scholarly journals Unresponsiveness of Experimental Canine Leishmaniosis to a New Amphotericin B Formulation

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Leticia Hernández ◽  
Francisco Bolás-Fernández ◽  
Ana Montoya ◽  
Rocío Checa ◽  
Diana Dado ◽  
...  

This study was designed to evaluate the efficacy and safety of a novel free polyaggregated amphotericin B (FPA) formulation used to treat experimental canine leishmaniosis (CanL) caused by Leishmania infantum. Eight healthy beagles were intravenously challenged with 5×107 promastigotes per mL of L. infantum. One year after infection, they received an intravenous dose of FPA (5 mg/kg) every 2 weeks three times. Dogs were assessed monthly for clinical signs, serology, and parasite detection during a follow-up period of 6 months. Transient adverse effects (i.e., hypotension, diarrhea, bodyweight loss, fever, and asthenia) were observed within 24–48 hours after treatment in 4 animals. In three dogs mean clinical signs scores were reduced. Antibody titers measured by immunofluorescence antibody test (IFAT) had significantly diminished at the end of the study, although according to bone marrow smears and cultures a high percentage of dogs tested positive for the parasite at 6 months posttreatment (PT6). Real-time quantitative PCR (rtQ-PCR) on blood, bone marrow, and urine samples revealed the presence of parasitic DNA in all animals at PT6, although blood loads of the parasite were reduced. These findings indicate that FPA at the dosing regimen used did not achieve clinical or parasitological cure in dogs experimentally infected with L. infantum.

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247560
Author(s):  
Valéria da Costa Oliveira ◽  
Artur Augusto Velho Mendes Junior ◽  
Luiz Claudio Ferreira ◽  
Tatiana Machado Quinates Calvet ◽  
Shanna Araujo dos Santos ◽  
...  

In canine leishmaniosis caused by the protozoan Leishmania infantum, little is known about how co-infections with or co-seropositivities for other pathogens can influence aggravation of this disease. Therefore, the objectives of this study were to evaluate the frequency of co-infections with or co-seropositivities for certain pathogens in dogs seropositive for L. infantum and their relationship with clinical signs, histological changes and L. infantum load. Sixty-six L. infantum-seropositive dogs were submitted to clinical examination, collection of blood and bone marrow, culling, and necropsy. Antibodies against Anaplasma spp., Borrelia burgdorferi sensu lato, Ehrlichia spp. and Toxoplasma gondii and Dirofilaria immitis antigens were investigated in serum. Samples from different tissues were submitted to histopathology and immunohistochemistry for the detection of Leishmania spp. and T. gondii. Quantitative real-time PCR was used to assess the L. infantum load in spleen samples. For detection of Coxiella burnetii, conventional PCR and nested PCR were performed using bone marrow samples. All 66 dogs tested positive for L. infantum by qPCR and/or culture. Fifty dogs (76%) were co-seropositive for at least one pathogen: T. gondii (59%), Ehrlichia spp., (41%), and Anaplasma spp. (18%). Clinical signs were observed in 15 (94%) dogs monoinfected with L. infantum and in 45 (90%) dogs co-seropositive for certain pathogens. The L. infantum load in spleen and skin did not differ significantly between monoinfected and co-seropositive dogs. The number of inflammatory cells was higher in the spleen, lung and mammary gland of co-seropositive dogs and in the mitral valve of monoinfected dogs. These results suggest that dogs infected with L. infantum and co-seropositive for certain pathogens are common in the region studied. However, co-seropositivities for certain pathogens did not aggravate clinical signs or L. infantum load, although they were associated with a more intense inflammatory reaction in some organs.


Phlebologie ◽  
2007 ◽  
Vol 36 (06) ◽  
pp. 309-312 ◽  
Author(s):  
T. Schulz ◽  
M. Jünger ◽  
M. Hahn

Summary Objective: The goal of the study was to assess the effectiveness and patient tolerability of single-session, sonographically guided, transcatheter foam sclerotherapy and to evaluate its economic impact. Patients, methods: We treated 20 patients with a total of 22 varicoses of the great saphenous vein (GSV) in Hach stage III-IV, clinical stage C2-C5 and a mean GSV diameter of 9 mm (range: 7 to 13 mm). We used 10 ml 3% Aethoxysklerol®. Additional varicoses of the auxiliary veins of the GSV were sclerosed immediately afterwards. Results: The occlusion rate in the treated GSVs was 100% one week after therapy as demonstrated with duplex sonography. The cost of the procedure was 207.91 E including follow-up visit, with an average loss of working time of 0.6 days. After one year one patient showed clinical signs of recurrent varicosis in the GSV; duplex sonography showed reflux in the region of the saphenofemoral junction in a total of seven patients (32% of the treated GSVs). Conclusion: Transcatheter foam sclerotherapy of the GSV is a cost-effective, safe method of treating varicoses of GSV and broadens the spectrum of therapeutic options. Relapses can be re-treated inexpensively with sclerotherapy.


2002 ◽  
Vol 46 (8) ◽  
pp. 2420-2426 ◽  
Author(s):  
Karl V. Clemons ◽  
Raymond A. Sobel ◽  
Paul L. Williams ◽  
Demosthenes Pappagianis ◽  
David A. Stevens

ABSTRACT The efficacy of intravenously administered liposomal amphotericin B (AmBisome [AmBi]) for the treatment of experimental coccidioidal meningitis was compared with those of oral fluconazole (FLC) and intravenously administered conventional amphotericin B (AMB). Male New Zealand White rabbits were infected by intracisternal inoculation of arthroconidia of Coccidioides immitis. Starting 5 days postinfection, animals received one of the following: 5% dextrose water diluent; AMB given at 1 mg/kg of body weight; AmBi given at 7.5, 15, or 22.5 mg/kg intravenously three times per week for 3 weeks; or oral FLC given at 80 mg/kg for 19 days. One week after the cessation of therapy, all survivors were euthanatized, the numbers of CFU remaining in the spinal cord and brain were determined, and histological analyses were performed. All AmBi-, FLC-, or AMB-treated animals survived and had prolonged lengths of survival compared with those for the controls (P < 0.0001). Treated groups had significantly lower numbers of white blood cells and significantly lower protein concentrations in the cerebrospinal fluid compared with those for the controls (P < 0.01 to 0.0005) and had fewer clinical signs of infection (e.g., weight loss, elevated temperature, and neurological abnormalities including motor abnormalities). The mean histological scores for AmBi-treated rabbits were lower than those for FLC-treated and control rabbits (P < 0.016 and 0.0005, respectively); the scores for AMB-treated animals were lower than those for the controls (P < 0.0005) but were similar to those for FLC-treated rabbits. All regimens reduced the numbers of CFU in the brain and spinal cord compared with those for the controls (P ≤0.0005). AmBi-treated animals had 3- to 11-fold lower numbers of CFU than FLC-treated rabbits and 6- to 35-fold lower numbers of CFU than AmB-treated rabbits. Three of eight animals given 15 mg of AmBi per kg had no detectable infection in either tissue, whereas other doses of AmBi or FLC cleared either the brain or the spinal cord of infection in fewer rabbits. In addition, clearance of the infection from both tissues was achieved in none of the rabbits, and neither tissue was cleared of infection in AMB-treated animals. Overall, these data indicate that intravenously administered AmBi is superior to oral FLC or intravenous AMB and that FLC is better than AMB against experimental coccidioidal meningitis. These data indicate that AmBi may offer an improvement in the treatment of coccidioidal meningitis. Additional studies are warranted.


2019 ◽  
Vol 40 (6Supl2) ◽  
pp. 3313
Author(s):  
Valéria Régia Franco Sousa ◽  
Álvaro Felipe de Lima Ruy Dias ◽  
Juliana Yuki Rodrigues ◽  
Mariana de Medeiros Torres ◽  
Janaína Marcela Assunção Rosa Moreira ◽  
...  

Visceral Leishmaniasis (VL) is a parasitic zoonosis expanding in Brazil. Several municipalities in the state of Mato Grosso including those on the river Cuiabá have reported the incidence of both human and canine cases and the identification of sandfly vector, Lutzomyia longipalpis and Lu. cruzi. Dogs are considered the main reservoir of Leishmania chagasi in the urban areas, hence, we devised a cross-sectional study aimed at assessing the prevalence of the infection in the dogs of riverside communities on Cuiabá River watershed by parasitological (parasitic isolation in culture), serological, and molecular methods. Of the 248 surveyed dogs, 24 were positive in enzyme linked immunosorbent assay (ELISA) or immunofluorescence antibody test (IFAT), with a prevalence of 9.7%. The riverside communities located in the town of Santo Antonio do Leverger displayed a higher prevalence of the disease than the cities of Cuiabá and Várzea Grande; however, the difference was not statistically significant (p > 0.05). Dogs born in the communities had a 3.24-fold higher risk of acquiring the infection. Promastigote were isolated in the axenic culture from the bone marrow samples and intact skin. Further, DNA of Leishmania sp. was detected in the bone marrow samples, lymph nodes, leukocyte cover, and skin of only one examined dog. These samples were sequenced and they showed 99% homology to L. infantum. To conclude, we observed a higher prevalence of infection in Riverside communities of Santo Antonio do Leverger and the confirmation of autochthony in these areas justifies the surveillance actions to minimise the risk of transmission within the riverine community itself, besides its dissemination to other areas by tourism.


Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 754
Author(s):  
Michela Pugliese ◽  
Alessandra Sfacteria ◽  
Gaetano Oliva ◽  
Annastella Falcone ◽  
Manuela Gizzarelli ◽  
...  

This study aimed to investigate the role of oxidative stress parameters (ROMs, OXY, SHp), the Oxidative Stress index (OSi), and High Mobility Group Box-1 protein (HMGB-1) in canine leishmaniosis (CanL). For this study, thirty dogs, naturally infected with Leishmania spp. (Leishmania Group, LEISH) and ten healthy adult dogs (control group, CTR) were included. The diagnosis of CanL was performed by a cytological examination of lymph nodes, real time polymerase chain reaction on biological tissues (lymph nodes and whole blood), and an immunofluorescence antibody test (IFAT) for the detection of anti-Leishmania antibodies associated with clinical signs such as dermatitis, lymphadenopathy, onychogryphosis, weight loss, cachexia, lameness, conjunctivitis, epistaxis, and hepatosplenomegaly. The HMGB-1 and oxidative stress parameters of the LEISH Group were compared with the values recorded in the CTR group (Mann Whitney Test, p < 0.05). Spearman rank correlation was applied to evaluate the correlation between the HMGB-1, oxidative stress biomarkers, hematological and biochemical parameters in the LEISH Group. Results showed statistically significant higher values of SHp in the LEISH Group. Specific correlation between the ROMs and the number of red blood cells, and between HGMB-1 and SHp were recorded. These preliminary data may suggest the potential role of oxidative stress in the pathogenesis of CanL. Further studies are undoubtedly required to evaluate the direct correlation between inflammation parameters with the different stages of CanL. Similarly, further research should investigate the role of ROMs in the onset of anemia.


2000 ◽  
Vol 74 (14) ◽  
pp. 6358-6367 ◽  
Author(s):  
Janet Welter ◽  
Jill Taylor ◽  
James Tartaglia ◽  
Enzo Paoletti ◽  
Charles B. Stephensen

ABSTRACT Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log10 inverse mean titer ± standard deviation of 2.30 ± 0.12 and 2.20 ± 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 ± 0.57 versus 0.40 ± 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 ± 0.54 and 1.28 ± 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 ± 0.59;n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 ± 0.32; n = 8,P = 7 × 10−6). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1.63 ± 0.25) than did i.n. immunization with NYVAC-HF (0.88 ± 0.36; n = 9) and ALVAC-HF (0.61 ± 0.43; n = 9, P = 3 × 10−7), and survival was also significantly better in the i.n.-parenteral group (3 of 9) than in the other HF-vaccinated animals (none of 18) or in controls immunized with RG (none of 5) (P = 0.0374). Multiple routes were not tested with the ALVAC vaccine. The results suggest that infant ferrets are less responsive to i.n. vaccination than are older ferrets and raises questions about the appropriateness of this route of immunization in infant ferrets or infants of other species.


PEDIATRICS ◽  
1949 ◽  
Vol 3 (2) ◽  
pp. 181-194
Author(s):  
PAUL A. DI SANT'AGNESE

Additional serologic studies are presented of a group of newborn infants whose antibody production following combined prophylactic inoculation against tetanus, diphtheria and pertussis was reported in a previous paper. Duration of Antibody Titers: In the 10 months following the last injection of triple combined antigen a steady decline in diphtheria antitoxin titers was observed which was more marked in patients who had achieved high antibody levels. A similar decrease was found in the percentage of infants with high titers of tetanus antitoxin, but there were no cases whose tetanus antitoxin level dropped to less than the "protective" titer (0.1 unit/cc.). Progressive decrease in diphtheria and tetanus antitoxin titers with passage of time is in agreement with findings of others. After the third and last immunizing injection, a rapid initial decrease was noted in the number of patients with "protective" pertussis agglutinin titers (1:400 or higher); then a levelling off took place and no further change was noted in the next six months. On the other hand, a steady decline was found in the percentage of infants with "high" agglutinin levels (1:3200). To our knowledge this has not been observed before. The young age of our patients at the time of the basic injections may have been responsible for the findings. Antibody Titers After Booster Dose: One group of infants was reinjected at the age of six months (four months after the third and last immunizing injection), another group at one year of age (10 months after the last injection). All booster doses consisted of 0.5 cc. of the same triple combined antigen used in basic immunization. After booster a marked increase was noted in diphtheria antitoxin titers to a level higher than that observed following the basic immunizing injections. Tetanus antitoxin response was considered to have been equally good, although more difficult to evaluate because of the high antitoxin levels present before reinjection. In the case of pertussis agglutinins, it appeared as if there were a "ceiling" of about 60% of infants who could, even after reinjection, develop a "protective" agglutinin titer (1:400 or higher). A striking difference was observed in both pertussis agglutinin levels and diphtheria antitoxin titers achieved by infants reinjected at six months and one year of age. This was thought to be due to immaturity of the immune mechanisms in the younger age group. An added factor in the case of diphtheria antitoxin in some patients may have been the persistence of passive antibodies acquired transplacentally. Antibody titers also were determined six months after booster dose in the infants who had been reinjected at the age of six months. A marked decrease was observed in the percentage of patients with "protective" pertussis agglutinin titers and "high" (1.0 unit/cc.) diphtheria antitoxin levels. No reduction was noted in tetanus antitoxin titers. Effects of Passive immunity to Diphtheria on Active immunization with Diphtheria Toxoid: With only one exception, all infants tested after a booster dose had been administered between 6 and 12 months of age had "protective" diphtheria antitoxin titers (0.03 units/cc. or more). Active immunization against diphtheria was therefore considered to have been achieved in all cases (with one exception) despite the passively transmitted antitoxin present at birth in over half the cases. While passive diphtheria antitoxin present at birth did not prevent "sensitization" of the antibody-forming tissues to the diphtheria antigen, it did decrease significantly the amounts of antitoxin actively produced in response to basic inoculation. Reasons for the success of active diphtheria immunization in this series are discussed. Arguments against active immunization of mothers in pregnancy for protection of their offspring are considered.


PEDIATRICS ◽  
1963 ◽  
Vol 32 (4) ◽  
pp. 497-500
Author(s):  
Rosa Lee Nemir ◽  
Donna O'Hare ◽  
Stanley Goldstein ◽  
Charles B. Hilton

Complement fixing antibody titers to the adenoviruses were determined in 251 newborn infants, using cord blood. Approximately 95% of these were found to have CF titers of 1:16 or over, the majority (75%) were 1:32 or more. Material from the pharyngeal and rectal swabs of these infants on tissue culture studies (542) on HeLa and amnion cells showed no cytopathic effect in oven 96% of these infants. A longitudinal study of 114 of these infants was made at 3 months intervals; 67 have been observed for one year. At 3 months, only 12% still showed CF antibody titers, and these were chiefly at a low level, 1:16. At the subsequent 3-month interval observations, a gradual rise in CF antibodies were found. At one year of age, approximately 37% had titers of 1:32 on over. The findings of this report support the statement that CF antibodies to adenovirus pass the placental barrier. There is a gradual increase in the percentage of infants with positive CF antibodies after 3 months.


PEDIATRICS ◽  
1981 ◽  
Vol 67 (2) ◽  
pp. 222-229 ◽  
Author(s):  
A. van der Does-van den Berg ◽  
J. Hermans ◽  
J. Nagel ◽  
G. van Steenis

Antibody titers to diphtheria, pertussis, tetanus, and poliomyelitis (types I to III) were measured in previously vaccinated children with acute lymphocytic leukemia in remission after cessation of therapy. The response to revaccination one year after therapy was stopped was also studied. The patients' antibody titers were compared with those of healthy children, matched for age and sex. Two groups of patients were studied: one group (group A, N = 30) was given two drugs (6-mercaptopurine, methotrexate); the other group (group B, N= 19) was given three drugs (6-mercaptopurine, methotrexate, and cyclophosphamide) for maintenance treatment. In general, the patients' antibody titers were lower than those of healthy children, but in most patients they were still at levels considered to be protective. No significant differences in antibody levels between the two patient groups were found. A spontaneous rise in antibody titers in the first year after termination of therapy was not observed. After revaccination the rise in antibody titers was correlated with preexisting antibody titers in the same way in patients as in healthy children, and the antibody titers in patients and in healthy control subjects were on roughly the same level.


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