Leishmaniasis: Vector-Host-Pathogen Interactions in Health and Disease

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: 6 July 2024 | Viewed by 7092

Special Issue Editors


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Guest Editor
Vector Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Rockville, MD, USA
Interests: leishmaniasis; Leishmania; sand flies; parasite development; parasite transmission; parasite tropism; determinants of infection/pathogenicity
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Affiliation Instituto Gonçalo Moniz—Fundação Oswaldo Cruz, Bahia, Brazil, Escola de Medicina Veterinária e Zootecnia—Universidade Federal da Bahia, Bahia, Brazil
Interests: leishmaniasis; canine leishmaniasis; animal reservoir; vector saliva; canine leishmaniasis biomarkers, visceral leishmaniasis molecular diagnosis; epidemiology of leishmaniasis

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Guest Editor
Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal
Interests: leishmaniasis; host-pathogen interaction, extra-cellular vesicles, drug development and disease management (diagnosis)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

More than 15 different Leishmania species cause disease in humans worldwide, but the poorest in society are disproportionately affected. Leishmaniasis is one of the Neglected Tropical Diseases with a higher disease burden, with significant morbidity and mortality. Interestingly, all but one of the Leishmania species that are pathogenic to humans are associated with zoonotic transmission. This adds another layer of complexity considering the control of Leishmaniasis, which should always contemplate vector, parasite, and host determinants. Of note, there is an absence of prophylactic measures available to humans, and the anti-Leishmanial drugs in the market are limited and less than optimal. In fact, some of these drugs are still used in veterinary settings, increasing the risk of resistance. Therefore, the development of new prophylactic/therapeutic options, or of reservoir- or vector-based control measures with a significant impact on parasite transmission, is still essential. An in-depth understanding of the sand fly vectors, the Leishmania etiologic agents, the hosts (including animal reservoirs and humans), and their interactions is essential to achieving this.

With this Special Issue, we hope to compile studies with a broad focus on Leishmaniasis and vector–host–pathogen interactions in health and disease, including those describing fundamental breakthroughts related to sandflies, Leishmania parasites and/or animal reservoirs, as well as those focused on applied approaches aiming toward disease control. Original research articles and reviews are welcome.

Dr. Pedro Cecílio
Dr. Manuela da Silva Solcá
Dr. Nuno Santarém
Guest Editors

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Keywords

  • leishmaniasis
  • Leishmania
  • sand flies
  • canine leishmaniosis
  • animal models of disease
  • anti-leishmanial drugs
  • vaccines
  • vector-based control approaches
  • reservoir-based control approaches
  • vector–host–pathogen interactions

Published Papers (5 papers)

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Research

18 pages, 3018 KiB  
Article
Human Dendritic Cell Maturation Is Modulated by Leishmania mexicana through Akt Signaling Pathway
by Jorge Rodríguez-González, Arturo A. Wilkins-Rodríguez and Laila Gutiérrez-Kobeh
Trop. Med. Infect. Dis. 2024, 9(5), 118; https://doi.org/10.3390/tropicalmed9050118 - 17 May 2024
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Abstract
Dendritic cells (DC) along with macrophages are the main host cells of the intracellular parasite Leishmania. DC traverse a process of maturation, passing through an immature state with phagocytic ability to a mature one where they can modulate the immune response through [...] Read more.
Dendritic cells (DC) along with macrophages are the main host cells of the intracellular parasite Leishmania. DC traverse a process of maturation, passing through an immature state with phagocytic ability to a mature one where they can modulate the immune response through the secretion of cytokines. Several studies have demonstrated that Leishmania inhibits DC maturation. Nevertheless, when cells are subjected to a second stimulus such as LPS/IFN-γ, they manage to mature. In the maturation process of DC, several signaling pathways have been implicated, importantly MAPK. On the other hand, Akt is a signaling pathway deeply involved in cell survival. Some Leishmania species have shown to activate MAPK and Akt in different cells. The aim of this work was to investigate the role of ERK and Akt in the maturation of monocyte-derived DC (moDC) infected with L. mexicana. moDC were infected with L. mexicana metacyclic promastigotes, and the phosphorylation of ERK and Akt, the expression of MHCII and CD86 and IL-12 transcript, and secretion were determined in the presence or absence of an Akt inhibitor. We showed that L. mexicana induces a sustained Akt and ERK phosphorylation, while the Akt inhibitor inhibits it. Moreover, the infection of moDC downregulates CD86 expression but not MHCII, and the Akt inhibitor reestablishes CD86 expression and 12p40 production. Thus, L. mexicana can modulate DC maturation though Akt signaling. Full article
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15 pages, 2867 KiB  
Article
A Contribution towards Sustainable Development in the Amazon Based on a Socioeconomic and Environmental Analysis of Visceral Leishmaniasis in the State of Pará, Brazil
by Claudia do Socorro Carvalho Miranda, Bruna Costa de Souza, Eric Renato Lima Figueiredo, João Simão de Melo Neto, Hilton Pereira da Silva, Marcos Valerio Santos da Silva, Sérgio Luiz Althoff, Tainara Carvalho Garcia Miranda Filgueiras, Debora do Socorro Carvalho Miranda and Nelson Veiga Gonçalves
Trop. Med. Infect. Dis. 2024, 9(3), 66; https://doi.org/10.3390/tropicalmed9030066 - 21 Mar 2024
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Abstract
Human Visceral Leishmaniasis is an endemic public health problem in the Amazon. This article analyzed the spatial distribution of this disease and its relationship with socioeconomic, environmental and public health policy variables in four mesoregions of the state of Pará, from 2011 to [...] Read more.
Human Visceral Leishmaniasis is an endemic public health problem in the Amazon. This article analyzed the spatial distribution of this disease and its relationship with socioeconomic, environmental and public health policy variables in four mesoregions of the state of Pará, from 2011 to 2022. This ecological study used secondary data obtained from official Brazilian agencies. Spatial analysis was performed using the Flow, Kernel and Global Moran bivariate techniques expressed in thematic maps. In the mesoregions studied, 2685 cases of the disease were confirmed, with the highest number of cases in Southeast Pará state. The epidemiological profile followed the national pattern of occurrence of the disease, with a higher number of cases in children below school age. Spatial dependence was observed between the prevalence of the disease and socio-economic indicators. The most intense movement of patients was towards the Belém Metropolitan mesoregion. The disease showed an inhomogeneous pattern of distribution of cases, with a direct relationship between areas with cases and deforestation associated with different anthropic activities. There is a socio-environmental production of the disease that goes beyond the border limits of the mesoregions, and its establishment is related to the unsustainable development model implemented in the region. Full article
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11 pages, 914 KiB  
Article
Ecology and Infection Status of Sand Flies in Rural and Urban Cutaneous Leishmaniasis Endemic Areas in Northwest Ethiopia
by Wondmeneh Jemberie, Abebe Animut, Sisay Dugassa, Araya Gebresilassie, Roma Melkamu, Esayas Aklilu, Mulugeta Aemero, Johan van Griensven and Myrthe Pareyn
Trop. Med. Infect. Dis. 2024, 9(3), 52; https://doi.org/10.3390/tropicalmed9030052 - 23 Feb 2024
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Abstract
Cutaneous leishmaniasis (CL) caused by Leishmania aethiopica is transmitted by Phlebotomus longipes in northern Ethiopia. No studies have been conducted to investigate the transmission dynamics of CL, despite its high endemicity in both rural and urban settings. Evidence on the ecology and behavior [...] Read more.
Cutaneous leishmaniasis (CL) caused by Leishmania aethiopica is transmitted by Phlebotomus longipes in northern Ethiopia. No studies have been conducted to investigate the transmission dynamics of CL, despite its high endemicity in both rural and urban settings. Evidence on the ecology and behavior of the vector from this area are required to develop integrated disease control strategies. Sand flies were collected in the dry and wet seasons in 2021 in CL-endemic rural Gindmeteaye and urban Addis-Alem in northwest Ethiopia. Trapping was performed with sticky and Centers for Disease Control and Prevention (CDC) light traps in three habitats, including inside patients’ houses, peridomestic areasand in caves/rocky areas. Sand flies were morphologically identified to species level. Female Phlebotomus species were categorized according to blood feeding status and tested by spliced-leader (SL-) ribonucleic acid (RNA) polymerase chain reaction (PCR) to screen for Leishmania infection. Of 1161 sand flies, the majority (77%) were P. longipes, six (0.5%) were P. orientalis and the remaining were Sergentomyia. The abundance of the 430 female P. longipes was significantly linked to seasonality (p < 0.001), with the majority in the dry season occurring in the outdoor rocky (37%) and peridomestic (34%) sites, while, in the wet season, most (62%) were captured indoors. This seasonality was more pronounced in rural Gindmeteaye, where housing construction is poor. The number of blood-fed and gravid P. longipes was significantly higher in the wet (31%; 22%), compared to the dry season (13%; 8%), and their proportion was highest indoors. Eighteen (4%) female P. longipes were Leishmania positive, with highest infection prevalence in caves (7% compared to 3% indoors, p = 0.022), and in the dry season (6%, p < 0.001). Phlebotomus orientalis specimens were all captured in May in rural Gindmeteaye, five indoors and one in a peridomestic site. Further research should be conducted to investigate the absolute contribution of humans and indoor transmission to the transmission cycle of CL. Inhabitants of endemic villages should be made aware that evening outdoor activities near caves may increase their exposure to infectious sand flies. Whether P. orientalis can breed and become infected at high altitudes should be further studied. Full article
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17 pages, 3579 KiB  
Article
In Vitro and Ex Vivo Synergistic Effect of Pyrvinium Pamoate Combined with Miltefosine and Paromomycin against Leishmania
by Estela Melcón-Fernández, Giulio Galli, Rafael Balaña-Fouce, Nerea García-Fernández, María Martínez-Valladares, Rosa M. Reguera, Carlos García-Estrada and Yolanda Pérez-Pertejo
Trop. Med. Infect. Dis. 2024, 9(2), 30; https://doi.org/10.3390/tropicalmed9020030 - 25 Jan 2024
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Abstract
One of the major drawbacks of current treatments for neglected tropical diseases is the low safety of the drugs used and the emergence of resistance. Leishmaniasis is a group of neglected diseases caused by protozoa of the trypanosomatidae family that lacks preventive vaccines [...] Read more.
One of the major drawbacks of current treatments for neglected tropical diseases is the low safety of the drugs used and the emergence of resistance. Leishmaniasis is a group of neglected diseases caused by protozoa of the trypanosomatidae family that lacks preventive vaccines and whose pharmacological treatments are scarce and unsafe. Combination therapy is a strategy that could solve the above-mentioned problems, due to the participation of several mechanisms of action and the reduction in the amount of drug necessary to obtain the therapeutic effect. In addition, this approach also increases the odds of finding an effective drug following the repurposing strategy. From the previous screening of two collections of repositioning drugs, we found that pyrvinium pamoate had a potent leishmanicidal effect. For this reason, we decided to combine it separately with two clinically used leishmanicidal drugs, miltefosine and paromomycin. These combinations were tested in axenic amastigotes of Leishmania infantum obtained from bone marrow cells and in intramacrophagic amastigotes obtained from primary cultures of splenic cells, both cell types coming from experimentally infected mice. Some of the combinations showed synergistic behavior, especially in the case of the combination of pyrvinium pamoate with paromomycin, and exhibited low cytotoxicity and good tolerability on intestinal murine organoids, which reveal the potential of these combinations for the treatment of leishmaniasis. Full article
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11 pages, 747 KiB  
Article
Co-Circulation of Leishmania Parasites and Phleboviruses in a Population of Sand Flies Collected in the South of Portugal
by Fátima Amaro, Anabela Vilares, Susana Martins, Tânia Reis, Hugo Costa Osório, Maria João Alves and Maria João Gargaté
Trop. Med. Infect. Dis. 2024, 9(1), 3; https://doi.org/10.3390/tropicalmed9010003 - 20 Dec 2023
Viewed by 2133
Abstract
In the Old World, phlebotomine sand flies from the genus Phlebotomus are implicated in the transmission of Leishmania spp. parasites (Kinetoplastida: Trypanosomatidae) and viruses belonging to the genus Phlebovirus (Bunyavirales: Phenuiviridae). Two of the five sand fly species known to occur in Portugal, [...] Read more.
In the Old World, phlebotomine sand flies from the genus Phlebotomus are implicated in the transmission of Leishmania spp. parasites (Kinetoplastida: Trypanosomatidae) and viruses belonging to the genus Phlebovirus (Bunyavirales: Phenuiviridae). Two of the five sand fly species known to occur in Portugal, Phlebotomus perniciosus and Ph. ariasi, the former being the most ubiquitous, are recognized vectors of Leishmania infantum, which causes visceral leishmaniasis, the most prevalent form of leishmaniasis in the country. Phlebotomus perniciosus is also the vector of the neurotropic Toscana virus, which can cause aseptic meningitis. Entomological surveillance is essential to provide fundamental data about the presence of vectors and the pathogens they can carry. As such, and given the lack of data in Portugal, an entomological survey took place in the Algarve, the southernmost region of the country, from May to October 2018. Polymerase chain reaction assays were performed in order to detect the presence of the above-mentioned pathogens in sand fly pools. Not only were both Leishmania parasites and phleboviruses detected during this study, but more importantly, it was the first time their co-circulation was verified in the same sand fly population collected in Portugal. Full article
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