Evidence exists of several changes in drug kinetics in the presence of malnutrition. However, there is limited information on the efficacy of many drugs in under-nourished children. In a two-phased project, UW START reviewed over 1,500 titles identified from EMBASE and MEDLINE from 1995-2015 to identify literature reporting on the effect of pediatric malnutrition on drug efficacy for the major infectious causes of morbidity and mortality in children in Asia and sub-Saharan Africa. The primary aim was to identify papers reporting pharmacokinetic (PK) outcomes (e.g.: max concentration), and secondarily, papers reporting both drug dosing and clinical outcomes (e.g.: parasite clearance for malaria, CD4 count for HIV).
Phase I: TB, Malaria, & HIV The START team identified 21 articles through the systematic literature review. The majority of papers reported PK outcomes, yet some papers that focused on clinical outcomes were included. Study heterogeneity, including malnutrition definitions and methodology, was high. The studies yielded mixed results for HIV treatments and mostly null results for TB pharmacokinetics. The search did not yield any PK studies for malaria. The results were summarized in an Excel database and additional references with potential data were provided.
Phase II: Amoxicillin for pneumonia & variety of NTD/EED drugs Through a systematic literature review and additional targeted searches, the START team identified six studies, primarily reporting clinical outcomes, for these drugs and indications. The studies were summarized in an annotated bibliography. Leading NTD and pediatric malnutrition researchers were contacted and confirmed the paucity of PK data in this area.