scholarly journals FML/QuilA-Vaccinated Dogs Naturally Infected with Leishmania infantum: Serum Cytokines, Clinicopathological Profile, and Parasitological Parameters

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Gregório Guilherme Almeida ◽  
Fernanda Morcatti Coura ◽  
Jonata de Melo Barbieri ◽  
Ana Carolina Junqueira Moura ◽  
Fabiola de Oliveira Paes-Leme ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Hematological Parameters ◽  
Parasite Burden ◽  
Parasite Load ◽  
Serum Levels ◽  
Canine Leishmaniasis ◽  
Th2 Response ◽  
Mild Disease ◽  
Clinicopathological Profile ◽  
G Ratio

Dogs are the main reservoir of Leishmania infantum in endemic regions. Canine leishmaniasis, caused by L. infantum, can progress to a chronic disease resulting in death. Vaccines have been developed with a certain degree of success. The pathogenesis of this disease is not completely understood, especially in previously vaccinated dogs. We herein described clinical data, parasite load, serum levels of cytokines, and the reservoir potential in vdogs vaccinated with the fucose-mannose ligand (FML)/QuilA saponin vaccine (Leishmune™) naturally infected (Vi) and compared to vaccinated not infected dogs (Vn). Thirty-four dogs from private owners were divided into two groups: vaccinated/infected and vaccinated/uninfected. Clinical evaluation, hematological and biochemical parameters, and serum levels of cytokines were measured by conventional methods. The parasite burden in the bone marrow was measured by quantitative real-time PCR, and the transmissibility of parasites to sand flies was assessed by xenodiagnosis. Clinical, biochemical, and hematological parameters of vaccinated infected dogs were mostly normal. Vi dogs developed mild disease with low clinical scores. Serum levels of IL-10 were higher in Vi dogs, and a strong correlation was observed in IL-4 levels and the A/G ratio in Vi dogs. These results suggest a role of TH2 response in Vi dogs, although more data is needed to better understand the disease in vaccinated dogs.

scholarly journals Mathematical Modelling Using Predictive Biomarkers for the Outcome of Canine Leishmaniasis upon Chemotherapy

2020 ◽  
Vol 8 (5) ◽  
pp. 745
Author(s):  
Rafaela de Sousa Gonçalves ◽  
Flaviane Alves de Pinho ◽  
Ricardo Jorge Dinis-Oliveira ◽  
Rui Azevedo ◽  
Joana Gaifem ◽  
...  
Keyword(s):  
Treatment Group ◽  
Animal Health ◽  
Early Period ◽  
Gene Expression Signature ◽  
Predictive Biomarkers ◽  
Parasite Load ◽  
Response To Therapy ◽  
Canine Leishmaniasis ◽  
Th2 Response ◽  
Therapeutic Decisions

Prediction parameters of possible outcomes of canine leishmaniasis (CanL) therapy might help with therapeutic decisions and animal health care. Here, we aimed to develop a diagnostic method with predictive value by analyzing two groups of dogs with CanL, those that exhibited a decrease in parasite load upon antiparasitic treatment (group: responders) and those that maintained high parasite load despite the treatment (group: non-responders). The parameters analyzed were parasitic load determined by q-PCR, hemogram, serum biochemistry and immune system-related gene expression signature. A mathematical model was applied to the analysis of these parameters to predict how efficient their response to therapy would be. Responder dogs restored hematological and biochemical parameters to the reference values and exhibited a Th1 cell activation profile with a linear tendency to reach mild clinical alteration stages. Differently, non-responders developed a mixed Th1/Th2 response and exhibited markers of liver and kidney injury. Erythrocyte counts and serum phosphorus were identified as predictive markers of therapeutic response at an early period of assessment of CanL. The results presented in this study are highly encouraging and may represent a new paradigm for future assistance to clinicians to interfere precociously in the therapeutic approach, with a more precise definition in the patient’s prognosis.

scholarly journals CD45+, CD68+ and E-cadherin+ Expressions in Skin Dogs Naturally Infected by Leishmania infantum

2017 ◽  
Vol 45 (1) ◽  
pp. 7
Author(s):  
Társsila Mara Vieira Ferreira ◽  
Tiago Cunha Ferreira ◽  
Fernanda Maria Aragão Ximenes Porto ◽  
Conceição Da Silva Martins ◽  
Berlamino Eugênio Lopes Neto ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Mononuclear Cells ◽  
Plasma Cells ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Canine Leishmaniasis ◽  
Control Group ◽  
Asymptomatic Group ◽  
G Ratio ◽  
E Cadherin

Background: In canine leishmaniasis (CanL), infection occurs through phlebotomine vectors that inoculate the protozoan Leishmania infantum into the skin that infected macrophages and activated dendritic cells (CD). Dogs with CanL present variable clinical manifestations, being common the presence of cutaneous lesions. The aim of this study was to evaluate the expression of CD45+, CD68+ and E-cadherin+  associating the skin sentinels cells and to compare the clinical-dermatological manifestations in the skin of dogs naturally infected by L. infantum.Materials, Methods & Results: Dogs infected (n = 22) by L. infantum were divided into asymptomatic group (AD, n = 9), and symptomatic group (SD, n = 13), according criteria based on the presence or absence of skin changes. Dogs non-infected (CD, n = 5) were included as control group. Samples of skin biopsies collected from scapular region were processed by routine histology and labeled by immunohistochemistry with monoclonal antibodies against CD45+, CD68+ and E-cadherin+, and were described as none, mild, moderate and intense. SD presented keratoconjunctivitis, onychogryphose, lichenification, depigmentation, alopecia, hypotrichosis, erythematous dermatitis, exfoliative dermatitis, ulcerative dermatitis and crusted dermatitis, and the frequency these alterations was expressed as percentage. The results of hematological and biochemical parameters were analyzed by Kruskal-Wallis test followed by the Dunn’s test and expressed as mean ± standard deviation, with values P < 0.05. Leukocytosis (not significant), red blood cells, hematocrit and hemoglobin (P < 0.05), total protein serum (P < 0.05), globulins (P < 0.05), albumin and A/G ratio (P < 0.01) were altered in SD in relation to CD. Cutaneous cellular infiltration, composed by macrophages, plasma cells, lymphocytes and neutrophils, was observed in CD. There was an increase of expression of the markers in SD when compared to the other groups, as moderate CD68+ expression and L. infantum, and intense CD45+ and E-cadherin+ expressions.Discussion: Cutaneous involvement is very important in CanL, as it corresponds to where is the first interaction between the parasite and the immune system. Dermatological clinical signs, leukocytosis, anemia, globulins levels have been reported for dogs naturally infected by L. infantum. Inflammatory infiltrate was distributed at superficial and deep dermis, which was composed by mononuclear cells as macrophages, plasma cells, lymphocytes and neutrophils. To characterize the immune sentinels cells in the skin it was evaluated CD45+, CD68+ and E-cadherin+ expressions. In syntomatic dogs, our results revelead an increase of expression of these markers. CD45+ is one of the most abundant molecules expressed on the white blood cell surface in various mammals, while CD68+ is a myelomonocytic marker that seems to be retained during monocyte differentiation. In the skin, increased numbers of CD68+ are related to dendritic epidermal cells, which can be expressed as CD45+/CD1a-/HLA-DR+. DCs of the skin, particularly epidermal Langerhans cells (LCs), form networks anchored to neighboring keratinocytes via E-cadherin. Thus, CD45+, CD68+ and E-cadherin+ expressions may be related to activation of skin sentinels cells in dogs naturally infected by L. infantum. Our results indicated that CanL modify the CD45+, CD68+ and E-cadherin+ expressions, which characterize the immune sentinels cells activation that promove the recruitment the cellular infiltrate, which was composed by macrophages, plasma cells, lymphocytes and neutrophils. Thus, these informations may contribute to the follow-up of CanL progression in skin.

scholarly journals Vaccination with the Leishmania infantum Acidic Ribosomal P0 Protein plus CpG Oligodeoxynucleotides Induces Protection against Cutaneous Leishmaniasis in C57BL/6 Mice but Does Not Prevent Progressive Disease in BALB/c Mice

2005 ◽  
Vol 73 (9) ◽  
pp. 5842-5852 ◽  
Author(s):  
Salvador Iborra ◽  
Javier Carrión ◽  
Charles Anderson ◽  
Carlos Alonso ◽  
David Sacks ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Infantum ◽  
Progressive Disease ◽  
Immunological Response ◽  
Parasite Load ◽  
Th2 Response ◽  
Suitable Alternative ◽  
Cpg Oligodeoxynucleotides ◽  
Potential Efficacy ◽  
Ifn Γ

ABSTRACT We have examined the efficacy of the administration in mice of a molecularly defined vaccine based on the Leishmania infantum acidic ribosomal protein P0 (rLiP0). Two different challenge models of murine cutaneous leishmaniasis were used: (i) subcutaneous inoculation of L. major parasites in susceptible BALB/c mice (a model widely used for vaccination analysis) and (ii) the intradermal inoculation of a low infective dose in resistant C57BL/6 mice (a model that more accurately reproduces the L. major infection in natural reservoirs and in human hosts). First, we demonstrated that C57BL/6 mice vaccinated with LiP0-DNA or rLiP0 protein plus CpG oligodeoxynucleotides (ODN) were protected against the development of dermal pathology and showed a reduction in the parasite load. This protection was associated with production of gamma interferon (IFN-γ) in the dermal site. Secondly, we showed that immunization with rLiP0 plus CpG ODN is able to induce only partial protection in BALB/c, since these mice finally developed a progressive disease. Further, we demonstrated that LiP0 vaccination induces a Th1 immunological response in both strains of mice. In both cases, the antibodies against LiP0 were predominantly of the immunoglobulin G2a isotype, which was correlated with an rLiP0-stimulated production of IFN-γ in draining lymph nodes. Finally, we demonstrated that LiP0 vaccination does not prevent the Th2 response induced by L. major infection in BALB/c mice. Taken together, these data indicate that the BALB/c model of cutaneous leishmaniasis may undervalue the potential efficacy of some vaccines based on defined proteins, making C57BL/6 a suitable alternative model to test vaccine candidates.

scholarly journals Leishmania infantum xenodiagnosis from vertically infected dogs reveals significant skin tropism

2021 ◽  
Vol 15 (10) ◽  
pp. e0009366
Author(s):  
Breanna M. Scorza ◽  
Kurayi G. Mahachi ◽  
Arin C. Cox ◽  
Angela J. Toepp ◽  
Adam Leal-Lima ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Severe Disease ◽  
Clinical Status ◽  
Parasite Burden ◽  
Parasite Load ◽  
Sand Fly ◽  
Lutzomyia Longipalpis ◽  
Sand Flies ◽  
Feeding Site ◽  
Transmission Potential

Background Dogs are the primary reservoir for human visceral leishmaniasis due to Leishmania infantum. Phlebotomine sand flies maintain zoonotic transmission of parasites between dogs and humans. A subset of dogs is infected transplacentally during gestation, but at what stage of the clinical spectrum vertically infected dogs contribute to the infected sand fly pool is unknown. Methodology/Principal findings We examined infectiousness of dogs vertically infected with L. infantum from multiple clinical states to the vector Lutzomyia longipalpis using xenodiagnosis and found that vertically infected dogs were infectious to sand flies at differing rates. Dogs with mild to moderate disease showed significantly higher transmission to the vector than dogs with subclinical or severe disease. We documented a substantial parasite burden in the skin of vertically infected dogs by RT-qPCR, despite these dogs not having received intradermal parasites via sand flies. There was a highly significant correlation between skin parasite burden at the feeding site and sand fly parasite uptake. This suggests dogs with high skin parasite burden contribute the most to the infected sand fly pool. Although skin parasite load and parasitemia correlated with one another, the average parasite number detected in skin was significantly higher compared to blood in matched subjects. Thus, dermal resident parasites were infectious to sand flies from dogs without detectable parasitemia. Conclusions/Significance Together, our data implicate skin parasite burden and earlier clinical status as stronger indicators of outward transmission potential than blood parasite burden. Our studies of a population of dogs without vector transmission highlights the need to consider canine vertical transmission in surveillance and prevention strategies.

scholarly journals Vitamins A and D and Zinc Affect the Leshmanicidal Activity of Canine Spleen Leukocytes

Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2556
Author(s):  
Fabiana M. de O. Hernandez ◽  
Marilene O. Santos ◽  
Gabriela L. Venturin ◽  
Jaqueline P. Bragato ◽  
Gabriela T. Rebech ◽  
...  
Keyword(s):  
Parasite Load ◽  
Serum Levels ◽  
Canine Leishmaniasis ◽  
Serum Retinol ◽  
Future Studies ◽  
Icp Ms ◽  
Tnf Α ◽  
Ifn Γ ◽  
Low Serum

Canine leishmaniasis (CanL) is a chronic disease caused by Leishmania infantum, and the limitations of the current treatments have encouraged new alternatives, such as the use of immunomodulatory nutrients. The objective of this study was to determine the serum levels of vitamin A (retinol), vitamin D (25(OH)VD3), and zinc (Zn) in dogs with CanL and the effect of in vitro supplementation with the respective active forms ATRA, 1,25(OH)2VD3, and SZn on spleen leukocyte cultures. Serum retinol, 25(OH)VD3, and Zn were determined by HPLC, ELISA, and ICP-MS, respectively. Spleen leukocyte cultures were used for the detection of NO and ROS by flow cytometry; the IFN-γ, TNF-α, and IL-10 levels were determined by ELISA; and the parasite load was determined by microscopy. We detected low serum levels of retinol and Zn and high levels of 25(OH)VD3 in the CanL group. The in vitro supplementation of CanL spleen leukocytes with ATRA, 1,25(OH)2VD3, and SZn, in addition to a soluble leishmania antigen (SLA) treatment, increased the NO and ROS levels, while the treatments with only ATRA and SZn increased the TNF-a levels. Increased IL-10 and IFN-g levels were observed with the addition of SLA to the medium, although the addition of the three nutrients led to a reduction of the IL-10 levels, and the addition of 1,25(OH)2VD3 and SZn led to a reduction of IFN-g. A supplementation with 1,25(OH)2VD3 and SZn reduced the parasite load but only in the absence of SLA. We suggest that the nutrients we tested are involved in the leishmanicidal mechanism, showing a potential for investigation in future studies.

scholarly journals Leishmania infantum xenodiagnosis from vertically infected dogs reveals significant skin tropism

2021 ◽  
Author(s):  
Breanna M. Scorza ◽  
Kurayi G. Mahachi ◽  
Arin Cox ◽  
Angela J. Toepp ◽  
Adam Leal Lima ◽  
...  
Keyword(s):  
Leishmania Infantum ◽  
Severe Disease ◽  
Clinical Status ◽  
Parasite Burden ◽  
Parasite Load ◽  
Sand Fly ◽  
Lutzomyia Longipalpis ◽  
Sand Flies ◽  
Feeding Site ◽  
Transmission Potential

Background: Dogs are the primary reservoir for human visceral leishmaniasis due to Leishmania infantum. Phlebotomine sand flies maintain zoonotic transmission of parasites between dogs and humans. A subset of dogs is infected transplacentally during gestation, but at what stage of the clinical spectrum vertically infected dogs contribute to the infected sand fly pool is unknown. Methodology/Principal Findings: We examined infectiousness of dogs vertically infected with L. infantum from multiple clinical states to the vector Lutzomyia longipalpis using xenodiagnosis and found that vertically infected dogs were infectious to sand flies at differing rates. Dogs with moderate disease showed significantly higher transmission to the vector than dogs with very mild or severe disease. We documented a substantial parasite burden in the skin of vertically infected dogs by RT-qPCR, despite these dogs not having received intradermal parasites via sand flies. There was a highly significant correlation between skin parasite burden at the feeding site and sand fly parasite uptake. This suggests dogs with high skin parasite burden contribute the most to the infected sand fly pool. Although skin parasite load and parasitemia correlated with one another, the average parasite number detected in skin was significantly higher compared to blood in matched subjects. Thus, dermal resident parasites were infectious to sand flies from dogs without detectable parasitemia. Conclusions/Significance: Together, our data implicate skin parasite burden and earlier clinical status as stronger indicators of outward transmission potential than blood parasite burden. Our studies of a population of dogs without vector transmission highlights the need to consider canine vertical transmission in surveillance and prevention strategies.

scholarly journals The Leishmania infantum Acidic Ribosomal Protein P0 Administered as a DNA Vaccine Confers Protective Immunity to Leishmania major Infection in BALB/c Mice

2003 ◽  
Vol 71 (11) ◽  
pp. 6562-6572 ◽  
Author(s):  
Salvador Iborra ◽  
Manuel Soto ◽  
Javier Carrión ◽  
Ana Nieto ◽  
Edgar Fernández ◽  
...  
Keyword(s):  
Ribosomal Protein ◽  
Leishmania Infantum ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Immunological Response ◽  
Humoral Response ◽  
Ifn Γ ◽  
Immunogenic Properties ◽  
Ribosomal Protein P0 ◽  
Acidic Ribosomal Protein

ABSTRACT In this study, we examined the immunogenic properties of the Leishmania infantum acidic ribosomal protein P0 (LiP0) in the BALB/c mouse model. The humoral and cellular responses induced by the administration of the LiP0 antigen, either as soluble recombinant LiP0 (rLiP0) or as a plasmid DNA formulation (pcDNA3-LiP0), were determined. Also, the immunological response associated with a prime-boost strategy, consisting of immunization with pcDNA3-LiP0 followed by a boost with rLiP0, was assayed. Immunization with rLiP0 induced a predominant Th2-like humoral response, but no anti-LiP0 antibodies were induced after immunization with pcDNA3-LiP0, whereas a strong humoral response consisting of a mixed immunoglobulin G2a (IgG2a)-IgG1 isotype profile was induced in mice immunized with the prime-boost regime. For all three immunization protocols, rLiP0-stimulated production of gamma interferon (IFN-γ) in both splenocytes and lymph node cells from immunized mice was observed. However, it was only when mice were immunized with pcDNA3-LiP0 that noticeable protection against L. major infection was achieved, as determined by both lesion development and parasite burden. Immunization of mice with LiP0-DNA primes both CD4+ and CD8+ T cells, which, with the L. major challenge, were boosted to produce significant levels of IL-12-dependent, antigen-specific IFN-γ. Taken together, these data indicate that genetic vaccination with LiP0 induces protective immunological effector mechanisms, yet the immunological response elicited by LiP0 is not sufficient to keep the infection from progressing.

Correlations between tissue parasite load and common clinical signs in dogs naturally infected by Leishmania infantum

2021 ◽  
Vol 291 ◽  
pp. 109368
Author(s):  
Úrsula Maira Russo Chagas ◽  
Daniel Moreira de Avelar ◽  
Andreza Pain Marcelino ◽  
Gustavo Fontes Paz ◽  
Célia Maria Ferreira Gontijo
Keyword(s):  
Leishmania Infantum ◽  
Clinical Signs ◽  
Parasite Load

scholarly journals Experimental Evaluation of Second-Line Oral Treatments of Visceral Leishmaniasis Caused by Leishmania infantum

1999 ◽  
Vol 43 (1) ◽  
pp. 172-174 ◽  
Author(s):  
Jean-Pierre Gangneux ◽  
Michael Dullin ◽  
Annie Sulahian ◽  
Yves Jean-Francois Garin ◽  
Francis Derouin
Keyword(s):  
Visceral Leishmaniasis ◽  
Murine Model ◽  
Experimental Evaluation ◽  
Leishmania Infantum ◽  
Parasite Load ◽  
Second Line ◽  
Meglumine Antimoniate ◽  
Marked Activity

ABSTRACT In a murine model of Leishmania infantum visceral leishmaniasis, metronidazole, ketoconazole, fluconazole, itraconazole, and terbinafine were less effective than antimonial agents in reducing hepatic parasite load. Ketoconazole potentiated the effect of meglumine antimoniate reference therapy through its marked activity against spleen infection.

scholarly journals Evaluation of Leishmania (Leishmania) infantum excreted-secreted antigens for detection of canine leishmaniasis

Acta Tropica ◽  
2016 ◽  
Vol 161 ◽  
pp. 41-43 ◽  
Author(s):  
Viviana Pinedo-Cancino ◽  
Márcia Dalastra Laurenti ◽  
Norival Kesper ◽  
Eufrosina Setsu Umezawa
Keyword(s):  
Leishmania Infantum ◽  
Canine Leishmaniasis ◽  
Secreted Antigens
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