MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed.  Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed.  Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

To the Editor-The rise in COVID-19 cases in India has become an important lesson to the global community 1 . Because certain parts of the world have been left vulnerable to COVID-19, a humanitarian crisis at an unprecedented scale has emerged and spread to the rest of the world. The SARS-CoV-2 Delta variant (B.1.617.2) that evolved from the outbreak in India has set back the success of COVID-19 control measures in several developed countries 2 . Southeast Asia and its population of more than 655 million people could be the next hotspot due to geographical and socioeconomic factors, such as ongoing political unrest and the emergence of new variants.Southeast Asia is now being bombarded with three known variants of concern: B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). The movement of workers between countries, often through illegal and unmonitored channels, in combination with a limited vaccine rollout, has put the whole region at risk from highly transmissible and immunoevasive variants. However, little information about this rising crisis is seen in the media or from the global medical community.In 2020, Southeast Asia was the role model in terms of COVID-19 control. The situation in mid-2021 has been transformed by the rise in case numbers. The average number of confirmed daily new cases in Southeast Asia has increased from more than 12,900 in March 2021 to 28,800 in June 2021, with a median time-varying reproduction number of 1.09, which indicates that the daily new cases are growing exponentially (Fig. 1a). The data are probably under-reported due to limited testing capacity.The degree of genetic variation in the available SARS-CoV-2 genomes in Thailand suggests that the virus has been propagating without detection for months 3 . From March 2021 to June 2021, the spread of the Alpha and Delta variants took over the region, which resulted in a collapse of the healthcare system. Starting in March 2021, the Alpha variant was circulating in Cambodia and Thailand (Fig. 1b). The public-health measures successfully implemented during the first wave in 2020 failed to control the new variant. The positivity rate of SARS-CoV-2 tests was as much as 60-90% in certain clusters in Thailand. Cases of

Artemisinin derivatives and their partner drugs in artemisinin combination therapies (ACTs) have played a pivotal role in global malaria mortality reduction during the last two decades. The loss of artemisinin efficacy due to evolving drug-resistant parasites could become a serious global health threat. Dihydroartemisinin-piperaquine is a well tolerated and generally highly effective ACT. The implementation of a partner drug in ACTs is critical in the control of emerging artemisinin resistance. Even though artemisinin is highly effective in parasite clearance, it is labile in the human body. A partner drug is necessary for killing the remaining parasites when the pulses of artemisinin have ceased. A population of Plasmodium falciparum parasites in Cambodia and adjacent countries has become resistant to piperaquine. Increased copy number of the genes encoding the haemoglobinases Plasmepsin II and Plasmepsin III has been linked with piperaquine resistance by genome-wide association studies and in clinical trials, leading to the use of increased plasmepsin II/plasmepsin III copy number as a molecular marker for piperaquine resistance. Here we demonstrate that overexpression of plasmepsin II and plasmepsin III in the 3D7 genetic background failed to change the susceptibility of P. falciparum to artemisinin, chloroquine and piperaquine by both a standard dose-response analysis and a piperaquine survival assay. Whilst plasmepsin copy number polymorphism is currently implemented as a molecular surveillance resistance marker, further studies to discover the molecular basis of piperaquine resistance and potential epistatic interactions are needed.