Haemolytic anaemia in an HIV-infected patient with severe falciparum malaria after treatment with oral artemether-lumefantrine

Abstract

Intravenous (i.v.) artesunate is now the recommended first-line treatment of severe falciparum malaria in adults and children by WHO guidelines. Nevertheless, several cases of haemolytic anaemia due to i.v. artesunate treatment have been reported. This paper describes the case of an HIV-infected patient with severe falciparum malaria who was diagnosed with haemolytic anaemia after treatment with oral artemether-lumefantrine.The patient presented with fever, headache, and arthromyalgia after returning from Central African Republic where he had been working. The blood examination revealed acute renal failure, thrombocytopaenia and hypoxia. Blood for malaria parasites indicated hyperparasitaemia (6%) and Plasmodium falciparum infection was confirmed by nested-PCR. Severe malaria according to the laboratory WHO criteria was diagnosed. A treatment with quinine and doxycycline for the first 12 hours was initially administered, followed by arthemeter/lumefantrine (Riamet®) for a further three days. At day 10, a diagnosis of severe haemolytic anaemia was made (Hb 6.9 g/dl, LDH 2071 U/l). Hereditary and autoimmune disorders and other infections were excluded through bone marrow aspiration, total body TC scan and a wide panel of molecular and serologic assays. The patient was treated by transfusion of six units of packed blood red cell. He was discharged after complete remission at day 25. At present, the patient is in a good clinical condition and there is no evidence of haemolytic anaemia recurrence.This is the first report of haemolytic anaemia probably associated with oral artemether/lumefantrine. Further research is warranted to better define the adverse events occurring during combination therapy with artemisinin derivatives.

Haemolysis associated with the treatment of malaria with artemisinin derivatives: a systematic review of current evidence

“…[12][13][14][15][16][17][18][19][21][22][23][24] One study was excluded from further analysis, 12 since the reported patients were part of a second publication, which was used for the purpose of this systematic review. 13 In addition to the above-mentioned scientific papers, reports by the Centers for Disease Control and Prevention (CDC, Atlanta, USA) 25 and by the Medicines for Malaria Venture (Geneva, Switzerland) were identified and included in this analysis 26 ( Figure 1).…”

“…[12][13][14][15][16][17][18][19]21,23,24,26 Thirty-three cases have been published in research papers and four cases are referred to in a meeting report (one from China, one from the USA, and two from Canada). 26 In addition, surveillance data from France were discussed in that report but have not yet been published and were therefore not available for the purpose of this review.…”

“…13 Finally, two adult patients experiencing late onset haemolysis following the use of oral ACTs were reported from Italy. 23,24 One of these patients was HIVpositive and was treated with intravenous quinine before receiving artemether-lumefantrine as follow-on treatment. 24 …”

“…23,24 One of these patients was HIVpositive and was treated with intravenous quinine before receiving artemether-lumefantrine as follow-on treatment. 24 …”

Clinical spectrum and severity of hemolytic anemia in glucose 6-phosphate dehydrogenase–deficient children receiving dapsone

“…43 There are a few cases in the literature of hemolytic anemia during or after treatment with intravenous artesunate alone or in combination with mefloquine, and one report after oral treatment with AL in a (G6PD normal) patient with HIV and severe falciparum malaria. 44 However, these are rare adverse events. It appears that clinically, in the majority of patients administered artemisinins, the presence of malaria and dehydration rather than the drug exert the most important effects on hematologic parameters.…”