Occurrence of Leishmania infantum in the central nervous system of naturally infected dogs: Parasite load, viability, co-infections and histological alterations.

Valéria Da Costa Oliveira,Francisco Das Chagas De Carvalho Rodrigues,Maria De Fátima Madeira,Luiz Claudio Ferreira,Viviane Cardoso Boechat,Rodrigo Caldas Menezes,Artur Augusto Velho Mendes Junior,Raquel De Vasconcellos Carvalhaes De Oliveira,Monique Paiva Campos,Fabiano Borges Figueiredo,Maria Regina Reis Amendoeira

doi:10.1371/journal.pone.0175588

Valéria Da Costa Oliveira, Francisco Das Chagas De Carvalho Rodrigues + Show 9 more

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https://doi.org/10.1371/journal.pone.0175588

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Abstract

Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and little is known about the occurrence and pathogenesis of this parasite in the CNS. The aims of this study were to evaluate the occurrence, viability and load of L. infantum in the CNS, and to identify the neurological histological alterations associated with this protozoan and its co-infections in naturally infected dogs. Forty-eight Leishmania-seropositive dogs from which L. infantum was isolated after necropsy were examined. Cerebrospinal fluid (CSF) samples were analyzed by parasitological culture, quantitative real-time PCR (qPCR) and the rapid immunochromatographic Dual Path Platform test. Brain, spinal cord and spleen samples were submitted to parasitological culture, qPCR, and histological techniques. Additionally, anti-Toxoplasma gondii and anti-Ehrlichia canis antibodies in serum and distemper virus antigens in CSF were investigated. None of the dogs showed neurological signs. All dogs tested positive for L. infantum in the CNS. Viable forms of L. infantum were isolated from CSF, brain and spinal cord in 25% of the dogs. Anti-L. infantum antibodies were detected in CSF in 61% of 36 dogs. Inflammatory histological alterations were observed in the CNS of 31% of the animals; of these, 66% were seropositive for E. canis and/or T. gondii. Amastigote forms were associated with granulomatous non-suppurative encephalomyelitis in a dog without evidence of co-infections. The highest frequency of L. infantum DNA was observed in the brain (98%), followed by the spinal cord (96%), spleen (95%), and CSF (50%). The highest L. infantum load in CNS was found in the spinal cord. These results demonstrate that L. infantum can cross the blood-brain barrier, spread through CSF, and cause active infection in the entire CNS of dogs. Additionally, L. infantum can cause inflammation in the CNS that can lead to neurological signs with progression of the disease.

Highlights

Zoonotic visceral leishmaniasis (ZVL) is a disease of public health importance, which occurs in different countries in Latin America, Africa, Asia, and Europe [1]
In Brazil, ZVL is caused by the protozoan Leishmania infantum and the sandfly Lutzomyia longipalpis is the main biological vector involved in the transmission of this parasite [3]
These results indicate that L. infantum can spread through cerebrospinal fluid (CSF) to the entire central nervous system (CNS) of dogs

Summary

Introduction

Zoonotic visceral leishmaniasis (ZVL) is a disease of public health importance, which occurs in different countries in Latin America, Africa, Asia, and Europe [1]. In Brazil, ZVL is caused by the protozoan Leishmania infantum and the sandfly Lutzomyia longipalpis is the main biological vector involved in the transmission of this parasite [3]. The dog (Canis familiaris) is the main reservoir of L. infantum and the source of infection of the vector [4]. Histological alterations in the central nervous system (CNS) such as meningitis, choroid plexitis, neuronal degeneration, perivascular cuffs, necrosis and myelitis have been reported in infected dogs with and without neurological signs [7, 9,10,11,12, 14,15,16,17,18,19]. Only few surveys exist on the occurrence and load of L. infantum in the CNS of dogs in which viable forms of the parasite are detected, especially in CSF and spinal cord

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