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.
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.
Malawi-Liverpool Wellcome Trust Clinical Research Programme , College of Medicine , Blantyre.
Tonney S
TS
Nyirenda
Malawi-Liverpool Wellcome Trust Clinical Research Programme , College of Medicine , Blantyre ; Liverpool School of Tropical Medicine , United Kingdom.
Malcolm E
ME
Molyneux
Institute of Immunity and Transplantation , University College London , Division of Infection and Immunity , United Kingdom.
Rupert
R
Kenefeck
Institute of Immunity and Transplantation , University College London , Division of Infection and Immunity , United Kingdom.
Lucy S K
LS
Walker
The Medical Research Council Centre for Immune Regulation and Clinical Immunology , Service, School of Immunity and Infection , College of Medicine and Dental Sciences , University of Birmingham , United Kingdom.
Calman A
CA
MacLennan
Malawi-Liverpool Wellcome Trust Clinical Research Programme , College of Medicine , Blantyre ; Liverpool School of Tropical Medicine , United Kingdom.
Robert S
RS
Heyderman
Malawi-Liverpool Wellcome Trust Clinical Research Programme , College of Medicine , Blantyre ; Basic Medical Sciences Department , College of Medicine , Blantyre, Malawi.
Wilson L
WL
Mandala
D002675:Child, Preschool; D015331:Cohort Studies; D003289:Convalescence; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D005260:Female; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000276:immunology*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000635:transmission; D008295:Malawi; D008297:Male; D018512:Parasitemia / Q000097:blood* / Q000209:etiology; D065129:Pre-Exposure Prophylaxis; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
D016207:Cytokines; C508609:IL10 protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
IL-10; convalescence; interleukin-10; lymphopenia; regulatory T cells; uncomplicated malaria