Vivax Malaria Human Infection Studies in Thailand

Inclusion Criteria:

• Healthy adult aged 20 to 55 years with weight more than 50 kg.

• Blood group O.

• Red blood cells positive for the Duffy antigen/chemokine receptor (DARC).

• Normal CYP2D6 genotype.

• Normal blood levels of Glucose-6-phosphate dehydrogenase (G6PDH) by the WHOdefinition.

• COVID-19 vaccination at least two doses of COVID-19 vaccine(s) approved by WHO.

• Agree to practice continuous effective contraception for the duration of studyperiod until 3 months post-challenge.

• Agreement to refrain from blood donation during the course of the study and for 1year after the end of their involvement in the study.

• Willing to take a curative antimalarial regimen following challenge.

• Willing to be admitted in the Hospital for Tropical Diseases for blood donation andclinical monitoring, until antimalarial treatment is completed and their symptomsare settling.

• Willing to reside in Bangkok for the duration of the study, until all antimalarialtreatment has been completed.

• Reachable (24/7) by mobile phone during the period between challenge CHMI andcompletion of all antimalarial treatment.

• Able to read and write in Thai and able to answer ALL questions on the informedconsent questionnaire correctly.

• Provided written informed consent to participate in the trial.

• Educational level: has at least an undergraduate degree.

• Cardiovascular risk assessment is low (less than 10% in the next 10 years accordingto the cardiovascular risk assessment from Thai NCD Division, DDC, MoPH (2016)

Exclusion Criteria:

• History of clinical malaria.

• Positive malaria PCR OR malaria film OR malaria serology (recent exposure)

• History of severe allergy to mosquito bite

• Presence of any medical condition (either physical or psychological) which in thejudgment of the investigator would place the participant at undue risk or interferewith the results of the study (e.g. serious underlying cardiac, renal, hepatic orneurological disease; severe malnutrition; congenital defects or febrile condition)

• Presence of chronic disease or chronically use of medication.

• Plan to travel outside of Bangkok within the period of challenge until 3 monthsafter.

• Use of systemic antibiotics with known antimalarial activity in the 30 days beforechallenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline,clindamycin, erythromycin, fluoroquinolones and azithromycin).

• Use of immunoglobulins or blood products (e.g. blood transfusion) at any time in the 1 year preceding enrolment.

• Venipuncture unlikely to allow blood donation according to the protocol asdetermined by the investigator.

• Receipt of an investigational product or any vaccine in the 30 days precedingenrolment (D0), or planned receipt during the study period.

• Prior receipt of an investigational vaccine likely to impact on interpretation ofthe trial data or the P. vivax parasite as assessed by the Investigator.

• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIVinfection, asplenia, history of splenectomy, recurrent, severe infections, andchronic infection.

• Immunosuppressant medication within the past 6 months preceding enrolment (D0) (inhaled and topical steroids are allowed).

• History of allergic disease or reactions likely to be exacerbated by malariainfection.

• Female participant who is pregnant, lactating or planning pregnancy during thecourse of the study.

• Contraindications to the use of antimalarial treatment (e.g. chloroquine orprimaquine or atovaquone / proguanil, DHA piperaquine). **

• Use of medications known to have a potentially clinically significant interactionwith antimalarial drug that will be used in this study (chloroquine or primaquine oratovaquone / proguanil, DHA/ piperaquine).

• Use of medications known to cause prolongation of the QT interval as state in thesection of prohibited drugs that may have effect on prolongation of the QT interval.

• Known existing positive family history in both 1st AND 2nd degree relatives < 50years old for cardiac disease.

• Family history of congenital QT prolongation or sudden death.

• Any clinical condition known to prolong the QT interval.

• History of cardiac arrhythmia, including clinically relevant bradycardia.

• Screening ECG demonstrates a QTc interval ≥ 450 ms

• Suspected or known or history of alcohol abuse

• Suspected or known or history of drug abuse.

• Concurrently participating in another clinical study, at any time during the studyperiod.

• Haemoglobin < 13 g/dL in male, < 12g/dL in female (Thai Red Cross).

• Finding on safety laboratory values as defined below:

• AST > 40 U/L for male, and > 32 U/L for female (upper normal range), or

• ALT > 41 U/L for male, and > 33 U/L for female (upper normal range), or

• Total Bilirubin > 1.2 mg/dL, (upper normal range), or

• Creatinine (Cr) > 1.17 mg/dL for male, and > 0.95 mg/dL for female (upper normalrange), or

• Abnormalities corrected calcium and magnesium blood levels, or

• Fasting blood sugar (FBS) > 100 mg/dL

• Thalassaemia disease or haemoglobinopathies.

• Positive for a blood borne or vector borne infectious disease (HIVI-II, HBV, HCV,Dengue, Zika, Chikungunya, Filariasis, JE, and malaria antigen, Anti HTLVI andAnti-HTLVII antibody, Syphilis test (TPHA)

• Positive for COVID-19 testing as diagnosed by RT-PCR ** Link of the lists ofmedications with QTc prolongation:https://crediblemeds.org/pdftemp/pdf/CombinedList.pdf