Individual risk of post-ivermectin serious adverse events in subjects infected with Loa loa

Abstract

Background: Implementation of onchocerciasis elimination programmes has been delayed in Central Africa because of the risk of ivermectin-related serious adverse events (SAEs) in individuals with high Loa loa microfilarial densities (MFD). We developed the first statistical models enabling prediction of SAE risk in individuals with a given MFD.

Methods: We used individual participant data from two trials conducted in loiasis-onchocerciasis co-endemic areas in Cameroon. among the 10 506 ivermectin-treated subjects included in the analysis, 38 (0·36%) developed an ivermectin-related SAE. To predict individual-level risk of SAE, we developed mixed multivariate logistic models including subjects' sex, age, pre-treatment L loa and Mansonella perstans MFDs, and study region.

Findings: The models predicted that regardless of sex, about 1% of people with 20 000 L loa microfilariae per millilitre of blood (mf/mL), 10% of people with 50 000 mf/mL and about one third of those with 100 000 mf/mL will develop an SAE. For a given MFD, males have a three-fold higher risk of developing an SAE than females.

Interpretation: By enabling the prediction of post-ivermectin SAE risk in communities with known distribution of L loa MFDs, our results can guide decisions on the choice of ivermectin-based treatment strategies. They also predict that 37 SAEs were prevented in 2015 by using a Test-and-Treat strategy in the Okola District of Cameroon.

Funding: UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases; Institut de Recherche pour le Développement; Mectizan Donation Program; Bill & Melinda Gates Foundation.

Keywords: Africa; Loiasis; Serious adverse events.

Fig. 1

Predicted probabilities of developing a post-ivermectin severe adverse event according to the individual L loa microfilarial density, overall.

Fig. 2

Predicted probabilities of developing a post-ivermectin of severe adverse event according to the individual L loa microfilarial density, according to the sex.