Table 1.
Protection against reinfection by exposure to sporozoites under pyrimethamine causal prophylaxisa
Drug | Initial challenge |
Rechallenge |
||||
---|---|---|---|---|---|---|
Time to challenge (days) | No. of animals protected/infected (%) | Prepatencyb (days) | Time to rechallenge (days) | No. of animals protected/infected (%) | Prepatency (days) | |
Pyrimethamine | 35 | 9/9 (100)c | N/A | 130 | 5/5 (100) | N/A |
64 | 4/4 (100) | N/A | 158 | 1/4 (25) | (8) | |
199 | 4/4 (100) | N/A | ||||
Noned | 0/5 (0) | 3 |
Pyrimethamine was administered orally with the drinking water for 42 h at a concentration of 70 μg/ml to C57BL/6 mice. Animals were immunized three times by intravenous injection of 10,000 sporozoites each time. Boosts were given at 2- to 4-week intervals under oral pyrimethamine. Animals were challenged by intravenous injection of 10,000 sporozoites or by bites from 5 to 10 infectious mosquitoes. Rechallenge was carried out by intravenous injection of 10,000 sporozoites. Animals were monitored for parasitemia for at least 14 days after challenge.
Defined as the time to detection of the first blood-stage parasite. N/A, not applicable.
In another experiment, 3 protected animals were challenged with 7,500 infected red blood cells; they developed parasitemia on the same day as the controls (day 5), indicating liver-stage-specific protection of the sporozoite immunization protocol.
Data for control animals are displayed from combined experiments. For all challenges, age-matched naïve control animals (at least 2) were infected in parallel.