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

Not Applicable

Completed

• Conditions: Sleeping Sickness; West African; West African; Trypanosomiasis; African Trypanosomiases; Trypanosoma Brucei Gambiense; Infection
• Interventions: Diagnostic Test: Rapid diagnostic test (RDT); Diagnostic Test: Serological and molecular tests on DBS

• Registration Number: NCT03356665
• Lead Sponsor: Institut de Recherche pour le Developpement

Brief Summary

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

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.

Study Timeline

• Study Start: 2017-08-01
• Study First Submitted: 2017-11-24
• Study First Submitted QC: 2017-11-24
• Study First Posted: 2017-11-29
• Primary Completion: 2021-01-31
• Study Completion: 2021-01-31
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-18
• Last Update Posted: 2021-02-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10700

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Clinical suspect	Serological and molecular tests on DBS	Diagnostic tests: Rapid diagnostic test (RDT); Serological and molecular tests on DBS
Clinical suspect	Rapid diagnostic test (RDT)	Diagnostic tests: Rapid diagnostic test (RDT); Serological and molecular tests on DBS

Primary Outcome Measures

Name	Time	Method
Specificity for HAT diagnosis of RDT, RDT combinations, algorithms of RDT and serological and/or molecular tests on HAT clinical suspects	6 months	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.
Sensitivity for HAT diagnosis of RDT, RDT combinations, algorithms of RDT and serological and/or molecular tests on HAT clinical suspects	6 months	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

Trial Locations

Locations (3)

Programme Nationale de Lutte contre la trypanosomiase humaine Africaine; 🇨🇩 Kinshasa, Congo, The Democratic Republic of the

Institut Pierre Richet, Institut National de Santé Publique; 🇨🇮 Bouaké, Côte D'Ivoire

Programme Nationale de Lutte contre la Trypanosomiase Humaine Africaine, Ministère de Santé, Division Prévention et Lutte contre la Maladie; 🇬🇳 Conakry, Guinea