Clarification of factors associated with post-artesunate delayed hemolysis (PADH): Analysis of 327 patients with severe imported Plasmodium falciparum malaria in France.

Background: Post-Artesunate delayed hemolysis (PADH) occurs in approximately 15 % of treated patients 2-3 weeks after artesunate administration. Identifying risk markers for PADH would help predict which patients are at higher risk.

Methods: In this prospective national cohort study conducted in a non-malaria endemic area from 2011 to 2016, a Cox proportional hazards model was used to assess the association between clinical and biological data available at Day 0 and the occurrence of PADH within 30 days of artesunate administration.

Results: In the analyzed population (n = 327), 49 PADH events occurred after a median time of 14 days (IQR, 13-17) after artesunate initiation. Higher initial parasitemia was associated with an increased risk of PADH, with a significant interaction found with patient origin. The cumulative probability of PADH event at Day 30 post-artesunate was 65 % (95 % confidence interval [CI], 44-79) for European patients vs. 14 % (95 % CI, 0-26) for those with recent African ancestry [RAA] when the initial parasitemia was >10 %. After adjustment for weight, history of malaria, initial hemoglobin, very severe malaria and residence in an endemic area, compared to recent African ancestry with initial parasitemia <4 %, the adjusted hazard ratio for PADH occurrence was 18.8 (95 % CI, 4-89) for Europeans and 4.77 (95 % CI, 0.8-29.2) for recent African ancestry with initial parasitemia >10 %.

Conclusions: This study showed that initial parasitemia and patient origin were the main predictors of developing PADH, with the highest risk observed in Europeans with an initial parasitemia >10 %.