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Unravelling the patterns of host immune responses in Plasmodium vivax malaria and dengue co-infection.

Mendonça VR, Andrade BB, Souza LC, Magalhães BM, Mourão MP, Lacerda MV, Barral-Netto M - Malar. J. (2015)

Bottom Line: The plasma levels of cytokines and chemokines were determined by multiplex assay.The group of individuals co-infected exhibited the highest median concentrations of IFN-γ, IL-6, CCL4 than the mono-infected groups.Further, parasitaemia levels displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue.

View Article: PubMed Central - PubMed

Affiliation: Laboratório Integrado de Microbiogia e Imunoregulação (LIMI), Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil. vitorrosaramos@hotmail.com.

ABSTRACT

Background: Concurrent malaria and dengue infection is frequently diagnosed in endemic countries, but its immunopathology remains largely unknown. In the present study, a large panel of cytokines/chemokines and clinical laboratory markers were measured in patients with Plasmodium vivax and dengue co-infection as well as in individuals with malaria or dengue mono-infections in order to identify biosignatures of each clinical condition.

Methods: Individuals from the Brazilian Amazon were recruited between 2009 and 2013 and classified in three groups: vivax malaria (n = 52), dengue (n = 30) and vivax malaria and dengue co-infection (n = 30). P. vivax malaria was diagnosed by thick blood smear and confirmed by PCR; dengue cases were detected by IgM ELISA or NS1 protein. The plasma levels of cytokines and chemokines were determined by multiplex assay.

Results: Individuals with malaria and dengue co-infection displayed lower levels of platelets and haemoglobin than those with malaria or dengue mono-infections (p = 0.0047 and p = 0.0001, respectively). The group of individuals co-infected exhibited the highest median concentrations of IFN-γ, IL-6, CCL4 than the mono-infected groups. Network analyses of plasma cytokines/chemokines revealed that malaria and dengue co-infection exhibits a distinct immune profile with critical roles for TNF, IL-6 and IFN-γ. Further, parasitaemia levels displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue. No differences were observed in distribution of dengue virus serotypes and Plasmodium parasitaemia levels between the groups.

Conclusions: The findings described here identify unique patterns of circulating immunological markers in cases of malaria and dengue co-infection and provide insights on the immunopathology of this co-morbid condition.

No MeSH data available.


Related in: MedlinePlus

Discrimation of malaria, dengue and co-infection groups by laboratory measures. Differentiation between dengue vs malaria, dengue vs co-infection and malaria vs co-infection groups were done by laboratory measures—HB haemoglobin, HT haematocrit, PTL platelets, AST aspartate aminotransferase, ALT alanine aminotransferase—through multinominal regression analysis with calculation of odds ratios (OR) and 95 % confidence intervals (CI), represented by the icons and bars, respectively (a). Red icons represent OR adjusted for age and gender and blue icons were unadjusted (univariate) (a).
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Fig1: Discrimation of malaria, dengue and co-infection groups by laboratory measures. Differentiation between dengue vs malaria, dengue vs co-infection and malaria vs co-infection groups were done by laboratory measures—HB haemoglobin, HT haematocrit, PTL platelets, AST aspartate aminotransferase, ALT alanine aminotransferase—through multinominal regression analysis with calculation of odds ratios (OR) and 95 % confidence intervals (CI), represented by the icons and bars, respectively (a). Red icons represent OR adjusted for age and gender and blue icons were unadjusted (univariate) (a).

Mentions: Univariate analyses revealed that individuals co-infected with malaria and dengue exhibited lower levels of HB and PTL than those with malaria or dengue mono-infections (p = 0.0047 and p = 0.0001, respectively; Table 1). On the other hand, plasma AST levels were elevated whereas ALT concentrations were decreased in individuals with malaria mono-infection compared to those with dengue or co-infection (p = 0.0186 and p < 0.0001, respectively; Table 1). Multinominal regression analyses adjusted for age and gender uncovered that higher levels of HB (adjusted OR: 23.344 95 % CI 2.534–215.023, p = 0.005) and PTL (adjusted OR: 8.065 95 % CI: 1.527–42.612, p = 0.014) were associated with dengue when compared to malaria (Fig. 1). Furthermore, higher levels of HB (adjusted OR: 6.264 95 % CI 1.535–25.553, p = 0.011) and PTL (adjusted OR: 21.471 95 % CI 3.077–149.827, p = 0.002) were associated with dengue mono-infection compared with dengue and malaria co-infection (Fig. 1). Higher levels of AST (unadjusted OR: 3.030 95 % CI 1.160–7.914, p = 0.024) and low levels of ALT (adjusted OR: 0.219 95 % CI 0.069–0.695, p = 0.010) were associated with malaria mono-infection compared with the malaria/dengue co-infection condition (Fig. 1).Fig. 1


Unravelling the patterns of host immune responses in Plasmodium vivax malaria and dengue co-infection.

Mendonça VR, Andrade BB, Souza LC, Magalhães BM, Mourão MP, Lacerda MV, Barral-Netto M - Malar. J. (2015)

Discrimation of malaria, dengue and co-infection groups by laboratory measures. Differentiation between dengue vs malaria, dengue vs co-infection and malaria vs co-infection groups were done by laboratory measures—HB haemoglobin, HT haematocrit, PTL platelets, AST aspartate aminotransferase, ALT alanine aminotransferase—through multinominal regression analysis with calculation of odds ratios (OR) and 95 % confidence intervals (CI), represented by the icons and bars, respectively (a). Red icons represent OR adjusted for age and gender and blue icons were unadjusted (univariate) (a).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4536664&req=5

Fig1: Discrimation of malaria, dengue and co-infection groups by laboratory measures. Differentiation between dengue vs malaria, dengue vs co-infection and malaria vs co-infection groups were done by laboratory measures—HB haemoglobin, HT haematocrit, PTL platelets, AST aspartate aminotransferase, ALT alanine aminotransferase—through multinominal regression analysis with calculation of odds ratios (OR) and 95 % confidence intervals (CI), represented by the icons and bars, respectively (a). Red icons represent OR adjusted for age and gender and blue icons were unadjusted (univariate) (a).
Mentions: Univariate analyses revealed that individuals co-infected with malaria and dengue exhibited lower levels of HB and PTL than those with malaria or dengue mono-infections (p = 0.0047 and p = 0.0001, respectively; Table 1). On the other hand, plasma AST levels were elevated whereas ALT concentrations were decreased in individuals with malaria mono-infection compared to those with dengue or co-infection (p = 0.0186 and p < 0.0001, respectively; Table 1). Multinominal regression analyses adjusted for age and gender uncovered that higher levels of HB (adjusted OR: 23.344 95 % CI 2.534–215.023, p = 0.005) and PTL (adjusted OR: 8.065 95 % CI: 1.527–42.612, p = 0.014) were associated with dengue when compared to malaria (Fig. 1). Furthermore, higher levels of HB (adjusted OR: 6.264 95 % CI 1.535–25.553, p = 0.011) and PTL (adjusted OR: 21.471 95 % CI 3.077–149.827, p = 0.002) were associated with dengue mono-infection compared with dengue and malaria co-infection (Fig. 1). Higher levels of AST (unadjusted OR: 3.030 95 % CI 1.160–7.914, p = 0.024) and low levels of ALT (adjusted OR: 0.219 95 % CI 0.069–0.695, p = 0.010) were associated with malaria mono-infection compared with the malaria/dengue co-infection condition (Fig. 1).Fig. 1

Bottom Line: The plasma levels of cytokines and chemokines were determined by multiplex assay.The group of individuals co-infected exhibited the highest median concentrations of IFN-γ, IL-6, CCL4 than the mono-infected groups.Further, parasitaemia levels displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue.

View Article: PubMed Central - PubMed

Affiliation: Laboratório Integrado de Microbiogia e Imunoregulação (LIMI), Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil. vitorrosaramos@hotmail.com.

ABSTRACT

Background: Concurrent malaria and dengue infection is frequently diagnosed in endemic countries, but its immunopathology remains largely unknown. In the present study, a large panel of cytokines/chemokines and clinical laboratory markers were measured in patients with Plasmodium vivax and dengue co-infection as well as in individuals with malaria or dengue mono-infections in order to identify biosignatures of each clinical condition.

Methods: Individuals from the Brazilian Amazon were recruited between 2009 and 2013 and classified in three groups: vivax malaria (n = 52), dengue (n = 30) and vivax malaria and dengue co-infection (n = 30). P. vivax malaria was diagnosed by thick blood smear and confirmed by PCR; dengue cases were detected by IgM ELISA or NS1 protein. The plasma levels of cytokines and chemokines were determined by multiplex assay.

Results: Individuals with malaria and dengue co-infection displayed lower levels of platelets and haemoglobin than those with malaria or dengue mono-infections (p = 0.0047 and p = 0.0001, respectively). The group of individuals co-infected exhibited the highest median concentrations of IFN-γ, IL-6, CCL4 than the mono-infected groups. Network analyses of plasma cytokines/chemokines revealed that malaria and dengue co-infection exhibits a distinct immune profile with critical roles for TNF, IL-6 and IFN-γ. Further, parasitaemia levels displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue. No differences were observed in distribution of dengue virus serotypes and Plasmodium parasitaemia levels between the groups.

Conclusions: The findings described here identify unique patterns of circulating immunological markers in cases of malaria and dengue co-infection and provide insights on the immunopathology of this co-morbid condition.

No MeSH data available.


Related in: MedlinePlus