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Despite major advances in our understanding of the molecular pathology, pathophysiology, and control and management of the inherited disorders of haemoglobin, thousands of infants and children with these diseases are dying through lack of appropriate medical care. This problem will undoubtedly increase over the next 20 years because, as the result of a reduction in childhood mortality due to infection and malnutrition, more babies with haemoglobin disorders will survive to present for treatment. Although WHO and various voluntary agencies have tried to disseminate information about these diseases, they are rarely mentioned as being sufficiently important to be included in setting health care priorities for the future. It takes considerable time to establish expertise in developing programmes for the control and management of these conditions, and the lessons learned in developed countries will need to be transmitted to those countries in which they occur at a high frequency.

In many Asian populations, the commonest form of severe thalassemia results from the coinheritance of HbE and/3 thalassemia. The management of this disease is particularly difficult because of its extreme clinical diversity; although some genetic and adaptive factors have been identified as phenotypic modifiers, the reasons remain unclear. Because the role of the environment in the course of severe thalassemia has been neglected completely and because malaria due to both Plasmodium falciparum and Plasrnodium vivax has been prevalent in Sri Lanka, we carried out a pilot study of patients with HbE [beta] thalassemia that showed high frequencies of antibodies to both parasite species and that 28.6% of the children had DNA-based evidence of current infection with P. vivax. Malarial antibodies then were assessed in patients with HbE [beta] thalassemia compared with those in age-matched controls. There was a significant increase in the frequency of antibodies in the thalassemic patients, particularly against P. vivax and in young children. There was also a higher frequency in those who had been splenectomized compared with those with intact spleens, although in the latter it was still higher than that in the controls. The thalassemic patients showed significant correlations between malaria antibody status and phenotype. Patients with HbE [beta] thalassemia may be more prone to malaria, particularly P. vivax, which is reflected in their clinical severity. Because Po vivax malaria is widespread in Asia, further studies of its interaction with HbE [beta] thalassemia and related diseases are required urgently as a part of ongoing thalassemia control programs. www.pnas.org/cgi/doi/10.1073/pnas.0910142106

Severe forms of anemia in children in the developing countries may be characterized by different clinical manifestations at particular stages of development. Whether this reflects developmental changes in adaptation to anemia or other mechanisms is not clear. The pattern of adaptation to anemia has been assessed in 110 individuals with hemoglobin (Hb) E [beta]-thalassemia, one of the commonest forms of inherited anemia in Asia. It has been found that age and Hb levels are independent variables with respect to erythropoietin response and that there is a decline in the latter at a similar degree of anemia during development. To determine whether this finding is applicable to anemia due to other causes, a similar study has been carried out on 279 children with severe anemia due to Plasmodium falciparum malaria; the results were similar to those in the patients with thalassemia. These observations may have important implications both for the better understanding of the pathophysiology of profound anemia in early life and for its more logical and cost-effective management. erythropoietin | malaria | thalassemia | hemoglobin

The thalassemias, together with sickle cell anemia and its variants, are by far the most common monogenic diseases. They occur at their highest frequency in countries of the developing world where their control and management is hampered by a lack of knowledge of their true prevalence, adequate services for their management and control, and support by their governments and international health agencies. However, there has been some progress recently in addressing these problems and there are several ways in which the lot of children with thalassemia in poor countries could be improved in the future. Over the last 20 years there has been considerable improvement in the control and management of the thalassemias in the richer countries of the world. Unfortunately, however, this is not the case for many of the developing countries, where there have been few improvements in the control of the numbers of births of babies with thalassemia or in the care of thalassemic children since the frequency of the problem started to become evident in the 1960s. Here, I will try to assess the current situation in these countries and examine some of the potential approaches for improving the current situation. [ABSTRACT FROM AUTHOR]

Recent studies have shown that the relatively short period of exposure of human populations to malaria has left in its wake a wide range of genetic diversity. And there is growing evidence that other infectious agents have, or are, having the same effect. By integrating further studies of human populations with genetic analyses of susceptibility to murine malaria it should now be possible to determine some of the mechanisms involved in the variation of susceptibility to infectious disease, information which may have important practical implications for both the diagnosis and better management of these conditions. [ABSTRACT FROM AUTHOR]

Haldane's attractive hypothesis that the high gene frequencies for thalassaemia in the Mediterranean population may have resulted from heterozygote advantage in regions where Plasmodium falciparum malaria was common in the past has been extremely difficult to verify at the population or experimental level. However, the molecular era has provided some powerful new tools to attack this old problem. It is now clear that the thalassaemias are the commonest monogenic diseases in man, with a broad distribution throughout the Mediterranean, Middle East, Indian sub-continent and South-east Asia. All these populations have specific types of thalassaemia mutations which, presumably, have arisen locally and been expanded by selection together with drift and founder effect. Recent work indicates that alpha thalassaemia provides protection against severe malaria. Quite unexpectedly, at least some of this protection may be mediated by rendering very young children more susceptible to both P. vivax and P. falciparum malaria; such early immunization may provide some protection against the disease in later life. [ABSTRACT FROM AUTHOR]

Provides a prospective case-control study of children with severe malaria on the north coast of Papua New Guinea, where malaria transmission is intense and ...+-thalassemia affects more than 90 percent of the population. Risk of having severe malaria; Risk of hospital admission with infections other than malaria; Demonstration that children are protected against disease caused by infections other than malaria by a malaria resistance gene.

Examines the development of mechanisms for the acquisition, transport and storage of iron in Great Britain. Significance of the siderophores; Importance of hypoferraemia as host defense mechanism; Studies on the relation between infection and iron availability; Formulation for the plans of adding iron to diets in the developing countries.