In vivo anti-Wolbachia efficacy of AWZ1066S. (A and B) Anti-Wolbachia efficacy against female adult-stage B. malayi in SCID mice (A) or L. sigmodontis in gerbils (B) after doxycycline (DOX), minocycline (MIN), or AWZ1066S oral treatments at the indicated doses. Tail and whisker plots are minimum, 25th, median, 75th, and maximum Wolbachia wsp or ftsz copy number per female worm in samples of 5 to 24 worms derived from groups of four to nine animals from an individual experiment. Significant differences compared with vehicle/untreated are indicated ****P < 0.0001, **P < 0.01 (Kruskal–Wallis with Dunn’s tests for intergroup Wolbachia variation). bid, twice a day. (C) Longitudinal effects on circulating L. sigmodontis microfilaremias −1 to 18 wk after DOX or AWZ1066S oral treatments at the indicated doses in gerbils. (D) Result of PK/PD Monte Carlo prediction of clinical activity of AWZ1066S when dosed at 600 mg given predicted PK properties in humans and established in vitro PD properties against Wolbachia.