Selected publications

• Premawardhena A, Fisher C A, Olivieri N F, de Silva S, Arambepola M, Perera W, O'Donnell A, Peto T EA, Viprakasit V, Merson L, Muraca G, and Weatherall D J (2005) Haemoglobin E beta thalassaemia in Sri Lanka. Lancet, 366(9495):1467-70.

• Premawardhena Anuja, Fisher Christopher A, Olivieri Nancy F, de Silva Shanthimala, Sloane-Stanley Jackie, Wood William G, and Weatherall David J (2005) A novel molecular basis for beta thalassemia intermedia poses new questions about its pathophysiology. Blood, 106(9):3251-5.

• Williams Thomas N, Mwangi Tabitha W, Wambua Sammy, Peto Timothy EA, Weatherall David J, Gupta Sunetra, Recker Mario, Penman Bridget S, Uyoga Sophie, Macharia Alex, Mwacharo Jedidah K, Snow Robert W, and Marsh Kevin (2005) Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait. Nat Genet, 37(11):1253-7.

• Weatherall D J, Akinyanju O, Fucharoen S, Olivieri N F, and Musgrove P (2006) Inherited Disorders of Hemoglobin In: Disease Control Priorities in Developing Countries, ed. by Jamison, D et al.. Oxford University Press and the World Bank, Oxford & Washington, chap. 34, pp. 663-680.

• O'Donnell Angela, Premawardhena A, Arambepola M, Allen S J, Peto T EA, Fisher C A, Rees D C, Olivieri Nancy F, and Weatherall D J (2007) Age-related changes in adaptation to severe anemia in childhood in developing countries. Proc Natl Acad Sci U S A, 104(22):9440-4.

The Population Genetics and Mechanisms of Phenotypic Variability for the Thalassaemias
The thalassaemias, the commonest monogenic diseases, are posing an increasingly important public health problem, particularly for the countries of South and Southeast Asia.  A major problem for health planning for the control of these conditions is lack of adequate knowledge about their true frequency; most estimations are based on work in one centre and it is becoming increasingly clear that the thalassaemias have a very uneven distribution among many populations.  We are currently micro-mapping the distribution and frequency of these conditions in Sri Lanka, Vietnam, and Indonesia.  At the same time we are trying to learn more about the reasons for their extremely high frequency.  We are investigating whether relative resistance on the part of carriers or those with milder forms of these conditions to P. falciparum, and possibly P. vivax malaria, is, as long suspected, the major reason for this high frequency.  We have obtained very strong evidence that this is the case for α thalassaemia in Papua New Guinea and are now attempting to obtain similar information regarding β thalassaemia and haemoglobin E, a mild form of thalassaemia, in Vietnam, Indonesia and Sri Lanka.

The world distribution of the Thalassaemias

Although the clinical course for the severe forms of â thalassaemia is fairly predictable, there are milder varieties, notably haemoglobin E β thalassaemia, which occur at a very high frequency throughout Asia. Very little is known about the natural history of these conditions or about the reasons for their remarkable clinical variability.  By detailed analysis of the molecular forms of these conditions, and by identifying potential modifying genes and environmental factors that may be involved, we are attempting to answer the problem of the mechanisms of phenotypic heterogeneity in a long term study of children with haemoglobin E β thalassaemia in Sri Lanka.  In addition, we are attempting to develop more logical and economical control programmes for these conditions in some of the Asian countries by evolving networks between countries with or without the expertise required.

The original transfusion ward catering for over 700 children with Thalassaemia in Kurunegala, Sri Lanka.  With the help of the Wellcome Trust this has now been replaced by a modern, three-storey Treatment Centre.