Safety and effectiveness of triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole in reducing lymphatic filariasis prevalence and clearing circulating filarial antigens in Mombasa, Kenya

Abstract

Background: In 2018, Kenya introduced triple-drug therapy with ivermectin, diethylcarbamazine, albendazole (IDA) through mass drug administration (MDA) to accelerate the elimination of lymphatic filariasis (LF). This community-based surveillance study assessed the safety and effectiveness of IDA-MDA in reducing LF-antigenemia prevalence and circulating filarial antigens (CFA) clearance among LF infected individuals.

Methods: A total of 8928 residents in Mombasa, Kenya, were screened for CFA using the Filarial Test Strip: 3464 were screened in 2018 and 5464 in 2021 after two annual IDA-MDA rounds. CFA-positive individuals in 2021 were re-tested at two and four months of post-MDA for CFA-clearance rates. Adverse events (AEs) associated with IDA-MDA were monitored via door-to-door visits on days 1, 2, and 7 post-MDA to document the incidence, type and risk factors. Efficacy outcomes included post-MDA LF-antigenemia prevalence reduction after two rounds of annual MDA and CFA clearance rate. Chi-square test compared proportions, and logistic regression analysis identified AE predictors.

Results: LF antigenemia prevalence significantly decreased from 1.39% (n = 48) in 2018 to 0.66% (n = 36) in 2021 [P < 0.001; 95% confidence interval (CI) for difference in proportions: 0.003-0.012]. CFA clearance rates were 63.2% (12/19, 95% CI: 41.0-80.1%) at 2 months and 68.4% (13/19, 95% CI: 46.0-86.6%) at 4 months post-MDA. Among 53 CFA-positive individuals monitored, the cumulative 7-day AE incidence was 37.7% (95% CI: 25.6-51.7), higher than the general population's 27.3% (95% CI: 26.4-28.2). Common AEs included nausea (11.3%), diarrhea (11.3%), abdominal pain (7.6%), and headache (5.7%). Risk factors for AEs included age, overweight status, concomitant medication use, chronic illness, and fasting before MDA.

Conclusions: Triple therapy with IDA is safe and well-tolerated, with some mild-to-moderate and transient adverse events among LF-infected individuals. The high incidence of AEs highlights the need for safety monitoring during MDA. The significant reductions in LF antigenemia prevalence and high CFA clearance rates underscore IDA's effectiveness in reducing LF transmission, positioning it as a key strategy for eliminating LF as a public health problem by 2030.

Keywords: Active safety surveillance; Adverse events; Albendazole; Diethylcarbamazine; Efficacy; Ivermectin; Lymphatic filariasis; Mass drug administration; Positive participants.

Fig. 1

Map of the Study Area––Jomvu Sub-County (left), Mombasa County (center), and Kenya (right)

Fig. 2

Study flowchart depicting the pre-screening and enrollment process of LF antigenemia positive (LF antigenemia + ve) individuals, along with the outcome of adverse event monitoring following mass drug administration with IDA (Post-MDA AEs)

Fig. 3

Proportion of MDA-associated adverse events (AEs) following triple therapy (IDA) stratified by type of the days of occurrence

Fig. 4

Comparison of the incidence and type of AEs associated with post-MDA using IDA between LF-infected individuals versus the general unscreened population