The prevalence and importance of malaria infections during pregnancy not detected by microscopy or rapid diagnostic testing

With the advent of rapid diagnostic tests (RDT) for malaria detection, parasitological confirmation of malaria diagnoses has become more readily accessible and increasingly more affordable. However, questions are being asked about how useful they are in screening programmes, particularly for pregnant women who very often may harbour placental malaria infections which may not be detected by peripheral blood smear microscopy. It is also necessary to examine how many malaria infections go undetected by RDTs and whether such undetected infections have any negative consequences for women who carry such RDT-negative infections. This sub-study was conducted as part of a large multi-country trial of intermittent preventive treatment with sulfadoxine pyrimethamine versus intermittent screening and treatment of malaria in pregnancy which in Burkina Faso, Gambia, Ghana and Mali. The study enrolled 5,354 primi- and secundigravidae who attended antenatal clinics at study sites in the four countries from May 2010 to October 2011. The sensitivity of the RDT to detect peripheral malaria in pregnancy using PCR as the reference declined from 89.3% (95% CI 85.5-92.4) on the day of enrollment to 57.7% (95% CI 46.5-73.0) at delivery. However, the sensitivity of the RDT to detect placental malaria was lower when placental histology was used as the reference ranging from 72% (95% CI 63.3-79.7) for any woman who tested RDT positive at any scheduled ANC visit, to 35.4% (95% CI 26.6-45.0) at the delivery visit. The prevalence of sub-RDT malaria was highest at delivery (6.3%). There was no significant association between sub-RDT malaria infection and low birth weight. Of the women in a sub-sample who were seen at first ANC visit, 39.0% had malaria infections out of which 1.7% were non-falciparum infections presenting as mono-infections or mixed infections with P. falciparum. Clinical symptoms and signs were not sensitive enough to predict a positive RDT test and therefore the presence of malaria parasites. Women whose malaria infections get missed by RDTs are not at great risk of developing adverse pregnancy outcomes when compared with women who had no malaria. All pregnant women should be screened with RDT if IST was considered to replace IPTp-SP in areas where SP resistance is too high or transmission intensity is very low.