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 <i>Leishmania infantum</i> in Dogs.

first_pagesettingsOrder Article Reprints Open AccessArticle 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 by Icíar Martínez-Flórez 1,Maria Jose Guerrero 2ORCID,Annabel Dalmau 3,Maria Cabré 1,4ORCID,Maria Magdalena Alcover 5ORCID,Diana Berenguer 5,Liam Good 6,Roser Fisa 5ORCID,Cristina Riera 5ORCID,Laura Ordeix 1,4 andLaia Solano-Gallego 1,*ORCID 1 Departament de Medicina i Cirurgia Animals, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain 2 Hospital Veterinario Alhaurín el Grande, 29120 Alhaurín el Grande, Spain 3 AniCura Mediterrani Hospital Veterinari, 43204 Reus, Spain 4 Fundació Hospital Clínic Veterinari, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain 5 Departament de Biologia, Sanitat i Medi Ambient, Secció de Parasitologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, 08028 Barcelona, Spain 6 Department of Pathobiology and Population Sciences, The Royal Veterinary College, University of London, London NW1 0TU, UK * Author to whom correspondence should be addressed. Pathogens 2023, 12(6), 821; https://doi.org/10.3390/pathogens12060821 Submission received: 28 March 2023 / Revised: 11 May 2023 / Accepted: 8 June 2023 / Published: 10 June 2023 (This article belongs to the Special Issue Parasitic Infections: Immunity, Vaccine and Drug Development) Downloadkeyboard_arrow_down Browse Figures Versions Notes Abstract 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 (χ2 = 5.78; df = 2, p = 0.06) and day 30 (χ2 = 4.; df = 2, p = 0.12), while local meglumine antimoniate administration demonstrated the fastest clinical resolution after 15 (χ2 = 12.58; df = 2, p = 0.002) and 30 days post-treatment (χ2 = 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) (χ2 = 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 agonis

Serological and molecular survey of Leishmania infection in dogs from Venezuela

Venezuela is a country where human and canine leishmaniosis due to Leishmania infantum, Leishmania braziliensis and other Leishmania spp. is endemic. However, only limited data is available on canine Leishmania infection in Venezuela. The aim of this cross-sectional study was to evaluate the prevalence of Leishmania infection in dogs (n = 152) from the states of Lara (n = 91) and Yaracuy (n = 61) in Venezuela by means of serological and molecular methods. Physical examination was performed and blood samples were collected from all dogs. Serology for antibodies reactive with L. infantum and L. braziliensis antigens was assessed by the enzyme-linked immunosorbent assay (ELISA) and detection of Leishmania DNA from blood samples was evaluated by kinetoplast Leishmania real-time polymerase chain reaction (RT-PCR). In addition, Leishmania internal transcribed spacer (ITS-1) RT-PCR was performed on the samples positive by kinetoplast RT-PCR. The prevalence of Leishmania infection based on serological and/or molecular techniques was 11.8%. The seroprevalence for L. infantum and L. braziliensis antigens were 2.1% (3/144) and 8.3% (12/144), respectively. All dogs from the state of Yaracuy were serologically negative to L. infantum while 4.6% (4/86) of the dogs were reactive to L. braziliensis antigen. Fourteen percent (8/58) of the dogs from the state of Lara were positive to L. infantum and 5.2% (3/58) to L. braziliensis antigen. Three dogs were positive to both Leishmania spp. antigens. By RT-PCR, 6.5% (4/61) and 4.4% (4/91) of the dog were positive for infection in the states of Lara and Yaracuy, respectively. The RT-PCR product of one dog from the state of Yaracuy was sequenced revealing a 100% identity with L. infantum. However, all RT-PCR positive dogs were seronegative to both Leishmania spp. antigens. In conclusion, the positivity for Leishmania spp. infections observed indicates that dogs are frequently infected by L. infantum, L. braziliensis or related Leishmania spp. in Venezuela

Clinical and diagnostic aspects of feline cutaneous leishmaniosis in Venezuela

Abstract Background: Venezuela is an endemic area for human and canine leishmaniosis due to Leishmania infantum and parasites of the Leishmania braziliensis and L. mexicana complexes. Limited data are available on feline leishmaniosis (FeL) in this region. The aim of this study was to describe clinical and diagnostic aspects of FeL in Venezuela. Results: Thirty-one domestic cats from urban areas of Lara State in Venezuela were enrolled. Twenty-five were healthy. Six other cats had solitary or multiple nodular lesions, which were located on the nose; ears; ears and nose; and nose, ears, tail and lower limbs. Cutaneous lesions were characterized by diffuse pyogranulomatous infiltrate in all sick cats with numerous intracellular and extracellular amastigotes, and immunohistochemistry was positive for Leishmania in five sick cats. All healthy cats were seronegative for L. infantum and L. braziliensis antigens by ELISA. Two out of five sick cats yielded a positive ELISA result to both Leishmania antigens with higher antibody levels to L. braziliensis compared to L. infantum. Significantly higher antibody levels by ELISA as well as a higher number of bands by Western blot (WB) were found for L. braziliensis when compared to L. infantum antigens in all sera from Venezuelan sick and healthy cats. All healthy cats were blood Leishmania spp. qPCR negative while three out of six sick cats were blood qPCR positive. All paraffin-embedded skin biopsies (n = 4) as well as cutaneous cytology (n = 3) were positive by Leishmania spp. qPCR in sick cats. Leishmania speciation was obtained only from the cutaneous lesion samples from cytological preparations of two out of three sick cats which were identified as infected with L. mexicana or a closely related specie. Conclusions: FeL should be included in the differential diagnosis list of nodular-ulcerative lesions. The most reliable diagnostic technique in sick cats is cytological or histopathological examination along with immunohistochemistry, since blood PCR and serology by ELISA might be negative. WB appears to be more sensitive in detecting infection. Cats with leishmaniosis from Venezuela are most likely infected with species of L. mexicana or a closely related species or the L. braziliensis species complex and not with L. infantum

Prevalence and Factors Associated with Leishmania infantum Infection of Dogs from an Urban Area of Brazil as Identified by Molecular Methods

Visceral leishmaniasis (VL) is a disease caused by the parasite Leishmania infantum, and dogs are the most important domestic reservoirs of the agent. During recent decades, VL has expanded to large Brazilian urban centers. In the present work, we have demonstrated by using molecular techniques that the rate of canine infection as detected by serology has been considerably underestimated. Two groups of seronegative dogs (infected and non-infected according to molecular methods) were further evaluated from data obtained through interviews with owners of the animals. The factors associated with Leishmania infection in dogs were a family income of less than two minimum salaries, the knowledge of the owner regarding the vector, the dog spending most of its time in the backyard and the dog never having had a previous serological examination. Awareness regarding the factors associated with canine infection will improve health services and the understanding of the disease's expansion in urban areas