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bioRxiv · 10.1101/2021.09.16.460686

Kinetics of the inflammatory response during experimental Babesia rossi infection of beagle dogs

Atkinson, B. K.·Thompson, P.·Van Zyl, E.·Goddard, A.·Rautenbach, Y.·Schoeman, J. P.·Mukorera, V.·Leisewitz, A.
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Abstract

Babesia rossi causes severe morbidity and mortality in dogs in sub-Saharan Africa, and the complications associated with this disease are likely caused by an unfocused, excessive inflammatory response. During this experimental B. rossi study we investigated inflammatory marker and cytokine kinetics during infection and after treatment. We aimed to determine whether infectious dose and treatment would influence the progression of the inflammatory response and clinical disease. Five healthy male beagle dogs were infected with B. rossi, three with a high infectious dose (HD group) and two with a low infectious dose (LD group). Clinical examination, complete blood count (CBC) and C-reactive protein (CRP) were determined daily. Cytokines were quantified on stored plasma collected during the study, using a canine specific cytokine magnetic bead panel (Milliplex(C)). The experiment was terminated when predetermined endpoints were reached. Parasitemia occurred on day 1 and 3 in the HD group and LD group respectively. The rate of increase in parasitemia in the HD group was significantly faster than that seen in the LD group. Significant differences were found in heart rate, blood pressure, interferon gamma (INF{gamma}), keratinocyte chemoattractant (KC), INF{gamma}-induced protein 10 (IP10), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP1), tumor necrosis factor alpha (TNF), interleukin 2 (IL-2), IL-6, IL-7, IL-8, IL-10 IL-15, IL-18, CRP, neutrophils and monocytes between groups at multiple time points during the course of the infection. Our findings suggest that the initiation of inflammation occurs before the onset of clinical disease in B. rossi infection and infectious dose influences the onset of the inflammatory response. Treatment not only fails to curb the inflammatory response but may enhance it. Finally, we found that there is an imbalance in pro/anti-inflammatory cytokine concentrations during infection which may promote parasite replication.

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Atkinson, B. K., Thompson, P., Van Zyl, E., Goddard, A., Rautenbach, Y., Schoeman, J. P., Mukorera, V., Leisewitz, A.. 2021-09-16. Kinetics of the inflammatory response during experimental Babesia rossi infection of beagle dogs. https://doi.org/10.1101/2021.09.16.460686

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