title: Investigation of the kinetics of histidine-rich protein 2 and of the antibody responses to this antigen, in a group of malaria patients from India.
abstract: Although immunological tests based on the detection of histidine-rich protein 2 (HRP2) from the parasites permit the rapid diagnosis of Plasmodium falciparum malaria, such tests are not yet sufficiently sensitive to detect every bloodsmear-positive case. Some individuals infected with P. falciparum may appear test-negative because of the presence of anti-HRP2 antibodies in their sera. A longitudinal follow-up of HRP2 antigenaemia and antibody responses to this antigen has now been conducted in a group of 45, bloodsmear-positive malaria cases of various ages, both during acute infection with P. falciparum and after antimalarial treatment. Pre-treatment, 'day-0' samples of fingerprick blood were tested for HRP2 (in antigen-capture ELISA) and for antigen-specific IgM and IgG (in indirect ELISA). The patients were then treated, with standard doses of chloroquine, before being retested, for HRP2 and anti-HRP2 antibodies, on days 7, 15 and 28. The level of antigenaemia, which on day 0 was found to be positively correlated with parasitaemia (r = 0.741; P < 0.001), had only fallen by an insignificant amount by day 7 but showed further, significant falls between days 7 and 15 (P < 0.001) and between days 15 and 28 (P < 0.01). Although no significant relationship was observed between the blood concentrations of HRP2 and anti-HRP2 IgM or IgG on days 0 or 7, the level of HRP2 antigenaemia was found to be positively correlated with the concurrent titre of anti-HRP2 IgM on day 15 (r = 0.612; P < 0.001) and day 28 (r = 0.501; P < 0.001). The titres of HRP2-specific IgG gradually increased over the 28 days of follow-up but were not found to be significantly correlated with the decreasing levels of HRP2 antigenaemia. When the 45 day-0 samples of blood were tested for HRP2 in a rapid diagnostic test (RDT), three appeared negative, probably because of interference from the circulating, free, anti-HRP2 antibodies in the plasma. The three RDT-negative samples were significantly different from the 42 RDT-positive, having relatively low HRP2 antigenaemias (P < 0.001) and relatively high titres of anti-HRP2 IgM (P < 0.05) and IgG (P < 0.001). Control samples of blood, from four patients infected with P. vivax and five healthy, normal individuals, were considered ELISA-negative for HRP2 and anti-HRP2 IgM or IgG. It appears that, during human infection with P. falciparum, serum levels of HRP2 antigen remain elevated for at least 7 days post-treatment, despite the host's development of antigen-specific immune responses both before and after treatment.
authors.affiliation: Malaria Research Centre (ICMR), Delhi, India. suklabiswas@yahoo.com
authors.forename: S
authors.initials: S
authors.lastname: Biswas
authors.forename: D
authors.initials: D
authors.lastname: Tomar
authors.forename: D N
authors.initials: DN
authors.lastname: Rao
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D000953:Antigens, Protozoan / Q000097:blood / Q000276:immunology*; D000962:Antimalarials / Q000627:therapeutic use; D001798:Blood Proteins / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007194:India / Q000453:epidemiology; D007223:Infant; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology*; D018512:Parasitemia / Q000453:epidemiology / Q000276:immunology; D010966:Plasmodium vivax / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D000962:Antimalarials; D001798:Blood Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C484005:histidine-rich alpha2 glycoprotein, human