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

J Pediatric Infect Dis Soc. 2015 Sep;4(3):232-41. doi: 10.1093/jpids/piu140. Epub 2015 Jan 7.

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.

Keywords: IL-10; convalescence; interleukin-10; lymphopenia; regulatory T cells; uncomplicated malaria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Cohort Studies
  • Convalescence
  • Cytokines / blood
  • Cytokines / immunology*
  • Disease Transmission, Infectious / prevention & control*
  • Female
  • HIV / immunology
  • HIV Infections / blood
  • HIV Infections / complications
  • HIV Infections / immunology*
  • Humans
  • Infant
  • Interferon-gamma / blood
  • Interferon-gamma / immunology
  • Interleukin-10 / blood
  • Interleukin-10 / immunology
  • Malaria / immunology*
  • Malaria / transmission
  • Malawi
  • Male
  • Parasitemia / blood*
  • Parasitemia / etiology
  • Pre-Exposure Prophylaxis
  • Prospective Studies
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / blood
  • Transforming Growth Factor beta / immunology
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Cytokines
  • IL10 protein, human
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma

Supplementary concepts

  • Acute malaria