Abstract
BackgroundIntermittent screening and treatment (IST) of malaria during pregnancy has been proposed as an alternative to intermittent preventive treatment in pregnancy (IPTp), where IPTp is failing due to drug resistance. However, the antenatal parasitaemias are frequently very low, and the most appropriate screening test for IST has not been defined.Methodology/Principal FindingsWe conducted a multi-center prospective study of 990 HIV-uninfected women attending ANC in two different malaria transmission settings at Tororo District Hospital, eastern Uganda and Colsama Health Center in western Burkina Faso. Women were enrolled in the study in the second or third trimester of pregnancy and followed to delivery, generating 2,597 blood samples for analysis. Screening tests included rapid diagnostic tests (RDTs) targeting histidine-rich protein 2 (HRP2) and parasite lactate dehydrogenase (pLDH) and microscopy, compared to nPCR as a reference standard. At enrolment, the proportion of pregnant women who were positive for P. falciparum by HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT, microscopy and PCR was 38%, 29%, 36% and 44% in Uganda and 21%, 16%, 15% and 35% in Burkina Faso, respectively. All test positivity rates declined during follow-up. In comparison to PCR, the sensitivity of the HRP2/pan pLDH RDT, Pf pLDH/pan pLDH RDT and microscopy was 75.7%, 60.1% and 69.7% in Uganda, 55.8%, 42.6% and 55.8% in Burkina Faso respectively for all antenatal visits. Specificity was greater than 96% for all three tests. Comparison of accuracy using generalized estimating equation revealed that the HRP2- detecting RDT was the most accurate test in both settings.Conclusions/SignificanceThe study suggests that HRP2-based RDTs are the most appropriate point-of-care test currently available for use during pregnancy especially for symptomatic women, but will still miss some PCR-positive women. The clinical significance of these very low density infections needs to be better defined.
Highlights
The negative effects of malaria infection in pregnancy have been long recognized [1,2,3,4]
Antigens detected by currently available rapid diagnostic tests (RDTs) include histidine-rich protein 2 (HRP2), which persists in circulation for a number of weeks and so can accumulate, and parasite lactate dehydrogenase that clears rapidly
At enrolment in Burkina Faso, the proportion of samples positive based on Polymerase Chain Reaction (PCR) for P. falciparum35%, HRP2 RDT 21% Pf parasite lactate dehydrogenase (pLDH) 16% RDT and expert microscopy 15%
Summary
The negative effects of malaria infection in pregnancy have been long recognized [1,2,3,4]. While often asymptomatic, has been clearly associated with poor outcomes including maternal anemia, low birth weight, infant mortality and delayed child development [5,6,7,8]. Because of these dangers, the World Health Organization (WHO) recommends, and many African countries implement, intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyramethamine (SP) in addition to other measures including long-lasting insecticide-treated nets (LLINs) and effective case management. A challenge of screening and ACT-based treatment in pregnancy is that P. falciparum malaria parasites, sequester in the placenta and may not be detected in maternal peripheral blood by routine laboratory testing, microscopy[10]. The antenatal parasitaemias are frequently very low, and the most appropriate screening test for IST has not been defined
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