Clinical and parasitological impact of short-term treatment using miltefosine and allopurinol monotherapy or combination therapy in canine visceral leishmaniasis

Sorte, Eveline da Cruz Boa; Dias, Álvaro Felipe de Lima Ruy; Monteiro, Bruna Ribeiro Gomes; Pazzini, Sarah Szimanski; Barbosa, Mateus Elias Chagas; Silva, Eveliny Barroso da; Macedo, Luis Felipe da Cruz; Sousa, Valéria Régia Franco; Dutra, Valéria; Nakazato, Luciano; Almeida, Arleana do Bom Parto Ferreira de

doi:10.1590/s1984-29612022040

Cited by 4 publications

(12 citation statements)

References 44 publications

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“…Studies have demonstrated a good clinical response in dogs naturally infected by L. infantum and treated with miltefosine alone or in combination with other drugs [11,13,14,19,20]. Our results showed that associating Milteforan ® with the continuous use of allopurinol contributes to controlling clinical signs of the disease.…”

Section: Discussionsupporting

confidence: 51%

“…Ramos et al (2023) [19] also observed a decrease, without significance, in antibody titers three months after treatment with miltefosine. Ayres et al (2022) [14] did not observe a reduction in antibody titers, but the evaluation was carried out 28 days after treatment with miltefosine and allopurinol. According to Paltrinieri et al (2016) [31], a decrease in antibody titers is expected six months after treatment, but in dogs living in endemic areas, the complete clearance of antibodies is unlikely.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have demonstrated a positive response in CVL dogs treated with miltefosine. Some studies have also associated the use of this drug with allopurinol, which, due to its leishmaniostatic activity, contributes to disease control [11][12][13][14]. However, most of these studies have evaluated the treatment of CVL dogs in controlled environments, such as screened kennels with regulated temperatures and a balanced diet, along with deworming and vaccination monitoring.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and Laboratory Response of Domiciled Dogs with Visceral Leishmaniasis Treated with Miltefosine and Allopurinol

Vaz,

Quaresma,

Rêgo

et al. 2023

TropicalMed

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Canine visceral leishmaniasis (CVL) remains a significant disease worldwide. In Brazil, its treatment is performed using miltefosine, which has demonstrated promising outcomes in dogs. This study represents the first attempt to treat and monitor dogs with CVL in natural conditions over the course of one year. The dogs were divided into two groups: G1 received miltefosine and allopurinol for 28 days, while G2 received miltefosine for 28 days, followed by allopurinol for one year. The follow-up involved clinical, hematological, and biochemical evaluations, as well as the detection of Leishmania DNA in skin and bone marrow samples. By the end of the follow-up, dogs in G2 exhibited improved staging compared to their initial conditions, whereas those in G1 showed worsened staging. Leishmania DNA in skin and bone marrow decreased between 6 and 12 months after treatment. Our observations indicate that the treatment using miltefosine reduces the detection of the parasite in the skin and bone marrow for up to one year following its administration. The continuous use of allopurinol contributes to control of the disease in dogs. These findings provide valuable insights into the response of dogs treated in natural conditions, offering essential information for veterinarians and public health authorities.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical and Laboratory Response of Domiciled Dogs with Visceral Leishmaniasis Treated with Miltefosine and Allopurinol

Vaz,

Quaresma,

Rêgo

et al. 2023

TropicalMed

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“…Table 1 presents the relevant data extracted from each of the 16 selected articles and the analysis of the different studies. In total, these studies included the evaluation of 598 dogs diagnosed with leishmaniosis; 15 dogs were subtracted from the total as they were shared in two publications [12,13]. Strength of evidence.Meta-analyses or systematic reviews [10]; Randomized controlled trials [11]; Cohort studies, non-randomized controlled trials [12,13];Case/control studies [7,14]; Case series, case reports [6,[15][16][17][18][19][20][21][22][23].…”

Section: Resultsmentioning

confidence: 99%

Critically Appraised Topic on Canine Leishmaniosis: Does Treatment with Antimonials and Allopurinol Have the Same Clinical and Clinicopathological Efficacy as Treatment with Miltefosine and Allopurinol, after One Month of Treatment?

García,

Ferrer,

Ordeix

2024

Veterinary Sciences

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The treatment of canine leishmaniosis commonly involves meglumine antimoniate with allopurinol or miltefosine with allopurinol. This study aims to compare the clinical and clinicopathological efficacy at 28–30 days of conventional dosing regimens for both treatments using the critically appraised topic methodology. A comprehensive search across three databases (PubMed, CAB Abstracts, and Web of Science) from March 2004 to September 2023 yielded 16 relevant articles, encompassing 325 ogs treated with meglumine antimoniate and allopurinol, and 273 dogs treated with miltefosine and allopurinol. The findings indicated a significantly higher rate of complete clinical cure in the group treated with meglumine antimoniate and allopurinol. Most dogs in both groups exhibited improvement in clinicopathological alterations after one month of treatment. No significant difference was observed in the number of dogs that showed a negative Leishmania qPCR between the two groups, one month post-treatment. However, quantitative serology results were not commonly reported in the available data and therefore this aspect could not be compared.

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“…Despite its efficacy, the use of miltefosine in monotherapy is not recommended due to a higher risk of therapeutic failure [ 15 ] or recurrences after the interruption of treatment [ 16 , 17 ]. Instead, the combined therapy of miltefosine and leishmaniostatic allopurinol is a protocol of documented efficacy [ 18 , 19 ] and is considered among those the first choice for CanL therapy [ 4 , 20 ]. Nevertheless, the Miltefosine-Allopurinol (MIL-AL) protocol is sometimes considered a second-choice treatment when compared to meglumine-antimoniate—allopurinol combination, mainly for the risk of earlier relapses [ 21 , 22 ] or the development of parasite drug resistance [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Retrospective Long-Term Evaluation of Miltefosine-Allopurinol Treatment in Canine Leishmaniosis

Gizzarelli

Manzillo

Inglese³

et al. 2023

Pathogens

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Miltefosine-Allopurinol (MIL-AL) combination is reported to be one of the most effective treatments for canine leishmaniosis, thanks to its oral administration and MIL-documented low impact on renal function. However, MIL-AL is considered a second-choice treatment when compared to meglumine-antimoniate—allopurinol combination, mainly due to the risk of earlier relapses. The aim of this study was to evaluate the efficacy of the MIL-AL protocol during a long-term follow-up with an average duration of nine years. Dogs were living in Southern Italy (Puglia, Italy) in an area considered endemic for Canine leishmaniosis (CanL). Inclusion criteria were clinical and/or clinicopathological signs consistent with CanL; positive result to Leishmania quantitative ELISA; and negativity to the most frequent canine vector-borne infections. All dogs received 2 mg/kg MIL for 28 days, and 10 mg/kg AL, BID, for a period varying between 2 and 12 months. Ancillary treatments were allowed according to the clinical condition of the dog. A total clinical score and a total clinicopathological score were calculated at each time point by attributing one point to each sign or alteration present and then by adding all points. Improvement after each treatment was defined by the reduction of at least 50% of the total score. A survival analysis (Kaplan–Meier curve) was performed for quantifying the probability of the events occurring during the study follow-up. The following events were considered: decreased and negative ELISA results; improvement/recovery of the clinical and clinicopathological alterations; and relapse of leishmaniasis. One hundred seventy-three dogs (75f and 98m) were retrospectively included in the study by examining their clinical records since the first diagnosis of CanL. One hundred forty-three (83%) dogs were under five years of age. The mean duration of the follow-up period was 5.4 (±1.1) years with a minimum of 3.2 years and a maximum of 9 years. All dogs received a first treatment of MIL-AL at inclusion; then, during the follow-up course, 30 dogs required a second treatment, 2 dogs required a third treatment and 1 dog required a fourth and a fifth treatment. The mean time interval between the first and the second treatment was 27.2 (±18.3) months. After the first treatment, all dogs had decreased ELISA levels, in an average interval of 2.6 (±1.6) months. One hundred seventy dogs (98%) experienced a clinical improvement (mean time 3.0 ± 4.9 months); 152 (88%) dogs were considered clinically recovered after a mean time of 16.7 ± 13.5 months. A similar trend was observed for clinicopathological alterations; interestingly, proteinuria decreased in most dogs (p < 0.0001—Chi-square for trends). Thirty dogs experienced relapses, the earliest after 4.8 months. The mean time without relapse was 90.4 (±2.5) months. In relapsed dogs, the mean time for clinical improvement after the second treatment was 8.6 (±12.6) months, whereas it was 11.0 (±15.4) months for clinicopathological alterations. Five dogs had limited gastrointestinal side effects associated with MIL treatment. The present study confirms that the MIL-AL protocol can be considered one of the most effective treatments for CanL therapy, mainly for its capacity to provide a long-time clinical improvement in a large majority of treated dogs. As reported in the literature, the clinical stabilization of dogs does not occur immediately after treatment, probably due to the particular pharmacokinetic properties of MIL. The efficacy of MIL-AL decreases in dogs that need more than one treatment, suggesting the necessity to alternate anti-Leishmania drugs for the treatment of relapses. Side effects were transient and slight, even in dogs that required several treatments.

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Clinical and parasitological impact of short-term treatment using miltefosine and allopurinol monotherapy or combination therapy in canine visceral leishmaniasis

Cited by 4 publications

References 44 publications

Clinical and Laboratory Response of Domiciled Dogs with Visceral Leishmaniasis Treated with Miltefosine and Allopurinol

Clinical and Laboratory Response of Domiciled Dogs with Visceral Leishmaniasis Treated with Miltefosine and Allopurinol

Critically Appraised Topic on Canine Leishmaniosis: Does Treatment with Antimonials and Allopurinol Have the Same Clinical and Clinicopathological Efficacy as Treatment with Miltefosine and Allopurinol, after One Month of Treatment?

Retrospective Long-Term Evaluation of Miltefosine-Allopurinol Treatment in Canine Leishmaniosis

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