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J Infect Dis. 2019 May 10. pii: jiz247. doi: 10.1093/infdis/jiz247. [Epub ahead of print]

The contribution of functional antimalarial immunity to measures of parasite clearance in therapeutic efficacy studies of artemisinin derivatives.

Author information

1
Burnet Institute, Melbourne, Australia.
2
Centre for Epidemiology and Biostatistics, Melbourne, School of Population and Global Health, The University of Melbourne, Melbourne Australia.
3
Department of Immunology, Monash University, Melbourne Australia.
4
Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.
5
Centre for Tropical Medicine and Global Health, University of Oxford, United Kingdom.
6
Department of Medicine, The University of Melbourne, Melbourne Australia.
7
Worldwide Antimalarial Resistance Network, Centre for Tropical Medicine and Global Health, University of Oxford, United Kingdom.
8
Howard Hughes Medical Institute, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD.
9
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD.
10
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
11
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
12
Department of Medical Research, Lower Myanmar, Yangon, Myanmar.
13
Lao-Oxford-Mahosot Hospital-Wellcome Trust-Research Unit, Mahosot Hospital, Vientiane, Lao PDR.
14
Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Lao PDR.
15
Malaria Research Group & Dev Care Foundation, Chittagong, Bangladesh.
16
Department of Microbiology and Central Clinical School, Monash University, Melbourne Australia.
17
Shoklo Malaria Research Unit, Mae Sot, Thailand.
18
Department of Infectious Diseases and Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia.

Abstract

BACKGROUND:

Antibodies to the blood-stages of malaria enhance parasite-clearance and antimalarial efficacy. The antibody subclass and functions that contribute to parasite-clearance during anti-malarial treatment and their relationship with malaria transmission intensity have not been characterised.

METHODS:

IgG subclasses and C1q-fixation in response to P. falciparum merozoite antigens (EBA-175RIII-V, MSP-2 and MSP-142), and opsonic-phagocytosis of merozoites were measured in a multinational trial assessing the efficacy of artesunate across 11 South-East Asian sites. Regression analyses assessed the effects of antibody seropositivity on parasite-clearance half-life (hours)(PC½), PC½≥5 hours, and day-3 parasitemia.

RESULTS:

IgG3, followed by IgG1, was the predominant IgG subclass detected (seroprevalence range IgG1: 5%-35% and IgG3: 27%-41%), 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 faster PC½ (mean reduction in PC½ range 0.47-1.16 (hours), p-range: 0.001-0.03) and reduced odds of PC½≥5 hours and day-3 parasitemia.

CONCLUSIONS:

Prevalence of IgG3, complement-fixing antibodies and merozoite phagocytosis vary according to transmission intensity, are associated with faster parasite-clearance and may be a sensitive surrogate of augmented clearance capacity of infected-erythrocytes. Determining the functional immune mechanisms associated with parasite-clearance will improve characterisation of artemisinin resistance.

KEYWORDS:

Malaria; antibody; artemisinin; drug resistance; immunity

PMID:
31075171
DOI:
10.1093/infdis/jiz247

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