Treatment of preschool children for schistosomiasis.

Abstract

In The Lancet Global Health, Jean T Coulibaly and colleagues1Coulibaly J T Panic G Silué KD Kovač J Hattendorf J Keiser J Efficacy and safety of praziquantel in preschool-aged and school-aged children infected with Schistosoma mansoni: a randomised controlled, parallel-group, dose-ranging, phase 2 trial.Lancet Glob Health. 2017; 5: e688-e698Summary Full Text Full Text PDF PubMed Scopus (46) Google Scholar report the efficacy and safety of different dosages of praziquantel in preschool children. In a randomised dose-ranging trial in southern Côte d'Ivoire, they compared the cure rate obtained with three different doses of praziquantel or placebo, in preschool and school-aged children infected with Schistosoma mansoni. 161 (24%) of 660 eligible preschool-aged children had a detectable S mansoni infection and 154 received treatment. 62% of preschool-aged children were cured with the 20 mg/kg dose, 72% with the 40 mg/kg dose, 71% with the 60 mg/kg dose, and 37% with placebo. 180 (80%) of 225 school-aged children were infected and 178 received treatment. In that group, the 20 mg/kg dose resulted in cure in 30% of the children, the 40 mg/kg in 69%, the 60 mg/kg in 83%, and placebo in 12%. The authors conclude that in the absence of other treatment options, a single dose of praziquantel of 40 mg/kg can be endorsed for preventive chemotherapy programs in children younger than 5 years of age. WHO has recognised the morbidity due to schistosomiasis in this preschool age group and has recommended to treat them on a case by case basis because of the absence of suitable paediatric formulation of praziquantel for inclusion in the preventive chemotherapy.2WHOReport of a meeting to review the results of studies on the treatment of schistosomiasis in preschool-age children. World Health Organization, Geneva2011http://www.who.int/schistosomiasis/resources/9789241501880/en/Google Scholar The challenge to ensure the correct dosage, safe administration, and conservation of the medicine has led WHO to recommend the flexible solid oral formulation for children younger than 5 years.3WHO Expert Committee on Specifications for Pharmaceutical Preparations Forty-sixth report. Annex 5, Development of paediatric medicines: points to consider in formulation. WHO Technical Report Series No. 970, pp 250. Geneva: World Health Organization, 2012. http://www.who.int/medicines/areas/quality_safety/quality_assurance/expert_committee/TRS-970-pdf1.pdf (accessed May 20, 2017).Google Scholar Therefore, preventive chemotherapy, the WHO recommended intervention for the control of schistosomiasis morbidity in endemic areas2WHOReport of a meeting to review the results of studies on the treatment of schistosomiasis in preschool-age children. World Health Organization, Geneva2011http://www.who.int/schistosomiasis/resources/9789241501880/en/Google Scholar, 4Gabrielli A Montresor A Engels D Savioli L Preventive chemotherapy in human helminthiasis: theoretical and operational aspects.Trans R Soc Trop Med Hyg. 2011; 105: 683-693Summary Full Text Full Text PDF PubMed Scopus (97) Google Scholar is currently not targeting pre-school children in areas endemic for schistosomiasis. Another reason for the exclusion is because the safety and dosage of praziquantel in this age group are not established.5Bustinduy AL Waterhouse D de Sousa-Figueiredo JC et al.Population pharmacokinetics and pharmacodynamics of praziquantel in Ugandan children with intestinal schistosomiasis: higher dosages are required for maximal efficacy.MBio. 2006; 7: 4Google Scholar The manufacturer indicates in the drug insert that “safety in children under 4 years has not been established”.6Bayer and Merck & Co, Biltricide insert https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018714s012lbl.pdf (accessed May 5, 2017).Google Scholar However, several studies show that schistosomiasis establishes early in life,2WHOReport of a meeting to review the results of studies on the treatment of schistosomiasis in preschool-age children. World Health Organization, Geneva2011http://www.who.int/schistosomiasis/resources/9789241501880/en/Google Scholar, 7Stothard JR Sousa-Figueiredo JC Betson M et al.Closing the praziquantel treatment gap: new steps taken in control of schistosomiasis in African infants and preschool children.Parasitology. 2011; 138: 1593-1606Crossref PubMed Scopus (77) Google Scholar and the study by Coulibaly and colleagues,1Coulibaly J T Panic G Silué KD Kovač J Hattendorf J Keiser J Efficacy and safety of praziquantel in preschool-aged and school-aged children infected with Schistosoma mansoni: a randomised controlled, parallel-group, dose-ranging, phase 2 trial.Lancet Glob Health. 2017; 5: e688-e698Summary Full Text Full Text PDF PubMed Scopus (46) Google Scholar greatly contributes to the literature not only showing the efficacy and safety of the drug, but also that the dose presently used in older age group (40 mg/kg) is also the best option in pre-school children. The Pediatric Praziquantel consortium, made up of several partners, including among others Merck KGaA (Germany), Astrellas Pharma (Japan), Swiss Tropical and Public Health Institute (Switzerland), and the Schistosomiasis Control Initiative (UK), is presently working to develop a paediatric formulation of praziquantel that, we hope, will address two additional problems linked with the administration of drugs to children: the risk of choking and the flavour of the present tablet that influence the drug compliance in very young children. Preventive chemotherapy for schistosomiasis is rapidly scaling up worldwide. The global coverage that was less than 10% in 2010 is now higher than 30%, however, the main limitation for the scaling up is the availability of donated drug. In school age children, the age group for which praziquantel is donated, the coverage is almost 45%, while the coverage in adults is less than 15% because of the absence of donation for this age group.8WHOIntegrating neglected tropical diseases into global health and development: fourth WHO report on neglected tropical diseases. World Health Organization, Geneva2017Google Scholar The present donation of praziquantel is expected to reach 250 million tablets in 2017 (corresponding to 100 million doses) but this quantity would be sufficient only to treat the school age children in need, assuming their appropriate allocation and distribution.8WHOIntegrating neglected tropical diseases into global health and development: fourth WHO report on neglected tropical diseases. World Health Organization, Geneva2017Google Scholar To reach the 2020 WHO target for schistosomiasis and to eliminate the disease, the treatment of all age groups is required.8WHOIntegrating neglected tropical diseases into global health and development: fourth WHO report on neglected tropical diseases. World Health Organization, Geneva2017Google Scholar It will be essential to obtain a donation of praziquantel for adults in need and if preschool children will be included in the preventive chemotherapy targeted group, the new formulation for their treatment must be available free of charge. In conclusion, the distribution of praziquantel for preventive chemotherapy is simple to implement and very low cost,9Fitzpatrick C Fleming FM Madin-Warburton M et al.Benchmarking the cost per person of mass treatment for selected neglected tropical diseases: an approach based on literature review and meta-regression with web-based software application.PLoS NTD. 2016; 1: e0005037https://doi.org/10.1371/journal.pntd.0005037Crossref Scopus (26) Google Scholar, 10Croce D Porazzi E Foglia E Restelli U Sinuon M Socheat D Montresor A Cost effectiveness of a successful schistosomiasis control programme in Cambodia 1995-2006.Acta Tropica. 2010; 113: 279-284Crossref PubMed Scopus (23) Google Scholar however, the availability of the drug is essential to treat all the people in need. WHO is looking forward to the development of a paediatric formulation of the drug provided it will be available as a donation. In the absence of treatment alternatives, a single dose of praziquantel of 40 mg/kg, recommended by the WHO for S mansoni infections in school-aged children can be endorsed for preschool-aged children in preventive chemotherapy programmes. AM and AG declare no competing interests. Efficacy and safety of praziquantel in preschool-aged and school-aged children infected with Schistosoma mansoni: a randomised controlled, parallel-group, dose-ranging, phase 2 trialPraziquantel shows a flat dose-response and overall lower efficacy in PSAC compared with in SAC. In the absence of treatment alternatives, a single dose of praziquantel of 40 mg/kg, recommended by the WHO for S mansoni infections in SAC can be endorsed for PSAC in preventive chemotherapy programmes. Full-Text PDF Open Access