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.

Fine-Scale Landscape Epidemiology: Sarcoptic Mange in Bare-Nosed Wombats (Vombatus ursinus)

“…Te pathogen is of global signifcance, present on all continents (except Antarctica) and documented in approximately 150 species across 12 mammalian orders, including humans, domestic animals, and wildlife [7]. Infection typically results in type I (immediate) or type IV (delayed) hypersensitivity reactions, characterized by a range of highly visible signs, such as alopecia, hyperkeratosis, emaciation, and pruritus [8,9]. Terefore, unlike many wildlife diseases that require laboratory diagnosis, mange can be diagnosed non-invasively via visual assessment and is thus more readily documented in free-ranging wildlife [10,11].…”

Diseases of Iberian ibex (Capra pyrenaica)

“…1 ). However, S. scabiei infestation has further multisystemic consequences beyond the local skin lesions (Espinosa et al 2020 ), including a reduction in body condition, hematological and serum biochemical disorders (Perez et al 2015 ), increase in oxidative stress with a decrease in the antioxidant status (Saleh et al 2011 ; Espinosa et al 2017b ; Naesborg-Nielsen et al 2022 ), and/or inflammatory acute phase protein response (Ráez-Bravo et al 2015 ; Pastor et al 2019 ), with amyloid deposits in parenchymal organs (Espinosa et al 2017d , 2020 ). All these changes contribute to the pathogenesis of the disease, reducing survival and/or hampering the recovery of ibexes in chronic stages of sarcoptic mange.…”

Commentary: Transcriptome analysis of host inflammatory responses to the ectoparasitic mite Sarcoptes scabiei var. hominis

“…Previous studies on scabies based on measurement of cytokines in peripheral blood stimulated with mite antigens have characterized ordinary scabies as a Th1 response, and crusted scabies as a non-protective, Th2 response ( 16 ). A recent meta-analysis ( 5 ) describes sarcoptic mange and evidence supporting either Type I or Type IV hypersensitivity, and unfortunately excluded studies on humans and the transcriptomic studies described herein. Such compartmentalization is too generalist.…”

“…There are few studies on the immunology of scabies, and those that do exist are mostly based on small case numbers, lack appropriate controls, or focus on a small number of candidate molecules ( 5 ). Relative to other parasitic diseases, scabies is especially difficult to study due to the inability to maintain mites in culture, and a historical lack of tractable animal models for in-vivo study ( 6 ).…”