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.

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.

In-Hospital Morbidity and Mortality Due to Severe Malarial Anemia in Western Kenya

2007 ◽  
Vol 77 (6_Suppl) ◽  
pp. 23-28 ◽  
Author(s):  
Charles O. Obonyo ◽  
John Vulule ◽  
Willis S. Akhwale ◽  
Diederick E. Grobbee
Keyword(s):  
Morbidity And Mortality ◽  
Western Kenya ◽  
Severe Malarial Anemia ◽  
Hospital Morbidity ◽  
Malarial Anemia

scholarly journals Acquisition of Hemozoin by Monocytes Down-Regulates Interleukin-12 p40 (IL-12p40) Transcripts and Circulating IL-12p70 through an IL-10-Dependent Mechanism: In Vivo and In Vitro Findings in Severe Malarial Anemia

2006 ◽  
Vol 74 (9) ◽  
pp. 5249-5260 ◽  
Author(s):  
Christopher C. Keller ◽  
Ouma Yamo ◽  
Collins Ouma ◽  
John Michael Ong'echa ◽  
David Ounah ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Interleukin 12 ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Severe Malarial Anemia ◽  
Tnf Α ◽  
Malarial Anemia

ABSTRACT Severe malarial anemia (SMA) is a primary cause of morbidity and mortality in immune-naïve infants and young children residing in areas of holoendemic Plasmodium falciparum transmission. Although the immunopathogenesis of SMA is largely undefined, we have previously shown that systemic interleukin-12 (IL-12) production is suppressed during childhood blood-stage malaria. Since IL-10 and tumor necrosis factor alpha (TNF-α) are known to decrease IL-12 synthesis in a number of infectious diseases, altered transcriptional regulation of these inflammatory mediators was investigated as a potential mechanism for IL-12 down-regulation. Ingestion of naturally acquired malarial pigment (hemozoin [PfHz]) by monocytes promoted the overproduction of IL-10 and TNF-α relative to the production of IL-12, which correlated with an enhanced severity of malarial anemia. Experiments with cultured peripheral blood mononuclear cells (PBMC) and CD14+ cells from malaria-naïve donors revealed that physiological concentrations of PfHz suppressed IL-12 and augmented IL-10 and TNF-α by altering the transcriptional kinetics of IL-12p40, IL-10, and TNF-α, respectively. IL-10 neutralizing antibodies, but not TNF-α antibodies, restored PfHz-induced suppression of IL-12. Blockade of IL-10 and the addition of recombinant IL-10 to cultured PBMC from children with SMA confirmed that IL-10 was responsible for malaria-induced suppression of IL-12. Taken together, these results demonstrate that PfHz-induced up-regulation of IL-10 is responsible for the suppression of IL-12 during malaria.

scholarly journals A Novel Functional Variant in the Stem Cell Growth Factor Promoter Protects against Severe Malarial Anemia

2009 ◽  
Vol 78 (1) ◽  
pp. 453-460 ◽  
Author(s):  
Collins Ouma ◽  
Christopher C. Keller ◽  
Gregory C. Davenport ◽  
Tom Were ◽  
Stephen Konah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Falciparum Malaria ◽  
Western Kenya ◽  
Production Index ◽  
Severe Malarial Anemia ◽  
Stem Cell Growth Factor ◽  
Reticulocyte Production ◽  
Malarial Anemia

ABSTRACT Plasmodium falciparum malaria is a leading global cause of infectious disease burden. In areas in which P. falciparum transmission is holoendemic, such as western Kenya, severe malarial anemia (SMA) results in high rates of pediatric morbidity and mortality. Although the pathophysiological basis of SMA is multifactorial, we recently discovered that suppression of unexplored hematopoietic growth factors that promote erythroid and myeloid colony development, such as stem cell growth factor (SCGF) (C-type lectin domain family member 11A [CLEC11A]), was associated with enhanced development of SMA and reduced erythropoietic responses. To extend these investigations, the relationships between a novel SCGF promoter variant (−539C/T, rs7246355), SMA (hemoglobin [Hb] < 6.0 g/dl), and reduced erythropoietic responses (reticulocyte production index [RPI], <2.0) were investigated with Kenyan children (n = 486) with falciparum malaria from western Kenya. Circulating SCGF was positively correlated with hemoglobin levels (r = 0.251; P = 0.022) and the reticulocyte production index (RPI) (r = 0.268; P = 0.025). Children with SMA also had lower SCGF levels than those in the non-SMA group (P = 0.005). Multivariate logistic regression analyses controlling for covariates demonstrated that individuals with the homologous T allele were protected against SMA (odds ratio, 0.57; 95% confidence interval [95% CI] 0.34 to 0.94; P = 0.027) relative to CC (wild-type) carriers. Carriers of the TT genotype also had higher SCGF levels in circulation (P = 0.018) and in peripheral blood mononuclear cell culture supernatants (P = 0.041), as well as an elevated RPI (P = 0.005) relative to individuals with the CC genotype. The results presented here demonstrate that homozygous T at −539 in the SCGF promoter is associated with elevated SCGF production, enhanced erythropoiesis, and protection against the development of SMA in children with falciparum malaria.

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.

Cost of Treatment of Severe Malarial Anemia in Children Living in Western Kenya

2018 ◽  
Vol 31 (3) ◽  
pp. 1-10
Author(s):  
Stacey Gondi ◽  
Collins Ouma ◽  
Harrysone Atieli ◽  
Walter Otieno
Keyword(s):  
Cost Of Treatment ◽  
Western Kenya ◽  
Severe Malarial Anemia ◽  
Malarial Anemia

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.

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 Profound Bias in Interferon‐γ and Interleukin‐6 Allele Frequencies in Western Kenya, Where Severe Malarial Anemia Is Common in Children

2002 ◽  
Vol 186 (7) ◽  
pp. 1007-1012 ◽  
Author(s):  
Ian S. Gourley ◽  
Jonathan D. Kurtis ◽  
Malek Kamoun ◽  
Joseph J. Amon ◽  
Patrick E. Duffy
Keyword(s):  
Interleukin 6 ◽  
Interferon Γ ◽  
Allele Frequencies ◽  
Western Kenya ◽  
Severe Malarial Anemia ◽  
Malarial Anemia

scholarly journals A Clinical Study of Platelet-Rich Fibrin Combined With Autologous High-Density Fat Transplantation in Augmentation Rhinoplasty

2021 ◽  
pp. 014556132110169
Author(s):  
Dan Yan ◽  
Shuai-Hua Li ◽  
An-Li Zhang ◽  
Yao Xiao ◽  
Ze-Chun Huang
Keyword(s):  
Retention Rate ◽  
Statistical Significance ◽  
High Density ◽  
Control Group ◽  
Long Term Effects ◽  
Fat Transplantation ◽  
Augmentation Rhinoplasty ◽  
Platelet Rich Fibrin ◽  
Autologous Fat

Objective: This study was designed to analyze the clinical effect of autologous fat-granule transplantation in augmentation rhinoplasty and explore methods to improve the fat retention rate. Methods: A total of 70 enrolled patients were randomly divided into 2 groups: the platelet-rich fibrin (PRF) combined with high-density fat transplantation group (combined group) and the conventional fat-granule transplantation group (control group; n = 35 in each group). In the combined group, an appropriate amount of autologous fat was extracted and centrifuged, and the lower layer of high-density fat was taken and mixed with PRF isolated from whole blood for autotransplantation. In the control group, only fat was extracted and centrifuged for transplantation. The patients were followed up with for more than one year to observe the short- and long-term effects, complications, safety, and patient satisfaction. Results: Six months after the operation, the nasal shape was stable, the contour was higher and more stereoscopic than before, the average increase of nasal height was 3.0 mm in the combined group and 2.0 mm in the control group. No complications, such as fat embolism, infection, or necrosis occurred during the 1-year follow-up. The satisfaction rate between the 2 groups has statistical significance ( P < .05). Conclusion: Overall, PRF combined with autologous high-density fat transplantation is simple to perform, has a significantly increased fat-retention rate than the control group, and has stable long-term effects without obvious adverse reactions. A sufficient amount of fat and PRF transplantation can achieve a good orthopedic effect. Thus, this method can be widely used in clinical augmentation rhinoplasty.

Sign in / Sign up

Export Citation Format

Share Document