The studies summarized in this report were concerned with the capacities of repository preparations of
cycloguanil pamoate (CGT-P) to protect rhesus monkeys against
infections with
drug-susceptible and
pyrimethamine-resistant strains of Plasmodium cynomolgi. Administered intramuscularly as a
suspension in an oleaginous vehicle, CGT-P (i) provided long-term protection against single and repetitive challenges of rhesus monkeys with sporozoites of the
drug-susceptible B and Ro strains, (ii) effected prompt clearance of
parasitemia in established
infections, and (iii) delayed relapse. Protection was equated to absence of parasites on thick blood films, negative results when blood was transferred to susceptible recipients, and inability to activate
infection by
splenectomy. Eventual loss of protection was not related to emergence of parasites resistant to
cycloguanil (CGT). Although protection varied from monkey to monkey, its mean duration was related directly to size of CGT-P dose and size of particles in the
suspension. Urinary excretion studies indicated that protection persisted as long as the daily output of CGT did not fall below that attained with the parenterally administered hydrochloride
salt at a dose equivalent to 0.015 mg of CGT per kg. Studies on
infections with the resistant Ro/PM strain showed that the activity of CGT-P was compromised severely by resistance to
pyrimethamine. Attempts to minimize this liability by concomitant administration of
4,4'-diacetyldiaminodiphenylsulfone met with limited success. These results suggest that even the best of the repository preparations of CGT-P, with or without
4,4'-diacetyldiaminodiphenylsulfone, would be useful only in areas where Plasmodium falciparum and Plasmodium vivax are fully susceptible to chlorguanide and
pyrimethamine.