Establishing a single-sex controlled human Schistosoma mansoni infection model for Uganda: safety and dose finding
Schistosomiasis
Healthy human volunteers will be enrolled from two settings; one with minimal prior schistosome exposure and another with intense prior exposure, both in Uganda. In each setting, groups of volunteers will be dermally exposed to single-sex (male) cercariae once at doses of between 10 and 30 cercariae. Depending on the outcome of the low dose infection, the dose will be escalated or additional volunteers will be exposed to the same number of cercariae. Volunteers will undergo intensive follow-up for 24 weeks and a late follow-up time point at 52 weeks. They will visit the clinical trial centre weekly after infection for 12 weeks. After this, two-weekly visits will continue until week 24. A final follow up visit will be after one year. During the visits, adverse events will be recorded, levels of Schistosoma mansoni circulating anodic antigen (CAA) will be measured and samples obtained for immunological analyses. Immediately CAA is detected (expected around 6 to 8 weeks after infection) the volunteers will be treated with praziquantel to cure the Schistosoma infection. Praziquantel may be repeated 4 weeks later if CAA levels do not fall to zero. Volunteers will be required to avoid contact with potentially Schistosoma mansoni-contaminated water until the controlled infection has been shown to have been effectively cured, potentially a period of up to 14 weeks. The trial is estimated to last 30 months.
1. Volunteer is aged ≥18 and ≤45 years and in good health 2. Volunteer is able to communicate well with the research team members and is available to attend all study visits 3. Volunteer has an adequate understanding of the procedures of the study and agrees to abide strictly thereby 4. Volunteer will remain within Uganda during the study period and is reachable by mobile telephone from until at least week 16 of the study period 5. Volunteer understands the need to avoid contact with waterbodies where Schistosoma is transmitted and can demonstrate that they are able and willing to do so for the full 12-16 week period until the controlled infection has been cured 6. Volunteer agrees to refrain from blood donation throughout the study period 7. For a female volunteer: volunteer agrees to use adequate contraception and not to breastfeed for the duration of the study 8. Volunteer has signed informed consent
1. Evidence of current Schistosoma infection based on highly sensitive CAA assay (at a conservative cut-off level of >0.5 pg/ml) 2. Evidence of malaria or of intestinal helminth infections (if identified, these will be treated and the volunteer may be reconsidered for inclusion) 3. 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, immune-deficient, 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. Note that volunteers may be reconsidered for inclusion following recovery from treatable conditions: 3.1. Temperature ≥37.5°C/99.5°F 3.2. Body weight <50 kg or Body Mass Index (BMI) <18.0 or >30.0 kg/m² at screening 3.3. Positive HIV, HBV or HCV screening tests 3.4. The use of 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 3.5. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years 3.6. Any history of treatment for severe psychiatric disease by a psychiatrist in the past year 3.7. History of drug or alcohol abuse interfering with normal social function in the period of 1 year prior to study onset 3.8. Any clinically significant abnormalities (including extended QT interval) on electrocardiogram 4. The chronic use of any drug known to interact with praziquantel, artesunate or lumefantrine metabolism (e.g. phenytoïn, carbamazepine, phenobarbital, primidone, dexamethasone, rifampicin, cimetidine, flecainide, metoprolol, imipramine, amitriptyline, clom