Contribution of Functional Antimalarial Immunity to Measures of Parasite Clearance in Therapeutic Efficacy Studies of Artemisinin Derivatives.
Adolescent
Adult
Aged
Antibodies, Protozoan
/ blood
Antigens, Protozoan
/ immunology
Antimalarials
/ therapeutic use
Artesunate
/ therapeutic use
Child
Child, Preschool
Drug Resistance, Microbial
Erythrocytes
/ immunology
Female
Humans
Immunity, Innate
Immunoglobulin G
/ blood
Infant
Malaria, Falciparum
/ drug therapy
Male
Merozoites
/ immunology
Middle Aged
Parasitemia
/ drug therapy
Phagocytosis
/ immunology
Plasmodium falciparum
/ drug effects
Protozoan Proteins
/ immunology
Seroepidemiologic Studies
Treatment Outcome
Young Adult
Malaria
antibody
artemisinin
drug resistance
immunity
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
30 08 2019
30 08 2019
Historique:
received:
21
02
2019
accepted:
09
05
2019
pubmed:
11
5
2019
medline:
28
5
2020
entrez:
11
5
2019
Statut:
ppublish
Résumé
Antibodies to the blood stages of malaria parasites enhance parasite clearance and antimalarial efficacy. The antibody subclass and functions that contribute to parasite clearance during antimalarial treatment and their relationship to malaria transmission intensity have not been characterized. Levels of immunoglobulin G (IgG) subclasses and C1q fixation in response to Plasmodium falciparum merozoite antigens (erythrocyte-binding antigen [EBA] 175RIII-V, merozoite surface protein 2 [MSP-2], and MSP-142) and opsonic phagocytosis of merozoites were measured in a multinational trial assessing the efficacy of artesunate therapy across 11 Southeast Asian sites. Regression analyses assessed the effects of antibody seropositivity on the parasite clearance half-life (PC½), having a PC½ of ≥5 hours, and having parasitemia 3 days after treatment. IgG3, followed by IgG1, was the predominant IgG subclass detected (seroprevalence range, 5%-35% for IgG1 and 27%-41% for IgG3), varied across study sites, and was lowest in study sites with the lowest transmission intensity and slowest mean PC½. IgG3, C1q fixation, and opsonic-phagocytosis seropositivity were associated with a faster PC½ (range of the mean reduction in PC½, 0.47-1.16 hours; P range, .001-.03) and a reduced odds of having a PC½ of ≥5 hours and having parasitemia 3 days after treatment. The prevalence of IgG3, complement-fixing antibodies, and merozoite phagocytosis vary according to transmission intensity, are associated with faster parasite clearance, and may be sensitive surrogates of an augmented clearance capacity of infected erythrocytes. Determining the functional immune mechanisms associated with parasite clearance will improve characterization of artemisinin resistance.
Sections du résumé
BACKGROUND
Antibodies to the blood stages of malaria parasites enhance parasite clearance and antimalarial efficacy. The antibody subclass and functions that contribute to parasite clearance during antimalarial treatment and their relationship to malaria transmission intensity have not been characterized.
METHODS
Levels of immunoglobulin G (IgG) subclasses and C1q fixation in response to Plasmodium falciparum merozoite antigens (erythrocyte-binding antigen [EBA] 175RIII-V, merozoite surface protein 2 [MSP-2], and MSP-142) and opsonic phagocytosis of merozoites were measured in a multinational trial assessing the efficacy of artesunate therapy across 11 Southeast Asian sites. Regression analyses assessed the effects of antibody seropositivity on the parasite clearance half-life (PC½), having a PC½ of ≥5 hours, and having parasitemia 3 days after treatment.
RESULTS
IgG3, followed by IgG1, was the predominant IgG subclass detected (seroprevalence range, 5%-35% for IgG1 and 27%-41% for IgG3), varied across study sites, and was lowest in study sites with the lowest transmission intensity and slowest mean PC½. IgG3, C1q fixation, and opsonic-phagocytosis seropositivity were associated with a faster PC½ (range of the mean reduction in PC½, 0.47-1.16 hours; P range, .001-.03) and a reduced odds of having a PC½ of ≥5 hours and having parasitemia 3 days after treatment.
CONCLUSIONS
The prevalence of IgG3, complement-fixing antibodies, and merozoite phagocytosis vary according to transmission intensity, are associated with faster parasite clearance, and may be sensitive surrogates of an augmented clearance capacity of infected erythrocytes. Determining the functional immune mechanisms associated with parasite clearance will improve characterization of artemisinin resistance.
Identifiants
pubmed: 31075171
pii: 5487931
doi: 10.1093/infdis/jiz247
pmc: PMC6735958
doi:
Substances chimiques
Antibodies, Protozoan
0
Antigens, Protozoan
0
Antimalarials
0
Immunoglobulin G
0
Protozoan Proteins
0
Artesunate
60W3249T9M
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1178-1187Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
Infect Immun. 2006 Jan;74(1):257-64
pubmed: 16368979
Clin Microbiol Rev. 2009 Jan;22(1):13-36, Table of Contents
pubmed: 19136431
Infect Immun. 2009 Mar;77(3):1165-74
pubmed: 19139189
N Engl J Med. 2009 Jul 30;361(5):455-67
pubmed: 19641202
Scand J Immunol. 2009 Dec;70(6):553-64
pubmed: 19906198
J Infect Dis. 2010 Feb 15;201(4):570-9
pubmed: 20085495
Clin Infect Dis. 2010 Oct 15;51(8):e50-60
pubmed: 20843207
J Immunol. 2010 Nov 15;185(10):6157-67
pubmed: 20962255
Malar J. 2011 Sep 22;10:278
pubmed: 21939506
Malar J. 2011 Nov 10;10:339
pubmed: 22074219
Vaccine. 2012 Mar 2;30(11):1972-80
pubmed: 22248820
Antimicrob Agents Chemother. 2013 Feb;57(2):914-23
pubmed: 23208708
J Infect Dis. 2013 Jun 1;207(11):1655-63
pubmed: 23448727
Nature. 2014 Jan 2;505(7481):50-5
pubmed: 24352242
BMC Med. 2014 Jul 01;12:108
pubmed: 24980799
N Engl J Med. 2014 Jul 31;371(5):411-23
pubmed: 25075834
J Infect Dis. 2015 Jan 15;211(2):290-7
pubmed: 25183768
Acta Trop. 2015 Feb;142:47-56
pubmed: 25446174
Immunity. 2015 Mar 17;42(3):580-90
pubmed: 25786180
Clin Infect Dis. 2015 Oct 15;61(8):1244-52
pubmed: 26136391
BMC Med. 2015 Jul 07;13:154
pubmed: 26149666
Sci Rep. 2016 Feb 10;6:20859
pubmed: 26861682
Malar J. 2017 Feb 23;16(1):88
pubmed: 28231817
Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):3515-3520
pubmed: 28289193
Malar J. 2017 Apr 20;16(1):158
pubmed: 28427418
Malar J. 2018 Jan 08;17(1):14
pubmed: 29310662
J Infect Dis. 2018 Aug 14;218(6):956-965
pubmed: 29733355
J Infect Dis. 2019 Apr 16;219(9):1483-1489
pubmed: 30657916
Nat Commun. 2019 Feb 5;10(1):610
pubmed: 30723225
J Exp Med. 1995 Aug 1;182(2):409-18
pubmed: 7629503
Am J Trop Med Hyg. 1998 Apr;58(4):406-13
pubmed: 9574783