Research on Leishmania and Leishmaniasis

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Parasitology".

Deadline for manuscript submissions: 15 April 2024 | Viewed by 6119

Special Issue Editors

Pathology Laboratory of Infectious Diseases (LIM50), Pathology Department, Medical School, São Paulo University, São Paulo 1246-903, São Paulo State, Brazil
Interests: immunopathology of leishmaniasis; infectious disease; immunopathology; immunity; diagnosis; treatment; leishmaniasis
Institute for Advanced Studies of Ocean, São Paulo State University (UNESP), São Vicente 11350-011, Brazil
Interests: neglected tropical diseases; parasite; bacteria; virus; fungus; oral and local treatment; formulations; dermatological cream; liposome; nanoparticles; immunity
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Special Issue Information

Dear Colleagues,

Leishmania are flagellated kinetoplastid parasites that infect phagocytic cells of the vertebrate host and the alimentary tract of sandfly vectors. Parasites that belong to the genus Leishmania cause a variety of devasting and ofen fatal diseases in humans and domestic animals worldwide depending on the parasite species and the host’s genetic and immunological background. The genus Leishmania comprises a wide range of species, and these different species have different tissue tropisms that are pathogenic to humans, resulting in different clinical forms of  human leishmaniasis such as: visceral, cutaneous, anergic diffuse cutaneous, mucocutaneous, or atypical cutaneous disease. The need for new therapeutic strategies is urgent because no vaccine is available, and treatment options are limited due to a lack of specificity, colateral effcts, and the emergence of drug resistance.

In this Special Issue of Microoganisms, we invite you to send your contributions concerning any aspects related to Leishmania and leishmaniasis. We sincerely hope this knowledge can improve the conditions of treatment, follow-up, and cure control of patients, minimize the potential damages this protozoosis can cause to infected individuals, and help establish the public polices for the control of this negleted tropical disease.

Dr. Mãrcia Dalastra Laurenti
Dr. Luiz Felipe Domingues Passero
Guest Editors

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Keywords

  • Leishmana
  • Leishmaniasis
  • drug treatment
  • vaccine
  • host-parasite interaction

Published Papers (6 papers)

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Research

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17 pages, 2619 KiB  
Article
Extracellular Vesicles from Leishmania (Leishmania) infantum Contribute in Stimulating Immune Response and Immunosuppression in Hosts with Visceral Leishmaniasis
Microorganisms 2024, 12(2), 270; https://doi.org/10.3390/microorganisms12020270 - 27 Jan 2024
Viewed by 585
Abstract
Visceral leishmaniasis (VL) is a chronic systemic disease. In Brazil this infection is caused by Leishmania (Leishmania) infantum. Extracellular vesicles (EVs) released by Leishmania species have different functions like the modulation of host immune systems and inflammatory responses, among others. This study [...] Read more.
Visceral leishmaniasis (VL) is a chronic systemic disease. In Brazil this infection is caused by Leishmania (Leishmania) infantum. Extracellular vesicles (EVs) released by Leishmania species have different functions like the modulation of host immune systems and inflammatory responses, among others. This study evaluated the participation of EVs from L. (L.) infantum (Leish-EVs) in recognition of the humoral and cellular immune response of hosts with VL. Promastigotes were cultivated in 199 medium and, in the log phase of growth, they were centrifuged, washed, resus-pended in RPMI medium, and incubated for 2 to 24 h, at 25 °C or 37 °C to release Leish-EVs. This dynamic was evaluated using transmission (TEM) and scanning (SEM) electron microscopies, as well as nanoparticle tracking analysis (NTA). The results suggested that parasite penetration in mammal macrophages requires more Leish-EVs than those living in insect vectors, since promastigotes incubated at 37 °C released more Leish-EVs than those incubated at 25 °C. Infected THP-1 cells produced high EV concentration (THP-1 cells-EVs) when compared with those from the control group. The same results were obtained when THP-1 cells were treated with Leish-EVs or a crude Leishmania antigen. These data indicated that host–EV concentrations could be used to distinguish infected from uninfected hosts. THP-1 cells treated with Leish-EVs expressed more IL-12 than control THP-1 cells, but were unable to express IFN-γ. These same cells highly expressed IL-10, which inhibited TNF-α and IL-6. Equally, THP-1 cells treated with Leish-EVs up-expressed miR-21-5p and miR-146a-5p. In conclusion, THP-1 cells treated with Leish-EVs highly expressed miR-21-5p and miR-146a-5p and caused the dysregulation of IL-10. Indirectly, these results suggest that high expression of these miRNAs species is caused by Leish-EVs. Consequently, this molecular via can contribute to immunosuppression causing enhanced immunopathology in infected hosts. Full article
(This article belongs to the Special Issue Research on Leishmania and Leishmaniasis)
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19 pages, 2872 KiB  
Article
Potential Effects of Essential Oil from Plinia cauliflora (Mart.) Kausel on Leishmania: In Vivo, In Vitro, and In Silico Approaches
Microorganisms 2024, 12(1), 207; https://doi.org/10.3390/microorganisms12010207 - 19 Jan 2024
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Abstract
In the search for new chemotherapeutic alternatives for cutaneous leishmaniasis (CL), essential oils are promising due to their diverse biological potential. In this study, we aimed to investigate the chemical composition and leishmanicidal and anti-inflammatory potential of the essential oil isolated from the [...] Read more.
In the search for new chemotherapeutic alternatives for cutaneous leishmaniasis (CL), essential oils are promising due to their diverse biological potential. In this study, we aimed to investigate the chemical composition and leishmanicidal and anti-inflammatory potential of the essential oil isolated from the leaves of Plinia cauliflora (PCEO). The chemical composition of PCEO showed β-cis-Caryophyllene (24.4%), epi-γ-Eudesmol (8%), 2-Naphthalenemethanol[decahydro-alpha] (8%), and trans-Calamenene (6.6%) as its major constituents. Our results showed that the PCEO has moderate cytotoxicity (CC50) of 137.4 and 143.7 μg/mL on mice peritoneal exudate cells (mPEC) and Vero cells, respectively. The PCEO was able to significantly decrease mPEC infection by Leishmania amazonensis and Leishmania braziliensis. The value of the inhibitory concentration (IC50) on amastigote forms was about 7.3 µg/mL (L. amazonensis) and 7.2 µg/mL (L. braziliensis). We showed that PCEO induced drastic ultrastructural changes in both species of Leishmania and had a high selectivity index (SI) > 18. The in silico ADMET analysis pointed out that PCEO can be used for the development of oral and/or topical formulation in the treatment of CL. In addition, we also demonstrated the in vivo anti-inflammatory effect, with a 95% reduction in paw edema and a decrease by at least 21.4% in migration immune cells in animals treated with 50 mg/kg of PCEO. Taken together, our results demonstrate that PCEO is a promising topical therapeutic agent against CL. Full article
(This article belongs to the Special Issue Research on Leishmania and Leishmaniasis)
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14 pages, 4850 KiB  
Article
Human Cutaneous Leishmaniasis in North Africa and Its Threats to Public Health: A Statistical Study Focused on Djelfa (Algeria)
Microorganisms 2023, 11(10), 2608; https://doi.org/10.3390/microorganisms11102608 - 22 Oct 2023
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Abstract
Cutaneous leishmaniasis, the most common form of leishmaniasis, causes long-term skin lesions on exposed areas of the skin. It is caused by a protozoan parasite belonging to the genus Leishmania and is transmitted via infected phlebotomine sand flies. In North Africa, particularly Algeria, [...] Read more.
Cutaneous leishmaniasis, the most common form of leishmaniasis, causes long-term skin lesions on exposed areas of the skin. It is caused by a protozoan parasite belonging to the genus Leishmania and is transmitted via infected phlebotomine sand flies. In North Africa, particularly Algeria, the disease represents a major public health problem. This retrospective study, which focuses on the agropastoral region of Djelfa (central Algeria) during a period of 16 years, from 2006 to 2021, is part of the surveillance of cutaneous leishmaniasis to identify the key factors favouring its probable spread. The analyzed data reveal that this disease is more prevalent in male patients (53.60%) and is highly widespread in this vast area of 66,415 km2 with a total of 3864 CL cases, reaching a peak of 1407 cases in 2006. Statistically, the Pearson correlation validated by the p-value shows, in an original and sometimes unexpected way, that certain factors, such as temperature linked to climate change, are playing a significant role in the probable spread of the disease in Djelfa and its surrounding regions. The concentration of the population in some specific rural areas with limited or nonexistent access to public health services is another potential factor in disease transmission. The results were highlighted by a significant correlation coefficient (r=0.66) with a p-value less than 0.01. While there is currently no vaccine or prophylactic drug available, our research represents a preliminary approach that addresses various epidemiological aspects of the disease. This paves the way for a proactive preventive strategy involving the control of vector-borne diseases. Full article
(This article belongs to the Special Issue Research on Leishmania and Leishmaniasis)
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13 pages, 1531 KiB  
Article
Exploring Host-Specificity: Untangling the Relationship between Leishmania (Viannia) Species and Its Endosymbiont Leishmania RNA Virus 1
Microorganisms 2023, 11(9), 2295; https://doi.org/10.3390/microorganisms11092295 - 12 Sep 2023
Cited by 1 | Viewed by 702
Abstract
A relevant aspect in the epidemiology of Tegumentary Leishmaniasis (TL) are the Leishmania parasites carrying a viral endosymbiont, Leishmania RNA Virus 1 (LRV1), a dsRNA virus. Leishmania parasites carrying LRV1 are prone to causing more severe TL symptoms, increasing the likelihood of unfavorable [...] Read more.
A relevant aspect in the epidemiology of Tegumentary Leishmaniasis (TL) are the Leishmania parasites carrying a viral endosymbiont, Leishmania RNA Virus 1 (LRV1), a dsRNA virus. Leishmania parasites carrying LRV1 are prone to causing more severe TL symptoms, increasing the likelihood of unfavorable clinical outcomes. LRV1 has been observed in the cultured strains of five L. (Viannia) species, and host specificity was suggested when studying the LRV1 from L. braziliensis and L. guyanensis strains. The coevolution hypothesis of LRV1 and Leishmania was based on phylogenetic analyses, implying an association between LRV1 genotypes, Leishmania species, and their geographic origins. This study aimed to investigate LRV1 specificity relative to Leishmania (Viannia) species hosts by analyzing LRV1 from L. (Viannia) species. To this end, LRV1 was screened in L. (Viannia) species other than L. braziliensis or L. guyanensis, and it was detected in 11 out of 15 L. naiffi and two out of four L. shawi. Phylogenetic analyses based on partial LRV1 genomic sequencing supported the hypothesis of host specificity, as LRV1 clustered according to their respective Leishmania species’ hosts. These findings underscore the importance of investigating Leishmania and LRV1 coevolution and its impact on Leishmania (Viannia) species dispersion and pathogenesis in the American Continent. Full article
(This article belongs to the Special Issue Research on Leishmania and Leishmaniasis)
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Review

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18 pages, 634 KiB  
Review
Drug Discovery for Cutaneous Leishmaniasis: A Review of Developments in the Past 15 Years
Microorganisms 2023, 11(12), 2845; https://doi.org/10.3390/microorganisms11122845 - 23 Nov 2023
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Abstract
Leishmaniasis is a group of vector-borne, parasitic diseases caused by over 20 species of the protozoan Leishmania spp. The three major disease classifications, cutaneous, visceral, and mucocutaneous, have a range of clinical manifestations from self-healing skin lesions to hepatosplenomegaly and mucosal membrane damage [...] Read more.
Leishmaniasis is a group of vector-borne, parasitic diseases caused by over 20 species of the protozoan Leishmania spp. The three major disease classifications, cutaneous, visceral, and mucocutaneous, have a range of clinical manifestations from self-healing skin lesions to hepatosplenomegaly and mucosal membrane damage to fatality. As a neglected tropical disease, leishmaniasis represents a major international health challenge, with nearly 350 million people living at risk of infection a year. The current chemotherapeutics used to treat leishmaniasis have harsh side effects, prolonged and costly treatment regimens, as well as emerging drug resistance, and are predominantly used for the treatment of visceral leishmaniasis. There is an undeniable need for the identification and development of novel chemotherapeutics targeting cutaneous leishmaniasis (CL), largely ignored by concerted drug development efforts. CL is mostly non-lethal and the most common presentation of this disease, with nearly 1 million new cases reported annually. Recognizing this unaddressed need, substantial yet fragmented progress in early drug discovery efforts for CL has occurred in the past 15 years and was outlined in this review. However, further work needs to be carried out to advance early discovery candidates towards the clinic. Importantly, there is a paucity of investment in the translation and development of therapies for CL, limiting the emergence of viable solutions to deal with this serious and complex international health problem. Full article
(This article belongs to the Special Issue Research on Leishmania and Leishmaniasis)
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Other

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17 pages, 5616 KiB  
Case Report
Visceral Leishmaniasis in Immunocompetent Hosts in Brescia: A Case Series and Analysis of Cytokine Cascade
Microorganisms 2024, 12(2), 394; https://doi.org/10.3390/microorganisms12020394 - 16 Feb 2024
Viewed by 244
Abstract
Visceral leishmaniasis (VL) is a parasitic zoonosis caused by Leishmania spp. that usually manifests itself in immunocompromised subjects. It is a rare and neglected disease, and it is not endemic in the province of Brescia (Italy). Three cases of human VL occurred in [...] Read more.
Visceral leishmaniasis (VL) is a parasitic zoonosis caused by Leishmania spp. that usually manifests itself in immunocompromised subjects. It is a rare and neglected disease, and it is not endemic in the province of Brescia (Italy). Three cases of human VL occurred in Brescia from October to December 2021 in immunocompetent patients. We evaluated the patients looking for signs of underlying immunodeficiencies and conducted further epidemiological evaluations in the province of Brescia without success. An analysis of the sera levels of the main cytokines involved in the immune response to VL was performed. All patients presented a significant augmentation of CXCL-10, CCL-4, and IL-6. The patients tested during the acute phase showed an elevation of IL-1α, IL-5, IL-10, and IL-12, while in the recovery phase, higher levels of TNF-α and IL-7 were detected. Altogether, a predominant activation of the T-helper-2 pathway emerged during the acute phase of the parasite infection, while the cytokines associated with the T-helper-1 pathway were less represented. This imbalanced immune response to the parasite infection might play a crucial role in the development of VL in immunocompetent patients. Full article
(This article belongs to the Special Issue Research on Leishmania and Leishmaniasis)
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