Advances in Leishmaniasis and Chagas Disease: Biology, Epidemiology, Treatment and Control

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Microbiology".

Deadline for manuscript submissions: 15 August 2024 | Viewed by 5863

Special Issue Editors


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Guest Editor
Postgraduate Program in Animal Science, State University of Maranhão, Sao Luis 65055-310, Brazil
Interests: immunology; pharmacology; pathology; inflammation; immunomodulators; Leishmaniasis; tumor; cellular biology; molecular biology; biochemistry

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Guest Editor
Laboratory of Immunomodulation and Protozoology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Interests: Leishmaniasis; Chagas disease; immunopathology; diagnosis; treatment; epidemiology; molecular biology

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Guest Editor
Laboratory of Immunomodulation and Protozoology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
Interests: Leishmaniasis; Chagas disease; inflammation; host-pathogen interaction; extracellular matrix; immunopathology; toxoplasmosis; vaccine; treatment, murine model

Special Issue Information

Dear Colleagues,

Leishmaniasis and Chagas disease are neglected tropical diseases, prevalent in tropical regions, especially developing countries. Leishmaniases are a group of diseases that affects around 700,000 to 1 million people worldwide annually. Chagas disease is caused by Trypanosoma cruzi, and it is estimated that there are about 6 to 7 million people infected with it worldwide. In Brazil, visceral leishmaniasis is considered one of the top parasitic diseases with outbreak and mortality potential, while Chagas disease is the fourth cause of death resulting from infectious and parasitic diseases. Clinical outcomes of both diseases depend on the complexity of the factors involved, related both to the parasite (genetic variability, inoculum, infectivity, pathogenicity, virulence, and inoculation pathways) and to the host (age, sex, nutrition, immune profile, and species). Few effective therapeutic options are available for both diseases, with considerable side effects and long treatment periods, in addition to an increasing development of parasite resistance to the drugs in current use. The complexity of the factors involved in the immunopathology of both Leishmaniasis and Chagas disease influences the disease pathogenesis, chemotherapy outcome, and control, highlighting the need for further studies to improve our understanding of these relationships.

This Special Issue aims to report new insights into interdisciplinary approaches covering host–parasite and vector interaction, immune response of hosts, new molecular pathways for parasite survival and persistence, new drug development and mechanisms of antiparasitic drugs, as well as control, epidemiology, and vaccine development. Studies focusing on immunopathogeny and diagnosis, host defense, survival–resistance mechanisms, host–pathogen interactions, immune response, virulence factors, molecular diagnosis, immunological diagnosis, drug and vaccine development, pharmacological resistance, phytotherapy, synthetic compounds, drug repurposing, mechanisms of action, toxicology, preclinical trials, vaccine adjuvant, vaccine antigen, antibody, clinical and epidemiological insights, clinical manifestations, risk factors, distribution, ecology transmission, life cycle, wild cycle, reservoirs, and species taxonomy are welcome. We envision that this Special Issue will introduce valuable insights regarding Leishmaniasis and Chagas disease management.

Prof. Dr. Fernando Almeida-Souza
Dr. Flávia De Oliveira Cardoso
Dr. Kátia Da Silva Calabrese
Guest Editors

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Keywords

  • Leishmaniasis
  • Chagas disease
  • immunopathogeny
  • diagnosis
  • epidemiology
  • control
  • clinical studies
  • treatment
  • vaccine
 

Published Papers (5 papers)

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Research

17 pages, 3835 KiB  
Article
Unveiling Lovastatin’s Anti-Inflammatory Potential in Mouse’s Brain during Acute Trypanosoma cruzi Infection
by Beatriz Matheus de Souza Gonzaga, Líndice Mitie Nisimura, Laura Lacerda Coelho, Roberto Rodrigues Ferreira, Samuel Iwao Maia Horita, Daniela Gois Beghini, Vanessa Estato, Tania Cremonini de Araújo-Jorge and Luciana Ribeiro Garzoni
Biology 2024, 13(5), 301; https://doi.org/10.3390/biology13050301 - 27 Apr 2024
Viewed by 741
Abstract
Neurological commitment is a neglected manifestation of Chagas disease (CD). Meningoencephalitis mainly affects children and immunosuppressed patients, while stroke can occur with or without cardiac compromise. One of the possible causes of stroke development is microvascular commitment. Our group previously described that experimental [...] Read more.
Neurological commitment is a neglected manifestation of Chagas disease (CD). Meningoencephalitis mainly affects children and immunosuppressed patients, while stroke can occur with or without cardiac compromise. One of the possible causes of stroke development is microvascular commitment. Our group previously described that experimental Trypanossoma cruzi acute infection leads to cerebral microvasculopathy. This condition is characterized by decreased capillary density, increased leukocyte rolling and adhesion, and endothelial dysfunction. CD was discovered 114 years ago, and until today, only two drugs have been available for clinical treatment: benznidazole and nifurtimox. Both present a high cure rate for the acute phase (80%) and small cure rate for the chronic phase (20%). In addition, the high occurrence of side-effects, without proper medical follow-up, can result in treatment abandonment. Therefore, the search for new therapeutic schemes is necessary. Statins are drugs already used in the clinic that have several pleiotropic effects including endothelial function improvement, anti-inflammatory action, as well as trypanocidal effects, making them a potential alternative treatment for brain microvasculopathy in CD. Here, we investigate the effect of lovastatin (LOV) on brain microvasculopathy and inflammatory parameters. Swiss Webster mice were intraperitoneally inoculated with the Y strain of T. cruzi. Treatment with lovastatin (20 mg/kg/day) was initiated 24 h after the infection and continued for 14 consecutive days. We observed that LOV treatment did not affect parasitemia, brain microcirculation alterations, or the reduction in cerebral blood flow caused by T. cruzi infection. Also, LOV did not prevent the increased number of CD3+ cells and eNOS levels in the T. cruzi-infected brain. No alterations were observed on VCAM-1 and MCP-1 expressions, neither caused by infection nor LOV treatment. However, LOV prevented the increase in F4/80+ cells and ICAM-1 levels in the brain caused by acute infection with T. cruzi. These results suggest an anti-inflammatory activity of LOV, but more studies are needed to elucidate the role of LOV in CD acute infection. Full article
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15 pages, 3461 KiB  
Article
Vascular Growth Factor Inhibition with Bevacizumab Improves Cardiac Electrical Alterations and Fibrosis in Experimental Acute Chagas Disease
by Lindice Mitie Nisimura, Roberto Rodrigues Ferreira, Laura Lacerda Coelho, Gabriel Melo de Oliveira, Beatriz Matheus Gonzaga, Marcelo Meuser-Batista, Joseli Lannes-Vieira, Tania Araujo-Jorge and Luciana Ribeiro Garzoni
Biology 2023, 12(11), 1414; https://doi.org/10.3390/biology12111414 - 10 Nov 2023
Cited by 1 | Viewed by 1170
Abstract
Chagas disease (CD) caused by Trypanosoma cruzi is a neglected illness and a major reason for cardiomyopathy in endemic areas. The existing therapy generally involves trypanocidal agents and therapies that control cardiac alterations. However, there is no treatment for the progressive cardiac remodeling [...] Read more.
Chagas disease (CD) caused by Trypanosoma cruzi is a neglected illness and a major reason for cardiomyopathy in endemic areas. The existing therapy generally involves trypanocidal agents and therapies that control cardiac alterations. However, there is no treatment for the progressive cardiac remodeling that is characterized by inflammation, microvasculopathy and extensive fibrosis. Thus, the search for new therapeutic strategies aiming to inhibit the progression of cardiac injury and failure is necessary. Vascular Endothelial Growth Factor A (VEGF-A) is the most potent regulator of vasculogenesis and angiogenesis and has been implicated in inducing exacerbated angiogenesis and fibrosis in chronic inflammatory diseases. Since cardiac microvasculopathy in CD is also characterized by exacerbated angiogenesis, we investigated the effect of inhibition of the VEGF signaling pathway using a monoclonal antibody (bevacizumab) on cardiac remodeling and function. Swiss Webster mice were infected with Y strain, and cardiac morphological and molecular analyses were performed. We found that bevacizumab significantly increased survival, reduced inflammation, improved cardiac electrical function, diminished angiogenesis, decreased myofibroblasts in cardiac tissue and restored collagen levels. This work shows that VEGF is involved in cardiac microvasculopathy and fibrosis in CD and the inhibition of this factor could be a potential therapeutic strategy for CD. Full article
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16 pages, 4616 KiB  
Article
Effectiveness of Systemic Insecticide Dog Treatment for the Control of Chagas Disease in the Tropics
by Edem Fiatsonu, Aniruddha Deka and Martial L. Ndeffo-Mbah
Biology 2023, 12(9), 1235; https://doi.org/10.3390/biology12091235 - 13 Sep 2023
Viewed by 1013
Abstract
Chagas disease, caused by Trypanosoma cruzi and transmitted by triatomines, can lead to severe cardiac issues and mortality in many mammals. Recent studies have shown that systemic insecticide treatment of dogs is highly effective in killing triatomines. Here, we assessed the impact of [...] Read more.
Chagas disease, caused by Trypanosoma cruzi and transmitted by triatomines, can lead to severe cardiac issues and mortality in many mammals. Recent studies have shown that systemic insecticide treatment of dogs is highly effective in killing triatomines. Here, we assessed the impact of dog treatment on T. cruzi transmission. We developed a mathematical model of T. cruzi transmission among triatomines, dogs, humans, and rodents. We used the model to evaluate the impact of dog treatment regimens on T. cruzi transmission dynamics to determine their effectiveness in reducing T. cruzi infection among hosts. We show that a 3-month treatment regimen may reduce T. cruzi incidence among humans by 59–80% in a high transmission setting, and 26–82% in a low transmission setting. An annual treatment may reduce incidence among humans by 49–74% in a high transmission setting, and by 11–76% in a low transmission setting. However, dog treatment may substantially increase T. cruzi prevalence among dogs if dog consumption of dead triatomines increases. Our model indicates that dog treatment may reduce T. cruzi infections among humans, but it may increase infections in dogs. Therefore, a holistic approach targeting different hosts is necessary for Chagas elimination. Full article
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18 pages, 5167 KiB  
Article
Antitrypanosomal Activity of 1,2,3-Triazole-Based Hybrids Evaluated Using In Vitro Preclinical Translational Models
by Lorraine Martins Rocha Orlando, Leonardo da Silva Lara, Guilherme Curty Lechuga, Giseli Capaci Rodrigues, Omar Ginoble Pandoli, Druval Santos de Sá and Mirian Claudia de Souza Pereira
Biology 2023, 12(9), 1222; https://doi.org/10.3390/biology12091222 - 8 Sep 2023
Viewed by 979
Abstract
Chagas disease therapy still relies on two nitroderivatives, nifurtimox and benznidazole (Bz), which have important limitations and serious adverse effects. New therapeutic alternatives for this silent disease, which has become a worldwide public health problem, are essential for its control and elimination. In [...] Read more.
Chagas disease therapy still relies on two nitroderivatives, nifurtimox and benznidazole (Bz), which have important limitations and serious adverse effects. New therapeutic alternatives for this silent disease, which has become a worldwide public health problem, are essential for its control and elimination. In this study, 1,2,3-triazole analogues were evaluated for efficacy against T. cruzi. Three triazole derivatives, 1d (0.21 µM), 1f (1.23 µM), and 1g (2.28 µM), showed potent activity against trypomastigotes, reaching IC50 values 10 to 100 times greater than Bz (22.79 µM). Promising candidates are active against intracellular amastigotes (IC50 ≤ 6.20 µM). Treatment of 3D cardiac spheroids, a translational in vitro model, significantly reduced parasite load, indicating good drug diffusion and efficacy. Oral bioavailability was predicted for triazole derivatives. Although infection was significantly reduced without drug pressure in a washout assay, the triazole derivatives did not inhibit parasite resurgence. An isobologram analysis revealed an additive interaction when 1,2,3-triazole analogs and Bz were combined in vitro. These data indicate a strengthened potential of the triazole scaffold and encourage optimization based on an analysis of the structure–activity relationship aimed at identifying new compounds potentially active against T. cruzi. Full article
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14 pages, 1718 KiB  
Article
In Vitro Antioxidant and Antitrypanosomal Activities of Extract and Fractions of Terminalia catappa
by Sandra Alves de Araújo, Aldilene da Silva Lima, Cláudia Quintino da Rocha, Henrique Previtalli-Silva, Daiana de Jesus Hardoim, Noemi Nosomi Taniwaki, Kátia da Silva Calabrese, Fernando Almeida-Souza and Ana Lucia Abreu-Silva
Biology 2023, 12(7), 895; https://doi.org/10.3390/biology12070895 - 22 Jun 2023
Cited by 2 | Viewed by 1342
Abstract
Chagas disease is a severe infectious and parasitic disease caused by the protozoan Trypanosoma cruzi and considered a public health problem. Chemotherapeutics are still the main means of control and treatment of the disease, however with some limitations. As an alternative treatment, plants [...] Read more.
Chagas disease is a severe infectious and parasitic disease caused by the protozoan Trypanosoma cruzi and considered a public health problem. Chemotherapeutics are still the main means of control and treatment of the disease, however with some limitations. As an alternative treatment, plants have been pointed out due to their proven pharmacological properties. Many studies carried out with Terminalia catappa have shown several biological activities, but its effect against T. cruzi is still unknown. The objective of this work is to evaluate the therapeutic potential of extracts and fractions obtained from T. catappa on the parasite T. cruzi, in addition to analyzing its antioxidant activity. T. catappa ethyl acetate fraction were produced and submitted the chemical characterization by Liquid Chromatography Coupled to Mass Spectrometry (LC-MS). From all T. catappa extracts and fractions evaluated, the ethyl acetate and the aqueous fraction displayed the best antioxidant activity by the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging method (IC50 of 7.77 ± 1.61 and 5.26 ± 1.26 µg/mL respectively), and by ferric ion reducing (FRAP) method (687.61 ± 0.26 and 1009.32 ± 0.13 µM of Trolox equivalent/mg extract, respectively). The ethyl acetate fraction showed remarkable T. cruzi inhibitory activity with IC50 of 8.86 ± 1.13, 24.91 ± 1.15 and 85.01 ± 1.21 µg/mL against epimastigotes, trypomastigotes and intracellular amastigotes, respectively, and showed no cytotoxicity for Vero cells (CC50 > 1000 µg/mL). The treatment of epimastigotes with the ethyl acetate fraction led to drastic ultrastructural changes such as the loss of cytoplasm organelles, cell disorganization, nucleus damage and the loss of integrity of the parasite. This effect could be due to secondary compounds present in this extract, such as luteolin, kaempferol, quercetin, ellagic acid and derivatives. The ethyl acetate fraction obtained from T. catappa leaves can be an effective alternative in the treatment and control of Chagas disease, and material for further investigations. Full article
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