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

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.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.Placental malaria was associated with reduced immune responses 12 months after immune challenge in infants apparently healthy at birth.Plasmodium falciparum malaria is endemic in much of Sub-Saharan Africa and commonly infects the placentas of pregnant women. The overt consequences of placental malaria (PM) include high risk of premature birth and low birth weight [1,2], increased neonatal mortality [3] and infant anaemia [4]. Exposure to PM has been associated with an increased risk for malaria during the first years of life [5].Placental malaria has been associated with poor cytokine production by T-cells [6,7] and induced tolerance to Plasmodium antigens [8], which may be associated with the induction of regulatory T-cells in PM-exposed infants [9-11]. These findings are consistent with earlier results that showed that malaria in children led to reduced antibody responses to vaccination with bacterial polysaccharide, glycoconjugate and protein antigens [12-16], and also that prenatal exposure to malaria is associated with relatively low cytokine responses to P. falciparum antigens for at least the first three years o