Open Access Research article

Intermittent preventive treatment with sulfadoxine-pyrimethamine does not modify plasma cytokines and chemokines or intracellular cytokine responses to Plasmodium falciparum in Mozambican Children

Diana Quelhas1, Laura Puyol2, Llorenç Quintó2, Tacilta Nhampossa13, Elisa Serra-Casas2, Eusébio Macete14, Pedro Aide13, Sergi Sanz2, John J Aponte12, Denise L Doolan5, Pedro L Alonso12, Clara Menéndez12 and Carlota Dobaño12*

Author Affiliations

1 Centro de Investigação em Saúde da Manhiça (CISM), Manhiça, Mozambique

2 Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Spain

3 Instituto Nacional de Saúde, Ministério da Saúde, Maputo, Mozambique

4 Direcção Nacional de Saúde, Ministério da Saúde, Maputo, Mozambique

5 Queensland Institute of Medical Research (QIMR), Brisbane, Australia

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BMC Immunology 2012, 13:5  doi:10.1186/1471-2172-13-5

Published: 26 January 2012

Abstract

Background

Cytokines and chemokines are key mediators of anti-malarial immunity. We evaluated whether Intermittent Preventive Treatment in infants with Sulfadoxine-Pyrimethamine (IPTi-SP) had an effect on the acquisition of these cellular immune responses in Mozambican children. Multiple cytokines and chemokines were quantified in plasma by luminex, and antigen-specific cytokine production in whole blood was determined by intracellular cytokine staining and flow cytometry, at ages 5, 9, 12 and 24 months.

Results

IPTi-SP did not significantly affect the proportion of CD3+ cells producing IFN-γ, IL-4 or IL-10. Overall, plasma cytokine or chemokine concentrations did not differ between treatment groups. Th1 and pro-inflammatory responses were higher than Th2 and anti-inflammatory responses, respectively, and IFN-γ:IL-4 ratios were higher for placebo than for SP recipients. Levels of cytokines and chemokines varied according to age, declining from 5 to 9 months. Plasma concentrations of IL-10, IL-12 and IL-13 were associated with current infection or prior malaria episodes. Higher frequencies of IFN-γ and IL-10 producing CD3+ cells and elevated IL-10, IFN-γ, MCP-1 and IL-13 in plasma were individually associated with increased malaria incidence, at different time points. When all markers were analyzed together, only higher IL-17 at 12 months was associated with lower incidence of malaria up to 24 months.

Conclusions

Our work has confirmed that IPTi-SP does not negatively affect the development of cellular immune response during early childhood. This study has also provided new insights as to how these cytokine responses are acquired upon age and exposure to P. falciparum, as well as their associations with malaria susceptibility.

Trial Registration

ClinicalTrials.gov: NCT00209795

Keywords:
cytokines; chemokines; IPTi; falciparum malaria; sulfadoxine-pyrimethamine