Periodic Reporting for period 1 - STROGHAT (Stop transmission of gambiense human African trypanosomiasis)
Periodo di rendicontazione: 2023-07-01 al 2024-12-31
Gambiense human African trypanosomiasis (gHAT) or sleeping sickness is a neglected tropical disease caused by trypanosome parasites that is endemic in central and western Africa. The disease affects mainly rural and poor populations, and more than half of worldwide gHAT cases are reported in the Democratic Republic of Congo (DRC). The disease is almost always fatal if left untreated. Thanks to sustained control efforts, the global number of reported gHAT cases has recently reached an all-time low, and the disease is considered eliminated as a public health problem in most countries. WHO is now aiming for interruption of transmission by 2030.
Until now, treatment options for gHAT have been limited and toxic, forcing control programs to avoid overtreatment through complex diagnostic procedures, including screening with a serological test, highly specialized laborious microscopic confirmation of seropositive subjects and lumbar puncture for disease staging. This resulted in up to 50% of gHAT cases remaining untreated and representing a human reservoir. Recently, acoziborole, a single-dose oral drug with a good safety profile and high effectiveness in both disease stages, completed phase III evaluations. This new drug removes the need for lumbar puncture and appears safe enough to treat serological suspects without microscopic confirmation (screen & treat), simplifying case management and increasing treatment coverage. The STROGHAT study therefore aims to evaluate whether an approach based on treating all screening test seropositive subjects can lead to the elimination of T.b. gambiense from its human reservoir, which would lead automatically to interruption of transmission. The study will also extend the safety documentation of acoziborole and perform costing analysis of the new screen & treat approach. The study will additionally prospectively evaluate the performance of the screening and diagnostic tests used.
To achieve these objectives, all screening test seropositive subjects with a negative parasitological examination, identified in the gHAT focus of Equateur Nord in DRC will be treated with acoziborole for 3 consecutive years. Parasitologically confirmed cases will be treated with standard of care. Study participants will be identified through active and passive case finding. Available geographic data will be exploited to target villages where gHAT has recently occurred or is still present. Immunological and molecular tests will be performed in a reference laboratory for all screening test seropositive subjects, and will be used to determine individual follow-up needs and the HAT prevalence . After 3 years of intervention, standard procedures will resume and a survey will be conducted in the study region to assess whether interruption of transmission has been achieved.
STROGHAT will contribute to the WHO goal of interrupting gHAT transmission by 2030 by providing evidence on the effectiveness, safety and feasibility of the screen & treat strategy. This will be useful for the sleeping sickness national control program of DRC, and as well for WHO, other national sleeping sickness control programs and donors to inform elimination strategies.
Until now, treatment options for gHAT have been limited and toxic, forcing control programs to avoid overtreatment through complex diagnostic procedures, including screening with a serological test, highly specialized laborious microscopic confirmation of seropositive subjects and lumbar puncture for disease staging. This resulted in up to 50% of gHAT cases remaining untreated and representing a human reservoir. Recently, acoziborole, a single-dose oral drug with a good safety profile and high effectiveness in both disease stages, completed phase III evaluations. This new drug removes the need for lumbar puncture and appears safe enough to treat serological suspects without microscopic confirmation (screen & treat), simplifying case management and increasing treatment coverage. The STROGHAT study therefore aims to evaluate whether an approach based on treating all screening test seropositive subjects can lead to the elimination of T.b. gambiense from its human reservoir, which would lead automatically to interruption of transmission. The study will also extend the safety documentation of acoziborole and perform costing analysis of the new screen & treat approach. The study will additionally prospectively evaluate the performance of the screening and diagnostic tests used.
To achieve these objectives, all screening test seropositive subjects with a negative parasitological examination, identified in the gHAT focus of Equateur Nord in DRC will be treated with acoziborole for 3 consecutive years. Parasitologically confirmed cases will be treated with standard of care. Study participants will be identified through active and passive case finding. Available geographic data will be exploited to target villages where gHAT has recently occurred or is still present. Immunological and molecular tests will be performed in a reference laboratory for all screening test seropositive subjects, and will be used to determine individual follow-up needs and the HAT prevalence . After 3 years of intervention, standard procedures will resume and a survey will be conducted in the study region to assess whether interruption of transmission has been achieved.
STROGHAT will contribute to the WHO goal of interrupting gHAT transmission by 2030 by providing evidence on the effectiveness, safety and feasibility of the screen & treat strategy. This will be useful for the sleeping sickness national control program of DRC, and as well for WHO, other national sleeping sickness control programs and donors to inform elimination strategies.
In reporting period 1 (01/07/2023–31/12/2024), the project was launched, and key milestones were achieved.
WP1: The study protocol was finalized and approved by the Institutional Review Board of the Institute of Tropical Medicine (Antwerp), the Ethical Committee of the University of Antwerp, and the Comité National d’Ethique de la Santé, DRC. In-vitro safety studies revealed interactions between acoziborole and certain cytochromes but did not present a safety concern. A major amendment to the study protocol was approved. All necessary authorizations from regulatory bodies were granted. The clinical trial data collection tool, MEDRIO, was developed and implemented. A training session for 30 clinical trial investigators was held, and the first patient was enrolled on 16 September 2024.
WP2: Field teams (76 staff) were trained in HAT diagnostics and study procedures. At the national reference laboratory (INRB) 8 staff were trained and immunological and molecular tests performed. A total of 1,100 sampling kits were produced and dispatched. In the reporting period, 634 kits were collected and sent to INRB, where 533 immune-trypanolysis, 533 ELISA, and 386 Trypanozoon-RT-qPCR tests were performed. A quality assurance system with SOPs, internal and external controls, and proficiency testing was established.
WP3: A screening plan for 2024 and 2025 was prepared, with training for 106 PNLTHA and Ministry of Health staff on HAT management ad, study procedures. Screening began in March 2024, with 177,307 subjects screened. Of these, 624 were seropositive and four gHAT cases were identified (prevalence of 2.26 per 100,000 screened). 299 patients were enrolled in the clinical trial and treated with acoziborole, with follow-up as planned. A cartography of endemic villages was started, and 230 villages were mapped.
WP4: No activities were carried out in the reporting period, apart from ongoing mapping and surveillance.
WP5: A study on the acceptability of the screen-and-treat strategy was conducted. Sensitization and communication materials were developed and adapted for local use. Information sessions were held for 91 local health and political authorities. Participation in screening activities was high (91.33%).
WP6: A study protocol for the costing of the new strategy was prepared and will be submitted to the Institutional Review Board of the Institute of Tropical Medicine in Antwerp in early 2025. A RedCap tool collects costing data.
WP7: The grant agreement was finalized, and a scientific advisory committee was set up. Regular project management committee (PMC) meetings were held, with 9 meetings in the reporting period. A scientific advisory committee meeting took place in Kinshasa, DRC, on 12 September 2024. Preliminary results were presented at the DRC HAT partners meeting in January 2025. The study protocol was published on Open Research Europe (DOI 10.12688/openreseurope.19077.1).
WP1: The study protocol was finalized and approved by the Institutional Review Board of the Institute of Tropical Medicine (Antwerp), the Ethical Committee of the University of Antwerp, and the Comité National d’Ethique de la Santé, DRC. In-vitro safety studies revealed interactions between acoziborole and certain cytochromes but did not present a safety concern. A major amendment to the study protocol was approved. All necessary authorizations from regulatory bodies were granted. The clinical trial data collection tool, MEDRIO, was developed and implemented. A training session for 30 clinical trial investigators was held, and the first patient was enrolled on 16 September 2024.
WP2: Field teams (76 staff) were trained in HAT diagnostics and study procedures. At the national reference laboratory (INRB) 8 staff were trained and immunological and molecular tests performed. A total of 1,100 sampling kits were produced and dispatched. In the reporting period, 634 kits were collected and sent to INRB, where 533 immune-trypanolysis, 533 ELISA, and 386 Trypanozoon-RT-qPCR tests were performed. A quality assurance system with SOPs, internal and external controls, and proficiency testing was established.
WP3: A screening plan for 2024 and 2025 was prepared, with training for 106 PNLTHA and Ministry of Health staff on HAT management ad, study procedures. Screening began in March 2024, with 177,307 subjects screened. Of these, 624 were seropositive and four gHAT cases were identified (prevalence of 2.26 per 100,000 screened). 299 patients were enrolled in the clinical trial and treated with acoziborole, with follow-up as planned. A cartography of endemic villages was started, and 230 villages were mapped.
WP4: No activities were carried out in the reporting period, apart from ongoing mapping and surveillance.
WP5: A study on the acceptability of the screen-and-treat strategy was conducted. Sensitization and communication materials were developed and adapted for local use. Information sessions were held for 91 local health and political authorities. Participation in screening activities was high (91.33%).
WP6: A study protocol for the costing of the new strategy was prepared and will be submitted to the Institutional Review Board of the Institute of Tropical Medicine in Antwerp in early 2025. A RedCap tool collects costing data.
WP7: The grant agreement was finalized, and a scientific advisory committee was set up. Regular project management committee (PMC) meetings were held, with 9 meetings in the reporting period. A scientific advisory committee meeting took place in Kinshasa, DRC, on 12 September 2024. Preliminary results were presented at the DRC HAT partners meeting in January 2025. The study protocol was published on Open Research Europe (DOI 10.12688/openreseurope.19077.1).
The STROGHAT study will provide data on the effectiveness of the screen-and-treat strategy and additional safety data on acoziborole use in seropositive subjects without microscopic confirmation of disease. Data on the cost-effectiveness of the strategy will inform donors and control programs. The study will assess the DRC national control program’s capacity for implementation and community participation, identifying barriers to screening and treatment and solutions. It will also strengthen the DRC national reference laboratory for future gHAT elimination. Video tutorials for relevant diagnostic tests have been made available to health workers. Quality control at field level has been extended, and an international quality control circuit for tests at the central laboratory has been implemented.