Antibodies to blood stage antigens of Plasmodium falciparum in rural Gambians and their relation to protection against infection

Abstract

Cross-sectional and longitudinal studies were performed in a rural population living in The Gambia to examine the relationship between several in vitro assays of the host immune response to asexual stages of Plasmodium falciparum and protection from malaria in vivo. Assays included an enzyme-linked immunosorbent assay for antibodies to schizont antigens; an indirect immunofluorescence assay for total antiblood-stage antibodies; an immunofluorescence assay on glutaraldehyde-fixed parasites to detect antibodies to antigen Pf 155; an assay for serum inhibition of red blood cell invasion; a micro-agglutination assay to detect antibodies to neo-antigens on the surface of infected red blood cells; and an assay using polymorphonuclear leucocytes to detect antibodies capable of opsonizing schizont infected red blood cells. There were marked differences in the age-related pattern of response for different assays performed on sera obtained at a cross-sectional survey of 280 individuals. Examination of the correlation between the various immune responses and malariometric indices at the population level and at the individual level provided no evidence that any of the in vitro assays were related to protective immunity. The relationship between in vitro measurements of the anti-malarial immune response and protection from clinical episodes of malaria was examined in a group of 134 children aged 11 years and under who were monitored weekly throughout an entire malaria transmission season. The only immune factor to show a consistent protective effect against clinical malaria was the titre of antibodies to neo-antigens on the infected erythrocyte surface (P = 0.01). The same longitudinal techniques were used to examine the effect of two non-immunological factors, sickle cell trait and mosquito net usage, both of which showed significant protection against clinical episodes and malaria.

Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania

“…However, in this study, only parasite density, not parasite prevalence, was significantly reduced in heterozygotes for the sickle cell trait. Similar patterns were found in children from Nigeria (Guggenmoos-Holzman et al 1981) and The Gambia (Marsh et al 1989). Conversely, in infants in Nigeria, parasite density and rate were similar in infants with normal haemoglobin or heterozygous for the sickle cell trait, except for infants 6 or 10 months of age where the parasite density or rate was significantly reduced or increased in heterozygotes, respectively (Achidi et al 1996).…”

Human genetic factors related to susceptibility to mild malaria in Gabon

“…21 Indeed, in asymptomatic children, mean parasite densities have been shown to be higher in HbAS than HbAA children less than 5 years old, 22 but similar in older individuals. [23][24][25] In the present study, higher GMAPD values in HbAS children may in part be attributed to the higher mean prevalence rate of P. falciparum infection among these children during the 16 cross-sectional surveys. Moreover, in holoendemic areas of Ghana 26 and The Gambia, 27 children with a moderate parasite count (less than 50/ l in Ghana and 500/ l in The Gambia) as observed in our sample, were more commonly seen among HbAS than in HbAA controls.…”

Immunization of Aotus monkeys with a functional domain of the Plasmodium falciparum variant antigen induces protection against a lethal parasite line

“…Children in Africa eventually develop immunity that protects against severe and clinical disease (1,6,8,31). In the course of developing this immunity, they experienced many infections, including some that can be life threatening, and continue to be routinely exposed to parasites for years (1,31,32).…”

“…Ample evidence indicates that antibodies to the variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) (2)(3)(4), are a major component of protective immunity, particularly during early childhood (5)(6)(7)(8). Variant antigens, however, are used by organisms to evade immunity and are not considered as good vaccine targets to control infection (9).…”