Antibodies to Plasmodium falciparum Glycosylphosphatidylinositols: Inverse Association with Tolerance of Parasitemia in Papua New Guinean Children and Adults

  title={Antibodies to Plasmodium falciparum Glycosylphosphatidylinositols: Inverse Association with Tolerance of Parasitemia in Papua New Guinean Children and Adults},
  author={Craig Steven Boutlis and D. Channe Gowda and Ramachandra S. Naik and Graeme P Maguire and Charles S. Mgone and Moses Bockarie and Moses Lagog and Erwin Ibam and Kerry Lorry and Nicholas M. Anstey},
  journal={Infection and Immunity},
  pages={5052 - 5057}
ABSTRACT Individuals living in regions of intense malaria transmission exhibit natural immunity that facilitates persistence of parasitemia at controlled densities for much of the time without symptoms. This aspect of immunity has been referred to as malarial “tolerance” and is thought to partly involve inhibition of the chain of events initiated by a parasite toxin(s) that may otherwise result in cytokine release and symptoms such as fever. Antibodies to the candidate Plasmodium falciparum… 
Differential Antibody Responses to P. falciparum Glycosylphosphatidylinositol Anchors in Patients With Cerebral and Mild Malaria
In this study, IgG responses against P. falciparum GPIs and a baculovirus recombinant MSP1p19 antigen evaluated in two distinct groups of 70 patients each, indicating a potential anti -toxin role for anti -GPI antibodies associated with protection against cerebra l malaria.
Antibodies to Plasmodium falciparum Rifin Proteins Are Associated with Rapid Parasite Clearance and Asymptomatic Infections
The likelihood that these antibodies could confer a certain degree of protection against malaria is supported by the findings of statistically higher levels of antirifin antibodies to all four rifin proteins in a group of 42 asymptomatic parasitemic children.
Neutralization of Malaria Glycosylphosphatidylinositol In Vitro by Serum IgG from Malaria-Exposed Individuals
It is demonstrated that IgG from Plasmodium falciparum-exposed individuals can significantly inhibit the GPI-induced activation of macrophages in vitro, as shown by reduced levels of tumor necrosis factor production and attenuation of CD40 expression.
Immunoglobulin G (IgG) responses to Plasmodium falciparum glycosylphosphatidylinositols are short-lived and predominantly of the IgG3 subclass.
This study shows that immunoglobulin G (IgG)-subclass responses elicited by the proposed P. falciparum toxin glycosylphosphatidylinositol (GPI) in Papua New Guinean subjects 5-60 years old predominantly involve IgG(3), with a lesser contribution from IgG1 and an absence of IgG2 and IgG3.
Glycosylphosphatidylinositols in malaria pathogenesis and immunity: potential for therapeutic inhibition and vaccination.
GPIs are potentially amenable to specific therapeutic inhibition and vaccination; more needs to be known about their dual roles in malaria pathogenesis and protection for these strategies to succeed.
Age-dependent impairment of IgG responses to glycosylphosphatidylinositol with equal exposure to Plasmodium falciparum among Javanese migrants to Papua, Indonesia.
Host age, independent of cumulative exposure, apparently represents a key determinant of the quantitative and qualitative nature of the IgG response to P. falciparum GPI.
IgG antibodies to synthetic GPI are biomarkers of immune-status to both Plasmodium falciparum and Plasmodium vivax malaria in young children
This study highlights that in young children, IgG to PfGPI might be a useful marker of immune-status to both P. falciparum and P. vivax infections, and potentially useful to help malaria control programs to identify populations at-risk.
Serum antibody levels to glycosylphosphatidylinositols in specimens derived from matched Malian children with severe or uncomplicated Plasmodium falciparum malaria and healthy controls.
Higher levels of IgM and IgG antibodies to GPI in young children were associated with disease severity and were short-lived, compared with matched healthy controls.
Asymptomatic infection in individuals from the municipality of Barcelos (Brazilian Amazon) is not associated with the anti-Plasmodium falciparum glycosylphosphatidylinositol antibody response
The data suggest that the Ab response against P. falciparum GPI is not associated with P. Falconerum asymptomatic infection in individuals who have been chronically exposed to malaria in the Brazilian Amazon, but this Ab response could be related to ongoing parasitaemia in the Angolan patients.


Glycosylphosphatidylinositol anchors of Plasmodium falciparum: molecular characterization and naturally elicited antibody response that may provide immunity to malaria pathogenesis.
Absence of a persistent anti- GPI antibody response correlated with malaria-specific anemia and fever, suggesting that anti-GPI antibodies provide protection against clinical malaria.
Rationale for malaria anti-toxin therapy.
Plasmodium falciparum clinical malaria: lessons from longitudinal studies in Senegal.
The intensive and longitudinal collection of entomological, parasitological and clinical data from the Senegalese populations of Dielmo and Ndiop, exposed to a perennial and intense transmission, allows to respond to many questions about the relationships between transmission, infection, immunity, morbidity and mortality.
A theoretical framework for the immunoepidemiology of Plasmodium falciparum malaria
Using mathematical methods to structure epidemiological and immunological information, a coherent theoretical framework is provided for the dissection of the important components of naturally acquired immunity to malaria, which shows that the average duration of parasitaemia increases with age, as previously encountered strains endure for longer periods at a subclinical level.
Evidence for an age-dependent pyrogenic threshold of Plasmodium falciparum parasitemia in highly endemic populations.
Evidence is provided for an age-dependent threshold effect of parasitemia that allows parasite density to be used to distinguish malaria attacks from other causes of fever within an individual and should facilitate the accurate evaluation of the incidence of clinical malaria in highly endemic areas.
Neutralizing monoclonal antibodies to glycosylphosphatidylinositol, the dominant TNF-alpha-inducing toxin of Plasmodium falciparum: prospects for the immunotherapy of severe malaria.
A central role for glycosylphosphatidylinositol of parasite origin in the aetiology of severe malaria is suggested and novel approaches for the immunotherapy or immunoprophylaxis of disease are suggested.
Host-parasite interaction and morbidity in malaria endemic areas.
  • K. Marsh, R. Snow
  • Medicine
    Philosophical transactions of the Royal Society of London. Series B, Biological sciences
  • 1997
It is proposed that the different manifestations of severe malarial morbidity arise from the interaction of a limited number of pathogenic processes: red cell destruction, toxin-mediated activation of cytokine cascades, and infected cell sequestration in tissue microvascular beds.
Relationships between Plasmodium falciparum infection and morbidity in a highly endemic area.
The maximum prevalence of parasitaemia in the community was in children aged 5-9 years, and the maximum age-specific incidence of attributable cases at the outpatient clinic was 2 cases per annum in the 2- to 4-year-old age group.
Malaria exoantigens induce T-independent antibody that blocks their ability to induce TNF.
Findings imply that it will be necessary to confer on these antigens the ability to stimulate T cells and generate memory before they can provide a useful basis for an anti-disease vaccine, and that vaccination with these exoantigens might provide a means of protection against the clinical effects of malaria.
Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites
The GPI of Plasmodium is a potent glycolipid toxin that may be responsible for a novel pathogenic process, exerting pleiotropic effects on a variety of host cells by substituting for the endogenous GPI-based second messenger/signal transduction pathways.