A symposium on containment of mefloquine-resistant falciparum malaria in Southeast Asia with special reference to border malaria.

Important questions related to the factors responsible for and contributing to the origin and spread of multi-drug resistant falciparum malaria at the Thai-Cambodian and Thai-Myanmar border areas are discussed, including the current geographical distribution of multi-drug resistance and the prevention and control of this phenomenon. Specific recommendations are made on epidemiological surveillance, drug deployment, vector control, and the problem of migration which plays a major role in the dissemination of resistant parasite populations. The recent advent of mefloquine resistance of P. falciparum in Thailand may serve as fair warning in the absence of stern measures for preventing the occurrence of resistance to the next and currently last line of antimalaria drugs, especially those with a long half-life, in areas with intensive, uncontrolled malaria transmission, such as tropical Africa.

The biological and epidemiological basis of drug resistance in malaria parasites.

Natural populations of Plasmodium falciparum without previous drug exposure are mixtures of individual parasites with different levels of response to a specific medicament. Exposure to sublethal drug concentrations will eliminate the highly and moderately sensitive individuals. The less sensitive part of the parasite population is being selected and given the opportunity of propagating. Underdosed mass drug administration and subcurative medication have this direct effect. An indirect effect with the same result is observed with drugs having a long half-life, where new infections invade the blood while subtherapeutic residual drug concentrations are still present. This militates against the use of drugs with long half-life in areas with intensive malaria transmission, and for a rational therapeutic use of alternative antimalarials based on reliable microscopic diagnosis, adequate dose regimens, post-treatment follow-up, further alternative treatment of recrudescences with the objective of radical cure.

In vitro sensitivity of multiresistant Plasmodium falciparum to new candidate antimalarial drugs in western Thailand.

The present study, carried out in 1987 in Thailand, has been designed to validate the in vitro microtest system, standardized by the World Health Organization (WHO), for the new antimalarials pyronaridine and halofantrine. The sensitivity of naturally acquired, multiresistant populations of Plasmodium falciparum has been assessed in order to develop a data base for further longitudinal investigations. For both drugs the in vitro microtest system seems to be suitable. The concentration range of plates can be considered as almost ideal for pyronaridine (0.1-6.40 mumol/l) while for halofantrine (0.002-0.128 mumol/l) an upward extension of the concentration range would be appropriate. Validation studies with artemisinin demonstrated the need for revising the protocol for the production of the dosing solutions. In the light of current knowledge about therapeutic concentration levels it would probably be appropriate to adopt a range of 0.2-12.8 mumol/l. All tested isolates, except possibly three, showed sensitive responses to pyronaridine. The high EC99 value of halofantrine could be indicative of some resistance to this drug. Rank correlation analysis suggested cross-resistance of pyronaridine and chloroquine which could be of consequence for the future introduction of pyronaridine.