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Chapter 38 : Cryptococcosis in AIDS
Category: Clinical Microbiology; Fungi and Fungal Pathogenesis
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Infection with HIV is the most common predisposing condition for developing cryptococcosis. This chapter focuses on aspects that are specific to the coinfection of HIV and Cryptococcus neoformans. These include clinical presentation, treatment regimens, alterations of the host immune response, and concerns about drug toxicities and interactions. Soon after the HIV pandemic was recognized in the United States and Europe, it became clear that cryptococcosis was an important opportunistic pathogen in patients with AIDS. C. neoformans infection in AIDS patients can either be the result of a newly acquired primary infection or alternatively constitute a reactivation of latent C. neoformans infection. Patients with AIDS who respond to highly active antiretroviral therapy (HAART) show a greatly reduced incidence of opportunistic infections such as cryptococcosis. Experimental evidence suggests that C. neoformans coinfection can affect HIV replication. Another factor that may affect HIV-infected patients’ ability to mount a successful antifungal host response is the common abuse of methamphetamine. This drug exposure facilitates intracellular replication and inhibits intracellular killing of C. neoformans and thus affects pathogenesis in these patients. The most common manifestation of cryptococcosis in patients with HIV infection is meningoencephalitis, and central nervous system (CNS) involvement is found in the vast majority of patients with AIDS in whom cryptococcal infection is diagnosed. The treatment of AIDS-associated cryptococcal meningitis is usually divided into three stages: induction, consolidation, and maintenance.
Key Concept Ranking
- Major Histocompatibility Complex Class II
Effect of indinavir on C. neoformans. Kinetics of IFN-γ and IL-2 production from splenocytes of mice treated with indinavir and challenged with C. neoformans. Cells were cultured for 18 h in the presence of heat-inactivated C. neoformans (E:T = 1:2), and supernatants were tested for (A) IFN-γ and (B) IL-2 levels by specific enzyme-linked immunosorbent assays. In selected experiments, 5 days after C. neoformans infection, unfractionated splenocytes were cultured as above, CD3+ T cells were subsequently purified, and intracellular staining for (C) IFN-γ and (D) IL-2 was evaluated. Data reported are mean ± SE from three separate experiments; *, P< 0.05 (indinavir + C. neoformans versus C. neoformans). (e) CFU recovery from the brain was determined 3, 5, 10, 15, and 20 days after fungal infection; indinavir (25 or 10 μmol/0.2 ml, days 3, 2, 1). Data reported are mean ± SE from five separate experiments; *, P< 0.05 (indinavir-treated versus C. neoformans). (f) Histological analysis of brains from mice treated with indinavir. Mice were treated with indinavir (10 μmol/0.2 ml, days 3, 2, 1) and subsequently infected with C. neoformans. Ten days after infection, animals were killed, brains were excised, and brain sections were stained with periodic acid-Schiff stain. (f–A, f–B) Brain sections from mice infected with C. neoformans. (f–C, f–D) Brain sections from mice treated with indinavir and infected with C. neoformans. Original magnification, x2.5 (f–A, f–C); x40 (f–B, f–D) ( 68 ).
Methamphetamine (Meth) and chloroquine (Clq) inhibit phagocytosis of fungi. (A) Cells were incubated in Meth or Clq for 2 h, and then immunoglobulin G (IgG)-coated erythrocytes were added. Extracellular uningested IgG-coated erythrocytes were lysed and removed. Phagocytic index was quantified and inhi bition is indicated as percentage of control. Data were collected from four to seven experiments (n = 300 cells; mean ± SEM; ***, P< 0.0001, two-tailed ANOVA). (B) Images of macrophage cells impaired in the phagocytosis of opsonized sheep erythrocytes after 2 h of Meth or Clq treatment. Arrows denote phagocytosed erythrocytes. Scale bar, 10 μm. (C, D) J774.16 cells were exposed to phosphate-buffered saline, Clq, or Meth for 2 h followed by incubation with C. neoformans or Candida albicans. The phagocytic indices were determined after 1 h or 30 min for C. neoformans and C. albicans, respectively (C). (Statistics: n= 300; mean ± SEM; *, P< 0.05, two-tailed ANOVA.) CFU after 24 h incubations (D). (n = 300 cells; mean ± SEM; *, P< 0.05, two-tailed ANOVA.) From reference 79 .
Characteristics of 575 patients presenting with AIDS-associated cryptococcal meningitis in two large treatment trials from 1988 to 1994