Vivax Malaria Human Infection Studies in Thailand (MIST1)

This is an interventional other trial for Plasmodium Vivax Infection Read More

Inclusion Criteria:

• Healthy adult aged 18 to 55 years.
• 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 WHO definition.
• Able and willing to comply with all study requirements.
• Must practice continuous effective contraception for the duration of the clinic visits (first 3 months post-challenge).
• 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.
• Willing to take a curative antimalarial regimen following challenge.
• Willing to be admitted to the FTMCTU in the Hospital of Tropical Medicine for blood donation and clinical monitoring, until antimalarial treatment is completed and their symptoms are settling.
• Willing to reside in Bangkok for the duration of the study, until all antimalarial treatment has been completed.
• Reachable (24/7) by mobile phone during the period between challenge CHMI and completion of all antimalarial treatment.
• Able to read and write and able to answer ALL questions on the informed consent questionnaire correctly.
• Provided written informed consent to participate in the trial.

Exclusion Criteria:

• History of clinical malaria.
• Positive malaria PCR OR malaria film OR malaria serology
• History of severe allergy to mosquito bite
• Presence of any medical condition (either physical or psychological) which in the judgment of the investigator would place the participant at undue risk or interfere with the results of the study (e.g. serious underlying cardiac, renal, hepatic or neurological disease; severe malnutrition; congenital defects or febrile condition).
• Plan to travel outside of Bangkok within the period of challenge until 3 months after.
• Use of systemic antibiotics with known antimalarial activity in the 30 days before challenge (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 past.
• Venipuncture unlikely to allow a 250 mL blood donation (as determined by the investigator).
• Receipt of an investigational product in the 30 days preceding enrolment (D0), 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, history of splenectomy, recurrent, severe infections, and chronic 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 malaria infection.
• Female participant who is pregnant, lactating or planning pregnancy during the course of the study.
• Contraindications to the use of antimalarial treatment (ex. chroroquine or primaquine).
• Use of medications known to have a potentially clinically significant interaction with antimalarial drug (ex. chroroquine or primaquine).
• Suspected or known current alcohol abuse
• Suspected or known injecting drug abuse.
• Use of medications known to cause prolongation of the QT interval and existing positive family history in both 1st AND 2nd degree relatives < 50 years 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.
• Concurrently participating in another clinical study, at any time during the study period.
• Screening ECG demonstrates a QTc interval ≥ 450 ms
• Haemoglobin < 13 g/dL in male, < 12g/dL in female (Thai Red Cross).
• Mean corpuscular volume (MCV) < 70 fL/cell
• Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination.
• Thalassemia or hemoglobinopathies.
• Positive for blood borne and vector borne infectious diseases (HIVI-II, HBV, HCV, Dengue, Zika, Chikungunya, Filariasis, JE, and malaria antigen, Anti HTLVI and Anti-HTLVII antibody, Syphilis test (VDRL, TPHA)
• Serum pregnancy test positive