Previous studies have suggested that B cell memory responses to blood stage antigens could be stably maintained over time in the absence of reinfection even in areas of low malaria transmission [43]. of populations in Thailand with poor susceptibility to 8-aminoquinolines. Electronic supplementary material The online version of this article (doi:10.1186/s12936-017-1877-x) contains supplementary material, which is available to MV1 authorized users. or treated with a schizontocidal drug is usually either a recrudescence due to erythrocytic parasites that have survived treatment, a re-infection, or a relapse consequent to merozoites released from a dormant liver stage, the hypnozoite, that has activated to resume normal development. Hypnozoites, which are not detectable, significantly lengthen the duration of the infection and the parasites potential to transmit, as a single infected mosquito bite can lead to multiple relapse episodes over many years. Relapse patterns vary between the parasite from temperate and tropical origin, and the risk for multiple relapse is usually highest in the tropics (50C80%) and least expensive in temperate MV1 regions (5C10%) [1]. In Southeast Asia, vivax infections are predicted to have a high relapse incidence rate (836 relapses per 100,000 person days) and a relatively rapid mean time from main episode to first relapse (41?days) [2]. The mechanisms behind the activation of hypnozoites and the determination of their periodicity remain unclear. Hypnozoites can only be eliminated by 8-aminoquinolines of primaquine which ARF6 is usually safely administered only to persons without glucose-6-phosphate dehydrogenase deficiency. Thus, relapses are a major concern for efforts to control and eliminate vivax malaria [3]. It was assumed that this parasite populations emerging during relapses would be identical to those present during the main episode, a notion that received support from early molecular studies [4, 5]. However, later investigations based more detailed genotyping analyses on relapses in diverse geographic regions revealed that this parasites in main and relapse episodes are often genetically unique, a phenomenon termed heterologous hypnozoite activation [6C8]. Thus, interpretation of drug efficacy studies against in endemic countries cannot be corrected by genotyping analyses, as these will not allow distinguishing between a re-infection, a recrudescence, or a heterologous relapse. The relapse pattern comprising the latency period and the number of relapse episodes is probably influenced by the level of immunity that MV1 this patients may have acquired during the main attack [1, 9]. A degree of immunity is generally acquired following the main contamination, and experimental vivax infections clearly show that protection is usually strain-specific [9C11]. However, although the number of investigations around the immune responses in is usually increasing, very few studies have resolved this in the context of relapse episodes [5, 12C16]. In Thailand patients diagnosed with receive a standard treatment of chloroquine and primaquine, though approximately 7% relapse within 6?months [17]. Patients who present with in Bangkok following a trip to endemic areas cannot be re-infected while they remain there, as malaria MV1 transmission does not occur in this city. This afforded the opportunity to recruit a cohort of vivax patients and to identify those with true relapse episodes during extended follow-up. In this manner a set 12 paired admission/relapse blood samples were obtained, and these were used to compare the genotypes of the parasites and a set of immune response markers. Methods Samples The stored packed reddish blood cells and plasma samples were obtained from Clinical Malaria Research Unit, Faculty of Tropical Medicine at Mahidol University or college (Bangkok, Thailand). The samples were collected between February 2012 and May 2013 prior to treatment by the Clinical Malaria Research Unit (Faculty of Tropical Medicine) from 12 patients (P1 to P12) on initial admission with and when presenting with renewed clinical symptoms during follow-up. These infections were acquired while visiting malaria endemic areas along the Thai-Myanmar border in the west (P1, P2, P3, P4, P5, P6, P7, P9), the ThaiCCambodian border in the east (P10, P11), and the Thai-Lao border in the north (P8, P12). All patients were treated the standard chloroquine/primaquine treatment: once-daily oral chloroquine on day 1 (600?mg), day 2 (600?mg), and day 3 (300?mg), and oral primaquine 15?mg for 14?days from day 2. The mean age (mean??SD) of the patients was 29.8??13.3?years. The.