Diagnosis of visceral and cutaneous leishmaniasis using loop-mediated isothermal amplification (LAMP) protocols: a systematic review and meta-analysis

Julia Walochnik,Gláucia Cota,Peter Julian Sandler,Astrid Christine Erber,Ines Swoboda,Daniel Moreira de Avelar

doi:10.1186/s13071-021-05133-2

Abstract

Sensitive, reliable and fast diagnostic tools that are applicable in low-resource settings, at the point of care (PoC), are seen as crucial in the fight against visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL). Addressing the need for a PoC test, several diagnostic tests, including serological and molecular methods, have been developed and evaluated in the past. One promising molecular method, already implemented for diagnosis of a range of diseases, is the loop-mediated isothermal amplification (LAMP) protocol. In this systematic review and meta-analysis, using a comprehensive search strategy, we focus on studies evaluating the performance of LAMP for the diagnosis of leishmaniasis in humans and other mammals such as dogs, compared with microscopy and/or any other molecular diagnostic method. A meta-analysis, pooling sensitivity and specificity rates and calculating areas under the curve (AUCs) in summary receiver operating characteristic (SROC) plots, was conducted on datasets extracted from studies, grouped by clinical condition and sample type. We found high sensitivity and specificity for LAMP when compared with microscopy and PCR using blood samples, with pooled estimate values of > 90% for all subgroups, corresponding to calculated AUC values > 0.96, except for LAMP compared to microscopy for diagnosis of CL. However, only a limited number of studies were truly comparable. Most of the observed heterogeneity is likely based on true differences between the studies rather than sampling error only. Due to simple readout methods and low laboratory equipment requirements for sample preparation compared to other molecular methods, LAMP is a promising candidate for a molecular (near-)PoC diagnostic method for VL and CL.Graphical

Highlights

Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania [1] and transmitted by the females of phlebotomine sand flies [2, 3]
Studies were excluded at the title/abstract screening stage for the following reasons: wrong pathogen, no loop-mediated isothermal amplification (LAMP) (LAMP was not used as a diagnostic test method) or wrong article type
Studies were excluded at the full-text assessment stage for the following reasons: lack of data, duplicate study, no LAMP (LAMP was not used as a diagnostic test method), no paired samples or promastigote form

Summary

Introduction

Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania [1] and transmitted by the females of phlebotomine sand flies [2, 3]. Factors such as proximity of animal reservoirs in the current model of peri-urban transmission, different susceptibilities of human populations and the environmental impact on vector distribution result in a complex interplay [4, 5]. Around 90% of VL cases occur in six countries: Bangladesh, Brazil, Ethiopia, India, South Sudan and Sudan. Due to climatic change, more habitats will become suitable for phlebotomine sand flies, resulting in a possible expansion of their geographic ranges and an establishment of endemic Leishmania transmission in more extreme latitudes throughout the world [19–22]

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