Uneke: Effects of placental malaria on perinatal outcome 99 utory role of placental malaria to fetal ane- mia has been evaluated in a number of stud- ies with varying results. In southern Malawi, a higher preva- lence of fetal anemia occurred with increas- ing peripheral P. falciparum parasite density, and geometric mean placental parasite den- sities were higher in babies with fetal ane- mia than in those without it [55]. Other studies have found no statistically signifi- cant connection between evidence of malaria infection and fetal anemia [58]. This lack of consistency in the findings from various studies may be explained by the fact that malaria in pregnancy varies with transmission intensity, access to treat- ment, coverage and quality of antenatal services, and drug resistance, among other factors [56,59,60]. The etiology of fetal ane- mia is complex and multifactorial; placental malaria could play either a major or minor role, depending on the local epidemiological situation [61]. It has been suggested that ex- posure of the fetus to malaria antigens due to damage of the placental barrier may make the newborn more susceptible to immuno- logically mediated hemolysis or to dysery- thropoiesis [61]. MOTHER-TO-CHILD TRANSMISSION OF HIV Maternal HIV infection Approximately 1 million pregnancies per year are thought to be complicated by co-infection with malaria and HIV in sub- Saharan Africa, because the two diseases are known to critically intersect in pregnancy [62,63]. HIV infection has been associated with an increased prevalence and density of malaria in pregnancy in a number of studies in sub-Saharan Africa [62,64-66]. In most studies, the prevalence of placental malaria infection was significantly more prevalent in HIV-positive compared with HIV-nega- tive mothers [66-70]. In one study in Malawi, however, HIV infection was not significantly related to the likelihood of malaria as detected by placental histology [71]. Nevertheless, the increased suscepti- bility to both peripheral malaria and placen- tal malaria by HIV infected pregnant women is likely due to immunodeficiency, as it has been shown that HIV may impair the im- mune response to malaria in pregnancy [65]. Although in vitro experiments showed that higher placental virus load was seen when malaria antigen was present [72,73], it was suggested it might be that this local increase in virus concentration is not re- flected in the systemic maternal virus load [69]. Furthermore, in Malawi, a similar two- fold increase in placental HIV-1 RNA con- centrations was found, with the greatest increase in women with the highest placental parasite densities [74]. It was noted that these observations were independent of the degree of immunosuppression as assessed by CD4 cell counts and thus cannot be ex- plained by an increased risk of malaria in subjects with more advanced immunosup- pression and potentially greater HIV-1 viral load [74]. Whether dual infection with placental malaria and HIV increases the risk of mother-to-child transmission of HIV (MTCT) is yet to be unequivocally estab- lished, as studies examining these relation- ships have inconsistent findings and a wide range of unanswered questions. Reported prevalence of MTCT ranges from 19.4 per- cent to 19.9 percent [64,68-69]. In some studies, no correlation was found between placental malaria and perinatal HIV trans- mission; in others, a higher prevalence of MTCT was observed among HIV-positive mothers with placental malaria, although other factors were not controlled for [68-69]. One report notes a lower prevalence of MTCT among HIV-positive mothers with placental malaria, and indicates that placen- tal malaria, especially at lower density par- asitemia (< 10,000 parasites/µL), is significantly associated with reduced risk for perinatal MTCT [64]. These conflicting results on the relation- ship between placental malaria and the risk of MTCT, ranging from an increased risk to no effect to a significant protective effect sug- gests there exists a complex interaction be- tween placental malaria and HIV infection.