A review of the leishmanin skin test: A neglected test for a neglected disease

Abstract

The leishmanin skin test (LST) has been used for decades to detect exposure and immunity to the parasite Leishmania, the causative agent of the neglected tropical disease leishmaniasis. In the LST, Leishmania antigen (leishmanin) is intradermally injected into the forearm. In an individual who has been previously infected, a delayed-type hypersensitivity (DTH) reaction results in a measurable induration at the site of the injection, indicating that previous exposure to Leishmania has resulted in the development of cell-mediated immunity. LST positivity is associated with long-lasting protective immunity against reinfection, most notably as reported for visceral leishmaniasis (VL). Despite efforts over the past few decades, leishmanin antigen is no longer produced under good manufacturing practice (GMP) conditions anywhere in the world. Consequently, the use of the LST in epidemiological studies has declined in favor of serological and molecular tests. In this review, we provide a historical overview of the LST and justification for the reintroduction of leishmanin. A GMP-grade leishmanin can be used to detect immunity in vivo by the LST and can be investigated for use in an interferon-γ release assay (IGRA), which may serve as an in vitro version of the LST. The LST will be a valuable tool for surveillance and epidemiological studies in support of the VL elimination programs and as a surrogate marker of immunity in vaccine clinical trials. Methods A review of the literature was conducted using PubMed as the primary database, with MeSH terms “leishmanin skin test” OR “Montenegro test” OR “Montenegro skin test.” Articles written in English that describe the history or standardization of leishmanin, the use of leishmanin in an IGRA, or the use of the LST in epidemiological studies or vaccine trials were prioritized in our appraisal of the literature.

Laboratory diagnostics for human Leishmania infections: a polymerase chain reaction-focussed review of detection and identification methods

“…Other, lesser-used, methods include the leishmanin (or Montenegro) skin test. In CL, this test can detect past and active cases with high sensitivity, whereas in active VL, the test shows negative as patients are anergic, so it is used in screening studies for an indication of past exposure only [ 57 , 114 ]. It involves intradermal injection of antigen, whereby induration of an area of the skin of 5 mm or greater is considered a positive test result; sensitivity and specificity with this cut-off point have been reported as 97.4% and 93.9%, respectively [ 15 , 115 , 116 ].…”

Cutaneous Leishmaniasis: A 2022 Updated Narrative Review into Diagnosis and Management Developments

“…The Leishmania intradermal skin test (LST) or Montenegro skin test (MST) is a marker of cellular immune response (a delay-type hypersensitivity response) and can be used for an indirect CL diagnosis because of its simple use and because of its high predictive value, being positive in more than 90% of CL cases with good sensitivity and specificity values [ 35 , 36 ]. In addition, the LST can be useful in epidemiological studies to monitor exposure and immunity to Leishmania as well as in vaccine studies as a surrogate marker of immunity [ 37 ]. The test, comparable to the well-known Mantoux tuberculosis test, is based on the intradermal injection of Leishmania extracts (leishmanin) and results in a cutaneous reaction.…”

“…The immune response against Leishmania is cell mediated, and depends on interferon (IFN)-γ induced activation of macrophages. Potentially, leishmanin can be used in a yet to be developed in vitro IFN-γ release assay (IGRA) with similar prognostic value as the LST test, but with the advantages of improved standardization and patient comfort [ 37 ].…”

A Promising Cutaneous Leishmaniasis Treatment with a Nanoemulsion-Based Cream with a Generic Pentavalent Antimony (Ulamina) as the Active Ingredient

“…4. Immune Diagnosis: Their immune responses were confirmed, using the Montenegro Test [84] as a test for Leishmania, by intradermal reaction with the figurative antigen from the promastigotes form of Leishmania (Viannia) braziliensis [82].…”