Bulletin of the World Health Organization, 2000, 78: 1412-1423.
Voir page 1419 le resume en francais. En la pagina 1420 figura un resumen en espanol.
Plasmodium falciparum malaria remains one of the three most important pathogen-specific causes of human mortality in the world today. The 1998 World Health Report stated that there are now more cases of malaria in the world, perhaps 300-500 million per year (a major underestimate in the minds of many) than there were in 1954 (then estimated at 250 million). More importantly, the annual number of deaths caused by malaria, estimated at between 1.5 and 2.7 million in 1997, seems to have remained stable or even risen over this period (1). The problem of malaria has been exacerbated in recent years by the development and rapid spread of resistance in P. falciparum to the more commonly used and affordable antimalarial drugs. Chloroquine resistance, which first appeared in East Africa in the late 1970s, has now spread throughout most of the continent, and resistance to pyrimethamine--sulfadoxine (Fansidar) has followed rapidly. The emergence of insecticide resistance in African malaria vectors (see below) threatens to exacerbate further the problem.
In 1990, the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), together with the John D. and Catherine T. MacArthur Foundation and the University of Arizona, convened a meeting in Tucson, Arizona. At this meeting, 36 specialists in entomology, genetics and biochemistry were brought together to discuss the prospects for malaria control by genetic modification of the vector competence of natural vector populations (2). In the decade since that meeting, an extraordinary amount of molecular research has been done on malaria vectors, particularly Anopheles gambiae, the principal vector of malaria in sub-Saharan Africa. A fine-scale A. gambiae genetic map based on microsatellite markers and other sequenced tagged sites has been developed (3, 4) and used to map both morphological markers (5) and genes affecting parasite development (6). These markers have also formed the basis of a rapidly increasing number of population genetic and ecological studies of A. gambiae and its sibling species. Studies of innate immunity in Anopheles have revealed an extraordinarily complex defence system, some of whose elements are responsive to malaria parasites (7-19). Several groups are also actively examining the complex interactions between the malaria parasite and its mosquito vector during both the midgut and the salivary gland phases of sporogony (20-31). Other investigators are characterizing genes expressed in the midgut, fat body and salivary, glands, with the long-range goal of developing Plasmodium-inhibiting constructs that can be expressed specifically in these tissues (32, 33).
Indeed, the past year has resulted in two additional important developments in malaria vector research. An efficient technique for Anopheles germ line transformation has been developed (34, 35), and an informal genome project for A. gambiae has been launched. More than 25 000 Anopheles sequences are now in GenBank, more than 6000 of which are cDNAs (36). Around 17 000 of these entries are the end-sequences of a fivefold coverage bacterial artificial chromosome genomic library of A. gambiae (X. Wang, Z. Ke and F. H. Collins, unpublished data), sequenced by the French national genomics centre Genescope. The combined total BAC end-sequence is more than 14 megabases (http://bioweb.pasteur.fr/BBMI), an amount equivalent to about 5.4% of the 260-megabase A. gambiae genome (37). End-sequencing has also begun on a second bacterial artificial chromosome library, containing about 30 000 clones with an almost 20-fold genome coverage (F. H. Collins and H. Zhang, unpublished data). The National Institute of Allergy and Infectious Diseases (National Institutes of Health) has recently reviewed proposals to initiate genomics projects for several new organisms, one of which is A. …