The Synaptic Leap

Parasitology Research (17 January 2012), pp. 1-6.

Echinostomiasis is a food-borne intestinal, snail-mediated parasitosis caused principally by ingestion of snails infected with digenean trematodes of the Echinostoma genus. The treatment and control of trematodiasis is usually done by administration of praziquantel (PZQ). In this study, we evaluated the effect on Echinostoma paraensei of different doses of praziquantel through analysis of morphological parameters using light microscopy, scanning electron microscopy, and confocal scanning laser microscopy along with parasitological data. We used 30 female mice aged 4 weeks. Each animal was given 40 metacercarie of E. paraensei by gavage. The animals were divided into five groups, each group containing six animals, where one group was utilized as untreated control. Two weeks after infection, the mice were given praziquantel by gavage at total dosages of 12.5, 25, 50 or 100 mg/kg by body weight. Two days after treatment, the mice were euthanized in a CO 2 chamber for recovery of helminths in the small intestine. The doses of 50 and 100 mg/kg of praziquantel eliminated all the worms. There were significant differences ( p < 0.05) between all the treated groups when compared to the control group. The body morphology showed contraction with vacuolization of the parenchyma, and the spine of the peristomic collar was not evident by light microscopy. The scanning electron microscopy revealed that the other doses caused retraction of spines of the peristomic collar and also the tegument spines at the body edge, as well as the development of vesicles and peeling; all these alterations were more evident at the dose of 25 mg/kg. In turn, the confocal scanning laser microscopy revealed vacuolization and disorganization of spines and vitelline glands. E. paraensei responds differently to experimental treatment with praziquantel according to the doses utilized causing morphological alteration and even worm elimination.
Juliana Ferraz, Joyce Souza, Michele Costa-Silva, Eduardo Torres, André Santana, Reinalda Lanfredi, Arnaldo Maldonado, Juberlan Garcia

Acta Tropica (January 2012)

Nigeria is highly endemic for infection with Schistosoma haematobium, which most commonly manifests itself with blood in urine. To monitor the impact of annual mass drug administration (MDA) with Praziquantel for S. haematobium in Delta State, Nigeria, cross-sectional hematuria surveys of school children were conducted in 8 sentinel villages (SVs) at baseline (n = 240) and after two annual doses (n = 402). We assessed the comparability of three assessments of hematuria (child's reported history, nurse visual diagnosis (NVD) and dipstick) to determine the need for mass treatment. Dipstick was considered to be the gold standard. Prior to treatment, history and NVD each identified only the 3 most highly prevalent SVs, and overall this represented just 37.5% of the 8 SVs in need of treatment. Following treatment, after dipstick prevalence decreased by 88.5% (p < 0.001), and history and NVD identified only one of two villages still needing treatment. The study suggests that dipsticks should be the recommended method for launching and monitoring mass treatment for S. haematobium. Praziquantel treatment for Schistosoma haematobium decreased dipstick prevalence of hematuria by 88.5%. Urine dipsticks were superior to history and NVD for identifying communities needing treatment. ⺠We monitored impact of annual Praziquantel for Schistosoma haematobium in Delta State, Nigeria. ⺠Cross-sectional surveys of school children conducted at baseline and after 2 years. ⺠Compared three assessments of hematuria to determine the need for mass treatment. ⺠Following treatment, dipstick prevalence of hematuria decreased by 88.5% (p < 0.001). ⺠History and NVD failed to identify all communities in need of treatment.
Emmanuel Emukah, Julie Gutman, John Eguagie, Emmanuel Miri, Paul Yinkore, Ndudi Okocha, Victoria Jibunor, Nebe Obiageli, Nwoye Ikenna, Frank Richards

Bioorganic & Medicinal Chemistry Letters (January 2012)

A praziquantel analog 10-hydroxy praziquantel and eight praziquantel/peroxide conjugates were synthesized. The biological activity of these compounds was evaluated against juvenile and adult stages of Schistosoma japonicum. Unlike praziquantel, 10-hydroxy praziquantel exhibits activity against both juvenile and adult Schistosoma japonicumin. All hybrid compounds displayed modest to significant worm killing activity. The present study has important significance for the development of hybrid antischistosomal drugs.
Wen-wen Duan, Si-jie Qiu, Yue Zhao, Huan Sun, Chunhua Qiao, Chao-ming Xia

Bioorganic & Medicinal Chemistry Letters (December 2011)

An efficient Synthesis of antischistosomal drug Praziquantel and analogues was achieved and the synthetic route designed was to afford structurally diverse analogues for better structure–activity relationship understanding. Total of nineteen PZQ analogues with structural variations at amide, piperazine and aromatic moieties have been synthesized and fully characterized. Among all the new analogues tested for antischistosomal activity, one dimethoxy tetrahydroisoquinoline analogue and two tetrahydro-β-carboline analogues exhibited modearate activity against adult Schistosomamansoni. Tetrahydro-β-carboline analogues showed moderate activity whereas the presence of p-trifluoromethylbenzoyl and p-toluenesulphonyl moieties resulted in complete suppression of antischistosomal activity.
Partha Sadhu, Singam Kumar, Malapaka Chandrasekharam, Livia Pica-Mattoccia, Donato Cioli, Vaidya Rao

Veterinary Parasitology (October 2011)

A new oil suspension containing 0.15% ivermectin and 15% praziquantel for intramuscular injection was developed, and corresponding pharmacokinetics studies were conducted in swine. The combination product is a white- to cream-colored oil suspension and its physical properties such as settling volume ratio, redispersibility, syringeability and flowability are well consistent with the Technical Standards by the Ministry of Agriculture of the People's Republic of China. The pharmacokinetic study consists of two parts. First, the experiments were carried out to compare the pharmacokinetic parameters of the combination product and those same products with praziquantel or ivermectin removed merely. The results showed that no significant change in the major pharmacokinetic parameters (t1/2z, Tmax, Cmax, AUCINF, TimeDur) was observed when either of the component was removed from the combination product, indicating that ivermectin and praziquantel do not interfere with each other when being used together. Second, the pharmacokinetics of the combination product was compared with those of their respective single product. The results showed that the Cmax (15.94 ng/mL) of ivermectin in combination product was 9.01 times higher than the single product, while the AUCINF (1925.61 ng·h/mL) was 6.02 times higher. Meanwhile, the Cmax (1.48 μg/mL), AUCINF (17.08 μg·h/mL), t1/2z (20.25 h), TimeDur3 (42.01 h) and TimeDur4 (16.60 h) of praziquantel in combination product were improved with a factor of 5.48, 13.66, 8.58, 10.10 and 7.31 times when compared with the single product, respectively. Therefore, the efficacy of the combination product was significantly prolonged, especially for praziquantel, so that comprehensive efficacy of controlling parasites sensitive to ivermectin and praziquantel can be achieved with one-single use of it.
Shusheng Tang, Linlin Chen, Zhaoxu Guo, Xiuzhi Hu, Jiakang He, Gang Wang, Tingting Zhao, Xilong Xiao

Parasitology Research (8 October 2011), pp. 1-7.

Praziquantel, due to high efficacy, excellent tolerability, few and transient side effects, simple administration, and competitive cost, is virtually the only drug of choice for treatment of human schistosomiasis. Treatment of schistosomiasis has shown great advances with the introduction of the drug into the therapeutic arsenal in areas that are endemic for the parasite. However, the drug presents various efficacies against different developmental stages of schistosomes, appearing an oddity intermitted mode. The present review article reviews the effects and mechanism of action of praziquantel against schistosomes briefly and suggests the research on this oddity phenomenon.
Wei Wu, Wei Wang, Yi-xin Huang