The challenge of serodiagnosis of sleeping sickness in the context of elimination
Authors: Vincent Jamonneau, Bruno Bucheton
Journal: The Lancet Global Health (2014)

Gambiense human African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease that has been targeted for elimination as a public health problem by 2020.1WHOAccelerating work to overcome the global impact of neglected tropical diseases: a roadmap for implementation.http://www.who.int/neglected_diseases/NTD_RoadMap_2012_Fullversion.pdfGoogle Scholar Although this goal is challenging, it now seems achievable. Control efforts, sustained mainly by mobile teams who screen populations at risk with the Card Agglutination Test for Trypanosomiasis (CATT) and treat patients if confirmed by microscopic parasitological tests, have led to a rapid decrease in disease prevalence. Incidence passed below the symbolic number of 10 000 newly reported cases in 2009 and reached 7216 in 2012.2WHOControl and surveillance of human African trypanosomiasis. WHO technical report series 984. World Health Organization, Geneva2013Google Scholar Furthermore, important innovations in terms of diagnosis and treatment are now in development, generating great hopes that sustainable control strategies could be implemented. Among these achievements is the forthcoming availability of lateral flow rapid diagnostic tests that might be used for serodiagnosis of infection in place of CATT, which requires an electrical supply, a cold chain, and trained personnel. Alongside the elimination process, decreased disease prevalence means that screening by mobile teams will become less and less cost effective. Thus, integration of HAT diagnosis into the endemic country health systems needs to be promoted. Rapid diagnostic tests that do not require any specific equipment and are easy to use should help greatly in the development of an effective passive surveillance system in primary health-care centres. In The Lancet Global Health, Philippe Büscher and colleagues3Büscher P Mertens P Leclipteux T et al.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; 2: e359-e365Summary Full Text Full Text PDF Scopus (61) Google Scholar present the first formal assessment under field conditions of the HAT Sero-K-SeT rapid diagnostic test and compared its diagnostic accuracy with two other current serological tests: CATT and immune trypanolysis (a very sensitive and specific test that requires laboratory conditions). The study was done in the Bandundu province of DR Congo during an active screening campaign. The investigators noted no significant difference in sensitivity and specificity between the three tests and concluded that the accuracy of HAT Sero-K-SeT is adequate for HAT serodiagnosis, and thus that the test could be implemented for passive surveillance at peripheral health facilities. Notably, another rapid diagnostic test developed by the Foundation for Innovative Diagnostics (FIND) in collaboration with SD Bioline4Lumbala C Bisser S Nguertoum E et al.Development and evaluation of a rapid screening test for sleeping sickness.Ann Afr Med. 2013; 6: 49Google Scholar has also been developed. The two tests are based on the antibody recognition of the same trypanosome variant surface glycoproteins (LiTat 1.3 and LiTat 1.5). Additional efforts are now needed to assess their accuracy and implementation as passive surveillance techniques in different areas in central and west Africa because the variable antigen type recognition pattern of Trypanosoma brucei (T b) gambiense is known to differ geographically5Van Meirvenne N Magnus E Büscher P Evaluation of variant specific trypanolysis tests for serodiagnosis of human infections with Trypanosoma brucei gambiense.Acta Tropica. 1995; 60: 189-199Crossref PubMed Scopus (93) Google Scholar, 6Dukes P Gibson WC Gashumba JK et al.Absence of the LiTat 1.3 (CATT antigen) gene in Trypanosoma brucei gambiense stocks from Cameroon.Acta Trop. 1992; 51: 123-134Crossref PubMed Scopus (63) Google Scholar, 7Enyaru JCK Matovu E Akol M et al.Parasitological detection of Trypanosoma brucei gambiense in serologically negative sleeping-sickness suspects from north-western Uganda.Ann Trop Med Parasitol. 1998; 92: 845-850Crossref PubMed Scopus (20) Google Scholar and because integration of HAT diagnosis in the primary health-care system is challenging.8Mitashi P Hasker E Lejon V et al.Human African trypanosomiasis diagnosis in first-line health services of endemic countries, a systematic review.PLoS Negl Trop Dis. 2012; 6: e1919Crossref PubMed Scopus (43) Google Scholar Nevertheless, availability of such rapid serodiagnostic tests only partly simplifies the diagnosis of HAT. As for CATT, these rapid diagnostic tests are only serological suspicion tests and parasitological confirmation by central laboratories is needed before treatment can be started. This issue arises because all available serological tests are hindered by insufficient specificity, and fears surround overtreatment with present drugs that are toxic, complex to administer, and require long-term admission to specific treatment centres. In this regard, new oral drugs such as fexinidazole2WHOControl and surveillance of human African trypanosomiasis. WHO technical report series 984. World Health Organization, Geneva2013Google Scholar, 9Torreele E Bourdin Trunz B Tweats D et al.Fexinidazole—a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness.PLoS Negl Trop Dis. 2010; 4: e923Crossref PubMed Scopus (224) Google Scholar have now entered phase 2 clinical trials and might soon become available. Second-generation rapid diagnostic tests, based on other recombinant proteins or peptides, are also under development as continuous efforts to improve HAT diagnosis. These efforts should be encouraged because they might (alone or in combination) significantly increase the specificity of serological diagnosis and thus simplify treatment decisions. The possibility of being able to treat patients with an oral drug on the basis of a rapid diagnostic test or combination of rapid diagnostic tests would be a giant leap towards the elimination of sleeping sickness: a dream that is now in sight. A healthy competition exists between several groups to develop HAT rapid diagnostic tests, which should improve quality and provide options in case one test fails to improve diagnostic accuracy. As a neglected tropical disease and with decreasing disease prevalence, progressive commercial disinterest is a possibility for HAT. Thus, reliance on a single rapid diagnostic test for which production could be stopped for economic reasons is dangerous, and could harm the elimination strategy. All the political, financial, and technical ingredients seem to be in place to make HAT elimination a success story.10Franco JR Simarro PP Diarra A Ruiz Postigo JA Jannin JG The journey towards elimination of gambiense human African trypanosomiasis: not far, nor easy.Parasitology. 2014; 141: 748-760Crossref PubMed Scopus (83) Google Scholar We should not miss this historical opportunity. We declare that we have no competing interests. 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 studyThe diagnostic accuracy of HAT Sero-K-SeT is adequate for T b gambiense antibody detection in local health centres and could be used for active screening whenever a cold chain and electricity supply are unavailable and CATT/T b gambiense cannot be done. Full-Text PDF Open Access