Abstract
BackgroundCysteine proteinases (CPs) from papaya (Carica papaya) possess anthelmintic properties against human soil-transmitted helminths (STH, Ascaris lumbricoides, Trichuris trichiura and hookworm), but there is a lack of supportive and up-to-date efficacy data. We therefore conducted two randomized controlled trials in pigs to assess the efficacy of papaya CPs against experimental infections with T. suis.MethodsFirst, we assessed efficacy by means of egg (ERR) and adult worm reduction rate (WRR) of a single-oral dose of 450 μmol active CPs (CP450) against low (inoculum of 300 eggs) and high (inoculum of 3,000 eggs) intensity T. suis infections and compared the efficacy with those obtained after a single-oral dose of 400 mg albendazole (ALB). In the second trial, we determined and compared the efficacy of a series of CP doses (45 [CP45], 115 [CP115], 225 [CP225], and 450 [CP450] μmol) against high intensity infections.ResultsCP450 was highly efficacious against both levels of infection intensity, resulting in ERR and WRR of more than 97%. For both levels of infection intensity, CP450 was significantly more efficacious compared to ALB by means of WRR (low infection intensity: 99.0% vs. 39.0%; high infection intensity; 97.4% vs. 23.2%). When the efficacy was assessed by ERR, a significant difference was only observed for high intensity infections, CP450 being more efficacious than ALB (98.9% vs. 59.0%). For low infection intensities, there was no significant difference in ERR between CP450 (98.3%) and ALB (64.4%). The efficacy of CPs increased as a function of increasing dose. When determined by ERR, the efficacy ranged from 2.1% for CP45 to 99.2% for CP450. For WRR the results varied from -14.0% to 99.0%, respectively. Pairwise comparison revealed a significant difference in ERR and WRR only between CP45 and CP450, the latter being more efficacious.ConclusionsA single dose of 450 μmol CPs provided greater efficacy against T. suis infections in pigs than a single-oral dose of 400 mg ALB. Although these results highlight the possibility of papaya CPs for controlling human STH, further development is needed in order to obtain and validate an oral formulation for human application.
Highlights
Cysteine proteinases (CPs) from papaya (Carica papaya) possess anthelmintic properties against human soil-transmitted helminths (STH, Ascaris lumbricoides, Trichuris trichiura and hookworm), but there is a lack of supportive and up-to-date efficacy data
Proof-of-principle trial Table 1 summarizes the number of animals, mean fecal egg counts (FEC) at D-1, the mean FECs at D+6 and the mean worm counts (WC) at D+7 for each of the three treatment groups, and the efficacy of CP450 and ALB for low and high intensity T. suis infections, separately
The ratio of mean FECs at D+6 and WCs at D+7 in the control animals inoculated with 3,000 eggs and the control animals inoculated with 300 eggs was 18.6 [95% CI: 5.2; 57.0] and 8.7 [95% CI: 6.3; 11.8], respectively
Summary
Cysteine proteinases (CPs) from papaya (Carica papaya) possess anthelmintic properties against human soil-transmitted helminths (STH, Ascaris lumbricoides, Trichuris trichiura and hookworm), but there is a lack of supportive and up-to-date efficacy data. Papaya CPs have a different mode of action to current anthelmintics (digestion of helminth cuticles) [25], and they are a serious contender for an alternative backup drug should anthelminthic resistance occur against the benzimidazoles. They are likely to have more than one target site on the cuticle, making rapid development of resistance very unlikely. Their impact is not restricted to STH, but may have a clear impact on other gastro-intestinal parasites, as shown by the in vitro experiments on animal tapeworms [25,26]
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