Efficacy of two praziquantel treatments among primary school children in an area of high Schistosoma mansoni endemicity, Nile Delta, Egypt.

Praziquantel is the cornerstone of schistosomiasis control. A number of reports from endemic areas suggest that resistance or tolerance to praziquantel might exist in Schistosoma mansoni. Several explanations were postulated. The present work was designed to test the hypothesis that a low praziquantel (pzq) cure rate in Egypt is due to survival and maturation of immature stages that escaped pzq, which is effective against mature S. mansoni worms only. The study sample included 1351 children attending El Rouse primary school located in El Rouse village, Nile Delta, Egypt. All children received 2 pzq doses (40 mg/kg) 4 weeks apart. Diagnosis of S. mansoni infection and cure assessment were based on examination of 2 Kato slides prepared from a single stool sample collected before and 4 weeks after the first and second treatments. The cure rate was 78·8% after the first treatment and increased significantly to 90·8% after the second treatment. Egg reduction rates were 71·2% and 77·2% after 1 and 2 treatments respectively. Pre-treatment intensity of infection has a great influence on cure and egg reduction rates. Our results confirmed that low praziquantel cure rate, in Egypt, might be attributed, even partially, to survival and maturation of the immature S. mansoni stages that escaped pzq that is effective against mature worms only.

In vitro cellular and humoral responses to Schistosoma mansoni vaccine candidate antigens.

Few studies comparing schistosomiasis vaccine candidate antigens between laboratories have been carried out and published. Generally, only the investigators who discovered the molecules have evaluated them in either experimental animal models or in human correlate studies. In an attempt to identify responses against specific antigens and investigate their association with resistance versus susceptibility to re-infection, we studied the serological reactions and the cytokine responses stimulated by a panel of 10 candidate vaccine molecules in 225 long-term residents of an area endemic for Schistosoma mansoni in Egypt. The panel consisted of four recombinant antigens (Sm62-Irv5, Sm37-G3PDH, Sm28-GST and Sm14-FABP), one full-length native protein (Sm97-paramyosin), two synthetic peptides (MAP3 and MAP4) and three unpublished antigens (PR52-filamin, PL45-phosphoglycerate kinase, PN18-cyclophilin). Two different study designs, one based on retrospective and the other on prospective parasitological data were applied in the evaluation of the immune responses. Using historical data collected over the previous 5 years, correlations between frequency of re-infection and antigen-specific immune responses were investigated. In the prospective arm of the study, the subjects were followed over time after treatment with praziquantel with periodic immunological tests and stool examinations. Thus, highly specific humoral and cellular immune reactions in response to the 10 antigens described above could be correlated, both prospectively and retrospectively, with detailed epidemiological data covering a 66-month period. The immune response profiles produced were unique to each antigen but no clear "winner" or "winners" were identified. However, markers for both resistance and susceptibility to re-infection were identified for each molecule indicating which types of responses to aim for in vaccination and which ones to avoid. The insights gained from this approach should be useful for antigen selection and ultimately for vaccine formulation prior to Phase I/II trials in humans.