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P. Ramakrishnan, S. Prakash, and D . S. Choudhury, Nature {London) 179, 974 (1957). 17. F. Hawking and K. Gammage, Trans. Roy. Soc. Trop. Med. Hyg. 56,263 (1962). 18. R. L. Jacobs, / . Parasitol. 51, 481 (1965). 19. D. C. Warhurst and R. Killick-Kendrick, Nature {London) 213,1048 (1967). 20. D. V. Moore and J. E. Lanier, Amer. J. Trop. Med. Hyg. 10, 5 (1961). 21. M. D. Young and D . V. Moore, Amer. J. Trop. Med. Hyg. 10, 317 (1961). 22. D. E. Eyles, C. C. Hoo, W. Warren, and A. A. Sandosham, Amer.

The gravity of the situation is aggravated by the fact that these drugs have been the mainstay in malaria chemotherapy because of important limitations of alternative agents. Chlorguanide and pyrimethamine, as mentioned previously, act too slowly for satisfactory effect in the treatment of acute P. 34 2. GEOGRAPHIC DISTRIBUTION AND GENERAL TYPES OF DRUG RESISTANCE falciparum infections. Some strains of P. falciparum, particularly in Southeast Asia, are resistant to all the above drugs and are commonly referred to as multiresistant strains.

Schmidt (4) and Peters (5) have pointed out that the slope of the dose-response curve, rate of action, and types of susceptible life cycle stages may be expected to be influential. If a drug has a relatively flat dose-response curve larger amounts are required to eradicate all parasites than are necessary for almost complete suppression of the parasitemia and they may exceed the safe dose; thus, conventional doses may fail to eradicate organisms at the extreme end of the spectrum of drug insensitivity.

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