Splenic clearance of rigid erythrocytes as an inherited mechanism for splenomegaly and natural resistance to malaria

Henry, B.; Volle, Geoffroy; Akpovi, Hilaire; Gineau, Laure; Roussel, Camille; Ndour, Papa Alioune; Tossou, Félicien; Suarez, Félipe; Palstra, Friso; Fricot, Aurélie; Chambrion, Charlotte; Solinc, Julien; Nguyen, Julie; Garé, Mathilde; Aussenac, Florentin; Cottart, Charles‐Henry; Keyser, Christine; Adamou, Rafiou; Tichit, Magali; Hardy, David; Fiévet, Nadine; Clain, Jérôme; Garcia, André; Courtin, David; Hermine, Olivier; Sabbagh, Audrey; Buffet, Pierre

doi:10.1016/j.ebiom.2022.104167

Cited by 10 publications

(6 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, impaired RBC production was a minor component of anemia in this cohort. In a subset of patients, microsphiltration of RBC directly confirmed that splenic biomechanical sensing of RBC is altered during and after malaria 22,23 and that retention rates of both peripheral and splenic RBCs were correlated with anemia. Taken together, these quantitative observations indicate that excessive spleen‐related RBC loss is the predominant cause of malarial anemia, as previously suggested by ex vivo perfusion of human spleens 24 …”

Section: Discussionmentioning

confidence: 73%

“…[9][10][11][12][30][31][32][33] We were unable to investigate the role of genetics on splenic RBC retention, clearance, and splenomegaly in our mixed cohort of Papuans and non-Papuans, processes recently shown to be genetically controlled in Fulani people. 22 In conclusion, our evaluation of human spleens from a prospective splenectomy series in a malaria-endemic region provides novel quantifications supporting splenic RBC congestion and expansion of red-pulp as key underlying mechanisms of malarial anemia and splenomegaly.…”

Section: Discussionmentioning

confidence: 88%

“…While the splenectomized population may not be wholly representative of the population at large, multiple studies in the general malaria‐exposed population have shown a robust correlation between splenomegaly and malarial anemia 9–12,30–33 . We were unable to investigate the role of genetics on splenic RBC retention, clearance, and splenomegaly in our mixed cohort of Papuans and non‐Papuans, processes recently shown to be genetically controlled in Fulani people 22 …”

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

“…Larger spleens in Pf than in Pv infections suggest a greater retention of uninfected RBCs in the red‐pulp cords, possibly from the greater reduction in deformability of uninfected RBCs apparent in falciparum malaria 50 , 51 or from greater splenic filtration stringency in Pf infection. 22 With Pf capable of infecting RBCs of all ages, the greater retention and congestion of RBCs provide an abundance of target cells favoring the recently identified endosplenic Pf lifecycle. 13 Our findings also challenge the assumptions underlying prevailing models of malarial anemia and the proportion of uninfected‐to‐infected erythrocytes lost in infection with both Plasmodium spp., 3 , 52 , 53 , 54 where all parasites have been previously assumed to circulate.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

Retention of uninfected red blood cells causing congestive splenomegaly is the major mechanism of anemia in malaria

Kho,

Siregar,

Qotrunnada

et al. 2023

American J Hematol

Self Cite

View full text Add to dashboard Cite

Splenomegaly frequently occurs in patients with Plasmodium falciparum (Pf) or P. vivax (Pv) malarial anemia, but mechanisms underlying this co‐occurrence are unclear. In malaria‐endemic Papua, Indonesia, we prospectively analyzed red blood cell (RBC) concentrations in the spleen and spleen‐mimetic retention in 37 subjects splenectomized for trauma or hyperreactive splenomegaly, most of whom were infected with Plasmodium. Splenomegaly (median 357 g [range: 80–1918 g]) was correlated positively with the proportion of red‐pulp on histological sections (median 88.1% [range: 74%–99.4%]; r = .59, p = .0003) and correlated negatively with the proportion of white‐pulp (median 8.3% [range: 0.4%–22.9%]; r = −.50, p = .002). The number of RBC per microscopic field (>95% uninfected) was correlated positively with spleen weight in both Pf‐infected (r = .73; p = .017) and Pv‐infected spleens (r = .94; p = .006). The median estimated proportion of total‐body RBCs retained in Pf‐infected spleens was 8.2% (range: 1.0%–33.6%), significantly higher than in Pv‐infected (2.6% [range: 0.6%–23.8%]; p = .015) and PCR‐negative subjects (2.5% [range: 1.0%–3.3%]; p = .006). Retained RBCs accounted for over half of circulating RBC loss seen in Pf infections. The proportion of total‐body RBC retained in Pf‐ and Pv‐infected spleens correlated negatively with hemoglobin concentrations (r = −.56, p = .0003), hematocrit (r = −.58, p = .0002), and circulating RBC counts (r = −.56, p = .0003). Splenic CD71‐positive reticulocyte concentrations correlated with spleen weight in Pf (r = 1.0; p = .003). Retention rates of peripheral and splenic RBCs were correlated negatively with circulating RBC counts (r = −.69, p = .07 and r = −.83, p = .008, respectively). In conclusion, retention of mostly uninfected RBC in the spleen, leading to marked congestion of the red‐pulp, was associated with splenomegaly and is the major mechanism of anemia in subjects infected with Plasmodium, particularly Pf.

show abstract

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Retention of uninfected red blood cells causing congestive splenomegaly is the major mechanism of anemia in malaria

Kho,

Siregar,

Qotrunnada

et al. 2023

American J Hematol

Self Cite

View full text Add to dashboard Cite

show abstract

Pro‐ and anti‐inflammatory cytokines mediate the progression of severe anemia in malaria‐infected children: A prospective study

Nkansah,

Osei‐Boakye,

Abbam

et al. 2024

Immunity Inflam & Disease

View full text Add to dashboard Cite

BackgroundSevere Plasmodium falciparum malarial anemia is still the principal cause of death in children in underdeveloped countries. An imbalance between proinflammatory and anti‐inflammatory cytokines is associated with malaria progression. This study evaluated circulating levels of selected inflammatory cytokines among malaria‐infected children in Ghana.MethodsThis case‐control study was conducted at Tamale Teaching Hospital, Ghana. One hundred and twenty children with malaria and 60 controls, aged 12−144 months were selected from April to July, 2023 for the study. Malaria was diagnosed through microscopy, full blood count was measured using hematology analyzer, and cytokines were measured using enzyme‐linked immunosorbent assay.ResultsMalaria‐infected children had higher tumor necrosis factor alpha (TNF‐α) (p < .001), interferon‐gamma (IFN‐ɣ) (p < .001), interleukin (IL)‐1β (p < .001), IL‐6 (p < .001), granulocyte macrophage‐colony stimulating factor (GM‐CSF) (p < .001), and IL‐10 (p < .001) levels than controls. Participants with high parasitemia had raised TNF‐α (p < .001), IFN‐ɣ (p < .001), IL‐1β (p < .001), IL‐6 (p < .001), GM‐CSF (p < .001), and IL‐10 (p < .001), but reduced IL‐3 (p < .001) and TGF‐β (p < .001) than those with low parasitemia. Severe malarial anemic children had elevated TNF‐α (p < .001), IFN‐ɣ (p < .001), IL‐1β (p < .001), IL‐6 (p < .001), GM‐CSF (p < .001), and IL‐10 (p < .001), but lower IL‐3 (p < .001) and TGF‐β (p < .001) than those with uncomplicated malaria.ConclusionParasite density was the principal predictor of the cytokine levels, as parasitemia positively associated with IL‐10, GM‐CSF, IL‐6, IL‐1β, IFN‐ɣ, and TNF‐α, but negatively associated with IL‐3 and TGF‐β. Malaria is associated with enhanced secretion of pro‐ and anti‐inflammatory cytokines in Ghanaian children. Inflammatory cytokines may be involved in the development of severe malarial anemia in children. However, IL‐3 and TGF‐β may offer protection against severe malarial anemia.

show abstract

Current Status of Malaria Control and Elimination in Africa: Epidemiology, Diagnosis, Treatment, Progress and Challenges

Li,

Docile,

Fisher

et al. 2024

J Epidemiol Glob Health

View full text Add to dashboard Cite

The African continent carries the greatest malaria burden in the world. Falciparum malaria especially has long been the leading cause of death in Africa. Climate, economic factors, geographical location, human intervention and unstable security are factors influencing malaria transmission. Due to repeated infections and early interventions, the proportion of clinically atypical malaria or asymptomatic plasmodium carriers has increased significantly, which easily lead to misdiagnosis and missed diagnosis. African countries have made certain progress in malaria control and elimination, including rapid diagnosis of malaria, promotion of mosquito nets and insecticides, intermittent prophylactic treatment in high-risk groups, artemisinin based combination therapies, and the development of vaccines. Between 2000 and 2022, there has been a 40% decrease in malaria incidence and a 60% reduction in mortality rate in the WHO African Region. However, many challenges are emerging in the fight against malaria in Africa, such as climate change, poverty, substandard health services and coverage, increased outdoor transmission and the emergence of new vectors, and the growing threat of resistance to antimalarial drugs and insecticides. Joint prevention and treatment, identifying molecular determinants of resistance, new drug development, expanding seasonal malaria chemo-prevention intervention population, and promoting the vaccination of RTS, S/AS01 and R21/Matrix-M may help to solve the dilemma. China’s experience in eliminating malaria is conducive to Africa’s malaria prevention and control, and China-Africa cooperation needs to be constantly deepened and advanced. Our review aims to help the global public develop a comprehensive understanding of malaria in Africa, thereby contributing to malaria control and elimination.

show abstract

Splenic clearance of rigid erythrocytes as an inherited mechanism for splenomegaly and natural resistance to malaria

Cited by 10 publications

References 86 publications

Retention of uninfected red blood cells causing congestive splenomegaly is the major mechanism of anemia in malaria

Retention of uninfected red blood cells causing congestive splenomegaly is the major mechanism of anemia in malaria

Pro‐ and anti‐inflammatory cytokines mediate the progression of severe anemia in malaria‐infected children: A prospective study

Current Status of Malaria Control and Elimination in Africa: Epidemiology, Diagnosis, Treatment, Progress and Challenges

Contact Info

Product

Resources

About