Potential antigenic targets used in immunological tests for diagnosis of tegumentary leishmaniasis: A systematic review

Abstract

Immunological tests may represent valuable tools for the diagnosis of human tegumentary leishmaniasis (TL) due to their simple execution, less invasive nature and potential use as a point-of-care test. Indeed, several antigenic targets have been used with the aim of improving the restricted scenario for TL-diagnosis. We performed a worldwide systematic review to identify antigenic targets that have been evaluated for the main clinical forms of TL, such as cutaneous (CL) and mucosal (ML) leishmaniasis. Included were original studies evaluating the sensitivity and specificity of immunological tests for human-TL, CL and/or ML diagnosis using purified or recombinant proteins, synthetic peptides or polyclonal or monoclonal antibodies to detect Leishmania-specific antibodies or antigens. The review methodology followed PRISMA guidelines and all selected studies were evaluated in accordance with QUADAS-2. Thirty-eight original studies from four databases fulfilled the selection criteria. A total of 79 antigens were evaluated for the detection of antibodies as a diagnostic for TL, CL and/or ML by ELISA. Furthermore, three antibodies were evaluated for the detection of antigen by immunochromatographic test (ICT) and immunohistochemistry (IHC) for CL-diagnosis. Several antigenic targets showed 100% of sensitivity and specificity, suggesting potential use for TL-diagnosis in its different clinical manifestations. However, a high number of proof-of-concept studies reinforce the need for further analysis aimed at verifying true diagnostic accuracy in clinical practice.

Fig 1. Flow diagram illustrating the study selection process according to PRISMA.

Fig 2. Forest plot representing sensitivity and specificity indices of ELISA using different antigenic targets for TL diagnosis.

Fig 3. Forest plot representing sensitivity and specificity indices of ELISA using different antigenic targets for CL-diagnosis.

Fig 4. Forest plot representing sensitivity and specificity indices of other immunological tests using different antigenic targets for CL-diagnosis.

Fig 5. Forest plot representing sensitivity and specificity indexes of other immunological tests using different antigenic targets for ML-diagnosis.

Fig 6. SROC curve for diagnosis of TL (a), CL (b) and ML (c) according to reference standard test.

Fig 7. Risk of bias assessed by the QUADAS-2 tool according to different study characteristics (patient selection, index test, reference standard and flow and timing).