bilharzia Schistosomiasis
Conditions
Interventions
24 volunteers will be randomised in a 1:1 ratio to the intervention group and
the control group. The intervention group (i.e. reinfection group) will be
exposed three times to 20 male Sm cercariae (
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Subject is aged >= 18 and
Exclusion criteria
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, immune-deficient, (severe) 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: - body weight 35.0 kg/m2 at screening; - positive HIV, HBV or HCV screening tests; - 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; - history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years; - any history of treatment for severe psychiatric disease by a psychiatrist in the past year; - history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset. 2. The chronic use of any drug known to interact with praziquantel, artesunate or lumefantrine metabolism (e.g. phenytoïn, carbamazepine, phenobarbital, primidon, dexamethason, rifampicine, cimetidine, flecaïnide, metoprolol, imipramine, amitriptyline, clomipramine, class IA and III anti-arrythmics, antipsychotics, antidepressants, macrolides, fluorchinolones, imidazole- and triazole antimycotics, antihistamines). Because lumefantrine may cause extension of QT-time, chronic use of drugs with effect on QT interval will result in exclusion from study participation. 3. For female subjects: positive urine pregnancy test at screening. 4. Any history of schistosomiasis or treatment for schistosomiasis. 5. Positive serology for schistosomiasis or elevated serum CAA at screening. 6. Known hypersensitivity to or contra-indications (including co-medication) for use of praziquantel, artesunate or lumefantrine. 7. Being an employee or student of the department of Parasitology or Infectious diseases of the LUMC.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - The protective efficacy of repeated exposure to male Sm cercariae measured by the difference in frequency of serum CAA positivity (>=1.0 pg/mL) between the reinfection group and the infection control group at any timepoint after the final infection at week 18; - Frequency and severity of adverse events after (repeated) human Sm infection with male cercariae | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory endpoints: - Comparison of time to positive serum and urine CAA test between the reinfection and infection control groups after the final infection at week 18; - Comparison of peak serum CAA concentration between the reinfection and infection control group after the final infection at week 18; - Comparison of eosinophil counts between the reinfection and infection control groups after challenge after the final infection at week 18; - Comparison of (glycan) antibody responses directed against Sm antigens between the reinfection and infection control participants as well as between protected and non-protected participants after the final infection at week 18 using protein and glycan arrays; - Comparison of cellular responses directed against Sm antigens between the reinfection and infection control participants as well as between protected and non-protected participants after the final infection at week 18 using flow cytometry; - The pooled attack rate after initial exposure to 20 male cercariae, i.e. proportion CAA positivity between week 0-8 for the reinfection participants and between week 18-26 for infection control participants. | — |
Countries
Netherlands
Outcome results
None listed