Table 1.
In vivo data associated with experimental results in Fig 3.
Table 2.
In vivo data associated with experimental results in Fig 6.
Table 3.
Inhibitory concentration 50% (IC50) values in μg/mL with standard error for two cyathostomin lines treated with either pyrantel or Cry5B.
Fig 1.
Dose response of tribendimidine against hookworm A. ceylanicum infections in hamsters.
(A), (C), and (E): Effects of tribendimidine at indicated doses on intestinal hookworm burdens in hookworm-infected hamsters. For (A), (C), and (E) and in similar figures below, the hookworm burdens in each hamster are indicated with a separate symbol, long horizontal bars represent mean hookworm burdens per group; small bars indicate standard error. (B), (D), and (F): Effects of tribendimidine at indicated doses on parasite egg production (fecal egg counts) in hookworm-infected hamsters. For (B), (D), and (F) and in similar figures below, shown are the average eggs per gram of feces in each group on day 4 post-treatment. The fecal egg counts in each animal are indicated with a separate symbol. Long horizontal bars represent mean eggs per gram of feces (EPG) per group; small bars indicate standard error. Panel (A) & (B); (C) & (D) and (E) & (F) came from three independent in vivo experiments. TrBD = tribendimidine.
Fig 2.
Dose response of Cry5B spore-crystal lysates (SCL) against hookworm A. ceylanicum infections in hamsters.
Effects of Cry5B SCL at indicated doses on (A) intestinal hookworm burdens and (B) fecal egg counts in hookworm-infected hamsters.
Fig 3.
Cry5B and tribendimidine in combination are synergistic in vivo against hookworm infections in hamsters.
Effects of individual treatment of Cry5B alone or tribendimidine alone and combination treatment of Cry5B plus tribendimidine at indicated doses on (A) intestinal hookworm burdens and (B) fecal egg counts in hookworm-infected hamsters. Brackets indicate statistical comparisons between groups, with p values shown. Data come from the combination of two independent in vivo experiments. TrBD = tribendimidine.
Fig 4.
The 1:1 Cry5B:tribendimidine combination at a higher dose eliminates hookworm infections in hamsters.
Effects of treatment of higher dose Cry5B alone or higher dose tribendimidine alone or higher dose Cry5B plus higher dose tribendimidine in combination on (A) intestinal hookworm burdens and (B) fecal egg counts in hookworm-infected hamsters. None of the individual drugs eradicated the hookworm infections in hamsters, but the combination of both drugs did. TrBD = tribendimidine.
Fig 5.
Dose response of pyrantel against hookworm A. ceylanicum infections in hamsters.
Effects of pyrantel at indicated doses on (A) intestinal hookworm burdens and (B) fecal egg counts in hookworm-infected hamsters. PYR = pyrantel.
Fig 6.
Cry5B and pyrantel in combination are synergistic in vivo against hookworm infections in hamsters.
Effects of individual treatment of Cry5B alone or pyrantel alone and combination treatment of Cry5B plus pyrantel at indicated doses on (A) intestinal hookworm burdens and (B) fecal egg counts in hookworm-infected hamsters. Black arrow indicates the effect of the combination of Cry5B and pyrantel at ratio of 3:1 (1 mg/kg Cry5B + 0.33 mg/kg pyrantel), showing greater than expected impact based on individual doses or next highest combination dose. PYR = pyrantel.
Fig 7.
The 3:1 Cry5B:pyrantel combination at a higher dose eliminates hookworm infections in hamsters.
Effects of treatment of higher dose Cry5B alone or higher dose pyrantel alone or higher dose Cry5B plus higher dose pyrantel in combination on (A) intestinal hookworm burdens and (B) fecal egg counts in hookworm-infected hamsters. None of the drugs individually eradicated the hookworm infections in hamsters but the combination of both drugs did. PYR = pyrantel.
Fig 8.
Pyrantel-resistant cyathostomins are hypersusceptible to Cry5B.
Dose-dependent developmental inhibition of a non-anthelmintic resistant population of cyathostomins (Barn 10; [62]) and of an anthelmintic-resistant population of cyathostomins (pyrantel-resistant Population S or PYR_R) to (A) pyrantel and (B) purified Cry5B. Each data point represents the % of larvae that matured to the infectious L3 stage (L3i). Error bars indicate standard error from three independent replicates. Susep = Barn 10, pyrantel susceptible; PYR_R = pyrantel-resistant population.