Evidence underscoring immunological and clinical pathological changes associated with Sarcoptes scabiei infection: synthesis and meta-analysis

Abstract

Background: Sarcoptes scabiei is one of the most impactful mammalian parasites. There has been much research on immunological and clinical pathological changes associated with S. scabiei parasitism across a range of host species. This rich body of literature is complex, and we seek to bring that complexity together in this study. We first (1) synthesise narrative reviews of immunopathological relationships to S. scabiei infection to construct overarching hypotheses; then (2) undertake a systematic meta-analysis of primary literature on immunological and clinical pathological changes; and lastly (3) contrast our findings from the meta-analysis to our synthesis from narrative reviews.

Methods: We synthesised 55 narrative reviews into two overarching hypotheses representing type I and type IV immune responses to S. scabiei infection. We then systematically extracted all literature reporting immunological variables, acute phase proteins, oxidant/antioxidant status, and erythrocytic, hepatological and nephrological changes, calculating 565 effect sizes between controls and sarcoptic mange affected groupings, refining (simplifying) hypotheses from narrative reviews.

Results: Immunological and clinical pathological parameters were most often studied in dogs (n = 12) and humans (n = 14). Combining immunological and clinical pathological information across mammalian species (n = 19) helped yield general insights into observed disease responses. This is evidenced by interspecific consensus in 27 immunological and clinical pathology variables (6/26 type I hypersensitivity, 3/20 type IV hypersensitivity, 6/10 oxidant/antioxidant status, 3/6 acute phase protein, 4/7 erythrocytic, and 5/10 hepatological/nephrological).

Conclusions: Elevated IgE, eosinophils and mast cells in type I hypersensitivity response corresponded to what was described in narrative reviews. Results from type IV hypersensitivity response suggested typical antibody response, however cell-mediated response was less evident. Some consensus of acute phase protein response and shifted oxidant/antioxidant balance and slight evidence of anemia. We highlight the need for mange/scabies studies to more routinely compare immunological and clinical pathological changes against controls, and include collection of a more standardised suite of variables among studies.

Keywords: Immunology; Meta-analysis; Pathology; Sarcoptes scabiei; Sarcoptic mange; Scabies.

Fig. 1

Diagrams of the immunopathological cascades arising from Sarcoptes scabiei infection depending on host hypersensitivity response (Type I or IV). Diagram A represents the immunopathological processes as currently proposed in narrative literature reviews of S. scabiei, and diagram B represents the Immunopathological relationships supported by the meta-analysis undertaken in this study. Solid arrow ( →) indicates a stimulation or influence from one parameter to the other, whereas a dashed arrow (– →) indicates a hypothesised link; small up or down triangle next to parameter indicates an increase or decrease; red text indicates missing immunological links considered likely to connect parameters; Parameters in non-bold indicates secreted cytokines or immunoglobulins; *in panel B IV indicates no direct measure of macrophages instead measured by MCP-1; **in panel A IV indicates epidermal cells to include keratinocytes, Langerhans cells and fibroblasts; *** in panel B indicates no direct measure of T cells or B cells however could be included in the measurement of lymphocytes. IL interleukin; IFN-γ Interferon gamma; TNF-α tumour necrosis factor alpha; TGF-ß transforming growth factor beta; CD4+= T helper cells; CD8+ cytotoxic T cells; Ig immunoglobulin; C3 complement 3; MCV mean corpuscular volume; TEC total erythrocyte concentration; PCV packed cell volume; AGP Acid(1)-alpha glycoprotein; SAA serum amyloid A; A:G ratio albumin:globulin ratio; ALT alanine aminotransferase; BUN blood urea nitrogen; MCHC mean corpuscular haemoglobin concentration; MCH mean corpuscular haemoglobin; LPO lipid peroxidation; CAT catalase; GSH:GSSH free glutathione:oxidized glutathione ratio; GGT Gamma-glutamyl transferase. Created in Inkscape

Fig. 2

Heatmap illustrating the four host species for which effect sizes were most commonly calculated (dog = 138, human = 76, bare-nosed wombat = 67 and Iberian ibex = 63). The heat reflects the percentage of studies for each category (immunological process) with each category amounting to a total of 100%. Parameters not falling directly into a definitive category, such as ‘Erythrocytic changes or ‘Acute phase proteins’, were included in the category ‘Other’