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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe here the screening of a small group of apparently healthy individuals belonging to the tribal communities of Koya Dora and Konda Reddi. A remarkably high incidence of deletion and nondeletion alpha + thalassemia mutants has been found with allele frequencies and distributions characteristic to each tribe. We have confirmed the strict relationship between Hb S levels and the number of alpha globin genes in double heterozygotes for the S gene and alpha thalassemia. In this population sample we did not find either heterozygous carriers of alpha 0 thalassemia (deletion of both alpha genes in "cis") or individuals showing hemolytic anemia due to inactivation of three alpha-globin genes (Hb H disease). Selection by malaria is most probably responsible for the prevalence of the various alpha + thalassemia haplotypes among the two tribal populations of Andhra Pradesh.
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PMID:Prevalence and molecular heterogeneity of alfa+ thalassemia in two tribal populations from Andhra Pradesh, India. 316 39

To investigate the protective effects of beta-thalassemia against malaria, rodent malaria parasites were studied in C57BL/6J mice with beta-thalassemia, in mice in which the thalassemia had been transgenically corrected with the human beta A-globin gene, and in hematologically normal mice. In thalassemic mice, Plasmodium chabaudi adami infection was inhibited and peak parasitemia was variably delayed. In transgenically corrected mice, infection proceeded as in normal mice. Plasmodium berghei infection proceeded more rapidly in thalassemic mice, but survival was not different. Splenectomized normal mice displayed high-level parasitemia that peaked twice and persisted as a low-level parasitemia for more than 20 days after normal intact mice were free of all parasites. Splenectomized thalassemic mice showed a delay of 5 days in attaining peak parasitemia, but the parasitemia persisted as in normal splenectomized mice. Thus, for P. chabaudi, which displayed no preference for immature erythrocytes, beta-thalassemia offers enhanced resistance for the host. However, for P. berghei, which preferentially invades reticulocytes, thalassemia is not protective. The protective effects of the normal mouse spleen were observed, but the paradoxical facilitation of parasite growth by the thalassemic spleen is a new finding that will require further experimentation to explain. This new in vivo laboratory documentation of thalassemic protection against some rodent malaria parasites may serve as a useful model in further efforts to control this major infectious disease.
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PMID:Malaria in beta-thalassemic mice and the effects of the transgenic human beta-globin gene and splenectomy. 333 24

DNA analysis of the alpha- and beta-globin gene clusters has revealed substantial variability between individuals and populations. As well as restriction enzyme site and length polymorphisms, variation in gene copy number and type is observed. Because of this extensive polymorphism DNA analysis offers a highly informative method of studying genetic affinities between human populations. Haplotypes, consisting of a set of restriction enzyme polymorphisms distributed along the cluster, have been developed for both loci. Analysis of the molecular basis of numerous beta-thalassaemia alleles has revealed, in general, different sets of mutations in different populations, indicating that these postdate the racial divergence. Recent microepidemiological studies on the distribution of alpha-thalassaemia support the hypothesis that this condition, like the beta s-mutation, has been selected because it confers protection against malaria. Population-specific DNA polymorphisms at these and other loci promise to be of considerable value to genetic anthropology.
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PMID:The evolution of the alpha- and beta-globin gene clusters in human populations. 353 Sep 78

A controlled trial of iron dextran prophylaxis in infants 2 months old was carried out on the north coast of New Guinea, where malaria is holoendemic. These infants have a high carrier rate (80%) for alpha + thalassaemia. The neighbouring highland area has a low rate of both malaria and alpha + thalassaemia. The results of clinical and haematological examination of these infants at 6 and 12 months were analysed to determine the relationship between alpha thalassaemia and susceptibility to malaria. Infants were divided according to haemoglobin Bart's levels found at birth into 3 groups corresponding to probable genotypes. Homozygotes had higher slide malarial positivity and spleen rates at 6 and 12 month than the normal or heterozygote groups. Analysis of variance of haemoglobin levels showed that the anaemia associated with malaria was greatest in the normals and least in the homozygotes at 6 months. A possible protective mechanism of alpha thalassaemia is discussed.
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PMID:The interaction of alpha thalassaemia with malaria. 361 98

Red blood cell (RBC) antioxidant defense was investigated in eight individuals with hemoglobin E (Six EE and two E-B(+) thalassemia) and compared to that in six individuals with thalassemia and ten normal subjects. Individuals with hemoglobin E had increased incubated Heinz body formation (68% +/- 18%; p less than 0.001) compared to normal and thalassemic RBC (10% +/- 2% and 11% +/- 5%, respectively). Stimulated pentose phosphate shunt activity was increased in the thalassemic and decreased in the hemoglobin E RBC as compared to normal. The 2,3-diphosphoglycerate (DPG) content of the EE RBC was increased to 5.59 +/- 0.69 mumol/ml RBC as compared to normal (4.51 +/- 0.77; p less than 0.001). In the EE RBC, there was a direct correlation between Heinz body formation and DPG content (r = 0.73). Ascorbic and dehydroascorbic acid (0.1 and 1.0 mM) were able to decrease the degree of Heinz body formation in the hemoglobin E RBC. Ascorbic acid (0.1 mM) prolonged the response of the pentose shunt. Thus impaired antioxidant defense may account for the persistence of the hemoglobin E gene in areas where malaria is endemic. Oxidant medications should be used with caution in individuals of Southeast Asian origin.
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PMID:Impaired antioxidant defense in hemoglobin E-containing erythrocytes: a mechanism protective against malaria? 367 3

A total of 1,112 randomly selected Saudi Arabs, of both sexes, living in Jeddah and the surrounding areas were screened for the phenotypic distribution of red cell glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD). They were also investigated for haemoglobin and for thalassaemia. Phenotyping of the haemoglobins and the red cell enzymes was carried out by starch gel electrophoresis and the dye-decolouration screening test, while the investigation for thalassaemia was carried out by globin-chain biosynthesis, followed by column chromatography. The red cell Gd- alleles were significantly associated with the sickle-cell gene in both the males (chi 2(1): AS-28.80; SS-4.89) and females (chi 2(1): AS-10.99; SS-13.16). A similar association was also observed between G6PD deficiency and thalassaemias in males (chi 2(1): alpha-thalassaemia - 3.13; beta-thalassaemia - 11.06) and females (chi 2(1): alpha-thalassaemia - 6.63). However, no such association was detected between red cell 6PGD types and haemoglobin genes. The results suggest that the red cell G6PD deficiency, sickle-cell and thalassaemia genes might have evolved as a result of the same ecological factor, probably malaria.
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PMID:Association of red cell glucose-6-phosphate dehydrogenase with haemoglobinopathies. 369 36

The frequency of alpha+-thalassaemia, but not other unlinked DNA polymorphisms, exhibits an altitude- and latitude-dependent correlation with malaria endemicity throughout Melanesia, supporting the hypothesis that protection against this parasitic disease is the major factor responsible for the high frequencies of haemoglobinopathies in many parts of the world.
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PMID:High frequencies of alpha-thalassaemia are the result of natural selection by malaria. 371 63

Studies of the ability of Plasmodium falciparum to grow in vitro in the red blood cells of subjects with certain beta-thalassemia syndromes are often difficult to interpret because of the known inhibitory effect of an elevated cellular content of human fetal hemoglobin (HbF). P falciparum therefore was cultured in vitro in the erythrocytes of subjects with hemoglobin H (HbH) disease and various other alpha-thalassemia genotypes that are unaccompanied by increased levels of HbF. Growth of the malaria parasite was markedly retarded in HbH red blood cells, when compared with growth in blood from normal control subjects. No consistent impairment of growth was seen in the erythrocytes of subjects having deletion of only one or two alpha-globin genes. These results indicate that erythrocytes with a severe thalassemia phenotype provide a less hospitable growth environment for P falciparum than normally hemoglobinized red blood cells, even in the absence of increased levels of HbF.
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PMID:Plasmodium falciparum in vitro: diminished growth in hemoglobin H disease erythrocytes. 388 Nov 44

Incidence of haemoglobin variants and G-6-PD deficiency among 1385 males belonging to 12 endogamous Dhangar castes of Maharashtra, India, have been reported. Of the 12 castes studied 11 lacked the allele for G-6-PD deficiency; 2.7% of the Thellaris were found to be deficient. Haemoglobin Hb-D trait is found in 2 of the 12 castes; the incidence among Ahirs and Hatkars being 0.82% and 1.91%, respectively. One case of Hb-J among the Ahirs, and 2 examples of thalassaemia trait, one each among Ahirs and Gadharis, have been detected. The low incidence of observed G-6-PD deficiency and the detection of Hb-D and J traits, as well as thalassaemia have been discussed in the light of the nomadic way of life of some of the Dhangar castes and prevalence of malaria in the region they occupy. The data strongly suggest that the Dhangars arrived in Maharashtra in the recent past from northwest.
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PMID:G-6-PD and haemoglobin variants among twelve endogamous Dhangar castes of Maharashtra, India. 406 62

The authors report data on the genetic distribution of thalassaemia and of glucose-6-phosphate dehydrogenase deficiency in the populations of certain Sardinian villages, many of which are not only of great antiquity but have maintained isolation for very long periods and therefore possess the following three requirements for suitability for investigation of the possible interrelationships among malaria, thalassaemia and G-6-PD deficiency: a reasonable degree of ethnic homogeneity, availability of reliable demographic data, and availability of malaria-free populations of adequate size and of ethnic background and genetic isolation similar to those of the malarial populations.Investigations including more than 6000 observations in 52 villages demonstrated a positive correlation between the incidences of thalassaemia and G-6-PD deficiency. It is suggested that the genotype that carries thalassaemia and/or the enzyme deficiency may have a high adaptive value in a malarial environment.It is concluded that there is a need further to investigate human genetic structure and the biological fitness of the principal genotype combinations in both existing environments and those that will result from continued cultural evolution.
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PMID:Population genetics of haemoglobin variants, thalassaemia and glucose-6-phosphate dehydrogenase deficiency, with particular reference to the malaria hypothesis. 529 98


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