Current chemotherapy arsenal for schistosomiasis mansoni: alternatives and challenges

Abdul‐Ghani, Rashad; Loutfy, Naguiba; Sahn, Amel El; Hassan, Azza

doi:10.1007/s00436-009-1371-7

Cited by 49 publications

(29 citation statements)

References 90 publications

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“…11 Accordingly, use of other schistosomicides alone or combined with PZQ was sought with variable results. [12][13][14][15] Arachidonic acid (ARA), also termed all-cis 5,8,11,14-eicosatetraenoic acid, is an omega-6 fatty acid 20:4 (n-6) that is present in the phospholipids (especially phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositides) of membranes of the body's cells, and it was recently found to be a potent schistosomicide able to in vitro kill juvenile and adult male and female Schistosoma mansoni and S. haematobium. [15][16][17] The proposed ARA killing mechanism was activation of parasite surface membrane-associated neutral sphingomyelinase with consequent apical bilayer SM hydrolysis and disruption of the SM-based hydrogen barrier shielding the worm from the hostile elements of the immune system.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Arachidonic Acid for Treatment of Schistosoma mansoni-Infected Children in Menoufiya, Egypt

Selim

Sagheer

Amir

et al. 2014

The American Journal of Tropical Medicine and Hygiene

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Abstract. Arachidonic acid (ARA), an omega-6 fatty acid, kills juvenile and adult schistosomes in vitro and displays highly significant and safe therapeutic effects in mice and hamsters infected with Schistosoma mansoni or S. haematobium. This study aims to examine the efficacy and safety of ARA in treatment of school-age children infected with S. mansoni. In total, 66 S. mansoni-infected schoolchildren (20-23 children/study arm) received a single dose of 40 mg/kg praziquantel (PZQ), ARA (10 mg/kg per day for 15 days), or PZQ combined with ARA. The children were examined before and after treatment for worm egg counts in stool and blood biochemical and immunological parameters. ARA proved to be as efficacious as PZQ in treatment of schoolchildren with low infection intensity (78% and 85% cure rates, respectively). For moderate-intensity infection, the ARA and PZQ combination led to 100% cure rate. Biochemical, hematological, and immunological parameters were either unchanged or ameliorated after ARA therapy.

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Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Arachidonic Acid for Treatment of Schistosoma mansoni-Infected Children in Menoufiya, Egypt

Selim

Sagheer

Amir

et al. 2014

The American Journal of Tropical Medicine and Hygiene

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“…Since in hamster model, OZ78 shows similar efficacy against adult S. mansoni and S. japonicum, the different efficacy of the same drug against the two species of schistosomes in mice model might be associated to the different mouse strains used in experimental chemotherapy, particularly, the difference of immunological response between the two mouse strains, which remains to be further elucidated. On the other hand, it has been reported that the susceptibility of various geographical strains of S. mansoni to oxamniquine is different (Foster and Cheetham 1973;Bruce et al 1987;Delgado et al 1992;Abdul-Ghani et al 2009). Particularly, there had been a naturally resistant strain of S. mansoni which is able to survive drug doses 1,000-fold higher than the effective dose against sensitive parasites (Abdul-Ghani et al 2009).…”

Section: Discussionmentioning

confidence: 96%

Effectiveness of synthetic trioxolane OZ78 against Schistosoma japonicum in mice and rabbits

et al. 2011

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Antischistosomal activities of a synthetic peroxide OZ78 (an ozonide carboxylic acid) against Schistosoma japonicum have been studied in mice and rabbits. Among 132 mice used, 30 of them were infected with 80-100 S. japonicum cercariae for collection of juvenile and adult schistosomes applied in in vitro tests. The remaining 102 mice were infected with 40 schistosome cercariae used for experimental treatment. Other 13 rabbits infected each with 200 schistosome cercariae were treated orally with OZ78 42 days post-infection. Most treated mice and rabbits were sacrificed 4 weeks post-treatment to collect residual schistosomes for evaluation of the drug efficacy. OZ78 and its sodium salt (OZ78-Na salt) 10-60 μg/mL alone exhibited no in vitro effect against day 14, day 21 schistosomula, and day 35 adult schistosomes. But OZ78 and OZ78-Na salt 10 and 20 μg/mL together with hemin 80 μg/mL showed decrease in worm motor activity and severe damage to the worm tegument and intestine, and all worms died within 3 days post-incubation. After infected mice were treated orally with OZ78 at a single dose of 400 mg/kg for 1 day, 34.9% of the worms shifted to the liver. Three and 7 days post-treatment, 100% of the worms were recovered from the liver. Fourteen days post-treatment, 92.3% of the worms still remained in the liver and 7.7% of the worms returned back to the mesenteric veins. Male and female worms shifted to the liver revealed in apparent shrinkage, degeneration of worm body, depigmentation in gut, and disappearance of ova in the uterus of some female worms. Meanwhile, dead worm and dead worm fragments were found in the liver tissues. In mice infected with various stages of schistosomes and treated orally with single OZ78 400 mg/kg, moderate or potential effect of the drug against day 0 (3-h-old worm), day 7, day 14, and day 21 juvenile worms and day 28, day 35 as well as day 42 adult worms were observed, the differences of total or female worm burdens between each treated group and control group were statistically significant (P < 0.01 or P < 0.05). Among the various stages of juveniles, day 7 worms were more susceptible to OZ78 with worm reduction of 83.8%, while the effect of OZ78 against day 28 to day 42 adult worms were similar. Finally, rabbits infected with adult schistosomes and treated with OZ78 at a single dose of 45 mg/kg or a daily dose of 35 mg/kg for three consecutive days resulted in significantly lower total and female worm burdens in comparison with that of control (P < 0.05) with total and female worm reductions of 84.1% and 84.7% as well as 74.3% and 77.4%, respectively. The results demonstrate that OZ78 possesses effect against both juvenile and adult S. japonicum in mouse model, and also shows effect against adult schistosomes in rabbits.

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“…It is most effective on the male parasite than on the female one. At therapeutic doses, it shows greater sensitivity to S. mansoni and has no notable effect on other Schistosoma spp which parasitize human beings (Abdul-Ghani et al, 2009). Several authors have demonstrated the presence of strains resistant to OXA in Brazil.…”

Section: Oxamniquinementioning

confidence: 99%

Medicinal plants and their bioactive constituents: A review of bioactivity against Schistosoma mansoni

Castro¹,

Mattos²,

Souza³

et al. 2013

J. Med. Plants Res.

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Schistosomiasis is a neglected disease that affects approximately 200 million people worldwide. In order to reduce the parasite prevalence, further researches aiming new treatment methods is necessary. Once infected by Shistossoma mansoni, one can have no symptoms in the acute phase, however, chronic phase is characterized by marked egg-induced hepatic granulomatous inflammation. To prevent the disease, the main prophylactic method is environmental sanitation which decreases the entrance of eggs into water bodies. In addition to fighting the snail, treatment of population is important. Currently, for treatment of schistosomisasis, the most used drugs are Praziquantel (PZQ) and Oxamniquine, whereas PZQ is the drug of choice. Each drug has a specific mechanism of action aimed at the elimination of the parasite. However, any parasite treatment based on the use of a single drug poses serious concerns regarding the onset of resistance. The search for new therapeutic agents derived from medicinal plants for schistosomiasis has progressed significantly in the last decade. The aim of this paper is to provide an updated survey on medicinal plants that have significant therapeutic effects in animal models of schistosomiasis. A considerable number of herbal constituents with schistosomicidal effect have been well characterized and may be good candidates for prospective studies and investigations that may result in clinical usage.

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Current chemotherapy arsenal for schistosomiasis mansoni: alternatives and challenges

Cited by 49 publications

References 90 publications

Efficacy and Safety of Arachidonic Acid for Treatment of Schistosoma mansoni-Infected Children in Menoufiya, Egypt

Efficacy and Safety of Arachidonic Acid for Treatment of Schistosoma mansoni-Infected Children in Menoufiya, Egypt

Effectiveness of synthetic trioxolane OZ78 against Schistosoma japonicum in mice and rabbits

Medicinal plants and their bioactive constituents: A review of bioactivity against Schistosoma mansoni

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