Study of Controlled Human Plasmodium Vivax Infection

Inclusion Criteria: * • Healthy adult aged 18 to 50 years. * Blood group O, Rhesus negative. * Red blood cells positive for the Duffy antigen/chemokine receptor (DARC). * High metaboliser of primaquine (as determined by CYP2D6 genotype). * Normal serum levels of Glucose-6-phosphate dehydrogenase (G6PDH). * Satisfactory serum levels of Primaquine (when administered as test dose). * Able and willing (in the Investigator's opinion) to comply with all study requirements. * Willing to allow the Investigators to discuss the volunteer's medical history with their General Practitioner. * Women only: Must practice continuous effective contraception\* for the duration of the clinic visits (first 3 months post-CHMI). * Agreement to refrain from blood donation during the course of the study and for at least 5 years after the end of their involvement in the study. * Written informed consent to participate in the trial. * Reachable (24/7) by mobile phone during the period between CHMI and completion of all antimalarial treatment. * Willing to take a curative anti-malaria regimen following CHMI. * Willing to be admitted to the research bay on the John Warin ward at the Churchill Hospital for blood donation and clinical monitoring, until antimalarial treatment is underway and their symptoms are settling. * Willing to reside in Oxford for the duration of the study, until all antimalarials have been completed. * Answer all questions on the informed consent quiz correctly. \* Female volunteers are required to use an effective form of contraception during the course of the study as malaria challenge could pose a serious risk to both maternal health and the unborn foetus. Acceptable forms of contraception for female volunteers include: * Established use of oral, injected or implanted hormonal methods of contraception (an additional form of contraception will be required when taking the antimalarial medication, as this can interfere with the efficacy of hormonal contraception). * Placement of an intrauterine device (IUD) or intrauterine system (IUS). * Total abdominal hysterectomy. * Barrier methods of contraception (condom or occlusive cap with spermicide). * Male sterilisation, if the vasectomised partner is the sole partner for the subject. * True abstinence, when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence and withdrawal are not acceptable methods of contraception). Exclusion Criteria: * • History of clinical malaria (any species). * Travel to a clearly malaria endemic locality during the study period or within the preceding six months. * Use of systemic antibiotics with known antimalarial activity within 30 days of CHMI (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin). * Blood group A/B and/or Rhesus positive. * Red blood cells negative for the Duffy antigen/chemokine receptor (DARC). * Glucose-6-phosphate dehydrogenase (G6PDH) deficient. * Inadequate serum levels of Primaquine (when administered as test dose). * Current anaemia (Haemoglobin \< 9 g/dL). * Use of immunoglobulins or blood products (e.g., blood transfusion) at any time in the past. * History of sickle cell anaemia, sickle cell trait, thalassaemia or thalassaemia trait or any haematological condition that could affect susceptibility to malaria infection. * Venepuncture unlikely to allow a 250 mL blood donation (as determined by the Investigator). * Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period. * Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data or the P. vivax parasite as assessed by the Investigator. * Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed). * History of allergic disease or reactions likely to be exacerbated by malaria infection. * Pregnancy, lactation or intention to become pregnant during the study. * Use of medications known to cause prolongation of the QT interval and existing contraindication to the use of Malarone. * Use of medications known to have a potentially clinically significant interaction with Riamet and Malarone. * Any clinical condition known to prolong the QT interval. * History of cardiac arrhythmia, including clinically relevant bradycardia. * Disturbances of electrolyte balance, e.g. hypokalaemia or hypomagnesaemia. * Family history of congenital QT prolongation or sudden death. * Contraindications to the use of both of the proposed anti-malarial medications; Riamet Malarone. * Contraindications to the use of Primaquine. * History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). * History of serious psychiatric condition that may affect participation in the study. * Any other serious chronic illness requiring hospital specialist supervision. * Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 standard UK units every week. * Suspected or known injecting drug abuse in the 5 years preceding enrolment. * Hepatitis B surface antigen (HBsAg) detected in serum. * Seropositive for HTLV I or II (antibodies to HTLV) at screening. * Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV RNA PCR at screening for this study). * Seropositive for RPR (antibodies to syphilis) at screening. * Positive family history in both 1st AND 2nd degree relatives \< 50 years old for cardiac disease. * Volunteers unable to be closely followed for social, geographic or psychological reasons. * Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. In the event of abnormal test results, confirmatory repeat tests will be requested. Procedures for identifying laboratory values meeting exclusion criteria are shown in Appendix A. * Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data. Testing for HIV, HTLV, hepatitis B and C and syphilis will be performed at screening and then repeated 1 week prior to CHMI (day C-7) to ensure no new acquisition of infection prior to blood donation. Other infections will be screened for if the volunteer has recently travelled to an area where they may have been exposed to a blood-borne infection that could theoretically be transmitted to another healthy volunteer during a future blood-stage challenge. \- Exclusion criteria on day of CHMI The following constitute absolute contraindications to CHMI: * Acute disease, defined as moderate or severe illness with or without fever. * Pregnancy.