Efficacy and Pharmacokinetics Evaluation of a Single Oral Dose of Afoxolaner against Sarcoptes scabiei in the Porcine Scabies Model for Human Infestation.

Scabies is a major and potentially growing public health problem worldwide with an unmet need for acaricidal agents with greater efficacy and improved pharmacological properties for its treatment. The objective of the present study was to assess the efficacy and describe the pharmacokinetics profile of a novel acaricide, afoxolaner (AFX), in a relevant experimental porcine model. Twelve pigs were experimentally infested and either treated with 2.5 mg/kg single dose oral AFX (n = 4) or 0.2 mg/kg, two doses 8 days apart, oral ivermectin ([IVM] n = 4) or not treated for scabies (n = 4). The response to treatment was assessed by the reduction of mite counts in skin scrapings as well as clinical and pruritus scores over time. Plasma and skin pharmacokinetics profiles for both AFX and IVM were evaluated. AFX efficacy was 100% at days 8 and 14 posttreatment and remained unchanged until the study end (day 45). IVM efficacy was 86% and 97% on days 8 and 14, respectively, with a few mites recovered at the study end. Clinical and pruritus scores decreased in both treated groups and remained constant in the control group. Plasma mean residence times (MRT) were 7.1 ± 2.4 and 1.1 ± 0.2 days for AFX and IVM, respectively. Skin MRT values were 16.2 ± 16.9 and 2.7 ± 0.5 days for AFX and IVM, respectively. Overall, a single oral dose of AFX was efficacious for the treatment of scabies in experimentally infested pigs and showed remarkably long MRTs in plasma and, notably, in the skin.

Acute phase proteins increase with sarcoptic mange status and severity in Iberian ibex (Capra pyrenaica, Schinz 1838).

Sarcoptic mange is a contagious skin disease caused by Sarcoptes scabiei, affecting both domestic and wild mammals, including the Iberian ibex (Capra pyrenaica), a medium-sized mountain ungulate almost endemic to the Iberian Peninsula. Acute phase proteins (APPs) could be an indicator of sarcoptic mange disease and severity in Iberian ibex. Serum samples from 131 healthy and sarcoptic mange-affected Iberian ibexes were collected from 2005 to 2012 in Sierra Nevada Natural Space in southern Spain. Serum alpha-1-acid glycoprotein (AGP), serum amyloid A (SAA) and haptoglobin (Hp) concentrations were quantified, and statistically significant differences according to sarcoptic mange disease and severity were assessed. Both AGP and SAA were significantly higher in the sarcoptic mange-affected ibexes than in the healthy ones as well as in the severely affected ibexes as compared to those with less than 50 % of the body surface affected. For the first time, changes in APP are reported in relation to sarcoptic mange in Iberian ibex. It is also reported for the first time that the intensity of APP increase depends on the severity of sarcoptic mange, which could be related with the pathological secondary amyloidosis, leading to organ dysfunction in severely mange-affected animals. Species and population differences in the increase of APP in response to sarcoptic mange could indicate individual and population differences in the immune capability of each population to deal with mange, population prevalence and mortality being the last indicators of such sensitivity.

Domestic mites on the hair/scalp, pillows, and mattresses of mite-sensitized children in a subtropical area

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Assay of alterations in oxidative stress markers in pigs naturally infested with Sarcoptes scabiei var. suis.

The present study aimed to examine the status of antioxidant systems of the pigs naturally suffering from sarcoptic mange. Fifty nine pigs were divided into three groups, healthy control (group I, n=15), subclinical sarcoptic mange (group II, n=22) and clinical sarcoptic mange (group III, n=22). To assess the status of antioxidant systems; lipid peroxides (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), ascorbic acid, zinc and copper concentrations in the blood samples as well as LPO, SOD, CAT and glutathione-s-transferase (GST) activities in the skin were measured. The GSH, SOD, GPx, ascorbic acid, zinc, copper concentrations in blood were significantly lower in the pigs suffering from clinical and subclinical sarcoptic mange, when compared with the healthy control. However, LPO content of these infested pigs was significantly higher. The CAT, SOD and GST activities in the skin of the diseased pigs were significantly lower, whereas LPO was significantly higher as compared to the healthy control. From the present study, it may be concluded that sarcoptic mange bestows remarkable alterations in the oxidative stress markers and imposes compromisation of the antioxidant status of the infested pigs.

Scabies mite inactive serine proteases are potent inhibitors of the human complement lectin pathway.

Scabies is an infectious skin disease caused by the mite Sarcoptes scabiei and has been classified as one of the six most prevalent epidermal parasitic skin diseases infecting populations living in poverty by the World Health Organisation. The role of the complement system, a pivotal component of human innate immunity, as an important defence against invading pathogens has been well documented and many parasites have an arsenal of anti-complement defences. We previously reported on a family of scabies mite proteolytically inactive serine protease paralogues (SMIPP-Ss) thought to be implicated in host defence evasion. We have since shown that two family members, SMIPP-S D1 and I1 have the ability to bind the human complement components C1q, mannose binding lectin (MBL) and properdin and are capable of inhibiting all three human complement pathways. This investigation focused on inhibition of the lectin pathway of complement activation as it is likely to be the primary pathway affecting scabies mites. Activation of the lectin pathway relies on the activation of MBL, and as SMIPP-S D1 and I1 have previously been shown to bind MBL, the nature of this interaction was examined using binding and mutagenesis studies. SMIPP-S D1 bound MBL in complex with MBL-associated serine proteases (MASPs) and released the MASP-2 enzyme from the complex. SMIPP-S I1 was also able to bind MBL in complex with MASPs, but MASP-1 and MASP-2 remained in the complex. Despite these differences in mechanism, both molecules inhibited activation of complement components downstream of MBL. Mutagenesis studies revealed that both SMIPP-Ss used an alternative site of the molecule from the residual active site region to inhibit the lectin pathway. We propose that SMIPP-Ss are potent lectin pathway inhibitors and that this mechanism represents an important tool in the immune evasion repertoire of the parasitic mite and a potential target for therapeutics.

Acute phase protein response in the capybara (Hydrochoerus hydrochaeris).

We evaluated the acute phase protein response in capybaras (Hydrochoerus hydrochaeris). Three animal groups were used: 1) healthy animals (n=30), 2) a group in which experimental inflammation with turpentine was induced (n=6), and 3) a group affected with sarcoptic scabies (n=14) in which 10 animals were treated with ivermectin. Haptoglobin (Hp), acid-soluble glycoprotein (ASG) and albumin were analyzed in all animals. In those treated with turpentine, Hp reached its maximum value at 2 wk with a 2.7-fold increase, whereas ASG increased 1.75-fold and albumin decreased 0.87-fold 1 wk after the induction of inflammation. Capybaras affected with sarcoptic scabies presented increases in Hp and ASG of 4.98- and 3.18-fold, respectively, and a 0.87-fold decrease in albumin, compared with healthy animals. Haptoglobin and ASG can be considered as moderate, positive acute phase proteins in capybaras because they showed less than 10-fold increases after an inflammatory process and reached their peak concentrations 1 wk after the induction of inflammation. Conversely, albumin can be considered a negative acute phase protein in capybaras because it showed a reduction in concentration after inflammatory stimulus.

Alterations in hepatic lipid peroxides and antioxidant profile in Indian water buffaloes suffering from sarcoptic mange.

The present study was aimed to examine the status of antioxidants in water buffaloes with sarcoptic mange. Sixty-three buffaloes were divided into three groups, healthy control (group I, n=19), subclinical sarcoptic mange (group II, n=22) and clinical sarcoptic mange (group III, n=22). Lipid peroxides (LPO), superoxide dismutase (SOD), catalase (CAT), zinc and copper in hepatic tissues and serum alpha-tocopherol concentrations were measured. In comparison to group I, LPO was significantly (P<0.05) higher, while SOD and CAT were significantly (P<0.05) lower in group III. LPO and SOD activities were comparable between group I and II, but CAT was significantly (P<0.05) lower in group II. In group III, zinc, copper and alpha-tocopherol concentrations were significantly (P<0.05) lower than group I. Decrease in antioxidant enzyme activities and trace mineral concentrations suggested that sarcoptic mange in buffaloes is associated with compromise in antioxidant defense and oxidative stress may play important role in pathogenesis.

Langerhans cell hyperplasia in scabies: a mimic of Langerhans cell histiocytosis.

AIM: In the absence of mites, the histologic diagnosis of human scabies can be difficult. Scabies can mimic a variety of inflammatory and lymphoproliferative disorders. It is under-recognized that scabies can also mimic Langerhans cell histiocytosis. METHODS: Sixteen examples of scabies were reviewed histologically and immunohistochemically (CD1a, CD3, CD20, CD30 and S100). RESULTS: Immunohistochemical labeling showed florid CD1a and S100 positivity in most cases, indicative of Langerhans cell hyperplasia. Scattered CD30+ lymphocytes were also typically present, within a dense infiltrate, primarily composed of T lymphocytes and eosinophils. CONCLUSION: Because of the prominent CD1a+/S100+ component, scabies can mimic Langerhans cell histiocytosis. This finding should be considered in conjunction with scattered CD30+ cells and clinical features to avoid misdiagnosis.

Dermal absorption of permethrin following topical administration.

OBJECTIVE: Permethrin is an insecticide used in the treatment of lice and scabies infections. Although its efficacy and safety have been well documented, pharmacokinetic data are sparse. The objective of this study was to determine the systemic exposure of permethrin and the duration of residence in the human body following topical administration. METHODS: The study consisted of three parts. In six young healthy men (part 1), 50 ml of an ethanolic solution containing 215 mg permethrin (cis/trans: 25/75) was administered to the hair of the head. In another six young healthy men (part 2) and in six male or female scabies patients (part 3), 60 g of cream containing 3 g permethrin was administered to the skin of the whole body. Urine was collected up to 168 h post-dose. Urinary excretion of the main metabolite of permethrin, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, and its conjugates was measured using a gas chromatography/electron capture detection method. RESULTS: Pharmacokinetics were similar in all study parts. The time of maximal urinary excretion rate was 12.3, 20.0 and 14.6 h, terminal elimination half-life was 32.7, 28.8 and 37.8 h and urinary recovery of the metabolite reached 0.35, 0.47 and 0.52 M percent of the permethrin dose, respectively, in parts 1, 2 and 3 (means). The treatment was well tolerated. CONCLUSIONS: The extent of systemic exposure following external therapeutic administration of permethrin is very low compared with doses used for preclinical toxicity studies, and elimination is virtually complete after 1 week. These data provide the pharmacokinetic basis for the clinical safety of topical permethrin.

Ascorbic acid content of blood plasma, erythrocytes, leukocytes and liver in camels (Camelus dromedarius) without or with parasite infections.

Healthy camels (Camelus dromedaris) and those naturally infected with trypanosomiasis, sarcoptic mange, and helminthiasis were compared as to ascorbic acid (vitamin C) contents of red blood cells, white blood cells, whole blood, plasma, and liver. The camels were kept under natural grazing conditions in Sudan. Reduced levels of vitamin C were found in camels with parasite infections, especially in animals with trypanosomiasis. It is suggested that the low vitamin C status in infected camels is caused by increased utilization and/or decreased synthesis of vitamin C.

Scabietic nodules: a dermatopathologic and immunofluorescent study.

Mites and their eggs were thought to be rarely found in nodular lesions of scabies. However, serial sections from 27 scabietic scrotal papules or nodules revealed mite parts in 22% (6/27). This supports the contention that scabietic nodules may result from persisting antigens of mite parts. In contrast to previous studies, vasculitis with fibrinoid degeneration was uncommon (3/27) in our series. This discrepancy may be due to the timing of the biopsies: 2 of 3 cases with vasculitis were associated with diffuse dense infiltration, and vasculitis may be a late event in the development of scabietic nodules. The specificity of immunoreactant deposits along the epidermodermal junction (EDJ) in scabies is controversial. In our study, direct immunofluorescence (DIF) was performed on 13 scabietic nodules. Four (31%) showed immunoreactants at the EDJ and two on blood vessels. Because of the relatively low positive rate, the low intensity of fluorescence, and 3 of 4 cases with positive immunoreactants having only a single class of immunoglobulin, the deposition may only be secondary to inflammation instead of a specific type II immunologic reaction to scabies.

Efficacy and transdermal absorption of permethrin in scabies patients.

The clinical efficacy and transdermal absorption of permethrin, a new synthetic insecticide was investigated in ten scabies patients. All patients were successfully treated with one application of a cream, containing 5% permethrin. Apart from mild postscabies dermatitis no side-effects were observed. The mean weight of cream used per patient was 25 g (range 21-32; mean content of permethrin 1250 mg). The degree of permethrin absorption was assessed indirectly by determination of conjugated and unconjugated cis- and trans-CVA (a metabolite of permethrin) excretion in urine using two dimensional gas chromatography mass spectrometry. It was found that during the first 48 hours the mean estimated absorption was 6 mg (range 3-11), which is approximately 0.5% of the total dose.

Similar epidermal changes in hyperkeratotic scabies of humans and pigs.

We compared some morphological and biochemical aspects of the epidermal changes occurring in hyperkeratotic scabies in humans and domestic pigs. Clinically and histologically, pig skin alterations look very similar to those observed in humans, i.e., brittle hyperkeratosis with parakeratotic crusting and thickening of the epidermis. Parakeratosis seems to correspond to previous passage of scabies mites through the incompletely differentiated layers of the epidermis. Indeed, by serial sectioning we observed beneath the stratum corneum cellular lysis some distance ahead of the mouth parts of the parasites. Epidermal cells surrounding this initial epidermolytic focus finally underwent disturbed terminal differentiation and appeared as parakeratotic cells. In pigs we observed intraepithelial microabscesses, but we rarely observed these in our human subjects.

Demonstration of the percutaneous resorption of a lipophilic pesticide and its possible storage in the human body.

The kinetics of lindane concentration in the serum and the time-dependent urinary excretion of two groups, one with healthy subjects and one with scabies-infested subjects, were comparatively analyzed by gas chromatography. Both groups showed similar cumulative excretion curves at completely different lindane concentrations in the serum. Comparison of serum concentration in healthy females (high lindane concentration in serum) and healthy males (low serum concentration) to the urinary excretion showed similar results. There appears to be a serum 'threshold concentration', above which it is possible that lindane is no longer primarily excreted by the kidney. Based on these results recommendations are presented, for the practical use of such data in the treatment of scabies.