Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age

<p>Abstract</p> <p>Background</p> <p>In <it>Plasmodium falciparum</it>-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults.</p> <p>Methods</p> <p>Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay.</p> <p>Results</p> <p>The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment.</p> <p>Conclusion</p> <p>The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.</p

Responses of Plasmodium falciparum infections to antimalarial drugs in north eastern Nigeria – Part 1: 1988 - 1995.

The responses of Plasmodium falciparum strains to different antimalarial drugs were assessed in the north east of Nigeria, using a modified version of the World Health Organization (WHO) extended in vivo field test protocol from 1988 to 1995. The sensitivity of the strains to chloroquine phosphate varied from a delayed clearance of parasitaemia, through Type-RI resistance or recrudescence to asymptomatic Type-RII resistance. Chloroquine was still clinically efficacious against P. falciparum malaria and continued to play a major role in reducing malaria-related morbidity. However, parasitological failure rates were on the increase as demonstrated in Damboa, where a 1.3-fold increase occurred in D7 failure rate over a 7-year period, from 18.7% in 1988 to 24.5% in 1995. This highlighted the need for continued monitoring of the performance of the drug against the parasites, in addition to evaluating the efficacy and tolerability of new products. Second-line drugs, particularly the combinations of pyrimethamine and sulphadoxine (SD-Pyr, Fansidar®), and pyrimethamine and sulfalene (SL-Pyr, Metakelfin®) were clinically and parasitologically efficacious, producing 100% and 97.1% cure rates, respectively. Self-medication, non-compliance with treatment regimens (particularly for multiple dose therapy), sub-standard or even fake drugs/products, in addition to parasite resistance were identified as factors compounding the treatment of P. falciparum malaria. Key Words: Antimalarial drugs; Plasmodium falciparum; North Eastern Nigeria; 1988 – 1995. Journal of Pharmacy and Bioresources Vol.1(1) 2004: 51-6

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in infected children under six years of age-6

<p><b>Copyright information:</b></p><p>Taken from "Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in infected children under six years of age"</p><p>http://www.malariajournal.com/content/7/1/41</p><p>Malaria Journal 2008;7():41-41.</p><p>Published online 29 Feb 2008</p><p>PMCID:PMC2275287.</p><p></p

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in infected children under six years of age-4

additive combinatorial effect of elevated IL-6 and IL-10 cytokine levels on TNF is significant (without random sampling error). Line, multivariate regression line (r= 0.726).<p><b>Copyright information:</b></p><p>Taken from "Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in infected children under six years of age"</p><p>http://www.malariajournal.com/content/7/1/41</p><p>Malaria Journal 2008;7():41-41.</p><p>Published online 29 Feb 2008</p><p>PMCID:PMC2275287.</p><p></p

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in infected children under six years of age-2

E Pre-Rx samples in (A) and (B) were collected before SP treatment. The Post-Rx samples in (A) and (B) were collected seven days after SP treatment. Samples from children exhibiting no evidence of falciparum infection were collected during a season of low transmission (A, LT). ANA Index values were calculated according to assay kit instructions and interpreted as negative, ≤0.90; equivocal, 0.91-1.09; and positive, ≥1.10. Anti-dsDNA levels were calculated according to assay kit instructions and interpreted as negative 200 IU/ml.<p><b>Copyright information:</b></p><p>Taken from "Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in infected children under six years of age"</p><p>http://www.malariajournal.com/content/7/1/41</p><p>Malaria Journal 2008;7():41-41.</p><p>Published online 29 Feb 2008</p><p>PMCID:PMC2275287.</p><p></p

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in infected children under six years of age-3

O top of box), the 90th and 10percentile values (high and low error bars respectively), and the mean value (dotted line). Closed circles represent the two highest values (above 90percentile). Open circles represent the two lowest values (below 10percentile; two open circles are superimposed in the plots where only one open circle is apparent). Horizontal bars on x-axes represent the upper limit of the range for normal healthy individuals determined with each assay kit by the manufacturer.<p><b>Copyright information:</b></p><p>Taken from "Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in infected children under six years of age"</p><p>http://www.malariajournal.com/content/7/1/41</p><p>Malaria Journal 2008;7():41-41.</p><p>Published online 29 Feb 2008</p><p>PMCID:PMC2275287.</p><p></p

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in infected children under six years of age-7

Atment (x) were classified into one of ten groups. The percentage of each group was calculated. Box plots indicating the 25, 50, and 75percentile (solid lines from bottom to top of box, respectively), the 90th and 10percentile values (high and low error bars respectively), and high and low outlier points are shown for each of the following leukocyte classes: 1) metamyelocytes, 2) segmented neutrophils, 3) bands, 4) hypersegmented neutrophils, 5) NETs, 6) monocytes, 7) lymphocytes, 8) smudge forms, 9) eosinophils, and 10) basophils.<p><b>Copyright information:</b></p><p>Taken from "Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in infected children under six years of age"</p><p>http://www.malariajournal.com/content/7/1/41</p><p>Malaria Journal 2008;7():41-41.</p><p>Published online 29 Feb 2008</p><p>PMCID:PMC2275287.</p><p></p

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in infected children under six years of age-5

<p><b>Copyright information:</b></p><p>Taken from "Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in infected children under six years of age"</p><p>http://www.malariajournal.com/content/7/1/41</p><p>Malaria Journal 2008;7():41-41.</p><p>Published online 29 Feb 2008</p><p>PMCID:PMC2275287.</p><p></p