Clinical trial NCT03356665: Diagnostic Tools for Human African Trypanosomiasis Elimination and Clinical Trials: WP2 Passive Case Detection
Official title: Diagnostic Tools for Human African Trypanosomiasis Elimination and Clinical Trials: WP2 Passive Case Detection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: African Trypanosomiases
West African; Trypanosomiasis
Sleeping Sickness; West African
Trypanosoma Brucei Gambiense; Infection
Keywords: diagnosis
sensitivity
specificity
rapid diagnostic test
molecular biology
LAMP
RT-PCR
serology
ELISA
immune trypanolysis
clinical symptom
Lead sponsor: Institut de Recherche pour le Developpement
Sponsor class: OTHER_GOV
Collaborators: name: Ministry of Public Health, Democratic Republic of the Congo
name: Ministry of Health, Guinea
name: Institut National de Sante Publique
name: Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
name: CIRDES
name: Institute of Tropical Medicine, Belgium
name: University of Liverpool
First posted: 2017-11-29
Enrollment: 10700
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Sequential assignement
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sensitivity for HAT diagnosis of RDT, RDT combinations, algorithms of RDT and serological and/or molecular tests on HAT clinical suspects
timeFrame: 6 months
measure: Specificity for HAT diagnosis of RDT, RDT combinations, algorithms of RDT and serological and/or molecular tests on HAT clinical suspects
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: Programme Nationale de Lutte contre la trypanosomiase humaine Africaine
city: Bouaké
country: Côte D'Ivoire
facility: Institut Pierre Richet, Institut National de Santé Publique
city: Conakry
country: Guinea
facility: Programme Nationale de Lutte contre la Trypanosomiase Humaine Africaine, Ministère de Santé, Division Prévention et Lutte contre la Maladie
Study officials:
affiliation: Institut de Recherche pour le Developpement
name: Veerle Lejon, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bisser S, Lumbala C, Nguertoum E, Kande V, Flevaud L, Vatunga G, Boelaert M, Buscher P, Josenando T, Bessell PR, Bieler 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.
citation: Buscher 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.
citation: Buscher 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.
citation: Camara O, Camara M, Lejon V, Ilboudo H, Sakande H, Leno M, Buscher 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.
citation: Hasker E, Lutumba P, Mumba D, Lejon V, Buscher 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.
citation: Jamonneau V, Bucheton B, Kabore J, Ilboudo H, Camara O, Courtin F, Solano P, Kaba D, Kambire R, Lingue K, Camara M, Baelmans R, Lejon V, Buscher 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.
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.
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.
citation: Mitashi P, Hasker E, Ngoyi DM, Pyana PP, Lejon V, Van der Veken W, Lutumba P, Buscher 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.
citation: Mumba D, Bohorquez E, Messina J, Kande V, Taylor SM, Tshefu AK, Muwonga J, Kashamuka MM, Emch M, Tidwell R, Buscher 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.
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. No abstract available.
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. doi: 10.1016/0001-706x(95)00127-z.
citation: Kone M, Kaba D, Kabore J, Thomas LF, Falzon LC, Koffi M, Kouame CM, Ahouty B, Compaore CFA, N'Gouan EK, Solano P, Fevre E, Buscher P, Lejon V, Jamonneau V. Passive surveillance of human African trypanosomiasis in Cote d'Ivoire: Understanding prevalence, clinical symptoms and signs, and diagnostic test characteristics. PLoS Negl Trop Dis. 2021 Aug 30;15(8):e0009656. doi: 10.1371/journal.pntd.0009656. eCollection 2021 Aug.