Antileishmanial efficacy and tolerability of combined treatment with non-ionic surfactant vesicle formulations of sodium stibogluconate and paromomycin in dogs

• Published in: Experimental parasitology 2021-01, Vol.220, p.108033, Article 108033
• Main Authors: Miret, Jorge A., Moreno, Javier, Nieto, Javier, Carter, Katharine C., Mullen, Alexander B., Ambros, Luis, Rodríguez, Casilda, San Andrés, Manuel Ignacio, González, Fernando
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Analysis of Variance; Animals; Antimony Sodium Gluconate - administration & dosage; Antimony Sodium Gluconate - pharmacology; Antimony Sodium Gluconate - therapeutic use; Antiprotozoal Agents - administration & dosage; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - therapeutic use; Blood Cell Count; Blood Chemical Analysis; Bone Marrow - parasitology; Canine leishmaniasis; Cricetinae; Disease Reservoirs; Dogs; Female; Leishmania donovani - drug effects; Leishmania donovani - immunology; Leishmania donovani - isolation & purification; Leishmania infantum; Leishmania infantum - drug effects; Leishmania infantum - immunology; Leishmania infantum - isolation & purification; Liver - parasitology; Lymph Nodes - parasitology; Male; Mesocricetus; Mice; Mice, Inbred BALB C; Non-ionic surfactant vesicles formulations; Paromomycin; Paromomycin - administration & dosage; Paromomycin - pharmacology; Paromomycin - therapeutic use; Skin - parasitology; Sodium stibogluconate; Spleen - parasitology
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2020.108033

Infection with Leishmania infantum causes the disease visceral leishmaniasis (VL), which is a serious clinical and veterinary problem. The drugs used to treat canine leishmaniasis (CanL) do not cause complete parasite clearance; they can be toxic, and emerging drug resistance in parasite populations limits their clinical utility. Therefore, in this study we have evaluated the toxicity and efficacy of joint treatment with a 1:1 mixture of sodium stibogluconate-NIV (SSG-NIV, 10 mg Sbv/day) and paromomycin-NIV (PMM-NIV, 10 mg PMM/kg/day), given intravenously daily for seven days from day 270 post-infection, to nine-month-old female beagle dogs (n = 6) experimentally infected with Leishmania infantum. Treatment significantly improved the clinical symptoms of VL infection in all the treated dogs, reduced parasite burdens in lymph nodes and bone marrow, and all symptomatic treated dogs, were asymptomatic at 90 days post-treatment. Treatment was associated with a progressive and significant decrease in specific IgG anti-Leishmania antibodies using parasite soluble antigen (p