Dataset Information

Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

ABSTRACT:

Background

Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.

Methodology/principal findings

We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms 'schistosomiasis', 'dosing' and 'praziquantel' and hand searches of personal collections and bibliographies of recovered articles. In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection. Observed cure rates (positive to negative conversion in egg detection assays) were, for S. mansoni, 69-91% cure after two doses vs. 42-79% after one dose and, for S. haematobium, 46-99% cure after two doses vs. 37-93% after a single dose. Treatment benefits in terms of reduction in intensity (mean egg count) were also different for the two species-for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose. Cost-effectiveness analysis was performed based on Markov life path modeling.

Conclusions/significance

Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni)-$211 (S. haematobium) per additional lifetime QALY gained by double treatment in school-based programs. More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be reduced through more effective coverage, significant additional benefits are expected to accrue in the targeted communities.

SUBMITTER: King CH

PROVIDER: S-EPMC3176745 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Publications

Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

King Charles H CH Olbrych Stephanie K SK Soon Margaret M Singer Mendel E ME Carter Jen J Colley Daniel G DG

PLoS neglected tropical diseases 20110920 9

<h4>Background</h4>Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.<h4>Methodology/principal findings</h4>We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms 'schisto ...[more]

PMID: 21949893

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Project description:Human schistosomiasis is a neglected tropical disease caused by Schistosoma mansoni, S. haematobium, and S. japonicum. Praziquantel (PZQ) is the method of choice for treatment. Due to constant selection pressure, there is an urgent need for new therapies for schistosomiasis. Previous treatment of S. mansoni included the use of oxamniquine (OXA), a drug that is activated by a schistosome sulfotransferase (SULT). Guided by data from X-ray crystallography and Schistosoma killing assays more than 350 OXA derivatives were designed, synthesized, and tested. We were able to identify CIDD-0150610 and CIDD-0150303 as potent derivatives in vitro that kill (100%) of all three Schistosoma species at a final concentration of 71.5 μM. We evaluated the efficacy of the best OXA derivates in an in vivo model after treatment with a single dose of 100 mg/kg by oral gavage. The highest rate of worm burden reduction was achieved by CIDD -150303 (81.8%) against S. mansoni, CIDD-0149830 (80.2%) against S. haematobium and CIDD-066790 (86.7%) against S. japonicum. We have also evaluated the ability of the derivatives to kill immature stages since PZQ does not kill immature schistosomes. CIDD-0150303 demonstrated (100%) killing for all life stages at a final concentration of 143 μM in vitro and effective reduction in worm burden in vivo against S. mansoni. To understand how OXA derivatives fit in the SULT binding pocket, X-ray crystal structures of CIDD-0150303 and CIDD-0150610 demonstrate that the SULT active site will accommodate further modifications to our most active compounds as we fine tune them to increase favorable pharmacokinetic properties. Treatment with a single dose of 100 mg/kg by oral gavage with co-dose of PZQ + CIDD-0150303 reduced the worm burden of PZQ resistant parasites in an animal model by 90.8%. Therefore, we conclude that CIDD-0150303, CIDD-0149830 and CIDD-066790 are novel drugs that overcome some of PZQ limitations, and CIDD-0150303 can be used with PZQ in combination therapy.

Project description:BackgroundSchistosomiasis is a serious public health burden in sub-Saharan Africa. Praziquantel is the only drug recommended by the World Health Organization to treat both urogenital and intestinal schistosomiasis. The reliance on a single drug to treat a disease with such a huge burden has raised concerns of possible drug resistance mainly in endemic areas. This systematic review was conducted to identify gaps and recent progress on the efficacy of different regimens of praziquantel in treating schistosomiasis among children in sub-Saharan Africa where Schistosoma mansoni and S. haematobium are endemic.Main textA literature search of peer-reviewed journals was done on Google Scholar, MEDLINE (under EBSCOhost) and PubMed databases using pre-defined search terms and Boolean operators. The search included studies published from 2008 to 2017 (August) with emphasis on the efficacy of praziquantel on S. haematobium and S. mansoni infections among preschool and school children. Nineteen publications satisfied the inclusion criteria for the review. The studies reviewed were from 10 sub-Saharan African countries and 7/19 of the studies (37%) were conducted in Uganda. Seven studies (37%) focused on Schistosoma mansoni, 6/19 (31.5%) on S. haematobium and another 6 on mixed infection. A single standard dose of 40 mg/kg body weight was the most used regimen (9) followed by the repeated single standard dose assessed for efficacy at 3-4 weeks post-treatment.ConclusionsA repeated standard dose of 40 mg/kg achieved satisfactory efficacy compared to a single dose against both parasite species. However, findings on efficacy of repeated doses in co-infection of S. mansoni and S. haematobium were not conclusive. Praziquantel administrated at 60 mg/kg was slightly more efficacious than the 40 mg/kg standard dose. Minor and transitory side-effects were reported for both regimens. The review indicates that further investigations are necessary to conclusively determine efficacy of praziquantel on coinfection of S. haematobium and S. mansoni to formulate concrete guidelines on the use of repeated doses at 40 or 60 mg/kg for treating schistosomiasis. We recommend the use of the egg reduction rate (ERR) formula recommended by the WHO for assessing praziquantel efficacy in order for the results to be comparable for different regions.

Project description:Over the past decade, a significant reduction in the prevalence of schistosomiasis has been achieved, partially explained by the large-scale administration of praziquantel. Yet, the burden of schistosomiasis remains considerable, and factors influencing intervention coverage are important. This study aimed to deepen the understanding of low treatment coverage rates observed in two schistosomiasis-endemic villages in Côte d'Ivoire. The research was conducted in August 2015, in Moronou and Bigouin, two villages of Côte d'Ivoire that are endemic for Schistosoma haematobium and S. mansoni, respectively. After completion of a clinical trial, standard praziquantel treatment (single 40 mg/kg oral dose) was offered to all village inhabitants by community health workers using a house-to-house approach. Factors influencing treatment coverage were determined by a questionnaire survey, randomly selecting 405 individuals. The overall treatment coverage rate was only 47.6% (2730/5733) with considerable intervillage heterogeneity (27.7% in Bigouin (302/1091) versus 52.3% in Moronou (2428/4642)). Among the 200 individuals interviewed in Moronou, 50.0% were administered praziquantel, while only 19.5% of the 205 individuals interviewed in Bigouin received praziquantel. The main reasons for low treatment coverage were work-related (agricultural activities), the bitter taste of praziquantel and previous experiences with adverse events. The most suitable period for treatment campaigns was reported to be the dry season. More than three-quarter of the interviewees who had taken praziquantel (overall, 116/140; Moronou, 84/100; Bigouin, 32/40) declared that they would not participate in future treatments (p < 0.001). In order to enhance praziquantel treatment coverage, careful consideration should be given to attitudes and practices, such as prior or perceived adverse events and taste of praziquantel, and appropriate timing, harmonized with agricultural activities. Without such understanding, breaking the transmission of schistosomiasis remains a distant goal.

Dataset Information

Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

Background

Methodology/principal findings

Conclusions/significance

Publications

Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

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