A screening method for tissue schizontocides with Plasmodium yoelii
Abstract
Primaquine pyrimethamine, chloroquine and long-acting blood schizontocide pyronaridine were tested with several causal prophylactic and tissue schizontocidal screening methods. The sporozoites of Plasmodium yoelii strain 265-By disappeared from the blood of mice 30 min after an ip inoculation and the prapatent period of the parasites was 48 h or less. A modified method for preliminary screening for tissue schizontocides is suggested:
(1) Test compound is dosed orally or parenterally to 2 groups of 10 mice each -1 h after an ip inoculation of P.yoelii sporozoites on d 0. The doses are 20 mg/kg and a maximal tolerable dose (or 100 mg/kg). Blood examinations are made on d 7 and d 14. Sign (-) denotes that at least 6/10 mice are negative for parasitemia. If the examinations on d 7 and /or d 14 are(+), the test compound is considered to have no tissue schizontocidal effect; if the result is(-) on d 14, it may be effective against tissue form and test (2) for differentiating residual blood schizontocidal action is needed.
(2) Adose is given to 10 mice 48 h before an inoculation of 5×106 parasitized rbc. Blood examinations are made on d 5 and d 10. If both examinations are (+), the drug is considered to have tissue schizontocidal action; if it is (-) on d 5, the drug may have residual schizontocidal action and test (3) is suggested to indentify long-acting tissue schizontocidal action.
(3) The days (a) of residual blood schizontocidal effect is first detected by giving a dose before the inoculation of parasitized rbc, then a dose is given to clean mice a-1 days before sporozoite inoculation. If parasitemia on d 14 is (-), a prolonged (a-1 days) tissue schizontocidal action is suggested.
Keywords:
(1) Test compound is dosed orally or parenterally to 2 groups of 10 mice each -1 h after an ip inoculation of P.yoelii sporozoites on d 0. The doses are 20 mg/kg and a maximal tolerable dose (or 100 mg/kg). Blood examinations are made on d 7 and d 14. Sign (-) denotes that at least 6/10 mice are negative for parasitemia. If the examinations on d 7 and /or d 14 are(+), the test compound is considered to have no tissue schizontocidal effect; if the result is(-) on d 14, it may be effective against tissue form and test (2) for differentiating residual blood schizontocidal action is needed.
(2) Adose is given to 10 mice 48 h before an inoculation of 5×106 parasitized rbc. Blood examinations are made on d 5 and d 10. If both examinations are (+), the drug is considered to have tissue schizontocidal action; if it is (-) on d 5, the drug may have residual schizontocidal action and test (3) is suggested to indentify long-acting tissue schizontocidal action.
(3) The days (a) of residual blood schizontocidal effect is first detected by giving a dose before the inoculation of parasitized rbc, then a dose is given to clean mice a-1 days before sporozoite inoculation. If parasitemia on d 14 is (-), a prolonged (a-1 days) tissue schizontocidal action is suggested.