A Cluster Randomized Study of The Safety of Integrated Treatment of Trachoma and Lymphatic Filariasis in Children and Adults in Sikasso, Mali.

Background: Neglected tropical diseases are co-endemic in many areas of the world, including sub Saharan Africa. Currently lymphatic filariasis (albendazole/ivermectin) and trachoma (azithromycin) are treated separately. Consequently, financial and logistical benefit can be gained from integration of preventive chemotherapy programs in such areas. Methodology/Findings: 4 villages in two co-endemic districts (Kolondièba and Bougouni) of Sikasso, Mali, were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). These villages had previously undergone 4 annual MDA campaigns with ivermectin/albendazole and 2 with azithromycin. One village was randomly assigned to each treatment arm in each district. There were 7515 eligible individuals in the 4 villages, 3011(40.1%) of whom participated in the study. No serious adverse events occurred, and the majority of adverse events were mild in intensity (mainly headache, abdominal pain, diarrhoea and "other signs/symptoms"). The median time to the onset of the first event, of any type, was later (8 days) in the two standard treatment villages than in the co-administration villages. Overall the number of subjects reporting any event was similar in the co-administration group compared to the standard treatment group [18.7% (281/1501) vs. 15.8% (239/1510)]. However, the event frequency was higher in the coadministration group (30.4%) than in the standard treatment group (11.0%) in Kolondièba, while the opposite was observed in Bougouni (7.1% and 20.9% respectively). Additionally, the overall frequency of adverse events in the co-administration group (18.7%) was comparable to or lower than published frequencies for ivermectin+albendazole alone. Conclusions: These data suggest that co-administration of ivermectin+albendazole and azithromycin is safe; however the small number of villages studied and the large differences between them resulted in an inability to calculate a meaningful overall estimate of the difference in adverse event rates between the regimens. Further work is therefore needed before co-administration can be definitively recommended. Trial Registration: ClinicalTrials.gov; NCT01586169 Author Summary: Neglected tropical diseases are co-endemic in many areas of the world. Currently lymphatic filariasis (albendazole+ivermectin) and trachoma (azithromycin) are treated separately. Benefits can be gained from integration of preventive chemotherapy programs in such areas. To assess the safety of this approach, 4 villages in two co-endemic districts in Mali were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). One village was randomly assigned to each treatment in each district. 3011(40.1%) of 7515 eligible individuals in the 4 villages participated in the study. No serious adverse events occurred, and most events were mild in intensity (mainly headache, abdominal pain, and diarrhoea). Overall the number of subjects reporting any event was similar with co-administration compared to standard treatment [18.7% (281/1501) vs. 15.8% (239/1510)]. The overall frequency of adverse events with co-administration was comparable to or lower than published frequencies for ivermectin/albendazole alone. These data suggest that co-administration is safe; however the small number of villages studied and the large differences between them meant that a meaningful estimate of the differences could not be calculated, and further work will be needed before a recommendation can be made. [ABSTRACT FROM AUTHOR]