SpotMalaria: a global collaborative platform to survey the major malaria parasites

Publicação: 26 de August de 2017

SpotMalaria, a project led by Malaria Genomic Epidemiology Network (MalariaGen)

Project uses state-of-the-art genomic technologies to rapidly generate usable information of Plasmodium falciparum and P. vivax, the two most common human malaria parasites

Cristina V. Ariani
Postdoctoral fellow at the Malaria Programme, Wellcome Trust Sanger Institute, Cambridge, United Kingdom

 

A major challenge in eliminating malaria, a mosquito-borne parasitic disease, is determining what, how and where control measures should be used. The same method applied in the same way in two different places may not have the same impact. Interventions need to be tailored to the specific conditions in the region. Understanding the local parasite and vector population is essential and can answer important questions such as, where are the transmission hotspots? What drugs are the parasites resistant to in a specific region? Does new resistance emerge as a result of a malaria control intervention?

SpotMalaria, a project led by Malaria Genomic Epidemiology Network (MalariaGen), uses state-of-the-art genomic technologies to rapidly generate usable information of Plasmodium falciparum and P. vivax, the two most common human malaria parasites. The aim is to understand what is going on with the local parasite population and provide this information to partners that can aid decisions made about malaria control. For each partner study, we produce a Genetic Report Card (GRC) with key information about drug resistance and infection complexity. We can also generate whole genome sequencing data for a deeper understanding of the evolution of both parasites species.

Project partners contribute samples from confirmed malaria cases as dried blood spots (DBS). We suggest a simple standardised operating procedure to collect, store and transport samples that can easily be implemented in the field with limited training. We can also provide the collection kits should the partners prefer to use our standard materials. We can also accept extracted parasite DNA from leucodepleted venous blood if this is the collection method of an ongoing project. Partners ship their samples to us, at the Wellcome Trust Sanger Institute in the United Kingdom, and we perform a series of laboratory procedures, including DNA extraction, selective whole genome amplification (Oyola et al 2016), and genotyping in order to generate parasite genetic data in a timely way.

For P. falciparum, the GRC contains genotype information for each sample on over 20 genetic variations that are relevant to drug resistance and over 100 barcoding single nucleotide polymorphisms (SNPs). For P. vivax, we provide data on 7 putative drug-resistance markers (Price et al 2012), 73 SNPs in regions of the genome under positive selection (Pearson et al 2016), and 40 barcoding SNPs (Baniecki et al 2015). These data can be used by our partners to understand the impact of an intervention on drug resistance by looking at the frequency of relevant markers; the clonality of parasites in the infecting parasite population by looking at the complexity of infection; and if the parasites originate from the collection location or are they migrating from an adjacent region? Answers to these questions are useful when making decisions on where and how to deploy malaria control resources.

As this data is of public health importance the genetic data generated by the project is made publically available. The genetic data is accompanied by very limited information (date and location of collection) meaning that partners who provided samples still have additional data and a deeper understanding of the field, empowering them to answer their own specific questions based on their better knowledge of the region, the population and the environment.

Genomic data across studies is used to perform global-scale analysis of the parasite genetic variation and evolution. Whenever we or the malaria research community find relevant genetic markers, we update our genotyping platform to include such information. For example, in 2016 our group led a collaboration that found a genetic marker responsible for conferring resistance to piperaquine, frequently used as a partner drug in artemisinin-based combination therapies for P. falciparum malaria (Amato et al 2016). Shortly after the discovery, the genetic marker was included in our genotyping panel. This is a very dynamic process in which new discoveries can be quickly incorporated and therefore we are able to provide the latest genetic information to our partners.

How can you get involved? SpotMalaria is a long-term project that is still at an early stage and our processes are still iteratively improving such as sample processing capacity and web applications to visualize the data. Currently we have funding to cover related to genotying and sequencing. Potential partners should get in touch to discuss your particular project and how we can work together.

SpotMalaria already counts with more than 30 partners, from 24 different countries. If you would like to find out more about it or get in touch, please check our website https://www.malariagen.net/about, email us info@malariagen.net or follow us on social media @malariagenomics.

References:

Amato R, Lim P, Miotto O et al (2016) Genetic markers associated with dihydroartemisinin–piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype–phenotype association study. Lancet Inf Dis 17(2): 164-173

Oyola S, Ariani CV, Hamilton W et al (2016) Whole genome sequencing of Plasmodium falciparum from dried blood spots using selective whole genome amplification. Mal J 15: 597

Pearson RD, Amato R, Auburn Set al (2016) Genomic analysis of local variation and recent evolution in Plasmodium vivax. Nature genetics 48: 959-64

Price RN, Auburn S, Marfurt J, & Cheng Q (2012) Phenotypic and genotypic characterisation of drug-resistant Plasmodium vivax. Trends in Parasitology, 28: 522-529