<i>In vitro</i> effects of artesunate on the survival of worm pairs and egg production of <i>Schistosoma mansoni</i>

Mitsui, Yoshinori; Miura, Mitsumasa; Aoki, Yoshiki

doi:10.1017/s0022149x08070235

Cited by 36 publications

(32 citation statements)

References 19 publications

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“…The slightly lower susceptibility of adult S. mansoni worms than NTS to artesunate might be due to the lack of hemin, a primary activator of the peroxide group, in the incubation medium (41). Overall, the findings on the individual parasite stages are consistent with previous in vitro studies with these drugs (2,10,24,27,40).…”

Section: Vol 49 2011 Microcalorimetry To Study Antischistosomal Drusupporting

confidence: 80%

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 Drusupporting

confidence: 80%

Isothermal Microcalorimetry To Study Drugs against Schistosoma mansoni

et al. 2011

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“…However, there was no differential sensitivity to piplartine between male and female worms in vitro (34) . In contrast, treatment with other compounds such as amino alkanethiosulfuric acids (40) , 2-(butylamino)-1-phenyl-1-ethanethiosulfuric acid (41) , and artesunate (42) produced higher mortality rates among female S. mansoni worms than among males.…”

Section: Discussionmentioning

confidence: 74%

In vitro antischistosomal activity of venom from the Egyptian snake Cerastes cerastes

Hassan

Abdel-Rahman

Ibrahim

et al. 2016

Rev. Soc. Bras. Med. Trop.

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Introduction:We studied the potential in vitro antischistosomal activity of Cerastes cerastes venom on adult Schistosoma mansoni worms. Methods: Live specimens of the horned viper snake, C. cerastes were collected from the Aswan Governorate (Egypt). Venom was collected from snakes by manual milking. Worms of S. mansoni were obtained from infected hamsters by perfusion and isolated from blood using phosphate buffer. Mortality rates of worms were monitored after 3 days of exposure to snake venom at LC 50 and various sublethal concentrations (10, 5, 2.5µg/ml). Scanning electron microscopy was used to investigate tegumental changes in treated worms after exposure to LC 50 doses of venom. Results: The LC 50 of C. cerastes venom was 21.5µg/ml. The effect of C. cerastes venom on Schistosoma worms varied according to their sex. The mortality rate of male and female worms after 48-h exposure was 83.3% and 50% , respectively. LC 50 of C. cerastes venom induced mild to severe tegumental damage in Schistosoma worms in the form of destruction of the oral sucker, shrinkage and erosion of the tegument, and loss of some tubercle spines. Conclusions: The present study demonstrated that C. cerastes venom exerts potential in vitro antischistosomal activity in a time and dose-dependent manner. These results may warrant further investigations to develop novel schistosomicidal agents from C. cerastes snake venom.

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“…Incubation of paired S. mansoni adult worms with AQ -The incubation of paired S. mansoni adult worms with AQ was conducted as previously described (Mitsui et al 2009), except for the differences in the test drug and incubation period. Briefly, each pair of adult S. mansoni worms was preincubated for one day with 0.5 mL of NCTC 135 medium in a single well of a 24-well plate (Sumitomo Bakelite Co, Ltd, Osaka, Japan), in a 5% CO 2 incubator at a temperature of 37ºC.…”

Section: Methodsmentioning

confidence: 99%