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

Cédric B Chesnais (1) , Sébastien D Pion (1) , Charlotte Boullé (1) , Jacques Gardon (2) , Nathalie Gardon-Wendel (3) , Joël Fokom-Domgue (4) , Joseph Kamgno (5) , Michel Boussinesq (1)

1 TransVIHMI - Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
2 HSM - Hydrosciences Montpellier
3 Centre Pasteur du Cameroun
4 The University of Texas M.D. Anderson Cancer Center [Houston]
5 University of Yaoundé [Cameroun]

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.

Mots clés: Loiasis; Serious adverse events; Africa

Domaines: Maladies infectieuses; Pharmacologie

Cédric B Chesnais, Sébastien D Pion, Charlotte Boullé, Jacques Gardon, Nathalie Gardon-Wendel, et al.. Individual risk of post-ivermectin serious adverse events in subjects infected with Loa loa. EClinicalMedicine, 2020, 28, pp.100582. ⟨10.1016/j.eclinm.2020.100582⟩. ⟨hal-03141579⟩