Prevention of disease progression in Leishmania infantum-infected dogs with dietary nucleotides and active hexose correlated compound

Abstract

BackgroundThe prevalence of Leishmania infantum infection in clinically healthy dogs can be several times higher than that of clinical disease in endemic areas. Although treatment is not recommended in dogs with subclinical infection, these animals should be managed to prevent disease progression and parasite transmission to human beings or to other dogs. Dietary nucleotides and active hexose correlated compound (AHCC) have been shown to modulate the immune response. A recent study in dogs with clinical leishmaniosis receiving an initial 28-day course of methylglucamine antimoniate showed that six-month administration of a dietary supplement containing nucleotides plus AHCC achieves similar efficacy to allopurinol. Since the type of immune response plays a key role in the evolution of patients with leishmaniosis, the present study was aimed at evaluating the preventive effect of this supplement in avoiding or delaying disease progression in clinically healthy Leishmania-infected dogs.MethodsForty-six dogs were included in this multicenter, randomized, double-blind, placebo-controlled trial. Dogs received once-daily oral administration of a placebo or a dietary supplement containing nucleotides plus AHCC. Disease progression was monitored throughout the study in both groups. At 0, 60, 180 and 365 days of treatment, clinical signs were evaluated using a validated clinical scoring system, and several analytes were measured from blood, urine, and bone marrow samples.ResultsDuring the study, a significantly lower (P = 0.047) proportion of dogs changed their clinical status and became sick in the supplement group (3/20; 15%), compared to the placebo group (10/22; 45.5%). ELISA-determined antibody titers were significantly reduced compared to baseline at all time points with the supplement (P < 0.01), but not with the placebo. The mean clinical score of disease severity was significantly lower in the supplement group after 180 days (P = 0.014). No significant differences were observed for the other parameters. The dietary supplement was well tolerated.ConclusionsOral administration of nucleotides plus AHCC for 365 days in clinically healthy L. infantum-infected dogs is safe, allows a significant reduction in anti-Leishmania antibodies, and leads to a lower disease progression rate, hence exerting a preventive effect.

Nucleotides and AHCC Enhance Th1 Responses In Vitro in Leishmania-Stimulated/Infected Murine Cells

“…The data reported herein, together with previously published clinical data on the use of nucleotides plus AHCC [ 24 , 25 ], further support the interest of these products for their potential use in the management of canine and human leishmaniasis. The control of such disease is complex due to the heterogeneity of the different species and genotypes and the reported resistance to the most commonly used drugs [ 34 ].…”

“…The production of NO by macrophages was not altered following the application of compounds alone or with any of the combinations (see Supplementary Material 2 ) suggesting that the in vivo efficacy of nucleotides plus AHCC in CanL patients previously reported [ 24 , 25 ] probably occurs through a different mechanism of action.…”

“…Our data reveal that there is a synergistic effect between both compounds, and that their 1:1 weight ratio combination leads to the best results. This positive impact on the immune system and enhancement of the Th1 response could explain the beneficial effects previously reported in vivo after the oral administration of nucleotides and AHCC in CanL patients using a similar ratio [ 24 , 25 ]. However, further studies evaluating the specific effects of such compounds on Th1 cells would be warranted.…”

“…The cytotoxicity assay was carried out as previously described [ 38 ]. J774 murine macrophages were grown in RPMI 1640 medium supplemented with 10% heat-inactivated FBS (30 min at 56 °C), penicillin G (100 U/mL) and streptomycin (100 μg/mL) [ 25 ]. For the experiments, cells in the preconfluence phase were harvested with 0.03% EDTA-0.05% trypsin in PBS for 20 min.…”

“…The combined use of MGA and nucleotides plus AHCC resulted in improved clinical scores and an overall amelioration in the biomarkers used to monitor response to treatment, showing similar efficacy to MGA plus allopurinol, and without producing xanthinuria [ 24 ]. Furthermore, in another recent multicenter, randomized, double-blind, placebo-controlled trial, 1-year administration of dietary nucleotides plus AHCC in clinically healthy dogs naturally infected with L. infantum led to a significantly reduced disease progression rate compared to placebo, and a decrease in the levels of anti- Leishmania antibodies indicating that dietary nucleotides plus AHCC could potentially be used as a preventive approach [ 25 ].…”