Brief overview of the paper and its main findings

The study aims to evaluate the pattern of ex vivo drug susceptibilities of P.vivax isolates from Greater Mekong subregion. Susceptibilities for seven antimalarial drugs (chloroquine, artesunate, 25 dihydroartemisinin, piperaquine, pyronaridine, mefloquine, and quinine) were tested on a total of forty six P.vivax clinical isolates. The recorded IC50s were in the range of 1.63nM to 96.48nM. With this the authors have also studied the genetic variations in the four drug resistance-associated genes (pvmdr1, pvmrp1, pvdhfr and pvdhps) in P.vivax. A number of non-synonymous mutations were found among the all the genes and G698S mutation was found to be associated with reduced sensitivity to CQ, artesunate and dihydroartemisnin.

Major and minor points

This is an interesting piece of work. The data generated will definitely add on to current knowledge of the P. vivax drug resistance. However, the manuscript would have been better if the authors: - Can add some detailed description of the antimalarial drug resistance of P.vivax in GMS region from in vitro or therapeutic efficacy study in the recent years. - It will be good to compare this study results (in the form of the table or graph) with the already published data from GMS region for the yearly trend of the IC50 values of the tested drugs. - Discuss in more detail about the usage of SP drugs in the GMS region - At some places English needs to be improved and there is a typo in the title - Work needs to be done on the quality of the figures The methods and results are all good overall. In inclusion criteria, authors can discuss about the clinical symptoms of the patients present at the time of enrollment. The tool used for polymorphism analysis is not mentioned in the methods section. What were the exclusion criteria and how many patients were excluded from the study? Do any of the patients enrolled in the study had clinical presentation of the severe malaria? It would be very informative for the readers if the authors can add the clinical parameters in the table form for the enrolled patients. In the abstract, the authors need to clearly define the number of patients tested for the drugs. As in the results section it is mentioned that only 39 isolates were tested for PPQ, PND, MFQ and QN. The abstract should have to be more descriptive, and authors should define the percentages of the different non-synonymous substitutions found in the study. Conflicts of interest

NO