Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria

Background: Placental malaria (PM) is an important cause of maternal and foetal mortality in tropical areas, and severe sequelae and mortality are related to inflammation in the placenta. Diagnosis is difficult because PM is often asymptomatic, peripheral blood smear examination detects parasitemia as few as half of PM cases, and no peripheral markers have been validated for placental inflammation. Methods: In a cohort of Tanzanian parturients, PM was determined by placental blood smears and placental inflammation was assessed by histology and TNF mRNA levels. Maternal peripheral blood levels of several immune mediators previously implicated in PM pathogenesis, as well as ferritin and leptin were measured. The relationship between the levels of these soluble factors to PM and placental inflammation was examined. Results: Peripheral levels of TNF, TNF-RI, TNF-RII, IL-1, IL-10, and ferritin were elevated during PM, whereas levels of IFN-[gamma], IL-4, IL-5 and IL-6 were unchanged and levels of leptin were decreased. In receiver operating characteristic curve analysis, IL-10 had the greatest area under the curve, and would provide a sensitivity of 60% with a false positive rate of 10%. At a cut off level of 15 pg/mL, IL-10 would detect PM with a sensitivity of 79.5% and a specificity of 84.3%. IL-10 levels correlated with placental inflammatory cells and placental TNF mRNA levels in first time mothers. Conclusion: These data suggest that IL-10 may have utility as a biomarker for inflammatory PM in research studies, but that additional biomarkers may be required to improve clinical diagnosis and management of malaria during pregnancy.This work was supported by grants from Bill and Melinda Gates Foundation (grant 29202), NIH (R01 AI52059 and TW05509) and Puget Sound Partners for Global Health to P.E.D

Relationship of peripheral IL-10 levels and placental TNF-α mRNA levels in first time mothers

Gene expression is presented as 2fold expression over KRT7. Simple regression analysis was used to calculate R and P-values.<p><b>Copyright information:</b></p><p>Taken from "Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria"</p><p>http://www.malariajournal.com/content/7/1/26</p><p>Malaria Journal 2008;7():26-26.</p><p>Published online 29 Jan 2008</p><p>PMCID:PMC2265723.</p><p></p

Independent lineages of highly sulfadoxine-resistant Plasmodium falciparum haplotypes, Eastern Africa

Sulfadoxine-resistant Plasmodium falciparum undermines malaria prevention with sulfadoxine/pyrimethamine. Parasites with a highly resistant mutant dihydropteroate synthase (dhps) haplotype have recently emerged in eastern Africa; they negated preventive benefits of sulfadoxine/pyrimethamine, and might exacerbate placental malaria. We explored emerging lineages of dhps mutant haplotypes in Malawi, the Democratic Republic of the Congo, and Tanzania by using analyses of genetic microsatellites flanking the dhps locus. In Malawi, a triple-mutant dhps SGEG (mutant amino acids are underlined) haplotype emerged in 2010 that was closely related to pre-existing double-mutant SGEA haplotypes, suggesting local origination in Malawi. When we compared mutant strains with parasites from the Democratic Republic of the Congo and Tanzania by multiple independent analyses, we found that SGEG parasites were partitioned into separate lineages by country. These findings support a model of local origination of SGEG dhps haplotypes, rather than geographic diffusion, and have implications for investigations of emergence and effects of parasite drug resistance

Receiver operator curve for peripheral IL-10 levels in first time mothers to detect PM

Solid line is the best fit curve; dashed lines show the 95% confidence intervals.<p><b>Copyright information:</b></p><p>Taken from "Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria"</p><p>http://www.malariajournal.com/content/7/1/26</p><p>Malaria Journal 2008;7():26-26.</p><p>Published online 29 Jan 2008</p><p>PMCID:PMC2265723.</p><p></p

Peripheral IL-10 levels stratified for maternal parity, PM and the presence of inflammatory cells by placental histology

P-value was calculated using Mann-Whitney test. P0, primigravidae; P1+, multigravidae.<p><b>Copyright information:</b></p><p>Taken from "Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria"</p><p>http://www.malariajournal.com/content/7/1/26</p><p>Malaria Journal 2008;7():26-26.</p><p>Published online 29 Jan 2008</p><p>PMCID:PMC2265723.</p><p></p