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Background. Placental malaria (PM) and maternal infection with human immunodeficiency virus (HIV) type 1 have been shown to affect infant morbidity and immune responses to Plasmodium falciparum. We studied the effects of PM and HIV infection on the antimalarial antibody responses and morbidity outcomes of infants throughout the first year of life.Methods. A total of 411 Kenyan infants who were born to mothers who were singly or dually infected with PM and/or HIV had their levels of immunoglobulin G antibody to 6 P. falciparum antigens/epitopes (apical membrane antigen-1, erythrocyte-binding antigen-175; liver-stage antigen-1 [LSA-1], circumsporozoite protein [CSP], merozoite surface protein-2, and rhoptry-associated protein-1 [RAP-1]) and to tetanus toxoid (TT) tested using enzyme-linked immunosorbent assay.Results. PM had little effect on the antibody responses of infants, whereas maternal HIV infection resulted in decreased levels of antibody to LSA-1, CSP, and RAP-1 epitopes at birth, compared with the absence of PM and maternal HIV infection (P < .0063). Levels of antibodies to TT were significantly reduced in infants born to mothers coinfected with HIV and PM, compared with the levels noted in infants born to HIV-negative mothers (P < .0003). In HIV-infected infants, levels of antibody to TT were reduced, but levels of antibody to malarial antigens were not. Antimalarial antibody levels were positively associated with malaria-related morbidity outcomes.Conclusion. Infant HIV infection and maternal coinfection with HIV and PM negatively influence antibody responses to TT, but not those to malarial antigens, in infants. Antimalarial antibodies rarely showed protective associations with morbidity in infants and were more often a marker for malaria exposure and risk of infection.

Background. HIV and malaria in sub-Saharan Africa are associated with poor pregnancy outcome and infant survival. We studied the association of placental malaria, infant malaria and anemia, and infant HIV status with postneonatal infant mortality (PNIM) among infants of HIV-seropositive women. Methods. During 1996–2001, infants born to 570 HIV-seropositive mothers in Kisumu, Kenya were monitored monthly for malaria (parasitemia or clinical malaria) and anemia (hemoglobin level !8 g/dL) and vital status. Results. Thirty-nine deaths occurred among 112 HIV-positive infants (420/1000 live births [LBs] [95% confidence interval {CI}, 318–522 LBs]), and 36 occurred among 458 HIV-negative infants (99/1000 LBs [95% CI, 68–130 LBs]) ( ). In multivariate Cox regression analysis among HIV-negative infants, PNIM was associated P ! .001 with infant anemia (adjusted hazard ratio [AHR], 5.03 [95% CI, 1.97–12.81]) but not with placental malaria (AHR, 1.22 [95% CI, 0.50–2.95]) or infant malaria (AHR, 0.35 [95% CI, 0.10–1.21]). Among HIV-positive infants, neither placental malaria (AHR, 0.34 [95% CI, 0.10–1.10]) nor infant malaria (AHR, 0.31 [95% CI, 0.07–1.33]) or anemia (AHR, 1.07 [95% CI, 0.32–3.61]) was significantly associated with PNIM. Conclusion. In this study population, placental malaria and infant parasitemia were not risk factors for PNIM among infants of HIV-seropositive women. The prevention of infant anemia may decrease PNIM among HIVnegative infants of HIV-seropositive women.

Background Genetic polymorphism of the Fc receptor IIa for immunoglobulin (Ig) G (Fc gamma RIIa) determines IgG subclass binding. Previous studies have shown that individuals with the IgG1/3-binding Fc gamma RIIa-Arg/Arg131 genotype are relatively protected against high-density malaria, whereas individuals with the IgG2-binding Fc gamma RIIa-His/His131 genotype are at increased risk for developing cerebral malaria. The present study was undertaken to examine the relationship between Fc gamma RIIa polymorphism and placental malaria (PM) in pregnant women of known human immunodeficiency virus (HIV)-1 status. Methods Fc gamma RIIa genotype was determined in 903 pregnant women who had participated in a study designed to assess the effect that PM has on vertical transmission of HIV-1. Fc gamma RIIa polymorphism was assessed in relation to PM. Results Among HIV-negative women, there was no difference in the distribution of the Fc gamma RIIa polymorphism by PM status. However, among HIV-positive women, the frequency of the Fc gamma RIIa-His/His131 genotype was significantly higher in women with PM than in women without PM (31% vs. 22%, respectively [P=.032]). In multivariate analysis, the adjusted odds ratio for PM in HIV-positive women with the Fc gamma RIIa-His/His131 genotype versus women in the Fc gamma RIIa-His/Arg131 reference group was 1.72 (95% confidence interval, 1.11-2.69 [P=.016]). Conclusions The present study suggests that the IgG2-binding Fc gamma RIIa-His/His131 genotype is associated with enhanced susceptibility to PM in HIV-positive women but not in HIV-negative women.

An association was demonstrated recently between elevated in vitro production of interferon (IFN)-gamma by intervillous blood mononuclear cells (IVBMCs) and protection against placental malaria (PM). Because human immunodeficiency virus (HIV)-infected pregnant women have increased susceptibility to PM, loss of the IFN-gamma response in these women may impair their ability to control PM. Measurement of cytokines in culture supernatants by ELISA revealed that IFN-gamma responses by HIV-positive IVBMCs were impaired, especially after malarial antigen stimulation. Interleukin (IL)-4 and IL-10 responses also were reduced in HIV-positive persons, the latter more so in HIV-positive, PM-positive persons. In contrast, tumor necrosis factor-alpha production generally was enhanced in PM-positive and HIV-positive persons. Overall, cytokine production was reduced in HIV-positive persons with CD4 T cell counts