Systematic analysis of direct antiglobulin test results in post-artesunate delayed haemolysis

Tommaso Ascoli Bartoli,Claudia Palazzolo,Nazario Bevilacqua,Alessandra D’Abramo,Luciana Lepore,Laura Scorzolini,Angela Corpolongo,Emanuele Nicastri,Giovanna Adamo,Pierre Buffet,Maria Letizia Giancola,Andrea Mariano,Giuseppe Ippolito

doi:10.1186/s12936-021-03735-w

Abstract

BackgroundPost-artesunate delayed haemolysis (PADH) is common after severe malaria episodes. PADH is related to the “pitting” phenomenon and the synchronous delayed clearance of once-infected erythrocytes, initially spared during treatment. However, direct antiglobulin test (DAT) positivity has been reported in several PADH cases, suggesting a contribution of immune-mediated erythrocyte clearance. The aim of the present study was to compare clinical features of cases presenting a positive or negative DAT.MethodsArticles reporting clinical data of patients diagnosed with PADH, for whom DAT had been performed, were collected from PubMed database. Data retrieved from single patients were extracted and univariate analysis was performed in order to identify features potentially related to DAT results and steroids use.ResultsTwenty-two studies reporting 39 PADH cases were included: median baseline parasitaemia was 20.8% (IQR: 11.2–30) and DAT was positive in 17 cases (45.5%). Compared to DAT-negative individuals, DAT-positive patients were older (49.5 vs 31; p = 0.01), had a higher baseline parasitaemia (27% vs 17%; p = 0.03) and were more commonly treated with systemic steroids (11 vs 3 patients, p = 0.002). Depth and kinetics of delayed anaemia were not associated with DAT positivity.ConclusionsIn this case series, almost half of the patients affected by PADH had a positive DAT. An obvious difference between the clinical courses of patients presenting with a positive or negative DAT was lacking. This observation suggests that DAT result may not be indicative of a pathogenic role of anti-erythrocytes antibodies in patients affected by PADH, but it may be rather a marker of immune activation.

Highlights

Post-artesunate delayed haemolysis (PADH) is common after severe malaria episodes
Twenty-two articles reporting clinical features of 38 patients affected by PADH, who had been tested with direct antiglobulin test (DAT), were identified
DAT results were reported in detail in 13 out of the 17 positive patients (76.5%): five of them presented an IgG pattern (38.5%), six showed a C3d positivity (46.1%), while the remaining two cases were characterized by a mixed condition (15.4%)

Summary

Introduction

Post-artesunate delayed haemolysis (PADH) is common after severe malaria episodes. PADH is related to the “pitting” phenomenon and the synchronous delayed clearance of once-infected erythrocytes, initially spared during treatment. Several reports described the occurrence of a late-onset haemolytic syndrome, related to the use of artesunate, defined postartesunate delayed haemolysis (PADH). It usually occurs more than 1 week after the iv artesunate course, in approximately 10–40% of hyperparasitaemic nonimmune travellers [5, 6]. Kurth et al reported a 27.1% incidence of PADH in a cohort of 70 patients with severe malaria managed in European countries [9]. Jauréguiberry et al described a French cohort of 123 imported severe malaria cases, in which 27% of patients experienced PADH after a successful antimalarial treatment [6]. Few PADH cases after oral artemisinin-based combination therapy (ACT) have been already reported [5, 10, 11]

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