Impact of seasonal variations in Plasmodium falciparum malaria transmission on the surveillance of pfhrp2 gene deletions
- Imperial College London, United Kingdom
- World Health Organisation, Switzerland
- University of Kinshasa, Democratic Republic of the Congo
- University of North Carolina, United States
Abstract
Ten countries have reported pfhrp2/pfhrp3 gene deletions since the first observation of pfhrp2-deleted parasites in 2012. In a previous study (Watson et al., 2017) we characterised the drivers selecting for pfhrp2/3 deletions, and mapped the regions in Africa with the greatest selection pressure. In February 2018, the World Health Organization issued guidance on investigating suspected false-negative rapid diagnostic tests (RDTs) due to pfhrp2/3 deletions. However, no guidance is provided regarding the timing of investigations. Failure to consider seasonal variation could cause premature decisions to switch to alternative RDTs. In response, we have extended our methods and predict that the prevalence of false-negative RDTs due to pfhrp2/3 deletions is highest when sampling from younger individuals during the beginning of the rainy season. We conclude by producing a map of the regions impacted by seasonal fluctuations in pfhrp2/3 deletions and a database identifying optimum sampling intervals to support malaria control programmes.
Data availability
All data generated are provided within the online database, hosted through a shiny application at https://ojwatson.shinyapps.io/seasonal_hrp2/. The raw data for the application is available within the github repository at https://github.com/OJWatson/hrp2malaRia.
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PfPR2-10 in Africa 2000-2015Malaria Atlas Project, http://www. map.ox.ac.uk/.
Article and author information
Author details
Oliver John Watson
Funding
Wellcome (109312/Z/15/Z)
- Oliver John Watson
Medical Research Council (MR/N01507X/1)
- Robert Verity
Department for International Development
- Azra C Ghani
Medical Research Council
- Tini Garske
National Institute of Allergy and Infectious Diseases (R01AI132547)
- Steven R Meshnick
- Jonathan B Parr
American Society for Tropical Medicine and Hygiene-Burroughs Wellcome Fund
- Jonathan B Parr
Imperial College London
- Hannah C Slater
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Watson 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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Impact of seasonal variations in Plasmodium falciparum malaria transmission on the surveillance of pfhrp2 gene deletions
eLife 8:e40339.
https://doi.org/10.7554/eLife.40339
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Methods: Untargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children's milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥ 1. The interaction between significant metabolites and the child's age was tested.
Results: Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child's nutritional status, diet quality, and infant age. Cresol sulfate (β = -0.07; adjusted-p < 0.001), hippuric acid (β = -0.06; adjusted-p < 0.001), phenylacetylglutamine (β = -0.06; adjusted-p < 0.001), and trimethylamine-N-oxide (β = -0.05; adjusted-p = 0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged -1 SD: β = -0.05; p =0.01; +1 SD: β = 0.05; p =0.02) and methylhistidine (-1 SD: β = - 0.04; p =0.04; +1 SD: β = 0.04; p =0.03).
Conclusion: Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.
Funding: Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.
