The complex relationship of exposure to new Plasmodium infections and incidence of clinical malaria in Papua New Guinea
- Swiss Tropical and Public Health Institute, Switzerland
- Walter and Eliza Hall Institute of Medical Research, Australia
- Papua New Guinea Institute of Medical Research, Papua New Guinea
Abstract
The molecular force of blood-stage infection (molFOB) is a quantitative surrogate metric for malaria transmission at population level and for exposure at individual level. Relationships between molFOB, parasite prevalence and clinical incidence were assessed in a treatment-to-reinfection cohort, where P.vivax (Pv) hypnozoites were eliminated in half the children by primaquine (PQ). Discounting relapses, children acquired equal numbers of new P. falciparum (Pf) and Pv blood-stage infections/year (Pf-molFOB=0-18, Pv-molFOB=0-23) resulting in comparable spatial and temporal patterns in incidence and prevalence of infections. Including relapses, Pv-molFOB increased >3-fold (relative to PQ-treated children) showing greater heterogeneity at individual (Pv-molFOB=0-36) and village levels. Pf- and Pv-molFOB were strongly associated with clinical episode risk. Yearly Pf clinical incidence rate (IR=0.28) was higher than for Pv (IR=0.12) despite lower Pf-molFOB. These relationships between molFOB, clinical incidence and parasite prevalence reveal a comparable decline in Pf and Pv transmission that is normally hidden by the high burden of Pv relapses.
Data availability
-
Data from: The complex relationship of exposure to new Plasmodium infections and incidence of clinical malaria in Papua New GuineaAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
Funding
Swiss National Science Foundation (310030-134889 310030-159580)
- Ingrid Felger
- Ivo Mueller
National Institute of Allergy and Infectious Diseases (South West Pacific International Centers of Excellence in malaria research U19 AI089686)
- Inoni Betuela
- Ingrid Felger
- Leanne J Robinson
- Ivo Mueller
Bill and Melinda Gates Foundation
- Inoni Betuela
- Ingrid Felger
- Leanne J Robinson
- Ivo Mueller
National Health and Medical Research Council (Project Grant #1021544)
- Inoni Betuela
- Ingrid Felger
- Leanne J Robinson
- Ivo Mueller
Cellex Foundation
- Inoni Betuela
- Ivo Mueller
National Health and Medical Research Council (Early Career Fellowship #1016443)
- Leanne J Robinson
National Health and Medical Research Council (Early Career Fellowship #1052760)
- Stephan Karl
National Health and Medical Research Council (Senior Research Fellowship #1043345)
- Ivo Mueller
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 received ethical clearance from the PNG IMR Institutional Review Board (0908), the PNG Medical Advisory Committee (09.11), the Ethics Committee of Basel 237/11 and was conducted in full concordance with the Declaration of Helsinki. Written informed consent was obtained from the parents/guardians of all children enrolled in the study.
Version history
- Received: December 7, 2016
- Accepted: August 18, 2017
- Accepted Manuscript published: September 1, 2017 (version 1)
- Version of Record published: September 20, 2017 (version 2)
Copyright
© 2017, Hofmann 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.
Metrics
-
- 1,437
- views
-
- 266
- downloads
-
- 22
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
The complex relationship of exposure to new Plasmodium infections and incidence of clinical malaria in Papua New Guinea
eLife 6:e23708.
https://doi.org/10.7554/eLife.23708
Further reading
-
- 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.
-
- Ecology
- Epidemiology and Global Health
Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.
