Leishmania Infection: Pathogenesis, Clinical and Epidemiological Aspects

A special issue of Veterinary Sciences (ISSN 2306-7381). This special issue belongs to the section "Veterinary Microbiology, Parasitology and Immunology".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 14505

Special Issue Editor


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Guest Editor
Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, Italy
Interests: leishmaniasis; biochemistry; chemotherapy; immunology; kinetoplastids

Special Issue Information

Dear Colleagues,

Leishmaniasis study is strictly related to the immunology field, the target of the parasite being part of the immunological compartment. Hence, its study is a model for the study of the immunity system and the many other pathologies and infections hitting it. Not only, it also is a paradigm for the study of inflammation, which is the pattern of the severe leishmaniasis, as well as of many diseases, COVID-19 the last among the world hitting plagues. Furthermore, climate change and conflicts can be a flywheel for leishmaniasis spread, threatening animal and human health.

Accordingly, this Special Issue aims to collect articles on all aspects of leishmaniasis, since all are important to allow advancing in fighting this vector-borne infection as well as in understanding of its etiopathogenesis. Thus, the following keywords cover only some of the invited issues since others are also welcome.

Hoping to give a contribution together to all kindly joining at this purpose.

Best Regards,

Dr. Stefania Hanau
Guest Editor

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Keywords

  • leishmaniasis
  • immunology
  • chemotherapy
  • biochemistry
  • epidemiology
  • diagnosis
  • virulence factors
  • vaccines
  • sand fly vectors
  • kinetoplastids
  • omics

Published Papers (7 papers)

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Research

12 pages, 695 KiB  
Article
Pilot Study on QTc Interval in Dogs Treated with Domperidone
by Giulia Donato, Tiziana Caspanello, Massimo De Majo, Marisa Masucci, Diego Iannelli, Silvia Santoro, Alessandra Caprì, Nicola Maria Iannelli and Maria Grazia Pennisi
Vet. Sci. 2024, 11(1), 39; https://doi.org/10.3390/vetsci11010039 - 18 Jan 2024
Viewed by 1536
Abstract
Domperidone is used as an immunomodulatory drug for Leishmania infantum infection and disease in dogs. However, a pro-arrhythmic side effect, caused by prolonged QT intervals, is reported in humans. This pilot study evaluated the corrected QT (QTc) interval in dogs treated with domperidone [...] Read more.
Domperidone is used as an immunomodulatory drug for Leishmania infantum infection and disease in dogs. However, a pro-arrhythmic side effect, caused by prolonged QT intervals, is reported in humans. This pilot study evaluated the corrected QT (QTc) interval in dogs treated with domperidone for preventive or therapeutic management of leishmaniosis. The electrocardiogram and blood concentration of creatinine, urea nitrogen, sodium, potassium, and chloride were evaluated seven days before the start and on the last day of therapy in 17 dogs receiving domperidone for four weeks. In two dogs, the QTc interval was measured before and 2 h, 3 h, and 12 h after administration of the drug on the first day of treatment. After treatment, QTc measures and chloride concentrations increased significantly, although the QTc value slightly exceeded the upper reference limit only in one dog, and chloride concentrations were always normal. Creatinine concentrations significantly decreased after therapy. In the two dogs monitored at different times on the first day of treatment, QTc values were always normal. Domperidone caused a slight prolongation of QTc interval, and further studies should be made for a risk assessment in dogs with cardiac diseases, electrolytic imbalance, and in those receiving drugs increasing QT interval or competing with domperidone metabolism. Full article
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14 pages, 3706 KiB  
Article
In Vitro and In Silico Evaluations of the Antileishmanial Activities of New Benzimidazole-Triazole Derivatives
by Mustafa Eser and İbrahim Çavuş
Vet. Sci. 2023, 10(11), 648; https://doi.org/10.3390/vetsci10110648 - 09 Nov 2023
Viewed by 1406
Abstract
Benzimidazole and triazole rings are important pharmacophores, known to exhibit various pharmacological activities in drug discovery. In this study, it was purposed to synthesize new benzimidazole-triazole derivatives and evaluate their antileishmanial activities. The targeted compounds (5a5h) were obtained after [...] Read more.
Benzimidazole and triazole rings are important pharmacophores, known to exhibit various pharmacological activities in drug discovery. In this study, it was purposed to synthesize new benzimidazole-triazole derivatives and evaluate their antileishmanial activities. The targeted compounds (5a5h) were obtained after five chemical reaction steps. The structures of the compounds were confirmed by spectral data. The possible in vitro antileishmanial activities of the synthesized compounds were evaluated against the Leishmania tropica strain. Further, molecular docking and dynamics were performed to identify the probable mechanism of activity of the test compounds. The findings revealed that compounds 5a, 5d, 5e, 5f, and 5h inhibited the growth of Leishmania tropica to various extents and had significant anti-leishmanial activities, even if some orders were higher than the reference drug Amphotericin B. On the other hand, compounds 5b, 5c, and 5g were found to be ineffective. Additionally, the results of in silico studies have presented the existence of some interactions between the compounds and the active site of sterol 14-alpha-demethylase, a biosynthetic enzyme that plays a critical role in the growth of the parasite. Therefore, it can be suggested that if the results obtained from this study are confirmed with in vivo findings, it may be possible to obtain some new anti-leishmanial drug candidates. Full article
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12 pages, 1363 KiB  
Article
Diagnostic Potential for the Detection of Canine Visceral Leishmaniasis of an ELISA Assay Based on the Q5 Recombinant Protein: A Large-Scale and Comparative Evaluation Using Canine Sera with a Positive Diagnosis from the Dual-Path-Platform (DPP) Test
by Larissa Ferreira de Araújo Paz, Adalúcia da Silva, Hemilly Rayanne Ferreira da Silva, Milena Paiva Cavalcanti, Valeria Marçal Felix de Lima, Maria Rosário Oliveira da Cunha Beltrão, Maria Beatriz Araújo Silva, Osvaldo Pompílio de Melo Neto, Zulma Maria Medeiros and Wagner José Tenório dos Santos
Vet. Sci. 2023, 10(10), 608; https://doi.org/10.3390/vetsci10100608 - 07 Oct 2023
Viewed by 1386
Abstract
Dogs are considered the major domestic reservoir for human visceral leishmaniasis, a serious disease caused by the Leishmania infantum parasite. Diagnosis of canine visceral leishmaniasis (CVL) is critical for disease control, with several methods currently available. Among the serological tests, the DPP rapid [...] Read more.
Dogs are considered the major domestic reservoir for human visceral leishmaniasis, a serious disease caused by the Leishmania infantum parasite. Diagnosis of canine visceral leishmaniasis (CVL) is critical for disease control, with several methods currently available. Among the serological tests, the DPP rapid test and the EIE-LVC, more commonly used in Brazil, are associated with variable sensitivity and specificity. Research with novel recombinant proteins such as the ELISA with the recombinant chimeric protein Q5 may therefore improve the CVL diagnosis. This study aimed to evaluate the true diagnostic potential of Q5 in an ELISA assay using a large number of CVL-suspected sera (406) with a previous positive diagnosis based on the rapid DPP test. Sera from the DPP-positive dogs, also assessed with the EIE-LVC test, were compared with sera from healthy dogs (n = 46) and used for ELISA tests using the recombinant Q5. The resulting data as well as the correlation with the clinical signs and the environmental characteristics of the animals were analyzed using Medal and GraphPad Prism 8.0. Overall, similar levels of lower sensitivity (67–68%) were seen for both the commercial EIE-LVC test and the Q5 ELISA when all assessed sera were considered, but a much greater sensitivity (92%) was seen for those samples from symptomatic dogs only. In contrast, many negative results were observed for the DPP-positive sera from asymptomatic dogs or those with no clinical information available. A selection of those sera were tested yet again in new ELISA assays using a second batch of the recombinant Q5, purified under milder denaturing conditions, as well as using another recombinant protein (Lci13). The results reveal a higher-than-expected incidence of likely false-positive results for DPP, reinforcing the need for other recombinant proteins, such as the chimeric Q5, to be investigated as possible alternatives to the currently used CVL diagnostic methods. Full article
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11 pages, 3757 KiB  
Article
Cultivation of Protozoa Parasites In Vitro: Growth Potential in Conventional Culture Media versus RPMI-PY Medium
by Germano Castelli, Eugenia Oliveri, Viviana Valenza, Susanna Giardina, Flavia Facciponte, Francesco La Russa, Fabrizio Vitale and Federica Bruno
Vet. Sci. 2023, 10(4), 252; https://doi.org/10.3390/vetsci10040252 - 27 Mar 2023
Cited by 2 | Viewed by 3809
Abstract
The in vitro cultivation of Leishmania and Trypanosoma parasites plays an important role in the diagnosis and treatment of parasitic diseases. Although Evans’s modified Tobie and Novy–MacNeal–Nicolle media, for Leishmania spp. and Trypanosoma cruzi, respectively, are the two commonly used media for [...] Read more.
The in vitro cultivation of Leishmania and Trypanosoma parasites plays an important role in the diagnosis and treatment of parasitic diseases. Although Evans’s modified Tobie and Novy–MacNeal–Nicolle media, for Leishmania spp. and Trypanosoma cruzi, respectively, are the two commonly used media for both isolation and maintenance of strains in vitro, their preparation is expensive and laborious and requires fresh rabbit blood from housed animals. The purpose of this study was to evaluate the in vitro growth of both parasites with an alternative monophasic, blood-free, easy, and affordable medium called RPMI-PY, which was previously demonstrated suitable for the in vitro growth of Leishmania infantum. The potential growth of different Leishmania species and Trypanosoma cruzi was evaluated in traditional culture media versus RPMI-PY medium, and we recorded the protozoa parasites’ morphology via orange acridine–ethidium bromide staining. The results of our study show that RPMI-PY medium can be used for Trypanosoma cruzi, Leishmania amazonensis, Leishmania major, and Leishmania tropica species since in all the species except Leishmania braziliensis, the exponential growth of the parasite was observed, in many cases higher than conventional media. The staining confirmed not only their growth during the 72 h investigation but also the optimal morphology and viability of the protozoa in the RPMI-PY medium. Full article
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14 pages, 1700 KiB  
Article
A Calcium- and GTP-Dependent Transglutaminase in Leishmania infantum
by Shawgi Hago Almugadam, Alessandro Trentini, Martina Maritati, Carlo Contini, Maria Cristina Manfrinato, Carlo Cervellati, Tiziana Bellini and Stefania Hanau
Vet. Sci. 2023, 10(3), 234; https://doi.org/10.3390/vetsci10030234 - 20 Mar 2023
Viewed by 1390
Abstract
While human and animal leishmaniasis affect several millions of people worldwide, L. infantum is the species responsible for visceral leishmaniasis in Europe, Middle East, and America. Antileishmanial drugs present issues associated with drug toxicity and increasing parasite resistance. Therefore, the study of this [...] Read more.
While human and animal leishmaniasis affect several millions of people worldwide, L. infantum is the species responsible for visceral leishmaniasis in Europe, Middle East, and America. Antileishmanial drugs present issues associated with drug toxicity and increasing parasite resistance. Therefore, the study of this parasite with a focus on new potential drug targets is extremely useful. Accordingly, we purified and characterized a transglutaminase (TGase) from L. infantum promastigotes. While Tgases are known to be involved in cell death and autophagy, it appears that these functions are very important for parasites’ virulence. For the first time, we showed a Ca2+- and GTP-dependent TGase in Leishmania corresponding to a 54 kDa protein, which was purified by two chromatographic steps: DEAE-Sepharose and Heparin-Sepharose. Using polyclonal antibodies against a 50-amino-acid conserved region of the catalytic core of human TGase 2, we revealed two other bands of 66 and 75 kDa. The 54 kDa band appears to be different from the previously reported TGase, which was shown to be Ca2+- independent. Future research should address the identification of the purified enzyme sequence and, subsequently, its cloning to more comprehensively investigate its pathophysiological function and possible differences from mammal enzymes. Full article
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14 pages, 343 KiB  
Article
Leishmania infantum Specific Humoral and Cellular Immune Responses in Cats and Dogs: A Comparative Cross-Sectional Study
by Vito Priolo, Pamela Martínez-Orellana, Maria Grazia Pennisi, Ana Isabel Raya-Bermúdez, Estefania Jurado-Tarifa, Marisa Masucci, Giulia Donato, Federica Bruno, Germano Castelli and Laia Solano-Gallego
Vet. Sci. 2022, 9(9), 482; https://doi.org/10.3390/vetsci9090482 - 07 Sep 2022
Cited by 4 | Viewed by 1983
Abstract
Dogs are the main reservoir of Leishmania infantum and display different immunological patterns correlating with the progression of infection to disease. Data about feline L. infantum adaptive immune response are scant. This study aimed to compare the prevalence and immune response in cats [...] Read more.
Dogs are the main reservoir of Leishmania infantum and display different immunological patterns correlating with the progression of infection to disease. Data about feline L. infantum adaptive immune response are scant. This study aimed to compare the prevalence and immune response in cats and dogs from the same endemic area of canine leishmaniosis. Stray cats (109) and rescued dogs (59) from Córdoba (Spain) were enrolled. Data about their exposure to L. infantum were analyzed by detection of parasite DNA, measurements of Leishmania-specific interferon-γ (whole blood assay in 57 cats and 29 dogs), and antibodies (enzyme-linked immunosorbent assay and immunofluorescence antibody test). An overall L. infantum prevalence of 30.5% in dogs and 30% in cats were found according to serology and PCR tests. Prevalence was 44.8% in dogs and 35.1% in cats tested also for interferon-γ production. Dogs showed higher anti-L. infantum antibody levels compared to cats. More than one-third of cats had contact with or were infected by L. infantum and they may contribute to the endemicity of leishmaniosis in the investigated region. The immunopathogenesis of feline L. infantum infection has similarities with dogs but cats show a lower level of adaptive immune response compared to dogs. Full article
11 pages, 1682 KiB  
Article
Clinical Case of Feline Leishmaniosis: Therapeutic Approach and Long-Term Follow-Up
by Ettore Napoli, Giovanni De Benedetto, Cristina Fazio, Francesco La Russa, Gabriella Gaglio and Emanuele Brianti
Vet. Sci. 2022, 9(8), 400; https://doi.org/10.3390/vetsci9080400 - 31 Jul 2022
Viewed by 1736
Abstract
The response to allopurinol treatment and survival time of a case of feline leishmaniosis in a FIV co-infected cat is herein reported. In May 2019, a 13-year-old neutered European Shorthair male was referred due to weight loss and exfoliative dermatitis. Lymphadenomegaly and splenomegaly [...] Read more.
The response to allopurinol treatment and survival time of a case of feline leishmaniosis in a FIV co-infected cat is herein reported. In May 2019, a 13-year-old neutered European Shorthair male was referred due to weight loss and exfoliative dermatitis. Lymphadenomegaly and splenomegaly were detected upon clinical inspection, while the presence of several Leishmania infantum amastigotes were detected on splenic and lymphonodal fine needle aspiration (FNA). Allopurinol (10 mg/kg PO q 12 h) was administered. After two months, the cat’s clinical symptoms disappeared, and the owners decided to interrupt the therapy. In February, two reddish nodular fleshy neoformations appeared in both eyes, and amastigotes of Leishmania were detected by cytology on conjunctival swabs. Allopurinol treatment was re-started at the same rate; the ocular lesions regressed in two weeks, and the owner again decided to interrupt the therapy. In July, the patient had a new relapse, but the owner, tired of continuous relapses, refused further treatment of the disease. The cat’s health condition continued to worsen: in October 2021, the ocular lesions appeared again, and in November the patient died. This case underlines the effectiveness of allopurinol and highlights how interruption of treatment frequently leads to relapse, impairing the animal’s health condition and prognosis. Full article
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