IL-10 deficiency protects hamsters from Leptospira infection

Leptospirosis is a globally spread zoonotic disease with outcomes ranging from subclinical infection to fatal Weil syndrome. In addition to antibiotics, some immune activators have shown protective effects against leptospirosis. However, the unclear relationship between Leptospira and cytokines, has limited the development of antileptospiral immunomodulators. In this study, the particular role of IL-10 in leptospirosis was explored by using IL-10 defective (IL-10 -/- ) hamsters. After Leptospira infection, an improved survival rate, reduced leptospiral burden and alleviation of organ lesions were found in IL-10 -/- hamsters compared with WT hamsters. In addition, the gene expression levels of IL-1β, IL-6 and TNF-α and the NO level were higher in IL-10 -/- hamsters than in WT hamsters. Our results indicate that IL-10 deficiency protects hamsters from Leptospira infection.

Risk Stratifying and Prognostic Analysis of Subclinical Cardiac Implantable Electronic Devices Infection: Insight From Traditional Bacterial Culture

Background Subclinical infection of cardiac implantable electronic devices (CIEDs) is a common condition and increases the risk of clinical infection. However, there are limited studies focused on risk stratifying and prognostic analysis of subclinical CIED infection. Methods and Results Data from 418 consecutive patients undergoing CIED replacement or upgrade between January 2011 and December 2019 were used in the analysis. Among the patients included, 50 (12.0%) were detected as positive by bacterial culture of pocket tissues. The most frequently isolated bacteria were coagulase‐negative staphylococci (76.9%). Compared with the noninfection group, more patients in the subclinical infection group were taking immunosuppressive agents, received electrode replacement, or received CIED upgrade and temporary pacing. Patients in the subclinical infection group had a higher PADIT (Prevention of Arrhythmia Device Infection Trial) score. Univariable and multivariable logistic regression analysis found that use of immunosuppressive agents (odds ratio [OR], 6.95 [95% CI, 1.44–33.51]; P =0.02) and electrode replacement or CIED upgrade (OR, 6.73 [95% CI, 2.23–20.38]; P =0.001) were significantly associated with subclinical CIED infection. Meanwhile, compared with the low‐risk group, patients in the intermediate/high‐risk group had a higher risk of subclinical CIED infection (OR, 3.43 [95% CI, 1.58–7.41]; P =0.002). After a median follow‐up time of 36.5 months, the end points between the subclinical infection group and noninfection group were as follows: composite events (58.0% versus 41.8%, P =0.03), rehospitalization (54.0% versus 32.1%, P =0.002), cardiovascular rehospitalization (32.0% versus 13.9%, P =0.001), CIED infection (2.0% versus 0.5%, P =0.32), all‐cause mortality (28.0% versus 21.5%, P =0.30), and cardiovascular mortality (10.0% versus 7.6%, P =0.57). Conclusions Subclinical CIED infection was a common phenomenon. The PADIT score had significant value for stratifying patients at high risk of subclinical CIED infection. Subclinical CIED infection was associated with increased risks of composite events, rehospitalization, and cardiovascular rehospitalization.

A Study of Hepatitis A Seroprevalence in a Paediatric and Adolescent Population of the Province of Florence (Italy) in the Period 2017–2018 Confirms Tuscany a Low Endemic Area

Background: Italy is considered an area with very low HAV (hepatitis A virus) endemicity. Currently in Italy the anti-HAV vaccine is recommended only for specific risk groups and there is no universal vaccination program. The aim of this study was to assess the level of immunity against hepatitis A in a sample of children and adolescents from the province of Florence. Methods: A total of 165 sera were collected from subjects aged 1 to 18 years, proportionally selected according to the general population size and stratified by age and sex. A qualitative evaluation of anti-HAV antibodies was performed using the enzyme-linked immunosorbent assay (ELISA). Anamnestic and vaccination status data were also collected. Results: Our study showed a hepatitis A seroprevalence of 9.1% in the enrolled population. A statistically significant difference in the prevalence of anti-HAV was found between Italian and non-Italian subjects. About half of the population having anti-HAV antibodies was reported to be vaccinated, and no cases of hepatitis A were found. Conclusions: The data from our study confirmed Tuscany as an area with low HAV endemicity and showed that hepatitis A seroprevalence is significantly higher in foreign children and adolescents. The presence of more seropositive subjects than those vaccinated was probably due to a natural immunization achieved through a subclinical infection and/or to underreporting of the surveillance systems.

Pancreatic candidiasis in a cat

Case summary An 11-year-old female spayed Maine Coon cat was referred for assessment of hyporexia, weight loss, vomiting and diarrhoea. An abdominal ultrasound revealed an enlarged and hypoechoic pancreas containing two large fluid-filled structures. Fine-needle aspiration of the cyst-like structures was performed, and cytology revealed moderate-to-marked predominantly suppurative inflammation with yeast cells. Candida glabrata was cultured from the fluid. The patient was treated with oral itraconazole and the clinical signs resolved, although repeat abdominal ultrasound and cytology revealed persistence of the infected cyst-like structures. The patient remained asymptomatic for 8 months after the discontinuation of antifungal medications, despite the persistence of the pancreatic infection with C glabrata. Relevance and novel information To our knowledge, this is the first report of pancreatic infection with Candida species in a cat, followed by a chronic subclinical infection persisting for at least 8 months after treatment discontinuation.

Alpha-1 Acid Glycoprotein as a Biomarker for Subclinical Illness and Altered Drug Binding in Rats

Alpha-1 acid glycoprotein (AGP) is a significant drug binding acute phase protein that is present in rats. AGP levels are known to increase during tissue injury, cancer and infection. Accordingly, when determining effective drug ranges and toxicity limits, consideration of drug binding to AGP is essential. However, AGP levels have not been well established during subclinical infections. The goal of this study was to establish a subclinical infection model in rats using AGP as a biomarker. This information could enhance health surveillance, aid in outlier identification, and provide more informed characterization of drug candidates. An initial study (n = 57) was conducted to evaluate AGP in response to various concentrations of Staphylococcus aureus (S. aureus) in Sprague–Dawley rats with or without implants of catheter material. A model validation study (n = 16) was then conducted using propranolol. Rats received vehicle control or S. aureus and when indicated, received oral propranolol (10 mg/kg). Health assessment and blood collection for measurement of plasma AGP or propranolol were performed over time (days). A dose response study showed that plasma AGP was elevated on day 2 in rats inoculated with S. aureus at 106, 107 or, 108 CFU regardless of implant status. Furthermore, AGP levels remained elevated on day 4 in rats inoculated with 107 or 108 CFUs of S. aureus. In contrast, significant increases in AGP were not detected in rats treated with vehicle or 103 CFU S. aureus. In the validation study, robust elevations in plasma AGP were detected on days 2 and 4 in S. aureus infected rats with or without propranolol. The AUC levels for propranolol on days 2 and 4 were 493 ± 44 h × ng/mL and 334 ± 54 h × ng/mL, respectively), whereas in noninfected rats that received only propranolol, levels were 38 ± 11 h × ng/mL and 76 ± 16. h × ng/mL, respectively. The high correlation between plasma propranolol and AGP demonstrated a direct impact of AGP on drug pharmacokinetics and pharmacodynamics. The results indicate that AGP is a reliable biomarker in this model of subclinical infection and should be considered for accurate data interpretation.

Herpes Zoster in an Immunocompetent Child without a History of Varicella

Herpes zoster is a relatively rare infectious disease in the pediatric population, as compared with adults, which is due to the reactivation of latent Varicella−Zoster virus. We report a 7-year-old child without any history of varicella, who first experienced skin pain and later presented skin lesions in dermatomal distribution. Finally, the patient was diagnosed with herpes zoster. We aim to emphasize that herpes zoster could occur in immunocompetent children and may be due to the reactivation of the vaccine strain or previous subclinical infection.

Subclinical Onychomycosis in Apparently Healthy Adults

<b><i>Introduction:</i></b> Onychomycosis is a frequent chronic nail infection, with a worldwide prevalence of 5.5% making it the most common nail disease, and its incidence increases with age. Clinically, it causes discoloration and thickening of the nail plate and may be accompanied by onycholysis. However, little is known of the subclinical infection. <b><i>Methods:</i></b> We studied adult male and female outpatients auto-referred as healthy and that had healthy appearing toenails. Nail distal clippings were obtained from the right first toenail. This sample was stained with PAS and observed by an expert dermatopathologist searching for fungal structures. <b><i>Results:</i></b> A total of 32 samples were included: 8 from men (25%) and 24 from women (75%), with ages ranging from 27 to 66 years (mean age of 43 years). Twenty-four patients did not present any histopathological finding suggestive of infection (75%), while 7 patients had a single finding (spores or hyphae) (21.8%), and 1 patient had both findings (3.12%). <b><i>Discussion/Conclusion:</i></b> We found 4 patients with yeasts, 3 with hyphae, and 1 patient with a combined infection with both yeasts and hyphae (3.1%). These add up to 25% of the clinically apparent healthy nails. Our results show that we still have much to learn from the initial stages of onychomycosis and that our population probably has higher incidence of this nail disease, so we must be alert to subtle nail changes. As our participants signed an informed consent, we will contact those that resulted positive for follow up consultations.