A safety and tolerability study in humans for chemically attenuated malaria parasites

Exclusion Criteria29

• Has increased cardiovascular disease risk (defined as >10%, 5 yr risk) as determined by the method of Gaziano et al. Risk factors include: sex, age, systolic blood pressure, smoking status, body mass index (BMI, kg/mm2), and reported diabetes status and blood pressure.
• History of splenectomy
• History of severe allergic reaction, anaphylaxis or convulsion following any vaccination, infusion or treatment with anti-malarial drugs artemether and/or lumefantrine.
• Presence of current or suspected chronic diseases such as cardiac or autoimmune disease (HIV or other immunodeficiencies), insulin dependent diabetes, progressive neurological disease, severe malnutrition, acute or progressive hepatic disease, acute or progressive renal disease, psoriasis, rheumatoid arthritis, asthma, epilepsy, obsessive compulsive disorder, skin carcinoma excluding non-spreadable skin cancers such as basal cell and squamous cell carcinoma.
• Known inherited genetic anomaly (known as cytogenic disorders) eg Down’s syndrome.
• Individuals wishing to donate blood to the Australian Red Cross Blood Service in the future.
• The volunteer has a diagnosis of schizophrenia, bi-polar disease, severe depression or other severe (disabling) chronic psychiatric disorder. Participants who are receiving a single anti-depressant drug and are stable for at least 3 months prior to enrollment without decompensating may be allowed to enroll in the study at the investigator’s discretion.
• Has been hospitalised in the past 5 years prior to enrolment for psychiatric illness, history of suicide attempt or confinement for danger to self or others.
• Known pre-existing prolongation of the QTc interval. Family history of congenital prolongation of the QTc interval on electrocardiograms or of sudden death or any other clinical conditions known to prolong the QTc interval eg volunteers with a history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease.
• Recent or current therapy with antibiotic or drug with potential antimalarial activity (tetracycline, azithromycin, clindamycin, hydroxychloroquine etc).
• Concomitant use of any drug which is metabolized by the cytochrome enzyme CYP2D6 (eg flecainide, metoprolol, imipramine, amitriptyline, clomipramine) OR drugs that are known to prolong the QTc interval e.g. antiarrhythmics of classes IA and III, neuroleptics, antidepressant agents, certain antibiotics (including some agents of the following classes: macrolides, fluoroquinolones, imidazole and triazole antifungal agents), certain nonsedating antihistamines (terfenadine, astemizole), cisapride.
• Use of corticosteroids, anti-inflammatory drugs, any immunomodulators or anticoagulants. Currently receiving or have previously received immunosuppressive therapy, including systemic steroids including ACTH or inhaled steroids in dosages which are associated with hypothalamic-pituitary axis suppression such as 1mg/kg/day or prednisone or its equivalent or chronic use of inhaled high potency corticosteroids (budesonide 800 microgram per day or fluticasone 750 microgram).
• Presence of acute infectious disease or fever (e.g. sub-lingual temperature greater than or equal to 38.5oC) within the five days prior to the study product administration.
• Evidence of acute illness within the 4 weeks before trial prior to screening and enrollment.
• Significant intercurrent disease of any type, in particular liver, renal, cardiac, pulmonary, neurologic, rheumatologic or autoimmune disease by history, physical examination and/or laboratory studies including urinalysis.
• Alcohol consumption greater than community norms (ie more than 21 standard drinks per week for males).
• A history of drug habituation, or any prior intravenous usage of an illicit substance.
• Medical requirement for intravenous administration of immunoglobulin or blood transfusions.
• Participation in any investigational product study within 8 weeks preceding the study.
• Participation in any research study involving significant blood sampling, or blood donation to Red Cross (or other) blood bank during the 8 weeks preceding the study.
• Have ever received a blood transfusion.
• Positive test for HIV, Hepatitis B, Hepatitis C, Human T-cell Lymphotropic Virus I and II(HTLV I and II), TB or syphilis.
• Any clinically significant biochemical or haematologic abnormality (Hb must be greater than or equal to 13.5g/dL).
• Ingestion of any poppy seeds within the 48 hours prior to the screening blood test (volunteers will be advised by phone not to consume any poppy seeds in this time period).
• Detection of any of the following drugs ( Amphetamines, Methamphetamines, Barbiturates, Benzodiazepines, Cocaine, Methadone, Opiates, Phencyclidine, Tetrahydrocannabinols, Tricyclic antidepressants) in the urine drug screen unless there is an explanation acceptable to the medical investigator (eg the subject has stated in advance that they consumed a prescription or OTC product which contained the detected drug) and/or the subject has a negative drug screen on retest by the pathology laboratory.
• Evidence of any condition that, in the opinion of the clinical investigator, might interfere with the evaluation of the study objectives or pose excessive risks to participants
• G-6-PD deficiency
• History of malaria
• Travelled to or lived ( greater than 2 weeks) in a malaria-endemic country during the past 12 months or planned to travel to a malaria-endemic country during the course of the study.