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Decreased prevalence of sepsis but not mild or severe P. falciparum malaria is associated with pre-existing filarial infection.

Panda M, Sahoo PK, Mohapatra AD, Dutta Sk, Thatoi PK, Tripathy R, Das BK, Satpathy AK, Ravindran B - Parasit Vectors (2013)

Bottom Line: In contrast to this, filarial infections have been consistently reported to be associated with an immunological hypo-responsive phenotype.Antibodies to four stage specific malarial recombinant proteins were measured by solid phase immunoassays and circulating CD4+CD25high T-cells were quantified by flow cytometry with an objective to study if pre-existing filarial infections influence antibody responses to malarial antigens or the levels of circulating T-regulatory cells in P. falciparum infected patients.Plasma TNF-a, RANTES and antibodies to recombinant malarial proteins as well as levels of circulating CD4+ CD25high cells were comparable in malaria patients with or without filarial infections.

View Article: PubMed Central - HTML - PubMed

Affiliation: Infectious Disease Biology group, Institute of Life Sciences, Bhubaneswar, Odisha, India.

ABSTRACT

Background: Enhanced inflammatory host responses have been attributed as the cellular basis for development of severe malaria as well as sepsis. In contrast to this, filarial infections have been consistently reported to be associated with an immunological hypo-responsive phenotype. This suggests that successful control of filariasis by employing mass drug administration, could potentially contribute to an increase in incidence of sepsis and cerebral malaria in human communities. A case control study was undertaken to address this critical and urgent issue.

Methods: Eighty-nine patients with sepsis and one hundred and ninety-six patients with P. falciparum malaria all originating from Odisha, were tested for prevalence of circulating filarial antigens - a quantitative marker of active filarial infection. Antibodies to four stage specific malarial recombinant proteins were measured by solid phase immunoassays and circulating CD4+CD25high T-cells were quantified by flow cytometry with an objective to study if pre-existing filarial infections influence antibody responses to malarial antigens or the levels of circulating T-regulatory cells in P. falciparum infected patients.

Results: Prevalence of filarial antigenemia was significantly less in sepsis patients as compared to controls suggesting that pre-existing filariasis could influence development of sepsis. On the other hand, levels of circulating filarial antigen were comparable in severe malaria cases and healthy controls suggesting that development of severe malaria is independent of pre-existing W. bancrofti infections. Plasma TNF-a, RANTES and antibodies to recombinant malarial proteins as well as levels of circulating CD4+ CD25high cells were comparable in malaria patients with or without filarial infections.

Conclusions: These observations imply that successful control of filariasis could have adverse consequences on public health by increasing the incidence of sepsis, while the incidence of severe malaria may not adversely increase as a consequence of elimination of filariasis.

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Related in: MedlinePlus

Profile of CD4+CD25+ve cells in malaria patients with and without CFA. PBMCs of study subjects at the time of recruitment were analyzed by flow-cytometry for CD4 and CD25 expression after staining with anti-human CD4-PE.cy5 and anti-human CD25-FITC. Percentage of CD4+ve T cells expressing CD25 are shown here, A: Zebra plot for CD4+CD25high T–cells, G1 represents CD4+cells, G4 represents CD25+cells, and G3 represents CD4 + CD25+ cells and G5 represents CD4+CD25 high cells. Percentage of CD4+CD25+ T cells (B) and CD4+CD25high T (C) cells in SM=91, NCM=58 and control=22 are shown. The association within the groups was analysed by one way analysis of variance (ANOVA) followed by Tukey’s post-hoc test. Percentages of CD4+CD25+ve T cells and CD4+CD25high T cells in severe malaria (CFA+ve=14, CFA-ve=64), non-complicated malaria (CFA+ve=13, CFA-ve=34) patients with or without active filarial infection are shown in D and E respectively. The association within the groups were analysed by one way analysis of variance (ANOVA) followed by Tukey’s post- hoc test.
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Figure 3: Profile of CD4+CD25+ve cells in malaria patients with and without CFA. PBMCs of study subjects at the time of recruitment were analyzed by flow-cytometry for CD4 and CD25 expression after staining with anti-human CD4-PE.cy5 and anti-human CD25-FITC. Percentage of CD4+ve T cells expressing CD25 are shown here, A: Zebra plot for CD4+CD25high T–cells, G1 represents CD4+cells, G4 represents CD25+cells, and G3 represents CD4 + CD25+ cells and G5 represents CD4+CD25 high cells. Percentage of CD4+CD25+ T cells (B) and CD4+CD25high T (C) cells in SM=91, NCM=58 and control=22 are shown. The association within the groups was analysed by one way analysis of variance (ANOVA) followed by Tukey’s post-hoc test. Percentages of CD4+CD25+ve T cells and CD4+CD25high T cells in severe malaria (CFA+ve=14, CFA-ve=64), non-complicated malaria (CFA+ve=13, CFA-ve=34) patients with or without active filarial infection are shown in D and E respectively. The association within the groups were analysed by one way analysis of variance (ANOVA) followed by Tukey’s post- hoc test.

Mentions: Statistical analyses were performed by using GraphPad Prism (version 5.01). For analysis of Figure 1(D and E) and Figure 2 (A, B, C and D) unpaired student’s t test was applied to determine differences between groups. For analysis of Figure 1A, B and Table 1, Fisher-exact test was employed to calculate Odds ratios (ORs) at 95% confidence intervals. For analysis of Figure 1C and Figure 3 (B, C, D and E) the association within the groups were analysed by one way analysis of variance (ANOVA) followed by Tukey’s post-hoc test. P-values<0.05 were considered to be statistically significant.


Decreased prevalence of sepsis but not mild or severe P. falciparum malaria is associated with pre-existing filarial infection.

Panda M, Sahoo PK, Mohapatra AD, Dutta Sk, Thatoi PK, Tripathy R, Das BK, Satpathy AK, Ravindran B - Parasit Vectors (2013)

Profile of CD4+CD25+ve cells in malaria patients with and without CFA. PBMCs of study subjects at the time of recruitment were analyzed by flow-cytometry for CD4 and CD25 expression after staining with anti-human CD4-PE.cy5 and anti-human CD25-FITC. Percentage of CD4+ve T cells expressing CD25 are shown here, A: Zebra plot for CD4+CD25high T–cells, G1 represents CD4+cells, G4 represents CD25+cells, and G3 represents CD4 + CD25+ cells and G5 represents CD4+CD25 high cells. Percentage of CD4+CD25+ T cells (B) and CD4+CD25high T (C) cells in SM=91, NCM=58 and control=22 are shown. The association within the groups was analysed by one way analysis of variance (ANOVA) followed by Tukey’s post-hoc test. Percentages of CD4+CD25+ve T cells and CD4+CD25high T cells in severe malaria (CFA+ve=14, CFA-ve=64), non-complicated malaria (CFA+ve=13, CFA-ve=34) patients with or without active filarial infection are shown in D and E respectively. The association within the groups were analysed by one way analysis of variance (ANOVA) followed by Tukey’s post- hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750550&req=5

Figure 3: Profile of CD4+CD25+ve cells in malaria patients with and without CFA. PBMCs of study subjects at the time of recruitment were analyzed by flow-cytometry for CD4 and CD25 expression after staining with anti-human CD4-PE.cy5 and anti-human CD25-FITC. Percentage of CD4+ve T cells expressing CD25 are shown here, A: Zebra plot for CD4+CD25high T–cells, G1 represents CD4+cells, G4 represents CD25+cells, and G3 represents CD4 + CD25+ cells and G5 represents CD4+CD25 high cells. Percentage of CD4+CD25+ T cells (B) and CD4+CD25high T (C) cells in SM=91, NCM=58 and control=22 are shown. The association within the groups was analysed by one way analysis of variance (ANOVA) followed by Tukey’s post-hoc test. Percentages of CD4+CD25+ve T cells and CD4+CD25high T cells in severe malaria (CFA+ve=14, CFA-ve=64), non-complicated malaria (CFA+ve=13, CFA-ve=34) patients with or without active filarial infection are shown in D and E respectively. The association within the groups were analysed by one way analysis of variance (ANOVA) followed by Tukey’s post- hoc test.
Mentions: Statistical analyses were performed by using GraphPad Prism (version 5.01). For analysis of Figure 1(D and E) and Figure 2 (A, B, C and D) unpaired student’s t test was applied to determine differences between groups. For analysis of Figure 1A, B and Table 1, Fisher-exact test was employed to calculate Odds ratios (ORs) at 95% confidence intervals. For analysis of Figure 1C and Figure 3 (B, C, D and E) the association within the groups were analysed by one way analysis of variance (ANOVA) followed by Tukey’s post-hoc test. P-values<0.05 were considered to be statistically significant.

Bottom Line: In contrast to this, filarial infections have been consistently reported to be associated with an immunological hypo-responsive phenotype.Antibodies to four stage specific malarial recombinant proteins were measured by solid phase immunoassays and circulating CD4+CD25high T-cells were quantified by flow cytometry with an objective to study if pre-existing filarial infections influence antibody responses to malarial antigens or the levels of circulating T-regulatory cells in P. falciparum infected patients.Plasma TNF-a, RANTES and antibodies to recombinant malarial proteins as well as levels of circulating CD4+ CD25high cells were comparable in malaria patients with or without filarial infections.

View Article: PubMed Central - HTML - PubMed

Affiliation: Infectious Disease Biology group, Institute of Life Sciences, Bhubaneswar, Odisha, India.

ABSTRACT

Background: Enhanced inflammatory host responses have been attributed as the cellular basis for development of severe malaria as well as sepsis. In contrast to this, filarial infections have been consistently reported to be associated with an immunological hypo-responsive phenotype. This suggests that successful control of filariasis by employing mass drug administration, could potentially contribute to an increase in incidence of sepsis and cerebral malaria in human communities. A case control study was undertaken to address this critical and urgent issue.

Methods: Eighty-nine patients with sepsis and one hundred and ninety-six patients with P. falciparum malaria all originating from Odisha, were tested for prevalence of circulating filarial antigens - a quantitative marker of active filarial infection. Antibodies to four stage specific malarial recombinant proteins were measured by solid phase immunoassays and circulating CD4+CD25high T-cells were quantified by flow cytometry with an objective to study if pre-existing filarial infections influence antibody responses to malarial antigens or the levels of circulating T-regulatory cells in P. falciparum infected patients.

Results: Prevalence of filarial antigenemia was significantly less in sepsis patients as compared to controls suggesting that pre-existing filariasis could influence development of sepsis. On the other hand, levels of circulating filarial antigen were comparable in severe malaria cases and healthy controls suggesting that development of severe malaria is independent of pre-existing W. bancrofti infections. Plasma TNF-a, RANTES and antibodies to recombinant malarial proteins as well as levels of circulating CD4+ CD25high cells were comparable in malaria patients with or without filarial infections.

Conclusions: These observations imply that successful control of filariasis could have adverse consequences on public health by increasing the incidence of sepsis, while the incidence of severe malaria may not adversely increase as a consequence of elimination of filariasis.

Show MeSH
Related in: MedlinePlus