18 Mar 08

Lots of red blood cells are good news for malaria sufferers

Researchers have moved a step closer to understanding why alpha-thalassaemia, an inherited blood disorder, appears to offer protection against severe malarial anaemia. The key appears to be in the abnormally large number of small red blood cells which characterises thalassaemia.

Alpha-thalassaemia, probably the most common monogenic disease in humans, is particularly common in people from Africa and southeast Asia. It is caused by the deletion of one or more of four "alpha-globin" genes involved in the production of haemoglobin, the protein in red blood cells that carries oxygen. In people missing two alpha-globin genes, it results in a very mild anaemia.

However, people with the blood disorder appear to have some resistance to severe forms of malaria, caused by a mosquito-borne parasite, which is endemic in the same regions as thalassaemia. Ironically, despite causing mild anaemia, alpha-thalassaemia appears to protect people from severe malaria-related anaemia.

Now, Oxford university researchers in collaboration with colleagues at New York University and Papua New Guinea, believe they have found a mechanism that might contribute to this protection. The study, supported by the Wellcome Trust, the European Community, the Medical Research Council and the New York University (NYU) School of Medicine, is published in the open access journal PLoS Medicine.

When malaria parasites enter the bloodstream, they invade red blood cells, which burst, allowing the parasite to multiply and spread. This can markedly reduce the number of red blood cells, and hence the amount of haemoglobin in the blood leading to severe anaemia. The researchers have shown that children suffering from alpha-thalassaemia have smaller red blood cells than healthy children, containing less haemoglobin, but that they have significantly more of these cells – between 10-20% more than normal.

Furthermore, the researchers found that for people deficient in one alpha gene on each copy of chromosome 16 (referred to as being "homozygous"), the large reduction in the number of red blood cells that may occur during malaria led to less haemoglobin loss than in a normal child.

'Children with alpha-thalassaemia have adapted to the loss of red blood cells associated with malarial disease by making more of these cells with less haemoglobin,’ says Professor Day at New York University, who is part of the research team. ‘These children do better because they end up with more haemoglobin overall when they have a malaria attack compared to normal children. It is really remarkable and so simple.’

The study was carried out using blood samples from over 800 children in Papua New Guinea, where almost seven out of ten children have alpha-thalassaemia. Although all the children had been infected with Plasmodium falciparum, the most deadly species of malaria parasite, the researchers believe that alpha- thalassaemia may protect against other causes of anaemia that involve red cell loss.

The study was carried out by Professor Day and her then-DPhil student Freya J.I. Fowkes, and colleagues from the University of Oxford, Papua New Guinea Institute of Medical Research, and Swansea University.