title: Severity of anaemia is associated with bone marrow haemozoin in children exposed to Plasmodium falciparum.
abstract: There are no large-scale ex vivo studies addressing the contribution of Plasmodium falciparum in the bone marrow to anaemia. The presence of malaria parasites and haemozoin were studied in bone marrows from 290 anaemic children attending a rural hospital in Mozambique. Peripheral blood infections were determined by microscopy and polymerase chain reactions. Bone marrow parasitaemia, haemozoin and dyserythropoiesis were microscopically assessed. Forty-two percent (123/290) of children had parasites in the bone marrow and 49% (111/226) had haemozoin, overlapping with parasitaemia in 83% (92/111) of cases. Sexual and mature asexual parasites were highly prevalent (62% gametocytes, 71% trophozoites, 23% schizonts) suggesting their sequestration in this tissue. Sixteen percent (19/120) of children without peripheral infection had haemozoin in the bone marrow. Haemozoin in the bone marrow was independently associated with decreased Hb concentration (P = 0·005) and was more common in dyserythropoietic bone marrows (P = 0·010). The results of this ex vivo study suggest that haemozoin in the bone marrow has a role in the pathogenesis of malarial-anaemia through ineffective erythropoiesis. This finding may have clinical implications for the development of drugs targeted to prevent and treat malarial-anaemia.
authors.affiliation: Barcelona Centre for International Health Research (CRESIB, Hospital Clínic - University of Barcelona), Barcelona, Spain; CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Spain; Manhiça Health Research Centre (CISM), Maputo, Mozambique.
authors.forename: Ruth
authors.initials: R
authors.lastname: Aguilar
authors.forename: Cinta
authors.initials: C
authors.lastname: Moraleda
authors.forename: Ariel H
authors.initials: AH
authors.lastname: Achtman
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.forename: Llorenç
authors.initials: L
authors.lastname: Quintó
authors.forename: Pau
authors.initials: P
authors.lastname: Cisteró
authors.forename: Augusto
authors.initials: A
authors.lastname: Nhabomba
authors.forename: Eusebio
authors.initials: E
authors.lastname: Macete
authors.forename: Louis
authors.initials: L
authors.lastname: Schofield
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Alonso
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
mesh_terms: D000328:Adult; D000740:Anemia / Q000097:blood / Q000469:parasitology*; D001853:Bone Marrow / Q000469:parasitology*; D016022:Case-Control Studies; D005260:Female; D006420:Hemeproteins / Q000378:metabolism*; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000473:pathology*; D008297:Male; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000378:metabolism; D055815:Young Adult
chemical_list: D006420:Hemeproteins; C020753:hemozoin
keywords: Plasmodium falciparum; anaemia; bone marrow; dyserythropoiesis; haemozoin