Peripheral adenosine deaminase 1 activity is a biomarker for placental malaria and inflammation

Abstract

CENTAL MALARIA AND INFLAMMATION DANAE STEELE, ATIS MUEHLENBACHS, MICHAL FRIED, THEONEST MUTABINGWA, PATRICK DUFFY, Seattle Biomedical Research Institute, Seattle, Washington OBJECTIVE: Placental malaria (PM) complicated by placental inflammation is associated with low birthweight (LBW) at delivery, and has been estimated to cause 75,000 to 200,000 infant deaths per year in sub-Saharan Africa. Peripheral blood smears detect parasitemia in only about half of women with PM, making diagnosis difficult. Our objective is to find a simple, inexpensive prenatal test that can detect PM and inflammation and thereby identify pregnant women who are at the highest risk for delivery of LBW infants. STUDY DESIGN: Placental and peripheral blood samples were obtained from consenting women age 18-45 years who delivered in Muheza, Tanzania, an area of intense malaria transmission. Microscopy of placental blood and placental tissue sections was used to detect PM and inflammation in mothers delivering singleton infants. Quantitative reverse transcriptase PCR and immunostaining were performed for adenosine deaminase 1 (ADA1). Total ADA plasma activity was assessed using a colorimetric assay, and ADA isotyping was performed by the addition of an ADA1 inhibitor, EHNA. RESULTS: Placental ADA1 mRNA levels were elevated during infection and correlated with inflammation. By immunohistochemistry, ADA1 protein was demonstrated to be produced only in PM-positive placentas, in maternal polynuclear cells located in intervillous spaces. Plasma ADA activity was elevated in women with PM compared to those without (p!0.001), in women with PM and inflammation compared to those with PM only (p=0.002), and in mothers of LBW infants compared to mothers of normal birthweight infants (p=0.01). Isotyping indicated that ADA1 is the predominant plasma isotype of women with PM. We estimate that the cost of reagents to measure ADA1 is approximately $0.01 per test. CONCLUSION: Plasma ADA1 activity is a simple and inexpensive test that may help to identify those women with PM who are at risk of LBW infants. Applied prenatally, this assay could allow more intensive anti-malarial treatment of women with inflammatory PM and thereby potentially improve outcomes for their infants.