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The bases of malaria

Sequencing the genomes of the causer and transmitter of the disease stimulates research into new drugs

EDUARDO CESARAnopheles and the most frequent victims of malaria: the populations of poor countriesEDUARDO CESAR

The sequencing of the genomes of the parasite that causes malaria, Plasmodium falciparum, published in the British magazine Nature, of October 3, and of the mosquito that transmits it, Anopheles gambiae, which came out in the American magazine Science on the following day are opening inaugurating a new era in parasitology. On the 2nd, to unveil the results, the two magazines sponsored an international teleconference, in which Pesquisa FAPESP took part. The specialists from the two projects stressed that releasing the two sequences of the bases of the DNA should speed up the development of tools for controlling malaria, which every year kills over a million people, although the definitive solution may still be far off.

“This is just the start, and anyone who claims that a vaccine against malaria is coming in a couple of years is lying”, comments Hernando Del Portillo, a researcher with the Institute of Biomedical Sciences of the University of São Paulo (ICB-USP). “We now have information for everyone to work 24 hours a day in search of solutions that may save millions of lives”, adds Carlos Morel, director of the Tropical Disease Research (TDR) program, of the World Health Organization (WHO), who coordinated the formation of the consortium for sequencing the Anopheles mosquito.

The genome of P. falciparum consists of 23 million base pairs, which form some 5,300 genes, distributed in 14 chromosomes. It has already been discovered, for example, that chromosome number 5 shows a high proportion of genes directly involved in the functioning of structures called apicoplasts, responsible for the synthesis of substances that are vital for the metabolism of the plasmodium. There was also a confirmation of the localization of variant antigen genes: related to the parasite’s skill in fooling the defense system of other organisms, they appear at all the ends (telomeres) of the protozoon’s chromosome. Then the genome of Anopheles gambiae, detailed in Science, with 278 million base pairs, proves to be distributed in some 14,000 genes. In total, the two magazines published 30 articles on the theme – one of them even showed a view of the proteins produced in the course of the plasmodium’s life cycle.

Both P. falciparum and its transmitter are common in Africa, where 90% of cases of malaria occur, but they appear less frequently in the Amazon, the region most hit by the disease. Here, it is Plasmodium vivax, another species of the protozoon, which causes about 80% of the cases. Furthermore, the transmitter is another mosquito, Anopheles darlingi (the African species is not found in Brazil). “The African malaria has a different biology from the malaria in the Amazon”, says Portillo, a Colombian was has settled in Brazil and been studying the problem for 15 years.

These differences, however, do not prevent the results of the genomes to help to solve the problem in Brazil. “It is wrong to imagine that the sequence of A. gambiae will serve for nothing in the case of Brazil”, explains Morel, who presided the Oswaldo Cruz Foundation, in Rio de Janeiro, before running the TDR. “We can think of the sequence of A. gambiae as a sort of platform, a starting point for studying A. darlingi without having to start from scratch”. According to him, researchers could select an excerpt of the genetic material of the African mosquito and try to develop some kind of insecticide to combat the Brazilian insect. “To see if this region also exists in the darlingi, there is no need to sequence the whole of the darlingi’s genome”, says Morel.

Portillo recalls that there are other difficulties that need to be overcome before arriving at new drugs or vaccines against malaria: for example, one has to know better the biology of the malaria found in the Amazon – a job that, according to him, will take at least another couple of years. Another problem: “We still do not know why the plasmodium becomes resistant to medicines”, says Portillo, who is carrying out research in biotechnology and genetics of populations, as well as tools in bioinformatics for studying the protozoon of Brazilian malaria in a thematic project financed by FAPESP.

Malaria, stresses the researcher from USP, represents a world public health problem related to poverty. “It will be very sad if we have to opt between fighting poverty or fostering basic research into malaria”, says he. “Public policies will need to take in both items”.