Treatment for Severe Malaria: Post-Artesunate Delayed Haemolysis and Neutropenia

Abstract

Parenteral artesunate (AS) is the WHO first-line treatment recommended in adults and children for severe malaria. Post-artesunate delayed haemolysis (PADH) is an uncommon adverse reaction to AS with a mechanism that is not fully understood, occurring in adults and children. Neutropenia is another possible finding after AS treatment, albeit rare. We present the case of a child who experienced both effects after treatment with AS for imported severe Falciparum malaria with very high parasitaemia. In addition, thirty-five paediatric cases of PADH, five cases of delayed anaemia without known haemolysis, and fourteen cases of neutropenia after artesunate treatment were identified from the literature review. PADH seems to be a dose-independent reaction and is not strongly related to hyperparasitaemia, although it is more frequent in this case. To date, the benefits of AS outweigh its potential side effects. However, haematological follow-up is mandatory to avoid possible complications from anaemia and neutropenia, especially in children treated with other contemporary drugs.

Post-Artesunate Delayed Hemolysis: A Review of Current Evidence

“…There needs to be an awareness of the overlapping clinical features between PADH and hemolytic anemia caused by malaria infection, such as blackwater fever and severe hemolysis. However, patients without clinical symptoms, but with a hemolytic anemia profile, have also been reported occasionally during malaria post-treatment follow-up visits [ 27 , 44 , 46 ]. PADH seems to be dose-independent [ 46 ].…”

“…However, patients without clinical symptoms, but with a hemolytic anemia profile, have also been reported occasionally during malaria post-treatment follow-up visits [ 27 , 44 , 46 ]. PADH seems to be dose-independent [ 46 ]. There was no evidence that supports the relationship between delayed parasite clearance and the development of PADH despite longer treatment duration.…”

“…Hemolytic anemia is defined as a 10% decrease in hemoglobin concentrations, haptoglobin concentrations < 0.1 g/L, and an increase in the lactate dehydrogenase concentration to 390 IU/L or a rise in lactate dehydrogenase concentration of at least 10% after starting artesunate for more than 7 days [ 26 ]. Apart from the hemolytic anemia profile, few studies have reported dose-dependent neutropenia in patients treated with artesunate [ 46 , 49 ]. A summary of case reports of PADH is shown in Table 3 .…”