Blood-Stage Plasmodium Vivax Cell Bank

Exclusion Criteria

• •A participant will be excluded from participating in this trial if any one of the following criteria is fulfilled:
• •Currently breastfeeding (if female).
• •Pregnant as determined by a positive urine or serum human choriogonadotropin (Beta-hCG) test (if female).
• •Planned travel to a malaria-endemic area during the study period and up to 2 weeks following the EOS visit.
• •History of recent travel to or residence in a P. vivax malaria-endemic region for more than 2 weeks during the past 5 years.
• •Planned travel to a malaria-endemic region during the course of the study (for endemic regions, see www.cdc.gov/malaria/travelers/country\_table).
• •Any history of confirmed malaria diagnosis on peripheral blood smear or by clinical history
• •Participation in a previous malaria challenge study.
• •Screening laboratory parameters outside of local lab normal range, to include serum-corrected calcium, creatinine, hepatic transaminase enzymes (ALT, AST), total bilirubin (unless the participant has documented Gilbert syndrome), and hemoglobin. Participants may be included at the investigator s discretion for not clinically significant values outside of normal range.
• •Abnormal urinalysis as defined by positive urine glucose, protein, and hemoglobin. Participant can be included if investigator determine the abnormality is not clinically significant.
• •Duffy blood group negative (male or female).
• •ABO blood type other than O (male or female).
• •Rh blood group negative (females of childbearing potential).
• •Anticipated use during the study period, or use within the following periods prior to enrollment of any of the following: Investigational malaria vaccine within the last 2 years; Malaria chemoprophylaxis within the past 6 months; Chronic systemic immunosuppressive medications (\>14 days) within 6 months; Blood products or immunoglobulins within the previous 6 months; Systemic antibiotics or medications with potential antimalarial effects within the past 6 weeks; Investigational or non-registered product or vaccine within 30 days; Receipt of any vaccination within 28 days prior to P. vivax IBSM; Medications known to interact with artemether/lumefantrine; Anticoagulants within the past 28 days.
• •History of:
• •* Sickle cell disease, sickle cell trait, or other hemoglobinopathies.
• •* Splenectomy or functional asplenia.
• •* Systemic anaphylaxis.
• •* Any allergic reactions to artemether/lumefantrine, chloroquine (or any 4-aminoquinolines), artemether or other artemisinin derivatives, or their excipients.
• •* History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within 5 years of screening, regardless of whether there is evidence of local recurrence or metastases.
• •* Blood transfusion.
• •Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history that may have clinically significant implications for current health status and participation in the study in the opinion of the investigator.
• •Vital signs taken after 5 minutes of resting in seated or supine position that fall outside the following ranges:
• •* Systolic blood pressure \<=90 mm Hg or \>=140 mm Hg.
• •* Diastolic blood pressure \<=50 mm Hg or \>=90 mm Hg.
• •* Heart rate \<=40 bpm or \>=100 bpm.
• •Body mass index less than 17.0 or greater than 35.0 kg/m2 at the time of screening.
• •History of, or known active cardiac disease including: (1) prior myocardial infarction (heart attack); (2) angina pectoris; (3) congestive heart failure; (4) valvular heart disease; (5) cardiomyopathy; (6) pericarditis; (7) stroke or transient ischemic attack; (8) exertional chest pain or shortness of breath; (9) symptomatic cardiac arrhythmias; (10) clinically relevant bradycardia; or (11) other heart conditions under the care of a doctor.
• •Clinically significant electrocardiogram (ECG) findings as determined by the expert study cardiologist, or QTcF \>=450 ms, or presence of second- or third-degree atrioventricular block or abnormal T wave morphology.
• •Moderate or high risk for coronary heart disease based on National Health and Nutrition Examination Survey (NHANES) I cardiovascular risk assessment (Appendix A).
• •Family history of sudden death or of congenital prolongation of the QTc interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval.
• •History of electrolyte disturbances, particularly hypokalemia, hypocalcemia, or hypomagnesemia.
• •Acute infectious disease or fever (e.g., temperature \>=38.5 degrees C) within the 5 days prior to inoculation with malaria parasites.
• •Evidence of acute illness within the 4 weeks prior to screening that the investigator deems may compromise participant safety.
• •Positive result on any of the following tests: hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV) antibodies, and anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab).
• •Positive urine drug test for any drug unless there is an explanation acceptable to the investigator.
• •Elevated serum ethanol level.
• •Psychiatric condition that precludes compliance with the protocol.
• •Suspected or known current alcohol or drug abuse as defined by the American Psychiatric Association in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, at the discretion of the investigator.
• •Smoking more than 5 cigarettes or equivalent per day and unable to stop smoking for the duration of admission. Participants may smoke up to 5 cigarettes or equivalent per day for the rest of the study.
• •History or presence of alcohol abuse (alcohol consumption of more than 4 standard drinks per day), drug habituation, or any prior intravenous usage of an illicit substance.
• •Excessive consumption of beverages or food containing xanthine bases (such as Red Bull, chocolate, etc.), or more than 400 mg of caffeine per day (equivalent to more than 4 cups of coffee per day).
• •Ingestion of any poppy seeds within the 24 hours prior to the screening blood test (participants will be advised by phone not to consume any poppy seeds in this time period).
• •Use of prescription drugs or non-prescription drugs and herbal supplements (such as St John's Wort) within 14 days or 5 half-lives (whichever is longer) prior to the inoculation administration. (Note: diazepam interferes with the analysis of blood levels of chloroquine and thus should not have been used for at least 8 weeks prior to administration of the study drug). If needed (i.e., an incidental and limited need), ibuprofen up to 1.2 g/day or acetaminophen up to 4 g/day is acceptable. The participant must inform the investigator of any ibuprofen or acetaminophen use at the next convenient time. Limited use of other non-prescription medications or dietary supplements not believed to affect participant safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor in consultation with the investigator. Participants are requested to refrain from taking non-approved concomitant medications from recruitment until the conclusion of the study.
• •Clinical trial staff with direct involvement in the conduct of the trial are excluded from participation.
• •Participating in other clinical trials involving investigational interventions or off-label medication use during the study period or within the 12 weeks preceding study day 0. Participation in other trials such as observational or imaging studies will be discussed with the investigators.
• •Blood donation of any volume within 4 weeks prior to study day 0, or participation in any research study involving blood sampling (more than 450 mL/unit of blood), or blood donation to Red Cross (or other) blood bank within 8 weeks prior to study day 0.
• •Unwillingness to defer blood donations for at least 3 years.
• •Unwillingness to abstain from consumption of quinine-containing foods/beverages, such as tonic water or lemon bitter, from inoculation (study day 0) to the end of antimalarial treatment.
• •Unwillingness to abstain from consumption of grapefruit or Seville oranges from inoculation (study day 0) to the end of antimalarial treatment.
• •Any participant without a good peripheral venous access.
• •Participant who, in the judgment of the investigator, is likely to be noncompliant during the study, or is unable to cooperate because of a language or mental deficit.
• •Any other finding that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a participant s ability to give informed consent