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

Trypanosoma Brucei Gambiense; Infection Clinical Trial

— DiTECT-WP2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03356665
• Other study ID #: DiTECT-HAT-WP2
• Status: Completed
• Phase: N/A
• Start date: August 1, 2017
• Est. completion date: January 31, 2021

Study information

• Verified date: February 2021
• Source: Institut de Recherche pour le Developpement
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10700
• Est. completion date: January 31, 2021
• Est. primary completion date: January 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Diagnostic Test:
• Rapid diagnostic test (RDT)
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.
• Serological and molecular tests on DBS
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

Locations

Country	Name	City	State
Congo, The Democratic Republic of the	Programme Nationale de Lutte contre la trypanosomiase humaine Africaine	Kinshasa
Côte D'Ivoire	Institut Pierre Richet, Institut National de Santé Publique	Bouaké
Guinea	Programme Nationale de Lutte contre la Trypanosomiase Humaine Africaine, Ministère de Santé, Division Prévention et Lutte contre la Maladie	Conakry

Sponsors (8)

Lead Sponsor	Collaborator
Institut de Recherche pour le Developpement	CIRDES, Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo, Institut National de Sante Publique, Institute of Tropical Medicine, Belgium, Ministry of Health, Guinea, Ministry of Public Health, Democratic Republic of the Congo, University of Liverpool

Countries where clinical trial is conducted

Congo, The Democratic Republic of the,  Côte D'Ivoire,  Guinea, 

References & Publications (12)

Bisser S, Lumbala C, Nguertoum E, Kande V, Flevaud L, Vatunga G, Boelaert M, Büscher P, Josenando T, Bessell PR, Biéler S, Ndung'u JM. Sensitivity and Specificity of a Prototype Rapid Diagnostic Test for the Detection of Trypanosoma brucei gambiense Infection: A Multi-centric Prospective Study. PLoS Negl Trop Dis. 2016 Apr 8;10(4):e0004608. doi: 10.1371/journal.pntd.0004608. eCollection 2016 Apr. — View Citation

Büscher P, Deborggraeve S. How can molecular diagnostics contribute to the elimination of human African trypanosomiasis? Expert Rev Mol Diagn. 2015 May;15(5):607-15. doi: 10.1586/14737159.2015.1027195. Epub 2015 Mar 18. Review. — View Citation

Büscher P, Mertens P, Leclipteux T, Gilleman Q, Jacquet D, Mumba-Ngoyi D, Pyana PP, Boelaert M, Lejon V. Sensitivity and specificity of HAT Sero-K-SeT, a rapid diagnostic test for serodiagnosis of sleeping sickness caused by Trypanosoma brucei gambiense: a case-control study. Lancet Glob Health. 2014 Jun;2(6):e359-63. doi: 10.1016/S2214-109X(14)70203-7. Epub 2014 May 9. — View Citation

Camara O, Camara M, Lejon V, Ilboudo H, Sakande H, Léno M, Büscher P, Bucheton B, Jamonneau V. Immune trypanolysis test with blood spotted on filter paper for epidemiological surveillance of sleeping sickness. Trop Med Int Health. 2014 Jul;19(7):828-31. doi: 10.1111/tmi.12316. Epub 2014 Apr 18. — View Citation

Hasker E, Lutumba P, Mumba D, Lejon V, Büscher P, Kande V, Muyembe JJ, Menten J, Robays J, Boelaert M. Diagnostic accuracy and feasibility of serological tests on filter paper samples for outbreak detection of T.b. gambiense human African trypanosomiasis. Am J Trop Med Hyg. 2010 Aug;83(2):374-9. doi: 10.4269/ajtmh.2010.09-0735. — View Citation

Jamonneau V, Bucheton B, Kaboré J, Ilboudo H, Camara O, Courtin F, Solano P, Kaba D, Kambire R, Lingue K, Camara M, Baelmans R, Lejon V, Büscher P. Revisiting the immune trypanolysis test to optimise epidemiological surveillance and control of sleeping sickness in West Africa. PLoS Negl Trop Dis. 2010 Dec 21;4(12):e917. doi: 10.1371/journal.pntd.0000917. — View Citation

Jamonneau V, Camara O, Ilboudo H, Peylhard M, Koffi M, Sakande H, N'Dri L, Sanou D, Dama E, Camara M, Lejon V. Accuracy of individual rapid tests for serodiagnosis of gambiense sleeping sickness in West Africa. PLoS Negl Trop Dis. 2015 Feb 2;9(2):e0003480. doi: 10.1371/journal.pntd.0003480. eCollection 2015 Feb. — View Citation

Mitashi P, Hasker E, Mbo F, Van Geertruyden JP, Kaswa M, Lumbala C, Boelaert M, Lutumba P. Integration of diagnosis and treatment of sleeping sickness in primary healthcare facilities in the Democratic Republic of the Congo. Trop Med Int Health. 2015 Jan;20(1):98-105. doi: 10.1111/tmi.12404. Epub 2014 Oct 20. — View Citation

Mitashi P, Hasker E, Ngoyi DM, Pyana PP, Lejon V, Van der Veken W, Lutumba P, Büscher P, Boelaert M, Deborggraeve S. Diagnostic accuracy of loopamp Trypanosoma brucei detection kit for diagnosis of human African trypanosomiasis in clinical samples. PLoS Negl Trop Dis. 2013 Oct 17;7(10):e2504. doi: 10.1371/journal.pntd.0002504. eCollection 2013. — View Citation

Mumba D, Bohorquez E, Messina J, Kande V, Taylor SM, Tshefu AK, Muwonga J, Kashamuka MM, Emch M, Tidwell R, Büscher P, Meshnick SR. Prevalence of human African trypanosomiasis in the Democratic Republic of the Congo. PLoS Negl Trop Dis. 2011 Aug;5(8):e1246. doi: 10.1371/journal.pntd.0001246. Epub 2011 Aug 2. — View Citation

Njiru ZK. Loop-mediated isothermal amplification technology: towards point of care diagnostics. PLoS Negl Trop Dis. 2012;6(6):e1572. doi: 10.1371/journal.pntd.0001572. Epub 2012 Jun 26. Review. — View Citation

Van Meirvenne N, Magnus E, Buscher P. Evaluation of variant specific trypanolysis tests for serodiagnosis of human infections with Trypanosoma brucei gambiense. Acta Trop. 1995 Dec;60(3):189-99. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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