A, experimental design. 8-week-old female mice (n = 5–8 mice/group) were infected naturally with L. sigmodontis. At 35dpi the animals were treated orally either with ABBV-4083 (1x (QD) or 2x (BID) 75mg/kg (mpk) per day) for 3, 5, 7 or 10 days with necropsies at 38, 40, 42, 45 & 63dpi or doxycycline (DOX, 2x 40mg/kg per day) for 10 days and necropsy at 63dpi. Controls received an equal amount of vehicle (VEH, necropsy 38, 40, 42, 45 or 63dpi). B, Wolbachia ftsZ/act per female adult worm was quantified by real-time PCR (38dpi: VEH 3d = 60 worms; ABBV-4083 QD 3d = 36 worms; 40dpi: VEH 3d = 57 worms; ABBV-4083 QD 5d = 52 worms; ABBV-4083 BID 5d = 59 worms; 42dpi: VEH 7d = 59 worms; ABBV-4083 QD 7d = 52 worms; 45dpi: VEH 10d = 51 worms; ABBV-4083 QD 10d = 41 worms; 63dpi: VEH 5d = 43 worms; ABBV-4083 QD 5d = 37 worms; ABBV-4083 BID 5d = 60 worms; ABBV-4083 QD 10d = 47 worms, DOX BID 10d = 48 worms). C, experimental design. 8- to 10-week-old female mice (n = 5 mice/group) were infected naturally with L. sigmodontis and treated orally with ABBV-4083 (1x 43mg/kg; 2x 43mg/kg; 1x 50mg/kg; 1x 75mg/kg per day) or VEH for 5 days starting 36dpi with necropsies at 41dpi. D, Wolbachia ftsZ/act per female worm (VEH 5d = 37 worms; ABBV-4083 43mg/kg QD 5d = 27 worms; ABBV-4083 43mg/kg BID 5d = 19 worms; ABBV-4083 50mg/kg QD 5d = 26 worms; ABBV-4083 75mg/kg QD 5d = 17 worms). Data were tested for normal distribution by d‘Agostino & Pearson test. Statistical significance of not normally distributed data (B, D) was analyzed by Kruskal-Wallis followed by Dunn’s multiple comparison test. The horizontal lines indicate the median. p*<0.05, **p<0.01, ***p<0.001, compared with VEH.