The Synaptic Leap

Veterinary Parasitology (30 August 2010)

This field trial was conducted to determine whether 40 or 75 mg/kg of praziquantel is suitable for treatment of fishborne zoonotic trematodes (FZT) in naturally infected dogs (n = 10) and cats (n = 11). Three days after treatment all animals at either dose were negative for small trematode eggs. In two cats and one dog treated with 75 mg/kg, however, a few damaged eggs were found three days-post treatment; no small trematode eggs were seen in these animals at day 14 post-treatment. In addition, at the 75 mg dose, 2 cats and 2 dogs experienced vomiting or diminished appetite. Therefore a praziquantel dose of 40 mg/kg is suggested for treatment of FZT in dogs and cats.
Nguyen Anh, Henry Madsen, Dao Thanh, Anders Dalsgaard, Darwin Murrell

The Lancet Infectious Diseases, Vol. 10, No. 9. (September 2010), pp. 603-611.

Summary Background Schistosomiasis is an important parasitic disease in Kenya. Decreasing susceptibility of schistosomes to praziquantel, the major drug used to reduce disease morbidity, has made assessment of new antischistosomal drugs a priority. We aimed to assess the safety and efficacy of an artesunate-based combination drug in the treatment of schistosomiasis. Methods In this open-label randomised trial in Rarieda district of western Kenya, we enrolled school children (aged 6–15 years) who had Schistosoma mansoni infection according to duplicate Kato-Katz thick smears from a stool sample. Computer-generated block randomisation was used to assign children (1:1) to receive artesunate (100 mg) with sulfalene (also known as sulfamethoxypyrazine; 250 mg) plus pyrimethamine (12·5 mg) as one dose every 24 h for 3 days or one dose of praziquantel (40 mg/kg per day). The primary efficacy endpoint was the number of participants cured 28 days after treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01054651. Results Between October and December, 2009, 212 children were enrolled and assigned to receive artesunate with sulfalene plus pyrimethamine (n=106) or praziquantel (n=106). 69 patients (65%) were cured in the praziquantel treatment group compared with 15 (14%) in the artesunate with sulfalene plus pyrimethamine treatment group (p<0·0001). Adverse events were less common in patients taking artesunate with sulfalene plus pyrimethamine than in those taking praziquantel (22% [n=23] vs 49% [n=52], p<0·0001), and no drug-related serious adverse events occurred. Interpretation The standard treatment with praziquantel is more effective than artesunate with sulfalene plus pyrimethamine in the treatment of children with S mansoni infection in western Kenya. Whether artemisinin-based combination therapy has a role in the treatment of schistosomiasis is unclear. Funding Dafra Pharma, Belgium.
Charles Obonyo, Erick Muok, Pauline Mwinzi

Parasitology International (08 July 2010)

Oxidative stress is a common mechanism contributing to hepatic damage and fibrogenesis in a variety of liver disorders. The liver is the target organ for many parasitic infections, hence there is a great demand for the development of novel treatment strategies. In the present study conducted on mice infected with larval stage of Mesocestoides vogae , we investigated effects of therapy with praziquantel (PZQ) alone and in combination with silymarin on liver GSH content, lipid peroxidation and larval reduction. Proliferation of liver cells by means of BrdU incorporation into DNA and production of superoxide anions by peritoneal adherent cells was measured to assess the antioxidant activity of silymarin. Drugs administration was carried on from day 15 post infection (p.i.) for ten consecutive days and examination was performed during 20 days of follow up the therapy. Larval M. vogae infection caused liver damage and triggered extensive oxidative stress, resulting in the abolishment of GSH redox balance and ROS-induced lipid peroxidation. PZQ administration caused short-term decline of GSH levels in healthy mice. Low GSH levels in infected mice were elevated gradually in response to the drug, but respiratory burst in cells was not reduced. Silymarin in combination with PZQ showed strong direct antioxidant capacity and stimulated the larvicidal effect of praziquantel. Treatment with PZQ and silymarin downregulated the generation of superoxide anions, prevented lipid peroxidation, stimulated GSH synthesis and proliferation of hepatocytes in infected livers. These findings demonstrated that silymarin can markedly decrease the liver injury and its co-administration with PZQ potentiate effect of therapy, probably due to the downregulation of fibrogenesis.
Samuel Velebný, Gabriela Hrčkova, Alžbeta Königová

The Journal of Infectious Diseases, Vol. 202, No. 3. (15 August 2010), pp. 399-405.

doi: 10.1086/653828 Background.  Age prevalence curves for areas in which schistosomiasis is endemic suggest that humans develop partial immunity to reinfection beginning in early adolescence. We conducted a 2‐year longitudinal study to determine whether children infected with Schistosoma mansoni develop protection‐related immune responses after treatment with praziquantel and whether the development of these immune responses is accelerated by frequent treatment after reinfection. Methods.  Children (8–10 years old) were tested for S. mansoni every 4 months and treated with praziquantel when positive (arm A; $n=68$ ) or were tested and treated at the end of the 2‐year follow‐up period (arm B; $n=49$ ). Results.  Children in arm A who remained free of infection during follow‐up had significantly higher baseline levels of schistosome‐specific immunoglobulin E (IgE) than did children with ⩾2 repeat diagnoses of S. mansoni infection. Children with ⩾2 repeat diagnoses of S. mansoni infection had significantly increased levels of anti‐schistosome IgE and CD23+ B cells after receiving ⩾3 praziquantel treatments over the course of follow‐up. No increase in either parameter was seen in children who received only the baseline praziquantel treatment. Conclusions.  B cell activation and anti‐schistosome IgE are associated with resistance to S. mansoni in children, and these immunological parameters can be increased by multiple rounds of infections and praziquantel‐induced cures.
Carla Black, Erick Muok, Pauline Mwinzi, Jennifer Carter, Diana Karanja, Evan Secor, Daniel Colley