Topic Editors

1. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
2. Rede Micologia RJ – Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro, Brazil
Dr. Koert Ritmeijer
Médecins Sans Frontières, Amsterdam, The Netherlands
Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Dr. Claudia Masini d'Avila-Levy
Laboratório de Estudos Integrados em Protozoologia, Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Coleção de Protozoários da Fiocruz, Rio de Janeiro, RJ, Brasil
Dr. Cátia Lacerda Sodré
Departamento de Biologia Celular e Molecular (GCM), Instituto de Biologia (IB), Universidade Federal Fluminense (UFF), Niterói-RJ, Brazil
Departamento de Produtos Naturais e Alimentos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil

Novel Therapeutic Strategies against Leishmania and Trypanosoma

Abstract submission deadline
closed (30 March 2023)
Manuscript submission deadline
closed (30 May 2023)
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15484

Topic Information

Dear Colleagues,

The so-called neglected tropical diseases comprise a group of infections that is especially endemic in low-income populations in developing countries of Africa, Asia and the Americas. In this group, the American (Trypanosoma cruzi) and African (Trypanosoma brucei complex) trypanosome species and parasites belonging to the Leishmania genus are the etiologic agents of major human and animal parasitic diseases worldwide, being responsible for large socio-economic losses, especially in developing countries. The effective treatment of diseases caused by these trypanosomatids is still an open issue, nevertheless of paramount importance. Chemotherapy still relies on drugs developed decades ago, showing limited efficacy and possibility of toxic side effects. Nowadays, new approaches have been employed to improve treatment, and research is being conducted to discover strategies that are safer, more efficacious and accessible. These strategies include the use of lipid formulations, such as amphotericin B or miltefosine, to treat the leishmaniasis and chemotherapeutic combinations for other parasitic diseases. However, this still remains expensive, considering the target population. Moreover, the emergence of resistance has been reported. Efforts to tackle these diseases require research on the molecular components that regulate the infection initiation, which is critical for a better understanding of the diseases’ pathogeneses. Considering that these infections represent a major health concern worldwide, the development of a new generation of chemotherapeutic agents is of extreme importance. For that, research on the relevant aspects of targeted drug development is a critical priority. In this context, potential lines of research have been aroused: the search for original drugs, the search for potential compounds in public databases and the application of drugs already approved for clinical use for a particular purpose (repurposing strategy) against novel targets (or pathogens). Of particular relevance, novel drugs must be capable of blocking crucial biological events in the parasite cell, leading to growth arrest, inhibition of virulence factors and, most importantly, death. The editors invite investigators to contribute original research articles, as well as review articles, that will stimulate continuing efforts in the search for novel potential antiparasitic compounds and/or novel chemotherapeutic strategies against infections caused by Leishmania spp. and Trypanosoma spp. Potential topics include but are not limited to:

  • Synthesis and/or discovery of new compounds with antiparasitic properties;
  • Old drugs with new prospective potential with antiparasitic action;
  • Description of the physiological effects of new/old compounds, including inhibition of nutrition, growth, proliferation, differentiation and adhesion;
  • Effects of new/old compounds on the expression/production of virulence factors by parasite cells;
  • In vitro and/or in vivo efficacy of new or old compounds in the infectious process.

Prof. Dr. André Luis Souza dos Santos
Dr. Koert Ritmeijer
Prof. Dr. Marta Helena Branquinha
Dr. Claudia Masini d'Avila-Levy
Dr. Cátia Lacerda Sodré
Dr. Igor de Almeida Rodrigues
Topic Editors

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Tropical Medicine and Infectious Disease
tropicalmed
2.8 3.9 2016 19.4 Days CHF 2700
Pathogens
pathogens
3.3 6.4 2012 16.4 Days CHF 2700

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Published Papers (5 papers)

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3 pages, 219 KiB  
Editorial
Therapeutic Strategies against Leishmania and Trypanosoma
by André L. S. Santos, Igor A. Rodrigues, Claudia M. d’Avila-Levy, Cátia L. Sodré, Koert Ritmeijer and Marta H. Branquinha
Pathogens 2023, 12(10), 1263; https://doi.org/10.3390/pathogens12101263 - 19 Oct 2023
Viewed by 1110
Abstract
Human African trypanosomiasis (also known as sleeping sickness, with Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense as etiological agents), American trypanosomiasis (also known as Chagas disease, with Trypanosoma cruzi as the etiological agent), and leishmaniasis (including cutaneous, mucocutaneous, and visceral forms, with multiple [...] Read more.
Human African trypanosomiasis (also known as sleeping sickness, with Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense as etiological agents), American trypanosomiasis (also known as Chagas disease, with Trypanosoma cruzi as the etiological agent), and leishmaniasis (including cutaneous, mucocutaneous, and visceral forms, with multiple species belonging to the Leishmania genus as etiological agents) are recognized as neglected tropical diseases (NTDs) [...] Full article
13 pages, 1656 KiB  
Article
The Natural Alkaloid Tryptanthrin Induces Apoptosis-like Death in Leishmania spp.
by Andreza R. Garcia, Yasmin P. G. Silva-Luiz, Celuta S. Alviano, Daniela S. Alviano, Alane B. Vermelho and Igor A. Rodrigues
Trop. Med. Infect. Dis. 2022, 7(6), 112; https://doi.org/10.3390/tropicalmed7060112 - 20 Jun 2022
Cited by 5 | Viewed by 1945
Abstract
Leishmaniasis is a vector-borne disease against which there are no approved vaccines, and the treatment is based on highly toxic drugs. The alkaloids consist of a chemical class of natural nitrogen-containing substances with a long history of antileishmanial activity. The present study aimed [...] Read more.
Leishmaniasis is a vector-borne disease against which there are no approved vaccines, and the treatment is based on highly toxic drugs. The alkaloids consist of a chemical class of natural nitrogen-containing substances with a long history of antileishmanial activity. The present study aimed at determining the antileishmanial activity and in silico pharmacokinetic and toxicological potentials of tryptanthrin alkaloid. The anti-Leishmania amazonensis and anti-L. infantum assays were performed against both promastigotes and intracellular amastigotes. Cellular viability was determined by parasites’ ability to grow (promastigotes) or differentiate (amastigotes) after incubation with tryptanthrin. The mechanisms of action were explored by mitochondrion dysfunction and apoptosis-like death evaluation. For the computational pharmacokinetics and toxicological analysis (ADMET), tryptanthrin was submitted to the PreADMET webserver. The alkaloid displayed anti-promastigote activity against L. amazonensis and L. infantum (IC50 = 11 and 8.0 μM, respectively). Tryptanthrin was active against intracellular amastigotes with IC50 values of 75 and 115 μM, respectively. Mitochondrial membrane depolarization was observed in tryptanthrin-treated promastigotes. In addition, parasites undergoing apoptosis-like death were detected after 18 h of exposure. In silico ADMET predictions revealed that tryptanthrin has pharmacokinetic and toxicological properties similar to miltefosine. The results presented herein demonstrate that tryptanthrin is an interesting drug candidate against leishmaniasis. Full article
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10 pages, 1811 KiB  
Article
Therapeutic Efficacy of Orally Administered Nitrofurantoin against Animal African Trypanosomosis Caused by Trypanosoma congolense Infection
by Keisuke Suganuma, David D. N’Da, Ken-ichi Watanabe, Yusuke Tanaka, Ehab Mossaad, Afraa Elata, Noboru Inoue and Shin-ichiro Kawazu
Pathogens 2022, 11(3), 331; https://doi.org/10.3390/pathogens11030331 - 9 Mar 2022
Cited by 9 | Viewed by 2795
Abstract
Animal African trypanosomosis (AAT) leads to emaciation and low productivity in infected animals. Only six drugs are commercially available against AAT; they have severe side effects and face parasite resistance. Thus, the development of novel trypanocidal drugs is urgently needed. Nitrofurantoin, an antimicrobial, [...] Read more.
Animal African trypanosomosis (AAT) leads to emaciation and low productivity in infected animals. Only six drugs are commercially available against AAT; they have severe side effects and face parasite resistance. Thus, the development of novel trypanocidal drugs is urgently needed. Nitrofurantoin, an antimicrobial, is used for treating bacterial urinary tract infections. Recently, we reported the trypanocidal effects of nitrofurantoin and its analogs in vitro. Furthermore, a nitrofurantoin analog, nifurtimox, is currently used to treat Chagas disease and chronic human African trypanosomiasis. Thus, this study was aimed at evaluating the in vivo efficacy of nitrofurantoin in treating AAT caused by Trypanosoma congolense. Nitrofurantoin was orally administered for 7 consecutive days from 4 days post-infection in T. congolense-infected mice, and the animals were observed for 28 days. Compared to the control group, the treatment group showed significantly suppressed parasitemia at 6 days post-infection. Furthermore, survival was significantly prolonged in the group treated with at least 10 mg/kg nitrofurantoin. Moreover, 100% survival and cure was achieved with a dose of nitrofurantoin higher than 30 mg/kg. Thus, oral nitrofurantoin administration has potential trypanocidal efficacy against T. congolense-induced AAT. This preliminary data will serve as a benchmark when comparing future nitrofurantoin-related compounds, which can overcome the significant shortcomings of nitrofurantoin that preclude its viable use in livestock. Full article
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15 pages, 2878 KiB  
Article
Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B
by Marta H. Branquinha, Pedro S. S. Araújo, Simone S. C. Oliveira, Leandro S. Sangenito, Diego S. Gonçalves, Sérgio H. Seabra, Claudia M. d’Avila-Levy and André L. S. Santos
Trop. Med. Infect. Dis. 2022, 7(2), 29; https://doi.org/10.3390/tropicalmed7020029 - 16 Feb 2022
Cited by 2 | Viewed by 2214
Abstract
The necessity of drug combinations to treat leishmaniasis came to the surface mainly because of the toxicity of current treatments and the emergence of resistant strains. The calpain inhibitor MDL28170 has previously shown anti-Leishmania activity, therefore its use in association with standard [...] Read more.
The necessity of drug combinations to treat leishmaniasis came to the surface mainly because of the toxicity of current treatments and the emergence of resistant strains. The calpain inhibitor MDL28170 has previously shown anti-Leishmania activity, therefore its use in association with standard drugs could provide a new alternative for the treatment strategy against leishmaniasis. In this study, we analyzed the potential of the combination of MDL28170 and the antileishmanial drug amphotericin B against Leishmania amazonensis and Leishmania chagasi. The compounds were tested in the combination of the ½ × IC50 value of MDL28170 plus the ¼ × IC50 value of amphotericin B, which led to an increment in the anti-promastigote activity when compared to the single drug treatments. This drug association revealed several and severe morphophysiological changes on parasite cells, such as loss of plasma membrane integrity, reduced size of flagellum, and depolarization of mitochondrial membrane potential besides increased reactive oxygen species production. In addition, the combination of both drugs had a deleterious effect on the Leishmania–macrophage interaction, reflecting in a significant anti-amastigote action, which achieved a reduction of 50% in the association index. These results indicate that the combination treatment proposed here may represent a new alternative for leishmaniasis chemotherapy. Full article
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9 pages, 922 KiB  
Article
Treatment of Complex Cutaneous Leishmaniasis with Liposomal Amphotericin B
by Maria Ubals, Pau Bosch-Nicolau, Adrián Sánchez-Montalvá, Fernando Salvador, Gloria Aparicio-Español, Elena Sulleiro, Aroa Silgado, Antoni Soriano-Arandes, Maria Espiau, Berta Ferrer, Diana Pou, Begoña Treviño, Israel Molina and Vicente García-Patos
Pathogens 2021, 10(10), 1253; https://doi.org/10.3390/pathogens10101253 - 28 Sep 2021
Cited by 7 | Viewed by 4032
Abstract
Background: There is no consensus for the best treatment of complex cutaneous leishmaniasis (CL). We aimed to describe a cohort of CL, focusing on liposomal amphotericin B (L-AmB) treatment outcome. Methods: We performed a retrospective study in Vall d’Hebron University Hospital (Barcelona, Spain). [...] Read more.
Background: There is no consensus for the best treatment of complex cutaneous leishmaniasis (CL). We aimed to describe a cohort of CL, focusing on liposomal amphotericin B (L-AmB) treatment outcome. Methods: We performed a retrospective study in Vall d’Hebron University Hospital (Barcelona, Spain). All patients with parasitologically proven CL diagnosed from 2012 to 2018 were included. Results: The analysis included 41 patients with CL. The median age was 39 years (IQR 12- 66); 12 (29%) were children, and 29 (71%) were men. Regarding treatment, 24 (59%) received local treatment, whereas 17 (41%) had complex CL and were offered intravenous systemic treatment. Sixteen patients received L-AmB; eight (50%) had adverse events, and three (19%) discontinued treatment for safety reasons. All cases were considered cured within the first year post-treatment. Conclusions: L-AmB for complex CL showed no treatment failures, offering an alternative treatment option for patients with complex CL. Clinicians should pay close attention to the potential adverse events of L-AmB and adopt an active drug safety surveillance scheme to rapidly detect reversible side effects. Full article
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