This page provides information about data generated during the first phase of the GenRe-Mekong project, and about the SPOTmalaria platform used to process samples collected by the project.
Background
GenRe-Mekong is a genetic surveillance project conceived to provide public health experts in the Greater Mekong Subregion (GMS) and neighboring countries with timely and actionable knowledge, to support their decision-making in malaria elimination efforts. In partnership with National Malaria Control Programmes (NMCPs) and regional research studies, GenRe-Mekong collects and analyzes small dried blood spots samples from patients with symptomatic malaria, and uses high-throughput technologies to extract large amounts of parasite genetic information from each sample. The results are captured in Genetic Report Cards, which consist of datasets and reports regularly delivered to NMCPs to keep them abreast of rapid epidemiological changes in the parasite population.
The processing of the samples, and delivery of the Genetic Report Cards, is powered by the SPOTmalaria genetic surveillance framework. SPOTmalaria implements standardized methodologies and processing pipelines for extracting and analyzing genetic data from malaria infected patients. It provides procedures for every step of the process: ethics submissions, dried blood spots sample collection, sample extraction, quality assurance, and genotyping. In addition, SPOTmalaria provides informatics support for sample management, data processing, storage and delivery. The framework is extensible, so that additional markers can be added, and new techniques can be implemented, as they become of interest. In addition, SPOTmalaria is adaptable to the needs of partners, and its laboratory components may be implemented in country laboratories, with the support of the Wellcome Sanger Institute.
About the publication
This resource page accompanies the article “Genetic surveillance in the Greater Mekong Subregion and South Asia to support malaria control and elimination”, by CJ Jacob et al. published by eLife: https://elifesciences.org/articles/62997. The paper presents results from over 9,600 samples collected and processed by GenRe-Mekong in the first phase of the project.
Here, you will find detailed genotypes and phenotype predictions for those samples, which are being made publicly available in line with MalariaGEN’s guiding principles on equitable data sharing. In addition, this page (under ‘Content of the data release’) links to full details of the SpotMalaria methodology, and of the rules used to make inferences from the genotypes.
Notes on framework versions
The SPOTmalaria framework has evolved over time, in order to engineer solutions that can be more easily adapted to the needs of our partners. The first version of the platform (SPOTmalaria V1) used the Agena MassArray mass spectrometry-based system for the analysis of multiplexed single-base extension primers. SPOTmalaria V2, the current platform, uses a more flexible and adaptable multiplexed amplicon sequencing method, implemented on Illumina sequencers.
Content of the data release
- Study information: Details of the 12 partner studies contributing to GenRe-Mekong, including study description, contact information and key people
- Sample provenance, genotype information and phenotype information: for the 9,623 samples analyzed
- Phenotype rules: details of the heuristics utilized to map genetic markers to drug resistance phenotype predictions
- Imputation rules: details of the heuristics utilized fill in missing genotypes in drug resistance-related genes based on genotypes at linked loci
- SPOTmalaria Technical Notes and Methods: contains technical details and procedures covering both SPOTmalaria V1 and SPOTmalaria V2 platforms. It references the following supplementary files:Supplementary File 1: Spreadsheet detailing genotyped loci and primer sequences
Supplementary File 2: Map of mitochondrial loci used for species detection
Supplementary File 3: FASTA file containing the kelch13 nucleotide sequence used
Publications that have used the SPOTmalaria framework to produce genotypes
- Chang HH, Wesolowski A, Sinha I, et al. Mapping imported malaria in Bangladesh using parasite genetic and human mobility data. Elife. 2019 Apr 2;8.
- Hamilton WL, Amato R, van der Pluijm RW, et al. Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study. Lancet Infect Dis. 2019 Sep;19(9):943-951.
- Knudson A, González-Casabianca F, Feged-Rivadeneira A, et al. Spatio-temporal dynamics of Plasmodium falciparum transmission within a spatial unit on the Colombian Pacific Coast. Sci Rep. 2020 Feb 28;10(1):3756.
- Apinjoh TO, Mugri RN, Miotto O, et al. Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study. Infect Dis Poverty. 2017 Nov 6;6(1):136.
- van der Pluijm RW, Imwong M, Chau NH, et al. Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study. Lancet Infect Dis. 2019 Sep;19(9):952-961.
- von Seidlein L, Peto TJ, Landier J, et al. The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: A cluster randomised trial. PLoS Med. 2019 Feb 15;16(2).
- Landier J, Parker DM, Thu AM, et al. Effect of generalised access to early diagnosis and treatment and targeted mass drug administration on Plasmodium falciparum malaria in Eastern Myanmar: an observational study of a regional elimination programme. Lancet. 2018 May 12;391(10133):1916-1926.
- van der Pluijm RW, Tripura R, Hoglund RM, et al. Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial. Lancet. 2020 Mar 11. pii: S0140-6736(20)30552-3.