title: Real-time quantitative PCR for determining the burden of Plasmodium falciparum parasites during pregnancy and infancy.
abstract: Real-time quantitative PCR (RTQ-PCR) provides a quick, accurate, and reproducible quantification of parasites. However, the value of RTQ-PCR for predicting clinical outcomes of malaria is unknown. Here, we compared RTQ-PCR to microscopy of blood smears, nested PCR (nPCR), and parasite circulating-antigen (CAg) assays for detection of Plasmodium falciparum in pregnant Kenyan women and their infants and related these findings to parity and birth weights in their newborns (n = 554). nPCR was the most sensitive assay for detection of malaria in pregnancy, followed in decreasing order of sensitivity by RTQ-PCR, CAg assays, and blood smears. RTQ-PCR detected a higher frequency of malaria infection (46%) in maternal peripheral blood in primiparous than in multiparous women (35%; P < 0.001), with a >12-fold difference in parasite burden (geometric mean = 25,870 versus 2,143 amplicons/microl blood; P < 0.0001). Similarly, the presence of placental malaria determined by RTQ-PCR was approximately twofold higher in primiparous versus multiparous women (21% versus 13%; P < 0.01). The presence and intensity of malaria infection in pregnant women estimated by RTQ-PCR strongly correlated with low-birth-weight babies, especially in those with high amplicon numbers. RTQ-PCR identified malaria-infected women, missed by blood smear, who were at risk for having underweight offspring. By contrast, malaria detected by nPCR and CAg assay showed a much weaker association with parity or low birth weight. Thus, RTQ-PCR provides an estimate of parasite burden that is more sensitive than blood smear and is predictive of clinical outcomes of malaria infection in pregnant women and newborns.
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, 2103 Cornell Rd., WRC Rm. 4132, Cleveland, OH 44106-7286, USA.
authors.forename: Indu
authors.initials: I
authors.lastname: Malhotra
authors.forename: Arlene
authors.initials: A
authors.lastname: Dent
authors.forename: Peter
authors.initials: P
authors.lastname: Mungai
authors.forename: Eric
authors.initials: E
authors.lastname: Muchiri
authors.forename: Christopher L
authors.initials: CL
authors.lastname: King
mesh_terms: D000818:Animals; D001724:Birth Weight; D017281:Cost of Illness; D005260:Female; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000469:parasitology*; D012680:Sensitivity and Specificity