Susceptibility of Gambian Adults to PfSPZ-Challenge Infection in the Controlled Human Malaria Infection Model (CHMI-Gambia1)

This is an interventional basic science trial for Malaria focused on measuring malaria, infection, controlled Read More

Inclusion Criteria:

• Males aged ≥ 18 and ≤ 35 years and in good health;
• At least 4 completed years of secondary education;
• Adequate understanding of the procedures of the study in English language;
• Willing (in the investigator's opinion) to comply with all study requirements;
• Willing to complete an informed consent questionnaire and is able to answer all questions correctly;
• Signed written informed consent to participate in the trial;
• Willing to take a course of curative anti-malaria medication;
• Able to communicate well with the investigator and is available to attend all study visits;
• Willing to stay in a hotel close to the trial centre OR willing to be hospitalized in the CSD of MRCG during a part of the study (day 5 post-infection until day 3 after treatment);
• Reachable (24/7) by mobile telephone throughout the entire study period;
• Agrees to refrain from blood donation or for other purposes throughout the study period and after the end of their involvement in the study according to the local blood banking eligibility criteria.
• Agrees to refrain from intensive physical exercise (disproportionate to the participant's usual daily activity or exercise routine) during the malaria challenge period;
• Hb ≥12 g/dl.

Exclusion Criteria:

1. Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine,malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the participant during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following

   1. Body weight <50 kg or Body Mass Index (BMI) <18 or >30 kg/m2 at screening.
   2. A heightened risk of cardiovascular disease, as determined by: an estimated ten year risk of fatal cardiovascular disease of ≥5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia's, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives <50 years old.
   3. A medical history of functional asplenia, G6PD disease or α-thalassaemia disease.
   4. Positive test for sickle cell disease.
   5. History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
   6. Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV).
   7. Chronic use of i) immunosuppressive drugs, ii) antibiotics, iii) or other immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period.
   8. Any recent or current systemic therapy with an antibiotic or drug with potential anti-malarial activity (chloroquine, doxycycline, tetracycline, piperaquine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, erythromycin, hydroxychloroquine, etc.) (Allowable timeframe for use at the Investigator's discretion).
   9. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
   10. Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.
   11. Suspicion or history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset.
   12. Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination.
2. qPCR positive for Pf parasites at screening or previous participation in any malaria (vaccine) study.
3. Known hypersensitivity to artemether-lumefantrine.
4. Current use of any drug that is metabolised by the cytochrome enzyme CYP2D6 (e.g. flecainide, metoprolol, imipramine, amitriptyline, clomipramine).
5. Current use of drugs that are known to prolong the QTc interval such as: antiarrhythmics of classes IA and III; neuroleptics and antidepressant agents; certain antibiotics including some agents of the following classes: macrolides, fluoroquinolones, imidazole, and triazole antifungal agents; certain non-sedating antihistaminics (terfenadine, astemizole); cisapride.
6. Disturbances of electrolyte balance, e.g. hypokalaemia.
7. Inability to consume food
8. Use of immunoglobulin or blood products within 3 months prior to enrolment.
9. Participation in any other clinical study in the 30 days prior to the start of the study or during the study period, or prior receipt of an investigational malaria vaccine.
10. Any other condition or situation that would, in the opinion of the investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol.
11. Any other significant disease, disorder or finding which may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study or impair interpretation of the study data.