A cluster randomized study of the safety of integrated treatment of trachoma and lymphatic filariasis in children and adults in Sikasso, Mali

Abstract

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.

Figure 1. Disposition of subjects.

Figure 2. Complaints at baseline.

Graph shows the incidence of specific complaints reported by 1% or more of subjects at baseline. Percentages are calculated using the total number of study subjects in each village. “Other” comprises any complaints not listed in the Case Report Form.

Figure 3. Overall incidences of adverse events.

Graph shows the overall incidence of adverse events in each village, calculated as the percentage of subjects in each village who reported at least one adverse event at any time after treatment, with associated 95% confidence intervals.

Figure 4. Incidence of most common adverse events.

Graph shows the incidence of the most commonly reported types of event overall. Percentages are calculated using the total number of treated subjects in each village. “Other” comprises any events not listed in the Case Report Form.

Figure 5. Most common adverse events.

Graph shows the incidence of the most commonly reported types of event overall, with 95% confidence intervals. Percentages are calculated using the total number of treated subjects in each village. “Other” comprises any events not listed in the Case Report Form.

Figure 6. Time to onset of adverse events.

The graph shows the estimated proportion of treated subjects in each village on each study day who had reported at least one adverse event from the time of receiving the study medication. The band represents the 95% confidence region for the estimates. Estimates were derived using survival analysis methods.