Accuracy of mucocutaneous leishmaniasis diagnosis using polymerase chain reaction: systematic literature review and meta-analysis

Abstract

The diagnosis of mucocutaneous leishmaniasis (MCL) is hampered by the absence of a gold standard. An accurate diagnosis is essential because of the high toxicity of the medications for the disease. This study aimed to assess the ability of polymerase chain reaction (PCR) to identify MCL and to compare these results with clinical research recently published by the authors. A systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement was performed using comprehensive search criteria and communication with the authors. A meta-analysis considering the estimates of the univariate and bivariate models was performed. Specificity near 100% was common among the papers. The primary reason for accuracy differences was sensitivity. The meta-analysis, which was only possible for PCR samples of lesion fragments, revealed a sensitivity of 71% [95% confidence interval (CI) = 0.59; 0.81] and a specificity of 93% (95% CI = 0.83; 0.98) in the bivariate model. The search for measures that could increase the sensitivity of PCR should be encouraged. The quality of the collected material and the optimisation of the amplification of genetic material should be prioritised.

Field Validation of SYBR Green- and TaqMan-Based Real-Time PCR Using Biopsy and Swab Samples To Diagnose American Tegumentary Leishmaniasis in an Area Where Leishmania (Viannia) braziliensis Is Endemic

“…A recent meta-analysis stated that the sensitivity of conventional PCR in ML was approximately 70%; however, at least half of the analyzed references were case-control accuracy studies and did not use a blinded evaluator (5). As the methodology of the present study was based on a cross-sectional/cohort design and used blinded evaluators, we expected a different outcome from that of other methodologies.…”

“…Primer pair choices were based on previously described sequences that amplify fragments of the Leishmania (V.) braziliensis minicircle kDNA (5,(32)(33)(34)(35)(36). We evaluated primer and probe specificity for Leishmania (V.) braziliensis using NCBI BLAST.…”

“…The accurate diagnosis of American tegumentary leishmaniasis (ATL) is an essential task due to the disease's associated morbidity (1,2) but is hindered by the lack of a gold-standard laboratory test (3)(4)(5). Currently available parasitological tests based on stained smears and culture offer low sensitivity, and other options, such as the Montenegro (leishmanin) skin test (MST), have high sensitivity but low specificity (3,6,7).…”

“…Additionally, serological techniques may yield widely varied accuracy values (3). In contrast, although not completely sensitive, PCR can improve the accuracy of ATL diagnosis (5,8,9). Strategies that might improve the sensitivity of PCR include the use of reliable DNA isolation methods, primer pairs that amplify the kinetoplast DNA (kDNA) sequences of Leishmania, and real-time PCR (qPCR) techniques (5,10,11).…”

“…The utility of swabbased diagnosis in mucosal leishmaniasis (ML) has not been completely explored, as most studies have been conducted in highly controlled environments, usually using healthy controls for comparison (5). These shortcomings have precluded the use of this technique in clinical practice (5,14).…”