| Eligibility |
Inclusion Criteria:
1. Subject is aged = 18 and = 35 years and in good health.
2. Subject has adequate understanding of the procedures of the study and agrees to abide
strictly thereby.
3. Subject is able to communicate well with the investigator and is available to attend
all study visits.
4. The subject will remain within the Netherlands during the challenge period, not travel
to a malaria-endemic area during the study period, and is reachable (24/7) by mobile
telephone throughout the entire study period.
5. Subject agrees to inform his/her general practitioner about participation in the study
and to sign a request to release by the General Practitioner (GP), and medical
specialist when necessary, any relevant medical information concerning possible
contra- indications for participation in the study.
6. The subject agrees to refrain from blood donation throughout the study period and for
a defined period thereafter according to current guidelines.
7. For female subjects: subject agrees to use adequate contraception and not to
breastfeed for the duration of study. Acceptable forms of contraception include:
established use of oral, injected or implanted hormonal contraceptives; intrauterine
device or intrauterine system; barrier methods (condoms or diaphragm with additional
spermicide); male partner's sterilisation (with appropriate post-vasectomy
documentation of absence of sperm in the ejaculate); true abstinence when this is in
line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g.,
calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not
acceptable methods of contraception.
8. Subject agrees to refrain from intensive physical exercise (disproportionate to the
subjects usual daily activity or exercise routine) during the malaria challenge
period.
9. Subject agrees to avoid additional triggers that may cause elevations in liver enzymes
including alcohol from baseline up to 1 week post treatment.
10. Subject has signed informed consent.
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 volunteer during the study or
interfere with the interpretation of the study results. These include, but are not
limited to, any of the following.
1.1 Body weight <50 kg or Body Mass Index (BMI) <18 or >30 kg/m2 at screening. 1.2 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 cardiovascular events
(including ischemia and myocarditis) in 1st or 2nd degree relatives <50 years old.
1.3 A medical history of functional asplenia, sickle cell trait/disease, thalassaemia
trait/disease or G6PD deficiency.
1.4 History of epilepsy in the period of five years prior to study onset, even if no
longer on medication.
1.5 Screening tests positive for Human Immunodeficiency Virus (HIV), or active
Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV).
1.6 Chronic use of i) immunosuppressive drugs, ii) antibiotics or antimalarials, 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.
1.7 History of malignancy of any organ system (other than localized basal cell
carcinoma of the skin), treated or untreated, within the past 5 years.
1.8 Any history severe psychiatric disease diagnosed by a psychiatrist. 1.9 History of
drug or alcohol abuse interfering with normal social function in the period of one
year prior to study onset, positive urine toxicology test for cocaine or amphetamines
at screening or inclusion, or positive urine toxicology test for cannabis at
inclusion.
2. For female subjects: positive urine pregnancy test at screening or at inclusion.
3. Any history of malaria, positive serology for P. falciparum, or previous participation
in any malaria (vaccine) study.
4. Known hypersensitivity to or contra-indications (including co-medication) for use of
Mefloquine, Malarone or artemether-lumefantrine, or history of severe (allergic)
reactions to mosquito bites.
5. Receipt of any vaccinations in the 3 months prior to the start of the study or plans
to receive any other vaccinations during the study period or up to 90 days thereafter.
6. Participation in any other clinical study in the 30 days prior to the start of the
study or during the study period.
7. Being an employee or student of the department of Medical Microbiology of the
Radboudumc or the department of Internal Medicine.
8. Any other condition or situation that would, in the opinion of the investigator, place
the subject at an unacceptable risk of injury or render the subject unable to meet the
requirements of the protocol.
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