“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.
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