Declining malaria transmission differentially impacts on the maintenance of humoral immunity to Plasmodium falciparum in children
File(s)Mugyenyi et al JID in press.pdf (4.85 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
BACKGROUND
We investigated the poorly understood impact of declining malaria transmission on maintenance of antibodies to P. falciparum merozoite antigens and infected erythrocytes (IEs), including functional immunity.
METHODS
In a 3-year longitudinal cohort of 300 Kenyan children, antibodies to different merozoite AMA1 and MSP2 alleles, IE surface antigens, and antibody functional activities were quantified.
RESULTS
Over a period in which malaria transmission declined markedly, AMA1 and MSP2 antibodies decreased substantially; estimated half-lives of antibody duration were 0.8 and 1-3 years, respectively. However, 69-74% of children maintained their sero-positivity to AMA1 alleles and 42-52% to MSP2 alleles. Levels and prevalence of anti-merozoite antibodies were consistently associated with increasing age and concurrent parasitaemia. Antibodies promoting opsonic phagocytosis of merozoites declined rapidly (half-life 0.15 years). In contrast, complement-fixing antibodies to merozoites did not decline and antibodies to IE surface antigens expressing virulent phenotypes were much better maintained (half-life 4-10 years).
CONCLUSIONS
A decline in malaria transmission is associated with reduction in naturally-acquired immunity. However, loss of immunity is not universal; some key functional responses and antibodies to IEs were better maintained and these may continue to provide some protection. Findings have implications for malaria surveillance and control measures and informing vaccine development.
We investigated the poorly understood impact of declining malaria transmission on maintenance of antibodies to P. falciparum merozoite antigens and infected erythrocytes (IEs), including functional immunity.
METHODS
In a 3-year longitudinal cohort of 300 Kenyan children, antibodies to different merozoite AMA1 and MSP2 alleles, IE surface antigens, and antibody functional activities were quantified.
RESULTS
Over a period in which malaria transmission declined markedly, AMA1 and MSP2 antibodies decreased substantially; estimated half-lives of antibody duration were 0.8 and 1-3 years, respectively. However, 69-74% of children maintained their sero-positivity to AMA1 alleles and 42-52% to MSP2 alleles. Levels and prevalence of anti-merozoite antibodies were consistently associated with increasing age and concurrent parasitaemia. Antibodies promoting opsonic phagocytosis of merozoites declined rapidly (half-life 0.15 years). In contrast, complement-fixing antibodies to merozoites did not decline and antibodies to IE surface antigens expressing virulent phenotypes were much better maintained (half-life 4-10 years).
CONCLUSIONS
A decline in malaria transmission is associated with reduction in naturally-acquired immunity. However, loss of immunity is not universal; some key functional responses and antibodies to IEs were better maintained and these may continue to provide some protection. Findings have implications for malaria surveillance and control measures and informing vaccine development.
Date Issued
2017-08-02
Date Acceptance
2017-07-26
Citation
Journal of Infectious Diseases, 2017, 216 (7), pp.887-898
ISSN
0022-1899
Publisher
Oxford University Press (OUP)
Start Page
887
End Page
898
Journal / Book Title
Journal of Infectious Diseases
Volume
216
Issue
7
Copyright Statement
This is a pre-copyedited, author-produced PDF of an article accepted for publication in Journal of Infectious Diseases following peer review. The version of record Cleopatra K Mugyenyi, Salenna R Elliott, Xi Zen Yap, Gaoqian Feng, Philippe Boeuf, Gregory Fegan, Faith F H Osier, Freya J I Fowkes, Marion Avril, Thomas N Williams, Kevin Marsh, James G Beeson; Declining malaria transmission differentially impacts on the maintenance of humoral immunity to Plasmodium falciparum in children, The Journal of Infectious Diseases, , jix370, https://doi.org/10.1093/infdis/jix370 is available online at: https://dx.doi.org/10.1093/infdis/jix370
Sponsor
Wellcome Trust
Wellcome Trust
Grant Number
091758/B/10/Z
C163
Subjects
11 Medical And Health Sciences
06 Biological Sciences
Microbiology
Publication Status
Published online