laminaran and Pneumonia--Pneumocystis

Non-HIV-infected populations are increasingly identified as being at risk for developing Pneumocystis jirovecii pneumonia (PJP). These patients typically present with severe disease and poorly tolerate invasive diagnostic procedures. This review examines recently reported risks for PJP in non-HIV populations and summarizes new diagnostic techniques.. PJP is associated with immunomodulatory drug therapies, including monoclonal antibody therapies such as tumour necrosis factor α antagonists, and calcineurin inhibitors. Underlying disease states include solid-organ transplantation, connective tissue and rheumatologic disorders, inflammatory bowel disease, haematological malignancies, and solid tumours. Modern diagnostic techniques [conventional PCR, quantitative PCR, (1→3)-β-D-glucan assays, and PET] are reviewed with respect to predictive value and clinical utility. In particular, current literature regarding validation and specificity of molecular diagnostic techniques is summarized, including application to minimally invasive specimens.. HIV-negative populations at risk for PJP can be identified. Conventional PCR increases diagnostic sensitivity but may detect asymptomatic colonization. Quantitative PCR demonstrates potential for distinguishing colonization from infection, but clinical validation is required. Serum (1→3)-β-D-glucan may be elevated in PJP, although standardized cut-off values for clinical infection have not been determined. Further validation of serum markers and molecular diagnostic methods is necessary for early and accurate diagnosis in non-HIV populations.

Topics: beta-Glucans; HIV Seronegativity; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Positron-Emission Tomography; Risk Factors

Topics: Aspergillosis; beta-Glucans; Candidiasis; Humans; Mycoses; Plasma; Pneumonia, Pneumocystis; Reagent Kits, Diagnostic; Sensitivity and Specificity; Serologic Tests; Serum

Diagnosis of pneumocystis pneumonia (PCP) relies on microscopic visualization of P. jirovecii, or detection of Pneumocystis DNA in respiratory specimens, which involves invasive procedures such as bronchoalveolar lavage. The (1-3)-β-D-glucan (BG) assay has been proposed as a less invasive and less expensive diagnostic test to rule out PCP. We therefore compared blood levels of BG in patients with PCP with those of patients with candidemia, chronic disseminated candidiasis (CDC), invasive aspergillosis, mucormycosis, and tuberculosis and those of healthy volunteers.. Adult patients who were diagnosed with PCP, candidemia, CDC, invasive aspergillosis, mucormycosis, and tuberculosis whose blood samples were available, and healthy volunteers were enrolled in a tertiary hospital in Seoul, South Korea, during a 21-month period. The blood samples were assayed with the Goldstream Fungus (1-3)-β-D-glucan test (Gold Mountain River Tech Development, Beijing, China).. A total of 136 individuals including 50 patients P. jirovecii,15 candidemia, 6 CDC, 15 invasive aspergillosis, 10 mucormycosis, and 40 controls (20 TB and 20 healthy volunteers) were included. The mean±SD of the concentration of 1-3-β-D-glucan in the patients with PCP (290.08 pg/mL±199.98) were similar to those of patients with candidemia (314.14 pg/mL±205.60, p = 0.90 at an α = 0.005) and CDC (129.74 pg/mL±182.79, p = 0.03 at an α = 0.005), but higher than those of patients with invasive aspergillosis (131.62 pg/mL±161.67, p = 0.002 at an α = 0.005), mucormycosis (95.08 pg/mL±146.80, p<0.001 at an α = 0.005), and tuberculosis (103.31 pg/mL±140.81, p<0.001 at an α = 0.005) as well as healthy volunteers (101.18 pg/mL±197.52, p<0.001 at an α = 0.005). At a cut-off value > 31.25 pg/mL, which is highly sensitive for PCP versus tuberculosis plus healthy volunteers at the expense of specificity, the BG assay had a sensitivity of 92% (95% CI 81%-98%) and a specificity of 55% (95% CI 39%-71%).. The BG assay appears to be a useful adjunct test for PCP.

Topics: Adult; Aged; Aspergillosis; beta-Glucans; Candidiasis; Case-Control Studies; Diagnosis, Differential; Female; Healthy Volunteers; Humans; Male; Middle Aged; Mucormycosis; Pneumocystis carinii; Pneumonia, Pneumocystis; Republic of Korea; Tuberculosis, Pulmonary

β-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis In the current study, we examined whether β-1,3-glucans are masked by surface proteins in Pneumocystis and what role β-glucans play in Pneumocystis-associated inflammation. For 3 species, including Pneumocystis jirovecii, which causes Pneumocystis pneumonia in humans, Pneumocystis carinii, and Pneumocystis murina, β-1,3-glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using quantitative polymerase chain reaction and microarray techniques, we demonstrated in a mouse model of Pneumocystis pneumonia that treatment with caspofungin, an inhibitor of β-1,3-glucan synthesis, for 21 days decreased expression of a broad panel of inflammatory markers, including interferon γ, tumor necrosis factor α, interleukin 1β, interleukin 6, and multiple chemokines/chemokine ligands. Thus, β-glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses.

Topics: Animals; Antifungal Agents; beta-Glucans; Caspofungin; Cytokines; Disease Models, Animal; Echinocandins; Lipopeptides; Mice, Knockout; Microarray Analysis; Pneumocystis; Pneumonia; Pneumonia, Pneumocystis; Real-Time Polymerase Chain Reaction

Topics: Anti-Infective Agents; beta-Glucans; Female; Glucans; Humans; Immunocompromised Host; Middle Aged; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

A 40-year-old man was admitted to our hospital with acute respiratory failure. The patient was given a diagnosis of Pneumocystis carinii pneumonia (PCP) associated with acquired immunodeficiency syndrome (AIDS). After treatment with trimethoprim-sulfamethoxazole and corticosteroid, the respiratory failure was improved and the abnormal shadows disappeared. The serum beta-D-glucan level, significantly elevated (76.0 pg/ml) on admission, returned to the normal range within two weeks. Serum KL-6 (max. 7580 U/ml) and surfactant protein-D (SP-D) (max. 235 ng/ml), which are produced by type II pneumocytes, increased after elevation of the beta-D-glucan level and decreased gradually following successful treatment. These findings suggest that beta-D-glucan may be a serological marker for PCP infection and KL-6 may be a serological marker for lung injury in PCP with AIDS.

Topics: Adult; AIDS-Related Opportunistic Infections; Antigens; Antigens, Neoplasm; beta-Glucans; Biomarkers; Glucans; Glycoproteins; Humans; Male; Mucin-1; Mucins; Peptide Fragments; Pneumonia, Pneumocystis; Procollagen; Pulmonary Surfactant-Associated Protein D; Pulmonary Surfactants

We report a case of Pneumocystis carinii pneumonia in a patient with acquired immunodeficiency syndrome diagnosed and monitored with polymerase chain reaction (PCR) for Pneumocystis carinii on sputum and measurement of plasma (1-->3)-beta-D-glucan (G-test). Results of both studies paralleled the clinical and radiographic improvement. However, the plasma (1-->3)-beta-D-glucan level remained higher than normal when PCR for Pneumocystis carinii became negative in sputum. Both PCR for Pneumocystis carinii on sputum and measurement of plasma (1-->3)-beta-D-glucan are useful for noninvasive diagnosis and monitoring of Pneumocystis carinii, although further investigation is necessary to quantify their relationship.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Infective Agents; beta-Glucans; Glucans; Glucocorticoids; Humans; Male; Methylprednisolone; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Radiography, Thoracic; Sputum; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

We detected (1 --> 3) beta-D-glucan (beta-glucan), which is one of the major components of the cyst wall of Pneumocystis carinii, in sera obtained from patients with P. carinii pneumonia (PCP). We confirmed that beta-glucan was detectable by a beta-glucan detection kit (G test; Seikagaku Corporation) in bronchoalveolar lavage fluids (BALFs). The mean concentration of beta-glucan in BALFs obtained from specific-pathogen-free nude mice infected with P. carinii (n = 7; mean, 2,631 [range, 1,031 to 9,095] pg/ml) was significantly higher (P < 0.001) than that in uninfected, specific-pathogen-free mice (n = 7; 6.5 [range, 4.0 to 8.3] pg/ml). The mean level of beta-glucan in BALFs from PCP patients was significantly higher (P < 0.05) than that in BALFs from patients with other lung diseases (7,268 [range, 1,355 to 15,500] pg/ml [n = 4] versus 242.5 [17 to 615] pg/ml [n = 4]). In sera from six of seven patients with PCP, significant levels of beta-glucan (494.1 [8.5 to 1,135] pg/ml) were detected, while it was undetectable in patients with other lung diseases and in a control group. In five patients at follow-up, the level of beta-glucan decreased with clinical improvement. These results suggest that beta-glucan is detectable in sera from patients with PCP and it is a practical serological marker for monitoring of the disease during treatment.

Topics: Animals; beta-Glucans; Biomarkers; Bronchoalveolar Lavage Fluid; Female; Glucans; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Pneumonia, Pneumocystis

A new beta-1,3-D-glucan synthesis inhibitor, L-687,781 is produced by the cultivation of Dictyochaeta simplex ATCC 20960. L-687,781 exhibits potent in vitro antifungal activity as well as anti-Pneumocystis activity in a rat model.

Topics: Animals; Antifungal Agents; beta-Glucans; Candida; Candidiasis; Cryptococcus neoformans; Disease Models, Animal; Fermentation; Fungi; Glucans; Male; Mice; Mitosporic Fungi; Pneumonia, Pneumocystis; Pyrans; Rats; Rats, Inbred Strains