Canine leishmaniasis (CanL) is a vector-borne disease caused by Leishmania infantum and is transmitted by female phlebotomine sand flies primarily between animals and secondarily to humans. The course of infection may be different from one individual dog to another, ranging from spontaneous cure to acute evolution that leads to death, if proper management and therapy are not adopted. A parasitological cure is rarely achieved and clinical recurrences in CanL are frequent. Vaccination associated with the use of topical insecticides is undoubtedly the most effective form of prevention and control of the disease. In order to integrate the most important scientific knowledge of the literature in one objective publication, this review proposes a short overview of the main points of CanL.
This paper aims at providing the prior and posterior interpretations for the parameters in the logistic regression model with random or cluster-level intercept when univariate and multivariate classes of skew normal distributions are assumed to model the random effects behavior. We obtain the prior distributions for the odds ratio and their medians under skew normality for the random effects. Original results related to linear combinations of skew-normal distributions are obtained as a by-product and, in the univariate case, a new class of log-skew-normal distribution is introduced. Robust results are obtained whenever a class of multivariate skew-normal distribution is assumed. We also evaluate the effect of the misspecification of the random effects distributions in the odds ratio estimation. We consider both simulated and the Teratogenic activity experiment datasets. The latter was previously analysed in the literature. We concluded that the misspecification of the random effects distribution yields poor odds ratios estimates and that the median odds ratio is not necessarily the best measure of heterogeneity among the clusters as suggested in the literature.
The treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote a marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP plus Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg of body weight/dose) at 4-day intervals plus allopurinol at 30 mg/kg/12 h per os (p.o.) during 130 days (LCP+Allop); LC plus Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) plus allopurinol during 130 days (LC+Allop); Allop, treated with allopurinol only; and a nontreated control. Parasite loads were evaluated by quantitative PCR in liver, spleen, and bone marrow tissue and by immunohistochemistry in the ear skin, before treatment, just after treatment, and 4 months later. The LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen, and bone marrow 4 months after treatment compared to the pretreatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin in comparison to the control group. On the basis of clinical staging and parasitological evaluations, the LCP formulation exhibited a more favorable therapeutic profile than the LC one, being therefore promising for the treatment of canine visceral leishmaniasis.
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