Effective immuno-therapeutic treatment of Canine Leishmaniasis

Ramos, Rafael Antonio Nascimento; Giannelli, Alessio; Fasquelle, François; Scuotto, Angelo; Betbeder, Didier

doi:10.1371/journal.pntd.0011360

Cited by 3 publications

(2 citation statements)

References 33 publications

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“…A 3-month study was conducted on naturally infected dogs in Brazil. Two nasal administrations, two weeks apart, induced a decrease in the parasite burden in both the skin and the bone marrow, and also sharply decreased the infection-related humoral response [ 84 ]. A slight improvement in the clinical scoring was also observed, although the dogs had other infections, and no side effects were reported.…”

Section: Lipidated Cationic Maltodextrin Nps For Antigen Deliverymentioning

confidence: 99%

“…A slight improvement in the clinical scoring was also observed, although the dogs had other infections, and no side effects were reported. Overall, the immunotreatment was safer and at least as efficient as the current Brazilian chemotherapy protocol, based on 28 oral administrations of milteforan over a period of one month [ 84 , 85 ].…”

Section: Lipidated Cationic Maltodextrin Nps For Antigen Deliverymentioning

confidence: 99%

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Maltodextrin-Nanoparticles as a Delivery System for Nasal Vaccines: A Review Article

Fasquelle,

Scuotto,

Howsam

et al. 2024

Pharmaceutics

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Nanoparticles are increasingly being studied as antigen delivery systems for immunization with nasal vaccines. The addition of adjuvants is still generally required in many nanoparticle formulations, which can induce potential side effects owing to mucosal reactogenicity. In contrast, maltodextrin nanoparticles do not require additional immunomodulators, and have been shown to be efficient vaccine delivery systems. In this review, the development of maltodextrin nanoparticles is presented, specifically their physico-chemical properties, their ability to load antigens and deliver them into airway mucosal cells, and the extent to which they trigger protective immune responses against bacterial, viral, and parasitic infections. We demonstrate that the addition of lipids to maltodextrin nanoparticles increases their potency as a vaccine delivery system for nasal administration.

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Section: Lipidated Cationic Maltodextrin Nps For Antigen Deliverymentioning

confidence: 99%

Section: Lipidated Cationic Maltodextrin Nps For Antigen Deliverymentioning

confidence: 99%

Maltodextrin-Nanoparticles as a Delivery System for Nasal Vaccines: A Review Article

Fasquelle,

Scuotto,

Howsam

et al. 2024

Pharmaceutics

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Pharmacokinetics, Dose-Proportionality, and Tolerability of Intravenous Tanespimycin (17-AAG) in Single and Multiple Doses in Dogs: A Potential Novel Treatment for Canine Visceral Leishmaniasis

Ferrante,

Leite,

Fontes

et al. 2024

Pharmaceuticals

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In the New World, dogs are considered the main reservoir of visceral leishmaniasis (VL). Due to inefficacies in existing treatments and the lack of an efficient vaccine, dog culling is one of the main strategies used to control disease, making the development of new therapeutic interventions mandatory. We previously showed that Tanespimycin (17-AAG), a Hsp90 inhibitor, demonstrated potential for use in leishmaniasis treatment. The present study aimed to test the safety of 17-AAG in dogs by evaluating plasma pharmacokinetics, dose-proportionality, and the tolerability of 17-AAG in response to a dose-escalation protocol and multiple administrations at a single dose in healthy dogs. Two protocols were used: Study A: four dogs received variable intravenous (IV) doses (50, 100, 150, 200, or 250 mg/m2) of 17-AAG or a placebo (n = 4/dose level), using a cross-over design with a 7-day “wash-out” period; Study B: nine dogs received three IV doses of 150 mg/m2 of 17-AAG administered at 48 h intervals. 17-AAG concentrations were determined by a validated high-performance liquid chromatographic (HPLC) method: linearity (R2 = 0.9964), intra-day precision with a coefficient of variation (CV) ≤ 8%, inter-day precision (CV ≤ 20%), and detection and quantification limits of 12.5 and 25 ng/mL, respectively. In Study A, 17-AAG was generally well tolerated. However, increased levels of liver enzymes–alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)–and bloody diarrhea were observed in all four dogs receiving the highest dosage of 250 mg/m2. After single doses of 17-AAG (50–250 mg/m2), maximum plasma concentrations (Cmax) ranged between 1405 ± 686 and 9439 ± 991 ng/mL, and the area under the curve (AUC) plotting plasma concentration against time ranged between 1483 ± 694 and 11,902 ± 1962 AUC 0–8 h μg/mL × h, respectively. Cmax and AUC parameters were dose-proportionate between the 50 and 200 mg/m2 doses. Regarding Study B, 17-AAG was found to be well tolerated at multiple doses of 150 mg/m2. Increased levels of liver enzymes–ALT (28.57 ± 4.29 to 173.33 ± 49.56 U/L), AST (27.85 ± 3.80 to 248.20 ± 85.80 U/L), and GGT (1.60 ± 0.06 to 12.70 ± 0.50 U/L)–and bloody diarrhea were observed in only 3/9 of these dogs. After the administration of multiple doses, Cmax and AUC 0–48 h were 5254 ± 2784 μg/mL and 6850 ± 469 μg/mL × h in plasma and 736 ± 294 μg/mL and 7382 ± 1357 μg/mL × h in tissue transudate, respectively. In conclusion, our results demonstrate the potential of 17-AAG in the treatment of CVL, using a regimen of three doses at 150 mg/m2, since it presents the maintenance of high concentrations in subcutaneous interstitial fluid, low toxicity, and reversible hepatotoxicity.

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

Vaz,

Quaresma,

Rêgo

et al. 2023

TropicalMed

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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.

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Effective immuno-therapeutic treatment of Canine Leishmaniasis

Cited by 3 publications

References 33 publications

Maltodextrin-Nanoparticles as a Delivery System for Nasal Vaccines: A Review Article

Maltodextrin-Nanoparticles as a Delivery System for Nasal Vaccines: A Review Article

Pharmacokinetics, Dose-Proportionality, and Tolerability of Intravenous Tanespimycin (17-AAG) in Single and Multiple Doses in Dogs: A Potential Novel Treatment for Canine Visceral Leishmaniasis

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

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