World distribution, population genetics, and health burden of the hemoglobinopathies.

Although information about the precise world distribution and frequency of the inherited hemoglobin disorders is still limited, there is no doubt that they are going to pose an increasing burden on global health resources in the future. Their high frequency is a reflection of natural selection combined with a high frequency of consanguineous marriages in many countries, together with an epidemiological transition; whereby, as public health measures improve in the poorer countries of the world, more babies with these disorders are surviving to present for treatment.

[1]  R. Kraaijenhagen,et al.  Effect of α+-thalassaemia on episodes of fever due to malaria and other causes: a community-based cohort study in Tanzania , 2011, Malaria Journal.

[2]  Peter D. Crompton,et al.  Hemoglobin S and C heterozygosity enhances neither the magnitude nor breadth of antibody responses to a diverse array of Plasmodium falciparum antigens. , 2011, The Journal of infectious diseases.

[3]  R. Hayes,et al.  Antibodies to blood stage antigens of Plasmodium falciparum in rural Gambians and their relation to protection against infection. , 1989, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[4]  T. Peto,et al.  Interaction of malaria with a common form of severe thalassemia in an Asian population , 2009, Proceedings of the National Academy of Sciences.

[5]  R. Nagel,et al.  Sickling rates of human AS red cells infected in vitro with Plasmodium falciparum malaria. , 1978, Science.

[6]  P. Deloron,et al.  Longitudinal study of Plasmodium falciparum infection and immune responses in infants with or without the sickle cell trait. , 1999, International journal of epidemiology.

[7]  C. Drakeley,et al.  Associations between alpha+-thalassemia and Plasmodium falciparum malarial infection in northeastern Tanzania. , 2007, The Journal of infectious diseases.

[8]  K. Marsh,et al.  High mortality from Plasmodium falciparum malaria in children living with sickle cell anemia on the coast of Kenya , 2010, Blood.

[9]  L. Tian,et al.  Invasion and growth of Plasmodium falciparum is inhibited in fractionated thalassaemic erythrocytes. , 1997, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[10]  A. Fleming,et al.  Abnormal haemoglobins in the Sudan savanna of Nigeria. I. Prevalence of haemoglobins and relationships between sickle cell trait, malaria and survival. , 1979, Annals of tropical medicine and parasitology.

[11]  A. Allison,et al.  Protection Afforded by Sickle-cell Trait Against Subtertian Malarial Infection , 1954, British medical journal.

[12]  A. Hill,et al.  Globin genes in Micronesia: origins and affinities of Pacific Island peoples. , 1990, American journal of human genetics.

[13]  A. Boyo,et al.  THE RELATIONSHIP OF SERUM GAMMA-GLOBULIN CONCENTRATION TO MALARIA AND SICKLING , 1960, Journal of clinical pathology.

[14]  Kevin Marsh,et al.  Relation between falciparum malaria and bacteraemia in Kenyan children: a population-based, case-control study and a longitudinal study , 2011, The Lancet.

[15]  F. B. Livingstone Data on the abnormal hemoglobins and glucose-6-phosphate dehydrogenase deficiency in human populations, 1967-1973 , 1973 .

[16]  H. Gilles,et al.  Glucose-6-phosphate-dehydrogenase deficiency, sickling, and malaria in African children in South Western Nigeria. , 1967, Lancet.

[17]  P. K. Seth,et al.  Prevalence of malaria in Ao Nagas and its association with G6PD and HbE. , 1992, Human biology.

[18]  E. A. Beet Sickle cell disease in Northern Rhodesia. , 1947, East African medical journal.

[19]  T. Wellems,et al.  Non‐opsonising aggregates of IgG and complement in haemoglobin C erythrocytes , 2007, British journal of haematology.

[20]  H. Shear,et al.  Transgenic mice expressing human sickle hemoglobin are partially resistant to rodent malaria , 1993 .

[21]  O. Doumbo,et al.  Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria , 2005, Nature.

[22]  S. Adjei,et al.  Differing effects of HbS and HbC traits on uncomplicated falciparum malaria, anemia, and child growth. , 2010, Blood.

[23]  Peter Donnelly,et al.  Genome-wide and fine-resolution association analysis of malaria in West Africa , 2009, Nature Genetics.

[24]  D. F. Roberts,et al.  The History and Geography of Human Genes , 1996 .

[25]  A. Clark,et al.  Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection. , 2004, American journal of human genetics.

[26]  Mario Recker,et al.  Negative epistasis between the malaria-protective effects of α+-thalassemia and the sickle cell trait , 2005, Nature Genetics.

[27]  M. Wahlgren,et al.  Natural protection against severe Plasmodium falciparum malaria due to impaired rosette formation. , 1994, Blood.

[28]  A. Allison,et al.  NOTES ON SICKLE‐CELL POLYMOKPHISM , 1954, Annals of human genetics.

[29]  Anand P. Patil,et al.  Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis , 2010, Nature communications.

[30]  P. Kremsner,et al.  The sickle cell trait is associated with enhanced immunoglobulin G antibody responses to Plasmodium falciparum variant surface antigens. , 2005, The Journal of infectious diseases.

[31]  Sammy Wambua,et al.  An Immune Basis for Malaria Protection by the Sickle Cell Trait , 2005, PLoS medicine.

[32]  T. Williams,et al.  Sickle cell disease and malaria morbidity: a tale with two tails. , 2011, Trends in parasitology.

[33]  O. Doumbo,et al.  Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S. , 2000, Blood.

[34]  Julie Simpson,et al.  Hemoglobin E: a balanced polymorphism protective against high parasitemias and thus severe P falciparum malaria. , 2002, Blood.

[35]  E. Dietz,et al.  α+-thalassemia protects African children from severe malaria , 2004 .

[36]  A. Allison The distribution of the sickle-cell trait in East Africa and elsewhere, and its apparent relationship to the incidence of subtertian malaria. , 1954, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[37]  A. Fleming,et al.  Abnormal haemoglobins in the Sudan savanna of Nigeria. III. Malaria, immunoglobulins and antimalarial antibodies in sickle cell disease. , 1979, Annals of tropical medicine and parasitology.

[38]  R. Olomi,et al.  Alpha+ -thalassemia protects against anemia associated with asymptomatic malaria: evidence from community-based surveys in Tanzania and Kenya. , 2008, The Journal of infectious diseases.

[39]  O. Pybus,et al.  Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean , 2009, Proceedings of the National Academy of Sciences.

[40]  A. Björkman,et al.  Falciparum malaria and beta-thalassaemia trait in northern Liberia. , 1983, Annals of tropical medicine and parasitology.

[41]  R. Nagel,et al.  The role of hemoglobins C, S, and Nbalt in the inhibition of malaria parasite development in vitro. , 1979, The American journal of tropical medicine and hygiene.

[42]  Y. Kan,et al.  Alpha globin gene number: population and restriction endonuclease studies. , 1980, Blood.

[43]  R. Eeckels,et al.  Abnormal Distribution of Haemoglobin Genotypes in Negro Children with Severe Bacterial Infections , 1967, Nature.

[44]  P. Arese,et al.  Enhanced phagocytosis of ring-parasitized mutant erythrocytes: a common mechanism that may explain protection against falciparum malaria in sickle trait and beta-thalassemia trait. , 2004, Blood.

[45]  I. Guggenmoos‐Holzmann,et al.  Plasmodium falciparum malaria and human red cells. II. Red cell genetic traits and resistance against malaria. , 1981, International journal of epidemiology.

[46]  Matthew Darlison,et al.  Global epidemiology of haemoglobin disorders and derived service indicators. , 2008, Bulletin of the World Health Organization.

[47]  J. B. Clegg,et al.  The thalassaemia syndromes , 1965 .

[48]  R. Wilson,et al.  The interaction of malaria parasites with red blood cells. , 1982, British medical bulletin.

[49]  T. Agbenyega,et al.  Hemoglobin variants and disease manifestations in severe falciparum malaria. , 2007, JAMA.

[50]  D. Weatherall,et al.  Cellular mechanism for the protective effect of haemoglobin S against P. falciparum malaria , 1978, Nature.

[51]  Sunetra Gupta,et al.  NEGATIVE EPISTASIS BETWEEN α+ THALASSAEMIA AND SICKLE CELL TRAIT CAN EXPLAIN INTERPOPULATION VARIATION IN SOUTH ASIA , 2011, Evolution; international journal of organic evolution.

[52]  R. Nagel,et al.  Synchronized cultures of P falciparum in abnormal red cells: the mechanism of the inhibition of growth in HbCC cells. , 1986, Blood.

[53]  G. Thompson Significance of Haemoglobins S and C in Ghana , 1962, British medical journal.

[54]  Jacques Simpore,et al.  Hemoglobins S and C Interfere with Actin Remodeling in Plasmodium falciparum–Infected Erythrocytes , 2011, Science.

[55]  L. Luzzatto,et al.  Increased sickling of parasitised erythrocytes as mechanism of resistance against malaria in the sickle-cell trait. , 1970, Lancet.

[56]  H. Webster,et al.  Alteration in cytoadherence and rosetting of Plasmodium falciparum-infected thalassemic red blood cells. , 1993, Blood.

[57]  E. Dietz,et al.  Hemoglobin C and resistance to severe malaria in Ghanaian children. , 2004, The Journal of infectious diseases.

[58]  B. Ringelhann,et al.  A new look at the protection of hemoglobin AS and AC genotypes against plasmodium falciparum infection: a census tract approach. , 1976, American journal of human genetics.

[59]  I. Guggenmoos‐Holzmann,et al.  Plasmodium falciparum malaria and human red cells. I. A genetic and clinical study in children. , 1981, International journal of epidemiology.

[60]  W. O'Sullivan,et al.  Genetic red cell disorders and severity of falciparum malaria in Myanmar. , 1995, Bulletin of the World Health Organization.

[61]  A. Olivieri,et al.  Haemoglobin C protects against clinical Plasmodium falciparum malaria , 2001, Nature.

[62]  Suthat Fucharoen,et al.  The hemoglobin E thalassemias. , 2012, Cold Spring Harbor perspectives in medicine.

[63]  D. Higgs The molecular basis of α-thalassemia. , 2013, Cold Spring Harbor perspectives in medicine.

[64]  J. Ouédraogo,et al.  Genetic variation in human HBB is associated with Plasmodium falciparum transmission , 2010, Nature Genetics.

[65]  K. Marsh,et al.  Malaria in patients with sickle cell anemia: burden, risk factors, and outcome at the outpatient clinic and during hospitalization. , 2010, Blood.

[66]  J. Flint,et al.  The population genetics of the haemoglobinopathies. , 1993, Bailliere's clinical haematology.

[67]  W. Brass,et al.  The variability of sickle-cell rates in the tribes of Kenya and the Southern Sudan. , 1954, British medical journal.

[68]  Odegbemi Jo,et al.  Immunoglobulin levels in malaria infected Nigerians with and without abnormal haemoglobin. , 1995 .

[69]  R. Snow,et al.  Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases. , 2005, The Journal of infectious diseases.

[70]  O. Gaye,et al.  Red blood cell polymorphisms in relation to Plasmodium falciparum asymptomatic parasite densities and morbidity in Senegal. , 2006, Microbes and infection.

[71]  T. Wellems,et al.  Aberrant development of Plasmodium falciparum in hemoglobin CC red cells: implications for the malaria protective effect of the homozygous state. , 2003, Blood.

[72]  M. Bockarie,et al.  A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[73]  T. Theander,et al.  Reduced risk of uncomplicated malaria episodes in children with alpha+-thalassemia in northeastern Tanzania. , 2008, The American journal of tropical medicine and hygiene.

[74]  R. Snow,et al.  The Effect of α +-Thalassaemia on the Incidence of Malaria and Other Diseases in Children Living on the Coast of Kenya , 2006, PLoS medicine.

[75]  M. Friedman Erythrocytic mechanism of sickle cell resistance to malaria. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[76]  O. Doumbo,et al.  Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin , 2008, Proceedings of the National Academy of Sciences.

[77]  A. Motulsky,et al.  Favism and Thalassæmia in Sardinia and their Relationship to Malaria , 1961, Nature.

[78]  Alberto Piazza,et al.  The History and Geography of Human Genes: Abridged paperback Edition , 1996 .

[79]  J. Haldane,et al.  THE RATE OF MUTATION OF HUMAN GENES , 2010 .

[80]  H. Foy,et al.  The distribution of sickle cell trait and the incidence of sickle cell anaemia in the Negro tribes of Portuguese East Africa. , 1952, East African medical journal.

[81]  T. Matsushima,et al.  Abnormal haemoglobins in the Sudan savanna of Nigeria. IV. Malaria, immunoglobulins and antimalarial antibodies in haemoglobin AC individuals. , 1979, Annals of tropical medicine and parasitology.

[82]  G. Serjeant Mortality from sickle cell disease in Africa , 2005, BMJ : British Medical Journal.

[83]  M. Grosso,et al.  Molecular Basis of Thalassemia , 2012 .

[84]  A. Dicko,et al.  A comparison of the incidence of severe malaria in Malian children with normal and C-trait hemoglobin profiles. , 1997, Acta tropica.

[85]  A. Hill,et al.  High frequencies of alpha-thalassaemia are the result of natural selection by malaria. , 1986, Nature.

[86]  Satyandra K. Gupta,et al.  Negative epistasis between the malaria-protective effects of alpha (+) thalassaemia and the sickle cell trait [MIM-TW-395505] , 2005 .

[87]  G. Bancone,et al.  Haemoglobin C and S in natural selection against Plasmodium falciparum malaria: a plethora or a single shared adaptive mechanism? , 2007, Parassitologia.

[88]  G. Thompson Malaria and Stress in Relation to Haemoglobins S and C* , 1963, British medical journal.

[89]  T. Theander,et al.  Cell-mediated immune responses to Plasmodium falciparum purified soluble antigens in sickle-cell trait subjects. , 1990, Immunology letters.

[90]  A. Di Rienzo,et al.  Protection against malaria morbidity: near-fixation of the alpha-thalassemia gene in a Nepalese population. , 1991, American journal of human genetics.

[91]  P. Hedrick Selection and Mutation for α Thalassemia in Nonmalarial and Malarial Environments , 2011, Annals of human genetics.

[92]  I. Mueller,et al.  Minimal association of common red blood cell polymorphisms with Plasmodium falciparum infection and uncomplicated malaria in Papua New Guinean school children. , 2010, The American journal of tropical medicine and hygiene.

[93]  K. Tokunaga,et al.  Lack of Association of the HbE Variant with Protection from Cerebral Malaria in Thailand , 2008, Biochemical Genetics.

[94]  Dianne J Terlouw,et al.  Protective effects of the sickle cell gene against malaria morbidity and mortality , 2002, The Lancet.

[95]  K. Aye,et al.  Hemoglobin E prevalence in malaria-endemic villages in Myanmar. , 2005, Acta medica Okayama.

[96]  A. Hill,et al.  Beta thalassemia in Melanesia: association with malaria and characterization of a common variant (IVS-1 nt 5 G----C). , 1988, Blood.

[97]  I. Danquah,et al.  Influence of haemoglobins S and C on predominantly asymptomatic Plasmodium infections in northern Ghana. , 2010, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[98]  W. Pollitzer Frequencies of Hemoglobin Variants. Frank B. Livingstone. , 1987 .

[99]  C. Newbold,et al.  High incidence of malaria in α-thalassaemic children , 1996, Nature.

[100]  T. Theander,et al.  Modulation of the cellular immune response during Plasmodium falciparum infections in sickle cell trait individuals , 1992, Clinical and experimental immunology.

[101]  C. Rogier,et al.  Heritability of the Human Infectious Reservoir of Malaria Parasites , 2010, PloS one.

[102]  G. Flatz,et al.  Haemoglobin E and β‐thalassaemia: their distribution in Thailand , 1965 .

[103]  I. Bechmann,et al.  Sickle Hemoglobin Confers Tolerance to Plasmodium Infection , 2011, Cell.

[104]  D. Conway,et al.  Haemoglobin C and S Role in Acquired Immunity against Plasmodium falciparum Malaria , 2007, PloS one.

[105]  M. Alpers,et al.  alpha+-Thalassemia protects children against disease caused by other infections as well as malaria. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[106]  Bernadette Modell,et al.  March of Dimes: global report on birth defects, the hidden toll of dying and disabled children. , 2005 .

[107]  K. Maitland,et al.  Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya. , 2005, Blood.

[108]  M. Alpers,et al.  Increased Microerythrocyte Count in Homozygous α+-Thalassaemia Contributes to Protection against Severe Malarial Anaemia , 2008, PLoS medicine.

[109]  E. A. Beet Sickle cell disease in the Balovale District of Northern Rhodesia. , 1946, East African medical journal.

[110]  A. Kulozik,et al.  Geographical survey of beta S-globin gene haplotypes: evidence for an independent Asian origin of the sickle-cell mutation. , 1986, American journal of human genetics.

[111]  D. Weatherall Thalassemia as a global health problem: recent progress toward its control in the developing countries , 2010, Annals of the New York Academy of Sciences.

[112]  P. Brain Sickle-cell Anaemia in Africa , 1952 .