Mathematical Modelling Using Predictive Biomarkers for the Outcome of Canine Leishmaniasis upon Chemotherapy

Abstract

Prediction parameters of possible outcomes of canine leishmaniasis (CanL) therapy might help with therapeutic decisions and animal health care. Here, we aimed to develop a diagnostic method with predictive value by analyzing two groups of dogs with CanL, those that exhibited a decrease in parasite load upon antiparasitic treatment (group: responders) and those that maintained high parasite load despite the treatment (group: non-responders). The parameters analyzed were parasitic load determined by q-PCR, hemogram, serum biochemistry and immune system-related gene expression signature. A mathematical model was applied to the analysis of these parameters to predict how efficient their response to therapy would be. Responder dogs restored hematological and biochemical parameters to the reference values and exhibited a Th1 cell activation profile with a linear tendency to reach mild clinical alteration stages. Differently, non-responders developed a mixed Th1/Th2 response and exhibited markers of liver and kidney injury. Erythrocyte counts and serum phosphorus were identified as predictive markers of therapeutic response at an early period of assessment of CanL. The results presented in this study are highly encouraging and may represent a new paradigm for future assistance to clinicians to interfere precociously in the therapeutic approach, with a more precise definition in the patient’s prognosis.

Feline Leishmaniasis Caused by Leishmania infantum: Parasite Sequencing, Seropositivity, and Clinical Characterization in an Endemic Area From Brazil

“…Moreover, studies have showed that a higher parasitic load in the canine host is associated with more intense disease, and that these more susceptible dogs are more infectious to the phlebotomine vectors ( 33 , 76 ). Factors such as the parasite's tissue tropism and intrinsic pathophysiological mechanisms make organs such as the spleen more intensely parasitised than other ones in infected dogs ( 77 – 79 ). Thus, in dogs, the use of samples from such organs is likely to improve diagnostic sensitivity of methods based on the detection of parasites and/or its DNA ( 71 , 75 , 80 ).…”

“…Besides, cross-reactions with other pathogens should be considered, as already reported for dogs ( 83 , 84 ). Susceptible canine hosts develop high antibody levels as the infection progresses, together with the development of clinical alterations and a higher chance to infect vectors ( 66 , 79 , 85 , 86 ). Based on our data, this does not seem to happen in cats.…”

Nutritional Modulation of the Immune Response Mediated by Nucleotides in Canine Leishmaniosis

“…In dogs, the type of immune response against the parasite also markedly determines whether a dog develops clinical disease or remains in a subclinical stage, and it also strongly affects the prognosis [3,7,9,17,[52][53][54][55][56]. It also seems that some canine breeds present a higher susceptibility to CanL (Boxer, Cocker Spaniel, Rottweiler, and German Shepherd), while the Ibizan Hound is a breed with reported resistance to Leishmania infection [51].…”

Agroclimatic Impact on Gastrointestinal Infection: A Mathematical Model

“…Alongside emerging infection kinetic preemptive models [20], mathematical modeling [21][22][23][24] is increasingly preferred as a non-invasive alternative to experimentation. It has the potential to compare existing strategies and predict future dynamics.…”