Diagnostic Tools for Human African Trypanosomiasis Elimination and Clinical Trials: WP2 Passive Case Detection

Study Overview
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Brief Summary
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The study determines the diagnostic performance and cost of rapid diagnostic tests (RDTs) performed on human African trypanosomiasis clinical suspects in peripheral health centres, whether or not followed by serological and/or molecular tests on dried blood spots done at regional reference centres

Detailed Description
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In the last decade, the prevalence of Trypanosoma brucei gambiense human African trypanosomiasis (HAT) has fallen and HAT has been targeted for elimination. At low disease prevalence, integration of case finding into routine activities of peripheral health centres becomes crucial. However, HAT case detection by the peripheral health system with limited resources requires adapted diagnostic tests and test algorithms. The objective of the DiTECT-HAT-WP2 study is to determine the diagnostic performance and cost of rapid diagnostic tests (RDTs) performed on clinical suspects in peripheral health centres, whether or not followed by serological and/or molecular tests on filter paper done at regional reference centres. The DiTECT-HAT-WP2 study will be conducted in centres for diagnosis and treatment and in sites for serological screening in Guinea, Côte d'Ivoire and DR Congo. In these centres and sites, clinical suspects will be tested with several commercially available RDTs for HAT. Clinical suspects with at least 1 RDT positive result, will 1° undergo parasitological examination and 2° blood collection on filter paper for reference analysis in trypanolysis, LAMP, ELISA and real-time PCR in the regional reference laboratory. If the reference laboratory tests and parasitological examinations are all negative, the suspect is informed and considered free of HAT. If at least 1 reference test is positive, parasitological examinations are repeated at least twice at three months interval, unless trypanosomes are detected. In order to assess the sensitivity, specificity, Positive Predictive Values and Negative Predictive Values of each assay in these multiple populations, the data from the multiple assays in the 3 countries will be used in a Bayesian formulation of the Hui-Walter latent class model, to estimate the assay performances in the absence of a gold standard. As we will collect full cost information for the different algorithms, we will, in addition to estimating the diagnostic effectiveness of the assay, be able to estimate the cost of each assay in each setting, and rank this jointly with assay performance. The results will enable us to propose cost-effective test algorithms to detect HAT, adapted to peripheral health centres. Algorithms with high positive predictive values might allow test-and-treat scenarios without the need for complicated parasitological confirmations, once safe oral easy to use drugs become available to treat HAT.

Official Title
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Diagnostic Tools for Human African Trypanosomiasis Elimination and Clinical Trials: WP2 Passive Case Detection

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

Intervention / Treatment
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* Diagnostic Test: Rapid diagnostic test (RDT)
* Diagnostic Test: Serological and molecular tests on DBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Visit of or residence in a HAT endemic area Clinical suspicion of HAT based on: Recurrent fever not responding to anti-malarial medication; or Headache for a long duration (>14 days); or presence of swollen lymph nodes in the neck; or Important weight loss; or Weakness; or Important scratching; or Amenorrhea, abortion(s), or sterility; or Coma; or Psychiatric problems (aggressiveness, apathy, mental confusion, increasing unusual hilarity, ...); or Sleep disruption (nocturnal insomnia and excessive diurnal sleeping); or Motor abnormalities (convulsions, abnormal movements, shaking, walking difficulties); or Speech disorders. Exclusion Criteria: Previously treated for HAT (irrespective of time elapsed since treatment) No informed consent < 4 years old

Ages Eligible for Study
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Minimum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Interventional Model Description: Sequential assignement
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clinical suspect<br>Diagnostic tests: Rapid diagnostic test (RDT); Serological and molecular tests on DBS | Diagnostic Test: Rapid diagnostic test (RDT)<br>* The 4 rapid diagnostic tests (RDT) will be carried out on fresh blood from clinical suspects. Only those subjects that are positive in at least 1 RDT will 1) undergo tests on DBS (immune trypanolysis, ELISA and DNA detection); 2) undergo parasitological confirmation (reference standard) at inclusion.<br>* Other names: SD Bioline HAT 2.0 (Standard Diagnostics Korea);Diagnostic Test: Serological and molecular tests on DBS<br>* Serological and molecular reference tests on dried blood spots (DBS) are carried out on RDT positive clinical suspects, which also undergo parasitological examination at inclusion (reference standard). If at least one of the serological or molecular reference tests on dried blood spots is positive, parasitological examination is repeated 3 and 6 months after inclusion. The combined results of parasitological examinations (at inclusion and if applicable at 3 and 6 months) serve as reference standard<br>* Other names: RT-PCR: Trypanozoon 18S, Tbg TgsGP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity for HAT diagnosis of RDT, RDT combinations, algorithms of RDT and serological and/or molecular tests on HAT clinical suspects | Index tests: 4 RDTs on fresh blood, and for RDT positives also immune trypanolysis on DBS, ELISA on DBS, LAMP on DBS, RT-PCR on DBS. Reference standard: for RDT positives only: combined results of parasitological examination at inclusion and if one of tests on DBS positive, at 3 and 6 months. Subjects negative in all RDTs are considered HAT negative | 6 months | 
| Specificity for HAT diagnosis of RDT, RDT combinations, algorithms of RDT and serological and/or molecular tests on HAT clinical suspects | Index tests: 4 RDTs on fresh blood, and for RDT positives also immune trypanolysis on DBS, ELISA on DBS, LAMP on DBS, RT-PCR on DBS. Reference standard: for RDT positives only: combined results of parasitological examination at inclusion and if one of tests on DBS positive, at 3 and 6 months. Subjects negative in all RDTs are considered HAT negative. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sensitivity, diagnosis, specificity, rapid diagnostic test, molecular biology, LAMP, RT-PCR, serology, ELISA, immune trypanolysis, clinical symptom