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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