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Open Access Research article

Placental malaria is associated with attenuated CD4 T-cell responses to tuberculin PPD 12 months after BCG vaccination

Brigitte Walther1, David JC Miles12*, Pauline Waight13, Melba S Palmero1, Olubukola Ojuola14, Ebrima S Touray1, Hilton Whittle1, Marianne van der Sande156, Sarah Crozier17 and Katie L Flanagan1

Author Affiliations

1 MRC Laboratories Gambia, PO Box 273, Banjul, Gambia

2 Malawi-Liverpool-Wellcome Trust Clinical Research Programme, PO Box 30096, Chichiri, Blantyre 3, Malawi

3 Immunisation Department, Health Protection Agency Centre for Infections, London, UK

4 Department of Pediatrics, Bronx Lebanon Hospital Center, 1650 Selwyn Avenue, Bronx, New York, USA

5 Epidemiology and Surveillance Unit, Centre for Infectious Diseases Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands

6 Julius Centre, University Medical Centre Utrecht, Utrecht, The Netherlands

7 MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, UK

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BMC Infectious Diseases 2012, 12:6  doi:10.1186/1471-2334-12-6

Published: 14 January 2012

Abstract

Background

Placental malaria (PM) is associated with prenatal malaise, but many PM+ infants are born without symptoms. As malaria has powerful immunomodulatory effects, we tested the hypothesis that PM predicts reduced T-cell responses to vaccine challenge.

Methods

We recruited healthy PM+ and PM- infants at birth. At six and 12 months, we stimulated PBMCs with tuberculin purified protein derivative (PPD) and compared expression of CD154, IL-2 and IFNγ by CD4 T-cells to a negative control using flow cytometry.

We measured the length, weight and head circumference at birth and 12 months.

Results

IL-2 and CD154 expression were low in both groups at both timepoints, without discernable differences. Expression of IFNγ was similarly low at 6 months but by 12 months, the median response was higher in PM- than PM + infants (p = 0.026). The PM+ infants also had a lower weight (p = 0.032) and head circumference (p = 0.041) at 12 months, indicating lower growth rates.

At birth, the size and weight of the PM+ and PM- infants were equivalent. By 12 months, the PM+ infants had a lower weight and head circumference than the PM- infants.

Conclusions

Placental malaria was associated with reduced immune responses 12 months after immune challenge in infants apparently healthy at birth.