Schistosoma mansoni: Schistosomicidal effect of mefloquine and primaquine in vitro

Holtfreter, Martha C.; Loebermann, Micha; Klammt, Sebastian; Sombetzki, Martina; Bodammer, Peggy; Riebold, D.; Kinzelbach, Ragnar; Reisinger, Emil C.

doi:10.1016/j.exppara.2010.08.008

Cited by 37 publications

(37 citation statements)

References 26 publications

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“…However, cercariae and tails also produce heat-flow signals, which might disturb the heat-flow signal of the parasites of interest. Furthermore, the drug susceptibilities of cercarial stages can be different from those of schistosomula (13,28), resulting in false-positive or -negative signals. Another explanation might be that the drugs analyzed impact motility and morphology (which are not detectable on NTS by IMC) rather than the metabolic activity of NTS.…”

Section: Vol 49 2011 Microcalorimetry To Study Antischistosomal Drumentioning

confidence: 99%

Isothermal Microcalorimetry To Study Drugs against Schistosoma mansoni

et al. 2011

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Alternative antischistosomal drugs are required since praziquantel is virtually the only drug available for treatment and morbidity control of schistosomiasis. Manual microscopic reading is the current "gold standard" to assess the in vitro antischistosomal properties of test drugs; however, it is labor-intensive, subjective, and difficult to standardize. Hence, there is a need to develop novel tools for antischistosomal drug discovery. The in vitro effects of praziquantel, oxamniquine, artesunate, and mefloquine on metabolic activity and parasite motility of Schistosoma mansoni (newly transformed schistosomula [NTS] and 49-day-old adult worms) were studied using isothermal microcalorimetry (IMC). Results were compared to morphological readouts of viability. Results obtained for the four drugs tested with phenotypic evaluation by microscopy and IMC showed a good correlation, but IMC also identified drug effects that were not visible by microscopic evaluation, and IMC precisely determined the onset of action of the test drugs. Similar sensitivities on NTS and adult schistosomes were observed for praziquantel and mefloquine, while slight differences in the drug susceptibilities of the two developmental stages were noted with oxamniquine and artesunate. IMC is a useful tool for antischistosomal drug discovery that should be further validated. In addition, our data support the use of NTS in in vitro antischistosomal drug assays.Schistosomiasis, caused by blood flukes of the genus Schistosoma, is an important health problem affecting 779 million people mainly in sub-Saharan Africa (36). Praziquantel is virtually the only drug available and is increasingly deployed in mass drug administration programs, advocated by the World Health Organization (11). The annual estimated need for praziquantel in Africa exceeds 400 million tablets (http://www .who.int/wormcontrol/newsletter/PPC7_Eng_min.pdf). Two alternative drugs, oxamniquine and metrifonate, exist; however, they are rarely used today as they have a rather narrow activity profile and multiple doses have to be administered (12, 37). The extensive use and reliance on one single agent have raised concerns about the emergence of praziquantel resistance (3,8), and indeed, schistosome strains with increased drug tolerance have already been isolated from patients as well as selected in the laboratory (9, 26). Therefore, there is growing consensus that novel antischistosomal drugs should be discovered and developed (8,15,33).Antischistosomal drug discovery at many academic institutions (e.g., the Special Programme for Research and Training in Tropical Diseases; screening centers in London, United Kingdom, and Cairo, Egypt; the University of California, San Francisco, Sandler Center in San Francisco, CA; and the Swiss Tropical and Public Health Institute [Swiss TPH] in Basel, Switzerland) is based on in vitro whole-organism drug screening assays followed by in vivo tests in infected mice (15, 31). Stages used for in vitro assays are 1-to 7-day-old schistosomula (newly transfor...

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Section: Vol 49 2011 Microcalorimetry To Study Antischistosomal Drumentioning

confidence: 99%

Isothermal Microcalorimetry To Study Drugs against Schistosoma mansoni

et al. 2011

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“…2C, D. These morphological alterations in male and female worms incubated with AQ had a very specific appearance. Although Holtfreter et al (2011) did not report the effect of PQ on the intestinal tract of male and female worms, PQ, which is similar in structure to AQ, most likely also causes morphological alterations in the intestinal tract of male and female worms.…”

Section: Discussionmentioning

confidence: 99%

“…Mitsui and Aoki (2010), however, demonstrated that not only MQ, but also other antimalarial drugs, such as AQ, chloroquine (CQ) and primaquine (PQ), exhibited in vitro antischistosomal activity at a concentration of 10 µg/mL. Subsequently, the in vitro antischistosomal activity of PQ was confirmed at concentrations lower than 2 µg/mL (Holtfreter et al 2011). Mitsui and Aoki (2010) observed that AQ exhibited higher in vitro antischistosomal activity than PQ at a concentration of 10 µg/mL and they cited AQ as a promising candidate for the treatment of schistosomiasis.…”

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

Kato

Miura

Mitsui

2013

Mem. Inst. Oswaldo Cruz

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“…Although PZQ has several advantages, including tolerability, safety, efficacy, and low cost, it does not protect individuals from reinfection and is not active against the immature stages of the worm, such as the schistosomula, pre-adult and juvenile adult stages 12 . Therefore, there is an urgent need to identify new drugs that can combat S. mansoni.…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural study of morphological changes in Schistosoma mansoni after in vitro exposure to the monoterpene rotundifolone

Rocha

Cavalcanti

Barbosa-Filho

et al. 2017

Rev. Soc. Bras. Med. Trop.

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Introduction: Schistosomiasis, a parasitic disease caused by trematode flatworms of the genus Schistosoma, affects more than 200 million people worldwide, and its control is dependent on a single drug, praziquantel. Here, we report the in vitro effect of rotundifolone, a monoterpene isolated from Mentha x villosa (Lamiaceae), on Schistosoma mansoni adult worms. Methods: The in vitro effect of rotundifolone on adult Schistosoma mansoni was evaluated by analysis of behavior and mortality and through a scanning electron microscopic analysis of ultrastructural changes in the tegument of the worms. Results: At concentrations of 3.54 and 7.09μg/mL -1 rotundifolone, no worm mortality was observed at any of the sampling intervals. A minor reduction in movement of the tail, suckers, and gynecophoral canal membrane was observed after 96 h of exposure to 7.09μg/mL -1 rotundifolone. At 70.96μg/mL -1 , a lack of movement was observed from 72h onwards and all worms were deemed dead; similar effects were observed at 48h with 177.4μg/mL -1 , and at 24h with 354.8μg/mL -1 and 700.96μg/mL -1 . Rotundifolone also caused death of all parasites and separation of coupled pairs into individual males and females after 24h at 354.8μg/mL -1 . Conclusions: The main changes in the tegument induced by the different ROT treatments were: after 24h incubation, bubble lesions spread over the entire body and loss of tubercles occurred in some regions of the ventral region.

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Schistosoma mansoni: Schistosomicidal effect of mefloquine and primaquine in vitro

Cited by 37 publications

References 26 publications

Isothermal Microcalorimetry To Study Drugs against Schistosoma mansoni

Isothermal Microcalorimetry To Study Drugs against Schistosoma mansoni

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

Ultrastructural study of morphological changes in Schistosoma mansoni after in vitro exposure to the monoterpene rotundifolone

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