We herein present a Brazilian guideline for the management of feline sporotrichosis, a mycosis caused by Sporothrix brasiliensis. This guideline is an effort of a national technical group organized by the Working Group on Sporothrix and Sporotrichosis of the International Society for Human and Animal Mycology (ISHAM). This publication intends to provide information on clinicalepidemiological aspects of this zoonosis, as well as a literature revision. Moreover, it gives some practical information on diagnosis and treatment of feline sporotrichosis. It also contains information that can be helpful for the prevention and control of S. brasiliensis transmission.

Although atopy and blood eosinophilia both influence exhaled nitric oxide (eNO) measurements, no study has quantified their single or combined effect. We assessed the combined effect of atopy and blood eosinophilia on eNO in unselected schoolchildren. In 356 schoolchildren (boys/girls: 168/188) aged 9.0-11.5 yr, we determined eNO, total serum IgE, blood eosinophil counts and did skin prick tests (SPT) and spirometry. Parents completed a questionnaire on their children's current or past respiratory symptoms. Atopy was defined by a SPT >3 mm and eosinophilia by a blood cell count above the 80th percentile (>310 cells/ml). eNO levels were about twofold higher in atopic-eosinophilic subjects than in atopic subjects with low blood eosinophils [24.3 p.p.b. (parts per billion) vs. 14.1 p.p.b.] and than non-atopic subjects with high or low blood eosinophils (24.3 p.p.b. vs. 12.2 p.p.b. and 10.9 p.p.b.) (p <0.001 for both comparisons). The additive effect of atopy and high eosinophil count on eNO levels remained unchanged when subjects were analyzed separately by sex or by a positive history of wheeze (n=60), respiratory symptoms other than wheeze (n=107) or without respiratory symptoms (n=189). The frequency of sensitization to Dermatophagoides (Dpt or Dpf) was similar in atopic children with and without eosinophilia (66.2% and 67.4%, respectively); eosinophilia significantly increased eNO levels in Dp-sensitized children as well in children sensitized to other allergens. In a multiple linear regression analysis, eNO levels were mainly explained by the sum of positive SPT wheals and a high blood eosinophil count (t=4.8 and 4.3, p=0.000), but also by the presence of respiratory symptoms (especially wheeze) and male sex (t=2.6 and 2.0, p=0.009 and 0.045, respectively). Measuring eNO could be a simple, non-invasive method for identifying subjects at risk of asthma in unselected school populations.

American Thoracic Society (ATS) guidelines recommend to refrain from spirometry or exercise before measuring fractional exhaled nitric oxide (FENO) because forced breathing maneuvers might influence FENO values. However the few studies already reported in children have given conflicting results. The aim of the study was to observe to what extent spirometry or exercise could affect FENO in asthmatic children. Twenty-four asthmatic children (mean age 12.8 yr) were enrolled. Measurements of FENO were performed before and 5, 15, 30, 45 and 60 min after spirometry or a 6-min walk test, on two separate days in random order. Geometric mean FENO at baseline was 25.6 parts per billion (ppb) before spirometry and 23.5 ppb before exercise. A small drop of FENO to 24.2 and 23.7 ppb was found 5 and 15 min after spirometry (both p = 0.04). After exercise, FENO values showed a larger drop to 18.5 ppb after 5 min and 20.7 ppb after 15 min (p < 0.001; p = 0.004 respectively). Changes in FENO occurred after exercise irrespective of baseline FENO and values returned to baseline within 30 min. We conclude that both spirometry and exercise affect FENO in asthmatic children. As the changes after exercise may lead to erroneous interpretations, children should refrain from physical exercise during at least 30 min before FENO measurements.

Lay Summary Cat-transmitted sporotrichosis is a zoonosis in geographic expansion from Brazil to other Latin American countries, and considered a public health problem. Data suggest that transmission can occur through the sneeze of an infected cat. The One Health approach is necessary to control the disease.

Sporotrichosis has become an important zoonosis in Brazil and Sporothrix brasiliensis is the primary species transmitted by cats. Improvement of animal treatment will help control and limit the spread and geographic expansion of sporotrichosis. Accordingly, buparvaquone, an antiprotozoal hydroxynaphthoquinone agent marketed as Butalex®, was evaluated in vitro and in vivo against feline-borne isolates of S. brasiliensis . Buparvaquone inhibited in vitro fungal growth at concentrations 4-fold lower than itraconazole (the first-choice antifungal used for sporotrichosis) and was 408 times more selective for S. brasiliensis than mammalian cells. Yeasts treated with a subinhibitory concentration of buparvaquone exhibited mitochondrial dysfunction, ROS and neutral lipid accumulation, and impaired plasma membranes. Also, scanning electron microscopy images revealed buparvaquone altered cell wall integrity and induced cell disruption. I n vivo experiments in a Galleria mellonella model revealed that buparvaquone (single dose of 5 mg/kg) is more effective than itraconazole against infections with S. brasiliensis yeasts. Combined, our results indicate that buparvaquone has a great in vitro and in vivo antifungal activity against S. brasiliensis , revealing the potential application of this drug as an alternative treatment for feline sporotrichosis.