f0fbbba648d7d42e3ccad6e8c376e372 pmc_10304710.pdf 807169670089627841c9549b639895e29c03ecca pmc_10304710.pdf 12a88ec131be384bc1a8f00f13be24038b1e00f9f70e8eea4506a1252b40f730 pmc_10304710.pdf Title: Effect of Local Administration of Meglumine Antimoniate and Polyhexamethylene Biguanide Alone or in Combination with a Toll-like Receptor 4 Agonist for the Treatment of Papular Dermatitis due to Leishmania infantum in Dogs Subject: Papular dermatitis is a cutaneous manifestation of canine Leishmania infantum infection associated with mild disease. Although it is a typical presentation, nowadays, there is still no established treatment. This study evaluated the safety and clinical efficacy of local meglumine antimoniate, locally administered polyhexamethylene biguanide (PHMB) alone or PHMB in combination with a Toll-like receptor 4 agonist (TLR4a) for the treatment of papular dermatitis due to L. infantum and assessed parasitological and immunological markers in this disease. Twenty-eight dogs with papular dermatitis were divided randomly into four different groups; three of them were considered treatment groups: PHMB (n = 5), PHMB + TLR4a (n = 4), and meglumine antimoniate (n = 10)), and the remaining were considered the placebo group (n = 9), which was further subdivided into two sub-groups: diluent (n = 5) and TLR4a (n = 4). Dogs were treated locally every 12 h for four weeks. Compared to placebo, local administration of PHMB (alone or with TLR4a) showed a higher tendency towards resolution of papular dermatitis due to L. infantum infection at day 15 (2 = 5.78; df = 2, p = 0.06) and day 30 (2 = 4.; df = 2, p = 0.12), while local meglumine antimoniate administration demonstrated the fastest clinical resolution after 15 (2 = 12.58; df = 2, p = 0.002) and 30 days post-treatment (2 = 9.47; df = 2, p = 0.009). Meglumine antimoniate showed a higher tendency towards resolution at day 30 when compared with PHMB (alone or with TLR4a) (2 = 4.74; df = 2, p = 0.09). In conclusion, the local administration of meglumine antimoniate appears to be safe and clinically efficient for the treatment of canine papular dermatitis due to L. infantum infection. Keywords: canine; cutaneous lesions; immunotherapy; leishmaniosis; local treatment; toll-like agonist Author: Icíar Martínez-Flórez, Maria Jose Guerrero, Annabel Dalmau, Maria Cabré, Maria Magdalena Alcover, Diana Berenguer, Liam Good, Roser Fisa, Cristina Riera, Laura Ordeix and Laia Solano-Gallego Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Jun 14 10:49:51 2023 CEST ModDate: Wed Jun 14 10:57:15 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1486200 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- VZGAER+VnURWPalladioL Type 1 Custom yes yes no 10 0 EOWADA+EURM10 Type 1 Builtin yes yes no 15 0 HSHVGP+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 DFSQCO+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 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GLEGBA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 283 0 MDIKPC+CMBSY10 Type 1 Builtin yes yes no 289 0 AKXRSZ+EURB10 Type 1 Builtin yes yes no 300 0 BCDEEE+Calibri TrueType WinAnsi yes yes no 315 0 Arial,Bold TrueType WinAnsi no no no 320 0 Arial TrueType WinAnsi no no no 323 0 Arial CID TrueType Identity-H yes no yes 326 0 GLEGAM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 345 0 GLEGAN+PalatinoLinotype CID TrueType Identity-H yes yes yes 348 0 GLEGAO+PalatinoLinotype TrueType WinAnsi yes yes no 354 0 GLEGBA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 357 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-09-16 02:34:21 CEST RepresentationInformation: pmc_10304710.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-09-09 02:19:51 CEST Size: 1486200 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 666 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Dogs and Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Treatment and Follow-Up Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Safety Assessment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: ELISA for specific L. infantum Antibody Detection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Cytokine Release Whole Blood Assay and Determination of Canine IFN- and IL-17a Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Nitroblue Tetrazolium Reduction Test Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Blood DNA Extraction and Leishmania Real-Time PCR Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Children: Item: Title: Dog Characteristics at the Time of Diagnosis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Safety and Clinical Efficacy of Treatments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Clinical Worsening (Withdrawal) and Lost to Follow-Up Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Leishmania Infantum-Specific Antibody Levels at the Time of Diagnosis and Follow-Up Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: IFN- Concentration at the Time of Diagnosis and During Treatment Follow-Up Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: IL-17a Concentration at Time of Diagnosis and During Treatment Follow-Up Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Correlation between Parameters Studied Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Nitroblue Tetrazolium Reduction Test Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Blood PCR Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Info: Title: Effect of Local Administration of Meglumine Antimoniate and Polyhexamethylene Biguanide Alone or in Combination with a Toll-like Receptor 4 Agonist for the Treatment of Papular Dermatitis due to Leishmania infantum in Dogs Author: Icíar Martínez-Flórez, Maria Jose Guerrero, Annabel Dalmau, Maria Cabré, Maria Magdalena Alcover, Diana Berenguer, Liam Good, Roser Fisa, Cristina Riera, Laura Ordeix and Laia Solano-Gallego Subject: Papular dermatitis is a cutaneous manifestation of canine Leishmania infantum infection associated with mild disease. Although it is a typical presentation, nowadays, there is still no established treatment. This study evaluated the safety and clinical efficacy of local meglumine antimoniate, locally administered polyhexamethylene biguanide (PHMB) alone or PHMB in combination with a Toll-like receptor 4 agonist (TLR4a) for the treatment of papular dermatitis due to L. infantum and assessed parasitological and immunological markers in this disease. Twenty-eight dogs with papular dermatitis were divided randomly into four different groups; three of them were considered treatment groups: PHMB (n = 5), PHMB + TLR4a (n = 4), and meglumine antimoniate (n = 10)), and the remaining were considered the placebo group (n = 9), which was further subdivided into two sub-groups: diluent (n = 5) and TLR4a (n = 4). Dogs were treated locally every 12 h for four weeks. Compared to placebo, local administration of PHMB (alone or with TLR4a) showed a higher tendency towards resolution of papular dermatitis due to L. infantum infection at day 15 (2 = 5.78; df = 2, p = 0.06) and day 30 (2 = 4.; df = 2, p = 0.12), while local meglumine antimoniate administration demonstrated the fastest clinical resolution after 15 (2 = 12.58; df = 2, p = 0.002) and 30 days post-treatment (2 = 9.47; df = 2, p = 0.009). Meglumine antimoniate showed a higher tendency towards resolution at day 30 when compared with PHMB (alone or with TLR4a) (2 = 4.74; df = 2, p = 0.09). In conclusion, the local administration of meglumine antimoniate appears to be safe and clinically efficient for the treatment of canine papular dermatitis due to L. infantum infection. 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