Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure
- University of California, San Francisco, United States
- Infectious Diseases Research Collaboration, Uganda
- Stanford University, United States
- Makerere University College of Health Sciences, Uganda
- Infectious Diseases Resarch Collaboration, Uganda
- London School of Hygiene and Tropical Medicine, United Kingdom
- University of Washington, United States
Abstract
Fundamental gaps remain in our understanding of how immunity to malaria develops. We used detailed clinical and entomological data from parallel cohort studies conducted across the malaria transmission spectrum in Uganda to quantify the development of immunity against symptomatic P. falciparum as a function of age and transmission intensity. We focus on: anti-parasite immunity (i.e; ability to control parasite densities) and anti-disease immunity (i.e; ability to tolerate higher parasite densities without fever). Our findings suggest a strong effect of age on both types of immunity, not explained by cumulative-exposure. They also show an independent effect of exposure, where children living in moderate/high transmission settings develop immunity faster as transmission increases. Surprisingly, children in the lowest transmission setting appear to develop immunity more efficiently than those living in moderate transmission settings. Anti-parasite and anti-disease immunity develop in parallel, reducing the probability of experiencing symptomatic malaria upon each subsequent P. falciparum infection.
Data availability
All the data used for these analyses as well as the R code used to reproduce the main study findings are available at https://github.com/isabelrodbar/immunity. Complete data from the 3 cohort studies are available at the CliEpiDB website (https://clinepidb.org/ce/app/record/dataset/DS_0ad509829e).
Article and author information
Author details
Isabel Rodriguez-Barraquer
Prasanna Jagannathan
Funding
National Institutes of Health (2U19AI089674)
- Isabel Rodriguez-Barraquer
- Emmanuel Arinaitwe
- Prasanna Jagannathan
- Moses R Kamya
- Phillip J Rosenthal
- John Rek
- Grant Dorsey
- Joaniter Nankabirwa
- Sarah G Staedke
- Maxwell Kilama
- Chris Drakeley
- Isaac Ssewanyana
- David L Smith
- Bryan Greenhouse
Bill and Melinda Gates Foundation (OPP1110495)
- David L Smith
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ben Cooper, Mahidol Oxford Tropical Medicine Research Unit, Thailand
Ethics
Human subjects: The study protocol was reviewed and approved by the Makerere University School of Medicine Research and Ethics Committee (Identification numbers 2011-149 and 2011-167, the Uganda National Council for Science and Technology, , the London School of Hygiene and Tropical Medicine Ethics Committee (Identification numbers 5943 and 5944), the Durham University School of Biological and Biomedical Sciences Ethics Committee (PRISM Entomology Uganda), and the University of California, San Francisco, Committee on Human Research (Identification numbers 11-05539 and 11-05995) and the Uganda National Council for Science and Technology (Identification numbers HS350 and HS-1019).. All parents/guardians were asked to provide written informed consent at the time of enrollment.
Version history
- Received: February 10, 2018
- Accepted: July 15, 2018
- Accepted Manuscript published: July 25, 2018 (version 1)
- Version of Record published: August 21, 2018 (version 2)
Copyright
© 2018, Rodriguez-Barraquer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure
eLife 7:e35832.
https://doi.org/10.7554/eLife.35832
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Background:
Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.
Methods:
We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.
Results:
Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.
Conclusions:
Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.
Funding:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
