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. 2017 May 1;215(9):1445-1451.
doi: 10.1093/infdis/jix129.

Maternal Microchimerism Predicts Increased Infection but Decreased Disease due to Plasmodium falciparum During Early Childhood

Whitney E Harrington  1 , Sami B Kanaan  2 , Atis Muehlenbachs  3 , Robert Morrison  4 , Philip Stevenson  2 , Michal Fried  4 , Patrick E Duffy  4 , J Lee Nelson  2   5
Affiliations

Maternal Microchimerism Predicts Increased Infection but Decreased Disease due to Plasmodium falciparum During Early Childhood

Whitney E Harrington et al. J Infect Dis. .

Abstract

Background: A mother's infection with placental malaria (PM) can affect her child's susceptibility to malaria, although the mechanism remains unclear. The fetus acquires a small amount of maternal cells and DNA known as maternal microchimerism (MMc), and we hypothesized that PM increases MMc and that MMc alters risk of Plasmodium falciparum malaria during infancy.

Methods: In a nested cohort from Muheza, Tanzania, we evaluated the presence and level of cord blood MMc in offspring of women with and without PM. A maternal-specific polymorphism was identified for each maternal-infant pair, and MMc was assayed by quantitative polymerase chain reaction. The ability of MMc to predict malaria outcomes during early childhood was evaluated in longitudinal models.

Results: Inflammatory PM increased the detection rate of MMc among offspring of primigravidae and secundigravidae, and both noninflammatory and inflammatory PM increased the level of MMc. Detectable MMc predicted increased risk of positive blood smear but, interestingly, decreased risk of symptomatic malaria and malaria hospitalization.

Conclusions: The acquisition of MMc may result in increased malaria infection but protection from malaria disease. Future studies should be directed at the cellular component of MMc, with attention to its ability to directly or indirectly coordinate anti-malarial immune responses in the offspring.

Keywords: Childhood malaria; Malaria; Microchimerism; Placental malaria; Pregnancy..

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Figures

Figure 1.
Figure 1.
Prevalence and level of cord blood maternal microchimerism (CB MMc) by placental malaria (PM) category. No PM: n = 26; noninflammatory PM: n = 14; inflammatory PM: n = 13. Not detected (n/d). A, Inflammatory PM was associated with increased prevalence of CB MMc among offspring of primigravidae and secundigravidae (adjusted odds ratio, 48.43; P = .003) but not multigravidae. B, Noninflammatory (detection rate ratio [DRR], 199; P < .001) and inflammatory PM (DRR, 466; P < .001) were associated with increased level of CB MMc.
Figure 2.
Figure 2.
Probability of malaria outcome by cord blood maternal microchimerism (MMc) detection. Offspring with no detectable MMc: n = 37; offspring with detectable MMc: n = 16. Solid line: no detectable MMc; dashed line: Detectable MMc. Age modeled as a cubic spline with 3 knots. A, MMc predicted increased risk of positive blood smear (BS) (adjusted odds ratio [AOR], 1.73; P = .03). B, MMc predicted decreased risk of symptomatic malaria, given a positive BS (AOR, 0.47; P = .001). C, MMc predicted decreased risk of malaria hospitalization, given a positive BS (AOR, 0.41; P = .03).
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