ABO blood group phenotypes and Plasmodium falciparum malaria: unlocking a pivotal mechanism.

Host susceptibility to Plasmodium falciparum infection is central for improved understanding of malaria in human populations. Red blood cell (RBC) polymorphisms have been proposed as factors associated with malaria infection or its severity, although no systematic appraisal of ABO phenotypes and malaria risk has been undertaken. This analysis summarises epidemiological, clinical and immunological evidence on the nature of ABO histo-blood antigens and their interaction with malaria in terms of population genetics, infection risk, severe malaria and placental malaria. In non-pregnant subjects, a meta-analysis showed no conclusive evidence associating ABO phenotypes with risk of uncomplicated malaria. There was stronger evidence that ABO phenotype modulates severity of P. falciparum malaria, with group A associated with severe disease and blood group O with milder disease. Among pregnant subjects, group O was associated with increased risk of placental malaria in primigravidae and reduced risk in multigravidae. The biological basis for ABO-related susceptibility to malaria is reviewed. Several mechanisms relate to these associations including affinity for Anopheles gambiae; shared ABO antigens with P. falciparum; impairment of merozoite penetration of RBCs; and cytoadherence, endothelial activation and rosetting. ABO phenotypic associations with malaria are related to its pathogenesis and improved understanding of these interactions is required for understanding the glycobiology of malaria infection.

ABO blood group phenotypes influence parity specific immunity to Plasmodium falciparum malaria in Malawian women.

BACKGROUND: Blood group O has been significantly associated with increased placental malaria infection in primiparae and reduced risk of infection in multiparae in the Gambia, an area with markedly seasonal malaria transmission. This study analyses the association between ABO blood group phenotypes in relation to placental malaria pathology and birth outcomes in southern Malawi, an area with perennial malaria transmission. METHODS: A cross-sectional study of 647 mother/child pairs delivering in Montfort Hospital, Chikwawa District between February-June 2004 and January-July 2005 was undertaken. Maternal peripheral and cord blood samples were obtained at delivery. Placental tissue was obtained and malaria histology classified as active, past or no malaria infection. Birth anthropometry was recorded. ABO blood group was measured by agglutination. RESULTS: In primiparae, blood group O was significantly associated with increased risk of active placental infection (OR 2.18, 95% CI 1.15-4.6, p = 0.02) and an increased foetal-placental weight ratio compared to non-O phenotypes (5.68 versus 5.45, p = 0.03) In multiparae blood group O was significantly associated with less frequent active placental infection (OR 0.59, 95% CI 0.36-0.98, p = 0.04), and a higher newborn ponderal index compared to non-O phenotypes (2.65 versus 2.55, p = 0.007). In multivariate regression parity was independently associated with increased risk of placental malaria (active andpast infection) in primiparae with blood group O (p = 0.034) and reduced risk in multiparae with the same phenotype (p = 0.015). CONCLUSION: Parity related susceptibility to placental malaria is associated with the mothers ABO phenotype. This interaction influences foetal and placental growth and could be an important modifying factor for pregnancy outcomes. The biological explanation could relate to sialic acid dependent placental membrane differences which vary with ABO blood group.

ABO phenotypes and malaria related outcomes in mothers and babies in The Gambia: a role for histo-blood groups in placental malaria?

BACKGROUND: Host susceptibility to P.falciparum is critical for understanding malaria in pregnancy, its consequences for the mother and baby, and for improving malaria control in pregnant women. Yet host genetic factors which could influence placental malaria risk are little studied and there are no reports of the role of blood group polymorphisms on pregnancy outcomes in malaria endemic areas. This study analyses the association between ABO blood group phenotypes in relation to placental malaria pathology. METHODS: A total of 198 mother/child pairs delivering in Banjul and the Kombo-St Mary District (The Gambia) were analysed. ABO blood group was measured by agglutination. Placental malaria parasites wee enumerated and the presence of malaria pigment noted. Birth anthropometry was recorded and placental weight. Maternal and infant haemoglobin was measured. RESULTS: 89 (45%) subjects were primiparae and 110 (55%)multiparae. The ABO phenotype distribution was 38(A), 52(B), 6(AB) and 102(O). Placental histo-pathology showed active placental malaria in 74 (37%), past infection in 42 (21%) and no infection in 82 cases (41%). In primiparae blood group O was associated with a higher risk of active infection (OR = 2.99; 95% CI = 1.24-7.25), and a lower risk of past infection (OR = 0.31, 0.10-1.01, p < 0.05). In multiparae the O phenotype was associated with reduced prevalence of active or past placental infection (OR = 0.45; 95% CI 0.21-0.98). The mean feto-placental weight ratio was significantly higher in multiparae with group O women compared to non-O phenotypes (5.74 vs 5.36; p = 0.04). Among primiparae with active placental infection, mean birth weight was higher in children of mothers with the O phenotype (p = 0.04). CONCLUSION: These results indicate that blood group O was significantly associated with increased placental malaria infection in primiparae and reduced risk of infection in multiparae. This parity related susceptibility was not present with other ABO phenotypes. Cell surface glycans, such as ABO and related antigens have special relevance in reproductive biology and could modulate specific cell interactions as those associated with the pathogenesis of placental malaria.

Antibody response after RSV infection in children younger than 1 year of age living in a rural area of Mozambique.

Serological responses have been studied in respiratory syncytial virus (RSV) infected children < 1 year of age attending the outpatient department of the Manhiça District Hospital (Mozambique). Molecular characterization of viral RNA in nasopharyngeal aspirates from the infected children indicated a high level of genetic uniformity among the infecting viruses, all of which belonged to a single genotype of RSV group A. A representative virus strain, Moz00, was isolated from one of the infants and was used, together with the group A strain A2 and the group B strain 8/60, as antigens in the quantification of infant antibody responses. In this study, 97.5% (39/40) and 96.4% (27/28) of infected children produced an antibody response against Moz00 detected by the membrane fluorescent antibody test (MFAT) and the neutralization test (NT), respectively. Seroconversion rates decreased when the A2 and 8/60 strains were used as antigen in MFAT (95.4% and 88.2%, respectively) or NT (81.8% and 54.5%, respectively), indicating that antibody responses had both group- and strain-specific components. Antibodies in convalescent sera of infected children were compared with maternally derived antibodies detected in a group of children also < 1 year of age, but with no evidence of RSV infection. The convalescent sera exhibited reduced neutralizing capacity when the 8/60 strain was used as antigen (P = 0.028), suggesting that the infant antibody response lacks neutralizing capacity against strains of the heterologous virus group. Restricted cross-reactivity and neutralizing capacity of antibodies generated by young children might be expected to induce only moderate protection in subsequent epidemics against genetically distant strains.