Diagnostic Tools for Human African Trypanosomiasis Elimination and Clinical Trials: WP4 Early test-of-cure

In the last decade, the prevalence of Trypanosoma brucei gambiense human African trypanosomiasis (HAT) has fallen and HAT has been targeted for elimination. Clinical trials on safe and efficacious drugs for HAT, applicable in an elimination context, would be accelerated by availability of an early test of cure. The objective of the DiTECT-HAT-WP4 study was to validate the diagnostic performance of cerebrospinal fluid neopterin quantification and of blood and cerebrospinal fluid trypanosomal spliced leader RNA detection for assessing treatment outcome.

The DiTECT-HAT-WP4 study was embedded into a therapeutic phase II/III study, DNDi-OXA-02-HAT, testing a new oral single dose drug against HAT, acoziborole. After acoziborole treatment, patients had post-treatment examinations, including blood and cerebrospinal fluid examination at day 11, and during follow-up at month 6, month 12 and month 18. Combination of DiTECT-HAT-WP4 with the DNDi-OXA-02-HAT study in 5 study sites in RD Congo, allowed evaluation of new treatment outcome assessment markers during follow-up in 97 confirmed HAT patients, without the need for additional lumbar or venipunctures. The volumes of venous blood and cerebrospinal fluid taken was increased by 2.5 mls for the DiTECT-HAT-WP4 study. Reverse transcriptase real time PCR for spliced leader RNA detection in blood and cerebrospinal fluid and neopterin detection were carried out in the reference laboratory in Kinshasa (index tests). For evaluation of diagnostic performance of the index tests, the reference standard consisted of classification of treatment outcome according to international standards applied for the DNDi-OXA-02-HAT trial but excluding for DiTECT-HAT-WP4 patients lost to follow-up (including those who died for other reasons than HAT). Sensitivity and specificity of the different index tests for treatment outcome assessment was determined at each follow-up time point. Trypanosomal spliced leader RNA detection in blood may allow post-treatment follow-up without the need for lumbar punctures. Improved treatment outcome assessment will not only facilitate follow-up by avoiding the feared lumbar puncture but also speed up the development and implementation of new drugs. In addition, it will also improve management of patients in routine.

The deposited files contain the DiTECT-HAT-WP4 study protocol and the informed consent form. After publication, DiTECT-HAT-WP4 data will be made available to qualified researchers, upon request after signing a confidentiallity agreement. Data requests may be sent to the coordinating investigator (for coordinates see study protocol). (2022-07-08)