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Background  While intensive  Plasmodium falciparum  multidrug resistance surveillance continues in Cambodia, relatively little is known about  Plasmodium vivax  drug resistance in Cambodia or elsewhere. To investigate  P. vivax  anti-malarial susceptibility in Cambodia, 76 fresh  P. vivax  isolates collected from Oddar Meanchey (northern Cambodia) in 2013–2015 were assessed for ex vivo drug susceptibility using the microscopy-based schizont maturation test (SMT) and a  Plasmodium  pan-species lactate dehydrogenase (pLDH) ELISA.  P. vivax  multidrug resistance gene 1 ( pvmdr1 ) mutations, and copy number were analysed in a subset of isolates.    Results  Ex vivo testing was interpretable in 80% of isolates using the pLDH-ELISA, but only 25% with the SMT.  Plasmodium vivax  drug susceptibility by pLDH-ELISA was directly compared with 58  P. falciparum  isolates collected from the same locations in 2013–4, tested by histidine-rich protein-2 ELISA. Median pLDH-ELISA IC 50  of  P. vivax  isolates was significantly lower for dihydroartemisinin (3.4 vs 6.3 nM), artesunate (3.2 vs 5.7 nM), and chloroquine (22.1 vs 103.8 nM) than  P. falciparum  but higher for mefloquine (92 vs 66 nM). There were not significant differences for lumefantrine or doxycycline. Both  P. vivax  and  P. falciparum  had comparable median piperaquine IC 50  (106.5 vs 123.8 nM), but some  P. falciparum  isolates were able to grow in much higher concentrations above the normal standard range used, attaining up to 100-fold greater IC 50 s than  P. vivax . A high percentage of  P. vivax  isolates had  pvmdr1  Y976F (78%) and F1076L (83%) mutations but none had  pvmdr1  amplification.    Conclusion  The findings of high  P. vivax  IC 50  to mefloquine and piperaquine, but not chloroquine, suggest significant drug pressure from drugs used to treat multidrug resistant  P. falciparum  in Cambodia.  Plasmodium vivax  isolates are frequently exposed to mefloquine and piperaquine due to mixed infections and the long elimination half-life of these drugs. Difficulty distinguishing infection due to relapsing hypnozoites  versus  blood-stage recrudescence complicates clinical detection of  P. vivax  resistance, while well-validated molecular markers of chloroquine resistance remain elusive. The pLDH assay may be a useful adjunctive tool for monitoring for emerging drug resistance, though more thorough validation is needed. Given high grade clinical chloroquine resistance observed recently in neighbouring countries, low chloroquine IC 50  values seen here should not be interpreted as susceptibility in the absence of clinical data. Incorporating pLDH monitoring with therapeutic efficacy studies for individuals with  P. vivax  will help to further validate this field-expedient method.    Electronic supplementary material  The online version of this article (doi:10.1186/s12936-017-2034-2) contains supplementary material, which is available to authorized users.

Measuring ex vivo drug susceptibility in Plasmodium vivax isolates from Cambodia