The genes which direct the structure of human fetal and adult haemoglobin consist of a linked pair of alpha-chain loci on chromosome 16 and the G gamma-A gamma-delta-beta loci complex on chromosome 11. The delta-and beta-chain genes contain inserts similar to those of the mouse and rabbit globin genes. The structure of the various messenger RNAs transcribed from these loci is now worked out although the function of the non-coding regions is not known. The abnormal haemoglobin disorders and thalassaemias result from a variety of lesions at these loci which include single base substitutions, deletions of one or more bases or entire loci, insertions, frame-shifts, fusion genes caused by abnormal crossing over, chain termination mutations and ill-defined defects which lead to a reduced rate of transcription or abnormal structure of messenger RNA. Some progress has been made towards an understanding of the cellular mechanisms whereby the haemoglobin polymorphisms have been maintained. Very little is known about the regulatory mechanisms involved in the switch from fetal to adult haemoglobin production, although it is likely that certain specific areas of the gamma-delta-beta gene complex are involved in its control.

Anemia, Sickle Cell↗

PubMedDate not supplied

The interaction between Plasmodium falciparum and P. vivax in children on Espiritu Santo island, Vanuatu.

Studies of the prevalence and incidence of malaria were conducted in children < 10 years old living in 10 rural villages on the island of Espiritu Santo, Vanuatu, south-west Pacific. Malaria prevalence remained stable at 30% throughout the year but the relative contributions of the 2 major species were highly dependent on season. Plasmodium falciparum predominated in the long wet season (November-May) and P. vivax in the dry season (June-October). Case definitions for malaria, derived using a multiple logistic regression method, showed that parasite densities associated with clinical disease were low; case definitions for P. falciparum (> 1000 parasites/microL in children > 1 year old and > 500 microL in infants) and P. vivax (> 500 parasites/microL at all ages) were both associated with a specificity and sensitivity of > 90%. Like prevalence data, malaria morbidity was highly seasonal; 80% of clinical P. falciparum infections occurred in the wet season and 66% of clinical P. vivax in the dry season. Mixed infections were rare. Malaria was important cause of morbidity with children < 5 years old experiencing 1.3-3.0 episodes of clinical malaria per year and 23% of fevers being attributable to malaria in this age group. Children aged 5-9 years continued to suffer one episode of clinical malaria per year. The peak incidence of P. vivax malaria occurred earlier in life than the peak incidence of P. falciparum malaria. The possible interactions between these 2 parasite species are discussed.

Animals↗

PubMedDate not supplied

Absence of malaria-specific mortality in children in an area of hyperendemic malaria.

We conducted a prospective community-based malaria surveillance study on a cohort of children < 10 years old living in an area of hyperendemic malaria (spleen rates > 50% in children aged 2-9 years) in Vanuatu, Melanesia, supported by a concurrent prospective descriptive study of malaria admissions to the local hospital. The incidence of clinical malaria in children < 10 years old was 1.9 episodes/year. The annual incidence of severe malaria (severe malarial anaemia and cerebral malaria) was only 2/1000 in children aged < 5 years. The only manifestation of severe malaria seen in indigenous children was anaemia. No death could be attributed to malaria. While the incidence of uncomplicated clinical malaria in this population was comparable to that in many parts of Africa, the incidence of severe forms of the disease was significantly lower. This could not be attributed to differing rates of malaria transmission, chloroquine resistance, or to host protective or behavioural factors. These findings suggest that studies which compare disease patterns in geographically disparate populations may be instrumental in developing a better understanding of the determinants of clinical outcome in Plasmodium falciparum malaria and that such regional differences must be considered when planning or interpreting the effects of malaria interventions.

Adolescent↗

PubMedDate not supplied

Haemoglobin E beta thalassaemia in Sri Lanka.

Haemoglobin E beta thalassaemia is the commonest form of severe thalassaemia in many Asian countries, but little is known about its natural history, the reasons for clinical diversity, or its management. We studied 109 Sri Lankan patients with the disorder over 5 years. 25 patients were not receiving transfusion; transfusion was stopped with no deleterious effect in a further 37. We identified several genetic and environmental factors that might contribute to the phenotypic diversity of the disorder, including modifiers of haemoglobin F production, malaria, and age-related changes in adaptive function. Our findings suggest that haemoglobin E beta thalassaemia can be managed without transfusion in many patients, even with low haemoglobin levels. Age-related changes in the pattern of adaptation to anaemia suggest that different and more cost-effective approaches to management should be explored.

Adolescent↗

PubMedDate not supplied

The global distribution of length polymorphisms of the promoters of the glucuronosyltransferase 1 gene (UGT1A1): hematologic and evolutionary implications.

The promoter region of the UDP glucuronosyltransferase 1 gene (UGT1A1) contains a run of thymine-adenine (TA) repeats, usually six (TA)(6). As well as its relationship to Gilbert's syndrome, homozygosity for the extended sequence, (TA)(7) (TA)(7), has been found to be an important risk factor for hyperbilirubinemia and gallstones in patients with hemoglobin E-beta-thalassemia and other intermediate forms of beta thalassemia. To assess the importance of this polymorphism in these common disorders a wide-scale population study of the relative frequency of the size alleles of the UGT1A1 promoter has been carried out. Homozygosity for the (TA)(7) allele occurs in 10-25% of the populations of Africa and the Indian subcontinent, with a variable frequency in Europe. It occurs at a much lower frequency in Southeast Asia, Melanesia, and the Pacific Islands, ranging from 0 to 5%. African populations show a much greater diversity of length alleles than other populations. These findings define those populations with a high frequency of hemoglobin E-beta-thalassemia and related disorders that are at increased risk for hyperbilirubinemia and gall bladder disease and provide evolutionary insights into how these polymorphisms have arisen and are so unequally distributed among human populations.

Animals↗

PubMedDate not supplied

Switch from foetal to adult haemoglobin synthesis in normal and hypophysectomised sheep.

Explore the source record for details and available documents.

Age Factors↗