Comparative Safety Surveillance of Triple (IDA) Versus Dual Therapy (DA) in Mass Drug Administration for Elimination of Lymphatic Filariasis in Kenya: A Cohort Event Monitoring Study.

INTRODUCTION: Dual diethylcarbamazine and albendazole (DA) therapy is the standard mass drug administration (MDA) regimen for lymphatic filariasis in Kenya. Following the recent World Health Organization recommendation, Kenya piloted triple therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) in MDA. OBJECTIVE: We conducted a community-based, observational, cohort event monitoring study to compare the types, frequency, severity, and predictors of adverse events following dual versus triple therapy in 20,421 eligible residents. METHODS: Residents in Kilifi (n = 10,010) and Mombasa counties (n = 10,411) received DA and IDA through MDA campaigns, respectively. Adverse events were actively monitored through house-to-house visits on days 1, 2, and 7 after MDA. Any clinical events reported before and after MDA were cross-checked and verified to differentiate pre-existing events from MDA-associated adverse events. RESULTS: Overall, 5807 and 3102 adverse events were reported by 2839 and 1621 individuals in the IDA and DA groups, respectively. The incidence of experiencing one or more adverse events was significantly higher (p < 0.0001) in the IDA group (27.3%; 95% confidence interval [CI] 26.4-28.2) than in the DA group (16.2%; 95% CI 15.5-16.9). Dizziness (15.9% vs 5.9%) and drowsiness (10.1% vs 2.6%) were the most common adverse events and significantly higher in the IDA group compared with the DA group (p < 0.0001). Most adverse events were mild or moderate with a few severe cases (IDA = 0.05%; 95% CI 0.35-0.78, DA = 0.03%; 95% CI 0.14-0.60). Female sex, obesity, taking three or more diethylcarbamazine or ivermectin tablets, and having pre-existing clinical symptoms were significant predictors of adverse events following IDA treatment. CONCLUSIONS: Ivermectin, diethylcarbamazine, and albendazole as a combination is as safe and well tolerated as DA to use in MDA campaigns with no serious life-threatening adverse events. Systemic mild-to-moderate adverse events with a few severe cases and transient adverse events are more common with IDA treatment than with DA treatment. Hence, integrating pharmacovigilance into a MDA program is recommended for the timely detection and management of adverse events.

Safety and Tolerability of Mass Diethylcarbamazine and Albendazole Administration for the Elimination of Lymphatic Filariasis in Kenya: An Active Surveillance Study.

Preventive chemotherapy with diethylcarbamazine citrate (DEC) and albendazole (ALB) is the core intervention strategy to eliminate lymphatic filariasis (LF). We conducted a large-scale prospective active safety surveillance study to identify the incidence, type, severity, and risk factors for adverse events (AEs) following mass drug administration (MDA) of single-dose DEC and ALB in 10,010 participants from Kilifi County, Kenya. AEs were actively monitored and graded at 24 h, 48 h, and on day 7 Post-MDA. Out of 10,010 enrolled study participants, 1621 participants reported a total of 3102 AEs during a seven-day follow-up. The cumulative incidence of AEs was 16.2% (95% CI, 15.5-16.9%). The proportion of participants who experienced one, two, or ≥three types of AEs was 9.2%, 4.6%, 2.4%, respectively. AEs were mild (87.3%), moderate (12.4%), and severe (0.3%) and resolved within 72 h. The five most common AEs were dizziness (5.9%), headache (5.6%), loss of appetite (3.3%), fever (2.9%), and drowsiness (2.6%). Older age, taking concurrent medications, ≥three tablets of DEC, and type of meal taken before MDA were significant predictors of AEs. One in six participants experienced systemic mild-to-moderate severity grading and transient AEs. DEC and ALB co-administration for the elimination of LF is generally safe and well-tolerated.