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Interferon‐γ induced lethality in the late phase of Plasmodium vinckei malaria despite effective parasite clearance by chloroquine

A combination therapy was tested consisting of chloroquine and interferon‐γ (IFN‐γ) in the late phase of blood‐stage Plasmodium vinckei malaria in BALB/c mice. When mice were treated with three times 300 μg chloroquine at 24‐h intervals starting at a parasitemia of 30%‐50%, only 5 of 14 mice (36%) died 2–4 days after initiation of therapy. However, when infected mice received chloroquine plus 1 μg IFN‐γ at the same time, 14 of 18 mice (78%) died 0.5–3 days after start of therapy (p < 0.05) despite clearance of parasitemia. The histopathology from mice dying after combination therapy revealed interstitial leukocyte infiltration of lung tissue, severe liver cell necrosis and kidney tubular necrosis.