[Resistance of Plasmodium falciparum to antimalarials: practical implications and control prospects]

The author reviews the present knowledge on the resistance of P. falciciparum to various antimalarials, such as the inhibitors of the dehydrofolate reductase (proguanil, pyrimethamine, cycloguanil embonate and trimethoprim), the 4-aminoquinolines, quinine and the combination of sulfadoxine-pyrimethamine and combinations of other antimalarials and outlines the geographical distribution of P. falciparum chloroquine-resistant strains. The genetic peculiarities of resistance to antimalarials and their possible relation to the actions exerted by the drugs in some biological processes of the parasite are described in the light of present knowledge. The classification of the response of P. falciparum to 4-aminoquinolines, proposed by a working group of the World Health Organization (sensitivity, resistance at R I, R II and R III levels) and the methods at present available to define the different responses (in vivo and in vitro methods) are described in detail. Attention is then drawn to the practical implications resulting from the continuous spreading of the phenomenon of drug-resistance, both in countries already affected by the problem and in those which are exposed to the risk of the importation of drug-resistant strains. Practical advice is given: (i) for the treatment of chloroquine- or poly-resistant P. falciparum strains with a brief description of the therapeutic potentialities of new antimalarials still at the experimental stage, especially mefloquine and (ii) on the measures to be taken to prevent the spreading and to control the phenomenon of drug-resistance. The future prospects for an efficacious control of the disease and of drug-resistance are viewed with some pessimism, due to the recent discovery of chloroquine-resistant P. falciparum strains in Africa and to the scarcity of the financial resources required to implement adequate control programmes.