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A group of 24 healthy volunteers are challenged one or three times with 20 male Schistosoma mansoni cercariae to investigate whether this leads to protection and to identify potential correlates of protection
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Reinfection group | Experimental | Participants will be exposed three times to 20 male Schistosoma mansoni cercariae (weeks 0, 9, and 18) |
|
| Infection control group | Active Comparator | 12 participants who will undergo a placebo mock infection with water twice (weeks 0 and 9) and will be exposed once to 20 male Schistosoma mansoni cercariae (week 18) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Schistosoma mansoni infection | Biological | 20 viable male Schistosoma mansoni cercariae of the Puerto Rican strain |
|
| Measure | Description | Time Frame |
|---|---|---|
| Protective efficacy | The protective efficacy of repeated exposure to male Sm cercariae measured by the difference in frequency of serum circulating aniodic antigen (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 and before week 30 | From week 18 until week 30 |
| Safety of (repeated) exposure to male Sm cercariae based on self-reported adverse events | Frequency and severity of adverse events after (repeated) human Sm infection with male cercariae | 38 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Time to CAA positivity | Comparison of time to positive serum and urine CAA test between the reinfection and infection control groups after the final infection at week 18 and before week 30 | From week 18 until week 30 |
| Peak serum CAA levels |
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Inclusion Criteria:
Exclusion Criteria:
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:
The chronic use of any drug known to interact with praziquantel, artesunate or lumefantrine metabolism (e.g. phenytoin, carbamazepine, phenobarbital, primidone, dexamethasone, rifampicin, cimetidine, flecainide, metoprolol, imipramine, amitriptyline, clomipramine, class IA and III anti-arrythmics, antipsychotics, antidepressants, macrolides, fluoroquinolones, 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.
For female subjects: positive urine pregnancy test at screening.
Any history of schistosomiasis or treatment for schistosomiasis.
Positive serology for schistosomiasis or elevated serum CAA at screening.
Known hypersensitivity to or contra-indications (including co-medication) for use of praziquantel, artesunate or lumefantrine.
Being an employee or student of the department of Parasitology or Infectious diseases of the LUMC.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Leiden University Medical Center | Leiden | 2333 ZA | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39666392 | Derived | Koopman JPR, Houlder EL, Janse JJ, Lamers OA, Roozen GV, Sijtsma JC, Casacuberta-Partal M, Hilt ST, van der Stoep MYEC, van Amerongen-Westra IM, Brienen EA, Wammes LJ, van Lieshout L, van Dam GJ, Corstjens PL, van Diepen A, Yazdanbakhsh M, Hokke CH, Roestenberg M. Clinical tolerance but no protective efficacy in a placebo-controlled trial of repeated controlled schistosome infection. J Clin Invest. 2024 Dec 12;135(4):e185422. doi: 10.1172/JCI185422. |
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| ID | Term |
|---|---|
| D012552 | Schistosomiasis |
| ID | Term |
|---|---|
| D014201 | Trematode Infections |
| D006373 | Helminthiasis |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
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| Placebo mock infection | Biological | Placebo mock infection with water |
|
Comparison of peak serum CAA concentration between the reinfection and infection control group after the final infection at week 18 and before week 30
| From week 18 until week 30 |
| Eosinophils | Comparison of eosinophil counts between the reinfection and infection control groups after challenge after the final infection at week 18 and before week 30 | From week 18 until week 30 |
| Antibody responses | 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 and before week 30 using protein and glycan arrays | From week 18 until week 30 |
| Cellular responses | 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 and before week 30 using flow cytometry | From week 18 until week 30 |
| Attack rate | 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 | 26 weeks |
| D000079426 |
| Vector Borne Diseases |