The OptiMAL test has been evaluated in both developing and developed countries for its ability to diagnose infection caused by Plasmodium
species, usually in individuals with symptoms suggestive of malaria infection (4
). In these circumstances, it has yielded high sensitivities and specificities when parasitemia is moderate to high (>500/μl).
We evaluated the OptiMAL test in pregnant Malawian women (test given at delivery) to determine whether it could detect placental parasitemia in women who had negative results by microscopy of peripheral blood samples. Such a tool would be useful in detection of occult infection, which may otherwise have negative consequences for fetal growth. However, we found the OptiMAL test to have a low sensitivity for the detection of placental P. falciparum infection in Malawian women and to be no more sensitive than conventional microscopy of peripheral blood for detection of placental parasites. In this study, only 1 of 171 women tested had placental infection and a positive OptiMAL test without peripheral infection. No infections with other Plasmodium spp. were recognized.
The sensitivity of the OptiMAL test agreed quite closely with peripheral parasitemia and somewhat less closely with placental parasitemia (Table ). No woman with a peripheral parasitemia of >1,500/μl (or approximately 0.03%) had a negative result by OptiMAL, whereas 12 of 20 with lower-grade parasitemia had negative OptiMAL test results. There were, however, moderate to dense placental infections which were associated with negative OptiMAL test results; this suggests that either placental parasites may have been nonviable or that P. falciparum
LDH levels in peripheral blood samples resulting from placental infection are not high enough to be detected by OptiMAL. We have previously shown that placental parasite isolates can adhere to host receptors and can be agglutinated by human serum (1
), and we have adapted isolates from placenta to ongoing culture (J. G. Beeson and S. J. Rogerson, unpublished data), which suggests that placental parasites are usually healthy. Leke et al. evaluated the ICT strip test for P. falciparum
HRP-2 in pregnant Cameroonian women and found it to have a sensitivity of 89% and specificity of 94% for malaria infection (7
). No breakdown of parasitemias was provided for this study, although in a related study of an HRP-2 ELISA, the sensitivity was less than 80% in women with placental parasitemia below 10% (7
). The densities of placental and peripheral parasitemia were generally low in our study, which may have contributed to the low sensitivity of the OptiMAL test. Our study was performed at a time of low malaria transmission and prevalence (13
). In a separate study comparing the OptiMAL test and a P. falciparum
-specific immunocapture enzyme activity assay performed in the same population, the sensitivities of both tests were below 50% for peripheral parasitemia and 40% for placental infection, respectively (S. Wurster et al., submitted for publication).
Of eight women with positive OptiMAL test results and negative peripheral blood films, one had placental malaria infection and seven had no malaria infection by microscopy. Two of these women were PCR positive; the other five were PCR negative and their false-positive OptiMAL test results are unexplained. It is possible that these women had peripheral blood malaria infection, which was not detected by microscopy (which had a threshold of 40 parasites/μl), or that infecting parasites were sequestered in sites other than the placenta. Recognized causes of false-positive OptiMAL test results include rheumatoid factor positivity (although rates are lower than for P. falciparum
HRP-2-based tests) (6
). We are not aware of other evaluations of OptiMAL in pregnant women, which might have identified other, pregnancy-specific causes of false-positive test results.
Importantly, those women who had positive OptiMAL test results had much higher rates of low-birth-weight babies and babies with lower mean birth weights than women with negative OptiMAL test results (Table ). We have previously found that women with placental malaria have approximately twice as many low-birth-weight babies as women without infection at delivery (12
). Placental malaria infection was associated with decreased birth weight, and of the women who had placental malaria, women in whom P. falciparum
LDH was detected had babies with lower birth weights than did women with placental malaria and negative OptiMAL test results. Women with negative OptiMAL test results had babies with similar birth weights and similar prevalence of low-birth-weight babies compared to the babies of those women screened but not recruited to the case-control study. This suggests the OptiMAL test may be detecting parasite burdens which are associated with poor infant outcome. Ours was a relatively small study, and while our findings are quite striking, a larger evaluation of the OptiMAL test as a potential predictor of low birth weight is indicated.
The low specificity of PCR is a reflection of the insensitivity of microscopy. Microscopy remains the “gold standard” for diagnosis of malaria infection. Although it is less sensitive than PCR in detecting infection, it has not been shown that infections in the submicroscopic range are associated with specific pathology. While PCR was more sensitive than OptiMAL in detecting malaria infection in the placenta, it still missed 16 of 32 (50%) placental infections associated with negative peripheral blood smears and detected malaria infection in 20 women without peripheral or placental parasitemia. These additional cases of malaria infection were without adverse associations with birth weight. PCR, therefore, does not appear to offer any advantage in detection of women at risk of low-birth-weight babies associated with malaria infection. We were not able to measure maternal hemoglobin in this study, but Mockenhaupt et al. reported that pregnant women with submicroscopic malaria infection had slightly lower mean hemoglobin concentration, but not a higher prevalence of anemia, than did PCR-negative women (9
). The importance of submicroscopic malaria for mother or baby seems to be low.
Although the OptiMAL test proved disappointing in its ability to detect placental malaria infection, it did appear to identify a group of women at high risk of having low-birth-weight babies. This observation, if supported by further studies, would suggest that OptiMAL screening in late pregnancy could be useful to identify women at high risk of delivering babies with low birth weight due to malaria infection, who might benefit from targeted antimalarial treatment.