Potential of Artesunate in the treatment of visceral leishmaniasis in dogs naturally infected by Leishmania infantum: Efficacy evidence from a randomized field trial (original) (raw)
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Clinical efficacy of two different drug combinations for the treatment of canine leishmaniasis
Veterinary Research Communications, 2008
IntroductionCanine Leishmaniasis (LC) therapy is one of the most studied aspects of the disease, also because of the efficacy limits of all the utilised drugs. A recent study has shown the therapeutic efficacy of spiramycin + metronidazole (Stomorgyl®) in LC treatment (Pennisi et al. 2005). Moreover, a study on the murine model (Gangneux et al. 1999) has shown the efficacy of the association of metronidazole + meglumine antimoniate in the infection determined by L. infantum. In this association there would be a synergy for the higher activity of metronidazole in the spleen and of antimony in the liver. To this end, the goal of this study is to compare the efficacy of the currently most widely used association - meglumine antimoniate (Glucantime®) + Allopurinol (Zyloric®) towards Glucantime® + Stomorgyl® in LC therapy (in both cases, antimony was given for 30 or 60 days).Materials and methodsThe study is a randomised non-blind field controlled trial, with a positive control group. Sympt ...
Experimental Parasitology, 2020
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Iranian journal of pharmaceutical research : IJPR, 2014
Toxicity and drug resistance against pentavalent antimonials, medications of choice in treatment of leishmaniasis for more than 5 decades, have become important subjects globally. This study was a randomized, open labeled trial that was designed to determine efficacy and safety of IMOD as a novel herbal immunomodulator drug for treatment of canine visceral leishmaniasis (CVL). Twenty healthy mongrel dogs were infected with Iranian strain of L. Infantum amastigotes and randomly divided to 5 groups with four animals for each included on: I: negative control (non-infected) II: Glucantime® III: Glucantime® plus IMOD (immune-chemotherapy) IV: IMOD and V: positive control (non-treated). Physical examination, hematological, biochemical, serological, parasitological, pathological and imaging evaluations were performed pre-/post- interventions every month for 3 months. Comparing with control groups (I&V), immune-chemotherapy group (Glucantime® plus IMOD) showed significantly higher efficacy ...
Treatment of canine leishmaniasis: long term molecular and serological observations
Medycyna weterynaryjna
The aim of the present paper was to evaluate the anti-Leishmania activity of 3 different protocols of treatment (miltefosine plus allopurinol, difloxacin cloridrate plus metronidazole and meglumine antimoniate plus allopurinol) in 42 dogs naturally infected by L. infantum, during a 24-months parasitological and clinical follow-up. Our results suggest that, apart from miltefosine, the other two therapeutic regimens could be evaluated to treat animals with canL in medium-endemicity areas.
Use of allopurinol for maintenance of remission in dogs with leishmaniasis
Journal of Small Animal Practice, 1998
Current treatments for infected dogs with leishmaniasis do not always provide long-term control of the disease and clinical relapses are common. In this study, the usefulness of long-term allopurinol administration in the maintenance of clinical remission in canine leishmaniasis was evaluated. Fifteen dogs with natural leishmania infection were subjected to an initial treatment based on the simultaneous administration of meglumine antimoniate (100 mg/kg/day) and allopurinol (30 mg/kg/day). Once clinical remission was achieved, a maintenance treatment with allopurinol (20 mg/kg/day) administered for one week a month was instituted. Results were compared with those of a retrospective control group comprising 15 infected dogs which only followed the induction treatment. Relapses occurred in 86 per cent of control dogs within 14 months of discontinuing treatment. In contrast, those dogs on intermittent oral allopurinol administration were successfully maintained in clinical remission for a follow-up period of 10 to 44 months. In this latter group, specific antibody titres decreased or were unchanged, no side effects directly attributable to allopurinol were seen and treatment was well accepted by the owners. It is concluded that long-term intermittent administration of allopurinol is an effective way of maintaining clinical remission in dogs with leishmaniasis.
Scientometric analysis of chemotherapy of canine leishmaniasis (2000-2020)
Research Square (Research Square), 2020
Background: Zoonotic visceral leishmaniasis by Leishmania infantum is a rst order pathology in veterinary clinics of dogs in endemic areas. Moreover, canine infections are considered the main reservoir for human disease; despite their importance in the control of the disease within a One Health approach no scientometric study has been published. Aims of the study included the impact of canine leishmaniasis (CanL) on scienti c literature, drugs or combinations used, trends in the period from 2000-2020 and e cacy criteria employed. Methods: A Web of Science (WOS) based analysis of publications on CanL and chemotherapy of the disease in the period 2000-2020 was carried out using a stepwise methodology. Data were analyzed by year, geographical origin, chemical groups, drugs and combinations, and e cacy criteria. Results: Reports on CanL (n=3,324) represented less than 16% of all publications on leishmaniasis (n=20,968) and from these around 18% (n=596) were related to chemotherapy. Publication records on CanL followed the distribution of the infection by L.infantum in endemic areas although Mediterranean countries were overrepresented in the reports on chemotherapy of CanL. Publications on the main antileishmanial drugs used in clinical practice showed a sustained tendency in the period analyzed. Pentavalent antimonials (Sb V), alone or in combination with allopurinol, represented over 50% of all publications on chemotherapy of CanL despite the availability of more recently marketed drugs. Conclusions: Chemotherapy of CanL still relies on Sb V and combinations and to a lesser extent on miltefosine (MIL). Reports on chemotherapy are scarce, mostly publicly funded and the variability of experimental conditions hampers the direct comparison of the e cacy of drugs, combinations and schedules. The vast majority of reports on e cacy do not include any information on supportive therapy; this reduces the actual value of the studies if intended for the practical management of the disease. Complete reports of the chemotherapy (etiological + symptomatic) would add value to the trials performed. Background Leishmaniasis is a widely distributed group of vector-borne parasitic diseases caused by kinetoplastids from the genus Leishmania. Clinical course relates to the Leishmania spp involved and the functionality of the immune system of the hosts. Visceral leishmaniasis (VL), provoked by Leishmania donovani and Leishmania infantum, is the most severe condition; it is prevalent in Asia, South America and southern Europe [1-3] and its expansion to northern latitudes has been reported [4,5]. Moreover, new transmission patterns have been identi ed linked to immunocompromised patients, non-vectorial transmission and solid organs transplant recipients [6,7]. Dogs can be infected by several Leishmania spp [8] and are considered the main reservoir for human infections by L. infantum [9]. Canine leishmaniasis (CanL) is very frequent reaching over 30% prevalence in some "hot spots" [10] and constitutes a rst order veterinary pathology in endemic areas. Control of CanL has important shortcomings since marketed vaccines have limitations [11,12], environmental control is unfeasible; culling of infected dogs is debatable and its actual impact has been challenged [13-15]. Therefore, control of CanL largely relies on the use of repellents and, mainly, on chemotherapy of infected dogs. Therapeutic arsenal includes the same compounds used for the treatment of human leishmaniasis: antimonials (Sb V), amphotericin (AmB), miltefosine (MIL), allopurinol, paromomycin, among other drugs and combinations [16-18]. Treatment schedules are highly variable among veterinarians, and some efforts to harmonize chemotherapy schemes have been made [19, 20]; for the time being, variability is the rule. Despite the importance of CanL by L.infantum in both dog clinics and public health by its zoonotic transmission-a clear example of the need of the One Health approach-few scientometric contributions on leishmaniasis are available and none focused on CanL [21-23]. On these grounds the aim of our study was the analysis of anti-leishmanial drugs employed in the treatment of CanL, using Web of Science (WOS) as data source, in the 21 st century. Time window (2000-2020) was selected by the growing awareness of the need of controlling the infection in the main reservoir, the launch of MIL, the only available antileishmanial oral drug, and the publication of several guidelines for CanL chemotherapy. Methods Documents and selection criteria Analysis followed a stepwise methodology [24] using WOS Core collection as data source. Documents containing the terms "leishmaniosis" or "leishmaniasis" in their titles, abstracts or key words were selected. Reports were further restricted to CanL (Leishmaniosis OR leishmaniasis + dogs OR canine) and, nally, those directly focused on chemotherapy (leishmaniosis OR leishmaniasis + dogs OR canine + treatment OR therapy). Data obtained were screened for chemotherapeutic agents (leishmaniosis OR leishmaniasis + dogs OR canine + Drugs).
Veterinary Parasitology, 2007
Aiming to evaluate the efficacy of the treatment of canine visceral leishmaniasis, to verify the occurrence of a possible disease relapse, and to search for the presence of the parasites after the end of the treatment, seven dogs naturally infected by Leishmania (Leishmania) chagasi were used. The dogs were subjected to a treatment with 75 mg/kg meglumine antimoniate subcutaneously every 12 h for 21 days, and followed-up for a period of 6 months. During the whole experimental period the animals wore deltamethrin collars and were kept in a screened kennel to avoid reinfection. Lymph node and bone marrow aspiration biopsy was carried out to search for the parasite at seven moments: before the treatment, 30, 60, 90, 120, 150 and 180 days after the start of the treatment. After the end of the experiment all dogs were humanely euthanized. Then, spleen and liver ''imprints'' and in vitro cultures were carried out to search for amastigote forms of the parasite. During the treatment all animals presented remission of symptoms. However, two dogs were observed to present new symptoms in the course of the experiment. At the end of the experiment, the presence of amastigote forms of the parasite was evidenced in five of the seven dogs. This enabled us to conclude that the treatment promoted clinical cure but did not eliminate the parasites completely.
The efficacy of i.v. versus s.c. administration of Glucantime (100 mg/kg of body weight/day) was studied in 41 dogs with leishmaniasis without serious renal insufficiency. Remission was obtained in 35 dogs (85.4%) after 3 to 6 weeks of treatment but there was a relapse within 1 year in 26 dogs (74.3%). The median period of remission was 6 months. Cross-over therapy resulted in remission in 17 of 20 dogs. The percentage of remission after initial and cross-over therapy, the median relapse free period, and survival did not differ significantly between the two groups. There were very few complications and most were of minor clinical importance. Thrombophlebitis developed in one dog after i.v. injection. In dogs with leishmaniasis without serious renal insufficiency, there is a 75% probability of survival for more than 4 years following treatment with Glucantime for 3 to 6 weeks, with additional treatment when relapses occur.
Environmental Toxicology and Pharmacology, 2020
Tellurium compounds have been described as potential leishmanicides, bearing promising leishmanicidal and antimalarial effects. Therefore, the present study investigated the pharmacological potential of the organotellurane compound RF07 through preADMET parameters, such as absorption, distribution, metabolism and excretion. After studying the pharmacokinetic properties of RF07, studies were carried out on dogs naturally infected with visceral leishmaniasis after the administration of RF07, in order to assess pathophysiological parameters. Thus, dogs were divided into 4 groups with administration of daily intraperitoneal injections for 3 weeks (containing RF07 or placebo). During the trial, hematological parameters, renal and hepatic toxicity were evaluated. Serum urea, creatinine, alkaline phosphatase, transaminases (GOT and GPT), as well as hemogram results, were evaluated before the first administration and during the second and third weeks after the start of the treatment. In dogs with VL, RF07 improved liver damage, regulated GPT levels and significantly decreased leukocyte count, promoting its regularization. These phenomena occurred at the end of the third week of treatment. The administration of RF07 promoted a significant decrease in the average levels of GOT and GPT after the third week of treatment and did not significantly alter the hematological parameters. The application of RF07 in the treatment of visceral leishmaniasis suggests that it is an alternative to the disease, since the reversal of clinical signs in dogs with VL requires the use of 0.6 mg/kg. as dogs (De Rycker et al., 2018; Jain and Jain, 2015; Oryan and Akbari, 2016). Leishmaniasis is a public health problem in more than 90 countries (Zhang et al., 2020). It is estimated that 12 million human beings carry leishmaniasis, with 1.5-2 million new cases reported each year, with 500,000 cases of visceral leishmaniasis and about 50,000 deaths per year (