The role of complement immune response on artemisinin-based combination therapy in a population from malaria endemic region of Western Kenya.
Adaptive Immunity
Adolescent
Adult
Antimalarials
/ therapeutic use
Artemisinins
/ therapeutic use
Child
Child, Preschool
Complement Activation
Drug Combinations
Female
Humans
Infant
Infant, Newborn
Kenya
Malaria, Falciparum
/ immunology
Male
Middle Aged
Plasmodium falciparum
/ drug effects
Young Adult
Artemisinin combination therapy
Complement
Malaria antibody
Malaria holoendemic areas
Malaria immunity
Western Kenya
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
29 Apr 2020
29 Apr 2020
Historique:
received:
09
12
2019
accepted:
18
04
2020
entrez:
1
5
2020
pubmed:
1
5
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Naturally acquired immunity (NAI), which is characterized by protection against overt clinical disease and high parasitaemia, is acquired with age and transmission intensity. The role of NAI on the efficacy of anti-malarial drugs, including artemisinin-based combinations used as the first-line treatment for uncomplicated Plasmodium falciparum, has not been fully demonstrated. This study investigated the role of NAI in response to artemisinin-based combination therapy (ACT), in symptomatic patients living in western Kenya, a high malaria transmission area. Sera samples from malaria immune participants (n = 105) in a therapeutic efficacy study were assessed for in vitro growth inhibitory activity against the 3D7 strain of P. falciparum using a fluorescent-based growth inhibition assay (GIA). Participants' age and parasite clearance parameters were used in the analysis. Pooled sera from malaria naïve participants (n = 6) with no Plasmodium infection from malaria non-endemic regions of Kenya was used as negative control. The key observations of the study were as follows: (1) Sera with intact complement displayed higher GIA activity at lower (1%) serum dilutions (p < 0.0001); (2) there was significant relationship between GIA activity, parasite clearance rate (p = 0.05) and slope half-life (p = 0.025); and (3) age was a confounding factor when comparing the GIA activity with parasite clearance kinetics. This study demonstrates for the first time there is synergy of complement, pre-existing immunity, and drug treatment in younger patients with symptomatic malaria in a high-transmission area.
Sections du résumé
BACKGROUND
BACKGROUND
Naturally acquired immunity (NAI), which is characterized by protection against overt clinical disease and high parasitaemia, is acquired with age and transmission intensity. The role of NAI on the efficacy of anti-malarial drugs, including artemisinin-based combinations used as the first-line treatment for uncomplicated Plasmodium falciparum, has not been fully demonstrated. This study investigated the role of NAI in response to artemisinin-based combination therapy (ACT), in symptomatic patients living in western Kenya, a high malaria transmission area.
METHODS
METHODS
Sera samples from malaria immune participants (n = 105) in a therapeutic efficacy study were assessed for in vitro growth inhibitory activity against the 3D7 strain of P. falciparum using a fluorescent-based growth inhibition assay (GIA). Participants' age and parasite clearance parameters were used in the analysis. Pooled sera from malaria naïve participants (n = 6) with no Plasmodium infection from malaria non-endemic regions of Kenya was used as negative control.
RESULTS
RESULTS
The key observations of the study were as follows: (1) Sera with intact complement displayed higher GIA activity at lower (1%) serum dilutions (p < 0.0001); (2) there was significant relationship between GIA activity, parasite clearance rate (p = 0.05) and slope half-life (p = 0.025); and (3) age was a confounding factor when comparing the GIA activity with parasite clearance kinetics.
CONCLUSION
CONCLUSIONS
This study demonstrates for the first time there is synergy of complement, pre-existing immunity, and drug treatment in younger patients with symptomatic malaria in a high-transmission area.
Identifiants
pubmed: 32349765
doi: 10.1186/s12936-020-03242-4
pii: 10.1186/s12936-020-03242-4
pmc: PMC7191791
doi:
Substances chimiques
Antimalarials
0
Artemisinins
0
Drug Combinations
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
168Subventions
Organisme : consortium for national health research
ID : RCDG-2012-032
Organisme : Armed Forces Health Surveillance Center - Department of Defense Global Emerging Infections System
ID : P0209_15_KY
Références
J Infect Dis. 2019 May 24;219(12):1969-1979
pubmed: 30649381
J Infect Dis. 2017 Oct 17;216(7):887-898
pubmed: 28973483
Trends Parasitol. 2008 Dec;24(12):578-84
pubmed: 18848497
PLoS One. 2008;3(10):e3557
pubmed: 18958285
PLoS One. 2016 Sep 09;11(9):e0162524
pubmed: 27611315
J Vector Borne Dis. 2013 Apr-Jun;50(2):85-92
pubmed: 23995309
Malar J. 2011 Nov 10;10:339
pubmed: 22074219
Antimicrob Agents Chemother. 2016 Mar 25;60(4):2417-24
pubmed: 26856829
Infect Immun. 2001 May;69(5):3286-94
pubmed: 11292751
Infect Immun. 2010 Feb;78(2):737-45
pubmed: 19917712
Science. 1976 Aug 20;193(4254):673-5
pubmed: 781840
Immunity. 2015 Mar 17;42(3):580-90
pubmed: 25786180
Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):3515-3520
pubmed: 28289193
PLoS One. 2008;3(10):e3571
pubmed: 18958278
Am J Trop Med Hyg. 2003 Nov;69(5):558-63
pubmed: 14695097
Infect Immun. 2008 May;76(5):2240-8
pubmed: 18316390
Antimicrob Agents Chemother. 2007 Jun;51(6):1926-33
pubmed: 17371812
Parasitology. 2016 Feb;143(2):139-53
pubmed: 26741253
Clin Microbiol Rev. 2009 Jan;22(1):13-36, Table of Contents
pubmed: 19136431
J Clin Invest. 2008 Jan;118(1):342-51
pubmed: 18064303
Parasite Immunol. 2006 Jan-Feb;28(1-2):51-60
pubmed: 16438676
Infect Immun. 2009 Oct;77(10):4510-7
pubmed: 19620342