In vitro effects of amodiaquine on paired Schistosoma mansoni adult worms at concentrations of less than 5 µg/mL

Kato, Kentaro; Miura, Mitsumasa; Mitsui, Yoshinori

doi:10.1590/0074-0276108022013011

Cited by 6 publications

(6 citation statements)

References 22 publications

(30 reference statements)

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“…Given that S. japiconium eggs are virtually spineless, it is unlikely that the schistosome spine plays a major function. In fact, a recent report comparing egg morphology between Praziquantel resistant and susceptible S. mansoni infection suggests that the spine actually hinders egg transit (47). More specifically, resistant strain eggs were shown to have smaller lateral spines than susceptible strain eggs, and were also more frequently shed into host feces (47).…”

Section: Endothelial Extravasationmentioning

confidence: 99%

“…In fact, a recent report comparing egg morphology between Praziquantel resistant and susceptible S. mansoni infection suggests that the spine actually hinders egg transit (47). More specifically, resistant strain eggs were shown to have smaller lateral spines than susceptible strain eggs, and were also more frequently shed into host feces (47). Thus, from an evolutionary standpoint, perhaps S. japiconium has taken advantage of spine absence.…”

Section: Endothelial Extravasationmentioning

confidence: 99%

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Schistosome Egg Migration: Mechanisms, Pathogenesis and Host Immune Responses

2018

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Many parasitic worms possess complex and intriguing life cycles, and schistosomes are no exception. To exit the human body and progress to their successive snail host, Schistosoma mansoni eggs must migrate from the mesenteric vessels, across the intestinal wall and into the feces. This process is complex and not always successful. A vast proportion of eggs fail to leave their definite host, instead becoming lodged within intestinal or hepatic tissue, where they can evoke potentially life-threatening pathology. Thus, to maximize the likelihood of successful egg passage whilst minimizing host pathology, intriguing egg exit strategies have evolved. Notably, schistosomes actively exert counter-inflammatory influences on the host immune system, discreetly compromise endothelial and epithelial barriers, and modulate granuloma formation around transiting eggs, which is instrumental to their migration. In this review, we discuss new developments in our understanding of schistosome egg migration, with an emphasis on S. mansoni and the intestine, and outline the host-parasite interactions that are thought to make this process possible. In addition, we explore the potential immune implications of egg penetration and discuss the long-term consequences for the host of unsuccessful egg transit, such as fibrosis, co-infection and cancer development.

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Section: Endothelial Extravasationmentioning

confidence: 99%

Section: Endothelial Extravasationmentioning

confidence: 99%

Schistosome Egg Migration: Mechanisms, Pathogenesis and Host Immune Responses

2018

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“…Furthermore, the one-day exposure to AQ also induced the specific alterations (severe swelling and/or localization of hemozoin) in the male and female adult worms at 5 and 10 μg/ml. The alterations were the same as those caused by continuous exposure to AQ [ 9 ]. With subsequent incubation in drug-free media, all the female worms maintained the AQ-specific morphological damage during the 14-day incubation period, while the male worms gradually regained their normal appearance.…”

Section: Discussionmentioning

confidence: 75%

“…On the other hand, Oliver et al showed that chloroquine [ 14 ], one of the 4-aminoquinoline derivatives similar in structure to AQ, exerted antischistosomal activities by inhibiting the formation of hemozoin, a detoxification product of free haem metabolized from haemoglobin. Similarly, it has been surmised that the free haem caused by AQ may be responsible for damaging the reproductive system of female worms and inducing the specific morphological alterations of male and female worms [ 9 ]. The differences in the mode of action of AQ and PZQ are thought to contribute to differences in the specific morphological alterations caused by the two drugs, as well as in the onset of morphological alterations.…”

Section: Discussionmentioning

confidence: 99%

“…These findings suggested that AQ exerted antischistosomal effects synergistically with ART. Mitsui and Aoki, and Kato et al demonstrated that continuous exposure to AQ exerted antischistosomal effects in vitro at concentrations of 1–10 μg/ml and proposed that the drug was a promising candidate for the treatment of schistosomiasis [ 8 , 9 ]. However, orally administered AQ reaches the blood stream within one or two hours, achieves a peak blood concentration and then gradually decreases [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Comparison of the in vitro Effects of One-day Exposure to Amodiaquine and Praziquantel on Schistosoma mansoni Adult Worm Pairs

Mitsui

2014

Trop.Med.Health

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It has been demonstrated that continuous exposure to amodiaquine (AQ) alone elicits in vitro antischistosomal activities at concentrations of 1–10 μg/ml. However, orally administered drugs reach a peak blood concentration within one or two hours and then gradually decrease. The blood concentration does not remain at a constant level over several days as in vitro concentration of continuous drug exposure. In vitro activities by one day exposure to AQ better reflect the actual antischistosomal activities after oral administration than those elicited by continuous exposure.The objective of the present study is to compare the antischistosomal potential of one-day exposure to AQ with that to praziquantel (PZQ), a current antischistosomal drug. Schistosoma mansoni adult worm pairs were incubated with 0 (control), 1, 2, 5 and 10 μg/ml AQ as well as 0.01, 0.02, 0.05 and 0.1 μg/ml PZQ for the first day, and were subsequently incubated in drug-free media for a period of 14 days. The one-day exposure to AQ significantly reduced the daily egg output of the worm pairs at 1–10 μg/ml. The inhibitory effect on egg production continued at 5 and 10 μg/ml but proved temporary at 1 and 2 μg/ml. Furthermore, AQ-induced specific morphological alterations (severe swelling and/or localization of hemozoin) were observed in the worms at 5 and 10 μg/ml. The AQ-specific appearance of the male worms gradually faded during subsequent incubation in drug-free media, although the female worms showed elongation. Meanwhile, PZQ inhibited the egg output of adult worm pairs at concentrations of 0.01–0.1 μg/ml during exposure. The inhibitory effect on egg production continued at 0.05 and 0.1 μg/ml but proved temporary at 0.01 and 0.02 μg/ml. Furthermore, PZQ induced a visible contraction and shortening of the male and female worms at 0.05 and 0.1 μg/ml during exposure, but the PZQ-specific alterations quickly disappeared during subsequent incubation in drug-free media. To our knowledge, this is the first report showing that one-day exposure to AQ inhibits the egg production of adult worm pairs at 1–10 μg/ml and induces specific morphological alterations in the worms at 5 and 10 μg/ml. The present findings have important implications for the evaluation of the therapeutic effects of both AQ monotherapy and combination therapy with artesunate on schistosomiasis in clinical field trials.

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