The CARD9 Gene in Koalas (Phascolarctos cinereus): Does It Play a Role in the Cryptococcus-Koala Interaction?

Cryptococcus is a genus of fungal pathogens that can infect and cause disease in a range of host species and is particularly prominent in koalas (Phascolarctos cinerus). Like other host species, koalas display a range of outcomes upon exposure to environmental Cryptococcus, from external nasal colonization to asymptomatic invasive infection and, in rare cases, severe clinical disease resulting in death. Host factors contributing to these varied outcomes are poorly understood. Due to their close relationship with eucalypt trees (a key environmental niche for Cryptococcus gattii) and suspected continual exposure to the pathogen, koalas provide a unique opportunity to examine host susceptibility in natural infections. Caspase recruitment domain-containing protein 9 (CARD9) is a key intracellular signaling protein in the fungal innate immune response. Humans with mutations in CARD9 succumb to several different severe and chronic fungal infections. This study is the first to sequence and explore CARD9 variation in multiple koalas using Sanger sequencing. Four CARD9 exons were successfully sequenced in 22 koalas from a New South Wales, Australia population. We found minimal variation between koalas across all four exons, an observation that was also made when CARD9 sequences were compared between koalas and six other species, including humans and mice. Ten single-nucleotide polymorphisms (SNP) were identified in this study and explored in the context of cryptococcal exposure outcomes. While we did not find any significant association with variation in cryptococcal outcomes, we found a high degree of conservation between species at several SNP loci that requires further investigation. The findings from this study lay the groundwork for further investigations of CARD9 and Cryptococcus both in koalas and other species, and highlight several considerations for future studies.

Neutrophil Oxidative Burst Profile Is Related to a Satisfactory Response to Itraconazole and Clinical Cure in Feline Sporotrichosis.

Despite the central role of cats in the transmission and amplification of Sporothrix, studies regarding immune response in feline sporotrichosis are scarce. In cats with sporotrichosis, neutrophil-rich lesions are usually associated to good general condition and lower fungal burden. However, the role of neutrophils in anti-Sporothrix immunity has been little explored in cats. Thus, the aim of this study was to evaluate the neutrophil oxidative burst in the blood of cats with sporotrichosis. Cats with sporotrichosis included in the study were treated with itraconazole (ITZ) alone or combined with potassium iodide (KI). The neutrophil oxidative burst was evaluated through a flow-cytometry-based assay using dihydrorhodamine 123 (background) and stimulation with Zymosan and heat-killed Sporothrix yeasts. The cure rate was 50.0% in cats under treatment with ITZ monotherapy and 90.9% in cats treated with ITZ + KI (p = 0.014), endorsing the combination therapy as an excellent alternative for the treatment of feline sporotrichosis. Higher percentages of Sporothrix-stimulated neutrophils were associated with good general condition (p = 0.003). Higher percentages of Sporothrix- (p = 0.05) and Zymosan-activated (p = 0.014) neutrophils before and early in the treatment were related to clinical cure in ITZ-treated cats. The correlation between oxidative burst and successful use of KI could not be properly assessed given the low number of failures (n = 2) in this treatment group. Nasal mucosa involvement, typically linked to treatment failure, was related to lower percentages of activated neutrophils in the background at the treatment outcome (p = 0.02). Our results suggest a beneficial role of neutrophils in feline sporotrichosis and a positive correlation between neutrophil activation and the cure process in ITZ-treated cats.

A Randomized Clinical Trial Comparing Itraconazole and a Combination Therapy with Itraconazole and Potassium Iodide for the Treatment of Feline Sporotrichosis.

Feline sporotrichosis is an endemic disease with high occurrence in Brazil. Itraconazole (ITZ) remains the drug of choice for treating this disease in cats, despite the increasing reports of therapeutic failure. A controlled, randomized clinical trial was performed on 166 naive cats with sporotrichosis to assess the effectiveness and safety of the combination therapy with ITZ and potassium iodide (KI) compared with ITZ monotherapy. Cats were randomly allocated into two treatment groups: G1-ITZ 100 mg/cat/day-and G2-ITZ 100 mg/cat/day + KI 2.5-20 mg/kg/day. Cats treated in G2 presented 77% more risk of reaching a clinical cure (a positive effect) than those treated in G1, even when controlled by negative predictors. The survival curves of the two treatment protocols indicate that a clinical cure was achieved faster in G2. An increase in the KI dose was necessary in 28 cats due to the persistence of clinical signs. Adverse reactions were equally frequent in both groups and manageable with a temporary drug suspension and/or a hepatoprotective therapy. The combination therapy was associated with a higher cure rate and a shorter treatment time, suggesting that ITZ+KI arises as a better option for treating feline sporotrichosis and should be considered the first-line treatment, especially in the presence of negative predictors.

A Challenge Called Ogilvie´s Syndrome.

Ogilvie´s syndrome is a colonic dilation without any existing mechanical obstruction. The risk factors that cause it are not completely understood, but if untreated, the distension can result in rupture or ischaemic bowel perforation. Additionally, the existing guidelines do not agree with each other about the next steps if conservative treatment fails. We report the case of a 71-year-old woman in whom Ogilvie´s syndrome was particularly difficult to manage, and with it, we try to add clinical data to a field with scarce evidence.

Advances and challenges in the management of feline sporotrichosis / Avances y desafíos en el manejo de la esporotricosis felina

The domestic cat is the most susceptible host to Sporothrix infection, developing severe clinical forms. Few effective antifungal agents are available for treating feline sporotrichosis, and cases of treatment failure are common. Treatment success depends on cat health status, therapy-related factors, as well as social/economic issues, but it is mainly contingent upon the host–fungus interaction. The owner's adherence is critical and should be reinforced throughout the treatment to increase the chances of a successful outcome. The antifungal agents described for feline sporotrichosis are most often used in monotherapy regimens. Due to cases in which the treatment with itraconazole failed, the use of antifungal agents in combination should be considered to achieve synergy. The combination of itraconazole and potassium iodide represents an important option for the treatment of naïve cats presenting multiple cutaneous lesions, nasal mucosal lesions and/or respiratory signs, as well as for refractory cases. However, the therapeutic options for unsuccessfully treated cases are scarce. Therefore new options are needed, even more taking into account that there are many in vitro potential molecules not available for use in cats yet. More studies are necessary to correlate in vitro antifungal susceptibility tests results and the outcome of cats treated due to sporotrichosis. This review will briefly discuss both the antifungal drugs and treatment protocols used in cats with sporotrichosis, as well as the determinants of treatment failure. (AU)

El gato doméstico es el huésped más susceptible a la infección por Sporothrix, llegando a desarrollar formas clínicas graves. Hay pocos agentes antimicóticos efectivos disponibles para tratar la esporotricosis felina, y los casos de fracaso terapéutico son habituales. El éxito del tratamiento depende del estado de salud del gato, los factores relacionados con la terapia y los problemas sociales/económicos, pero se asocia principalmente con la interacción huésped-hongo. El cumplimiento del tratamiento por parte del propietario es fundamental y debe reforzarse durante todo el proceso para aumentar las posibilidades de éxito. Los agentes antimicóticos descritos para la esporotricosis felina se usan con mayor frecuencia en monoterapia. Debido a los casos de fallo terapéutico en el tratamiento con itraconazol se debe considerar el uso combinado de agentes antifúngicos en sinergia. La combinación de itraconazol y yoduro de potasio es una buena opción en el caso de gatos no tratados previamente y con múltiples lesiones cutáneas, en la mucosa nasal y/o con signos respiratorios, así como para casos refractarios. Sin embargo, las opciones terapéuticas para la mayoría de los casos que fracasan son escasas. Por tanto, son necesarias nuevas opciones terapéuticas, más aún cuando existen muchas moléculas potenciales in vitro, no disponibles de momento para su uso en gatos. Son necesarios más estudios que correlacionen los resultados de las pruebas de sensibilidad in vitro a los antifúngicos con aquellos del tratamiento de gatos con esporotricosis. Esta revisión discutirá brevemente los fármacos antimicóticos y los protocolos terapéuticos utilizados para tratar gatos con esporotricosis, así como los factores determinantes del fracaso del tratamiento. (AU)

Spatial Distribution of Canine Sporotrichosis in Rio de Janeiro, Brazil (1998-2018) and Its Correlation with Socioeconomic Conditions.

Canine sporotrichosis is a poorly described global disease and a spatial approach has not yet been used to assess the disease in dogs. Therefore, this study aimed to describe the occurrence of canine sporotrichosis in the state of Rio de Janeiro, Brazil, from 1998 to 2018 and its correlation with socioeconomic characteristics using exploratory spatial data analysis. A total of 295 cases of canine sporotrichosis were identified and 249 were georeferenced. There was a higher concentration of cases in the municipality of Rio de Janeiro, as well as along the border of the city and the adjacent municipalities in the great metropolitan area. The cases occurred in areas where most of the dwellings are houses. Moreover, no focus of disease density was found in the southern part of Rio de Janeiro city over the period studied, possibly due to better socioeconomic conditions. Areas with a high concentration of canine sporotrichosis cases coincided with regions that possessed a low proportion of households without paving, suggesting that the disease is not necessarily linked to extreme poverty. The mapping of areas with a greater density of cases is fundamental to formulate targeted and strategic plans in order to implement effective public health prevention and control measures.

Two Years of Evolutionary Dynamics of SARS-CoV-2 in Mexico, With Emphasis on the Variants of Concern.

Background: The advance of the COVID-19 pandemic and spread of SARS-CoV-2 around the world has generated the emergence of new genomic variants. Those variants with possible clinical and therapeutic implications have been classified as variants of concern (VOCs) and variants of interest (VOIs). Objective: This study aims to describe the COVID-19 pandemic and build the evolutionary and demographic dynamics of SARS-CoV-2 populations in Mexico, with emphasis on VOCs. Methods: 30,645 complete genomes of SARS-CoV-2 from Mexico were obtained from GISAID databases up to January 25, 2022. A lineage assignment and phylogenetic analysis was completed, and demographic history for Alpha, Gamma, Delta and Omicron VOCs, and the Mexican variant (B.1.1.519) was performed. Results: 148 variants were detected among the 30,645 genomes analyzed with the Delta variant being the most prevalent in the country, representing 49.7% of all genomes. Conclusion: The COVID-19 pandemic in Mexico was caused by several introductions of SARS-CoV-2, mainly from the United States of America and Europe, followed by local transmission. Regional molecular epidemiological surveillance must implement to detect emergence, introductions and spread of new variants with biologically important mutations.

Advances and challenges in the management of feline sporotrichosis.

The domestic cat is the most susceptible host to Sporothrix infection, developing severe clinical forms. Few effective antifungal agents are available for treating feline sporotrichosis, and cases of treatment failure are common. Treatment success depends on cat health status, therapy-related factors, as well as social/economic issues, but it is mainly contingent upon the host-fungus interaction. The owner's adherence is critical and should be reinforced throughout the treatment to increase the chances of a successful outcome. The antifungal agents described for feline sporotrichosis are most often used in monotherapy regimens. Due to cases in which the treatment with itraconazole failed, the use of antifungal agents in combination should be considered to achieve synergy. The combination of itraconazole and potassium iodide represents an important option for the treatment of naïve cats presenting multiple cutaneous lesions, nasal mucosal lesions and/or respiratory signs, as well as for refractory cases. However, the therapeutic options for unsuccessfully treated cases are scarce. Therefore new options are needed, even more taking into account that there are many in vitro potential molecules not available for use in cats yet. More studies are necessary to correlate in vitro antifungal susceptibility tests results and the outcome of cats treated due to sporotrichosis. This review will briefly discuss both the antifungal drugs and treatment protocols used in cats with sporotrichosis, as well as the determinants of treatment failure.

A Possible Link between the Environment and Cryptococcus gattii Nasal Colonisation in Koalas (Phascolarctos cinereus) in the Liverpool Plains, New South Wales.

Cryptococcosis caused by yeasts of the Cryptococcus gattii species complex is an increasingly important mycological disease in humans and other mammals. In Australia, cases of C. gattii-related cryptococcosis are more prevalent in the koala (Phascolarctos cinereus) compared to humans and other animals, likely due to the close association that both C. gattii and koalas have with Eucalyptus species. This provides a cogent opportunity to investigate the epidemiology of spontaneous C. gattii infections in a free-living mammalian host, thereby offering insights into similar infections in humans. This study aimed to establish a link between nasal colonisation by C. gattii in free-ranging koalas and the tree hollows of Eucalyptus species, the key environmental source of the pathogen. We (i) detected and genotyped C. gattii from nine out of 169 free-ranging koalas and representative tree hollows within their home range in the Liverpool Plains, New South Wales, and (ii) examined potential environmental predictors of nasal colonisation in koalas and the presence of C. gattii in tree hollows. Phylogenetic analyses based on multi-locus sequence typing (MLST) revealed that the koalas were most likely colonised by the most abundant C. gattii genotypes found in the Eucalyptus species, or closely related genotypes. Importantly, the likelihood of the presence of C. gattii in tree hollows was correlated with increasing hollow size.

Hepato-pathological hallmarks for the surveillance of Yellow Fever in South American non-human primates.

The early detection and diagnosis of deaths in free-ranging non-human primates (NHPs) are key points for the surveillance of Yellow Fever (YF) in Brazil. The histopathological identification of infectious diseases remains very useful and reliable in the screening and detection of emerging zoonotic diseases such as YF. We surveyed data records and liver slides stained with hematoxylin and eosin from the Epizootics Surveillance Network to control YF, Ministry of Health of Brazil, to evaluate histopathological hallmarks for the diagnosis of the YF virus infection. We selected natural fatal cases in NHPs from the genera Alouatta spp., Callithrix spp., and Sapajus spp. with a positive immunohistochemical assay for YF in liver samples. Our findings showed the full-spectrum YF-associated hepatic lesions in all NHPs, but some histopathological findings differed in the distribution and intensity between the three genera. In our study, South American NHPs showed significant differences in the YF-associated hepatic histopathological features compared to fatal cases reported in humans.

Associations Between Depressive Symptoms and Physical Activity Intensity in an Older Adult Population During COVID-19 Lockdown.

INTRODUCTION: The COVID-19 pandemic led to the implementation of physical-social distancing measures-including self-isolation, home confinement, and quarantine around the world, with psychological consequences such as depression. Older adults are especially likely to develop depressive symptomatology. This study aims to investigate the association between physical activity intensities and sedentary behavior with depression levels among previously active older adults during the COVID-19 lockdown. METHODS: A total of 1,123 physically active older Brazilian adults (67.68 ± 5.91 years, 91.00% female) were interviewed by telephone in regard to sociodemographic, general health status, depression (GDS-15), and physical activity (IPAQ-SV) after being home-confined for 11.59 ± 2.42 weeks. Participants were also asked to self-report changes in their physical activity levels and time spent sitting. Descriptive statistics (mean, frequencies), between-groups comparisons (t-tests and chi-square), and hierarchical regression analysis were used. RESULTS: About 83.80% of older adults self-reported a decrease in daily physical activity levels and 73.90% increased sitting time. Overall, depressive symptoms were observed in 30.40, and 20.80% met physical activity recommendations. Daily moderate (ß = -0.174; 95% CI = -0.026; -0.012) and moderate-to-vigorous (ß = -0.183; 95% CI = -0.023; 0.011) physical activity intensities were negatively associated with depression score explaining 2.6 and 2.9% of depression variability, respectively, after adjusting for age, gender, education level, body mass index, and polypharmacy. Daily walking and sitting time were not associated with the depression score (p > 0.05). CONCLUSION: The results provide empiric suggestion supporting moderate to vigorous physical activity as a way to reduce depressive levels among older adults during COVID-19 confinement. Supervised home-based exercise programs, specifically designed for older adults, might be an important strategy to maintain and improve older adults' mental health.

Predictors of Lower Depression Levels in Older Adults During COVID-19 Lockdown.

BACKGROUND: Social distancing during the COVID-19 pandemic may lead to adverse mental health consequences, such as depression, among older adults. This study aimed to investigate the predictors of lower depression scores in older adults living under lockdown. METHODS: 1,123 older Brazilian adults were cross-sectionally assessed for depression, physical activity (PA), pet ownership (dogs, cats, and birds), ability to make video calls, leaving home during lockdown, and not living alone. The statistical procedures included linear regression and analysis of covariance (ANCOVA). RESULTS: After adjusting for age, sex, and race, moderate to vigorous PA (ß = -0.014, p < .001), it was found that PA (ß = -0.905, p < .001) and dog ownership (ß = -0.545, p = .004) were associated with lower depression. No association was observed between depression and other conditions. CONCLUSIONS: With the likelihood of subsequent COVID-19 waves, remotely delivered PA programs might be a strategy to counteract the negative psychological effects of lockdown on older adults.

Physical Fitness and Health-related Quality of Life in Patients with Colorectal Cancer.

Colorectal cancer is now a frequently treatable illness for most and a chronic disease for many. The number of people living with a diagnosis of colorectal cancer is thus expected to rise. Yet even after successful treatment, colorectal cancer survivors, mostly the elderly, frequently experience health problems and impaired health-related quality of life. We investigated the cross-sectional association between physical fitness, measured with the 6-min walk test, 30-second chair-stand test, and isometric handgrip strength, as well as health-related quality of life, in a cohort of colorectal cancer patients (n=71, mean [SD] age 67±10 years, 63% men; 35, 39 and 25% in stages I, II and III, respectively). Greater performance in the 6-minute walk test and 30-second chair-stand test was associated with higher levels of global health status (p<0.001, p=0.001 respectively), higher functioning (p<0.001) and lower levels of symptomatology (p<0.001; pain and fatigue). Additionally, greater 6-min walk test performance was associated with a better cognitive function (p=0.005). Our results suggest that greater aerobic fitness and lower-extremity muscle strength are cross-sectionally associated with higher levels of global health status, higher functioning and lower levels of symptomatology such as pain and fatigue in colorectal cancer patients.

Cryptococcus in Wildlife and Free-Living Mammals.

Cryptococcosis is typically a sporadic disease that affects a broad range of animal species globally. Disease is a consequence of infection with members of the Cryptococcus neoformans or Cryptococcus gattii species complexes. Although cryptococcosis in many domestic animals has been relatively well-characterized, free-living wildlife animal species are often neglected in the literature outside of occasional case reports. This review summarizes the clinical presentation, pathological findings and potential underlying causes of cryptococcosis in various other animals, including terrestrial wildlife species and marine mammals. The evaluation of the available literature supports the hypothesis that anatomy (particularly of the respiratory tract), behavior and environmental exposures of animals play vital roles in the outcome of host-pathogen-environment interactions resulting in different clinical scenarios. Key examples range from koalas, which exhibit primarily C. gattii species complex disease presumably due to their behavior and environmental exposure to eucalypts, to cetaceans, which show predominantly pulmonary lesions due to their unique respiratory anatomy. Understanding the factors at play in each clinical scenario is a powerful investigative tool, as wildlife species may act as disease sentinels.

Risco-espetáculo: novas modalidades do risco na era digital / Risk-spectacle: new modalities of risk in digital era

Este artigo tem como finalidade discutir o engendramento do risco-espetáculo enquanto uma nova modalidade de risco e também como vetor de subjetivação na contemporaneidade. Neste sentido, o risco-espetáculo se configura como uma leitura possível acerca de um fenômeno da era digital que tem alcançado enorme popularidade entre o público infanto-juvenil: os desafios do youtube. Muitos desafios se popularizaram ao serem publicados por famosos youtubers, as celebridades da Internet. Como consequência, jovens e crianças passam a reproduzir tais práticas em suas casas. Apesar do caráter lúdico e aparentemente seguro, alguns desafios do youtube implicam em risco à saúde e à vida, sendo enquadrados no rol das brincadeiras perigosas. Estas práticas de risco se desenrolam, na maior parte das vezes, alheias à tutela e à supervisão da família. Isto nos leva a interrogar que modos de governamentalidade operam no ambiente virtual, de forma a gerir condutas que incidem no mundo concreto e que modos de subjetivação estão sendo produzidos a partir destas práticas.

This article aims to discuss the engendering of risk-spectacle as a new modality of risk and also as a subjectivation vector in contemporary times. In this sense, the risk-spectacle is configured as a possible reading about a phenomenon of the digital age that has reached enormous popularity among the children and youth public: the YouTube challenges. Many challenges become popular when published by famous youtubers, the Internet celebrities. As a result, young people begin to replicate such practices in their homes. Despite the playful and seemingly safe character, some youtube challenges imply a risk to health and life, being framed in the roll of dangerous games. These risk-taking practices occur, most of the time, without the supervision of the family. This leads us to question which kinds of governmentality operate in the virtual environment, in order to manage conducts that affect the concrete world and which modes of subjectivation are being produced from these practices.

The receptor binding domain of SARS-CoV-2 spike protein is the result of an ancestral recombination between the bat-CoV RaTG13 and the pangolin-CoV MP789.

OBJECTIVE: In December 2019 a novel coronavirus (SARS-CoV-2) that is causing the current COVID-19 pandemic was identified in Wuhan, China. Many questions have been raised about its origin and adaptation to humans. In the present work we performed a genetic analysis of the Spike glycoprotein (S) of SARS-CoV-2 and other related coronaviruses (CoVs) isolated from different hosts in order to trace the evolutionary history of this protein and the adaptation of SARS-CoV-2 to humans. RESULTS: Based on the sequence analysis of the S gene, we suggest that the origin of SARS-CoV-2 is the result of recombination events between bat and pangolin CoVs. The hybrid SARS-CoV-2 ancestor jumped to humans and has been maintained by natural selection. Although the S protein of RaTG13 bat CoV has a high nucleotide identity with the S protein of SARS-CoV-2, the phylogenetic tree and the haplotype network suggest a non-direct parental relationship between these CoVs. Moreover, it is likely that the basic function of the receptor-binding domain (RBD) of S protein was acquired by the SARS-CoV-2 from the MP789 pangolin CoV by recombination and it has been highly conserved.

Geographic Expansion of Sporotrichosis, Brazil.

Brazil has experienced geographic expansion of zoonotic sporotrichosis. Social problems in the country contribute substantially to the expansion. A comprehensive sporotrichosis control program is beyond the sphere of public health. A One Health approach is needed to control the disease in animals and humans.

Synthesis and Identification of Pentathiepin-Based Inhibitors of Sporothrix brasiliensis.

Sporothrix brasiliensis is the causative agent of zoonotic sporotrichosis in Brazil and is currently referred to as the most virulent species among those of clinical importance within the genus. Sporotrichosis is an emergent disease that has come to the forefront over two decades with a recent hot spot of sporotrichosis infection emerging in the state of Rio de Janeiro. The source of these infections is now at epidemic proportions with more than 4000 cases reported in Rio de Janeiro, Brazil, alone since 1998. We developed a focused library of a rare pentathiepin ring system and identified a potent substitution pattern that yielded compounds 21 and 22. These compounds were more potent than itraconazole which is the current standard of care for sporotrichosis.

Parasite load, iNOS and cytokine profiles, and histopathological aspects of Leishmania infantum infection in dogs with different clinical presentations / Carga Parasitária, iNOS, citocinas e histopatologia na infecção por Leishmania infantum em cães com apresentações clínicas distintas

ABSTRACT: Visceral leishmaniasis (VL) is a zoonotic disease with a canine urban reservoir in South America. Dogs from an endemic area within Brazil, which were naturally infected with Leishmania infantum, and those presenting severe clinical (SC), mild, or no clinical (MNC) disease, were evaluated. Parasite load, histopathology, and cytokine and iNOS mRNA expressions were assessed in the spleen and liver in order to determine the potential markers for disease susceptibility or resistance. As a result, dogs with both SC and MNC had high parasite loads; IFN-γ was the most expressive cytokine in both organs, along with IL-6 and IL-4 being detected in the spleen and liver, and IL-10 only in liver. The hepatic tissue presented higher medians for IFN-γ and IL-10, and was the main organ to produce cytokines with hepatic IL-10 suggesting a regulatory follow up. Granulomas were detected in both organs; however, when absent in spleen, they were associated with elevated IL-6 levels, thus highlighting the anti-inflammatory role of IL-6. Microscopic lesions in the spleen were predominantly characterized by an extensively disorganized white pulp and splenic response was suggested as sub optimized. Parasite load, tissue damage, and immunological response may vary in the dogs with similar clinical symptoms, which may not be a good parameter for assessing the animal's susceptibility to VL.

RESUMO: A Leishmaniose visceral (LV) é uma doença zoonótica com reservatório canino na América do Sul. Cães oriundos de área endemica brasileira, naturalmente infectados por Leishmania infantum, apresentando doença clínica severa (CS) ou doença branda ou ausente (BA) foram avaliados. Carga parasitária, histopatologia e expressão de mRNA de citocinas e iNOS foram analisados em baço e fígado, buscando determinar possíveis marcadores de susceptibilidade ou resistência à doença. Como principais resultados, tanto cães CS como BA apresentaram alta carga parsitária. IFN-γ foi a citocina mais expressiva em ambos os órgãos, sendo IL-6 e IL-4 também detectadas em baço e fígado e IL-10 em fígado. No tecido hepático foram encontradas as maiores medianas de IFN-γ e IL-10, sendo o fígado o principal órgão produtor de citocinas, com IL-10 sugerindo acompanhamento regulatório. Granulomas foram detectados em ambos os órgãos. Quando de sua ausência no baço, essa foi associada à elevação dos níveis de IL-6, salientando o papel anti-inflamatório dessa citocina. Alterações microscópicas foram principalmente caracterizadas por extensiva desorganização de polpa branca, com a resposta esplência sendo sugerida como subotimizada. Carga parasitária, dano tecidual e resposta immune variaram mesmo em cães com quadros clínicos similares, não sendo, portanto, a análise clínica um bom parâmetro para avaliação de susceptibilidade animal à LV.

Co-infection with feline retrovirus is related to changes in immunological parameters of cats with sporotrichosis.

Feline sporotrichosis due to Sporothrix brasiliensis is frequently severe and often correlated to zoonotic transmission. Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) cause immunodeficiency in cats; no association has been identified with critical cases of sporotrichosis. Moreover, the cytokine profile in Sporothrix-infected cats and a potential impact of retrovirus co-infections on their immunity is unknown. This study assessed immunological parameters in cats with sporotrichosis with and without FIV or FeLV co-infection. FeLV infection was detected by antigen ELISA and by provirus PCR. FIV infection was investigated through ELISA and Western blot. Cytokine transcription (IFN-γ, IL-4, IL-5, IL-6, IL-10, IL-12, TNF-α) was quantified using RT-qPCR and lymphocyte subpopulations (CD4, CD8, CD5 and CD21) were assessed by flow cytometry. Thirty cats with sporotrichosis were recruited to the study, including three FIV-positive and five FeLV-positive (progressive infection) cats. One cat with regressive FeLV infection was excluded from statistics. In comparison to retrovirus-negative cats, FIV-positive cats and FeLV-positive cats had higher IL-10 levels, FeLV-positive cats had lower IL-4 levels and FIV-positive cats had lower IL-12 levels and a lower CD4+/CD8+ ratio. Remarkably, all cats with poor general condition were FeLV (progressive infection) or FIV-positive, but the retrovirus status was not associated with the sporotrichosis treatment length or outcome. The immunological changes and the more severe clinical presentation observed in cats with retrovirus co-infections encourage future prospective studies that address the impact of these changes on prognostic determinants of feline sporotrichosis and the development of new therapy strategies that control disease spread.