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

PLoS Negl Trop Dis. 2013 May 9;7(5):e2221. doi: 10.1371/journal.pntd.0002221. Print 2013.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Albendazole / adverse effects
  • Albendazole / therapeutic use
  • Anthelmintics / adverse effects*
  • Anthelmintics / therapeutic use
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Azithromycin / adverse effects
  • Azithromycin / therapeutic use
  • Chemoprevention / adverse effects
  • Chemoprevention / methods
  • Child
  • Child, Preschool
  • Coinfection / drug therapy
  • Coinfection / prevention & control
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / methods
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Elephantiasis, Filarial / drug therapy*
  • Elephantiasis, Filarial / prevention & control*
  • Female
  • Humans
  • Ivermectin / adverse effects
  • Ivermectin / therapeutic use
  • Male
  • Mali
  • Middle Aged
  • Neglected Diseases / drug therapy
  • Neglected Diseases / prevention & control
  • Trachoma / drug therapy*
  • Trachoma / prevention & control*
  • Young Adult

Substances

  • Anthelmintics
  • Anti-Bacterial Agents
  • Ivermectin
  • Azithromycin
  • Albendazole

Associated data

  • ClinicalTrials.gov/NCT01586169

Grants and funding

The study was funded in its entirety by a portion of grant number 37666 from the Bill & Melinda Gates Foundation (http://www.gatesfoundation.org) to the International Trachoma Initiative. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.