Transcript Slide 1

EPIDEMIOLOGY of Non-Transfusion Dependent
Thalassaemias: An Emerging Global Concern
Painting by: Loizos Loizou
25 OCTOBER 2012
For β-thalassaemia major:
I.Identification and recognition of essential components for effective CONTROL
strategies;
Prevention Management
II. Significant advances and initial optimistic outcome of research on FINAL CURE;
III. From childhood fatal disease to a chronic one with high survival rates and
good quality of life;
IV. POLITICAL COMMITMENT – PREREQUISITE – NATIONAL PROGRAMMES
LIMITED GLOBALLY.
Haemoglobin disorders, beyond β-thalassaemia major –
most prevalent in the developing world
Under-recognition of clinical importance of other Hb Disorders:
(i) β-thalassaemia intermedia and α-thalassaemia;
(ii) abnormal (or variant) haemoglobins, and;
(iii) combined forms.
Recognition of the problem and its magnitude came from improvements
(in more recent years) of:



Health Infrastructures;
Nutrition;
Public Health Sector:
Communicable diseases prevention;
Reduced Infant Mortality rates/ Under 5-years of age of mortality;
 Policies for Non-Communicable diseases (WHO Strategic Plan)
Adoption of one WHA (WHA59. R20) and one EB (EB118.R1) resolutions
on SCD and thalassaemia and Haemoglobin disorders, respectively
EPIDEMIOLOGIC TRANSITION
The Story Beyond β-thalassaemia major – Milder Phenotypes
 IMPROVEMENTS AT NATIONAL LEVEL HAVE ALLOWED:
BETTER SURVIVAL - PREVIOUSLY DIED UNDIAGNOSED/
MISDIAGNOSED
 REGIONAL AND GLOBALCOLLABORATIONS HAVE STRENGTHENED
OBSERVATIONS, STUDIES AND COMPILATION OF INFORMATION:
MOLECULAR BASIS,
GENETIC BACKGROUNDS
NATURAL HISTORY AND
CLINICAL PHENOTYPES.
BEYOND TRANSFUSION DEPENDENT THALASSAEMIAS –
MILDER FORMS
Primary forms include:
• β-thalassaemia intermedia
• Hb E/β-thalassaemia
• Hb H disease, and
• Combined forms (Extensive interactions between
different Hb genes).
Molecular studies and genotype/phenotype work have
confirmed - in recent years:
• Extensive phenotype variation from mild to moderate to
severe  TRANSFUSION DEPENDENCY
C.K.Li – 1st Pan-South China Workshop – Nanning 2012
-Thal/Hb
-Thal/HbEE
-Thal 2/Hb E
Hb E
-Thal 2
Hb
HbH
HDisease
Disease
-Thal
-Thal/Hb E
c --Thal 2
-Thal 1/-Thal
(-Thal 1)2
-Thal 1
-Thal 1
Hb
HbBart’s
Bart’sHydrops
Hydrops
,
Hb
Hb-H
HDisease
Disease
ccHb
HbCS
CS
,
Hb
Hb-AEBart
AEBartssDisease
Disease
ccHb
HbCS
CS
Hb Constant Spring
(Hb CS)
2
(Hb
(HbCS)
CS) 2
2
((-Thal)
-Thal)2
-Thal 1/Hb E
Hb E
(Hb E) 2
(More than 60 genotypes )
P. Fucharoen – 1st Pan-South China Workshop - Nanning September 2012
-Thalassemia / Hb E
990cases
Two mild alleles
+/E 24 (2.42%)
One mild allele
0/E 966 (97.58%)
Mild 22 (2.22%)
Intermediate 2 (0.2%)
-thalassemia
82 cases (8.28%)
Mild 80 (8.08%)
Intermediate 2 (0.2%)
Xmn I-158 G-gene
+/+
Mild 30 (3.03% )
Severe 6 (0.61%)
No known
modulating factor
Mild 178 (17.98%)
Intermediate 350 (35.35%)
Severe 320 (32.32%)
P. Fucharoen – 1st Pan-South Chine Workshop – Nanning 2012
β-thalassaemia intermedia
β-thalassaemia intermedia
“severe”β-thalassaemia intermedia
EPIDEMIOLOGY:
 7,000,000 children are born annually with either a
congenital abnormality or genetic disease;
- Up to 90% of the births occur in Low and medium
Resourced countries;
- Approximately 25% are comprised of five (5) disorders:
two (2) of which are the monogenic diseases:
Inherited Haemoglobin disorders
&
G-6-P Dehydrogenase Deficiency
64TH WORLD HEALTH ASSEMBLY – May 2011
World map of Hb disorders
7% of the global population are carriers of an abnormal Haemoglobin (Hb)
gene
(World Bank 2006, report of a joint WHO – March of Dimes meeting 2006)
EPIDEMIOLOGY:
It is estimated that about:
 7% of the global population carriers a pathological
Haemoglobin gene;
 In excess of 300,000 children with either thalassaemia or sickle
cell disease are born annually;
 > 80% of annual homozygous births occur in Low- and Medium
Resourced Countries;
 > 80% are affected with Sickle Cell Disease – About 70,000 with
thalassaemia of highly variable clinical course and depending
on the mixture of inherited alleles;
 > 80% of SCD patients die annually
For β-thalassaemia major age distribution, carrier rates, anticipated births and
number of registered patients: reflect lack of or suboptimal prevention and
management strategies – NO DATA OR ESTIMATIONS FOR MILDER PHENOTYPES
WHO-TIF Joint Meeting - 2007
- BREAKDOWN
Stock of foreign-born in selected EU countries and the US between 1997 and 2006
MIGRATIONS
HbE
β-Thal.
MIGRATIONS
MIGRATIONS
SCD
Survival by 10-yr birth cohort, all UK
ALIVE (%)
1975-84
1965-74
1955-64
Before 1955
Modell et al., Lancet 2000; 9220:2051-2
Ethnicity and region of residence Thal
600
Unknown
No of patients recorded
500
SE Asian
400
Bangladeshi
Other
300
Indian
200
Pakistani
100
Cypriot
0
S East
Midlands
Angl Oxf
Trent
N East
N West
Other
UK Thalassaemia register, 2002
60
TOTAL
70
W Midlands
N Western
The rest
Oxford
Yorkshire
Trent
NW Thames
NE Thames
S Thames
% of at risk pregnancies with PND
80
Utilisation of PND
for Hb disorders 1990-94 in UK
Thalassaemias
Sickle cell disorders
50
40
30
20
10
0
Newborn Screening Programmes
• Haemoglobinopathies
- a public health concern in UK
• 7.1% (4.2 million) of UK population “at risk”
• 10% of UK births from “at risk” group
Ethnicity and Year of Birth of
Current UK Thalassaemia patients
160
Unknown
120
SE Asian
100
Bangladeshi
80
Other
60
Indian
40
Pakistani
20
Cypriot
2000-2004
1995-1999
1990-1994
1985-1989
1980-1984
1975-1979
1970-1974
1965-1969
1960-1964
1955-1959
1950-1954
1945-1949
1940-1944
0
Before 1940
Number of patients
140
UK Thalassaemia register 2002
EPIDEMIOLOGICAL WORK IS NEEDED:
 BETTER
SUPPORT AND STRENGTHEN PROGNOSIS;
DEVELOP APPROPRIATE MANAGEMENT AND
MONITORING PROTOCOLS;
GUIDE POLICY MAKERS TO PLAN AND DEVELOP
APPROPRIATE SERVICES, INCLUDING REGISTRIES
SUPPORT OF COMPILATION OF MORE ROBUST
INFORMATION ON NATURAL HISTORY, MEDICAL
COMPLICATIONS, MORBIDITY AND MORTALITY
RATES CONTRIBUTING TO THE
GLOBAL DISEASE BURDEN OF DISORDERS