Introduction

GenRe-Mekong (Genetic Reconnaissance of Malaria in the Greater Mekong Subregion) is a genetic surveillance project, aiming to provide National Malaria Control Programmes (NMCPs) in the Greater Mekong Subregion and other public health stakeholders with timely and actionable knowledge to support their decision-making in activities relevant to malaria elimination efforts.

Objectives & Coordination

In the Greater Mekong Subregion (GMS, comprising Cambodia, Vietnam, Laos, Thailand, Myanmar and parts of China), National Malaria Control Programs (NMCPs) are called upon to take difficult policy decisions in the face of a rapidly changing epidemiological landscape. These decisions include: assessing treatment efficacy, reviewing frontline drug policies, assessing the effectiveness of targeted interventions, identifying transmission hubs to target, and monitoring imported cases. To support their decision-making, NMCPs make use of clinical and epidemiological data, as well as results of therapeutic efficacy studies. GenRe-Mekong adds to this evidence base by providing comprehensive genetic information about the parasite populations.

GenRe-Mekong analyzes small dried blood spots samples, collected using a simple standardised operating procedure that is easy to implement at public health sites, even in resource-constrained endemic regions. Samples are processed by the SpotMalaria genotyping platform, which leverages on leading-edge high-throughput technologies to extract large amounts of parasite genetic information from each sample. The results are captured in Genetic Report Cards (GRCs), datasets regularly delivered to NMCPs to keep them abreast of rapid epidemiological changes. The underlying technological platform is designed to keep sample processing costs low, enabling large-scale genetic epidemiology survey with dense geographical coverage and large sample sizes.

The most urgent problem faced by NMCPs in the GMS is the rapid emergence and spread of strains resistance to antimalarial drugs. Accordingly, GenRe-Mekong has focussed in its first phase on use cases relevant to drug resistance, by genotyping variants known to be associated with resistance to several antimalarials. To facilitate integration into NMCP decision-making workflows, our analysis pipelines translate genotypes associated with drug resistance into phenotype predictions, producing maps which can be more easily interpreted by public health officials.

GenRe-Mekong protects individual patient privacy, but encourages aggregation and sharing of standardized data across national borders, to answer regional questions about epidemiology, gene flow and parasite evolution. To maximize benefits to the research community, GenRe-Mekong also conducts whole-genome sequencing of selected high-quality samples, which are contributed to the MalariaGEN Plasmodium falciparum Community Project to support high-resolution genetic epidemiology analyses of population structure, gene flow and association with phenotypes.

For in-depth details of the project, please refer to the first GenRe-Mekong publication.

Genetic Report Cards

We use ‘Genetic Report Cards‘ to provide information on genetic variation relevant to drug resistance for each sample. Currently, we report on genetic variations that are relevant to resistance to several antimalarial drugs:

• artemisinin (kelch13, arps10, mdr2, fd, crt genes)
• piperaquine (plasmepsin2-3, exo)
• chloroquine, amodiaquine, mefloquine (crt, mdr1)
• sulfadoxine, pyrimethamine (dhfr, dhps)

In addition, we report on other genetic variations relevant to parasite epidemiology:

• Detection of additional species of Plasmodium in a P. falciparum infection, such as P. vivax, P. knowlesi, P. malariae, P. ovale
• Genetic barcodes (101 high-diversity SNPs across the genome), used to estimate complexity of infection (COI), identify expanding strains and reconstruct the geographic origins of samples.

GenRe-Mekong is funded by the Bill & Melinda Gates Foundation.

Sampling locations

Bangladesh, Cambodia, India, Laos, Myanmar, Thailand, Vietnam.

Data

We routinely release genotype data to our partner studies; in addition, we periodically release public access datasets. This is the first public release of the GenRe-Mekong v1.0 data set and samples from this collection contribute to the P. falciparum community project data release

Current

For partners

The DBS collection protocol for GenRe-Mekong is available in parasite partner study resources.

Additionally, video guides specific to GenRe-Mekong sample collection are available with subtitles in English.

• A Thai subtitled video guide to GenRe-Mekong 2 dot collection of DBS
• A Vietnamese subtitled video guide to GenRe-Mekong 2 dot collection of DBS
• A video guide to GenRe-Mekong 2 dot collection of DBS
• A video guide to GenRe-Mekong 3 dot collection of DBS

Partner studies

To date, GenRe-Mekong has worked with NMCPs in seven countries (Lao PDR, Vietnam, Cambodia, Myanmar, Thailand India and Bangladesh), and supported large-scale multisite research and elimination projects across the region.

Publications

• Genetic Epidemiology Use Cases for Malaria Control Programmes: A Methodology
  Olivo Miotto, Principal Investigator, GenRe-Mekong Project
  Genetic Epidemiology Use Cases for Malaria Control Programmes: A Methodology, 2023;
• Pf7: An open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples
  MalariaGEN et. al
  Wellcome Open Research, 2023; 8 22
  10.12688/wellcomeopenres.18681.1
• Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study
  Imwong et al
  The Lancet Infectious Diseases, 2020; 20(12) 1470-1480
  10.1016/S1473-3099(20)30228-0
• Genetic surveillance in the Greater Mekong Subregion and South Asia to support malaria control and elimination: about the data
  Jacob CG, Thuy-Nhien N, Mayxay M, et al.
  eLife, 2021; 10:e62997
  10.7554/eLife.62997
• Mass drug administration for the acceleration of malaria elimination in a region of Myanmar with artemisinin-resistant falciparum malaria: a cluster-randomised trial
  McLean ARD et al
  The Lancet Infectious Diseases, 2021; 21 1579
  10.1016/S1473-3099(20)30997-X
• Mapping the travel patterns of people with malaria in Bangladesh
  Sinha et al.
  BMC Medicine, 2020; 18(1) 45
  10.1186/s12916-020-1512-5
• Mass drug administrations with dihydroartemisinin-piperaquine and single low dose primaquine to eliminate Plasmodium falciparum have only a transient impact on Plasmodium vivax: Findings from randomised controlled trials
  Phommasone K et al.
  PloS One, 2020; 15 e0228190
  10.1371/journal.pone.0228190
• Intracluster correlation coefficients in the Greater Mekong Subregion for sample size calculations of cluster randomized malaria trials
  Peerawaranun P et al.
  Intracluster correlation coefficients in the Greater Mekong Subregion for sample size calculations of cluster randomized malaria trials, 2019; 18 428
  10.1186/s12936-019-3062-x
• Mapping imported malaria in Bangladesh using parasite genetic and human mobility data
  Chang et al.
  eLife, 2019; 8 e43481
  https://doi.org/10.7554/eLife.43481
• The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: A cluster randomised trial
  von Seidlein L et al
  PLOS Medicine, 2019; 16 e1002745
  10.1371/journal.pmed.1002745
• Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar
  Landier J et al
  Wellcome Open Research, 2017; 2 81
  10.12688/wellcomeopenres.12240.1
• Persistent Plasmodium falciparum and Plasmodium vivax infections in a western Cambodian population: implications for prevention, treatment and elimination strategies
  Tripura R et al.
  Persistent Plasmodium falciparum and Plasmodium vivax infections in a western Cambodian population: implications for prevention, treatment and elimination strategies, 2016; 15 181
  10.1186/s12936-016-1224-7