Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

About 120,000 infants are born each year with sickle cell disease (SCD) in Africa. The majority have Hb SS, but Hb SC and Hb S/beta+ thalassaemia are common in west Africa. The development of Plasmodium falciparum and P. malariae is partially inhibited in the Hb SS red cells, but malaria precipitates both haemolytic and infarctive crises, and is the commonest and most important cause of morbidity and mortality. The pneumococcus is likely to be the second major infectious cause of sickness and death. In one rural community, there were less than 2% of the expected number of subjects with SCD surviving beyond 5 years of age. Genetic factors improving prognosis include (1) the Senegal beta chain haplotype, which is linked to a high level of Hb F, and (2) alpha+ thalassaemia. Of environmental factors improving prognosis, the family is of first importance. The commonest age of presentation is 1-3 years. Children present with anaemic crises (malaria, splenic sequestration, folate deficiency, and possibly aplastic), infarctive crises (hand-foot syndrome, bone-pain, pulmonary and abdominal) or acute infections (malaria, pneumonia, septicaemia, meningitis, osteomyelitis). Tragically, many patients in central Africa have been infected by the human immunodeficiency virus (HIV) through blood transfusions; they present with generalised lymphadenopathy and other features of the acquired immunodeficiency syndrome (AIDS). The principles of management are (1) to ensure freedom from malaria, (2) to continue folic acid supplements, (3) to give blood transfusions only when anaemia endangers life, (4) to control pain, (5) to restore hydration, and (6) to prescribe broad spectrum antibiotics in large dosage and without delay, but only when there are definite indications, such as fever (greater than 39 degrees C), acute pulmonary disease, meningitis, and acute osteomyelitis. The advent of HIV and AIDS makes the control of SCD of even greater importance. Principles of control are (1) early diagnosis through appropriate laboratory techniques and selective screening, (2) education of parents, patients, health professionals and public, and (3) the maintenance of health at sickle cell clinics; measures must include antimalarial prophylaxis. SCD programmes should be integrated with primary health care and AIDS control programmes.
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PMID:The presentation, management and prevention of crisis in sickle cell disease in Africa. 265 Jul 73

Malaria parasites are very vulnerable to oxidant stress during the part of their life cycle when they inhabit erythrocytes. As the infection progresses they also activate macrophages, one consequence of which is extracellular release of reactive oxygen species. For these reasons free radicals are frequently discussed in the literature on antimalarial drugs, malarial immunity, and disease pathogenesis. They are also central to arguments explaining how the genetic mutations that lead to sickle cell disease, thalassemia and glucose-6-phosphate dehydrogenase have become so common in tropical regions. This review summarizes how these links between free radicals and this disease came to be understood, and the present state of the field.
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PMID:Some roles of free radicals in malaria. 266 64

In 18 beta-thalassaemia families from the Ferrara area the incidence of an inherited low flavin mononucleotide (FMN)-dependent pyridoxine phosphate (PNP) oxidase activity, a sensitive indicator of red-cell FMN deficiency, is higher in related members in these families than in the unrelated spouses and controls subjects without family history of thalassaemia. This suggests slower red-cell riboflavin metabolism in thalassaemia families, which may have resulted from selection in combination with thalassaemia by malaria. However, there was a markedly higher incidence of red-cell flavin adenine dinucleotide (FAD) deficiency in thalassaemia heterozygotes than in their normal relatives. This was indicated by higher stimulation of FAD-dependent glutathione reductase (GR) activity by FAD and lower GR activity per red cell, and suggests a marked additive effect by thalassaemia on the red cell FAD deficiency that results from the inherited slow riboflavin metabolism. There is evidence that diversion of FAD to other FAD-dependent enzymes might be an important factor.
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PMID:Genetic and other influences on red-cell flavin enzymes, pyridoxine phosphate oxidase and glutathione reductase in families with beta-thalassaemia. 272 60

During a study on malaria in pregnant women in Burkina Faso, the authors gave a particular attention to the hemoglobin of a mother and her new-born child (blood of cord) and they noticed an hemoglobin migrating before the HbA which was identified by isoelectric focusing (IEF). The child is a composite HbK/HbC heterozygote. A survey was carried out to check the transmission of such a K Woolwich hemoglobin within the family of the mother. Out of 40 people, 17 got HbKw. A noticeable anemia was found in HbKw/HbC heterozygote. The authors tried to identified a possible thalassemia. There was little probability for an association of a minor alpha-thalassemia in the absence of Bart's hemoglobin in the blood of the cord (IEF test) and there was no associated beta-thalassemia.
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PMID:[A case of a combination heterozygote with hemoglobin K Woolwich and hemoglobin C (Hb Kw/HbC) discovered in Bobo-Dioulasso (Burkina Faso)]. 272 43

The frequency of the beta S mutation in the district of Coruche/Portugal is estimated to be about 4% from analysis of a group of 181 school children and their teachers in an area in which malaria has been endemic until recently. Several white Portuguese patients with sickle cell disease (six homozygous SS and one S beta degree thalassaemia) were found in a group of 309 further patients who were known and followed up by local medical practitioners. These patients had clinical and haematological features similar to patients of African origin, although their growth and sexual development appeared to be normal. The analysis of an array of polymorphic restriction sites within the beta S globin gene cluster (beta S haplotype) showed patterns that are known to occur in Africa. The frequencies of the three main African beta S haplotypes termed Senegal, Bantu, and Benin reflect the extent of Portuguese naval explorations. It is concluded that the sickle cell gene in Portugal has probably been imported from Africa and has been amplified in comparison with other genes characteristic for African races because of the selective advantage of AS heterozygotes in an area endemic for malaria.
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PMID:The frequency and origin of the sickle cell mutation in the district of Coruche/Portugal. 273 37

A study of the distribution of alpha-thalassemia in Papua New Guinea (PNG) was carried out by DNA analysis. A total of 664 DNA samples were screened for alpha-thalassemia 2 and alpha-thalassemia 1 caused respectively by either deletion of one or both of the duplicated alpha-globin genes. alpha-Thalassemia 2 was detected in high frequencies in coastal and lowland regions where malaria has been holo- to hyperendemic but in low frequencies in non-malarious highland regions. The highest frequency was observed in the north coast of PNG. The distribution of alpha-thalassemia 2 seems to be in accordance with other conditions such as ovalocytosis and G6PD deficiency which are also prevalent in this population, suggesting that they may interact in protection against malaria. However, it appears to be negatively correlated with beta-thalassemia and alpha-thalassemia 1, the latter being extremely rare in this population. Analysis of the types and subtypes of the single alpha-globin gene deletion revealed a predominance of the -alpha 4.2 type in general, except in some regions in the south where the -alpha 3.7 type is prevalent. The -alpha 3.7 I subtype is the common form of the -alpha 3.7 deletion in the PNG mainland. The -alpha 3.7 III subtype, previously reported to be unique in Melanesians and Polynesians, was detected in an offshore island of PNG. However, this subtype is very rare in Melanesians from the PNG mainland.
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PMID:Alpha-thalassemia in Papua New Guinea. 287 71

Data on the distribution of beta thalassemia among over 6,000 Melanesians reveals a major difference in the carrier rates between populations in the malarious coastal regions of New Guinea and those living in the historically malaria-free Highlands. The island of Maewo in Vanuatu has a particularly high incidence of beta + thalassemia associated with a single restriction enzyme haplotype. Direct cloning into a plasmid vector and sequence analysis demonstrate that the mutation is a G to C transversion at position 5 of intron 1 of the beta-globin gene. Oligonucleotide probe surveys indicate that this variant accounted for all cases of beta thalassemia studied from Maewo. It is also common in coastal Papua New Guinea where haplotype and oligonucleotide probe data suggest that the molecular basis of beta thalassmia is more heterogeneous.
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PMID:Beta thalassemia in Melanesia: association with malaria and characterization of a common variant (IVS-1 nt 5 G----C). 289 55

The discovery that mutant beta-globin genes arise on different chromosomal backgrounds has allowed studies of the origin and spread of some of the common haemoglobinopathies. The beta S mutation has a wide geographic distribution and is found on many different haplotypes, suggesting that it has had multiple independent origins. In contrast, the Indian beta 0 deletion thalassaemia has a restricted geographic distribution and is present on a single haplotype, suggesting a single origin. The limited evidence for the beta-thalassaemia mutations indicates that most have had a single origin and have subsequently reached polymorphic frequencies by selection pressure from malaria.
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PMID:The origin of mutant beta-globin genes in human populations. 312 Apr 65

Recent population genetic studies of the distribution of alpha+-thalassaemia in Melanesia using DNA analysis have provided strong support for the hypothesis that high frequencies of this genetic disorder are the result of natural selection by malaria.
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PMID:Alpha-thalassaemia and the malaria hypothesis. 312 Apr 67

The frequencies of the hemoglobin E gene (HBB*E) and the beta-thalassemia gene(s) (HBB*T) were determined in 890 healthy adult males from three areas at the Thai-Kampuchean border in Northeastern Thailand. The population of the three study areas differs ethnically: area I is inhabited by Khmer-speaking people, area II has an ethnically mixed population (Tai-Lao, Soui and Khmer), and area III is predominantly Lao. In view of the topographic differences in malaria endemicity in the pre-eradication era, the probands from the three study areas were divided into subgroups "hills" and "plains" according to the location of their home villages. The frequencies of HBB*T were generally low, but the difference between the HBB*E frequencies in the "hills" (0.3295) and "plains" (0.2455) subgroups was highly significant. This is interpreted as environmental effect due to selection by malaria. A "hemoglobin E belt" with HBB*E frequencies between 0.3 and 0.35 extends along the Dangraek mountain chain at the border between Thailand and Kampuchea.
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PMID:The hemoglobin E belt at the Thailand-Kampuchea border: ethnic and environmental determinants of hemoglobin E and beta-thalassemia gene frequencies. 315 22


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