Dataset Information

Mesenteric cryptococcal granuloma in a dog caused by Cryptococcus neoformans var. grubii.

ABSTRACT: Although cryptococcosis is usually associated with respiratory and neurologic signs in domestic species (such as sneeze, cough, nasal discharge, seizures, ataxia), clinical manifestations of the disease may be more subtle and nonspecific. A 3-year-old male castrated Boxer dog presented with a history of chronic vomiting, diarrhea, weight loss, and lethargy. At no time had respiratory or neurologic signs been noted by the owners or the primary care veterinarian. Palpation of an abdominal mass revealed an atypical lesion location: a large (16 × 9 × 7 cm) mass at the root of the mesentery. Diagnosis was achieved through cytology of this mass and a positive serologic Cryptococcus capsular antigen titer; polymerase chain reaction was utilized for speciation of the abdominal isolate as Cryptococcus neoformans variety grubii. The animal was euthanized due to poor prognosis. After necropsy and histopathologic analysis, the mesenteric mass and associated lymph nodes were identified as large fungal granulomas. This is a rare manifestation of cryptococcosis, involving several visceral organs, with no remaining evidence of the route of entry of the organism. As prompt diagnosis of mycotic illness is paramount to successful management, this case indicates that cryptococcal infection should be considered as a differential diagnosis in dogs with gastrointestinal signs and lymphadenopathy. The protean nature of cryptococcosis is discussed within the context of a brief review of emerging and unresolved issues in pathogenesis.

SUBMITTER: Cook JR

PROVIDER: S-EPMC6067525 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Mesenteric cryptococcal granuloma in a dog caused by <i>Cryptococcus neoformans</i> var. <i>grubii</i>.

Cook Jennifer R JR Russell Karen E KE Eden Kristin B KB Rodrigues-Hoffmann Aline A

Veterinary medicine (Auckland, N.Z.) 20120927

Although cryptococcosis is usually associated with respiratory and neurologic signs in domestic species (such as sneeze, cough, nasal discharge, seizures, ataxia), clinical manifestations of the disease may be more subtle and nonspecific. A 3-year-old male castrated Boxer dog presented with a history of chronic vomiting, diarrhea, weight loss, and lethargy. At no time had respiratory or neurologic signs been noted by the owners or the primary care veterinarian. Palpation of an abdominal mass rev ...[more]

PMID: 30101089

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Project description:Cryptococcal meningoencephalitis (CM) remains the most prevalent invasive fungal infection worldwide. The main objective of this study was to describe the prevalence of CM and cryptococcal infection in HIV-infected patients in Madagascar. The secondary objectives were to assess the adjusted prevalence of CM according to clinical presentation and patient characteristics, to determine crude 90-day survival according to cryptococcal antigen (CrAg) status and CM, and to identify the genotypes of Cryptococcus clinical isolates. This cross-sectional study was carried out at two urban hospitals in Antananarivo (central highlands) and Toamasina (east coast) between November 2014 and December 2016. Consecutive HIV-infected adults presenting with CD4 cell counts ≤200/μl were enrolled. Lateral flow immunoassays of CrAg were performed on serum for all patients, and on cerebrospinal fluid for patients with CM symptoms. MALDI-ToF MS, ITS sequencing, and determinations of the molecular and mating types of the isolates were performed. Fluconazole is the only drug for CM treatment available in Madagascar. Patients were treated orally, with high doses (1200 mg/day) for 10-12 weeks and then with 200 mg/day. Minimum inhibitory concentrations were determined for amphotericin B, flucytosine, voriconazole and fluconazole in E-tests. Overall prevalence was 13.2% (95% CI 7.9-20.3) for cryptococcal infection and 10.9% (95% CI 6.1-17.5) for CM, among the 129 HIV-infected patients studied. The 90-day mortality rate was 58.8% (10/17) in CrAg-positive patients and 17.9% (20/112) in CrAg-negative patients (p<0.001). The 13 Cryptococcus strains obtained at baseline were all Cryptococcus neoformans var. grubii, genotypes VNI-αA (3 isolates), VNII-αA (4 isolates) or hybrid VNI/VNII-αAAα (6 isolates), suggesting high diversity. Two strains acquired fluconazole resistance after four and five months of exposure, respectively. The prevalence of cryptococcosis is high in Madagascar and this serious condition is life-threatening in HIV-infected patients. These findings will be used to raise the awareness of national authorities to strengthen the national HIV/AIDS control program.

Project description:The pathogenic species of Cryptococcus are a major cause of mortality owing to severe infections in immunocompromised as well as immunocompetent individuals. Although antifungal treatment is usually effective, many patients relapse after treatment, and in such cases, comparative analyses of the genomes of incident and relapse isolates may reveal evidence of determinative, microevolutionary changes within the host. Here, we analyzed serial isolates cultured from cerebrospinal fluid specimens of 18 South African patients with recurrent cryptococcal meningitis. The time between collection of the incident isolates and collection of the relapse isolates ranged from 124 days to 290 days, and the analyses revealed that, during this period within the patients, the isolates underwent several genetic and phenotypic changes. Considering the vast genetic diversity of cryptococcal isolates in sub-Saharan Africa, it was not surprising to find that the relapse isolates had acquired different genetic and correlative phenotypic changes. They exhibited various mechanisms for enhancing virulence, such as growth at 39°C, adaptation to stress, and capsule production; a remarkable amplification of ERG11 at the native and unlinked locus may provide stable resistance to fluconazole. Our data provide a deeper understanding of the microevolution of Cryptococcus species under pressure from antifungal chemotherapy and host immune responses. This investigation clearly suggests a promising strategy to identify novel targets for improved diagnosis, therapy, and prognosis.IMPORTANCE Opportunistic infections caused by species of the pathogenic yeast Cryptococcus lead to chronic meningoencephalitis and continue to ravage thousands of patients with HIV/AIDS. Despite receiving antifungal treatment, over 10% of patients develop recurrent disease. In this study, we collected isolates of Cryptococcus from cerebrospinal fluid specimens of 18 patients at the time of their diagnosis and when they relapsed several months later. We then sequenced and compared the genomic DNAs of each pair of initial and relapse isolates. We also tested the isolates for several key properties related to cryptococcal virulence as well as for their susceptibility to the antifungal drug fluconazole. These analyses revealed that the relapsing isolates manifested multiple genetic and chromosomal changes that affected a variety of genes implicated in the pathogenicity of Cryptococcus or resistance to fluconazole. This application of comparative genomics to serial clinical isolates provides a blueprint for identifying the mechanisms whereby pathogenic microbes adapt within patients to prolong disease.

Project description:BackgroundMost cases of cryptococcal meningitis occur in patients with HIV infection: the course and outcome of disease in the apparently immunocompetent is much more poorly understood. We describe a cohort of HIV uninfected Vietnamese patients with cryptococcal meningitis in whom underlying disease is uncommon, and relate presenting features of patients and the characteristics of the infecting species to outcome.MethodsA prospective descriptive study of HIV negative patients with cryptococcal meningitis based at the Hospital for Tropical Diseases, Ho Chi Minh City. All patients had comprehensive clinical assessment at baseline, were cared for by a dedicated study team, and were followed up for 2 years. Clinical presentation was compared by infecting isolate and outcome.Results57 patients were studied. Cryptococcus neoformans var grubii molecular type VN1 caused 70% of infections; C. gattii accounted for the rest. Most patients did not have underlying disease (81%), and the rate of underlying disease did not differ by infecting species. 11 patients died while in-patients (19.3%). Independent predictors of death were age > or = 60 years and a history of convulsions (odds ratios and 95% confidence intervals 8.7 (1 - 76), and 16.1 (1.6 - 161) respectively). Residual visual impairment was common, affecting 25 of 46 survivors (54.3%). Infecting species did not influence clinical phenotype or outcome. The minimum inhibitory concentrations of flucytosine and amphotericin B were significantly higher for C. neoformans var grubii compared with C. gattii (p < 0.001 and p = 0.01 respectively).ConclusionIn HIV uninfected individuals in Vietnam, cryptococcal meningitis occurs predominantly in people with no clear predisposing factor and is most commonly due to C. neoformans var grubii. The rates of mortality and visual loss are high and independent of infecting species. There are detectable differences in susceptibility to commonly used antifungal drugs between species, but the clinical significance of this is not clear.

Dataset Information

Mesenteric cryptococcal granuloma in a dog caused by Cryptococcus neoformans var. grubii.

Publications

Mesenteric cryptococcal granuloma in a dog caused by <i>Cryptococcus neoformans</i> var. <i>grubii</i>.

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