Genomes of the malaria mosquito and parasite are sequenced

Celebration greeted last week's announcements by international teams of scientists that they have sequenced the genomes of the principal malaria parasite, Plasmodium falciparum, and the mosquito that carries it.

But the consensus emerging among researchers as they digest the findings is that the greatest barrier to overcoming malaria, the killer of more than a million children a year, is not a lack of knowledge but a severe lack of funding to develop new candidate vaccines and drugs.

“My guess is that in 10 years' time this probably will be seen as a very important event,” said Professor Brian Greenwood, a malaria expert at the London School of Hygiene and Tropical Medicine. But although better knowledge of the parasite's proteins will enable immunologists to identify more candidate molecules for vaccines, this will not in itself bring vaccines to market more quickly, he warned. “It is not a lack of candidates that is the problem; it is pushing them through the whole system that is so costly and time consuming.”

About 500 million people suffer from malaria every year. The disease is on the increase in sub-Saharan Africa, where resistance to existing drugs is spreading. Few of the major pharmaceutical companies currently invest any money in malaria vaccines, because they doubt that the poor countries worst affected could afford to buy them. The cost of developing a vaccine has been estimated as high as $500m (£320m; €510m).

GlaxoSmithKline has one candidate in development, called RTS,S, which is currently in field trials. Several small biotechnology companies are supporting early vaccine studies, but a major company is needed to support a candidate through large and complex clinical trials in countries where malaria is endemic.

“Development is a lot more expensive than research,” said Professor Adrian Hill, whose team at the University of Oxford is developing candidate malaria vaccines. Also, thanks to the “brain drain” from many countries and lack of investment in training, there are relatively few scientists and institutions in countries where malaria is endemic to conduct the trials.

The World Health Organization has estimated that funding for malaria control alone needs to increase to $2.5bn a year by 2007 and to $3.1bn by 2015 to achieve results. This covers only existing measures, including bed nets treated with insecticide, prompt treatment of sick people, and prophylaxis for all pregnant women in endemic regions, who are at increased risk. If new drugs and vaccines are added the bill will be higher. Yet currently the world's spending on malaria research and control is only about $200m.

The prospects for drug development are slightly better than for vaccines and have been boosted by the genome studies. “We will have new drugs much sooner than we would otherwise have done,” said Professor Greenwood. Researchers will be able to screen existing drugs for their actions against key proteins in the parasite's metabolism. Already, a compound used in mouthwash, triclosan, and a drug developed to treat persistent urinary infections, fosmidomycin, are being tested as antimalarials.

The $29m project to sequence P falciparum was led by the Wellcome Trust Sanger Institute, near Cambridge, the Institute for Genomic Research in Rockville, Maryland, and Stanford University . The genome of the mosquito Anopheles gambiae was sequenced by a consortium of 19 institutions .

The sequencing of the two genomes is in itself a huge technical feat. Dr Bart Barrell at the Sanger Institute said P falciparum had been “dreadful” to sequence, partly because of its large repeated sequences.

The genome shows that the parasite's capacity to vary its appearance to the immune system is even greater than previously believed, emphasising the difficulties of developing effective vaccines.

Researchers were surprised to discover that a set of genes responsible for this variation is present not only in the blood stage of the parasite's complex life cycle but also in the sporozoite stages that develop in the liver.

This raises questions about what other functions these genes might have. The functions of fully 60% of the parasite's genes are unknown: they do not match sequences on any genetic databases. The finding suggests that the parasite has an ancient evolutionary history and a highly specialised niche, say researchers.

LIFE CYCLE OF THE MALARIA PARASITE, PLASMODIUM FALCIPARUM