In areas where Plasmodium falciparum is endemic, immunoglobulin G is acquired by the fetus in utero, mainly during the third trimester of pregnancy. The potential protective effect of transferred anti-P. falciparum maternal antibodies was examined in a longitudinal study of 100 infants from birth to 1 year of age. The probability of acquiring a P. falciparum infection and developing an episode of clinical malaria was determined in relation to the P. falciparum-specific antibody level of the infant at birth against P. falciparum schizont antigen or recombinant merozoite surface protein MSP1 19 antigen. The risk of acquiring an episode of clinical malaria increased from birth to 6 months of age, after which it decreased. The overall prevalence of P. falciparum parasitemia was highest (48.9%) in the 6-month-old infants. The age-specific hematocrit value showed the lowest mean value (30.2) from 6 to 9 months, and the spleen rate was the highest (69.8%) at the same age. There was a lower risk of developing an episode of clinical malaria during the first year of life in the infants with high levels of anti-MSP1 19 antibodies at birth. The level of maternally derived overall anti-schizont antigen antibodies did not seem to play a role in the relative risk of developing malaria infection or disease during the first year of life, though the level of specific anti-MSP1 19 antibodies may be associated with protection.
Immune responses to defined antigens may differ between individuals in a population as the reflection of differences in genetic regulation. In experimental animals, variation in responsiveness to a given epitope may be due to major histocompatibility complex (HLA, in hans) class II restrictions, implying serious limitations for the development of subunit vaccines. For human populations, knowledge of the relative importance of genetic as opposed to environmental factors affecting the immune response is scarce. We have compared antibody levels after immunization through repeated infections to a major malarial antigen (Pf155/RESA) in monozygotic twins with those in dizygotic twins, siblings, or unrelated controls. Antibody responses to the intact antigen and to some of its immunodominant epitopes were found to be more concordant within monozygotic twin pairs than in dizygotic pairs or age-and sex-matched siblings living under similar environmental conditions. The results support the conclusion that the antibody responses were genetically regulated. When the responses were assessed for possible associations with different HLA class II DRB, DQA, and DQB alleles and haplotypes, no associations were found. This suggests that the regulation of the Pf155/RESA antibody responses seen in this study reflects the impact of factors encoded by genes outside the HLA class II region.The occurrence and degree of an immune response to a given antigen following infection or vaccination are governed by both genetic and environmental factors. The effects of different genetic factors such as major histocompatibility complex (MHC) restriction or macrophage function (1) have to a large extent been clarified by studies of inbred animals (2). However, in human populations, immune responses to an infectious agent are strongly biased by environmental factors, including intensity of exposure to the pathogen and immune or health status or socioeconomic conditions of the hosts. Therefore, it may be difficult to decide whether different levels of responsiveness in individual human responders represent an intrinsic genetic regulation of the response or external factors.In this work, we have attempted to approach these questions for the humoral response in Plasmodium falciparum malaria, one of the most significant infectious diseases worldwide. The major antigen studied here was Pfl55/RESA (3-6), a polypeptide that the P. falciparum merozoite deposits in the membrane of erythrocytes at invasion. Of clinically immune adults living in villages of northern Liberia where malaria is holoendemic and perennial, -75% have antiPf155/RESA antibodies, as detected by a modified erythrocyte membrane immunofluorescence (EMIF) assay (3), although all have elevated antibodies to intracellular P. falciparum antigens. When assayed in ELISA with short synthetic peptides, concentrations of antibodies to different immunodominant epitopes of Pf155/RESA vary in different donors, resulting in individual antibody profiles that are characteristic for each donor, r...
Abstract. A randomized controlled trial investigated the impact of community-wide use of mosquito nets impregnated with lambda-cyhalothrin alone or with dapsone/pyrimethamine (d/p) prophylaxis on clinical malaria due to perennially transmitted Plasmodium falciparum in children in the Bo district of Sierra Leone. The 17 study communities were pair-matched and randomly allocated to receive treated mosquito nets or no nets and the children (age range ϭ 3 months-6 years) in each community were randomly allocated to receive d/p or placebo individually every two weeks. This resulted in each of the approximately 2,000 children recruited being in one of four study groups (impregnated mosquito nets and d/p prophylaxis, impregnated mosquito nets, d/p prophylaxis, and controls). The intervention phase of the study lasted 12 months. A total of 1,800 children attended more than 25% of the 48 total weekly morbidity surveillance surveys and were included in the analysis.
118 adult Liberians from 2 villages were studied prospectively for one year with monthly blood examinations for malaria parasites. The crude parasite rate was 41.5% and the crude gametocyte rate was 6.1%. The inoculation rate varied between 0.075 in the dry season and almost 0.4 in the rainy season, which is in accordance with other data from holoendemic areas. 47.5% (56) had a titre to the Pf155/RESA antigen less than or equal to 1/50 ('low responders') and 52.5% (62) had a titre of greater than or equal to 1/250 ('high responders'). The response was not age-dependent in this adult population, which may suggest that genetic factors are determining whether the individual become a high or low responder. Antibodies against the Pf155/RESA antigen were measured in 2 surveys 8 months apart, and the mean antibody response to Pf155/RESA and its EENV sequence was constant without seasonal variation. Pf155/RESA high responders had lower parasite densities during all 3 seasons surveyed, and Pf155/RESA high responders, with high antibody reactivity against the (EENV)6 sequence from the 3' repeat region of Pf155/RESA, had significantly lower parasite densities in the rainy season of 1987. The data suggest that high titres of antibodies to the Pf155/RESA antigen, and especially to its EENV sequence, might play a role in protective immunity in adults.
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