The accuracy of the Montenegro skin test for leishmaniasis in PCR-negative patients

Abstract

Introduction: As highly specific molecular biology-based techniques may not be sensitive enough for the diagnosis of American tegumentary leishmaniasis (ATL), clinicians frequently rely on immunological tests before treatment initiation. Hence, the correct combination of diagnostic tests is imperative for ATL diagnosis. We aimed to evaluate the accuracy of the Montenegro (Leishmanin) skin test (MST) in polymerase chain reaction (PCR)-negative patients to accurately detect ATL. Methods: Patients with a clinical picture compatible with ATL were divided into ATL (confirmed by lesion smear, culture indirect immunofluorescence, and/or histopathology) and no-ATL (diseases that can mimic leishmaniasis) groups. Conventional PCR for the minicircle kDNA of Leishmania was performed, and the MST was carried out for PCR-negative patients. Results: Ninety-nine patients were included in this study, including 79 diagnosed with ATL (6 with mucocutaneous leishmaniasis) and 20 without ATL (no-ATL group). The MST showed a high sensitivity of 90.0% (95% confidence interval [CI] = 69.90-97.21) in PCR-negative patients that was 10% higher than the sensitivity reported in PCR-positive population (79.66%; 95% CI = 67.73-87.96). Conclusions: One of the most important reasons for PCR negativity among patients with active ATL is the presence of a strong cellular immunological response, especially in chronic and mucocutaneous leishmaniasis. This reinforces the considerable utility of the tests that detect cellular responses against Leishmania antigens such as the MST in PCR-negative patients when the performance in screening situations is questionable.

Accuracy of diagnostic tests for American tegumentary leishmaniasis: a systematic literature review with meta‐analyses

“…It is interesting to note that the values of accuracy of the qPCR of these studies were lower than that of conventional PCR obtained in the other studies included in the review. Pinheiro et al [50] analysed different tests and obtained similar values of sensitivity to those of the metaanalysis performed in our study, with the exception of the conventional PCR, which had a sensitivity of 74.68%. They also demonstrated a great proportion of MIR positive reactions in individuals with negative PCR tests and Strong, strong recommendation for using the test; Weak, weak recommendation for using the intervention.…”

“…The reference standards used in three studies [48][49][50], in addition to considering the criteria defined in the present review, also classified as positives the individuals with: a compatible histopathological examination; a positive MIR or indirect immunofluorescence; no confirmation of a differential diagnosis; and a complete response to pentavalent antimonial treatment. In this way, Gomes et al [48] demonstrated that real-time PCR (qPCR) assays performed better than histopathology, smears or culture and that swabs had similar sensitivity to that of biopsy samples and Sevilha-Santos et al [49] showed the best diagnostic accuracy of qPCR in swabs of the superior dermis.…”

“…After reading of the titles and abstracts, 3334 studies were excluded because they did not meet the inclusion criteria. After full reading of the remaining 53 studies, 15 papers were excluded and 38 were included in the systematic review [10,20–56]. Of these, 27 were conducted in Brazil, 3 in Colombia and 2 in Ecuador.…”

“…The reference standards used in three studies [48‐50], in addition to considering the criteria defined in the present review, also classified as positives the individuals with: a compatible histopathological examination; a positive MIR or indirect immunofluorescence; no confirmation of a differential diagnosis; and a complete response to pentavalent antimonial treatment. In this way, Gomes et al .…”

“…In addition to its high accuracy, PCR can detect parasite DNA in different samples and independently of isolation and culture of the parasite, providing a faster diagnosis and the possibility of timely adoption of the treatment [59]. However, given the possibility of negative results in individuals with intense cellular response [50], negative results do not rule out the presence of infection and PCR must be applied together with another technique.…”