The origins and relatedness structure of mixed infections vary with local prevalence of P. falciparum malaria
- University of Oxford, United Kingdom
Abstract
Individual malaria infections can carry multiple strains of Plasmodium falciparum with varying levels of relatedness. Yet, how local epidemiology affects the properties of such mixed infections remains unclear. Here, we develop an enhanced method for strain deconvolution from genome sequencing data, which estimates the number of strains, their proportions, identity-by-descent (IBD) profiles and individual haplotypes. Applying it to the Pf3k data set, we find that the rate of mixed infection varies from 29% to 63% across countries and that 51% of mixed infections involve more than two strains. Furthermore, we estimate that 47% of symptomatic dual infections contain sibling strains likely to have been co-transmitted from a single mosquito, and find evidence of mixed infections propagated over successive infection cycles. Finally, leveraging data from the Malaria Atlas Project, we find that prevalence correlates within Africa, but not Asia, with both the rate of mixed infection and the level of IBD.
Data availability
Metadata on samples is available from ftp://ngs.sanger.ac.uk/production/pf3k/release_5/pf3k_release_5_metadata_20170804.txt.gz. Sequence data (aligned to Plasmodium falciparum strain 3D7 v3.1 reference genome sequences, for details see ftp://ftp.sanger.ac.uk/pub/project/pathogens/gff3/2015-08/Pfalciparum.genome.fasta.gz) is available from ftp://ngs.sanger.ac.uk/production/pf3k/release_5/5.1/. Diagnostic plots for the deconvolution of all samples can be found at https://github.com/mcveanlab/mixedIBD-Supplement and deconvolved haplotypes can be accessed at ftp://ngs.sanger.ac.uk/production/pf3k/technical_working/release_5/mixedIBD_paper_haplotypes/. Code implementing the algorithms described in this paper, DEploidIBD, is available at https://github.com/mcveanlab/DEploid.
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The Pf3k Project (2016): pilot data release 5Wellcome Trust Sanger public ftp site, 5.1 Data.
Article and author information
Author details
Richard D. Pearson
Funding
Wellcome (206194)
- Jacob Almagro-Garcia
Wellcome (090770)
- Jacob Almagro-Garcia
- Richard D. Pearson
- Roberto Amato
- Alistair Miles
- Dominic Kwiatkowski
Wellcome (100956/Z/13/Z)
- Sha Joe Zhu
- Gil McVean
Li Ka Shing Foundation (NA)
- Gil McVean
Wellcome (204911)
- Jacob Almagro-Garcia
- Richard D. Pearson
- Roberto Amato
- Alistair Miles
- Dominic Kwiatkowski
Medical Research Council (G0600718)
- Jacob Almagro-Garcia
- Richard D. Pearson
- Roberto Amato
- Alistair Miles
- Dominic Kwiatkowski
Department for International Development (M006212)
- Jacob Almagro-Garcia
- Richard D. Pearson
- Roberto Amato
- Alistair Miles
- Dominic Kwiatkowski
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Eduardo Franco, McGill University, Canada
Version history
- Received: August 9, 2018
- Accepted: July 10, 2019
- Accepted Manuscript published: July 12, 2019 (version 1)
- Version of Record published: August 6, 2019 (version 2)
Copyright
© 2019, Zhu 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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The origins and relatedness structure of mixed infections vary with local prevalence of P. falciparum malaria
eLife 8:e40845.
https://doi.org/10.7554/eLife.40845
Further reading
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- Epidemiology and Global Health
Paxlovid, a SARS-CoV-2 antiviral, not only prevents severe illness but also curtails viral shedding, lowering transmission risks from treated patients. By fitting a mathematical model of within-host Omicron viral dynamics to electronic health records data from 208 hospitalized patients in Hong Kong, we estimate that Paxlovid can inhibit over 90% of viral replication. However, its effectiveness critically depends on the timing of treatment. If treatment is initiated three days after symptoms first appear, we estimate a 17% chance of a post-treatment viral rebound and a 12% (95% CI: 0%-16%) reduction in overall infectiousness for non-rebound cases. Earlier treatment significantly elevates the risk of rebound without further reducing infectiousness, whereas starting beyond five days reduces its efficacy in curbing peak viral shedding. Among the 104 patients who received Paxlovid, 62% began treatment within an optimal three-to-five-day day window after symptoms appeared. Our findings indicate that broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-Cov-2.
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- Epidemiology and Global Health
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.
