Intraleucocytic malaria pigment and clinical severity of malaria in children

Amodu, Olukemi K.; Adeyemo, Adebowale; Olumese, P.E.; Gbadegesin, R.A.

doi:10.1016/s0035-9203(98)90952-x

Cited by 95 publications

(87 citation statements)

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“…Recent studies of individuals with malaria suggest that phagocytosis of pfHz by monocytes and neutrophils is an important predictor of clinical severity (4,18,39,48). Additional studies have demonstrated that sHz enhanced MIF production in mouse peritoneal macrophages and human mononuclear cells (43).…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, our findings do not exclude the possibility that MIF may be increased in the local milieu within the bone marrow of the children in our cohort despite the reduced concentrations of MIF in the peripheral circulation. Previous studies in malaria-endemic regions illustrate that phagocytosis of pfHz by monocytes and neutrophils is a better index of disease severity than peripheral parasitemia (4,18,39,45,48). This may be related to the fact that concomitant peripheral parasitemia does not account for parasite sequestration within microvascular networks and/or the duration of infection.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Role of Monocyte-Acquired Hemozoin in Suppression of Macrophage Migration Inhibitory Factor in Children with Severe Malarial Anemia

Awandare

Ouma

et al. 2007

Infect Immun

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Severe malarial anemia (SMA), caused by Plasmodium falciparum infections, is one of the leading causes of childhood mortality in sub-Saharan Africa. Although the molecular determinants of SMA are largely undefined, dysregulation in host-derived inflammatory mediators influences disease severity. Macrophage migration inhibitory factor (MIF) is an important regulator of innate inflammatory responses that has recently been shown to suppress erythropoiesis and promote pathogenesis of SMA in murine models. To examine the role of MIF in the development of childhood SMA, peripheral blood MIF production was examined in Kenyan children (aged <3 years, n ‫؍‬ 357) with P. falciparum malarial anemia. All children in the study were free from bacteremia and human immunodeficiency virus type 1. Since deposition of malarial pigment (hemozoin [Hz]) contributes to suppression of erythropoiesis, the relationship between MIF concentrations and monocytic acquisition of Hz was also examined in vivo and in vitro. Circulating MIF concentrations declined with increasing severity of anemia and significantly correlated with peripheral blood leukocyte MIF transcripts. However, MIF concentrations in peripheral blood were not significantly associated with reticulocyte production. Multivariate regression analyses, controlling for age, gender, and parasitemia, further revealed that elevated levels of pigment-containing monocytes (PCM) was associated with SMA and decreased MIF production. In addition, PCM levels were a better predictor of hemoglobin and MIF concentrations than parasite density. Additional experiments in malaria-naive individuals demonstrated that hemozoin caused both increased and decreased MIF production in cultured peripheral blood mononuclear cells (PBMC) in a donor-specific manner, independent of apoptosis. However, PBMC MIF production in children with acute malaria progressively declined with increasing anemia severity. Results presented here demonstrate that acquisition of hemozoin by monocytes is associated with suppression of peripheral blood MIF production and enhanced severity of anemia in childhood malaria.Annually, there are 350 to 500 million clinical cases of malaria that result in over 1 million deaths (69). The majority of malaria-related mortalities are due to infections with Plasmodium falciparum and occur in immune-naive infants and young children in sub-Saharan Africa, accounting for 18% of all deaths before 5 years of age (69). Severe malarial anemia (SMA) accounts for the greatest proportion of malaria-related morbidity and mortality worldwide (13). In holoendemic P. falciparum transmission areas, SMA is the commonest clinical presentation of severe malaria in children less than 3 years of age, with cerebral malaria occurring only in rare cases (44, 51).Markedly reduced hemoglobin (Hb) concentrations in children with SMA result from overlapping but distinct processes, including direct and indirect destruction of parasitized red blood cells (pRBC), increased clearance of uninfected erythrocytes, and suppres...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Role of Monocyte-Acquired Hemozoin in Suppression of Macrophage Migration Inhibitory Factor in Children with Severe Malarial Anemia

Awandare

Ouma

et al. 2007

Infect Immun

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“…3,4 Phagocytosis of malaria pigment by monocytes/macrophages, and less frequently by neutrophils, has been observed in peripheral blood cells and bone marrow of patients with malaria. 3,6,8 Erythrophagocytosis of infected and uninfected red cells by monocytes/macrophages has also been observed. 6 ' 8 In some of the peripheral blood smears examined during this study, monocytes and rarely neutrophils (Figure 2), contained malaria pigment and in very rare cases, erythrophagocytosis by monocytes was also observed.…”

Section: Discussionmentioning

confidence: 99%

“…3,6,8 Erythrophagocytosis of infected and uninfected red cells by monocytes/macrophages has also been observed. 6 ' 8 In some of the peripheral blood smears examined during this study, monocytes and rarely neutrophils (Figure 2), contained malaria pigment and in very rare cases, erythrophagocytosis by monocytes was also observed. Also, three patients needed bone marrow examination, two for pancytopenia with a positive malaria smear to exclude bone marrow etiology.…”

Section: Discussionmentioning

confidence: 99%

Malaria: Hematological Aspects

et al. 2002

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“…Beyond the health dimension, malaria leaves untold social and economic consequences on people and nations alike. It causes great misery to sufferers, and adversely affects the social and psychological well-being of individuals, families and the nation at large (Amodu et al, 1998).…”

mentioning

confidence: 99%