Global epidemiology of haemoglobin disorders and derived service indicators

480 Bulletin of the World Health Organization | June 2008, 86 (6) Introduction Inherited haemoglobin disorders (sickle- cell disorders and thalassaemias) were originally characteristic of the tropics and subtropics but are now common worldwide due to migration.1–4 Since they can be controlled cost-effectively by programmes that integrate treat- ment with carrier detection and genetic counselling, WHO has recommended global development of these services.5,6 However, service development can be unexpectedly challenging, because it requires inclusion of genetic approaches in health systems. The diversity and heterogeneous distribution of haemoglobin disorders make it necessary to develop strategies at the country level. To assist policy- makers, we use haemoglobin disorders as an example to show how genetic epidemiological data can be interpreted in terms of administrative boundaries (and/or ethnic group) and practical Global epidemiology of haemoglobin disorders and derived service indicators Bernadette Modell a & Matthew Darlison a Abstract To demonstrate a method for using genetic epidemiological data to assess the needs for equitable and cost-effective services for the treatment and prevention of haemoglobin disorders. We obtained data on demographics and prevalence of gene variants responsible for haemoglobin disorders from online databases, reference resources, and published articles. A global epidemiological database for haemoglobin disorders by country was established, including five practical service indicators to express the needs for care (indicator 1) and prevention (indicators 2–5). Haemoglobin disorders present a significant health problem in 71% of 229 countries, and these 71% of countries include 89% of all births worldwide. Over 330 000 affected infants are born annually (83% sickle cell disorders, 17% thalassaemias). Haemoglobin disorders account for about 3.4% of deaths in children less than 5 years of age. Globally, around 7% of pregnant women carry b or a zero thalassaemia, or haemoglobin S, C, D Punjab or E, and over 1% of couples are at risk. Carriers and at-risk couples should be informed of their risk and the options for reducing it. Screening for haemoglobin disorders should form part of basic health services in most countries. Bulletin of the World Health Organization 2008;86:480–487. Une traduction en français de ce résumé figure à la fin de l’article. Al final del artículo se facilita una traducción al español. .ةلاقلما هذهل لماكلا صنلا ةياهن في ةصلاخلا هذهل ةيبرعلا ةمجترلا Public health reviews a WHO Collaborating Centre for Community Control of Hereditary Disorders, UCL Centre for Health Informatics and Multiprofessional Education (CHIME), Archway Campus, Highgate Hill, London N19 5LW, England. Correspondence to Bernadette Modell (e-mail: b.modell@pcps.ucl.ac.uk). doi:10.2471/BLT.06.036673 (Submitted: 11 September 2006 – Revised version received: 14 June 2007 – Accepted: 5 July 2007 – Published online: 4 March 2008 ) service indicators. The work was initi- ated for WHO 7,8 and further devel- oped in the United Kingdom,9,10 where it is used for local needs-assessment.11 Global data are available at: www. chime.ucl.ac.uk/work-areas/cab/. Genetic terminology can be im- penetrable to non-specialists. In this paper, we use terms proposed for more general use by the Professional Educa- tion for Genetic Assessment and Screen- ing (PEGASUS) Genetic Education Programme of the United Kingdom National Screening Committee:11 hae- moglobin disorders include sickle-cell disorders and thalassaemias; haemo- globin gene variants are haemoglobin- opathies; significant variants are gene variants that can cause a serious disor- der; carriers are healthy heterozygotes; people with combinations of gene vari- ants are homozygotes and compound heterozygotes; and a thalassaemia major is haemoglobin Barts hydrops fetalis. Genetic background Haemoglobin comprises four globin chains: fetal haemoglobin (Hb F) has two a and two gamma chains (a2γ2) and adult haemoglobin (Hb A) has two a and two b chains (a2b2). Genes in the a-globin and b-globin gene clusters (on chromosomes 16 and 11) control globin-chain production. Due to spon- taneous mutation, haemoglobin gene variants are present at low prevalence (carriers 1–1.5/1000) in all sizeable populations.2,12 They fall into two broad groups – structural variants that change the amino acid sequence and produce an unusual haemoglobin,13 and thalas- saemias that lower or abolish produc- tion of globin chains.14 Most haemo- globin gene variants are rare and many are harmless, but some are common because carriers are less likely than oth- ers to die from falciparum malaria. The most common such variant, a plus (a+) thalassaemia, is usually harmless. Public health reviews Global epidemiology of haemoglobin disorders 481 Bernadette Modell & Matthew Darlison Bulletin of the World Health Organization | June 2008, 86 (6) However, people who inherit combi- nations of haemoglobins S, C, E, D Punjab, b thalassaemia, or a zero (a0) thalassaemia may have a serious hae- moglobin disorder. In populations in which malaria is (or was) endemic, 3 to 40% of individuals carry one of these significant variants, and the prevalence of haemoglobin disorders ranges from 0.3 to 25 per 1000 live births.8 Carriers are easily detected by rou- tine haematological methods and can be forewarned of their reproductive risk. Carriers of structural variants have 30–50% of the variant haemoglobin in their red cells: thalassaemia carriers have small red blood cells and some- times mild anaemia,3 and b thalassaemia carriers also have over 3.5% of Hb A2. The resemblance between thalassaemia and iron deficiency can confuse the diagnosis of either disorder.15 Requirements for treatment b thalassaemia major causes profound anaemia that kills untreated affected children before the age of 3 years. However, the life expectancy of patients treated with regular blood transfusion and iron-chelation therapy, or bone- marrow transplantation, is approach- ing normal.16,17 a thalassaemia major causes hydrops fetalis and perinatal death, often with life-threatening ob- stetric complications for the mother,3 and prenatal diagnosis usually leads to termination of pregnancy. Some cases have recently been saved by intrauterine transfusion, despite a high risk of severe mental and physical handicap.18 In sickle-cell disorders, sickled red blood cells block small blood vessels and cause anaemia, functional asplenia, episodes of severe pain, and residual organ damage. Most untreated affected children die from infection in early life,19 but simple steps including neona- tal diagnosis, prophylactic antimalarials and antibiotics, access to hospital treat- ment when needed, and information and support for families greatly im- prove quality and length of life.20 Requirements for prevention A policy of detecting carriers and in- forming them of their risk, and pos- sibilities for reducing it, usually leads to a fall in births and deaths of affected children. Requirements are the same for thalassaemias and sickle-cell disor- ders. In most countries, the approach develops in three stages.21 First, retrospectively informing parents with affected children of their 25% recurrence risk allows them to limit family size22 and, where average family sizes are typically large, this ap- proach can significantly reduce affected birth prevalence. Second, introduction of prenatal diagnosis for couples with affected children enables them to have a family, but has little further effect on affected birth prevalence.21 Access may also be limited by economic, medical, social or legal factors. Third, informa- tion and prospective carrier screening is provided for the whole popula- tion. Choice of strategy varies with social attitudes, costs and opportunities within the health system. The offer of testing in high school23,24 or before marriage 25–28 allows a wide range of choices and requires the least number of laboratory tests.26,28 Screening during pregnancy29,30 enables fewer options, requires more tests, is ethical only if prenatal diagnosis is freely available, and often identifies risk too late for the option of prenatal diagnosis.31 When carrier screening is provided without the option of prenatal diagnosis it usually creates public demand for this service.26,32 Population screening is not the only useful strategy: family studies can be cost-effective where consanguin- eous marriage is common33 or carrier prevalence is low.34 The effects of screening depend on the choices made by informed indi- viduals. Birth prevalence of thalassae- mia can fall by over 90%25–28,35 because most at-risk couples limit their family to two healthy children,22,25,26 there is very high uptake of prenatal diagnosis, and some carriers avoid risk by select- ing a non-carrier partner.25,26 Available data for sickle-cell disorders shows lower use of prenatal diagnosis36,37 and improved survival of affected children with neonatal diagnosis. Methods Acquisition of data The necessary data sets are available for most countries. We gathered demo- graphic data: population number, age distribution, crude birth rate and infant mortality from the 2003 United Na- tions Demographic Yearbook;38 under-5 mortality from the United Nations Chil- dren’s Fund (UNICEF);39 supplementary information from national statistics on the internet, and the Encyclopaedia Bri- tannica. Livingstone’s 1985 database of 1351 epidemiological studies of haemo- globin disorders2 provides robust global data on carrier prevalence (and so gene frequencies) for structural variants, but is less informative for thalassaemias. Data for thalassaemias were obtained from re- search reviews,3,4 country visits, and the former WHO Working Group on Haemoglobin Disorders.7 Data for a+ thalassaemias are from Weatherall and Clegg.3 Detailed sources and references are available at: www.chime.ucl.ac.uk/ work-areas/cab/. For populations where consanguineous marriage is common, a population coefficient of consanguinity (F) must be included when calculating the prevalence of affected concep- tions from gene frequencies.40 Values for population F were obtained from Dr Alan Bittles’ database41 and older ethnographic sources.42 Calculation of birth prevalences and service indicators Prevalences of conceptions with 12 combinations of gene variants were calculated for each country from gene frequencies using the Hardy–Weinberg equation:40 (p² + Fpq) + 2(pq – Fpq) + (q² + Fpq) = 1 where p is the gene frequency of variant 1, q is the gene frequency of variant 2, and F is the population coefficient of consanguinity. The results are aggregated here into conceptions per 1000 of: (1) sickle cell disorders (SS, SC, S/b thalassae- mia), (2) b thalassaemias (homozygous b thalassaemia, Hb E/b thalassaemia), (3) a thalassaemias (homozygous a0 thalassaemia, a0/a+ thalassaemia), and (4) harmless combinations (CC, C/b thalassaemia, EE, DD, D/b thalassae- mia, etc.). The following five service indicators were obtained for every country by com- bining prevalences of carriers and affected births with demographic data. Indicator for patient care (1. N) is the annual conceptions with a hae- moglobin disorder in the absence of prevention. Where treatment is not available, N is a measure of child- hood mortality due to haemoglo- Public health reviews Global epidemiology of haemoglobin disorders 482 Bernadette Modell & Matthew Darlison Bulletin of the World Health Organization | June 2008, 86 (6) bin disorders. Where treatment is available, N indicates the potential annual increase in patients needing care, and enables cost projections.43 Where prevention is available, N provides a baseline for measuring its effect on patient numbers. Indicator for carrier screening2. is the annual carrier tests required. With antenatal screening this is the annual number of pregnancies (~ births) in risk groups. With pre- marital or prepregnancy screening, this is the annual number of young people in risk groups reaching repro- ductive age. Indicator for carrier information 3. and offer of partner testing is the annual carriers detectable by the cho- sen strategy. Indicator for expert risk assess-4. ment and genetic counselling is the annual pregnancies to carrier couples, or new carrier couples, de- tectable by the chosen strategy. Indicator for the offer of prenatal 5. diagnosis is the annual pregnancies actually at risk (~ 3N to 4 N). The indicator for neonatal screening for sickle-cell disorders differs with poli- cy. When there is no adult carrier screen- ing, all newborns in risk groups must be tested (indicator 2). When there is prior carrier screening, only infants born to carrier mothers (indicator 3), or to at-risk couples (indicator 5) may need to be tested. Country estimates The calculations use the most detailed country data available. These data range from limited historical surveys to de- tailed micromapping by geographi- cal area or ethnicity. Estimates for 24 countries (including China and India) were derived by aggregating more de- tailed data. Estimates for 19 countries where haemoglobin disorders occur primarily as a result of migration were obtained by combining data on resi- dents’ ethnicity or country of birth with gene frequencies in countries of origin.12 All estimates are the most con- servative permitted by the data (i.e. give minimum figures). Individual country estimates are available at: www.chime. ucl.ac.uk/work-areas/cab. Findings Haemoglobin disorders were originally endemic in 60% of 229 countries, po- tentially affecting 75% of births, but Table 1. Estimated prevalences of carriers of haemoglobin gene variants and affected conceptions WHO region Demography 2003 % of the population carrying Affected conceptions (per 1000) Affected births (% of under-5 mortality)Population (millions) Crude birth rate Annual births (1000s) Under-5 mortality rate Sig- nificant varianta a+ thalas- saemiab Any variantc Sickle- cell disordersd Thalas- saemiase Total African 586 39.0 22 895 168 18.2 41.2 44.4 10.68 0.07 10.74 6.4 American 853 19.5 16 609 27 3.0 4.8 7.5 0.49 0.06 0.54 2.0 Eastern Mediterra- nean 573 29.3 16 798 108 4.4 19.0 21.7 0.84 0.70 1.54 1.4 European 879 11.9 10 459 25 1.1 2.3 3.3 0.07 0.13 0.20 0.8 South-east Asian 1 564 24.4 38 139 83 6.6 44.6 45.5 0.68 0.66 1.34 1.6 Western Pacific 1 761 13.6 23 914 38 3.2 10.3 13.2 0.00 0.76 0.76 2.0 World 6 217 20.7 128 814 81 5.2 20.7 24.0 2.28 0.46 2.73 3.4 a Significant variants include Hb S, Hb C, Hb E, Hb D etc. b thalassaemia, a0 thalassaemia. b a+ thalassaemia includes heterozygous and homozygous a+ thalassaemia. c Allows for (1) coincidence of a and b variants, and (2) harmless combinations of b variants. d Sickle-cell disorders include SS, SC, S/b thalassaemia. e Thalassaemias include homozygous b thalassaemia, haemoglobin E/b thalassaemia, homozygous a0 thalassaemia, a0/ a+ thalassaemia (haemoglobin H disease). are now sufficiently common in 71% of countries among 89% of births (either in the whole population or among minorities) to require policy-makers to consider the most appropriate strategy for treatment and prevention. Table 1 shows conservative prevalence estimates by WHO region. At least 5.2% of the world population (and over 7% of pregnant women) carry a significant variant. Haemoglobin S accounts for 40% of carriers but causes over 80% of disorders because of localized very high carrier prevalence: around 85% of sickle-cell disorders, and over 70% of all affected births occur in Africa. In addition, at least 20% of the world population carry a+ thalassaemia. Around 1.1% of couples world- wide are at risk for having children with a haemoglobin disorder and 2.7 per 1000 conceptions are affected. Preven- tion is making only a small impression: affected birth prevalence is estimated at 2.55 per 1000. Most affected chil- dren born in high-income countries survive with a chronic disorder, while most born in low-income countries die before the age of 5 years: haemoglobin disorders contribute the equivalent of 3.4% of mortality in children aged under 5 years worldwide or 6.4% in Africa. Public health reviews Global epidemiology of haemoglobin disorders 483 Bernadette Modell & Matthew Darlison Bulletin of the World Health Organization | June 2008, 86 (6) Table 2. Indicators of annual service needs for haemoglobin disorders WHO and component regions Indicator 1 Indicator 2 Indicator 3 Indicators 4 and 5 Annual affected conceptions Total annual births (1000s) Annual pregnant carriers (1000s) Annual pregnancies Sickle cell disorders b thalas- saemias a thalas- saemias Total disorders Both parents carriers At risk African region 233 289 1 520 11 234 819 22 895 4 363 1 005 752 939 277 Northern Africa 181 337 0 518 627 35 2 882 2 073 Western Africa 167 224 971 0 168 195 9 622 2 551 738 373 672 781 Middle Africa 40 688 27 0 40 715 4 184 804 162 934 162 861 Eastern Africa 25 184 183 11 25 377 6 974 966 101 510 101 509 Southern Africa 11 2 0 13 1 487 7 53 53 American region 9 047 533 442 10 022 16 483 523 44 769 40 088 Northern America 2 637 268 429 3 334 4 435 122 15 780 13 337 Central America 175 2 0 176 3 627 20 724 705 Caribbean 3 333 16 0 3 349 778 4 505 14 369 13 394 South America 2 902 248 13 3 163 7 643 278 13 895 12 651 Eastern Mediter- ranean region 6 491 9 715 1 16 207 16 776 670 66 079 64 828 Northern Africa 1 456 1 829 0 3 285 3 776 152 13 986 13 140 Eastern Africa 8 19 0 27 3 067 19 109 109 Western Asia 4 479 1 815 1 6 294 3 540 218 25 178 25 178 South central Asia 547 6 053 0 6 600 6 393 281 26 806 26 401 European region 1 292 1 347 162 2 800 10 459 153 12 064 11 201 Northern Europe 429 82 73 533 1 162 15.0 2 660 2 333 Western Europe 387 78 56 521 1 949 23.2 2 556 2 085 Southern Europe 204 313 33 550 1 458 39 2 263 2 202 Eastern Europe 0 25 0 25 2 881 8 98 98 South central Asia 0 365 0 365 1 190 27 1 461 1 461 Western Asia 272 484 0 756 1 819 41 3 027 3 023 South-east Asian region 26 037 21 693 1 383 49 114 38 139 2 363 421 398 196 454 South central Asia 26 037 9 348 0 35 386 31 210 1 476 230 905 141 542 South-eastern Asia 0 12 345 1 383 13 728 6 929 887 190 493 54 912 Western Pacific region 13 7 601 10 524 18 138 23 914 1 038 191 045 72 554 Eastern Asia 0 1 672 8 106 9 778 18 592 420 39 129 39 110 South-eastern Asia 0 5 846 2 373 8 219 4 774 607 151 173 32 878 Melanesia, Micronesia, Polynesia 0 54 0 54 242 6 214 214 Australia and New Zealand 13 29 45 88 307 4.7 529 351 World 276 168 42 409 13 466 332 043 128 667 9 111 1 744 877 1 328 172 Table 2 presents the five service indicators by WHO region and geo- graphical subregion. It also shows the rapid recent spread of haemoglobin disorders with migration (e.g. affected conceptions are now more common in northern and western than in southern Europe). Indicator 1. Annually there are over 332 000 affected conceptions or births. About 275 000 have a sickle-cell disorder, and need early diagnosis and prophylaxis. About 56 000 have a major thalassaemia, including at least 30 000 who need regular transfusions to sur- vive and 5500 who die perinatally due to a thalassaemia major. Indicator 2. Most births, 75%, are in countries where haemoglobin disor- ders are endemic and 13% occur where they are common because of migration, so in principle, 88% of the 128 million women who become pregnant annually should be offered screening. Indicator 3. Over 9 million carri- ers become pregnant annually. The risk that their partner is also a carrier ranges from 0.1–40% (global average 14%). In principle, all need information and the offer of partner testing. Indicator 4. Annually there are at least 948 000 new carrier couples, and over 1.7 million pregnancies to carrier Public health reviews Global epidemiology of haemoglobin disorders 484 Bernadette Modell & Matthew Darlison Bulletin of the World Health Organization | June 2008, 86 (6) Table 3. Estimated reach of treatment for b thalassaemia in each WHO regiona WHO region Estimated annual births b thalassaemias Transfusion No. of known patients Adequate iron chelation Inadequate or no iron chelation Total Transfusion- dependent Annual no. starting transfusion % of transfusion- dependent patients transfused Annual deaths because not transfused % with chelation No. with chelation No. of patients Annual deaths due to iron overload African 1 386 1 278 35 2.7 1 243 – – – – – American 341 255 134 52.4 121 2 750 58 1 604 1 146 57 Eastern Mediter- ranean 9 914 9 053 1 610 17.8 7 443 39 700 27 10 818 28 882 1 444 European 1 019 920 140 15.5 780 16 230 91 14 754 1 476 74 South-east Asian 20 420 9 983 962 9.6 9 021 35 500 19 6 621 28 879 1 444 Western Pacific 7 538 4 022 108 2.7 3 914 3 450 44 1 504 1 946 97 World 40 618 25 511 2 989 11.7 22 522 97 630 39 37 866 59 764 2 988 a All figures are minimum estimates. couples. Around 75% are actually at risk. In principle, all need expert risk assessment and genetic counselling. Indicator 5. Annually there are 1.33 million at-risk pregnancies. In principle, all need the offer of prenatal diagnosis. Table 3 shows that about 12% of children born with transfusion- dependent b thalassaemia are actually transfused, and less than 40% of those transfused obtain adequate iron-chela- tion therapy. About 100 000 patients are currently living with regular trans- fusions, and at least 3000 die annually in their teens or early 20s from un- controlled iron overload. No compa- rable data are available for sickle-cell disorders. Estimated reach of prevention Systematic carrier screening with the option of prenatal diagnosis is estab- lished in parts of Asia (in parts of China, including Hong Kong Special Administrative Region (SAR), Macao SAR, some southern regions and the province of Taiwan, parts of India, the Islamic Republic of Iran, the Maldives and Singapore), parts of the Caribbean and most of southern Europe (except Albania). In Australia, much of north- west Europe, New Zealand and North America, prenatal diagnosis is available and antenatal carrier screening is stan- dard practice. In the United Kingdom this policy identifies only a minority of at-risk couples in time for a truly informed choice: for timely risk de- tection, screening must be provided through primary health care.35 The same may apply for many countries where the disorders affect primarily ethnic minorities. The aggregated global data suggest a 16% reduction in births of children with thalassaemia and a 4% reduction in births of children with sickle-cell disorders. The greater part of the estimated reduction is attributed to reduced reproduction by informed at-risk couples, rather than prenatal diagnosis. Discussion Global burden of haemoglobin disorders The yardstick of under-5 mortality can be used to assess the broad effect of haemoglobin disorders on health, because most affected children die in early childhood and most survivors have chronic disease. Table 1 shows that they cause the equivalent of at least 3.4% of deaths in children aged under 5 years. However, this still underesti- mates their burden because inherited disorders affect families. Worldwide, over 1% of couples are at risk for haemoglobin disorders, most have at least one affected child, and most af- fected children die in early childhood. Although the west African death rate in children aged under 5 years is 18.4%, the rate is 16.5% for children born to couples not at risk for sickle-cell disor- ders compared with 40% for children born to couples who are at risk. Clearly, methods to assess the health burden of inherited disorders must include a fam- ily perspective.44 Thalassaemias Most children with thalassaemia are born in low-income countries. World- wide, transfusion is available for a small fraction of those who need it, and most transfused patients will die from iron overload unless an available and potentially inexpensive oral iron chelator is licensed more widely.45 The patients’ predicament underlines the need for combined treatment and prevention programmes.43 Wherever combined programmes exist survival is steadily improving,16,17 affected births are falling,25–28,30 and numbers of patients are stabilizing. The policy is spreading because of its demonstrable cost-effectiveness, and thalassaemia is gradually becoming contained.43 Sickle-cell disorders In high-income countries that provide neonatal diagnosis and care for patients, most survive well into adult life46 and, because there is limited use of prenatal diagnosis,36,37 numbers of patients are Public health reviews Global epidemiology of haemoglobin disorders 485 Bernadette Modell & Matthew Darlison Bulletin of the World Health Organization | June 2008, 86 (6) Résumé Epidémiologie mondiale des troubles de l’hémoglobine et indicateurs de service dérivés Présentation d’une méthode utilisant des données d’épidémiologie génétique pour évaluer les besoins en matière de services équitables et d’un bon rapport coût/efficacité pour le traitement et la prévention des troubles de l’hémoglobine. Des données démographiques et de prévalence concernant les variants génétiques responsables des troubles de l’hémoglobine ont été réunies à partir de bases de données en ligne, de sources de références et d’articles publiés. Une base de données épidémiologiques mondiale sur les troubles de l’hémoglobine par pays a été mise en place, en même temps que cinq indicateurs de service pratiques, destinés à évaluer les besoins en termes de soins (indicateur 1) et de prévention (indicateurs 2 à 5). Les pays où les troubles de l’hémoglobine sont un problème de santé important représentent 71 % des 229 pays considérés et totalisent aussi 89 % de la natalité mondiale. Plus de 330 000 nourrissons naissent chaque année avec de tels troubles (83 % avec une drépanocytose, 17 % avec une thalassémie). Les troubles de l’hémoglobine sont responsables d’environ 3,4 % des décès chez les moins de 5 ans. A l’échelle mondiale, 7 % environ des femmes enceintes sont porteuses d’une bêta-thalassémie ou d’une alpha-zéro-thalassémie, ou encore d’une hémoglobine S, C, D-Punjab ou E, et plus de 1 % des couples sont à risque. Les porteurs et les couples à risques doivent être informés des dangers qu’ils encourent et des solutions pour les réduire. Le dépistage des troubles de l’hémoglobine doit faire partie des services sanitaires de base de la plupart des pays. Resumen Epidemiología mundial de las hemoglobinopatías e indicadores de los servicios correspondientes Demostrar la validez de un método basado en datos de epidemiología genética para evaluar las necesidades de servicios equitativos y costoeficaces de tratamiento y prevención de las hemoglobinopatías. Se obtuvieron datos demográficos y sobre la prevalencia de las distintas variantes de genes causantes de hemoglobinopatías a partir de bases de datos en línea, de referencias y de artículos publicados. Se creó una base de datos epidemiológica mundial sobre las hemoglobinopatías por países, incluidos cinco indicadores prácticos de servicios para expresar las necesidades de atención (indicador 1) y de prevención (indicadores 2 a 5). Las hemoglobinopatías representan un importante problema sanitario en un 71% de los 229 países considerados, y en ese 71% se producen el 89% de todos los nacimientos. Cada año nacen más de 330 000 niños afectados (83% de casos de anemia de células falciformes y 17% de casos de talasemia). rising steadily. Most affected children born in low-income countries still die undiagnosed, usually from malaria,19 but things are changing. About 40% of Africa is now urbanised, and im- proved access to health care is leading to increased survival and rising demand for hospital services.47 Community- based services including information, prophylactic antimalarials or antibiot- ics, and social support greatly improve survival and quality of life and reduce demand for acute hospital services – in short, it is less costly to make organized care available than not.47 If average survival reaches only half the African norm, over six million Africans will be living with a sickle cell disorder – clearly, care for these disorders must become part of primary care wherever they are common. There is a strong case for carrier screening in Africa. Cheap and simple methods for testing adults and new- borns exist. Knowledge of risk allows a range of options, including limiting of family size, ensuring that at-risk in- fants are tested at birth, and requesting prenatal diagnosis. DNA-based early prenatal diagnosis is available at several African centres and is relatively inex- pensive when only the sickle variant is sought. However, as few couples can afford even a subsidised fee,32 there is insufficient information on likely up- take if the service were freely available. Relevance to diagnosis of iron deficiency WHO recommends the use of hae- moglobin concentrations to assess prevalence of iron deficiency in a lower-income setting.48 However, the recommended cut-off values for hae- moglobin concentrations are derived from populations of northern European origin and can lead to overestimation of iron deficiency where thalassaemias are common.49,50 The high global preva- lence of thalassaemias (Table 3) means that each population should use their own baseline normal ranges in the as- sessment of iron deficiency. Conclusion The data summarized here confirm that screening and genetic counselling for haemoglobin disorders should be an intrinsic part of health care in most countries, as recommended by the WHO.5,6 The country estimates (avail- able at: www.chime.ucl.ac.uk/work- areas/cab) provide a starting point for local needs assessment, service planning and evaluation. Because haemoglo- bin disorders are commonly a point of entry for genetic approaches into health systems,43,44 services should be designed to provide a foundation for more comprehensive community ge- netics services.26 ■ Acknowledgements We thank numerous international col- leagues for helping to collect the data summarized here. We are grateful to the late Frank Livingstone for his invalu- able global database of epidemiological studies. Funding: Bernadette Modell is a retired Wellcome Principal Research Fellow. Matthew Darlison is partly funded by PEGASUS, the Genetic Education Programme of the United Kingdom National Screening Committee. Competing interests: None declared. Public health reviews Global epidemiology of haemoglobin disorders 486 Bernadette Modell & Matthew Darlison Bulletin of the World Health Organization | June 2008, 86 (6) Las hemoglobinopatías causan aproximadamente un 3,4% de las defunciones entre los niños menores de 5 años. A nivel mundial, en torno a un 7% de las mujeres embarazadas son portadoras de talasemia b o a cero, o de hemoglobina S, C, D Punjab o E, y más de un 1% de las parejas corren riesgo. Se debería informar a los portadores y a las parejas en riesgo de ese peligro y de las opciones para mitigarlo. El cribado de las hemoglobinopatías debería formar parte de los servicios básicos de salud en la mayoría de los países. صخلم اهعقاو نم ةدمتسلما تامدخلا تا ِّرشؤمو ينبولغوميهلا تابارطضلا ةيلماعلا تايئابولا تاجايتحلاا ميـيقتل ،ةينيجلا ةيئابولا تايطعلما مادختسلا ةقيرط حيضوت ينبولغوميهلا تابارطضا ةجلاعلم دودرلما ةيلاعلاو ةلداعلا تامدخلا نم ةيفارغيمدلا تماسلا لوح تايطعم لىع نوثحابلا لصح .اهنم ةياقولاو ينبولغوميهلا تابارطضا نع ةلوؤسلما ةينيجلا بوضرلا راشتنا تلادعمو نمو ةيعجرلما رداصلما في تنرـتنلإا لىع ةحاتلما تايطعلما دعاوق نم كلذو تابارطضا تايئابول ةيلماع تايطعم ةدعاق اوسسأو ،ةروشنلما تلااقلما تا ِّرشؤم ةسمخ ن َّمضتت يهو ،نادلبلا في اهعيزوتل ًاقفو ينبولغوميهلا ةياقوللو )1 مقر ِّرشؤلما( ةياعرلل تاجايتحلاا حيضوتل ةيلمعلا تامدخلل .)5 لىإ 2 نم تا ِّرشؤلما( نم ًادلب 71 في ةميسج ةيحص ةلكشم ينبولغوميهلا تابارطضا لِّرثتم هذه في باصي نأ لمتحي يتلاو 229 اهددع غلبي يتلا نادلبلا لمجم ينب دولوم 330 000 دلوي ماع لك يفف .تادلاولا نم %89 ،71 ـلا نادلبلا ،ةيلجنلما ةيلخلا تابارطضاب مهنم %83( ينبولغوميهلا تابارطضاب باصم تايفو نم %3.4 ينبولغوميهلا تابارطضا بِّربستو ؛)ةيميسلاثلاب %17 لمحي يلماعلا ديعصلا لىعو ،تاونس 5 نع مهرماعأ لقت نيذلا لافطلأا وأ S ينبولغوميهلا وأ ةيميسلاث فلأ وأ بي لماوحلا تاهملأا نم ًابيرقت %7 .جاوزلأا نم %1 نم ثركأ ةباصلإا رطخل ضَّرعتي ماك ،E وأ باجنب D وأ C نوضرعم مه ام نع ،عفترم راطتخلا ينضَّرعلما جاوزلأاو ةَلَمَحـلا ةيعوت يغبني نوكي نأ يغبنيو .رطخلا ليلقتل مهل ةحاتلما تارايتخلاا نعو رطخ نم هل في ةيساسلأا ةيحصلا تامدخلا نم ًاءزج ينبولغوميهلا تابارطضا يِّررحت .نادلبلا مظعم References Livingstone FB. 1. 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