Figure 4.

Effect of primaquine and atovaquone on liver-stage parasite phenotype

(A) Number of parasites present with and without 10 mg/kg atovaquone (ATQ) treatment (days −1 to 7). Control versus treatment for schizonts (p < 0.05, Mann-Whitney) and control versus treatment for hypnozoites (p = 0.468, Mann-Whitney). (B) Log₁₀ 18S rRNA per μg of liver 7 days post-treatment with 10 mg/kg ATQ from days −1 to 7 (control versus ATQ treated, p < 0.001, ANOVA, Tukey’s multiple comparisons) and 28 days post-treatment (control versus ATQ treated, p = 0.325, ANOVA, Tukey’s multiple comparisons). (C) Log₁₀ 18S rRNA per μg of liver 7 days post-infection following treatment with or without 10 mg/kg ATQ from days 4 to 7 (control versus treatment, p = 0.2415, unpaired t test). (D) Number of schizonts and (E) hypnozoites present in the liver 8 days post-infection (primary model) after 2-day treatment with primaquine (PQ) (60 mg/kg) beginning at different days post-treatment. For treatment days 0–1, the number of schizonts in control versus untreated (p < 0.05, Kruskal-Wallis test), treatment days 1–2 (p = 0.267, Kruskal-Wallis test), and treatment days 3–4 (p > 1.0, Kruskal-Wallis test). For the number of hypnozoites in control versus untreated animals treatment days 0–1 (p = 0.119, Kruskal-Wallis test) and treatment days 1–2 and 3–4 (p > 1.0, Kruskal-Wallis test). (F) Number of parasites present 16 days post-infection after treatment with different doses of PQ from day 7 to 16. Control versus treated (all concentrations) schizonts (p = 0.533, Kruskal-Wallis test) and hypnozoites (p = 0.867, Kruskal-Wallis test). (G) Total log₁₀ 18S rRNA per μg of liver following treatment with different concentrations of PQ from days 7 to 16 post-infection. Control versus 15 mg/kg (p = 0.023, ANOVA), 30 mg/kg (p = 0.841, ANOVA), and 60 mg/kg (p = 0.0148, ANOVA) (H) Log₁₀ 18S rRNA per μg of liver 16 (control versus treated, p = 0.0354, unpaired t test) and 21 days post-infection after treatment with different doses of PQ from day 7 to 16. (I) Parasite sizes before and after treatment with PQ (60 mg/kg) for 5 days (3–8 days post-infection) measured 8 and 15 days post-treatment. The parasite isolate used for the control and PQ treament groups was VUBR6. Each dot represents measurements from one animal except in (I). Each dot represents the area measured for one parasite in (I). Barplot error bars represent 95% confidence interval.