Global landscape of molecular and immunological diagnostic tests for human leishmaniasis: a systematic review and meta-analysis

Background: Leishmaniasis constitutes a serious global public health concern. It is a complex parasitic disease characterized by a spectrum of clinical forms with varying severity, driven by host immune responses and immunopathology. Its accurate diagnosis is essential for guiding timely treatment. Yet, diagnosing leishmaniasis is challenging and requires a combination of tests. Methodology/Principal findings: We conducted a systematic review and meta-analysis to evaluate the applicability and diagnostic accuracy of molecular and immunological tests for the laboratory diagnosis of human tegumentary leishmaniasis (TL) and visceral leishmaniasis (VL). We searched the PubMed database for studies published between 1990 and 2021 on leishmaniasis diagnosis. Following PRISMA statement recommendations, we included 165 publications that met the selection criteria. Among the evaluated tests, polymerase chain reaction (PCR)-based tests showed good diagnostic performance, with area under the curve values (restricted to observed FPRs, AUCFPR) of 0.919 and 0.965 for the diagnosis of TL and VL, respectively. For TL, serological tests showed median sensitivities ranging from 83.3% to 88.1% and median specificities ranging from 82.0% to 92.4%, whereas the leishmanin (Montenegro) skin test had a median sensitivity of 91.7% and a median specificity of 83.4%. For VL, the direct agglutination test (DAT) and enzyme-linked immunosorbent assay (ELISA) exhibited higher sensitivity (median 93.0-93.8%) than rapid diagnostic tests (RDT, 89.1%) and the immunofluorescence antibody test (IFAT, 82.0%). These four tests displayed high specificity (median 95.5-96.9%). DAT showed comparable performance to molecular tests, with an AUCFPR of 0.966. Conclusions/Significance: Molecular tests exhibited high accuracy in diagnosing tegumentary and visceral leishmaniasis. Nevertheless, these tests have yet to be incorporated into routine clinical practice in endemic regions, as they still require specialized technical expertise and robust laboratory infrastructure. We advocate for the development and implementation of diagnostic procedures tailored to the needs of each endemic setting, considering local contexts and available resources, wherein molecular tests could facilitate early, accurate diagnosis of leishmaniasis.