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



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.



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.



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.
Department of Pediatrics, University of Washington School of Medicine/Seattle Children's Hospital, Washington.
Whitney E
WE
Harrington
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Sami B
SB
Kanaan
Department of Pathology, University of Washington, Seattle, Washington.
Atis
A
Muehlenbachs
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
Robert
R
Morrison
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Philip
P
Stevenson
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
Michal
M
Fried
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
Patrick E
PE
Duffy
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Division of Rheumatology, University of Washington, Seattle.
J Lee
JL
Nelson
D000328:Adult; D002675:Child, Preschool; D046528:Chimerism / Q000706:statistics & numerical data*; D015331:Cohort Studies; D004198:Disease Susceptibility; D005260:Female; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D010922:Placenta Diseases / Q000453:epidemiology / Q000235:genetics*; D010963:Plasmodium falciparum; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000453:epidemiology / Q000235:genetics*; D015995:Prevalence; D055815:Young Adult
Childhood malaria; Malaria; Microchimerism; Placental malaria; Pregnancy.