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
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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.
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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
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of SARS-CoV-2.
Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than six months earlier, spike levels fell notably and continuously for the nine months post-vaccination. By contrast, among adults infected within six months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than six months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% CI 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the COVID-19 weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected dried blood spots are a practicable biological surveillance platform.
Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
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- Computational and Systems Biology
- Epidemiology and Global Health
The chemical composition of foods is complex, variable, and dependent on many factors. This has a major impact on nutrition research as it foundationally affects our ability to adequately assess the actual intake of nutrients and other compounds. In spite of this, accurate data on nutrient intake are key for investigating the associations and causal relationships between intake, health, and disease risk at the service of developing evidence-based dietary guidance that enables improvements in population health. Here, we exemplify the importance of this challenge by investigating the impact of food content variability on nutrition research using three bioactives as model: flavan-3-ols, (–)-epicatechin, and nitrate. Our results show that common approaches aimed at addressing the high compositional variability of even the same foods impede the accurate assessment of nutrient intake generally. This suggests that the results of many nutrition studies using food composition data are potentially unreliable and carry greater limitations than commonly appreciated, consequently resulting in dietary recommendations with significant limitations and unreliable impact on public health. Thus, current challenges related to nutrient intake assessments need to be addressed and mitigated by the development of improved dietary assessment methods involving the use of nutritional biomarkers.
