Prospective Evaluation of the Specificity of Serological Tests for Human African Trypanosomiasis

Study Overview
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Brief Summary
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This study evaluates and compares the diagnostic specificity of 5 serological field tests for screening of the population at risk for human African trypanosomiasis due to Trypanosoma brucei gambiense.

Detailed Description
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In the last decade, the prevalence of Trypanosoma brucei gambiense (Tbg) human African trypanosomiasis (HAT) has fallen and HAT has been targeted for transmission interruption by 2030. To achieve this goal, disease surveillance remains essential and is based on the identification of cases after screening carried out in the field with a serological test. The SpeSerTryp study is a prospective evaluation of the specificity of serological field tests for the diagnosis of HAT in Côte d'Ivoire and Guinea. Since the prevalence of HAT is low in these countries, sensitivity will not be assessed. The main objective is to evaluate and compare the specificity of 5 serological field tests: Bioline HAT 2.0 (Abbott, South Korea), HAT Sero-K-SeT & HAT 2.0 Sero-K-SeT (Coris BioConcept, Belgium ), TDR DCN (USA), and the CATT/T.b. gambiense (Institute of Tropical Medicine Antwerp, Belgium). The secondary objectives are: 1° to assess the specificity of the 5 serological field tests according to malaria status; and 2° to compare the performance of immunological laboratory tests (trypanolysis, ELISA/T.b.gambiense, g-iELISA) and molecular laboratory tests (Trypanozoon RT-qPCR multiplex, SNP RT-qPCR and SHERLOCK) as reference tests to differentiate false positive subjects to serological field tests from subjects who had contact with Tbg. Specificity values will be determined against a composite reference test consisting of the most sensitive HAT parasitological methods. SpeSerTryp is a prospective study that will take place in the endemic health districts of Bonon and Sinfra in Côte d'Ivoire and in the endemic health districts of Forécariah, Dubréka and Boffa in Guinea. In each country, 500 participants will be actively recruited by mobile teams. The inclusion criteria are: Age greater than or equal to 10 years and obtaining signed informed consent. The exclusion criteria are: Severe anemia preventing blood sampling; serious illness preventing the obtaining of informed consent and participation in the study; or history of HAT. After obtaining informed consent, a venous blood sample will be taken (6 mL). This specimen will be used to carry out the 5 serological tests for HAT, the RDT for malaria, and for participants with at least one of the 5 serological tests positive, parasitological confirmation of HAT and molecular and immunological laboratory tests . The duration of participant recruitment is estimated to be around 30 days, while laboratory analyses will take about 6 months. HAT cases identified during the study will be treated in accordance with current national guidelines. This study will be conducted in accordance with the protocol, the current version of the Declaration of Helsinki, ICH-BPC E6/R2 guidelines, and all national legal and regulatory requirements.

Official Title
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Prospective Evaluation of the Specificity of Serological Tests for Human African Trypanosomiasis in Côte d'Ivoire and Guinea

Conditions
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Human African Trypanosomiasis, Sleeping Sickness, Trypanosoma Brucei Gambiense; Infection, West African Sleeping Sickness

Intervention / Treatment
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* Diagnostic Test: Serological field test for HAT
* Diagnostic Test: malaria rapid test
* Diagnostic Test: Immunologic laboratory tests
* Diagnostic Test: Molecular laboratory tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: at least 10 years old signed the informed consent form (in case of minor: parent or tutor signs informed consent form and minor signs ascent form) Exclusion Criteria: severe anemia hindering blood sampling severe illness hindering obtention of informed consent (eg coma, cognitive deficiency etc) history of sleeping sickness

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: participant<br>All eligible participants will undergo 5 serological field tests for HAT and a malaria test. Those testing positive in at least 1 serological field test will undergo parasitology to confirm HAT and immunological and molecular laboratory tests | Diagnostic Test: Serological field test for HAT<br>* Whole blood is tested by lateral flow or agglutination (CATT) for the presence of trypanosome specific antibody. Participants testing positive for at least one of these tests will undergo microscopic examination to detect trypanosomes (lymph, mAECT on blood) and DBS will be prepared for immunological and molecular laboratory testing.<br>* Other names: Bioline HAT 2.0 (Abbott, South Korea), HAT Sero-K-SeT (Coris BioConcept, Belgium), HAT 2.0 Sero-K-SeT (Coris BioConcept, Belgium), RDT DCN (USA), CATT/Tb gambiense (ITM Antwerp, Belgium);Diagnostic Test: malaria rapid test<br>* RDT detecting HRP2 plasmodium antigen.<br>Diagnostic Test: Immunologic laboratory tests<br>* Laboratory tests detecting trypanosoma brucei gambiense specific (VSG) antibodies in DBS. These tests will only be carried out on participants that are positive in at least on of the rapid serological tests<br>* Other names: trypanolysis, ELISA/T.b.gambiense, g-iELISA;Diagnostic Test: Molecular laboratory tests<br>* Laboratory tests detecting Trypanozoon specific nucleic acids. These tests will only be carried out on participants that are positive in at least on of the rapid serological tests<br>* Other names: Trypanozoon RT-qPCR multiplex, SNP RT-qPCR, SHERLOCK;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specificity of serological field test for diagnosis of HAT during active screening in Côte d'Ivoire and Guinea | Index tests: Bioline HAT 2.0 (Abbott, South Korea), HAT Sero-K-SeT (Coris BioConcept, Belgium), HAT 2.0 Sero-K-SeT (Coris BioConcept, Belgium), RDT DCN (USA), CATT/Tb gambiense (ITM Antwerp, Belgium). Reference test: parasitological confirmation by combined lymph and blood (mAECT) examination | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Specificity of serological field test for diagnosis of HAT during active screening in Côte d'Ivoire and Guinea, in function of malaria status | Index tests: Bioline HAT 2.0 (Abbott, South Korea), HAT Sero-K-SeT (Coris BioConcept, Belgium), HAT 2.0 Sero-K-SeT (Coris BioConcept, Belgium), RDT DCN (USA), CATT/Tb gambiense (ITM Antwerp, Belgium). Reference test: parasitological confirmation by combined lymph and blood (mAECT) examination. The malaria status will be determined using an RDT detecting HRP2 | 1 month | 
| Specificity of immunologic and molecular laboratory tests for diagnosis of HAT in serological suspects | Index tests: trypanolysis, ELISA/T.b.gambiense, g-iELISA, Trypanozoon RT-qPCR multiplex, SNP RT-qPCR, SHERLOCK. Reference test: parasitological confirmation by combined lymph and blood (mAECT) examination. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diagnosis