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

Abstract

Background: Post-Artesunate delayed hemolysis (PADH) occurs in approximately 15% of treated patients 2 to 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%.