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

National Institute for Infectious Diseases Lazzaro Spallanzani, Via Portuense 292, 00149 Rome, Italy.
Malaria Journal (Impact Factor: 3.49). 03/2012; 11:91. DOI: 10.1186/1475-2875-11-91
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Within 24 hr after oral administration of the antimalarial artesunate to rats on Day 10 or 11 postcoitum (pc), there is depletion of embryonic erythroblasts (EEbs), leading to embryo malformation and death. The proximate agent is dihydroartemisinin (DHA), the primary metabolite. We investigated the causes of EEb depletion by evaluating effects of DHA on EEbs in whole embryo culture (WEC). Rat embryos cultured starting on Day 9 pc were treated with 1 or 7 μM DHA for 24 hr starting after 19 hr of culture (∼Day 10 pc) and for 2 to 12 hr starting after 43 hr of culture (∼Day 11 pc). DHA effects indicating the depletion of EEbs were paling of the visceral yolk sac and reductions in visible blood cells, H&E-stained normal (Type II or III) EEbs, and dividing (BrdU-stained) EEbs. DHA-induced abnormal cell division was indicated by increases in symmetric and asymmetric binuclear cells. DHA-induced apoptosis was indicated by increases in TUNEL- and Caspase-3-positive cells and EEbs with fragmented nuclei. In addition, although the overall number of EEbs was decreasing, DHA caused increases in the numbers of circulating early-stage (Type I or earlier) EEbs that could not be accounted for by cell division, suggesting the release of new, less sensitive erythroblasts from the yolk sac. In summary, treatment of Day 10 or 11 pc rat embryos with DHA in WEC resulted in defective and arrested cell division in EEbs followed by apoptosis, suggesting a mechanism for their depletion after artesunate treatment in vivo.
    Birth Defects Research Part B Developmental and Reproductive Toxicology 01/2014; · 1.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Parenteral artesunate is recommended as first-line therapy for severe malaria. While its efficacy is firmly established, data on safety are still incomplete. Delayed hemolysis has been described in hyperparasitemic non-immune travelers but it is unknown if African children are equally at risk.Methods. Children aged six to 120 months with severe malaria were followed up after treatment with parenteral artesunate in Lambaréné, Gabon, and Kumasi, Ghana. The primary outcome was incidence of delayed hemolysis on Day 14.Results. 72 children contributed complete data sets necessary for primary outcome assessment. Delayed hemolysis was detected in 5 children (7%), with one child reaching a nadir in hemoglobin of 2.8 g/dl. Patients with delayed hemolysis had higher parasite counts on admission (geometric mean parasite densities (GMPD) 306,968/µl vs. 92,642/µl, p=0.028) and were younger (median age: 24 months vs. 43 months, p=0.046) than the rest of the cohort. No correlation with sickle cell trait or glucose-6-phosphate-dehydrogenase deficiency was observed.Conclusions. Delayed hemolysis is a frequent and relevant complication in hyperparasitemic African children treated with parenteral artesunate for severe malaria. Physicians should be aware of this complication and consider prolonged follow-up.Trial registration. Pan-African Clinical Trials Registry: PACTR201102000277177 (
    The Journal of Infectious Diseases 12/2013; · 5.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In sub-Saharan Africa, artemisinin-based combination therapy (ACT) and injectable artesunate are the first-line treatments for uncomplicated and severe Plasmodium falciparum malaria, respectively. However, recent studies suggest that delayed anaemia is associated with these treatments in non-immune travellers. This paper aimed to assess the risk factors associated with delayed anaemia after falciparum malaria treatment with artemisinin-containing drugs in malaria-endemic populations.
    Malaria Journal 09/2014; 13(1):358. · 3.49 Impact Factor

Full-text (2 Sources)

Available from
Jun 4, 2014