Biomarkers for susceptibility to infection and disease severity in human malaria

Andrade, Bruno B.; Barral‐Netto, Manoel

doi:10.1590/s0074-02762011000900009

Cited by 31 publications

(37 citation statements)

References 92 publications

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“…As a consequence, the onset of symptoms is prevented by limiting parasite burden and controlling inflammation. Such asymptomatic carriers develop just enough immunity to protect them from malarial illness, but not from malarial infection [1]. In the present study, asymptomatic carriers displayed the highest density values in the networks interactions, which argue that there may exist a complex regulatory mechanism behind the susceptibility to infection and tolerance and/or resistance against malaria.…”

Section: Discussionmentioning

confidence: 53%

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Networking the host immune response in Plasmodium vivax malaria

Mendonça

Queiroz

Lopes

et al. 2013

Malar J

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106

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BackgroundPlasmodium vivax malaria clinical outcomes are a consequence of the interaction of multiple parasite, environmental and host factors. The host molecular and genetic determinants driving susceptibility to disease severity in this infection are largely unknown. Here, a network analysis of large-scale data from a significant number of individuals with different clinical presentations of P. vivax malaria was performed in an attempt to identify patterns of association between various candidate biomarkers and the clinical outcomes.MethodsA retrospective analysis of 530 individuals from the Brazilian Amazon, including P. vivax-infected individuals who developed different clinical outcomes (148 asymptomatic malaria, 187 symptomatic malaria, 13 severe non-lethal malaria, and six severe lethal malaria) as well as 176 non-infected controls, was performed. Plasma levels of liver transaminases, bilirubins, creatinine, fibrinogen, C-reactive protein, superoxide dismutase (SOD)-1, haem oxygenase (HO)-1 and a panel composed by multiple cytokines and chemokines were measured and compared between the different clinical groups using network analysis.ResultsNon-infected individuals displayed several statistically significant interactions in the networks, including associations between the levels of IL-10 and IL-4 with the chemokine CXCL9. Individuals with asymptomatic malaria displayed multiple significant interactions involving IL-4. Subjects with mild or severe non-lethal malaria displayed substantial loss of interactions in the networks and TNF had significant associations more frequently with other parameters. Cases of lethal P. vivax malaria infection were associated with significant interactions between TNF ALT, HO-1 and SOD-1.ConclusionsThe findings imply that clinical immunity to P. vivax malaria is associated with multiple significant interactions in the network, mostly involving IL-4, while lethality is linked to a systematic reduction of complexity of these interactions and to an increase in connections between markers linked to haemolysis-induced damage.

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Section: Discussionmentioning

confidence: 53%

“…Besides factors related to the Plasmodium parasite itself, malaria is a consequence of multiple host molecular and genetic alterations compounded by environmental factors [1]. Most of the studies in malaria immunopathogenesis are focused on the identification of one or a small group of candidate molecules related to disease severity.…”

Section: Introductionmentioning

confidence: 99%

Networking the host immune response in Plasmodium vivax malaria

Mendonça

Queiroz

Lopes

et al. 2013

Malar J

Self Cite

106

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“…Both infections cause hemolysis, for example. However, there are important and well-described differences between P. vivax and P. falciparum that result in different parasitemia thresholds for triggering severe malaria (2). The different clinical outcomes of these diseases make it important to expand the studies investigating the factors that are associated with the susceptibility to infection and disease severity in P. vivax malaria.…”

Section: Discussionmentioning

confidence: 99%

Association between the Haptoglobin and Heme Oxygenase 1 Genetic Profiles and Soluble CD163 in Susceptibility to and Severity of Human Malaria

et al. 2012

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ABSTRACTIntravascular hemolysis is a hallmark event in the immunopathology of malaria that results in increased systemic concentrations of free hemoglobin (Hb). The oxidation of Hb by free radicals causes the release of heme, which amplifies inflammation. To circumvent the detrimental effects of free heme, hosts have developed several homeostatic mechanisms, including the enzyme haptoglobin (Hp), which scavenges cell-free Hb, the monocyte receptor CD163, which binds to Hb-Hp complexes, and heme oxygenase-1 (HO-1), which degrades intracellular free heme. We tested the association between these three main components of the host response to hemolysis and susceptibility to malaria in a Brazilian population. The genetic profiles of theHMOX1andHpgenes and the plasma levels of a serum inflammatory marker, the soluble form of the CD163 receptor (sCD163), were studied in 264 subjects, including 78 individuals with symptomatic malaria, 106 individuals with asymptomatic malaria, and 80 uninfected individuals. We found that long (GT)nrepeats in the microsatellite polymorphism region of theHMOX1gene, theHp2allele, and theHp2.2genotype were associated with symptomatic malaria. Moreover, increased plasma concentrations of heme, Hp, HO-1, and sCD163 were associated with susceptibility to malaria. The validation of these results could support the development of targeted therapies and aid in reducing the severity of malaria.

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“…Considering the needs to identify biomarkers to leishmaniasis that can be used to diagnose disease, predict clinical outcome, monitor therapeutic responses and immunity [33,40], we have examined the tissue expression of some inflammatory and stress markers during cutaneous murine leishmaniosis. The predictive or diagnostic values of proteins markers have been suggested for many diseases, for example, hypoxia-inducible factor (HIF-1a) for rectal cancer [43], heme oxygenase (HO-1) for malaria [4] and bladder cancer [41], vascular endothelial growth factor (VEGF) for Sjögren's syndrome [60] and CD31/VEGF for asthma [54]. Thus, similar knowledge could help to determine the relevance of different host mediators in relation to leishmaniasis control or exacerbation and their predictive value.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis

Araújo

Giorgio

2015

Arch Dermatol Res

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Leishmanioses are chronic parasitic diseases and host responses are associated with pro- or anti-inflammatory cytokines involved, respectively, in the control or exacerbation of infection. The relevance of other inflammatory mediators and stress markers has not been widely studied and there is a need to search for biomarkers to leishmaniasis. In this work, the stress and inflammatory molecules p38 mitogen-activated protein kinase, cyclooxygenase-2, migration inhibitory factor, macrophage inflammatory protein 2, heat shock protein 70 kDa, vascular endothelial factor (VEGF), hypoxia-inducible factors (HIF-1α and HIF-2α), heme oxygenase and galectin-3 expression were assessed immunohistochemically in self-controlled lesions in C57BL/6 mice and severe lesions in Balb/c mice infected with Leishmania amazonensis. The results indicated that the majority of molecules were expressed in the cutaneous lesions of both C57BL/6 and Balb/c mice during various phases of infection, suggesting no obvious correlation between the stress and inflammatory molecule expression and the control/exacerbation of leishmanial lesions. However, the cytokine VEGF was only detected in C57BL/6 footpad lesions and small lesions in Balb/c mice treated with antimonial pentavalent. These findings suggest that VEGF expression could be a predictive factor for murine leishmanial control, a hypothesis that should be tested in human leishmaniosis.

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Biomarkers for susceptibility to infection and disease severity in human malaria

Abstract: Malaria remains a major infectious disease that affects millions of people. Once infected with

Cited by 31 publications

References 92 publications

Networking the host immune response in Plasmodium vivax malaria

Networking the host immune response in Plasmodium vivax malaria

Association between the Haptoglobin and Heme Oxygenase 1 Genetic Profiles and Soluble CD163 in Susceptibility to and Severity of Human Malaria

Immunohistochemical evidence of stress and inflammatory markers in mouse models of cutaneous leishmaniosis

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