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Emerging Topics in Leishmaniasis Research

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A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Neglected and Emerging Tropical Diseases".

Deadline for manuscript submissions: closed (30 July 2023) | Viewed by 19762

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Dr. Sandra Regina Maruyama

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Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos-UFSCar, São Carlos 13565-905, Brazil
Interests: functional genomics; comparative genomics; infectious diseases

Special Issue Information

Dear Colleagues,

Leishmaniases are vector-borne parasitic diseases caused by dixenous trypanosomatids from the Leishmaniinae subfamily. The three main clinical forms of these diseases are visceral, cutaneous and mucocutaneous. Visceral leishmaniasis is a systemic disease mainly affecting tissues, such as bone marrow, spleen and liver; it is fatal for most untreated or misdiagnosed cases. Cutaneous form is characterized by ulcerative skin lesions in exposed body parts, and is the most common form of Leishmaniases. The mucocutaneous form is characterized by destructive lesions in mucosal membranes of mouth, throat and nose. These diseases can cause serious disability, life-long scars and stigma since they are heavily associated with poverty and its impact. Leishmaniases are complex diseases involving a wide range of species in parasite, vector sand fly, and natural reservoir hosts. Factors such as urbanization, environmental impacts, and climate change influence in the epidemiology of these diseases. There is no licensed vaccine for humans, prevention and control measures are limited, and available treatment drugs have a high toxicity with many side effects. Diagnosis is primarily clinical and is usually confirmed using serological devices that have a high cross-reactivity with other trypanosomatids. Moreover, co-infections with other microbes or even poorly known microorganisms add extra complexity to these diseases. Thus, a paradigm shift and several research directions are required to tackle this disease. We invite investigators to contribute original research articles, case reports, and review articles on emerging topics in both fundamental science and applied research in Leishmaniasis. Potential topics include but are not limited to:

New molecular players in parasite/host, parasite/vector or vector/host interactions;
New tools/approaches to identify parasites and/or to diagnose disease;
Case reports with atypical and severe clinical manifestations or unusual findings;
Epidemiological studies in supposedly non-endemic regions;
Vector fauna and potential new vector species;
Studies with domestic and wild reservoirs hosts;
Comparative studies between Leishmania and monoxenous trypanosomatid species;
Co-infection studies.

Dr. Sandra Regina Maruyama
Guest Editor

Manuscript Submission Information

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Keywords

visceral leishmaniasis
mucocutaneous leishmaniasis
cutaneous leishmaniasis
sand fly vectors
reservoirs
leishmaniinae
human and animal infections.

Published Papers (10 papers)

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Research

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13 pages, 1337 KiB

Open AccessEditor’s ChoiceArticle

Infection of Leishmania donovani in Phlebotomus orientalis Sand Flies at Different Microhabitats of a Kala-Azar Endemic Village in Eastern Sudan

by Altayeb Khogali, Dia-Eldin A. Elnaiem, Ramón Díaz-Regañón, Tayseer Jibreel, Bakri Y. M. Nour, Samira Hamid Abdelrahman, Ricardo Molina and Maribel Jiménez

Trop. Med. Infect. Dis. 2024, 9(2), 40; https://doi.org/10.3390/tropicalmed9020040 - 2 Feb 2024

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Abstract

A study was carried out to compare the infection rates of Leishmania donovani in Phlebotomus orientalis sandflies at different microhabitats of a VL endemic village in Gedarif state, Sudan. DNA extracts of 1078 P. orientalis sand fly females sampled by CDC light traps from indoor, outdoor, peri-domestic, and sylvatic sites, in three transmission seasons, March–June 2016–18, in Helat-Belo village, were subjected to independent PCR amplifications targeting Leishmania kDNA and the cpb gene followed by ITS1 region sequencing. Leishmania kDNA was detected in 1.4% of the 1078 P. orientalis females captured in the area. Two of these specimens showed a characteristic 741 bp band of L. donovani after cpb gene amplification. The DNA sequence of the ITS1 region of the parasites matched the ITS1 L. donovani genotype F. There were no signficant differences between rates of infection of L. donovani in P. orientalis captured at different sites. Blood meals found in infected flies origninated from human (5 specimens), cattle (4 specimens) and donkey (2 specimens). The finding of fresh cow and donkey blood in the infected flies suggests the possible role of these animals in the zoopotentiation and/or zooprophylaxis against VL. The study provides important information for VL transmission models and control programs in East Africa. Full article

(This article belongs to the Special Issue Emerging Topics in Leishmaniasis Research)

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10 pages, 415 KiB

Open AccessArticle

Cutaneous Leishmaniasis Prevalence and Clinical Overview: A Single Center Study from Saudi Arabia, Eastern Region, Al-Ahsa

by Mahdi Al-Dhafiri, Abdulmohsen Alhajri, Zahraa Ali Alwayel, Jasmine Ahmed Alturaiki, Shaima Ali Bu Izran, Fatimah Ahmed Alhammad and Ryhana Mohammed Aljumaiah

Trop. Med. Infect. Dis. 2023, 8(12), 507; https://doi.org/10.3390/tropicalmed8120507 - 24 Nov 2023

Viewed by 1745

Abstract

Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease that is transmitted via the bites of infected female sandflies. CL has been endemic in several countries worldwide for many decades, and numerous cases have been reported in Saudi Arabia, particularly across six regions; one of which is AL-Ahsa. Our research aimed to evaluate the epidemiological situation of CL among the patients in Al-Ahsa, Eastern region, Kingdom of Saudi Arabia, during the period from 2017 to 2023. The data were collected from the patients’ registries and included 245 patients who were diagnosed with CL in Al-Ahsa, Saudi Arabia. Fewer than half of the cases (47.8%) were Saudi patients, with a significant number of them being males (84.5%). Over half of the cases (52.7%) were aged between 21 and 40 years, and about three-quarters (74.7%) of the cases resided in rural areas. Regarding the nature of the lesions, 38.4% of the cases had one lesion, which was mainly distributed on a lower extremity (62.0%) or an upper extremity (52.2%). A high percentage of the lesions (75.2%) were wet lesions and caused by L. major. Concerning risk factors, a greater number of patients (71.4%) had been in rural areas within the last three months. Additionally, more than half of the cases (54.3%) had close contact with rodents, followed by birds (28.2%), sheep (22.0%), dogs (16.3%), and other animals (1.2%). The results showed a low number of reported CL cases in 2020 and 2021, followed by a surge in 2022 and 2023. The study shows that cutaneous leishmaniasis is still a public health problem in Al-Ahsa and is primarily associated with rural areas. Full article

(This article belongs to the Special Issue Emerging Topics in Leishmaniasis Research)

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11 pages, 970 KiB

Open AccessArticle

Evaluation of Proinflammatory Chemokines in HIV Patients with Asymptomatic Leishmania Infantum Infection

by Bruna Eduarda Freitas Monteiro, Elis Dionísio da Silva, Gilberto Silva Nunes Bezerra, Marton Kaique de Andrade Cavalcante, Valéria Rêgo Alves Pereira, Maria Carolina Accioly Brelaz Castro, Luiz Gustavo Mendes, Diego Lins Guedes, Walter Lins Barbosa Júnior and Zulma Maria de Medeiros

Trop. Med. Infect. Dis. 2023, 8(11), 495; https://doi.org/10.3390/tropicalmed8110495 - 9 Nov 2023

Cited by 1 | Viewed by 1506

Abstract

Asymptomatic Leishmania infantum, when associated with HIV, can become severe and potentially fatal. In this co-infection, the worst prognosis may be influenced by the host’s immunological aspects, which are crucial in determining susceptibility. Chemokines play an important role in this process by influencing the cellular composition at affected sites and impacting the disease’s outcome. Therefore, the aim of this study was to evaluate proinflammatory chemokines in HIV patients with the asymptomatic L. infantum infection. In this cross-sectional study, the levels of CCL2, CCL5, CXCL8, MIG, and IP-10 were measured in 160 serum samples from co-infected patients (n = 53), patients with HIV (n = 90), and negative controls (n = 17). Quantification was determined by flow cytometry. The obtained data were statistically analyzed using the Kruskal–Wallis test, followed by the Dunn’s post-test and the Spearman’s correlation coefficient. Significance was set at p < 0.05. The chemokines CCL2, CCL5, MIG, and IP-10 exhibited higher levels in the HIV group compared to co-infection. However, the elevated levels of all these chemokines and their increased connectivity in co-infected patients appear to be important in identifying proinflammatory immune responses associated with the asymptomatic condition. Furthermore, a weak negative correlation was observed between higher levels of CXCL8 and lower viral loads in co-infected patients. Full article

(This article belongs to the Special Issue Emerging Topics in Leishmaniasis Research)

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12 pages, 630 KiB

Open AccessArticle

Clinical and Laboratory Response of Domiciled Dogs with Visceral Leishmaniasis Treated with Miltefosine and Allopurinol

by Talita Pereira Vaz, Patrícia Flávia Quaresma, Felipe Dutra Rêgo, Camila Binder Souza, Gilberto Fontes and Célia Maria Ferreira Gontijo

Trop. Med. Infect. Dis. 2023, 8(10), 472; https://doi.org/10.3390/tropicalmed8100472 - 10 Oct 2023

Cited by 1 | Viewed by 1826

Abstract

Canine visceral leishmaniasis (CVL) remains a significant disease worldwide. In Brazil, its treatment is performed using miltefosine, which has demonstrated promising outcomes in dogs. This study represents the first attempt to treat and monitor dogs with CVL in natural conditions over the course of one year. The dogs were divided into two groups: G1 received miltefosine and allopurinol for 28 days, while G2 received miltefosine for 28 days, followed by allopurinol for one year. The follow-up involved clinical, hematological, and biochemical evaluations, as well as the detection of Leishmania DNA in skin and bone marrow samples. By the end of the follow-up, dogs in G2 exhibited improved staging compared to their initial conditions, whereas those in G1 showed worsened staging. Leishmania DNA in skin and bone marrow decreased between 6 and 12 months after treatment. Our observations indicate that the treatment using miltefosine reduces the detection of the parasite in the skin and bone marrow for up to one year following its administration. The continuous use of allopurinol contributes to control of the disease in dogs. These findings provide valuable insights into the response of dogs treated in natural conditions, offering essential information for veterinarians and public health authorities. Full article

(This article belongs to the Special Issue Emerging Topics in Leishmaniasis Research)

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11 pages, 1530 KiB

Open AccessEditor’s ChoiceArticle

Entomological Survey and Leishmania (Leishmania) mexicana Prevalence in Sand Fly Species during an Outbreak of Cutaneous Leishmaniasis in Quintana Roo State, Mexico

by Isabel C. Cañeda-Guzmán, Ana C. Montes de Oca-Aguilar, Carlos I. Miranda-Caballero, Estefania Grostieta, Fabián Correa-Morales, Raquel Romero-Pérez, Francisco E. Romero-Contreras, José A. Rodríguez-Atanacio, Karina Ruiz-Tovar, Herón Huerta, Pedro. C Mis-Avila, Marco R. Quintanilla-Cedillo, Miguel A. Lammoglia-Villagómez, Selene Blum-Domínguez, Paulino Tamay-Segovia, Rebeca Rojas-Ronquillo, Sokani Sánchez-Montes and Ingeborg Becker

Trop. Med. Infect. Dis. 2023, 8(10), 465; https://doi.org/10.3390/tropicalmed8100465 - 5 Oct 2023

Cited by 2 | Viewed by 2297

Abstract

(1) Background: Localized cutaneous leishmaniasis is a neglected vector-borne disease that has become a serious public health problem in the Yucatan Peninsula. Although more than 60% of cases originate from the state of Quintana Roo, it is one of the least explored areas in terms of incriminating vectors of the Leishmania parasite. Additionally, cases of leishmaniasis have increased substantially in that region in recent years. For this reason, we explored and provided primary evidence of Leishmania DNA in sand fly species from four localities during outbreaks of leishmaniasis in Quintana Roo. We also contributed information on the regional genetic diversity of Leishmania parasites. (2) Methods: Sand flies were collected during several periods from November 2022 to April 2023 using Mosquito Light Circle and Shannon traps, as well as an active entomological search in refuges. For Leishmania detection, we amplified a fragment of 300–350 bp of the internal transcribed spacer subunit 1 (ITS-1). (3) Results: Of the 242 females collected, we detected Leishmania DNA in 25 specimens represented by Bichromomyia olmeca (1), Psathyromyia shannoni (17), Lutzomyia cruciata (4), Psathyromyia undulata (2), and Dampfomyia deleoni (1). The detection of Leishmania in these last two species represents new records for the Yucatan Peninsula and for Mexico. Leishmania (Leishmania) mexicana was the only species detected in the Phlebotominae species, with prevalence values that ranked between 7.41% and 33.33% from specimens collected in the sylvatic areas of Cozumel Island and Petcacab. (4) Conclusions: This study provides the first evidence of infection of Da. deleoni and Pa. undulata by L. (L.) Mexicana. In addition, the presence of three dominant haplotypes in all the evaluated localities was evidenced using the analysis of genetic diversity, and the locality of Petcacab was the one with the circulation of two new haplotypes not previously described in Mexico or neighboring countries. These results highlight the importance of intensive epidemiological surveillance due to the dynamics of transmission of Leishmania between different species. Full article

(This article belongs to the Special Issue Emerging Topics in Leishmaniasis Research)

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25 pages, 4109 KiB

Open AccessEditor’s ChoiceArticle

Parasite Detection in Visceral Leishmaniasis Samples by Dye-Based qPCR Using New Gene Targets of Leishmania infantum and Crithidia

by Nayore Tamie Takamiya, Luana Aparecida Rogerio, Caroline Torres, João Augusto Franco Leonel, Geovanna Vioti, Tricia Maria Ferreira de Sousa Oliveira, Karoline Camila Valeriano, Gabriane Nascimento Porcino, Isabel Kinney Ferreira de Miranda Santos, Carlos H. N. Costa, Dorcas Lamounier Costa, Tauana Sousa Ferreira, Rodrigo Gurgel-Gonçalves, João Santana da Silva, Felipe Roberti Teixeira, Roque Pacheco De Almeida, José M. C. Ribeiro and Sandra Regina Maruyama

Trop. Med. Infect. Dis. 2023, 8(8), 405; https://doi.org/10.3390/tropicalmed8080405 - 8 Aug 2023

Viewed by 3653

Abstract

Visceral leishmaniasis (VL) is a neglected disease considered a serious public health problem, especially in endemic countries. Several studies have discovered monoxenous trypanosomatids (Leptomonas and Crithidia) in patients with VL. In different situations of leishmaniasis, investigations have examined cases of co-infection between Leishmania spp. and Crithidia spp. These coinfections have been observed in a wide range of vertebrate hosts, indicating that they are not rare. Diagnostic techniques require improvements and more robust tools to accurately detect the causative agent of VL. This study aimed to develop a real-time quantitative dye-based PCR (qPCR) assay capable of distinguishing Leishmania infantum from Crithidia-related species and to estimate the parasite load in samples of VL from humans and animals. The primer LinJ31_2420 targets an exclusive phosphatase of L. infantum; the primer Catalase_LVH60-12060_1F targets the catalase gene of Crithidia. Therefore, primers were designed to detect L. infantum and Crithidia sp. LVH60A (a novel trypanosomatid isolated from VL patients in Brazil), in samples related to VL. These primers were considered species-specific, based on sequence analysis using genome data retrieved from the TriTryp database and the genome assembling of Crithidia sp. LVH60A strain, in addition to experimental and clinical data presented herein. This novel qPCR assay was highly accurate in identifying and quantifying L. infantum and Crithidia sp. LVH60A in samples obtained experimentally (in vitro and in vivo) or collected from hosts (humans, dogs, cats, and vectors). Importantly, the screening of 62 cultured isolates from VL patients using these primers surprisingly revealed that 51 parasite cultures were PCR+ for Crithidia sp. In addition, qPCR assays identified the co-infection of L. infantum with Crithidia sp. LVH60A in two new VL cases in Brazil, confirming the suspicion of co-infection in a previously reported case of fatal VL. We believe that the species-specific genes targeted in this study can be helpful for the molecular diagnosis of VL, as well as for elucidating suspected co-infections with monoxenous-like trypanosomatids, which is a neglected fact of a neglected disease. Full article

(This article belongs to the Special Issue Emerging Topics in Leishmaniasis Research)

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14 pages, 1042 KiB

Open AccessEditor’s ChoiceReview

Schistosoma and Leishmania: An Untold Story of Coinfection

by Genil Mororó Araújo Camelo, Jeferson Kelvin Alves de Oliveira Silva, Stefan Michael Geiger, Maria Norma Melo and Deborah Aparecida Negrão-Corrêa

Trop. Med. Infect. Dis. 2023, 8(8), 383; https://doi.org/10.3390/tropicalmed8080383 - 27 Jul 2023

Cited by 2 | Viewed by 1458

Abstract

A remarkable characteristic of infectious diseases classified as Neglected Tropical Diseases (NTDs) is the fact that they are mostly transmitted in tropical and subtropical regions with poor conditions of sanitation and low access to healthcare, which makes transmission areas more likely to overlap. Two of the most important NTDs, schistosomiasis and leishmaniasis, despite being caused by very different etiological agents, have their pathogenesis heavily associated with immune-mediated mechanisms, and Schistosoma spp. and Leishmania spp. have been shown to simultaneously infect humans. Still, the consequences of Schistosoma–Leishmania coinfections remain underexplored. As the inflammatory processes elicited by each one of these parasites can influence the other, several changes have been observed due to this coinfection in naturally infected humans, experimental models, and in vitro cell assays, including modifications in susceptibility to infection, pathogenesis, prognostic, and response to treatment. Herein, we review the current knowledge in Schistosoma–Leishmania coinfections in both human populations and experimental models, with special regard to how schistosomiasis affects tegumentary leishmaniasis, discuss future perspectives, and suggest a few steps to further improve our understanding in this model of parasite–host–parasite interaction. Full article

(This article belongs to the Special Issue Emerging Topics in Leishmaniasis Research)

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24 pages, 1459 KiB

Open AccessEditor’s ChoiceSystematic Review

Systematic Review of Treatment Failure and Clinical Relapses in Leishmaniasis from a Multifactorial Perspective: Clinical Aspects, Factors Associated with the Parasite and Host

by Gustavo de Almeida Santos, Juliana Mendes Sousa, Antônio Henrique Braga Martins de Aguiar, Karina Cristina Silva Torres, Ana Jessica Sousa Coelho, André Leite Ferreira and Mayara Ingrid Sousa Lima

Trop. Med. Infect. Dis. 2023, 8(9), 430; https://doi.org/10.3390/tropicalmed8090430 - 29 Aug 2023

Cited by 2 | Viewed by 1813

Abstract

Leishmaniasis is a disease caused by protozoa of the genus Leishmania. Treatment options are limited, and there are frequent cases of treatment failure and clinical relapse. To understand these phenomena better, a systematic review was conducted, considering studies published between 1990 and 2021 in Portuguese, English, and Spanish. The review included 64 articles divided into three categories. Case reports (26 articles) focused on treatment failure and clinical relapse in cutaneous leishmaniasis patients (47.6%), primarily affecting males (74%) and children (67%), regardless of the clinical manifestation. Experimental studies on the parasite (19 articles), particularly with L. major (25%), indicated that alterations in DNA and genic expression (44.82%) played a significant role in treatment failure and clinical relapse. Population data on the human host (19 articles) identified immunological characteristics as the most associated factor (36%) with treatment failure and clinical relapse. Each clinical manifestation of the disease presented specificities in these phenomena, suggesting a multifactorial nature. Additionally, the parasites were found to adapt to the drugs used in treatment. In summary, the systematic review revealed that treatment failure and clinical relapse in leishmaniasis are complex processes influenced by various factors, including host immunology and parasite adaptation. Full article

(This article belongs to the Special Issue Emerging Topics in Leishmaniasis Research)

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9 pages, 601 KiB

Open AccessBrief Report

Rectal Administration of Leishmania Cells Elicits a Specific, Th1-Associated IgG2a Response in Mice: New Perspectives for Mucosal Vaccination against Leishmaniasis, after the Repurposing of a Study on an Anti-Viral Vaccine Candidate

by Ilaria Varotto-Boccazzi, Sara Epis, Giulia Maria Cattaneo, Noemi Guerrini, Alessandro Manenti, Diego Rubolini, Paolo Gabrieli, Domenico Otranto, Gianvincenzo Zuccotti, Emanuele Montomoli and Claudio Bandi

Trop. Med. Infect. Dis. 2023, 8(8), 406; https://doi.org/10.3390/tropicalmed8080406 - 9 Aug 2023

Cited by 1 | Viewed by 1189

Abstract

The mucosal immune system plays a pivotal role in the control of infections, as it represents the first line of defense against most pathogens, from respiratory viruses to intestinal parasites. Mucosal vaccination is thus regarded as a promising strategy to protect animals, including humans, from infections that are acquired by ingestion, inhalation or through the urogenital system. In addition, antigens delivered at the mucosal level can also elicit systemic immune responses. Therefore, mucosal vaccination is potentially effective also against systemic infections acquired through non-mucosal routes, for example, through the bite of hematophagous insects, as in the case of leishmaniasis, a widespread disease that affects humans and dogs. Here, we explored the potential of antigen rectal administration for the generation of anti-Leishmania immunity. Mice were immunized through rectal administration of whole cells of the model parasite Leishmania tarentolae (using a clone engineered to express the spike protein of the SARS-CoV-2 virus generated in a previous study). A specific anti-Leishmania IgG antibody response was detected. In addition, the recorded IgG2a/IgG1 ratio was higher than that of animals injected subcutaneously; therefore, suggesting a shift to a Th1-biased immune response. Considering the importance of a Th1 polarization as a protective response against Leishmania infections, we suggest that further investigation should be focused on the development of novel types of vaccines against these parasites based on rectal immunization. Full article

(This article belongs to the Special Issue Emerging Topics in Leishmaniasis Research)

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9 pages, 1077 KiB

Open AccessEditor’s ChoiceBrief Report

In Vitro Drug Susceptibility of a Leishmania (Leishmania) infantum Isolate from a Visceral Leishmaniasis Pediatric Patient after Multiple Relapses

by Bianca A. Ferreira, Gustavo de A. Santos, Elizabeth M. Coser, Juliana M. Sousa, Mônica E. A. Gama, Leônidas L. B. Júnior, Fabrício S. Pessoa, Mayara I. S. Lima, Silvia R. B. Uliana and Adriano C. Coelho

Trop. Med. Infect. Dis. 2023, 8(7), 354; https://doi.org/10.3390/tropicalmed8070354 - 4 Jul 2023

Viewed by 1572

Abstract

The parasitic protozoan Leishmania (Leishmania) infantum is the etiological agent of human visceral leishmaniasis in South America, an infectious disease associated with malnutrition, anemia, and hepatosplenomegaly. In Brazil alone, around 2700 cases are reported each year. Treatment failure can occur as a result of drug, host, and/or parasite-related factors. Here, we isolated a Leishmania species from a pediatric patient with visceral leishmaniasis that did not respond to chemotherapy, experiencing a total of nine therapeutic relapses and undergoing a splenectomy. The parasite was confirmed as L. (L.) infantum after sequencing of the ribosomal DNA internal transcribed spacer, and the clinical isolate, in both promastigote and amastigote forms, was submitted to in vitro susceptibility assays with all the drugs currently used in the chemotherapy of leishmaniasis. The isolate was susceptible to meglumine antimoniate, amphotericin B, pentamidine, miltefosine, and paromomycin, similarly to another strain of this species that had previously been characterized. These findings indicate that the multiples relapses observed in this pediatric patient were not due to a decrease in the drug susceptibility of this isolate; therefore, immunophysiological aspects of the patient should be further investigated to understand the basis of treatment failure in this case. Full article

(This article belongs to the Special Issue Emerging Topics in Leishmaniasis Research)

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