**3. CSP variants in** *plasmodium vivax* **isolates from malaria-endemic region and to profile these variants based on sensitivity to antimalarial drugs**

As described above, *P. vivax* has a complex life cycle distinct with different stages between vector and host with a dormant liver stage. To achieve optimal results for *P. vivax* infections, effective clearance of both blood-stage parasites to treat the acute infection and liver-stage parasites (radical cure) to prevent relapse is required; however, the continual rise and propagation of resistance against antimalarial drugs are of great concern to successfully [64]. Despite increasing reports of resistance, chloroquine (CQ ) remains highly effective for treatment of strains from temperate South American countries, some parts of Eastern Mediterranean, and parts of Southeast Asia [65]. The first evidence that *P. vivax* is developing resistance to CQ was reported in Papua New Guinea by Rieckmann et al. [66]. It is difficult to ascertain how common CQ resistance is in *P. vivax* infection, particularly as resistance does not appear to be absolute [67]. On the other hand, reduction in susceptibility to CQ was reported from Solomon Island [68], Papua New Guinea [69, 70], and India [71]. Brazilian studies also assessed the efficiency of standard supervised therapy or the *in vitro* profile of mefloquine (MQ ) and CQ resistance showing failure of the treatment [72–74].

Another important issue is that the response to the treatment might possibly differ depending on the genotype of the parasite. However, the influence of these variants on drug response remains unclear. Studies conducted by Kain et al. [75] showed that the response to CQ may vary depending on the type of *P. vivax* variant, as both single VK210 and VK210/VK247 mixed infections took longer to clear when compared with single VK247 infection in Thailand. Later, two studies conducted in Brazil showed contradictory results. One demonstrates a correlation between the *P. vivax* variant and the response to CQ [56], and the other does not observe any difference in the frequency of the resistant isolates and in the IC50 mean for CQ or mefloquine, according to VK210 subtypes [74]. Additional studies will be necessary to enable a better understanding of whether individuals in endemic areas acquire *P. vivax* CSP variants that have preferential ability to malarial drug resistance.
