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
glycosylphosphatidylinositol (GPI) toxin have been viewed as likely mediators of such tolerance. In this study, the relationship between
antibodies to P. falciparum GPIs, age, and
parasitemia was determined in asymptomatic children and adults living in Madang, Papua New Guinea. The prevalence and intensity of antibody responses increased with age and were lowest in children 1 to 4 years old with the highest-density
parasitemias. In children of this age group who were tolerant of
parasitemia during the study, only 8.3% had detectable
immunoglobulin G (
IgG) and none had
IgM antibodies to GPI. This suggests that anti-GPI
antibodies are unlikely to be the sole mediator of malarial tolerance, especially in children younger than 5 years. Following
antimalarial treatment, clearance of
parasitemia led to a fall in anti-GPI
IgG response in children and adolescents within 6 weeks. As anti-GPI
antibodies potentially play a role in protecting against
disease progression, our results caution against the treatment of asymptomatic
parasitemia and suggest that generation of a sustained antibody response in children poses a challenge to novel antitoxic vaccination strategies.