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. 2019 Aug 5;13(8):e0007636. doi: 10.1371/journal.pntd.0007636

Fig 4. Continuous daily treatments with ABBV-4083 are not required for depletion of Wolbachia and microfilariae.

Fig 4

A, experimental design. L. sigmodontis-infected jirds were treated orally either with ABBV-4083 1x 25mg/kg (mpk) QD consecutively for 7, 10 or 14 days (n = 6–7, consecutively (Con) treated group), or discontinuously (Dis) for 7 days total with skipped treatments on days 6 and 8 or discontinuously for 14 days with skipped treatments on days 6, 8, 13, and 15 (n = 6). Vehicle treated animals served as negative controls (VEH, n = 7), ABBV-4083 1x 50mg/kg for 14 day treated animals served as positive control. B, Wolbachia ftsZ/act ratio of isolated female adult worms at 8 weeks after treatment start (VEH = 12 worms; ABBV-4083 50mg/kg Con = 16 worms; ABBV-4083 25mg/kg 7d Con = 23 worms; ABBV-4083 25mg/kg 7d Dis = 9 worms; ABBV-4083 25mg/kg 10d Con = 19 worms; ABBV-4083 25mg/kg 14d Con = 27 worms; ABBV-4083 25mg/kg 14d Dis = 13 worms). Data were tested for normality by d‘Agostino & Pearson test. Statistical significance of not normally distributed data shown in B was analyzed by Kruskal-Wallis followed by Dunn’s multiple comparison test. ***p<0.001. C, Wolbachia ftsZ/microfilaria over time (mean + SEM). D, Spearman correlation of Wolbachia ftsZ/microfilariae and median ftsZ/female adult worms from the same animals at 8wpt. E, Microfilariae counts over time (mean + SEM) and F, embryograms from female adult worms (VEH = 6 worms; ABBV-4083 50mg/kg Con = 6 worms; ABBV-4083 25mg/kg 7d Con = 10 worms; ABBV-4083 25mg/kg 7d Dis = 1 worm; ABBV-4083 25mg/kg 10d Con = 7 worms; ABBV-4083 25mg/kg 14d Con = 16 worms; ABBV-4083 25mg/kg 14d Dis = 8 worms). The following embryonic stages were counted: egg, morula, pretzel and stretched MF, as well as degenerated early (egg, morula) and late (pretzel, stretched MF) stages. Data are presented as median.