Interleukin-10 and soluble tumor necrosis factor receptor II are potential biomarkers of Plasmodium falciparum infections in pregnant women: a case-control study from Nanoro, Burkina Faso

Abstract

BackgroundDiagnosis of malaria in pregnancy is problematic due to the low sensitivity of conventional diagnostic tests (rapid diagnostic test and microscopy), which is exacerbated due to low peripheral parasite densities, and lack of clinical symptoms. In this study, six potential biomarkers to support malaria diagnosis in pregnancy were evaluated.MethodsBlood samples were collected from pregnant women at antenatal clinic visits and at delivery. Microscopy and real-time PCR were performed for malaria diagnosis and biomarker analyses were performed by ELISA (interleukin 10, IL-10; tumor necrosis factor-α, TNF-α; soluble tumor necrosis factor receptor II, sTNF-RII; soluble fms-like tyrosine kinase 1, sFlt-1; leptin and apolipoprotein B, Apo-B). A placental biopsy was collected at delivery to determine placental malaria.ResultsIL-10 and sTNF-RII were significantly higher at all time-points in malaria-infected women (p < 0.001). Both markers were also positively associated with parasite density (p < 0.001 and p = 0.003 for IL-10 and sTNF-RII respectively). IL-10 levels at delivery, but not during pregnancy, were negatively associated with birth weight. A prediction model was created using IL-10 and sTNF-RII cut-off points. For primigravidae the model had a sensitivity of 88.9% (95%CI 45.7–98.7%) and specificity of 83.3% (95% CI 57.1–94.9%) for diagnosing malaria during pregnancy. For secundi- and multigravidae the sensitivity (81.8% and 56.5% respectively) was lower, while specificity (100.0% and 94.3% respectively) was relatively high. Sub-microscopic infections were detected in 2 out of 3 secundi- and 5 out of 12 multigravidae.ConclusionsThe combination of biomarkers IL-10 and sTNF-RII have the potential to support malaria diagnosis in pregnancy. Additional markers may be needed to increase sensitivity and specificity, this is of particular importance in populations with sub-microscopic infections or in whom other inflammatory diseases are prevalent.Electronic supplementary materialThe online version of this article (10.1186/s40364-017-0114-7) contains supplementary material, which is available to authorized users.

Early malaria infection, dysregulation of angiogenesis, metabolism and inflammation across pregnancy, and risk of preterm birth in Malawi: A cohort study

“…These proteins play a key role in the interaction between inflammation and vascular function, and alterations in their levels are associated with an increased risk of poor birth outcomes, including PTB [18,42]. We also show that the inflammatory markers, CRP and sTNFRII, were elevated in MIP, in agreement with previous data [21,43–47]. Tight control of inflammation is required for healthy pregnancies, especially for proper placentation and fetal development, whereas dysregulated inflammation is associated with poor placental function and adverse pregnancy outcomes, including preeclampsia [48–50].…”

“…Another central metabolic protein is Leptin, which plays roles in embryonic implantation, placental endocrine function, fetal development, and immune regulation [58–60]. In this study, lower levels of Leptin were observed in women with malaria over the course of pregnancy, consistent with prior findings [43,44,61,62]. Lower Leptin levels have previously been linked to adverse birth outcomes, including PTB, miscarriage, and intrauterine growth restriction [18,58,63].…”

“…sFlt-1 is another anti-angiogenic mediator; however, its role in MIP remains unclear. When measured at antenatal visits across pregnancy in women with MIP, Bostrom and colleagues showed no significant differences in peripheral levels of sFlt-1 [55], and Ruizendaal and colleagues showed a trend towards lower levels of sFlt-1 in women with peripheral malaria in the second trimester but no difference in sFlt-1 levels in the third trimester or at delivery [43]. Whereas Conroy and colleagues [16] and Muehlenbachs and colleagues [56] reported that when measured at delivery, women with smear-positive malaria have elevated peripheral and placental levels of sFlt-1.…”

Submicroscopic Plasmodium infection during pregnancy is associated with reduced antibody levels to tetanus toxoid

“…As for IL‐10, we did not observe any significant differences between the no‐SPIP and SPIP groups; however, an increase in the expression of IL‐10 was evident in the SPIP group. In different studies, IL‐10 is increased in cases of acute and asymptomatic malaria and is associated with protection against symptoms and immunopathology of the disease. In the SPIP study group with chronic submicroscopic infections, a positive correlation was found between the expression of IL‐10 and CTLA‐4 (i.e.…”

Testing an infection model to explain excess risk of preterm birth with long-term iron supplementation in a malaria endemic area

“…The induction of inflammatory cytokines can modulate pregnancy outcomes with beneficial and/or detrimental effects [48]. Maintenance of an appropriate ratio of pro-and anti-inflammatory responses at the feto-maternal interface is a hallmark of successful pregnancy A systemic inflammatory response to malaria during pregnancy leads to increased interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-22, interferon (INF)-Ɣ and soluble tumour necrosis factor (sTNF)-RII in maternal blood [3, 41, 45–51]. Placental IL-6 and IL-8 have been associated with pregnancy loss and PTB [3, 47–49].…”