The Anaemia of <i>P. falciparum</i> Malaria

Abdalla, Saad; Weatherall, D. J.; Wickramasinghe, S. N.; Hughes, Martha

doi:10.1111/j.1365-2141.1980.tb05956.x

Cited by 263 publications

(165 citation statements)

References 25 publications

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“…Several studies 1,2,29 have clearly demonstrated a slow rate of compensation of the massive erythrocyte loss in anemic subjects because of defective erythropoiesis. Acutely infected children have normal or small numbers of erythroid precursors in their bone marrow.…”

Section: Discussionmentioning

confidence: 99%

“…Several recent studies have indicated that P falciparum-induced anemia is associated principally with the destruction of UEs 1,2,27 and is exacerbated by defects in erythropoiesis. 1,28,29 Extravascular hemolysis of IEs and UEs occurs in hyperparasitemic P falciparum infections and is thought to result from destruction by the "pitting" of parasites-macrophages in the spleen-decreasing the deformability of these cells. 2,5,29 The reasons for UE elimination remained enigmatic.…”

Section: Discussionmentioning

confidence: 99%

“…Anemia is undoubtedly the most common complication of Plasmodium falciparum infection 1,2 and is particularly severe in children and pregnant women living in endemic areas. Anemia is caused partly by the loss of red blood cells, both infected erythrocytes (IEs) and uninfected erythrocytes (UEs), which are destroyed by hemolysis or phagocytosis.…”

Section: Introductionmentioning

confidence: 99%

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Plasmodium falciparum rhoptry protein RSP2 triggers destruction of the erythroid lineage

Layez

Nogueira²,

Combes³

et al. 2005

Blood

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The destruction of erythrocytes and defects in erythropoiesis are among the most frequently observed causes of morbidity in severe Plasmodium falciparum malaria. The molecular mechanisms involved remain unclear, despite extensive investigation. We show here, for the first time, that tagging with the parasite rhoptry protein ring surface protein 2 (RSP2) is not restricted to the surfaces of normal erythrocytes, as previously reported, but that it extends to erythroid precursor cells in the bone marrow of anemic malaria patients. Monoclonal mouse antibodies and human sera from patients with severe anemia, reacting with RSP2-tagged erythrocytes, induced cell destruction by phagocytosis and complement activation in vitro. Our observations reveal a new parasite mechanism implicated in the destruction of normal erythrocytes and probably dyserythropoiesis in malaria patients. These data suggest that the tagging of host cells with RSP2 may trigger anemia in falciparum malaria. IntroductionAnemia is undoubtedly the most common complication of Plasmodium falciparum infection 1,2 and is particularly severe in children and pregnant women living in endemic areas. Anemia is caused partly by the loss of red blood cells, both infected erythrocytes (IEs) and uninfected erythrocytes (UEs), which are destroyed by hemolysis or phagocytosis. 3 Rigidification of the membranes of IEs and UEs during infection may be an important factor in the destruction of these cells during passage through the spleen. 4,5 There seem to be many causes of anemia, and the underlying mechanisms remain elusive.Our recent studies on ring surface protein 2 (RSP2) suggest that this rhoptry molecule occasionally binds to the surface of UEs. 6 RSP2 has been identified as the highly conserved Rap2 gene found in all P falciparum isolates examined to date 7 (Sterkers Y., L. C., da Rocha M., Scheidig C., Lepolard C., Cowman A., G. J., and Scherf A., manuscript in preparation). Experimental evidence indicates that merozoites transfer RSP2 to the surfaces of erythrocytes, probably during aborted invasions, 6 suggesting a possible link to anemia in malaria patients.In this work, we used anti-RSP2 monoclonal antibodies and sera from P falciparum-infected anemia patients to investigate the role of RSP2 in the destruction of red blood cells. By modeling in vitro and ex vivo observations, we show that anti-RSP2 antibodies specifically react with cells of the erythroid lineage tagged with RSP2. We present experimental evidence that the antibody response against RSP2 can induce phagocytosis and complement binding to RSP2-tagged erythrocytes, leading to the destruction of otherwise normal erythrocytes. Finally, we show that merozoites can also label leukemic erythroblasts in vitro and erythroid precursors in the bone marrow of malaria patients with RSP2, possibly leading to erythropoietic dysfunction. Thus, we describe here a novel molecular mechanism of host-parasite interaction that may have severe consequences in malaria patients. Materials and methods Parasites and ce...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Plasmodium falciparum rhoptry protein RSP2 triggers destruction of the erythroid lineage

Layez

Nogueira²,

Combes³

et al. 2005

Blood

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“…2 Those patients they classified as having "acute malaria" (short history and high parasitemia) experienced a drop in hemoglobin when parasites disappeared as a result of drug treatment. They also observed that reticulocytosis developed 5 days after treatment-that is, after parasitemia had fallen.…”

Section: Discussionmentioning

confidence: 99%

Anemia in parasite- and recombinant protein-immunized aotus monkeys infected with Plasmodium falciparum.

Jones

Stroncek²,

Gozalo³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. Plasmodium falciparum-induced anemia was characterized in Aotus monkeys repeatedly immunized by infection with P. falciparum (FVO strain) parasites, then cross-challenged with CAMP strain, or in monkeys receiving blood stage challenges as part of malaria vaccine trials. In 4 studies, 25 (30.5%) of 82 monkeys had at least a 50% reduction in hematocrit; mean day of maximum parasitemia was 12.5, whereas the mean day of minimum hematocrit was 18.8 (P < 0.0009). Decreased hematocrit levels were not associated with reticulocytosis until parasite densities decreased significantly from peak levels. Direct antibody tests to detect IgG and C3d on the surface of erythrocytes were negative. Nonantibody/noncomplement-mediated lysis of uninfected erythrocytes seems to be the principal cause of the anemia, and it also seems that bone marrow suppression and lysis of infected erythrocytes contributed to the anemia. Partial immunity-whether induced by repeated immunization with whole parasites or with vaccine-seems important to the development of anemia.

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“…16,[18][19][20][21][22] The frequency of parasitemia was not a significant risk factor in the multivariate model, suggesting that the mechanism responsible for malaria-related anemia involved predominantly acute hemolysis as compared with dyserythropoiesis or ineffective erythropoiesis due to recurrent parasitemia. 19,20,23,24 The role of the parasite density is still unclear. In our study among parasitemic children, the Hb level was not related to parasite density.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of and risk factors for anemia in young children in southern Cameroon.

Cornet¹,

Hesran²,

Fiévet³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. Anemia during childhood remains a major public health challenge in sub-Saharan Africa. To determine the prevalence of and the main risk factors for anemia in young children, we conducted a longitudinal survey in Ebolowa in southern Cameroon. Children were enrolled in two cohorts and followed during a three-year period: the first cohort was composed of 122 children from 0 to 36 months of age and the second cohort was composed of 84 children from 24 to 60 months of age. The two cohorts were followed weekly for symptomatic malaria, monthly for both symptomatic and asymptomatic malaria, and every six months for hematologic data; the children were grouped into six-month age groups. The prevalence of anemia (hemoglobin [Hb] level Ͻ 11 g/dl) was the highest in the sixmonth-old age group (47%) and the age-related evolution clearly showed a decrease in the prevalence from three years of age. Thus, 42% of the children less than three years of age were anemic, while 21% of the children between three and five years of age were anemic. The lowest mean Ϯ SD Hb content (10.7 Ϯ 2.1 g/dl) was observed in the six-month-old children and a regular improvement in the Hb level occurred from six months to three years of age. A stabilization was observed at a level of approximately 12 g/dl. At any age, there was no difference in mean Hb levels between children with AS and AA Hb genotypes. Hookworm infection was diagnosed in two children in the study population. Results of a multivariate analysis showed that placental malaria infection was the strongest risk factor for anemia in the six-month-old children (odds ratio [OR] ϭ 3.6; 95% confidence interval [CI] ϭ 1.1-12.3) and was independent of the frequency of parasitemia, parasitemia at the time of Hb measurement, or microcytosis. In the one-year-old age group, microcytosis was a significant factor related to anemia (OR ϭ 2.8, 95% CI ϭ 1-7.8) pointing out the role of iron deficiency at this age. Parasitemia at the time of Hb measurement was significantly associated with anemia in all age groups (except in 54-and 60-month-old groups). Strategies to decrease the prevalence of anemia in young children in southern Cameroon should include chemoprophylaxis for pregnant women, prevention of acquired malaria infection in both pregnancy and infancy, and prevention of nutritional iron deficiency.Anemia impairs normal development in children and it constitutes a major public health problem in young children in the developing world with wide social and economic implications. Thus, decreased physical exercise tolerance and intellectual performance have been associated with mild anemia, which may lead to a slowdown of growth in children. 1, 2In sub-Saharan Africa in children less than five years of age, the prevalence of anemia varies from 43% in Zaire to 74% in Tanzania. 3, 4 Its etiology in tropical countries is multifactorial: thus, the most important risk factors need to be identified for prevention strategy. Anemia is commonly associated with nutritional deficiencies such as iron defic...

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The Anaemia of P. falciparum Malaria

Cited by 263 publications

References 25 publications

Plasmodium falciparum rhoptry protein RSP2 triggers destruction of the erythroid lineage

Plasmodium falciparum rhoptry protein RSP2 triggers destruction of the erythroid lineage

Anemia in parasite- and recombinant protein-immunized aotus monkeys infected with Plasmodium falciparum.

Prevalence of and risk factors for anemia in young children in southern Cameroon.

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