Persistence of antibodies to Trypanosoma brucei gambiense after treatment of human trypanosomiasis in Uganda

Pascal, Christophe; Ancelle, T.; Gastellu-Etchegorry, M.; Castilla, Jorge; Harndt, Irena

doi:10.1016/0140-6736(92)90524-7

Cited by 16 publications

(14 citation statements)

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“…It has been described that antibodies can persist up to 3 years post cure, however it is not known which class of antibodies persist or which antigens they recognise [52]. Ideally, a longitudinal study could be carried out to gain a greater insight into this and how it could affect the diagnostic potential of any future lateral flow test relying on antibodies [32].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Selection of Immunodiagnostic Antigens for Human African Trypanosomiasis and Generation of a Prototype Lateral Flow Immunodiagnostic Device

Sullivan

Wall²,

Carrington

et al. 2013

PLoS Negl Trop Dis

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BackgroundThe diagnosis of Human African Trypanosomiasis relies mainly on the Card Agglutination Test for Trypanosomiasis (CATT). While this test is successful, it is acknowledged that there may be room for improvement. Our aim was to develop a prototype lateral flow test based on the detection of antibodies to trypanosome antigens.Methodology/Principal FindingsWe took a non-biased approach to identify potential immunodiagnostic parasite protein antigens. The IgG fractions from the sera from Trypanosoma brucei gambiense infected and control patients were isolated using protein-G affinity chromatography and then immobilized on Sepharose beads. The IgG-beads were incubated with detergent lysates of trypanosomes and those proteins that bound were identified by mass spectrometry-based proteomic methods. This approach provided a list of twenty-four trypanosome proteins that selectively bound to the infection IgG fraction and that might, therefore, be considered as immunodiagnostic antigens. We selected four antigens from this list (ISG64, ISG65, ISG75 and GRESAG4) and performed protein expression trials in E. coli with twelve constructs. Seven soluble recombinant protein products (three for ISG64, two for ISG65 and one each for ISG75 and GRESAG4) were obtained and assessed for their immunodiagnostic potential by ELISA using individual and/or pooled patient sera. The ISG65 and ISG64 construct ELISAs performed well with respect to detecting T. b. gambiense infections, though less well for detecting T. b. rhodesiense infections, and the best performing ISG65 construct was used to develop a prototype lateral flow diagnostic device.Conclusions/SignificanceUsing a panel of eighty randomized T. b. gambiense infection and control sera, the prototype showed reasonable sensitivity (88%) and specificity (93%) using visual readout in detecting T. b. gambiense infections. These results provide encouragement to further develop and optimize the lateral flow device for clinical use.

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Section: Discussionmentioning

confidence: 99%

Proteomic Selection of Immunodiagnostic Antigens for Human African Trypanosomiasis and Generation of a Prototype Lateral Flow Immunodiagnostic Device

Sullivan

Wall²,

Carrington

et al. 2013

PLoS Negl Trop Dis

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“…Current serological tests detect antibodies after 3 to 4 weeks of infection (126). Seropositivity must be interpreted with caution in previously treated patients since antibodies can persist for up to 3 years after cure (91).…”

Section: Antibody Detectionmentioning

confidence: 99%

Options for Field Diagnosis of Human African Trypanosomiasis

et al. 2005

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Human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense or T. b. rhodesiense remains highly prevalent in several rural areas of sub-Saharan Africa and is lethal if left untreated. Therefore, accurate tools are absolutely required for field diagnosis. For T. b. gambiense HAT, highly sensitive tests are available for serological screening but the sensitivity of parasitological confirmatory tests remains insufficient and needs to be improved. Screening for T. b. rhodesiense infection still relies on clinical features in the absence of serological tests available for field use. Ongoing research is opening perspectives for a new generation of field diagnostics. Also essential for both forms of HAT is accurate determination of the disease stage because of the high toxicity of melarsoprol, the drug most widely used during the neurological stage of the illness. Recent studies have confirmed the high accuracy of raised immunoglobulin M levels in the cerebrospinal fluid for the staging of T. b. gambiense HAT, and a promising simple assay (LATEX/IgM) is being tested in the field. Apart from the urgent need for better tools for the field diagnosis of this neglected disease, improved access to diagnosis and treatment for the population at risk remains the greatest challenge for the coming years

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“…Furthermore, cured patients can remain CATT seropositive for up to three years due to persisting circulating antibodies, thus prohibiting the use of antibody tests for assessment of treatment success. 13 For reasons of erroneous stage determination or treatment refractoriness, patients sometimes relapse after treatment. Studies on improved stage determination, therapy, drug resistance, and new drugs are being undertaken but are hampered by the low sensitivity of the parasitologic diagnostic methods.…”

Section: Introductionmentioning

confidence: 99%

Novel primer sequences for polymerase chain reaction-based detection of Trypanosoma brucei gambiense.

Radwanska¹,

Claes²,

Magez³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

141

143

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Abstract. Progress in diagnosis, treatment, and epidemiology of human African trypanosomiasis (sleeping sickness) depends on the existence of specific and sensitive diagnostic tools. Inherent shortcomings of serologic and parasitologic diagnostic methods can be overcome by molecular techniques. Therefore, we have developed a new polymerase chain reaction (PCR) test using primers derived from the recently identified sequence of the Trypanosoma brucei gambiensespecific glycoprotein (TgsGP). The specificity of the TgsGP-PCR was evaluated on DNA extracted from 73 different trypanosome populations belonging to diverse taxonomic groups that were isolated from various host species, and from different geographic origins. The TgsG-PCR was shown to be specific for T. b. gambiense and was suitable for detection of trypanosome DNA in blood samples of patients with confirmed sleeping sickness.

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Persistence of antibodies to Trypanosoma brucei gambiense after treatment of human trypanosomiasis in Uganda

Cited by 16 publications

References 0 publications

Proteomic Selection of Immunodiagnostic Antigens for Human African Trypanosomiasis and Generation of a Prototype Lateral Flow Immunodiagnostic Device

Proteomic Selection of Immunodiagnostic Antigens for Human African Trypanosomiasis and Generation of a Prototype Lateral Flow Immunodiagnostic Device

Options for Field Diagnosis of Human African Trypanosomiasis

Novel primer sequences for polymerase chain reaction-based detection of Trypanosoma brucei gambiense.

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