic and complex
conditions is difficult. Pakistan, through an increasing private/public collaboration,
acknowledged during a TIF visit in 2016, has been making serious efforts to raise
standards. More control of the NGO / charity services, especially concerning quality of
blood for transfusion is in progress.
PALESTINE: The development of healthcare services is challenging in Palestine, with a
population divided between the West Bank and Gaza. This division, as well as other
political and social considerations is reflected in the health indicators which are
moderately high - IMR is 16.6/1000lbs (2019) and under-5 mortality rate of 19.4/1000lbs.
The carrier rate for β-thalassaemia in Gaza, calculated from 21,825 samples from the
premarital screening programme, has been found to be 2.6%43
. Prevalence rate of
carriers of the beta globin gene is 3.5 – 4% (1996). The prevalence of β-thalassaemia trait
in West Bank region is 3.5%44
. The sickle cell gene is less prevalent, and reported to be
1.2% in the West Bank and 1% in Gaza.
Based on these estimates, the birth rate for β-thalassaemia patients is expected to be
0.4/1000lbs, 0.04/1000lbs for HbSS and 0.25/1000lbs for β thalassaemia/HbS. Therefore,
in accordance to the current total births, and without considering prevention, the
expected annual affected births would about 53 with thalassaemia and 39 with sickle
cell disease. The most recent information (2018) from the local patient association
indicate the existence of 689 thalassaemia patients and about 200 with sickle cell
disease.
Obligatory premarital tests were adopted in Gaza in 2000, and within ten years the
number of new β-thalassaemia births had dropped to zero43
. Similar results have been
shown in the West Bank. Some residual births do occur, but prevention remains effective
with an over 90% reduction of new affected births. Prenatal diagnosis is accepted as part
of the programme. For more information see Chapter on Prevention.
Government health insurance covers 75% of the population in both Gaza and the West
Bank. This allows free treatment for all thalassaemia patients since 2009. However, the

47
political instability, especially in Gaza, limits the possibility of introducing services such
as multidisciplinary care. Despite this, basic care (including blood transfusion and iron
chelation) are provided and many patients are now in adulthood.
QATAR: A country with a well-developed economy and an income per capita of 65,000$,
which allows for well-developed health services. Infant mortality is at 5.7/1000lbs and
under-5 mortality rate of 6.8/1000. Carrier rates for β-thalassaemia are estimated to be
2 – 3%, while for sickle cell the rate is 5 – 6% in the indigenous population. However, 88%
of residents in Qatar are foreign migrants, mainly from the Indian subcontinent. With
such a large proportion of the population unstudied the number of carriers cannot
accurately estimated and thus predictions of affected births cannot be made.
According to TIF’s latest reports there are 500 patients being followed with sickle cell
disease and around 150 with β-thalassaemia in the country. The high standards of care
are reflected in the many publications made by the Hamad Medical Centre. Expatriate
patients can be covered by a Qatar expat health insurance plan.
TUNISIA: A country of the Mediterranean basin, Tunisia has both sickle cell and
thalassaemia.β-thalassaemia carriers are reported to be 2.21% of the population, while
the HbS trait is 1.89%46, 47
. Expected annual affected births are 0.122/1000lbs for β-
thalassaemia and 0.3/1000lbs for sickle cell syndromes. Despite the lack of systematic
prevention programme, prenatal diagnosis has been available since 199448
. The latest
report is of 742 thalassaemia patients and 1,526 sickle cell disease patients.
The HDI level is in the high level group (0.739), but health expenditure per capita is rather
low (250.5$), and income per capita at 4,405$. It is a middle-income country and health
services are producing indices which are as expected (IMR at 12.25/1000lbs and under-
5 mortality rate of 16/1000). Healthcare is free for all but there is a quality gap between
the capital city and the periphery, especially as far as the haemoglobin disorders are
concerned. The low level of health expenditure restricts the provision of
multidisciplinary care to few centres. In a centre-based study it was found that LIC was
over 15 mg/g dw in 25 % of patient 49
. This is in line with many clinical services across the
world and supports the presumption of suboptimal treatment being provided, especially
iron chelation.
UNITED ARAB EMIRATES: A Gulf State in the high income bracket and in the very high HDI
rank, the United Arab Emirates have an income per capita at 43,000$; about ten times
higher than that of Tunisia in terms of current USD. This is reflected in the health indices
where IMR is at 5.3/1000lbs and under-5 mortality rate of 7.5/1000.
Approximately 88% of the population are expatriates, with almost 4 million of which
originating from the Indian subcontinent. The burden of haemoglobin disorders is
expected to be high, as shown by Table 4.
SAMPLE TYPE
SAMPLE SIZE Β-THAL
CARRIERS
HBE
CARRIERS
HBS CARRIERS HBC
CARRIERS
REFERENCE
EMIRATI CHILDREN
262 9.7% 4.6% Miller CJ et al
2003 [50]
UAE NATIONALS,
REGIONAL,
PREMARITAL
6,420 4.73% (Hb
Lepore
added)
0.03% 2.9% Belhoul et al
2013 [51]
REGIONAL,
TRIBAL,
PREMARITAL
5,672 2.3% Denice y al 2013
[52]
BEDOUIN
394 3% Al-Dabbagh
2014 [53]
PREMARITAL,
REGIONAL
17,862 2.98% 1.05% Salama et al
2016 [54]
NEONATAL
SCREENING
NATIONWIDE
22,200 0.58% 1.5% Emirati
0.8% non-
citizens
3.2% Al Hosani et al
2005 [55]
NEONATAL
SCREENING
NATIONWIDE
750 365 0.83% (overall) 0.02% Al Hosani et al
2014 [56]
Table 4. Carrier rates in the United Arab Emirates
These studies demonstrate that there is an uneven distribution of haemoglobin
disorders across the Emirates. It should be noted that most of these studies refer to the
indigenous population, while the migrant population (around 80% of the total national
population) may also contribute to the disease burden, since as seen in the other Gulf
States, migrants are mostly from the Indian subcontinent, with a high
haemoglobinopathy prevalence. Since only the neonatal studies refer to the total
population and not just to Emirati citizens, we can only conclude that the HbS gene is
carried by around 1% of the indigenous population. The β-thalassaemia gene frequency
is less clear. The premarital screening sample of nearly 18,000 individuals54
however has
shown a 3% carrier rate and is most likely to approximate the truth. With these figures

49
the expected annual affected births of β-thalassaemia syndromes would be
0.230/1000lbs and 0.175/1000lbs with sickle cell syndromes.
Reported thalassaemia patients are about 1,000, and the number of sickle cell patients
is unknown. The level of care is high with reference centres in major cities, which adhere
to good clinical care guidelines. The large expat population is not covered by the national
system, but by private insurance, and charity organisations support thalassaemia
patients to a significant degree. Even though reports on clinical outcomes are not
published, the increasing use of the electronic medical records for thalassaemia in the
United Arab Emirates57
is expected to provide such data in the future.
EUROPEAN REGION
The countries selected for this report are generally chosen because of their high birth
incidence of β-thalassaemia; nonetheless, in Europe a broader epidemiological study is
attempted to include countries where at the present time migrations are impacting the
epidemiological scene. The extent to which this is happening may challenge, now and in
the future, the already robust national health services of many EU Member States.
Considered under the umbrella term ‘rare disorders’ (as defined by the European Union),
the increasing prevalence of this complex group of disorders requires further
monitoring in the years to come.
ALBANIA: This is a country of just over 3 million people, which has been developing
economically over the last few years; the HDI score was 0.644 (medium) in 1990, rising
to 0.791 (high) in 2018. Income per capita was 5,353$ in 2019 however out-of-pocket
health expenditure is still high. Nonetheless, health indices are improving and the IMR
is now at 8.6/1000lbs from a recent (2011) 10.8/1000. Under-5 mortality rate is at
9.7/1000. A good level of care for thalassaemia patients is therefore expected; this seems
to be best achieved in Tirana and Lushnja. The rest of the country, especially in the
southern high prevalence regions, services for thalassaemia are still very basic. Full free
iron chelation was introduced in the list of reimbursable drugs in 2018, according to the
Compulsory Health Insurance Fund (HSCSA); this involved mainly generic deferasirox.
The β-thalassaemia carrier rate is recorded as being 5%, while HbS is 1.4%. It is estimated
that the overall carrier frequency of β-thalassaemia and sickle cell anaemia is about 8%.
The distribution is not even; the Adriatic coast, especially the region of Lushnja, has a
high prevalence of β-thalassaemia (5.2%) as well as HbS (3.2%)58
. A complete nationwide
survey has not been conducted to-date. Based on limited data, the birth estimate for β-
thalassaemia is estimated at 0.6250/1000lbs and 0.350/1000lbs for sickle cell
syndromes. According to recent figures from the patients’ association, there are 356
thalassaemia patients and 174 sickle cell patients.
Albania has a universal healthcare system which is as yet underfunded, and thus
thalassaemia patients do not benefit from coordinated multidisciplinary monitoring.
Rough indicators of clinical outcomes include a rate of alloimmunization of 22.8%59
, HCV
positivity of 28% and 12.6% HBsAg positivity60
. Shortages in blood supply were still
reported in 2017 and hospital conditions where patients receive treatment rather poor.
There is no MRI T2* scanning in Albania.
AZERBAIJAN: Micromapping of Azerbaijan for β-thalassaemia carriers has been reported
by Hajiyev AB. at the 5th
International Summer school 200861
(Figure 11). From this map
the great variability in the distribution of carriers is demonstrated, showing the existence
of hot spots. An overall carrier rate of about 10% is estimated based on this data. Earlier
similar studies by Kuliev62
(1994) suggested a 6% carrier rate. A more recent summation
of the premarital screening programme (2015 – 2018) with 430,668 individuals tested,
found 3.71% to be carriers (Asadov C et al, abstract at the 10th Eurasian EHOC
Congress63,64
). These are widely disparate results.
Figure 10. Micromap
Borrowed from Kuliev, 1994

51
Figure 11. Regional mapping. Borrowed from Hajiyev 2008:
Reports on the premarital screening programme in 2017 and 2018 are based on large
population samples from all over the country, and include molecular verification where
necessary; these are likely to be the closest to the truth. If 20% of these marriages are
consanguineous (previously reported coefficient 0.0103), then the true carrier rate may
be even lower, taking into account that in recent years’ urbanization may have reduced
this practice. The national screening programme shows an expected annual birth rate
for β-thalassaemia of 0.344/1000lbs and 0.148/1000lbs for sickle cell syndromes.
The total thalassaemia patients are estimated to be 1,300 while there are also around
200 sickle cell patients. Most patients are treated in the Republican Thalassaemia Centre
in the capital city of Baku, including those living outside the city.
Treatment is provided free for all patients. However, multidisciplinary care is not
established and patient referrals to specialists is largely for treatment, rather than for
monitoring and secondary prevention. The low blood donation rate is speculated to be
the cause of a low pre-transfusion Hb. There are also concerns about the high
transmission of hepatitis C (20 – 25%). Measurement of cardiac and liver iron by MRI is
not available. Despite these drawbacks, still true in 2019, there is a steady improvement
in patients’ care. This also reflects the steady improvement of the overall health
performance in the country, as shown in the decline of the IMR from 54.6/1000lbs in
2009 to 18.2/1000lbs in 2020. Likewise, the under-5 mortality rate was at 45.6 in 2007
and is now at 20.4/1000.
BULGARIA: The carrier frequency of β-thalassaemia in Bulgaria has been found to be
2.5%65
, with no HbS in the indigenous population. As in other countries the geographical
distribution of the affected population is not even, and according to local experts
(unpublished) there is an average of 6% carriers in coastal areas. By calculation, the
expected births are 0.1563/1000lbs, which roughly translates 9 – 10 cases per year.
There is no national registry but an estimated total of 270 – 300 patients are followed in
the 3 main centres (Sofia, Plovdiv and Varna). Thalassaemia patients are covered by the
National Health Insurance Fund.
The health services in Bulgaria are able to support chronic diseases like thalassaemia
and the main treatment centres are able to offer treatment according to accepted
guidelines. The effectiveness of the health infrastructure is reflected in an IMR of
5.6/1000lbs and an under-5 mortality rate of 6.7/1000lbs.
AUSTRIA: A central European country with a very low carrier rate of haemoglobin
disorders in the indigenous population. Recent migrations from countries of high
prevalence have introduced increasing numbers of carriers, and presumably patients,
suffering from these conditions. The carrier rate and patient prevalence for either
condition (v. thalassaemia or sickle cell disease) in Austria are not known since there is
no national registry. Physicians estimate around 60 patients throughout the country.
COUNTRY OF ORIGIN IMMIGRANTS MPI DATA CARRIER RATE (%) EST. TOTAL NUMBER OF CARRIERS
Albania 1,834 1.4 26
Brazil 2,722 9.8 267
Greece 3,060 0.53 16
India 8,163 6 490
Iran 11,459 1 100
Iraq 3,101 1 22
Italy 26,099 2 522
Lebanon 1,147 2 23
North Africa 13,433 1.64 220
Nigeria 2,913 22 641
Other Africa 6,205 12 744
Pakistan 2,197 0.25 5
Turkey 125,026 0.44 550
TOTAL 207359 1.75 3,626
Table 5. Sickle Cell carriers in Austria

53
In a study conducted by TIF in 2015 (unpublished), it was noted that 3.3% of the Austrian
population i.e. 285,538 were migrants, all originating from high prevalence countries;
170,000 of these had arrived within the last 5 years. This number may have increased
even more during the 2016 refugee crises. It is expected that since 2010 haemoglobin
disorders would have increased considerably across the country. Sickle cell is not
included in the national neonatal screening programme.
Like most European countries, Austria has robust health infrastructure with an IMR of
3/1000lbs and an under-5 mortality rate of 3.5/1000lbs. Haemoglobin disorders are still
very rare and treated in paediatric and adult haematology departments, mostly in
Vienna. Each clinic has a small number of thalassaemia patients, with the adult clinic in
Vienna having 15 – 20 patients (TIF visit report 2019), and the paediatric clinic 20.
Expertise in case management and the development of reference centres in Vienna to
support peripheral centres are ongoing initiatives.
BELGIUM: Academic centres introduced a neonatal screening programme for major
haemoglobinopathies in Brussels in 1994 which has since expanded across Belgium.
The first 10-year report of this programme was reported in 2006 [66] indicating that
1:1,849 new-borns were identified as having sickle cell disease. Three years later (2009)
this rose to 1:1,559 [67]. This did not change significantly in subsequent years [68], until
2017 (for both homozygotes and heterozygotes). These results are based on data from
Brussels and Liege, while other regions do not participate in the neonatal screening
programme.
A haemoglobinopathy patient register is maintained in the country, according to which
at the end of 2012 a total of 469 sickle cell disease patients were registered; in 2018 this
had risen to 538 patients, of which 285 were born in Belgium while the rest were born
in other regions than those covered by the neonatal screening programme, or from new
immigrant families. Thalassaemia patients are fewer in numbers, estimated to be less
than 100 however, and recent data have not transpired. Survival data on sickle cell
disease are reported [69], but none on thalassaemia due to the extremely confined
number of patients. Belgium has robust health infrastructure with an IMR of 5.6/1000lbs
and an under-5 mortality rate of 6.7/1000lbs.
CYPRUS: A small island in the eastern corner of the Mediterranean Sea, Cyprus has a
population of 1.2 million inhabitants. Its two main ethnic communities, Greek and
Turkish, have the same carrier rates for both β-thalassaemia and sickle cell disease [70]
and the same molecular distribution. The prevalence of thalassaemia is one of the
highest in the world, posing a major public health challenge. More specifically, β-
thalassaemia carrier rate was estimated to be around 12% - 15%, while sickle cell disease
carriers are significantly less at 0.2% of the population [71, 72]. The α-thalassaemia
carrier rate was estimated to be around 20% [73]. With these figures the expected β-
thalassaemia birth rate is expected to be a high 5.5/1000lbs without any prevention
programme.
An interesting observation is that for the more rare haemoglobin variants, including the
sickle cell variant, there is a distinct geographical distribution, even on this small island.
During the screening process to identify carriers, the origin of parents is noted and so
geographical distribution is possible. This in recent years is a situation which has
changed with urbanisation and populations moving as political developments created
an internal refugee issue. According to the parental origins of individuals carrying the
sickle cell gene, HbS is almost confined to the north and east of the island, while the Hb
Lepore variant is confined to one district in the south and alpha chain variants to the
north and west. These are indications of a possible founder effect, which may not be so
obvious in larger populations. This is in contrast to the common β and α thalassaemia
mutations which are evenly distributed across the island.
Another interesting observation is the carrier rate of β thalassaemia in the indigenous
population appears to be falling in the generations following the eradication of malaria
in 1948 [72]. This may be the effect of removing the selection advantage of malaria
where haemoglobin disorders are concerned.
It should also be noted that Cyprus is receiving migrant populations from the Middle
East mainly amounting to 4% of the total population in 2021. These may affect
prevalence of haemoglobin disorders. At the same time intermarriage with northern
European groups has also reached significant proportions (having peaked at 25% of
marriages in the 1990s).
Cyprus was one of the first countries to introduce a successful population-wide
prevention programme for β-thalassaemia based on premarital screening, and, as a
result, the annual affected birth rate has decreased to less than five cases from an
expected 50 – 70 [71, Christou S., 2020, personal communication]. For more information
see Chapter on Prevention.

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