Clinical features of invasive fungal disease in children with no underlying disease

There is limited research into Invasive fungal disease (IFD) in children with no underlying disease. We undertook a retrospective study of children with IFD who did not suffer from another underlying disease, from June 2010 to March 2018 in Changsha, China. Nine children were identified. Eosinophil counts were elevated in six cases. The level of procalcitonin (PCT) was elevated in six cases. Fungal culture was positive in all patients, including eight cases of Cryptococcus neoformans and one case of Candida parapsilosis. 8.33 days following antifungal treatment, the body temperature of the eight patients affected by cryptococcal disease had returned to normal. Our study indicates that the primary pathogen in IFD was Cryptococcus neoformans in children who had no other underlying disease. Eosinophils can be considered to be indicators of cryptococcal infection. IFD in children with no other underlying disease has a satisfactory prognosis.

Cryptococcal Meningoencephalitis in an Immunosuppressed Patient with Chronic Lymphocytic Leukemia

Cryptococcal meningoencephalitis, an invasive fungal infection caused by an encapsulated fungus Cryptococcus neoformans should be suspected in immune compromised individuals with defective cell-mediated immunity and patients on immunosuppressive drugs with recent development of fever, confusion and loss of consciousness. A rapid diagnosis is fundamental for decreasing morbidity and mortality from cryptococcal disease. Cerebrospinal fluid (CSF) study and simple stain like India Ink Stain can be performed for diagnosis of cryptococcal meningoencephalitis. Here, we report a case of cryptococcal meningoencephalitis in chronic lymphocytic leukemia (CLL) patient on immunosuppressive drugs diagnosed by CSF study and India ink stain which responded dramatically with antifungal agents after diagnosis. JAFMC Bangladesh. Vol 16, No 2 (December) 2020: 87-89

A hyper-immunogenic and slow-growing fungal strain induces a murine granulomatous response to cryptococcal infection

Many successful pathogens cause latent infections, remaining dormant within the host for years but retaining the ability to reactivate to cause symptomatic disease. The human opportunistic pathogen Cryptococcus neoformans is a ubiquitous yeast that establishes latent pulmonary infections in immunocompetent individuals upon fungal inhalation from the environment. These latent infections are frequently characterized by granulomas, or foci of chronic inflammation, that contain dormant cryptococcal cells. Immunosuppression causes these granulomas to break down and release viable fungal cells that proliferate, disseminate, and eventually cause lethal cryptococcosis. This course of C. neoformans dormancy and reactivation is understudied due to limited models, as chronic pulmonary granulomas do not typically form in most mouse models of cryptococcal infection. Here, we report that a previously characterized Cryptococcus-specific gene which is required for host-induced cell wall remodeling, MAR1, inhibits murine granuloma formation. Specifically, the mar1Δ loss-of-function mutant strain induces mature pulmonary granulomas at sites of infection dormancy in mice. Our data suggest that the combination of reduced fungal burden and increased immunogenicity of the mar1Δ mutant strain stimulates a host immune response that contains viable fungi within granulomas. Furthermore, we find that the mar1Δ mutant strain has slow growth and hypoxia resistance phenotypes, which may enable fungal persistence within pulmonary granulomas. Together with the conventional primary murine infection model, latent murine infection models will advance our understanding of cryptococcal disease progression and define fungal features important for persistence in the human host.

Disseminated Cryptococcal Disease in a Patient with Chronic Chylothorax and a Pleurovenous Catheter: A Case Report with Autopsy Findings

Cryptococcus species are ubiquitous in the environment with a global distribution. Whilst causing disease predominantly in immunocompromised hosts such as those with advanced HIV, HIV-uninfected patients are increasingly recognized to be affected. The most common forms of infection are cryptococcal pneumonia and meningitis. HIV-uninfected patients and extrapulmonary infections have worse outcomes, likely due to delayed diagnosis and treatment. Cryptococcus infections involving chylothorax or chyloabdomen have rarely been reported in humans. We describe a case of fulminant disseminated cryptococcosis with fungemia, peritonitis, and empyema in a patient with chronic chylothorax treated with an indwelling pleurovenous shunt. Key autopsy findings included cryptococcal organisms identified on calcified lymphadenopathy, pleural adhesions, and pericardium. We discuss the importance of identifying patients with non-traditional risks factors for cryptococcal disease, such as lymphopenia and hypogammaglobulinemia, and the potential implications of pleurovenous catheters in Cryptococcus dissemination.

Associations between Cryptococcus Genotypes, Phenotypes, and Clinical Parameters of Human Disease: A Review

The genus Cryptococcus contains two primary species complexes that are significant opportunistic human fungal pathogens: C. neoformans and C. gattii. In humans, cryptococcosis can manifest in many ways, but most often results in either pulmonary or central nervous system disease. Patients with cryptococcosis can display a variety of symptoms on a spectrum of severity because of the interaction between yeast and host. The bulk of our knowledge regarding Cryptococcus and the mechanisms of disease stem from in vitro experiments and in vivo animal models that make a fair attempt, but do not recapitulate the conditions inside the human host. To better understand the dynamics of initiation and progression in cryptococcal disease, it is important to study the genetic and phenotypic differences in the context of human infection to identify the human and fungal risk factors that contribute to pathogenesis and poor clinical outcomes. In this review, we summarize the current understanding of the different clinical presentations and health outcomes that are associated with pathogenicity and virulence of cryptococcal strains with respect to specific genotypes and phenotypes.

The granuloma in cryptococcal disease

Although we have recognized cryptococcosis as a disease entity for well over 100 years, there are many details about its pathogenesis which remain unknown. A major barrier to better understanding is the very broad range of clinical and pathological forms cryptococcal infections can take. One such form has been historically called the cryptococcal granuloma, or the cryptococcoma. These words have been used to describe essentially any mass lesion associated with infection, due to their presumed similarity to the quintessential granuloma, the tubercle in tuberculosis. Although clear distinctions between tuberculosis and cryptococcal disease have been discovered, cellular and molecular studies still confirm some important parallels between these 2 diseases and what we now call granulomatous inflammation. In this review, we shall sketch out some of the history behind the term “granuloma” as it pertains to cryptococcal disease, explore our current understanding of the biology of granuloma formation, and try to place that understanding in the context of the myriad pathological presentations of this infection. Finally, we shall summarize the role of the granuloma in cryptococcal latency and present opportunities for future investigations.