Distinct surrogate markers for protection against Plasmodium falciparum infection and clinical malaria identified in a Senegalese community after radical drug cure.
Plasmodium falciparum expresses many antigens, which elicit various immune responses in exposed individuals, but no simple surrogate marker for protection has yet been developed. In this prospective survey, we looked for immune responses predictive of protection at various stages of progression from parasite inoculation to onset of disease. We studied 110 Senegalese volunteers from an area in which malaria is mesoendemic after they had received eradication therapy. We evaluated 4 protection-related outcomes (reappearance of parasitemia, duration of asymptomatic carriage, time to first clinical episode, and incidence of clinical episodes) in terms of levels of immunoglobulin G (IgG) against 3 crude parasite extracts and 5 conserved antigens during a 5-month period. Kaplan-Meier estimates and age-adjusted regression models showed these 4 outcomes to be associated with different patterns of IgG response to PfEMP3-cl5 (derived from P. falciparum erythrocyte membrane protein 3), PfEB200, MSP-1(19) (derived from merozoite surface protein-1), [NANP]10, infected red blood cell membrane, and merozoite and schizont extracts. It should, therefore, be possible to develop surrogate markers for each end point on the basis of IgG response to a limited number of conserved antigens.
Perraut
Ronald
R
Unité d'Immunologie, Institut Pasteur de Dakar, Senegal. perraut@pasteur.sn
Marrama
Laurence
L
Diouf
Babacar
B
Fontenille
Didier
D
Tall
Adama
A
Sokhna
Cheikh
C
Trape
Jean-François
JF
Garraud
Olivier
O
Mercereau-Puijalon
Odile
O
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002353:Carrier State / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D015994:Incidence; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology / Q000302:isolation & purification*; D015800:Protozoan Proteins / Q000276:immunology; D012424:Rural Population; D012675:Senegal / Q000453:epidemiology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015415:Biomarkers; C411566:EMP3 protein, Plasmodium falciparum; D007074:Immunoglobulin G; D008565:Membrane Proteins; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; C089133:merozoite surface protein 3, Plasmodium