Cryptococcus neoformans (Cn) and Cryptococcus gattii (Cg) cause cryptococcosis, a life-threatening systemic mycosis of global distribution affecting mainly immunocompromised adults. Although a humoral response occurs during cryptococcosis, the role of antibody production against this mycosis is not fully understood. We aimed to determine total and specific antibodies against cryptococcal protein antigens in sera from people with and without diagnosis of cryptococcosis from Colombia. Using ELISA, total and specific levels of immunoglobulin (Ig)G, IgA and IgM were determined in sera from children and adults with (n = 109) and without (n = 119) cryptococcosis. Specific antibodies were those binding Cn- and Cg-protein antigens. In general, the mean of the total IgG production was higher in cryptococcosis patients than in controls (13 942.32 vs. 6459.91 µg/ml), while levels of IgA (488.13 vs. 1564.53 µg/ml) and IgM (775.69 vs. 1014.72 µg/ml) were higher in controls than in cryptococcosis patients (p ≤ 0.05). In patients with cryptococcosis, total IgG, IgA and IgM levels were higher in HIV + compared with HIV- (p ≤ 0.05). Specific antibodies tended to be higher in cryptococcosis patients than in controls and in adults than in children, with a positive correlation between antibody reactivity and age. All immunoglobulins were more reactive against Cn-proteins than Cg-proteins. Overall, a positive weak correlation between total and specific antibodies was found, although not always statistically significant. In patients with cryptococcosis from Colombia, the levels of immunoglobulins, total and specific, differ with respect to people without cryptococcosis. Variations in antibody production among adults and children with cryptococcosis and between Cn- and Cg-protein antigens were as well established. Our findings encourage further studies to determine the role of humoral immunity for host defence against cryptococcosis.

Cryptococcus gattii infection is a rare cause of severe pulmonary disease and meningoencephalitis that has only recently been detected in the southeastern United States. We describe an organ transplant-associated outbreak of C. gattii infection involving an HIV-negative immunosuppressed donor in this region who died following new-onset headache and seizure of unknown cause. Retrospective cryptococcal antigen (CrAg) testing of donor serum was positive. Two of the three transplant recipients developed severe C. gattii infection 11 and 12 weeks following transplantation. One recipient died from severe pulmonary infection, identified on autopsy, and the other ill recipient survived following treatment for cryptococcal meningitis. This outbreak underscores the importance of considering cryptococcosis in patients with clinical findings suggestive of subacute meningitis or other central nervous system (CNS) pathology, and the potential benefit of routine pre-transplant donor CrAg screening using lateral flow assay to guide recipient antifungal prophylaxis. The case also adds to emerging evidence that C. gattii is a potential threat in the southeastern United States.

Members of the Cryptococcus gattii species complex are notorious causes of cryptococcosis as they often cause severe, life-threatening infections. Here we describe a case of a severe disseminated C. deuterogattii infection in a previously healthy patient who was initially treated with amphotericin B, 5-fluorocytosine and fluconazole, which led to a good neurological response, but the infection in the lungs remained unaltered and was not completely resolved until switching the antifungal therapy to isavuconazole. The infection was likely acquired during a one-month stay at the Azores Islands, Portugal. Environmental sampling did not yield any cryptococcal isolate; therefore, the source of this apparent autochthonous case could not be determined. Molecular typing showed that the cultured C. deuterogattii isolates were closely related to the Vancouver Island outbreak-genotype.

The breadth of fungi causing human disease and the spectrum of clinical presentations associated with these infections has widened. Epidemiologic trends display dramatic shifts with expanding geographic ranges, identification of new at-risk groups, increasing prevalence of resistant infections, and emergence of novel multidrug-resistant pathogenic fungi. Certain fungi have been transmitted between patients in clinical settings. Major health events not typically associated with mycoses resulted in larger proportions of the population susceptible to secondary fungal infections. Many health care-related, environmental, and socioeconomic factors have influenced these epidemiologic shifts. This review summarizes updates to clinically significant fungal pathogens in North America.

The increase in international travel in recent decades has contributed to the risk of acquiring diseases considered endemic to a region or country and the change in the epidemiology of these diseases. Endemic mycoses that may be acquired by travelers in the short or long term are endemic subcutaneous mycoses such as sporotrichosis and lobomycosis, while endemic systemic mycoses are a group of serious diseases including histoplasmosis and coccidioidomycosis. Herein, we review the current knowledge and highlight the most important aspects of these fungal infections in travelers.

The most relevant advances in the study of these mycoses involve the epidemiological distribution; human mycoses can be fatal and there are few antifungal drugs available, increasing drug resistance, and a risk of emerging fungal diseases associated with climate change, as well as the increasing virulence, and the diagnostic strategies that may be limited in many countries.

Although endemic mycoses are relatively rare, they should be considered as potentially travel-related illnesses. A recent or late trip to an endemic country may guide the clinical suspicion, an early diagnosis, and the institution of effective therapy.

Fungal infections of the central nervous system (CNS) are relatively uncommon but associated with significant morbidity and mortality. We reviewed recent literature highlighting new approaches to management of these complex patients.

Fungal infections are increasingly recognized as important causes of CNS disease in both immunocompromised and immunocompetent hosts. Globally, cryptococcal meningitis remains a leading cause of death in HIV-infected persons in resource-limited settings. Emerging fungal pathogens with increased virulence and resistance to numerous classes of antifungal agents have been identified and represent a management challenge. Newer diagnostic techniques focused on antigen detection or molecular amplification of fungal pathogens offer promise in the expediated diagnosis and treatment of CNS fungal infections.

Meningitis and brain abscess because of invasive fungal pathogens are frequently fatal infections. Newer laboratory tests allowing antigen detection or molecular amplification from cerebrospinal fluid are more sensitive than culture and allow earlier initiation of effective therapy.

Cryptococcosis is a serious environmentally acquired endemic fungal infection commonly associated with immunocompromised hosts. Little is known regarding frequency or distribution in Wisconsin. We explored the geodemographic and clinical features of patients tested with cryptococcal antigen tests (CrAg) - previously shown to be >90% sensitive and >90% specific - within a large health care system located in eastern Wisconsin. To examine this, we retrospectively analyzed 1465 CrAg tests on 1211 unique patients (female: 50.2%; white race: 73.9%; mean age: 53.7 ± 16.5 years). At least one CrAg result was positive in 23 of 1211 patients (1.9%). From these, 21 of 23 were immunocompromised. Positive patients were disproportionately male (82.6%) and nonwhite (3.8% of those tested vs 1.2% of whites tested); P<0.01 for both. These associations remained in multivariable models. Positive patients were not significantly older (59.1 vs 53.6 years; P=0.07). Overall, 17 separate zip codes had at least one positive case. Positive patients were more prevalent in the zip codes that included the city of Milwaukee (11 of 377 [2.9% of those tested] vs 12 of 834 [1.4% of all those tested in the remaining area of the state]), but this difference was not statistically significant. No other case clustering or close proximity to waterways was observed (41% were <162 m from green space, similar to historical controls). Overall, male sex, nonwhite race/ethnicity, and immunocompromised status, not zip code, were statistically associated with positive CrAg.

Cryptococcus neoformans, a soil-dwelling fungus found worldwide, can cause cryptococcosis, an opportunistic fungal infection of the lungs and central nervous system. One former member of the C neoformans complex, Cryptococcus gattii, has caused meningitis in immunosuppressed and immunocompetent persons in endemic regions in Africa and Asia. Between 1999 and 2004, C gattii caused outbreaks of human cryptococcosis in unexpected, nonendemic, nontropical regions on Vancouver Island, Canada, and throughout the US Pacific Northwest and California. C gattii was recognized as an emerging species with several genotypes and a unique environmental relationship with trees that are often encountered in the wilderness and in landscaped parks. Because C gattii infections have a high case-fatality rate, wilderness medicine clinicians should be aware of this emerging pathogen, its disease ecology and risk factors, its expanding geographic distribution in North America, and its ability to cause fatal disease in both immunosuppressed and immunocompetent persons.

Cryptococcus gattii represents an emerging fungal pathogen of immunocompromised and immunocompetent hosts in the United States. To our knowledge, this is the first case of posttransplant immune reconstitution syndrome due to C. gattii meningoencephalitis successfully treated with corticosteroids. We also report successful maintenance phase treatment with isavuconazole, a novel triazole, following fluconazole-induced prolonged QT syndrome.