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The combination of synthetic anthelmintics and bioactive phytochemicals may be a pharmacological tool for improving nematode control in livestock. Carvone (R-CNE) has shown in vitro activity against gastrointestinal nematodes; however, the anthelmintic effect of bioactive phytochemicals either alone or combined with synthetic drugs has been little explored in vivo. Here, the pharmacological interaction of abamectin (ABM) and R-CNE was assessed in vitro and in vivo. The efficacy of this combination was evaluated in lambs naturally infected with resistant gastrointestinal nematodes. Additionally, the ligand and molecular docking of both molecules to P-glycoprotein (P-gp) was studied in silico. The presence of R-CNE produced a significant (p < 0.05) increase of Rho123 and ABM accumulation in the intestinal explants. After 60 min of incubation, Rho123 incubated with R-CNE had a 67 ± 21% higher concentration (p < 0.01) than when it was incubated alone. In the case of ABM, a significant increase in the intestinal concentrations was observed at 15 and 30 min after incubation with R-CNE. In the in vivo assay, no undesirable effects were observed after the oral administration of R-CNE. The coadministration of the natural compound prolonged ABM absorption in lambs. ABM T½ absorption was 1.57-fold longer (p < 0.05) in the coadministered group. Concentrations of R-CNE between 420 and 2,593 ng/mL were detected in the bloodstream between 1 and 48 h posttreatment. The in vivo efficacy of ABM against gastrointestinal nematodes increased from 94.9 to 99.8% in the presence of R-CNE, with the lower confidence interval limit being >90%. In vitro/in vivo pharmacoparasitological studies are relevant for the knowledge of the interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics. While ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions and the molecular docking study showed a good interaction between ABM and P-gp, R-CNE does not appear to modulate this efflux protein. Therefore, the pharmacokinetic–pharmacodynamic effect of R-CNE on ABM should be attributed to its effect on membrane permeability. The development of pharmacology-based information is critical for the design of successful strategies for the parasite control.

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Four outbreaks of Egg Drop Syndrome '76 (EDS '76) were diagnosed between April 1993 and July 1993 in the Santa Cruz Department of Bolivia, around the department capital Santa Cruz. Three outbreaks involved commercial laying birds and the fourth a broiler breeder unit. Clinical signs were typical of EDS '76 with decreases in egg production of up to 55% being recorded as well as the production of thin shelled and shell-less eggs. A total of 183 serum samples from the 4 farms were tested for the presence of antibodies to the EDS '76 virus using a haemagglutination inhibition test, with titres of 16 or above being considered as a positive result. Of 63 samples from groups of birds showing signs of EDS '76, 58 (92.1%) had positive titres, and 88 out of 90 samples (97.8%) from unaffected groups of birds had negative titres. Out of 30 samples from birds not yet in lay from the affected farms 28 (93.3%) had tires below 16. EDS '76 had not been reported in Bolivia prior to these outbreaks and vaccination was not practised. The most probable source of virus was from day old chicks imported from South American countries which had recorded outbreaks of EDS '76 before April 1993. The source of the virus, its spread and the control measures implemented in the Santa Cruz area are discussed.