“Mass drug administration and lymphatic filariasis:  an assessment of different dosing strategies” 

Abstract: Lymphatic filariasis (LF) is a mosquito-borne parasitic disease that primarily affects people in tropical and sub-tropical regions.  Drugs used to treat LF include ivermectin (IVM) and diethylcarbamazine citrate (DEC), and weight-based dosing is considered the “gold standard” for determining the appropriate dosage.  To simplify delivery for mass treatment of LF, the WHO recommends height-based dosing for IVM (dose pole with 4 height groups) and age-based dosing for DEC (3 age groups); however, it is uncertain how these approaches compare to weight-based dosing.  In the present study we used data from a multi-country study of LF (>23,000 subjects enrolled) to compare age and height-based dosing to weight-based dosing.  Additionally, we used a gamma-regression modelling approach to develop model-based dosing poles for IVM and DEC and assessed whether these poles improved upon existing WHO dosing methods.  Results indicated that WHO height and age-based dosing markedly deviate from the recommended weight-based dosage, ranging from 19-26% of subjects below the recommended dose to 23% of subjects above the recommended dose.  The model-based dosing poles for DEC showed under-dosing for as much as 12% fewer subjects compared to the age-based WHO approach, and our models correctly dosed up to 17% more subjects.  The discrepancy for DEC under-dosing was magnified for adult males (a group of particular concern), with 46% under-dosed based on the WHO height pole compared to 18-26% based on our model predictions.  Discrepancies between the WHO height pole and the model-based height poles were less marked for IVM, but the WHO pole still resulted in markedly higher (up to 11%) under-dosing for adult males.  When we combined the DEC and IVM dosing poles into a single pole, we found that it performed similarly to our drug-specific dosing poles.  We conclude that models based on this multi-country LF dataset improve upon existing dosing strategies.  Furthermore, a single dose pole may provide a simple, effective way to treat LF in areas where mass drug administration (MDA) programs are employed.  Results from this study provide valuable tools for MDA programs aimed at eliminating LF worldwide.    

Division of Biostatistics seminars.

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