Studies on the efficacy of atabrine suppression of malaria in American and Australian troops in New Guinea and Australia from June 1943 to January 1945 are presented. The concentration of atabrine present in the plasma of those developing malaria despite supposed suppression is compared with data from adequately suppressed troops. This comparison shows that clinical malaria develops in the presence of inadequate amounts of atabrine. The concentration of atabrine present in “break-throughs” is the same in chronic relapses and “primary” attacks of malaria. It is possible that P. falciparum requires in the field a slightly greater amount of atabrine to be completely suppressed. Our data would support but not establish such a contention. The difference is not great enough to be of practical importance.
The difficulty of obtaining any large number of cases of malaria who consistently claim to have regularly taken 0.1 gram or more of atabrine every day and who have nevertheless developed clear-cut malaria emphasizes the fact that atabrine suppression is mainly a problem of drug administration. However, the development of malaria in an individual can not be taken as definite proof that that individual has failed to take atabrine regularly even if his drug level is low. Variation of drug level obtained with a standard dose is so great that, granting concentration is related to protection, a small percentage would be unprotected by the standard dosage of 0.7 grm of atabrine per week.
The evaluation of several different dosages of atabrine by studies of the concentration of atabrine in the plasma under different conditions and at different times fails to indicate any need for a dosage greater than 0.1 gram per day. Atabrine levels are adequate between doses when 0.4 gram or 0.5 gram is given twice a week. This dosage scheme must be judged on the realtive value of giving the drug fewer times during the week, the increased nausea produced by larger doses, and the greater hazard of more serious reactions when such amounts of atabrine are ingested over a long period.
On leave from The Rockefeller Institute, Princeton, N. J.
On leave from the International Health Division of the Rockefeller Foundation.