Diagnostic Tools for Human African Trypanosomiasis Elimination and Clinical Trials: WP3 Post Elimination Monitoring

Not Applicable

Completed

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

• Registration Number: NCT04099628
• Lead Sponsor: Institut de Recherche pour le Developpement

Brief Summary

This study determines the feasibility, diagnostic performance and cost for monitoring of eliminated human African trypanosomiasis (HAT) foci using diagnostic algorithms of serological and molecular high throughput tests with and without previous rapid diagnostic test blood screening for early detection of Trypanosoma brucei gambiense HAT re-emergence.

Detailed Description

In the last decade, the prevalence of Trypanosoma brucei gambiense (Tbg) human African trypanosomiasis (HAT) has fallen and HAT has been targeted for elimination. At low disease prevalence, HAT control is increasingly integrated into routine activities of peripheral health centres. However, the weak capacity of fixed health structures to implement control activities, lack of coverage, the unspecific clinical picture of HAT, and the existence of asymptomatic cases and animal reservoirs may result in under detection of HAT. To ensure sustainability of zero transmission and to avoid re-emergence caused by remaining Tbg reservoirs, continued post-elimination monitoring is therefore required.

Health workers performing house to house visits in foci with very low HAT prevalence can easily collect blood on filter paper and send it to regional HAT reference centres for analysis. The objective of the DiTECT-HAT-WP3 study is to determine the feasibility and cost of diagnostic algorithms of serological and molecular high-throughput tests on blood on filter paper for post-elimination monitoring, with or without a previous screening with rapid diagnostic tests.

In villages in low to zero prevalence foci in Democratic Republic (DR) Congo, Côte d'Ivoire and Burkina Faso, a health worker will go from house to house to 1) register all consenting inhabitants in a Personal Digital Assistant; 2) take a blood sample on filter paper 3) perform 3 rapid diagnostic tests. All dried blood spots (DBS) are sent to the reference laboratory for high-throughput testing (ELISA, trypanolysis, loop-mediated isothermal amplification method (LAMP) and real time (RT) -PCR). Subjects positive in at least 1 test - the RDTs or high-throughput tests - are revisited twice for parasitological confirmation.

In each country, blood specimens of 6000 persons will be tested. The relative effectiveness and overall cost of the different diagnostic algorithms will be investigated. We will quantify the break-even point for an imperfect test algorithm by formulating a decision criterion to assess how many false negatives, but particularly how many false positives can be tolerated while still achieving an intervention with a reasonable cost burden. The results will enable us to propose a test algorithm and a threshold to send out specialised mobile teams for stopping HAT re-emergence, without unnecessarily raising the alarm.

Study Timeline

• Study Start: 2019-09-01
• Study First Submitted: 2019-09-19
• Study First Submitted QC: 2019-09-20
• Study First Posted: 2019-09-23
• Primary Completion: 2021-01-31
• Study Completion: 2021-01-31
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-14
• Last Update Posted: 2022-04-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13747

Inclusion Criteria

• Permanent resident of village (in low to zero prevalence HAT focus) for minimum 1 year

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
Diagnostic tests	Rapid diagnostic test (RDT); Serological and molecular tests on DBS	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 the population at risk	6 months	Index tests: 3 RDTs on fresh blood, immune trypanolysis on DBS, ELISA on DBS, LAMP on DBS, RT-PCR on DBS.; Reference standard: for index test positives only: combined results of 2 parasitological examinations. Subjects negative in all index tests are considered HAT negative.
Sensitivity for HAT diagnosis of RDT, RDT combinations, algorithms of RDT and serological and/or molecular tests on the population at risk	6 months	Index tests: 3 RDTs on fresh blood, immune trypanolysis on DBS, ELISA on DBS, LAMP on DBS, RT-PCR on DBS.; Reference standard: for index test positives only: combined results of 2 parasitological examinations. Subjects negative in all index tests are considered HAT negative.

Trial Locations

Locations (3)

CIRDES; 🇧🇫 Bobo Dioulasso, Burkina Faso

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