Over-abundance of smaller red blood cells may help protect against severe malarial anaemia
18 March 2008
Alpha-thalassaemia, probably the most common monogenic disease in humans, is particularly common in people from Africa and South-east 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, Professor Karen Day from New York University (NYU) and colleagues 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 NYU School of Medicine, is published today 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.
Children suffering from alpha-thalassaemia have smaller red blood cells than healthy people, containing less haemoglobin; however, they have significantly more of these cells - between 10-20 per cent 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 healthy 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. "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-PhD student Freya J I Fowkes, Professor Sir David Weatherall from the University of Oxford, Dr Michael Alpers from the Papua New Guinea Institute of Medical Research and Drs Stephen and Angela Allen from Swansea University's School of Medicine.
Contact
Craig Brierley
Media Officer
Wellcome Trust
T +44 (0)20 7611 7329
E
c.brierley@wellcome.ac.uk
Notes for editors
1. Fowkes FJI et al. Increased microerythrocyte count in homozygous α-thalassaemia contributes to protection against severe malarial anaemia. PLoS Medicine, 18 March 2008.
Download a preview copy of the paper [PDF 256KB]
2. The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £650 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.
3. Oxford University's Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one-third of Oxford University's income and expenditure, and two-thirds of its external research income. Oxford's world-renowned global health programme is a leader in the fight against infectious diseases (such as malaria, HIV/AIDS, tuberculosis and avian flu) and other prevalent diseases (such as cancer, stroke, heart disease and diabetes). Key to its success is a long-standing network of dedicated Wellcome Trust-funded research units in Asia (Thailand, Laos and Vietnam) and Kenya, and work at the MRC Unit in The Gambia. Long-term studies of patients around the world are supported by basic science at Oxford and have led to many exciting developments, including potential vaccines for TB, malaria and HIV, which are in clinical trials.
4. The School of Medicine at Swansea University is one of the UK's fastest growing research-led graduate entry medical schools. Its interdisciplinary research is focused around the new Institute of Life Science, a £50 million partnership between the Welsh Assembly Government, IBM and Swansea University to discover new ways to treat disease and deliver healthcare, while contributing to the economic development of the region.