Artemisinin Molecular Surveyor

The discovery of molecular markers of resistance in the Kelch 13 gene gives us the unusual opportunity to monitor the emergence and spread of resistance nearly in real time. Assessing the prevalence of these molecular markers in other regions can provide an early warning system to trigger rapid responses to develop control strategies.

The Artemisinin Molecular Surveyor is an interactive map that summarises the prevalence of these molecular markers in the propeller region of the Kelch 13 gene of the malaria parasite by location and year, providing a clear and standardised visualisation of the evidence to date to inform key international, regional and national monitoring strategies.

The Artemisinin Molecular Surveyor

• Displays the distribution of resistance markers found on the Plasmodium falciparum malaria parasite Kelch 13 gene according to WHO classification of the markers;
  1. WHO Validated markers
  2. WHO candidate or associated markers
  3. Other markers (mutations that are neither validated nor candidate)
• Displays data from 321 published studies, covering sites in 77 countries
• Samples tested in these publications were collected between 1980 and 2023
• Presents molecular analyses of K13 genotypes,
• Flexible default settings can be altered easily by the user,
• Can be filtered by continent,country,year of sample collection and sample size of samples tested

Methodology

The data included were either shared directly with WWARN or extracted from publications and stored in a standardised secure database.

All non-synonymous mutations at any K13 locus >440 (i.e. within the propeller region) are captured along with a date of sample collection and geospatial information. In some studies, a non- synonymous mutation in locus 252, outside the propeller domain, was captured. Any samples collected after treatment with an antimalarial are not included.

The mutations are displayed according to the WHO classification;

Validated PfK13 markers of artemisinin partial resistance

1. A statistically significant association (p <0.05) between a PfK13 mutation and clearance half-life >5 hours or day 3 parasitaemia via a chi-squared test or appropriate multivariable regression model on a sample of at least 20 clinical cases
   AND
2. Survival of >1% using the RSA^0–3h in at least five individual isolates with a given mutation or a statistically significant difference (p <0.05) in the RSA^0–3h assay between culture-adapted recombinant isogenic parasite lines, produced using transfection and gene editing techniques, which express a variant allele of PfK13 as compared with the wild-type allele

Candidate or associated PfK13 markers of artemisinin partial resistance

1. A statistically significant association (p <0.05) between a PfK13 mutation and clearance half-life >5 hours or day 3 parasitaemia via a chi-squared test or appropriate multivariable regression model on a sample of at least 20 clinical cases
   OR
2. Survival of >1% using the RSA^0–3h in at least five individual isolates with a given mutation or a statistically significant difference (p <0.05) in the RSA^0–3h assay between culture-adapted recombinant isogenic parasite lines, produced using transfection and gene editing techniques, which express a variant allele of PfK13 as compared with the wild-type allele

The pins are coloured according to the prevalence of mutations associated with slow clearance:

• A site where prevalence of all validated markers or candidate/associated markers is 0% ( all mutations are neither validated nor candidate/asociated markers or all are wildtype) is coloured green.
• A site where prevalence of any validated marker or candidate/associated marker is  >0 - <5% is coloured yellow.
• A site where prevalence of any validated marker or candidate/associated marker is ≥5% - <10% is coloured amber.
• A site where prevalence of any validated marker or candidate/associated marker is ≥10% is coloured red.

To simplify the visualisation, all data within the database at the same location (even if they are from different studies) are pooled for each year.

Each pin can be clicked to produce a pop-up which presents four tabs:

1. Site details-Provide more information on the site where samples were collected.
2. K13 mutations table-Provide details of the mutations tested,number of samples tested,number of samples found with particular mutations and years of sample collection.
3. K13 Graph- Charts number of samples tested and those found with mutations.
4. Publication- Provides Title of the publication ,PubMed ID and authors

When the exact site of sample origin is not available, the pin points to the capital of the country of origin.

This is a fast-evolving field of research and therefore the rules and filters will be adapted to reflect new information as it is received.

We welcome your questions and suggestions, please email WWARN at wwarn@wwarn.org

Part of this data has been collected from the WHO Malaria Threats Maps. You have the royalty-free, worldwide, non-exclusive right to use, reproduce, extract, download, copy, distribute, display or include the Datasets and data contained therein in other products for public health purposes. 

To find out more information about the tool or how to contribute data please email wwarn@wwarn.org

To learn more or optimise your tools for reporting artemisinin drug resistance, view our kelch markers toolkit for minimal criteria in reporting Plasmodium falciparum kelch13 (pfkelch13) markers.

Citation

Infectious Diseases Data Observatory (IDDO) (2015): Artemisinin Molecular Surveyor. Infectious Diseases Data Observatory. (InteractiveResource). https://www.iddo.org/wwarn/tracking-resistance/artemisinin-molecular-surveyor

References:

World Health Organisation Status report on artemisinin resistance and ACT efficacy (August 2019)

WWARN K13 Genotype-Phenotype Study Group. Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin- based treatments-a WWARN individual patient data meta-analysis. BMC Med. 2019 Jan 17;17(1):1..