Host-Pathogen Interactions during Leishmania Infections—a Special Issue in Honor of Prof. Dr. John David

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 17848

Special Issue Editors


E-Mail Website
Guest Editor
Instituto de Ciencias Biomédicas, Universidade de São Paulo, Sao Paulo, Brazil
Interests: biological sciences; collective health; ecology; health sciences; parasitology

E-Mail Website
Guest Editor
Department of Microbiology, The Ohio State University, Columbus, OH 43210, USA
Interests: parasitic diseases; leishmaniasis; immunology; vaccines
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

John R. David graduated in Medicine in Chicago and joined the house staff of the Massachusetts General Hospital in Boston, moving to New York University where he discovered the macrophage migration inhibitory factor (MIF) in the mid-1960s. This monumental discovery opened the door to understanding how macrophages communicate. From there, he went to Harvard where he made ground-breaking contributions in the early 1970s on the function of cytokines in allergies. He sensed the gap between technical advances and tropical medicine and dedicated his forces to closing it, especially in leishmaniasis. This began with the production of the first leishmanial-specific monoclonal antibodies in the 1980s with Diana McMahon-Pratt. Latterly, he established a long-term collaborative project between Harvard and Brazil on the disease. He also sensed the need for simpler, less aggressive methods of treatment and personally pioneered the use of radiofrequency-induced heat therapy for cutaneous leishmaniasis in the Middle East and South America. Under his guidance, research in tropical diseases at the Harvard Medical School flourished, and upon his retirement, he became the Richard Pearson Strong Emeritus Professor of Tropical Public Health in the Harvard Faculty of Public Health. John’s enthusiasm has no limits and is contagious, as can be seen by the trail of discoveries that his work has led to. This Special Issue is in honour of John’s amazing contributions, with a focus on the many fields of neglected pathological diseases.

Prof. Dr. Jeffrey Jon Shaw
Prof. Dr. Abhay Satoskar
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • leishmaniasis
  • prevention
  • pathology
  • cytokines
  • macrophages
  • vaccination
  • parasite diversity
  • treatment
  • genomics
  • transmission

Published Papers (14 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Other

1 pages, 122 KiB  
Editorial
A Tribute to a Visionary Scientist—John R. David—Richard Pearson Strong, Professor of Tropical Public Health, Emeritus, Harvard
by Jeffrey J. Shaw and Abhay Satoskar
Pathogens 2024, 13(3), 208; https://doi.org/10.3390/pathogens13030208 - 27 Feb 2024
Viewed by 782
Abstract
There are rare individuals whose insatiable curiosity and boundless intellect propel them into multiple frontiers of science, leaving an indelible mark on the fields that they venture into [...] Full article

Research

Jump to: Editorial, Other

12 pages, 2541 KiB  
Article
In Situ versus Systemic Immune Response in the Pathogenesis of Cutaneous Leishmaniasis
by Augusto M. Carvalho, Rúbia S. Costa, Alexsandro Lago, Olívia Bacellar, Daniel P. Beiting, Phillip Scott, Lucas P. Carvalho and Edgar M. Carvalho
Pathogens 2024, 13(3), 199; https://doi.org/10.3390/pathogens13030199 - 23 Feb 2024
Viewed by 846
Abstract
The role of the immune response in the pathogenesis of cutaneous leishmaniasis (CL) due to Leishmania (Viannia) braziliensis is predominantly carried out via blood cells. Here, we evaluate whether cytokine production by peripheral blood mononuclear cells (PBMCs) reflects what has been documented at [...] Read more.
The role of the immune response in the pathogenesis of cutaneous leishmaniasis (CL) due to Leishmania (Viannia) braziliensis is predominantly carried out via blood cells. Here, we evaluate whether cytokine production by peripheral blood mononuclear cells (PBMCs) reflects what has been documented at the lesion site. The participants included 22 CL patients diagnosed with a positive PCR. PBMCs were stimulated for 72 h with a soluble leishmania antigen (SLA). Biopsies obtained from the edge of the ulcers were incubated for the same period. Cytokines in supernatants were assessed via ELISA. TNF, IL-1β, IL-6, IL-17, and granzyme B (GzmB) were higher in the supernatants of biopsies than in PBMCs, but IFN-γ was higher in the supernatants of PBMCs than in biopsies. There was a positive correlation between IFN-γ and TNF in PBMCs, and an inverse correlation between TNF and IL-10 in the cells from the lesion site. A strong correlation between IL-1β, IL-17, and GzmB was observed in the biopsies, and a positive correlation was detected between these cytokines and the lesion size. Our results indicate that the immune response in L. braziliensis lesions is different from that observed in peripheral blood, and our data suggest that in addition to IL-1β and GzmB, IL-17 participates in the pathology of CL. Full article
Show Figures

Figure 1

9 pages, 617 KiB  
Article
Impact of 4% Deltamethrin-Impregnated Dog Collars on the Incidence of Human Visceral Leishmaniasis: A Community Intervention Trial in Brazil
by Guilherme Loureiro Werneck, Fabiano Borges Figueiredo and Maria do Socorro Pires e Cruz
Pathogens 2024, 13(2), 135; https://doi.org/10.3390/pathogens13020135 - 01 Feb 2024
Viewed by 852
Abstract
Background: In Brazil, human visceral leishmaniasis (HVL) is caused by the protozoan parasite Leishmania infantum, primarily transmitted by the sand fly Lutzomyia longipalpis, with dogs acting as the main urban reservoir. This study aims to evaluate the effectiveness of 4% deltamethrin-impregnated [...] Read more.
Background: In Brazil, human visceral leishmaniasis (HVL) is caused by the protozoan parasite Leishmania infantum, primarily transmitted by the sand fly Lutzomyia longipalpis, with dogs acting as the main urban reservoir. This study aims to evaluate the effectiveness of 4% deltamethrin-impregnated dog collars (DMC) on HVL incidence. Methods: This is a community intervention study carried out from 2012 to 2015 in the municipalities of Araguaína, State of Tocantins, and Montes Claros, State of Minas Gerais, Brazil. Two areas in each were randomly allocated to either (1) culling seropositive dogs + residual insecticide spraying (control area—CA) or (2) culling seropositive dogs + residual insecticide spraying + DMC fitted to dogs every six months for two years (intervention area—IA). Cases of HVL (n = 1202) occurring from 2008 to 2020 were identified from the Brazilian Reportable Diseases Information System and georeferenced to the control and intervention areas. The HVL cases from 2008 to 2012 were considered as occurring in the “pre-intervention” period. Those cases from 2013 to 2016 and from 2017 to 2020 were regarded as occurring in the “intervention” and “post-intervention” periods, respectively. We used a mixed-effects Poisson regression model to estimate the effectiveness of the intervention, comparing the changes from the pre-intervention period to the intervention and post-intervention periods in the control and intervention areas. Results: In Araguaína, there was a statistically significant reduction in the incidence of HVL in both the control and intervention areas, comparing both the intervention and post-intervention periods with the pre-intervention period. The intervention with DMC was significantly associated with a reduction in HVL when comparing the intervention and pre-intervention periods, yielding an effectiveness estimate of the DMC of 27% (IC95% 1–46%, p = 0.045). No differences were observed when comparing the pre- and post-intervention periods (p = 0.827). In Montes Claros, cases reduced in both the control and intervention areas from the pre-intervention period to the intervention period (p = 0.913). In the post-intervention period, the incidence increased in the control area, while cases continued to decrease in the DMC area (p = 0.188). Conclusions: The use of DMC was associated with a reduction of 27% in the incidence of HVL during the period of DMC delivery, indicating that DMC is effective as an additional strategy for controlling visceral leishmaniasis in Brazil. However, no significant reduction associated with DMC was detected after the intervention period, suggesting that a control program based on the large-scale deployment of DMC might have to be maintained for more extended periods without interruption. Full article
Show Figures

Figure 1

21 pages, 17880 KiB  
Article
Genomes of Endotrypanum monterogeii from Panama and Zelonia costaricensis from Brazil: Expansion of Multigene Families in Leishmaniinae Parasites That Are Close Relatives of Leishmania spp.
by Percy O. Tullume-Vergara, Kelly Y. O. Caicedo, Jose F. C. Tantalean, Myrna G. Serrano, Gregory A. Buck, Marta M. G. Teixeira, Jeffrey J. Shaw and Joao M. P. Alves
Pathogens 2023, 12(12), 1409; https://doi.org/10.3390/pathogens12121409 - 30 Nov 2023
Viewed by 1712
Abstract
The Leishmaniinae subfamily of the Trypanosomatidae contains both genus Zelonia (monoxenous) and Endotrypanum (dixenous). They are amongst the nearest known relatives of Leishmania, which comprises many human pathogens widespread in the developing world. These closely related lineages are models for the genomic [...] Read more.
The Leishmaniinae subfamily of the Trypanosomatidae contains both genus Zelonia (monoxenous) and Endotrypanum (dixenous). They are amongst the nearest known relatives of Leishmania, which comprises many human pathogens widespread in the developing world. These closely related lineages are models for the genomic biology of monoxenous and dixenous parasites. Herein, we used comparative genomics to identify the orthologous groups (OGs) shared among 26 Leishmaniinae species to investigate gene family expansion/contraction and applied two phylogenomic approaches to confirm relationships within the subfamily. The Endotrypanum monterogeii and Zelonia costaricensis genomes were assembled, with sizes of 29.9 Mb and 38.0 Mb and 9.711 and 12.201 predicted protein-coding genes, respectively. The genome of E. monterogeii displayed a higher number of multicopy cell surface protein families, including glycoprotein 63 and glycoprotein 46, compared to Leishmania spp. The genome of Z. costaricensis presents expansions of BT1 and amino acid transporters and proteins containing leucine-rich repeat domains, as well as a loss of ABC-type transporters. In total, 415 and 85 lineage-specific OGs were identified in Z. costaricensis and E. monterogeii. The evolutionary relationships within the subfamily were confirmed using the supermatrix (3384 protein-coding genes) and supertree methods. Overall, this study showed new expansions of multigene families in monoxenous and dixenous parasites of the subfamily Leishmaniinae. Full article
Show Figures

Figure 1

16 pages, 1221 KiB  
Article
Incidence of Human and Free-Ranging Wild Rodent Infections with Leishmania (Viannia) braziliensis, Aetiological Agent of Cutaneous Leishmaniasis
by Orin Courtenay, José F. Marinho-Júnior, Maria Edileuza F. Brito, Juliana F. C. L. S. Monteiro, Jeffrey J. Shaw and Sinval P. Brandão-Filho
Pathogens 2023, 12(12), 1395; https://doi.org/10.3390/pathogens12121395 - 28 Nov 2023
Viewed by 1128
Abstract
Background. Human and wild rodent infection rates with Leishmania (Viannia) braziliensis are needed to differentiate transmission pathways in anthropogenically altered habitats. Methods. Human participants in northeast Brazil were tested by the leishmanin skin test (LST) and inspected for lesions/scars characteristic of [...] Read more.
Background. Human and wild rodent infection rates with Leishmania (Viannia) braziliensis are needed to differentiate transmission pathways in anthropogenically altered habitats. Methods. Human participants in northeast Brazil were tested by the leishmanin skin test (LST) and inspected for lesions/scars characteristic of American clinical leishmaniasis (ACL). Molecular (PCR/qPCR) test records of free-ranging rodents were available from a concurrent capture–mark–recapture study. Force of Infection (λ) and recovery (ρ) rates were estimated from cross-sectional and longitudinal datasets. Results. Cumulative prevalences of human LST+ves and ACL scar+ves were 0.343–0.563 (n = 503 participants) and 0.122–0.475 (n = 503), respectively. Active ACL lesions were not detected. Annual rates of LST conversions were λ = 0.03–0.15 and ρ = 0.02–0.07. The probability of infection was independent of sex and associated with increasing age in addition to the period of exposure. Rodents (n = 596 individuals of 6 species) showed high rates of exclusively asymptomatic infection (λ = 0.222/month) and potential infectiousness to the sand fly vector. Spatially concurrent rodent and household human infection prevalences were correlated. Conclusions. Human exposure to L. (V.) braziliensis continues to be high despite the substantial drop in reported ACL cases in recent years. Spill-over transmission risk to humans from rodents in peridomestic habitats is likely supported by a rodent infection/transmission corridor linking houses, plantations, and the Atlantic Forest. Full article
Show Figures

Figure 1

20 pages, 4370 KiB  
Article
Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi
by Danielle Pessôa-Pereira, Breanna M. Scorza, Karen I. Cyndari, Erin A. Beasley and Christine A. Petersen
Pathogens 2023, 12(9), 1128; https://doi.org/10.3390/pathogens12091128 - 04 Sep 2023
Viewed by 1846
Abstract
Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, [...] Read more.
Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, the specific cellular mechanisms of how coinfections affect microbicidal responses against L. infantum are unknown. We hypothesized that B. burgdorferi coinfection impacts host macrophage effector functions, prompting L. infantum intracellular survival. In vitro experiments demonstrated that exposure to B. burgdorferi spirochetes significantly increased L. infantum parasite burden and pro-inflammatory responses in DH82 canine macrophage cells. Induction of cell death and generation of mitochondrial ROS were significantly decreased in coinfected DH82 cells compared to uninfected and L. infantum-infected cells. Ex vivo stimulation of PBMCs from L. infantum-seronegative and -seropositive subclinical dogs with spirochetes and/or total Leishmania antigens promoted limited induction of IFNγ. Coexposure significantly induced expression of pro-inflammatory cytokines and chemokines associated with Th17 differentiation and neutrophilic and monocytic recruitment in PBMCs from L. infantum-seropositive dogs. Excessive pro-inflammatory responses have previously been shown to cause CanL pathology. This work supports effective tick prevention and risk management of coinfections as critical strategies to prevent and control L. infantum progression in dogs. Full article
Show Figures

Graphical abstract

11 pages, 1089 KiB  
Article
Potential Biomarkers for Asymptomatic Visceral Leishmaniasis among Iraq-Deployed U.S. Military Personnel
by Fernanda Fortes de Araujo, Ines Lakhal-Naouar, Nancy Koles, Sorana Raiciulescu, Rupal Mody and Naomi Aronson
Pathogens 2023, 12(5), 705; https://doi.org/10.3390/pathogens12050705 - 12 May 2023
Cited by 3 | Viewed by 1348
Abstract
Visceral leishmaniasis (VL) is a chronic infection caused by Leishmania (L.) donovani or L. infantum parasites. Despite having the infection, most individuals never develop the clinical disease and are able to control the parasite and remain asymptomatic. However, some progress to [...] Read more.
Visceral leishmaniasis (VL) is a chronic infection caused by Leishmania (L.) donovani or L. infantum parasites. Despite having the infection, most individuals never develop the clinical disease and are able to control the parasite and remain asymptomatic. However, some progress to symptomatic VL, leading to death if untreated. The host immune response has a major role in determining the progression and severity of the clinical manifestations in VL; several immune biomarkers of symptomatic VL have been described with interferon-gamma release as a surrogate biomarker of host cellular immunity. However, new biomarkers to identify asymptomatic VL (AVL) are needed for the identification of people at risk for VL activation. In our study, levels of chemokine/cytokine in the supernatants of peripheral mononuclear blood cells (PBMC) from 35 AVL+ Iraq-deployed participants, stimulated in vitro with soluble Leishmania antigen for 72 h, were assessed by a bead-based assay that allows the measurement of multiple analytes. PBMC of AVL-negative military beneficiaries were used as controls. Monocyte Chemoattractant Protein-1, Monokine Induced by Gamma Interferon and Interleukin-8, were detected at high levels in AVL+ stimulated cultures from Iraq deployers compared to uninfected controls. Measurement of chemokine/cytokine levels can identify cellular immune responses in AVL+ asymptomatic individuals. Full article
Show Figures

Figure 1

10 pages, 1055 KiB  
Article
Infectiousness of Asymptomatic Meriones shawi, Reservoir Host of Leishmania major
by Jovana Sadlova, Barbora Vojtkova, Tereza Lestinova, Tomas Becvar, Daniel Frynta, Kamal Eddine Benallal, Nalia Mekarnia, Zoubir Harrat and Petr Volf
Pathogens 2023, 12(4), 614; https://doi.org/10.3390/pathogens12040614 - 18 Apr 2023
Cited by 1 | Viewed by 1186
Abstract
Leishmaniases are neglected diseases caused by protozoans of the genus Leishmania that threaten millions of people worldwide. Cutaneous leishmaniasis (CL) caused by L. major is a typical zoonosis transmitted by phlebotomine sand flies and maintained in rodent reservoirs. The female sand fly was [...] Read more.
Leishmaniases are neglected diseases caused by protozoans of the genus Leishmania that threaten millions of people worldwide. Cutaneous leishmaniasis (CL) caused by L. major is a typical zoonosis transmitted by phlebotomine sand flies and maintained in rodent reservoirs. The female sand fly was assumed to become infected by feeding on the skin lesion of the host, and the relative contribution of asymptomatic individuals to disease transmission was unknown. In this study, we infected 32 Meriones shawi, North African reservoirs, with a natural dose of L. major obtained from the gut of infected sand flies. Skin manifestations appeared in 90% of the animals, and xenodiagnosis with the proven vector Phlebotomus papatasi showed transmissibility in 67% of the rodents, and 45% were repeatedly infectious to sand flies. Notably, the analysis of 113 xenodiagnostic trials with 2189 sand flies showed no significant difference in the transmissibility of animals in the asymptomatic and symptomatic periods; asymptomatic animals were infectious several weeks before the appearance of skin lesions and several months after their healing. These results clearly confirm that skin lesions are not a prerequisite for vector infection in CL and that asymptomatic animals are an essential source of L. major infection. These data are important for modeling the epidemiology of CL caused by L. major. Full article
Show Figures

Figure 1

10 pages, 1936 KiB  
Article
Leishmania Infection-Induced Proteolytic Processing of SIRPα in Macrophages
by Hana Hirai, Jing Hong, Wataru Fujii, Chizu Sanjoba and Yasuyuki Goto
Pathogens 2023, 12(4), 593; https://doi.org/10.3390/pathogens12040593 - 13 Apr 2023
Cited by 1 | Viewed by 1456
Abstract
The shedding of cell surface receptors may bring synergistic outcomes through the loss of receptor-mediated cell signaling and competitive binding of the shed soluble receptor to its ligand. Thus, soluble receptors have both biological importance and diagnostic importance as biomarkers in immunological disorders. [...] Read more.
The shedding of cell surface receptors may bring synergistic outcomes through the loss of receptor-mediated cell signaling and competitive binding of the shed soluble receptor to its ligand. Thus, soluble receptors have both biological importance and diagnostic importance as biomarkers in immunological disorders. Signal regulatory protein α (SIRPα), one of the receptors responsible for the ‘don’t-eat-me’ signal, is expressed by myeloid cells where its expression and function are in part regulated by proteolytic cleavage. However, reports on soluble SIRPα as a biomarker are limited. We previously reported that mice with experimental visceral leishmaniasis (VL) manifest anemia and enhanced hemophagocytosis in the spleen accompanied with decreased SIRPα expression. Here, we report increased serum levels of soluble SIRPα in mice infected with Leishmania donovani, a causative agent of VL. Increased soluble SIRPα was also detected in a culture supernatant of macrophages infected with L. donovani in vitro, suggesting the parasite infection promotes ectodomain shedding of SIRPα on macrophages. The release of soluble SIRPα was partially inhibited by an ADAM proteinase inhibitor in both LPS stimulation and L. donovani infection, suggesting a shared mechanism for cleavage of SIRPα in both cases. In addition to the ectodomain shedding of SIRPα, both LPS stimulation and L. donovani infection induced the loss of the cytoplasmic region of SIRPα. Although the effects of these proteolytic processes or changes in SIRPα still remain unclear, these proteolytic regulations on SIRPα during L. donovani infection may explain hemophagocytosis and anemia induced by infection, and serum soluble SIRPα may serve as a biomarker for hemophagocytosis and anemia in VL and the other inflammatory disorders. Full article
Show Figures

Figure 1

16 pages, 2583 KiB  
Article
Toll-like Receptor-9 (TLR-9) Signaling Is Crucial for Inducing Protective Immunity following Immunization with Genetically Modified Live Attenuated Leishmania Parasites
by Parna Bhattacharya, Sreenivas Gannavaram, Nevien Ismail, Ankit Saxena, Pradeep K. Dagur, Adovi Akue, Mark KuKuruga and Hira L. Nakhasi
Pathogens 2023, 12(4), 534; https://doi.org/10.3390/pathogens12040534 - 29 Mar 2023
Viewed by 1560
Abstract
No human vaccine is available for visceral leishmaniasis (VL). Live attenuated centrin gene-deleted L. donovani (LdCen−/−) parasite vaccine has been shown to induce robust innate immunity and provide protection in animal models. Toll-like receptors (TLRs) are expressed in innate immune [...] Read more.
No human vaccine is available for visceral leishmaniasis (VL). Live attenuated centrin gene-deleted L. donovani (LdCen−/−) parasite vaccine has been shown to induce robust innate immunity and provide protection in animal models. Toll-like receptors (TLRs) are expressed in innate immune cells and are essential for the early stages of Leishmania infection. Among TLRs, TLR-9 signaling has been reported to induce host protection during Leishmania infection. Importantly, TLR-9 ligands have been used as immune enhancers for non-live vaccination strategies against leishmaniasis. However, the function of TLR-9 in the generation of a protective immune response in live attenuated Leishmania vaccines remains unknown. In this study, we investigated the function of TLR-9 during LdCen−/− infection and found that it increased the expression of TLR-9 on DCs and macrophages from ear-draining lymph nodes and spleen. The increase in TLR-9 expression resulted in changes in downstream signaling in DCs mediated through signaling protein myeloid differentiation primary response 88 (MyD88), resulting in activation and nuclear translocation of nuclear factor-κB (NF-κB). This process resulted in an increase in the DC’s proinflammatory response, activation, and DC-mediated CD4+T cell proliferation. Further, LdCen−/− immunization in TLR-9−/− mice resulted in a significant loss of protective immunity. Thus, LdCen−/− vaccine naturally activates the TLR-9 signaling pathway to elicit protective immunity against virulent L. donovani challenge. Full article
Show Figures

Figure 1

Other

Jump to: Editorial, Research

10 pages, 1057 KiB  
Brief Report
Activity of the Di-Substituted Urea-Derived Compound I-17 in Leishmania In Vitro Infections
by José Vitorino dos Santos, Jorge Mansur Medina, Karina Luiza Dias Teixeira, Daniel Marcos Julio Agostinho, Michael Chorev, Aurora Diotallevi, Luca Galluzzi, Bertal Huseyin Aktas and Ulisses Gazos Lopes
Pathogens 2024, 13(2), 104; https://doi.org/10.3390/pathogens13020104 - 24 Jan 2024
Viewed by 687
Abstract
Protein synthesis has been a very rich target for developing drugs to control prokaryotic and eukaryotic pathogens. Despite the development of new drug formulations, treating human cutaneous and visceral Leishmaniasis still needs significant improvements due to the considerable side effects and low adherence [...] Read more.
Protein synthesis has been a very rich target for developing drugs to control prokaryotic and eukaryotic pathogens. Despite the development of new drug formulations, treating human cutaneous and visceral Leishmaniasis still needs significant improvements due to the considerable side effects and low adherence associated with the current treatment regimen. In this work, we show that the di-substituted urea-derived compounds I-17 and 3m are effective in inhibiting the promastigote growth of different Leishmania species and reducing the macrophage intracellular load of amastigotes of the Leishmania (L.) amazonensis and L. major species, in addition to exhibiting low macrophage cytotoxicity. We also show a potential immunomodulatory effect of I-17 and 3m in infected macrophages, which exhibited increased expression of inducible Nitric Oxide Synthase (NOS2) and production of Nitric Oxide (NO). Our data indicate that I-17, 3m, and their analogs may be helpful in developing new drugs for treating leishmaniasis. Full article
Show Figures

Figure 1

8 pages, 411 KiB  
Brief Report
Mucosal Relapse of Visceral Leishmaniasis in a Child with SARS-CoV-2 Infection
by Claudia Colomba, Giovanni Boncori, Chiara Albano, Valeria Garbo, Sara Bagarello, Anna Condemi, Salvatore Giordano and Antonio Cascio
Pathogens 2023, 12(9), 1127; https://doi.org/10.3390/pathogens12091127 - 03 Sep 2023
Viewed by 904
Abstract
Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania and is transmitted through the bite of infected female sandflies. In the Mediterranean region, visceral leishmaniasis is caused by Leishmania. infantum, and it is usually responsible for symptoms such as [...] Read more.
Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania and is transmitted through the bite of infected female sandflies. In the Mediterranean region, visceral leishmaniasis is caused by Leishmania. infantum, and it is usually responsible for symptoms such as fever, pancytopenia and enlargement of the liver and spleen. Relapse is rare in immunocompetent patients as much as the mucous involvement. We present a rare case of mucosal relapse of visceral leishmaniasis in a child with SARS-CoV-2 infection and perform an extensive review of the literature about leishmaniasis relapses in children. Atypical mucosal involvement during Leishmaniasis relapse is an eventuality in pediatric patients. Clinical follow-up and periodic PCR tests must be considered essential for the early recognition and treatment of an eventual relapse. Full article
Show Figures

Figure 1

9 pages, 21999 KiB  
Case Report
The Extraordinary Case of a Woman with a 30-Year-Long Diffuse Leishmaniasis Cured with One Single Ampoule of Intranasal Pentavalent Antimoniate
by Sheila V. C. B. Gonçalves, Dorcas L. Costa, João da J. Cantinho-Junior, José N. Vieira-Junior, Edna A. Y. Ishikawa, Rubens N. Costa, Antônio C. G. Costa-Filho, Ronald da C. Araújo, Silvia R. B. Uliana, Jenicer K. U. Y. Yasunaka, Adriano C. Coelho, Jackson M. L. Costa and Carlos H. N. Costa
Pathogens 2023, 12(7), 890; https://doi.org/10.3390/pathogens12070890 - 29 Jun 2023
Viewed by 928
Abstract
Infection with Leishmania amazonensis and L. mexicana may lead to diffuse cutaneous leishmaniasis. The cure is exceptional, especially for the strange case of this lady. Case report: The patient acquired the disease in childhood and remained with lesions for over 30 years, albeit [...] Read more.
Infection with Leishmania amazonensis and L. mexicana may lead to diffuse cutaneous leishmaniasis. The cure is exceptional, especially for the strange case of this lady. Case report: The patient acquired the disease in childhood and remained with lesions for over 30 years, albeit several treatments. She worsened after a pregnancy, developing disseminated lesions. Miltefosine with amphotericin B and pentamidine resulted in remission. Lesions reappeared after one year, accompanied by intra-nasal infiltration of the disease. The nasal spraying of a single ampoule of pentavalent antimoniate resulted in the sustained disappearance of the nasal symptoms and all the cutaneous lesions. After over eight years, she remains disease-free, albeit under renal replacement therapy. The high nasal mucosal antimonial concentration may explain the long-lasting cure via new MHC class I epitope-specific CD8+ cell clones against L. amazonensis present in the nasal mucosa. Full article
Show Figures

Figure 1

9 pages, 294 KiB  
Perspective
Leishmaniosis in Greece: The Veterinary Perspective
by Isaia Symeonidou, Georgios Sioutas, Athanasios I. Gelasakis, Constantina N. Tsokana and Elias Papadopoulos
Pathogens 2023, 12(6), 769; https://doi.org/10.3390/pathogens12060769 - 26 May 2023
Viewed by 1445
Abstract
Leishmaniosis caused by the protozoon Leishmania infantum that is transmitted through the bites of infected phlebotomine sandflies is of major veterinary concern in Greece. The country is endemic with particularly favourable environmental conditions for the spread of this infection. Moreover, Greece remains a [...] Read more.
Leishmaniosis caused by the protozoon Leishmania infantum that is transmitted through the bites of infected phlebotomine sandflies is of major veterinary concern in Greece. The country is endemic with particularly favourable environmental conditions for the spread of this infection. Moreover, Greece remains a popular touristic destination, and the continuous travel of pets raises concern regarding the possible dissemination of infection from endemic to non-endemic areas. Dogs are the main reservoir host, although other animal species, including humans, may also be infected. Canine leishmaniosis manifests as a visceral disease that can result in death if left untreated. Serological and molecular epizootiological studies have confirmed circulation of the parasite in Greek canine and feline populations as well as in other mammals. As a result, constant surveillance and identification of high-risk localities are necessary to establish chemoprophylactic protocols for travelling animals to safeguard animal and public health. Full article
Back to TopTop