Alterations in cytokines and haematological parameters during the acute and convalescent phases of Plasmodium falciparum and Plasmodium vivax infections

Rodrigues-da-Silva, Rodrigo Nunes; Lima-Junior, Josué da Costa; Fonseca, Bruna de Paula Fonseca e; Antas, Paulo Renato Zuquim; Baldez, Arlete; Storer, Fábio Luiz; Santos, Fernando J.; Banic, Dalma Maria; Oliveira-Ferreira, Joseli

doi:10.1590/0074-0276140275

Cited by 44 publications

(60 citation statements)

References 52 publications

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“…Evaluation of clinical data between categorical groups of parasitemia identified significant differences in levels of hemoglobin ( P = 0.0005), RBC ( P < 0.0001), white blood cell (WBC) ( P = 0.0055), platelets ( P = 0.0211), ALT ( P = 0.033) and AST ( P = 0.034). Consistent with previous reports, we also identified significant correlations between parasitemia and levels of clinical parameters that include hemoglobin, RBCs, WBCs and platelets (Ketema and Bacha, 2013; Kotepui et al, 2015; Demissie and Ketema, 2016; Rodrigues-da-Silva et al, 2014). Demographics and clinical characteristics of the study population are described in Table 1.…”

Section: Resultssupporting

confidence: 91%

Metabolome-wide association study of peripheral parasitemia in Plasmodium vivax malaria

Gardinassi

Cordy

Lacerda

et al. 2017

International Journal of Medical Microbiology

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Background Plasmodium vivax is one of the leading causes of malaria worldwide. Infections with this parasite cause diverse clinical manifestations, and recent studies revealed that infections with P. vivax can result in severe and fatal disease. Despite these facts, biological traits of the host response and parasite metabolism during P. vivax malaria are still largely underexplored. Parasitemia is clearly related to progression and severity of malaria caused by P. falciparum, however the effects of parasitemia during infections with P. vivax are not well understood. Results We conducted an exploratory study using a high-resolution metabolomics platform that uncovered significant associations between parasitemia levels and plasma metabolites from 150 patients with P. vivax malaria. Most plasma metabolites were inversely associated with higher levels of parasitemia. Top predicted metabolites are implicated into pathways of heme and lipid metabolism, which include biliverdin, bilirubin, palmitoylcarnitine, stearoylcarnitine, phosphocholine, glycerophosphocholine, oleic acid and omega-carboxytrinor-leukotriene B4. Conclusions The abundance of several plasma metabolites varies according to the levels of parasitemia in patients with P. vivax malaria. Moreover, our data suggest that the host response and/or parasite survival might be affected by metabolites involved in the degradation of heme and metabolism of several lipids. Importantly, these data highlight metabolic pathways that may serve as targets for the development of new antimalarial compounds.

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Section: Resultssupporting

confidence: 91%

Metabolome-wide association study of peripheral parasitemia in Plasmodium vivax malaria

Gardinassi

Cordy

Lacerda

et al. 2017

International Journal of Medical Microbiology

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“…In the present study, it was shown that P. vivax infection induced increased levels of IL-6 and, after treatment, the plasma levels were restored. These findings were in agreement with previous studies during acute phase [11, 15, 17, 18] although the controversial data in the literature with reduction [10, 14] or increase [11] of IL-6 after the treatment, which might be attributed to convalescence period range (7–45 days) in the different studies [8, 10, 11, 13, 14]. …”

Section: Discussionsupporting

confidence: 93%

“…Concomitantly, it seems to be a consensus that P. vivax infection induces higher levels of IL-10 during acute phase of vivax malaria [7, 8, 10–13, 15, 17–19] and that the cytokine levels were restored to baseline after treatment [8, 10, 11, 14]. Indeed, a previous study demonstrated that CD4 + CD25 + T cells producing IL-10 play a significant role during Plasmodium infection, possibly controlling the pro-inflammatory cytokines IFN-γ and TNF [6].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the majority of patients of this group presented higher production of IL-17. However, reports on IL-17 production in the human malarial infection are poorly described [9, 11] and further investigations are required. It is important to highlight that IL-17 may be produced by macrophages, dendritic cells, NK, NKT, γdT cells, CD8 + and Th17 [23, 24] and the source of this cytokine during P. vivax infection needs more investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have focused on the profile of plasma cytokines and chemokines in vivax malaria infection, comparing the repertoire of cytokines/chemokines elicited between P. vivax and Plasmodium falciparum infection [7–11] and further association with disease severity, determined by clinical symptoms, or immunological profile after treatment with anti-malarial drugs [8–15]. Overall the profile of cytokine/chemokine production is still contradictory due to differences in study population, degree of endemicity in the region, among other factors, requiring further investigations.…”

Section: Introductionmentioning

confidence: 99%

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On the cytokine/chemokine network during Plasmodium vivax malaria: new insights to understand the disease

Hojo-Souza

Pereira

Souza

et al. 2017

Malar J

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BackgroundThe clinical outcome of malaria depends on the delicate balance between pro-inflammatory and immunomodulatory cytokine responses triggered during infection. Despite the numerous reports on characterization of plasma levels of cytokines/chemokines, there is no consensus on the profile of these mediators during blood stage malaria. The identification of acute phase biomarkers might contribute to a better understanding of the disease, allowing the use of more effective therapeutic approaches to prevent the progression towards severe disease. In the present study, the plasma levels of cytokines and chemokines and their association with parasitaemia and number of previous malaria episodes were evaluated in Plasmodium vivax-infected patients during acute and convalescence phase, as well as in healthy donors.MethodsSamples of plasma were obtained from peripheral blood samples from four different groups: P. vivax-infected, P. vivax-treated, endemic control and malaria-naïve control. The cytokine (IL-6, IL-10, IL-17, IL-27, TGF-β, IFN-γ and TNF) and chemokine (MCP-1/CCL2, IP-10/CXCL10 and RANTES/CCL5) plasma levels were measured by CBA or ELISA. The network analysis was performed using Spearman correlation coefficient.Results Plasmodium vivax infection induced a pro-inflammatory response driven by IL-6 and IL-17 associated with an immunomodulatory profile mediated by IL-10 and TGF-β. In addition, a reduction was observed of IFN-γ plasma levels in P. vivax group. A lower level of IL-27 was observed in endemic control group in comparison to malaria-naïve control group. No significant results were found for IL-12p40 and TNF. It was also observed that P. vivax infection promoted higher levels of MCP-1/CCL2 and IP-10/CXCL10 and lower levels of RANTES/CCL5. The plasma level of IL-10 was elevated in patients with high parasitaemia and with more than five previous malaria episodes. Furthermore, association profile between cytokine and chemokine levels were observed by correlation network analysis indicating signature patterns associated with different parasitaemia levels.ConclusionsThe P. vivax infection triggers a balanced immune response mediated by IL-6 and MCP-1/CCL2, which is modulated by IL-10. In addition, the results indicated that IL-10 plasma levels are influenced by parasitaemia and number of previous malaria episodes.

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Correlation of APRIL with production of inflammatory cytokines during acute malaria in the Brazilian Amazon

Pinna

Santos

Perce-da-Silva

et al. 2018

Immunity Inflam & Disease

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IntroductionA proliferation‐inducing ligand (APRIL) and B cell activation factor (BAFF) are known to play a significant role in the pathogenesis of several diseases, including BAFF in malaria. The aim of this study was to investigate whether APRIL and BAFF plasma concentrations could be part of inflammatory responses associated with P. vivax and P. falciparum malaria in patients from the Brazilian Amazon.MethodsBlood samples were obtained from P. vivax and P. falciparum malaria patients (n = 52) resident in Porto Velho before and 15 days after the beginning of treatment and from uninfected individuals (n = 12). We investigated APRIL and BAFF circulating levels and their association with parasitaemia, WBC counts, and cytokine/chemokine plasma levels. The expression levels of transmembrane activator and calcium‐modulating cyclophilin ligand interactor (TACI) on PBMC from a subset of 5 P. vivax‐infected patients were analyzed by flow cytometry.ResultsAPRIL plasma levels were transiently increased during acute P. vivax and P. falciparum infections whereas BAFF levels were only increased during acute P. falciparum malaria. Although P. vivax and P. falciparum malaria patients have similar cytokine profiles during infection, in P. vivax acute phase malaria, APRIL but not BAFF levels correlated positively with IL‐1, IL‐2, IL‐4, IL‐6, and IL‐13 levels. We did not find any association between P. vivax parasitaemia and APRIL levels, while an inverse correlation was found between P. falciparum parasitaemia and APRIL levels. The percentage of TACI positive CD4+ and CD8+ T cells were increased in the acute phase P. vivax malaria.ConclusionThese findings suggest that the APRIL and BAFF inductions reflect different host strategies for controlling infection with each malaria species.

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Alterations in cytokines and haematological parameters during the acute and convalescent phases of Plasmodium falciparum and Plasmodium vivax infections

Cited by 44 publications

References 52 publications

Metabolome-wide association study of peripheral parasitemia in Plasmodium vivax malaria

Metabolome-wide association study of peripheral parasitemia in Plasmodium vivax malaria

On the cytokine/chemokine network during Plasmodium vivax malaria: new insights to understand the disease

Correlation of APRIL with production of inflammatory cytokines during acute malaria in the Brazilian Amazon

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