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

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.

Exploring the Relationship between Neutrophil Activation and Different States of Canine L. infantum Infection: Nitroblue Tetrazolium Test and IFN-γ

“…Notably, dogs with papular dermatitis are markedly younger than their counterparts, boasting a median age of 6 months, with ages ranging from 3 months to 7 years. This is in line with previous studies, as papular dermatitis is consistently diagnosed in dogs under one year of age [ 39 , 48 , 49 ]. This has been theorized to be attributed to the condition’s propensity to manifest during the initial encounter between the parasite and the host’s immune system, making it more prevalent in young dogs, particularly in areas where the parasite is endemic [ 39 ].…”

“…This particular clinical presentation is commonly associated with a robust and protective immune response. Notably, these dogs spontaneously resolve cutaneous lesions, as evidenced by long-term follow-up, which also indicates an absence of clinical relapse or the emergence of systemic clinical signs, and thus, they are more likely to be representative of an effective immune response and not just an early phase of the disease [ 39 , 45 , 46 , 47 , 49 ]. To further support this, the long-term follow-up in the current study showed that only three animals out of 25 were considered to get worse without systemic treatment, and the other 22 dogs resolved cutaneous lesions and remained healthy.…”

“…A total of 128 dogs were enrolled in this study and divided into five groups according to the LeishVet staging system [ 1 ]: Group 1 included healthy seronegative dogs with no clinical signs or hematological or biochemical abnormalities ( n = 25); Group 2 included Leishmania -seropositive but clinically healthy dogs with no clinical signs, hematological and serum and urinary biochemical parameters within normal limits, and presenting low to medium antibody levels ( n = 21); Group 3 included dogs with mild disease-LeishVet stage I presenting papular dermatitis as the sole clinical sign [ 39 ], the identification of intralesional amastigotes via cytology, hematological, serum, and urinary biochemical parameters within normal limits (including creatinine < 1.4 mg/dL), and presenting negative to low antibody levels ( n = 25); Group 4 included dogs with moderate disease-LeishVet stage II, including the characteristic clinical signs (diffuse clinical manifestations, like extensive skin lesions, widespread lymph node enlargement, or weight loss among others), hematological and serum biochemical abnormalities with normal creatinine values (<1.4 mg/dL), and medium-to-high antibody levels ( n = 41); Group 5 included dogs with severe disease-LeishVet stage III and very severe disease-Leishvet stage IV, including the characteristic clinical signs, hematological, biochemical abnormalities (including creatinine values of 1.4–2.8 mg/dL or UPC > 1 for stage III and creatinine values > 2.8 for stage IV or UPC > 5), and presenting positive antibody levels ( n = 16) [ 1 ]. The urine protein creatinine ratio was assessed in 12/25 dogs in stage I and in all dogs in stages II, III, and IV.…”

“…A follow-up of up to one year was available for all dogs with papular dermatitis without conventional anti- Leishmania systemic treatment instituted. Some dogs in this group received local treatment whit either topical meglumine antimoniate as a lotion spray ( n = 6/25), polyhexamethylene biguanide alone or in combination with Toll like receptor 4 agonist as a spray ( n = 9/25), or placebo ( n = 9/25), and one received no treatment at all [ 39 ].…”

“…The threshold was established at 35 EU [ 39 ]. Serum samples were categorized as negative when their value fell below 35 EU.…”