scholarly journals Lymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria

2015 ◽  
Vol 23 (2) ◽  
pp. 95-103 ◽  
Author(s):  
Wilson L. Mandala ◽  
Chisomo L. Msefula ◽  
Esther N. Gondwe ◽  
James J. Gilchrist ◽  
Stephen M. Graham ◽  
...  
Keyword(s):  
Cerebral Malaria ◽  
Severe Malaria ◽  
Uncomplicated Malaria ◽  
Lymphocyte Activation ◽  
Lymphocyte Subset ◽  
Memory Cells ◽  
Age Assessment ◽  
Immune Priming ◽  
Severe Malarial Anemia ◽  
Malarial Anemia

ABSTRACTLymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (n= 113) and healthy aparasitemic children (n= 42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status. Children with cerebral malaria were older than those with severe malarial anemia. We found panlymphopenia in children presenting with cerebral malaria (median lymphocyte count, 2,100/μl) and uncomplicated malaria (3,700/μl), which was corrected in convalescence and was absent in severe malarial anemia (5,950/μl). Median percentages of activated CD69+NK (73%) and γδ T (60%) cells were higher in cerebral malaria than in other malaria types. Median ratios of memory to naive CD4+lymphocytes were higher in cerebral malaria than in uncomplicated malaria and low in severe malarial anemia. The polarized lymphocyte subset profiles of different forms of severe malaria are independent of age. In conclusion, among Malawian children cerebral malaria is characterized by lymphocyte activation and increased memory cells, consistent with immune priming. In contrast, there are reduced memory cells and less activation in severe malaria anemia. Further studies are required to understand whether these immunological profiles indicate predisposition of some children to one or another form of severe malaria.

scholarly journals Circulatory hepcidin is associated with the anti-inflammatory response but not with iron or anemic status in childhood malaria

Blood ◽  
2013 ◽  
Vol 121 (15) ◽  
pp. 3016-3022 ◽  
Author(s):  
Florence Burté ◽  
Biobele J. Brown ◽  
Adebola E. Orimadegun ◽  
Wasiu A. Ajetunmobi ◽  
Nathaniel K. Afolabi ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cerebral Malaria ◽  
Severe Malaria ◽  
Severe Malarial Anemia ◽  
Key Points ◽  
Mild Malaria ◽  
Anti Inflammatory ◽  
Childhood Malaria ◽  
Malarial Anemia

Key Points Hepcidin rises more dramatically in mild malaria than in severe malaria. Hepcidin levels are linked to inflammation, not anemia, in severe malarial anemia and cerebral malaria.

scholarly journals 963. Whole Blood Transcriptome Analysis Reveals Differences in Erythropoiesis and Neurologically Relevant Pathways Between Cerebral Malaria and Severe Malarial Anemia

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S35-S35
Author(s):  
Srinivas Nallandhighal ◽  
Gregory Park ◽  
Yen-Yi Ho ◽  
Robert Opoka ◽  
Chandy John ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebral Malaria ◽  
Severe Malaria ◽  
Whole Blood ◽  
Heme Oxygenase 1 ◽  
Specific Gene ◽  
Severe Malarial Anemia ◽  
Specific Gene Expression ◽  
Blood Transcriptome ◽  
Malarial Anemia

Abstract Background Plasmodium falciparum malaria can rapidly progress to severe disease that can lead to death if left untreated. Severe malaria cases commonly present as severe malarial anemia (SMA), defined in children as hemoglobin (Hb) <5 g/dL with parasitemia, or as cerebral malaria (CM), which manifests as parasitemia with acute neurological deficits and has an inpatient mortality rate of ~20%. The molecular and cellular processes that lead to CM and SMA are unclear. Methods In a cross-sectional study, we compared genome-wide transcription profiles of whole blood obtained from Ugandan children with acute CM (n = 17) or SMA (n = 17) and community children without P. falciparum infection (n = 12) who were enrolled in a parent cohort study of severe malaria. We determined the relationships between gene expression, hematological indices, and plasma biomarkers, including inflammatory cytokines. Results Both CM and SMA demonstrated enrichment of dendritic cell activation, inflammatory/TLR/chemokines, monocyte, and neutrophil modules but depletion of lymphocyte modules. Neurodegenerative disease and neuroinflammation pathways were enriched in CM. Increased Nrf2 pathway gene expression corresponded with increased plasma heme oxygenase-1 and the heme catabolite bilirubin in a manner specific to children with both SMA and sickle cell disease. Reticulocyte-specific gene expression was markedly decreased in CM relative to SMA despite higher Hb levels and appropriate increases in plasma erythropoietin. Viral sensing/interferon regulatory factor (IRF) 2 module (M111) expression and plasma IP-10 levels both negatively correlated with reticulocyte-specific signatures, but only M111 expression independently predicted decreased reticulocyte-specific gene expression after controlling for leukocyte count, Hb level, parasitemia, and clinical syndrome by multiple regression. Conclusion Differences in the blood transcriptome of CM and SMA relate to neurologically relevant pathways and erythropoiesis. Erythropoietic suppression during severe malaria is more pronounced during CM versus SMA and is positively associated with IRF2 blood signatures. Future studies are needed to validate these findings. Disclosures All authors: No reported disclosures.

scholarly journals Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria

2017 ◽  
Vol 24 (4) ◽  
Author(s):  
Wilson L. Mandala ◽  
Chisomo L. Msefula ◽  
Esther N. Gondwe ◽  
Mark T. Drayson ◽  
Malcolm E. Molyneux ◽  
...  
Keyword(s):  
Cerebral Malaria ◽  
Proinflammatory Cytokines ◽  
Uncomplicated Malaria ◽  
Acute Infection ◽  
Healthy Controls ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Severe Malarial Anemia ◽  
Tnf Α ◽  
Malarial Anemia

ABSTRACT Proinflammatory cytokines are involved in clearance of Plasmodium falciparum, and very high levels of these cytokines have been implicated in the pathogenesis of severe malaria. In order to determine how cytokines vary with disease severity and syndrome, we enrolled Malawian children presenting with cerebral malaria (CM), severe malarial anemia (SMA), and uncomplicated malaria (UCM) and healthy controls. We analyzed serum cytokine concentrations in acute infection and in convalescence. With the exception of interleukin 5 (IL-5), cytokine concentrations were highest in acute CM, followed by SMA, and were only mildly elevated in UCM. Cytokine concentrations had fallen to control levels when remeasured at 1 month of convalescence in all three clinical malaria groups. Ratios of IL-10 to tumor necrosis factor alpha (TNF-α) and of IL-10 to IL-6 followed a similar pattern. Children presenting with acute CM had significantly higher concentrations of TNF-α (P < 0.001), interferon gamma (IFN-γ) (P = 0.0019), IL-2 (P = 0.0004), IL-6 (P < 0.001), IL-8 (P < 0.001), and IL-10 (P < 0.001) in sera than healthy controls. Patients with acute CM had significantly higher concentrations of IL-6 (P < 0.001) and IL-10 (P = 0.0003) than those presenting with acute SMA. Our findings are consistent with the concept that high levels of proinflammatory cytokines, despite high levels of the anti-inflammatory cytokine IL-10, could contribute to the pathogenesis of CM.

Altered Immune Response in Severe Malaria Anemia in Children.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1303-1303 ◽  
Author(s):  
Victor R. Gordeuk ◽  
Ishmael Kasvosve ◽  
Janneke van Dijk ◽  
Guenter Weiss ◽  
Zufan Debebe ◽  
...  
Keyword(s):  
Severe Malaria ◽  
Interferon Gamma ◽  
Plasma Levels ◽  
Uncomplicated Malaria ◽  
Interleukin 10 ◽  
Tnf Alpha ◽  
Severe Anemia ◽  
Severe Malarial Anemia ◽  
Younger Age ◽  
Malarial Anemia

Abstract We prospectively assessed immune markers in children &lt;6 years with severe malarial anemia (hemoglobin &lt;5.0 g/dL; n = 72) and uncomplicated malaria (n = 69) who presented to Macha Mission Hospital in Zambia’s Southern Province. We also studied 70 children &lt;6 years who presented to well child clinics in Harare, Zimbabwe as controls. Compared to controls, children with uncomplicated malaria had significantly higher temperatures and parasite counts, lower hemoglobin and platelet concentrations, higher plasma levels of interferon-gamma, tumor necrosis factor alpha, and interleukin 10 and lower levels of monocyte inhibitory factor (MIF). Compared to uncomplicated malaria, severe malaria anemia was associated with younger age, longer duration of fever and lower temperature on admission. Reticulocyte index and serum concentrations of bilirubin and LDH did not differ between the malaria groups, suggesting that unusually severe extra- or intra-medullary hemolysis did not explain the severe anemia. Higher white blood cell and platelet counts in the severe malaria group suggested that pan-suppression of the marrow was also not the primary cause. Of originally selected measures of inflammation, plasma levels of TNF-alpha and MIF did not differ between the malaria groups, but concentrations of both interferon-gamma and interleukin-10 were significantly lower in the severe anemia group (P &lt;0.006). Additional testing revealed levels of interleukin-1alpha, interleukin-6, and IP-10 to be lower and levels of sFAS to be higher in the children with severe anemia versus uncomplicated malaria (P &lt;0.0005). In a logistic regression model, severe malarial anemia was associated with younger age (P = 0.010), prior treatment with sulfadoxine/pyrimethamine or traditional medicine (P &lt;0.32), lower levels of Interleukin-10 (P = 0.025) and higher levels of sFAS (P = 0.003) and TNFa (P = 0.013). Our results are consistent with a multifactorial cause of severe malarial anemia, possibly including infection with resistant plasmodia, over-expression of TNF-alpha in conjunction with under-expression of IL-10, and increased apoptosis.

scholarly journals Distinct Clinical and Immunologic Profiles in Severe Malarial Anemia and Cerebral Malaria in Zambia

2010 ◽  
Vol 203 (2) ◽  
pp. 211-219 ◽  
Author(s):  
P. E. Thuma ◽  
J. van Dijk ◽  
R. Bucala ◽  
Z. Debebe ◽  
S. Nekhai ◽  
...  
Keyword(s):  
Cerebral Malaria ◽  
Severe Malarial Anemia ◽  
Malarial Anemia

scholarly journals Association of Plasma Tau With Mortality and Long-term Neurocognitive Impairment in Survivors of Pediatric Cerebral Malaria and Severe Malarial Anemia

2021 ◽  
Vol 4 (12) ◽  
pp. e2138515
Author(s):  
Dibyadyuti Datta ◽  
Paul Bangirana ◽  
Robert O. Opoka ◽  
Andrea L. Conroy ◽  
Katrina Co ◽  
...  
Keyword(s):  
Cerebral Malaria ◽  
Neurocognitive Impairment ◽  
Severe Malarial Anemia ◽  
Malarial Anemia

scholarly journals Delayed iron improves iron status without altering malaria risk in severe malarial anemia

2020 ◽  
Vol 111 (5) ◽  
pp. 1059-1067 ◽  
Author(s):  
Sarah E Cusick ◽  
Robert O Opoka ◽  
Andrew S Ssemata ◽  
Michael K Georgieff ◽  
Chandy C John
Keyword(s):  
Iron Deficiency ◽  
Severe Malaria ◽  
Malaria Incidence ◽  
Iron Status ◽  
Hemoglobin Concentration ◽  
Malaria Risk ◽  
Antimalarial Treatment ◽  
Severe Malarial Anemia ◽  
Iron Treatment ◽  
Malarial Anemia

ABSTRACT Background WHO guidelines recommend concurrent iron and antimalarial treatment in children with malaria and iron deficiency, but iron may not be well absorbed or utilized during a malaria episode. Objectives We aimed to determine whether starting iron 28 d after antimalarial treatment in children with severe malaria and iron deficiency would improve iron status and lower malaria risk. Methods We conducted a randomized clinical trial on the effect of immediate compared with delayed iron treatment in Ugandan children 18 mo–5 y of age with 2 forms of severe malaria: cerebral malaria (CM; n = 79) or severe malarial anemia (SMA; n = 77). Asymptomatic community children (CC; n = 83) were enrolled as a comparison group. Children with iron deficiency, defined as zinc protoporphyrin (ZPP) ≥ 80 µmol/mol heme, were randomly assigned to receive a 3-mo course of daily oral ferrous sulfate (2 mg · kg–1 · d–1) either concurrently with antimalarial treatment (immediate arm) or 28 d after receiving antimalarial treatment (delayed arm). Children were followed for 12 mo. Results All children with CM or SMA, and 35 (42.2%) CC, were iron-deficient and were randomly assigned to immediate or delayed iron treatment. Immediate compared with delayed iron had no effect in any of the 3 study groups on the primary study outcomes (hemoglobin concentration and prevalence of ZPP ≥ 80 µmol/mol heme at 6 mo, malaria incidence over 12 mo). However, after 12 mo, children with SMA in the delayed compared with the immediate arm had a lower prevalence of iron deficiency defined by ZPP (29.4% compared with 65.6%, P = 0.006), a lower mean concentration of soluble transferrin receptor (6.1 compared with 7.8 mg/L, P = 0.03), and showed a trend toward fewer episodes of severe malaria (incidence rate ratio: 0.39; 95% CI: 0.14, 1.12). Conclusions In children with SMA, delayed iron treatment did not increase hemoglobin concentration, but did improve long-term iron status over 12 mo without affecting malaria incidence. This trial was registered at clinicaltrials.gov as NCT01093989.

scholarly journals Relationship between Plasma Interleukin-12 (IL-12) and IL-18 Levels and Severe Malarial Anemia in an Area of Holoendemicity in Western Kenya

2003 ◽  
Vol 10 (3) ◽  
pp. 362-366 ◽  
Author(s):  
Sujittra Chaisavaneeyakorn ◽  
Caroline Othoro ◽  
Ya Ping Shi ◽  
Juliana Otieno ◽  
Sansanee C. Chaiyaroj ◽  
...  
Keyword(s):  
Uncomplicated Malaria ◽  
Response Rate ◽  
High Density ◽  
Interleukin 12 ◽  
Control Group ◽  
Western Kenya ◽  
Severe Malarial Anemia ◽  
Mild Malaria ◽  
Study Support ◽  
Malarial Anemia

ABSTRACT In this study, we investigated whether levels of interleukin-12 (IL-12) and IL-18 in plasma are associated with severe malarial anemia outcomes in an area of holoendemicity in western Kenya. We compared plasma IL-12 and IL-18 levels in six groups of children grouped into the categories aparasitemic, asymptomatic, mild malaria, high-density uncomplicated malaria (UC), moderate malarial anemia (MMA), or severe malarial anemia (SMA). IL-12 levels were significantly reduced in children with SMA (P < 0.05) but not in other groups compared to children in the aparasitemic control group. IL-18, a cytokine known to be critical for the induction of gamma interferon along with IL-12, was produced more frequently (70%) in children with UC (P = 0.06) than in children in the aparasitemic control group (32%). However, in the SMA group the IL-18 response rate declined to 30%, which was similar to that in the aparasitemic control group, which showed a 32% response rate. This finding suggests that the IL-18 response may be impaired in children with SMA. In summary, the results from this study support the hypothesis that impairment of IL-12 and/or IL-18 response may contribute to the development of severe malarial anemia in areas of holoendemicity for malaria.

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