leishmania infantum
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Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 463
Luca Pozzetti ◽  
Roberta Ibba ◽  
Sara Rossi ◽  
Orazio Taglialatela-Scafati ◽  
Donatella Taramelli ◽  

The potential of natural and synthetic chalcones as therapeutic leads against different pathological conditions has been investigated for several years, and this class of compounds emerged as a privileged chemotype due to its interesting anti-inflammatory, antimicrobial, antiviral, and anticancer properties. The objective of our study was to contribute to the investigation of this class of natural products as anti-leishmanial agents. We aimed at investigating the structure–activity relationships of the natural chalcone lophirone E, characterized by the presence of benzofuran B-ring, and analogues on anti-leishmania activity. Here we describe an effective synthetic strategy for the preparation of the natural chalcone lophirone E and its application to the synthesis of a small set of chalcones bearing different substitution patterns at both the A and heterocyclic B rings. The resulting compounds were investigated for their activity against Leishmania infantum promastigotes disclosing derivatives 1 and 28a,b as those endowed with the most interesting activities (IC50 = 15.3, 27.2, 15.9 μM, respectively). The synthetic approaches here described and the early SAR investigations highlighted the potential of this class of compounds as antiparasitic hits, making this study worthy of further investigation.

2022 ◽  
Ian Wright ◽  
Vanessa Whitfield ◽  
Runa Hanaghan ◽  
Melissa Upjohn ◽  
Paula Boyden

Abstract Background: Increased dog relocation can cause dissemination of parasite and vector populations and this is being recognised in countries across Northern Europe, including the UK. Data regarding the prevalence of exotic infections entering the UK would be beneficial to vets to help assess pets entering the UK from abroad, and to help calculate risk of establishment of novel pathogens. One such group of dogs were seized as part of an RSPCA-led animal welfare investigation and blood tested for exotic pathogens. Methods: As part of the RSPCA investigation, 151 dogs were removed from the site. Blood tests were performed for Babesia. canis, Ehrlichia canis, Hepatozoon canis and Leishmania infantum by PCR, Br.canis by antibody serology and D.immitis by blood antigen. In addition to pathogen screening, a serology titre for Rabies was measured for each dog. A clinical examination was performed by a veterinary surgeon and clinical signs recorded. Clinical signs data were analysed by the Fisher-Freeman-Halton Exact TestResults: Overall, 24% of the dogs tested positive for an infection. Two dogs were positive for Br.canis antibodies and had no clinical signs indicative of infection. Leishmania infantum was identified in 10.5% of dogs with all but two cases being diagnosed in dogs whose microchip originated in Romania. Hepatozoon canis was identified in 9.6% of dogs, all of which had a Romanian microchip. Dirofilaria immitis was identified in 4.1% of dogs, B.canis in 2.3% of dogs and E.canis was only present in 1.5% of dogs tested. Only four dogs were found to have co-infections. No significant association was found between the pathogens detected and presenting clinical signs. Conclusions: This study demonstrates a range of exotic pathogens entering the UK including Br.canis and demonstrates the importance of screening imported dogs. The emphasis for early recognition of exotic pathogens in imported dogs has relied on screening based on relevant clinical signs and the country of origin. While these factors are useful, this study demonstrated no significant association between presenting clinical signs and the pathogens carried.

2022 ◽  
Endrias Zewdu Gebremedhin ◽  
Weraka Weya ◽  
Chala Dima ◽  
Demeke Zewde ◽  
Vincenzo Di Marco Lo Presti ◽  

Abstract Background Canine Leishmania infantum infection is a major vector-borne zoonosis. Most cases of canine leishmanias are caused by Leishmania infantum, but other species can also be found. In the Old and New Worlds, leishmaniasis is spread by the bite of phlebotomine female sandflies of the genera Phlebotomus and Lutzomyia respectively. The objectives of the study were to estimate the seroprevalence and associated risk factors in Weliso, Ambo, and Ejaji towns of South-West and West Shewa Zones, Oromia, Ethiopia. Methods A cross-sectional study was conducted from October 2019 to September 2020. The study population consists of dogs found in the study towns. The study subjects include 368 dogs selected by using a simple random sampling method. A blood sample (5 ml) was collected to test for the presence of rK39 antigen inducing specific antibodies using an Indirect ELISA kit. All the data were analyzed using the STATA version 14 software program. Pearson’s Chi-square and logistic regression tests were used to evaluate the association between the seropositivity of canine Leishmania infantums and hypothesized risk factors. Results An overall canine Leishmania infantum seroprevalence of 84.24% (95% confidence interval [CI]: 80 - 88%) was obtained. In Weliso, Ambo, and Ejaji towns canine Leishmania infantum seroprevalence of 79.82% (95% CI: 71- 87%), 76.11% (95% CI: 67- 84%), and 93.84% (95% CI:89 – 97%) were found respectively. Univariable logistic regression analysis showed that town (P=0.001), season (P=0.001), mixed living environment (P=0.003), and Kebele (P<0.05) were significantly associated with Leishmania infantum seropositivity. However, the multivariable analysis indicated that wet season (P = 0.001) and a mixed living environment (P = 0.025) were independent predictors of canine Leishmania infantum seropositivity. Conclusion The seroprevalence of canine Leishmania infantum in dogs was very high. Wet season and mixed living environment are predictors of seropositivity. The high percentage of seropositive dogs indicates the potential role of dogs to maintain the infection and the possible spread of L. infantum infection to humans. Therefore, improvement of the living environment and health care facilities of domesticated dogs, community awareness and health education, and further epidemiological studies are suggested.

2022 ◽  
Vol 58 (1) ◽  
Jacobo Giner ◽  
Sergio Villanueva-Saz ◽  
Antonio Fernández ◽  
María Asunción Gómez ◽  
Madis Podra ◽  

2022 ◽  
Vol 12 ◽  
Carolina R. Sanz ◽  
Guadalupe Miró ◽  
Natalia Sevane ◽  
Armando Reyes-Palomares ◽  
Susana Dunner

Leishmania infantum, the etiological agent of canine leishmaniosis (CanL) in Europe, was responsible of the largest outbreak of human leishmaniosis in Spain. The parasite infects and survives within myeloid lineage cells, causing a potentially fatal disease if left untreated. The only treatment option relies on chemotherapy, although immunotherapy strategies are being considered as novel approaches to prevent progression of the disease. To this aim, a deeper characterization of the molecular mechanisms behind the immunopathogenesis of leishmaniosis is necessary. Thus, we evaluated, for the first time, the host immune response during L. infantum infection through transcriptome sequencing of the popliteal lymph nodes aspirates of dogs with CanL. Differential expression and weighted gene co-expression network analyses were performed, resulting in the identification of 5,461 differentially expressed genes (DEGs) and four key modules in sick dogs, compared to controls. As expected, defense response was the highest enriched biological process in the DEGs, with six genes related to immune response against pathogens (CHI3L1, SLPI, ACOD1, CCL5, MPO, BPI) included among the ten most expressed genes; and two of the key co-expression modules were associated with regulation of immune response, which also positively correlated with clinical stage and blood monocyte concentration. In particular, sick dogs displayed significant changes in the expression of Th1, Th2, Th17 and Tr1 cytokines (e. g. TNF-α, IFN-γ, IL-21, IL-17, IL-15), markers of T cell and NK cell exhaustion (e. g. LAG3, CD244, Blimp-1, JUN), and B cell, monocyte and macrophage disrupted functionality (e. g. CD40LG, MAPK4, IL-1R, NLRP3, BCMA). In addition, we found an overexpression of XBP1 and some other genes involved in endoplasmic reticulum stress and the IRE1 branch of the unfolded protein response, as well as one co-expression module associated with these processes, which could be induced by L. infantum to prevent host cell apoptosis and modulate inflammation-induced lymphangiogenesis at lymph nodes. Moreover, 21 lncRNAs were differentially expressed in sick dogs, and one key co-expression module was associated with chromatin organization, suggesting that epigenetic mechanisms could also contribute to dampening host immune response during natural L. infantum infection in the lymph nodes of dogs suffering from clinical leishmaniosis.

2022 ◽  
Vol 78 (01) ◽  
pp. 6615-2022

The study of potential wild mammal reservoirs is necessary for the surveillance of leishmaniosis, as Leishmania protozoans have been isolated from a wide range of wild and domestic animal species, including Leporidae. Recently, it has been demonstrated that both hares and wild rabbits can act as sylvatic reservoirs of Leishmania. In Spain, most of the research involving wild rabbits has been developed in the central area of Madrid and in the southeastern Mediterranean coast. We studied the presence of Leishmania infantum in 116 wild rabbits (Oryctolagus cuniculus) captured in Santovenia de Pisuerga, Valladolid, Spain. Hair samples were analyzed by real time PCR. L. infantum kinetoplast DNA (kDNA) was detected and quantified in 4 out of 116 analyzed animals. The estimated number of parasites obtained were quite variable, ranging from 2.60 to 276.60. Hair samples can be collected by non-invasive methods, being a proper sample for Leishmania detection in wild Leporidae, which have an important role as reservoirs of Leishmania. Our findings enhance the need for more extensive studies in different geographical areas.

2021 ◽  
Jady Moreira da Silva ◽  
Victor Vaitkevicius Antão de Souza ◽  
Maria Gabriella Nunes de Melo ◽  
Isabelle Barreto da Silva Moreira Reino ◽  
José Noé da Silva Júnior ◽  

Introdução: As leishmanioses são um complexo de doenças infecciosas com amplo espectro de manifestações clínicas, variando de formas cutâneas à uma forma visceral. Apresentam diversas características clínicas e com diferentes graus de gravidade a depender da espécie parasitária envolvida e da resposta imune do hospedeiro1. A Leishmaniose Visceral (LV) é a forma clínica mais grave, resultando em altas taxas de morbidade e mortalidade caso não seja tratada adequadamente2. Com as limitações dos atuais tratamentos para a LV, como a resistência do parasito e a alta toxicidade3, aumenta a necessidade da busca por novos candidatos terapêuticos mais eficazes e seguros. Dentre os produtos naturais, os microrganismos fotossintetizantes de origem marinha estão se destacando, devido a sua diversidade de metabólitos bioativos e suas propriedades biológicas4,5. Objetivo: Avaliar in vitro os índices de seletividade do extrato bioativo da Chlorella vulgaris e compará-lo com a droga de referência para o tratamento da leishmaniose visceral humana. Métodos: O extrato bioativo foi obtido após cultivo da microalga, através do processo de sonicação. Células mononucleares do sangue periférico de humanos saudáveis foram tratadas com o extrato e com a droga de referência (antimoniato pentavalente - Sbv) em concentrações seriadas de 1000μg/ml a 62,5μg/ml e, a partir disso, a concentração citotóxica de 50% (CC50) foi determinada através de ensaios de viabilidade celular pelo método de MTT. Promastigotas de Leishmania infantum foram tratadas com o extrato bioativo e com o Sbv em concentrações seriadas de 500μg/ml a 15,63μg/ml para determinação da concentração inibitória de 50% (IC50) através de contagem celular por microscopia óptica. Os índices de seletividade (IS) foram determinados pela razão entre o valor de CC50 e IC50. Resultados: O extrato de C. vulgaris apresentou uma menor toxicidade às células humanas (CC50=999,66μg/ml) quando comparado com a droga de referência (SbV= 412,43μg/ml). Em relação a IC50, quando comparado com o Sbv, o extrato demostrou uma maior atividade leishmanicida (IC50= 192,12). Ao determinar o IS do extrato, foi possível observar que este indicou ser cerca de 5 vezes mais seletivo ao parasito do que às células humanas (IS= 5,2). Enquanto o Sbv expressou uma menor seletividade ao parasito (IS= 2,11). Conclusão: Diante dos resultados obtidos, o extrato bioativo de Chlorella vulgaris apresenta-se promissor. Os resultados contribuirão para futuros estudos para o desenvolvimento de novas terapias para o tratamento da leishmaniose visceral humana.

2021 ◽  
Vol 9 (12) ◽  
pp. 2616
Labrini V. Athanasiou ◽  
Eleni G. Katsogiannou ◽  
Constantina N. Tsokana ◽  
Sofia G. Boutsini ◽  
Marina G. Bisia ◽  

Wild rabbits (Oryctolagus cuniculus) can be important sentinel species for the presence of zoonotic pathogens. Therefore, we collected blood samples from wild rabbits harvested by hunters during the hunting season 2019–2020 on the island of Lemnos, to determine exposure of wild rabbits to the zoonotic pathogens Leishmania infantum, Toxoplasma gondii, Anaplasma phagocytophilum and Babesia caballi, as well as aqueous humor to assess its diagnostic performance in terms of sensitivity, specificity, positive and negative likelihood ratios. Antibodies against these pathogens were detected by Indirect Immunofluorescence Antibody (IFA) assay. Out of the 72 wild rabbits included in the study, 4.2%, 5.5%, 18% and 9.7% were seropositive to L. infantum, T. gondii, A. phagocytophilum and B. caballi, respectively. Although less frequently, antibodies were also detected in aqueous humor of wild rabbits. The antibody detection in aqueous humor presented 100% specificity but decreased sensitivity compared to serum suggesting that aqueous humor could be successfully used in epidemiological studies to confirm exposure at the population level but has little diagnostic value at the individual level. This is the first report on the seropositivity of wild rabbits to A. phagocytophilum and B. caballi and the detection of antibodies against A. phagocytopylum, L. infantum, T. gondii and B. caballi in the aqueous humor.

Caio Campolongo ◽  
Ryan Emiliano da Silva ◽  
Roberta Carvalho de Freitas e Azevedo ◽  
Isabella Pereira Pesenato ◽  
Ana Carolina Fernandes Carioca ◽  

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