Cryptococcus neoformans is an encapsulated yeast responsible for disseminated meningitis in immunocompromised hosts. Controversies persist on the existence of primary cutaneous cryptococcosis (PCC) versus cutaneous cryptococcosis being only secondary to hematogenous dissemination. Thus, we reviewed cryptococcosis cases associated with skin lesions reported in the French National Registry. Patients with PCC (n=28) differed significantly from those with secondary cutaneous cryptococcosis (n=80) or other forms of the disease (n=1866) by living area (mostly rural), age (older), ratio of men to women (approximately 1:1), and the lack of underlying disease. Evidence of PCC included the absence of dissemination and, predominantly, a solitary skin lesion on unclothed areas presenting as a whitlow or phlegmon, a history of skin injury, participation in outdoor activities, or exposure to bird droppings, and isolation of C. neoformans serotype D. Therefore, PCC is a distinct epidemiological and clinical entity with a favorable prognosis even for immunocompromised hosts.

The pathogenesis of cerebral infection after Cryptococcus neoformans fungemia in outbred mice was investigated. Confocal microscopy and cultures on ficoll-hypaque gradient-separated blood cells were used to detect yeasts in the cytoplasms of monocytes. In semithin brain sections, poorly capsulated yeasts were seen in macrophages in the leptomeningeal space, in monocytes circulating in leptomeningeal capillaries, or in the endothelial cells themselves, strengthening the hypothesis that monocytes and endothelial cells play key roles in the pathogenesis of cryptococcal meningitis. Similar fungal loads and cellular reactions were seen in mice and in 1 patient with acquired immune deficiency syndrome (AIDS), all with acute cryptococcal meningoencephalitis, and in mice and in 1 patient with AIDS, all with cured cryptococcal infection. Immunostaining revealed both the presence of cryptococcal polysaccharide in various brain cells and antigenic variability both from yeast cell to yeast cell and over time. Thus, our data established the relevance and interest that this experimental model has for investigation of the pathogenesis of human cryptococcal meningitis.

Overall survival after cryptococcosis has dramatically improved at the cART era. Immune restoration and low serum cryptococcal antigen titres are associated with lower cryptococcosis relapse rates.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

We determined the prevalence and indicators of infection in intensive care unit (ICU) patients with diabetic ketoacidosis (DKA) by performing a retrospective analysis of 123 episodes of DKA (in 113 patients) managed in a medical ICU between 1990 and 1997. In univariate analysis, features associated with infection were female sex, neurological symptoms at admission, fever during the week before admission, a need for colloids, a high blood lactate level at admission, and lack of complete clearance of ketonuria within 12 h. Multivariate analysis identified 3 independent predictors of infection: female sex (odds ratio [OR], 2.31; confidence interval [CI], 1.05-5.35), neurological symptoms at admission (OR, 2.83; CI, 1.18-6.8), and lack of complete clearance of ketonuria within 12 h (OR, 3.73; CI, 1.58-9.09). Infection is the leading trigger of DKA in ICU patients. Neurological symptoms at admission and lack of complete clearance of ketonuria within 12 h are useful warning signals of infection.

Two human immunodeficiency virus-infected patients who needed etoposide therapy to control exacerbations of Castleman disease received four infusions of rituximab. Clinical and virologic relapses with increased blood human herpesvirus-8 DNA levels occurred in both patients 4 and 24 weeks later and were associated with a worsening of Kaposi sarcoma. Am.

The kinetics of the humoral response to Cryptococcus neoformans proteins were studied in outbred mice infected with isolate NIH52D. Future nonsurvivors had earlier and stronger (i.e., more bands recognized) humoral responses than survivors. In addition, antibodies to a 56-to 60-kDa membrane antigen and to a 39-to 40-kDa cytosolic antigen were detected more frequently in samples from future nonsurvivors and from survivors, respectively (P < 0.05).

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