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    • The points of agreement of the models

    2019-04-17

    The points of agreement of the models in the study by Brady and colleagues make sense—eg, it is intuitive that the post-MDA prevalence of malaria is strongly related to the proportion of individuals in the purchase EZ Cap Reagent GG missed by an MDA campaign, as well as the pre-MDA endemic prevalence. Although it may be more difficult than discovering and documenting consensus, explaining discrepancy between models is also useful. We quickly move into philosophical territory when we ask questions such as: what does it mean to make a consensus prediction based on model structures that disagree? Or can Modelling Consortia devise experiments to reconcile (or refute) competing model structures? Forecasting and classification based on the averaged outcomes of an ensemble of models has become a standard method in machine learning; but ensemble approaches have not yet been taken up by the infectious disease modelling community, whose models are more mechanistic and therefore have a stronger link to underlying biological processes than machine learning or statistical approaches. However, when more data become available from, and become more consistent between, control programmes, we can expect to see statistical forecasts going head-to-head with mechanistic models in model comparison studies.
    In , Jean T Coulibaly and colleagues 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 . 161 (24%) of 660 eligible preschool-aged children had a detectable 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 Null mutation 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. 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. Therefore, preventive chemotherapy, the WHO recommended intervention for the control of schistosomiasis morbidity in endemic areas 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. The manufacturer indicates in the drug insert that “safety in children under 4 years has not been established”. However, several studies show that schistosomiasis establishes early in life, and the study by Coulibaly and colleagues, 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 , 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.