Volume 26, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



The experiments described in this report have dealt with the dimensions of therapeutic potentiation achieved when combinations of pyrimethamine and sulfadiazine were administered to rhesus monkeys infected with a drug-susceptible strain of or its pyrimethamine-resistant variant and to owl monkeys infected with strains of and of varying degrees of resistance to this pyrimidine. These evaluations showed: 1) that when delivered in combination, the activities of pyrimethamine and sulfadiazine against infections with any of the above strains were enhanced significantly; 2) that in infections with the and strains of and the Vietnam Palo Alto strain of , concomitant delivery of the two agents resulted in a 32-fold increase in the activity of pyrimethamine and a 50- to 100-fold increase in the activity of sulfadiazine; 3) that as a result of this synergism, infections with the pyrimethamine resistant and Palo Alto strains could be cured with a fraction of the maximum tolerated dose of this drug; 4) that in marked contrast to the above result, infections with the Malayan Camp and Vietnam Smith strains of could not be cured regularly by combination regimens which included the maximally tolerated dose of pyrimethamine. This poor response has been attributed to the high levels of pyrimethamine-resistance possessed by these strains. It is believed that the comparatively small but not insignificant incidences of treatment failures associated with delivery of pyrimethamine-sulfonamide combinations to both patients and human volunteers infected with multidrug-resistant strains of rest on a similar basis.


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