LONDON ¿ The discovery that a particular variant of the gene encoding the hemoglobin molecule provides malaria protection to more than nine out of 10 people who have a double copy of it could lead to new drugs. Studies to elucidate how the resulting mutant hemoglobin protein has this effect will suggest new strategies to defeat the malaria parasite, which infects an estimated 130 million to 150 million people worldwide each year, and kills about 2 million.

A team of researchers from Italy and the West African country of Burkina Faso reported their findings in a paper in Nature titled, ¿Hemoglobin C protects against clinical Plasmodium falciparum malaria.¿

It is well known that some variants of the genes encoding the hemoglobin molecule can alter a person¿s susceptibility to malaria. For example, people with one copy of the mutation known as HbS, which is common throughout Africa, have some protection against malaria. Unfortunately, those who inherit both copies of HbS develop sickle cell anemia, which is frequently fatal in childhood.

David Modiano, of the University of Rome ¿La Sapienza,¿ together with colleagues at the World Health Organization Collaborating Center for Malaria Epidemiology and Control, also in Rome, and at the Ministry of Health and Ouagadougou University Hospital, both in Ouagadougou, Burkina Faso, decided to study the mutant hemoglobin molecule known as HbC. This mutation gives rise to a single nucleotide substitution in one of the beta chains of the molecule, so that the amino acid lysine appears instead of glutamine. HbC is common in parts of West Africa where malaria occurs, particularly Burkina Faso.

Earlier studies by other groups on the influence of the HbC mutation on malaria susceptibility were inconclusive. Several laboratory studies had shown that Plasmodium falciparum, the parasite that causes malaria, does not multiply in red blood cells from people with two copies of the HbC gene. In the field, one study in Mali, also in West Africa, showed that HbC protected against severe malaria, but two other studies found no such link.

Modiano and his colleagues studied more than 3,500 healthy children from local schools and 835 children with malaria recruited from the pediatric ward of Ouagadougou University Hospital, looking at how the genotypes of these individuals varied between those who were healthy and those who had severe or non-severe malaria.

They found that people who had two copies of HbC, known as CC, were much less common in the group with malaria than in the healthy subjects. Statistically, the researchers would have expected 13.8 people in the malaria group with CC, but they found only one.

Overall, the study showed that people who have one copy of HbC and one copy of HbA (the normal form of hemoglobin), who are known as HbAC, had a risk of developing clinical malaria that was 29 percent less than someone who is HbAA. Those who were HbCC had a risk of clinical malaria that was a startling 93 percent less than those who were HbAA. This level of protection is greater than that normally associated with the HbAS genotype: People who are HbAS have a 73 percent less risk of clinical malaria.

Writing in Nature, Modiano and his colleagues conclude that eventually, in the absence of malaria control programs, HbC would replace HbS in central West Africa.