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T-Regulatory Cells and Inflammatory and Inhibitory Cytokines in Malawian Children Residing in an Area of High and an Area of Low Malaria Transmission During Acute Uncomplicated Malaria and in Convalescence.

Nyirenda TS, Molyneux ME, Kenefeck R, Walker LS, MacLennan CA, Heyderman RS, Mandala WL - J Pediatric Infect Dis Soc (2015)

Bottom Line: Concentrations of TGF-β were higher at time points for the study participants and in controls from Blantyre compared with those recruited in Chikwawa.The high transmission area was associated with high Tregs counts and IL-10 concentrations in convalescence, which could have an effect on parasite clearance.We recommend that children recovering from UCM, especially those from high transmission area, should sleep under insecticide-treated nets, be screened for parasitemia, and a provision of antimalarial prophylaxis should be considered.

View Article: PubMed Central - PubMed

Affiliation: Malawi-Liverpool Wellcome Trust Clinical Research Programme , College of Medicine , Blantyre.

ABSTRACT

Background: Malaria still infects many Malawian children, and it is a cause of death in some of them. Regulatory T cells (Tregs) help in negating immune-related pathology, it but can also favor multiplication of malaria parasites. The question remains whether children recovering from uncomplicated malaria (UCM) have higher Tregs and interleukin (IL)-10 levels in convalescence.

Methods: We recruited children between the ages of 6 and 60 months presenting with acute UCM in Blantyre (low transmission area) and Chikwawa (high transmission area). We observed the children after 1 month and 3 months and analyzed their blood samples for parasitemia, lymphocyte subsets, and levels of the cytokines interferon (IFN)-γ, IL-10, and transforming growth factor (TGF)-β. Blood samples from age-matched controls were also analyzed for the same parameters.

Results: Compared with controls, acute UCM was associated with mild lymphopenia, splenomegaly, and high levels of IFN-γ, tumor necrosis factor-α, and IL-10, which normalized in convalescence. In Chikwawa, Treg counts were significantly (P < .0001) higher in convalescence compared with acute disease, whereas in Blantyre, these were as low as in healthy controls both during acute disease and in convalescence. Blantyre had a higher percentage of parasiteamic children (15% versus 12%) in convalescence compared with Chikwawa, but none of these developed symptomatic malaria during the study duration. Concentrations of TGF-β were higher at time points for the study participants and in controls from Blantyre compared with those recruited in Chikwawa.

Conclusions: The high transmission area was associated with high Tregs counts and IL-10 concentrations in convalescence, which could have an effect on parasite clearance. We recommend that children recovering from UCM, especially those from high transmission area, should sleep under insecticide-treated nets, be screened for parasitemia, and a provision of antimalarial prophylaxis should be considered.

No MeSH data available.


Related in: MedlinePlus

Proportions of median values of lymphocytes, CD4+ T cells and regulatory T cells (Tregs) at different stages of infection in children recruited with uncomplicated malaria and in healthy controls presented as percentage for the Blantyre (A) and Chikwawa (B) sites and presented as absolute counts for the Blantyre (C) and Chikwawa (D) sites.
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PIU140F2: Proportions of median values of lymphocytes, CD4+ T cells and regulatory T cells (Tregs) at different stages of infection in children recruited with uncomplicated malaria and in healthy controls presented as percentage for the Blantyre (A) and Chikwawa (B) sites and presented as absolute counts for the Blantyre (C) and Chikwawa (D) sites.

Mentions: When lymphocytes were presented as a percentage of total WBCs (Figure 2A and B) and when they were presented as absolute counts (Figure 2C and D), acute UCM was characterized by lymphopenia, which normalized in convalescence. CD4+ T cell-specific lymphopenia in acute UCM was only significant when the subset was presented as absolute counts at both sites, and this too normalized during convalescence (Figure 2C and D). When presented as percentages of total CD4+ T cells, acute UCM was characterized by higher than normal levels of Tregs, although the difference between levels observed during acute malaria and those in controls was only significant in Chikwawa (P = .0342) (Figure 2A and 2B). Regulatory T cell percentages significantly decreased in Chikwawa from the high levels observed during acute infection to low levels during the second follow up (P = .0494). Although a similar trend was observed in Blantyre, the decrease in percentage Tregs during convalescence was not significant.Figure 2.


T-Regulatory Cells and Inflammatory and Inhibitory Cytokines in Malawian Children Residing in an Area of High and an Area of Low Malaria Transmission During Acute Uncomplicated Malaria and in Convalescence.

Nyirenda TS, Molyneux ME, Kenefeck R, Walker LS, MacLennan CA, Heyderman RS, Mandala WL - J Pediatric Infect Dis Soc (2015)

Proportions of median values of lymphocytes, CD4+ T cells and regulatory T cells (Tregs) at different stages of infection in children recruited with uncomplicated malaria and in healthy controls presented as percentage for the Blantyre (A) and Chikwawa (B) sites and presented as absolute counts for the Blantyre (C) and Chikwawa (D) sites.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554200&req=5

PIU140F2: Proportions of median values of lymphocytes, CD4+ T cells and regulatory T cells (Tregs) at different stages of infection in children recruited with uncomplicated malaria and in healthy controls presented as percentage for the Blantyre (A) and Chikwawa (B) sites and presented as absolute counts for the Blantyre (C) and Chikwawa (D) sites.
Mentions: When lymphocytes were presented as a percentage of total WBCs (Figure 2A and B) and when they were presented as absolute counts (Figure 2C and D), acute UCM was characterized by lymphopenia, which normalized in convalescence. CD4+ T cell-specific lymphopenia in acute UCM was only significant when the subset was presented as absolute counts at both sites, and this too normalized during convalescence (Figure 2C and D). When presented as percentages of total CD4+ T cells, acute UCM was characterized by higher than normal levels of Tregs, although the difference between levels observed during acute malaria and those in controls was only significant in Chikwawa (P = .0342) (Figure 2A and 2B). Regulatory T cell percentages significantly decreased in Chikwawa from the high levels observed during acute infection to low levels during the second follow up (P = .0494). Although a similar trend was observed in Blantyre, the decrease in percentage Tregs during convalescence was not significant.Figure 2.

Bottom Line: Concentrations of TGF-β were higher at time points for the study participants and in controls from Blantyre compared with those recruited in Chikwawa.The high transmission area was associated with high Tregs counts and IL-10 concentrations in convalescence, which could have an effect on parasite clearance.We recommend that children recovering from UCM, especially those from high transmission area, should sleep under insecticide-treated nets, be screened for parasitemia, and a provision of antimalarial prophylaxis should be considered.

View Article: PubMed Central - PubMed

Affiliation: Malawi-Liverpool Wellcome Trust Clinical Research Programme , College of Medicine , Blantyre.

ABSTRACT

Background: Malaria still infects many Malawian children, and it is a cause of death in some of them. Regulatory T cells (Tregs) help in negating immune-related pathology, it but can also favor multiplication of malaria parasites. The question remains whether children recovering from uncomplicated malaria (UCM) have higher Tregs and interleukin (IL)-10 levels in convalescence.

Methods: We recruited children between the ages of 6 and 60 months presenting with acute UCM in Blantyre (low transmission area) and Chikwawa (high transmission area). We observed the children after 1 month and 3 months and analyzed their blood samples for parasitemia, lymphocyte subsets, and levels of the cytokines interferon (IFN)-γ, IL-10, and transforming growth factor (TGF)-β. Blood samples from age-matched controls were also analyzed for the same parameters.

Results: Compared with controls, acute UCM was associated with mild lymphopenia, splenomegaly, and high levels of IFN-γ, tumor necrosis factor-α, and IL-10, which normalized in convalescence. In Chikwawa, Treg counts were significantly (P < .0001) higher in convalescence compared with acute disease, whereas in Blantyre, these were as low as in healthy controls both during acute disease and in convalescence. Blantyre had a higher percentage of parasiteamic children (15% versus 12%) in convalescence compared with Chikwawa, but none of these developed symptomatic malaria during the study duration. Concentrations of TGF-β were higher at time points for the study participants and in controls from Blantyre compared with those recruited in Chikwawa.

Conclusions: The high transmission area was associated with high Tregs counts and IL-10 concentrations in convalescence, which could have an effect on parasite clearance. We recommend that children recovering from UCM, especially those from high transmission area, should sleep under insecticide-treated nets, be screened for parasitemia, and a provision of antimalarial prophylaxis should be considered.

No MeSH data available.


Related in: MedlinePlus