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Joseph A Kovacs - One of the best experts on this subject based on the ideXlab platform.
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Humans Are Selectively Exposed to Pneumocystis jirovecii
'American Society for Microbiology', 2020Co-Authors: Ousmane H Cisse, Chao Jiang, Michael Snyder, Joseph A KovacsAbstract:Environmental exposure has a significant impact on human health. While some airborne fungi can cause life-threatening infections, the impact of environment on fungal spore dispersal and transmission is poorly understood. The democratization of shotgun metagenomics allows us to explore important questions about fungal propagation. We focus on Pneumocystis, a genus of host-specific fungi that infect mammals via airborne particles. In humans, Pneumocystis jirovecii causes lethal infections in immunocompromised patients if untreated, although its environmental reservoir and transmission route remain unclear.Environmental exposure has a significant impact on human health. While some airborne fungi can cause life-threatening infections, the impact of environment on fungal spore dispersal and transmission is poorly understood. The democratization of shotgun metagenomics allows us to explore important questions about fungal propagation. We focus on Pneumocystis, a genus of host-specific fungi that infect mammals via airborne particles. In humans, Pneumocystis jirovecii causes lethal infections in immunocompromised patients if untreated, although its environmental reservoir and transmission route remain unclear. Here, we attempt to clarify, by analyzing human exposome metagenomic data sets, whether humans are exposed to different Pneumocystis species present in the air but only P. jirovecii cells are able to replicate or whether they are selectively exposed to P. jirovecii. Our analysis supports the latter hypothesis, which is consistent with a local transmission model. These data also suggest that healthy carriers are a major driver for the transmission
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characterization of Pneumocystis murina bgl2 an endo β 1 3 glucanase and glucanosyltransferase
The Journal of Infectious Diseases, 2019Co-Authors: Geetha Kutty, Sally A Davis, Kaitlynn N Schuck, Mya Masterson, Honghui Wang, Yueqin Liu, Joseph A KovacsAbstract:Glucan is the major cell wall component of Pneumocystis cysts. In the current study, we have characterized Pneumocystis Bgl2 (EC 3.2.1.58), an enzyme with glucanosyltransferase and β-1,3 endoglucanase activity in other fungi. Pneumocystis murina, Pneumocystis carinii, and Pneumocystis jirovecii bgl2 complementary DNA sequences encode proteins of 437, 447, and 408 amino acids, respectively. Recombinant P. murina Bgl2 expressed in COS-1 cells demonstrated β-glucanase activity, as shown by degradation of the cell wall of Pneumocystis cysts. It also cleaved reduced laminaripentaose and transferred oligosaccharides, resulting in polymers of 6 and 7 glucan residues, demonstrating glucanosyltransferase activity. Surprisingly, confocal immunofluorescence analysis of P. murina-infected mouse lung sections using an antibody against recombinant Bgl2 showed that the native protein is localized primarily to the trophic form of Pneumocystis in both untreated mice and mice treated with caspofungin, an antifungal drug that inhibits β-1,3-glucan synthase. Thus, like other fungi, Bgl2 of Pneumocystis has both endoglucanase and glucanosyltransferase activities. Given that it is expressed primarily in trophic forms, further studies are needed to better understand its role in the biology of Pneumocystis.
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a molecular window into the biology and epidemiology of Pneumocystis spp
Clinical Microbiology Reviews, 2018Co-Authors: Ousmane H Cisse, Joseph A KovacsAbstract:SUMMARY Pneumocystis, a unique atypical fungus with an elusive lifestyle, has had an important medical history. It came to prominence as an opportunistic pathogen that not only can cause life-threatening pneumonia in patients with HIV infection and other immunodeficiencies but also can colonize the lungs of healthy individuals from a very early age. The genus Pneumocystis includes a group of closely related but heterogeneous organisms that have a worldwide distribution, have been detected in multiple mammalian species, are highly host species specific, inhabit the lungs almost exclusively, and have never convincingly been cultured in vitro , making Pneumocystis a fascinating but difficult-to-study organism. Improved molecular biologic methodologies have opened a new window into the biology and epidemiology of Pneumocystis. Advances include an improved taxonomic classification, identification of an extremely reduced genome and concomitant inability to metabolize and grow independent of the host lungs, insights into its transmission mode, recognition of its widespread colonization in both immunocompetent and immunodeficient hosts, and utilization of strain variation to study drug resistance, epidemiology, and outbreaks of infection among transplant patients. This review summarizes these advances and also identifies some major questions and challenges that need to be addressed to better understand Pneumocystis biology and its relevance to clinical care.
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Pneumocystis Encodes a Functional Endo-β-1,3-glucanase That is Expressed Exclusively in Cysts
The Journal of infectious diseases, 2014Co-Authors: Geetha Kutty, A. Sally Davis, Jeffery K. Taubenberger, Joseph A KovacsAbstract:β-1,3-glucan is a major cell wall component of Pneumocystis cysts. We have characterized endo-β-1,3-glucanase (Eng) from 3 species of Pneumocystis. The gene eng is a single-copy gene that encodes a protein containing 786 amino acids in P. carinii and P. murina, and 788 amino acids in P. jirovecii, including a signal peptide for the former 2 but not the latter. Recombinant Eng expressed in Escherichia coli was able to solubilize the major surface glycoprotein of Pneumocystis, thus potentially facilitating switching of the expressed major surface glycoprotein (Msg) variant. Confocal immunofluorescence analysis of P. murina–infected mouse lung sections localized Eng exclusively to the cyst form of Pneumocystis. No Eng was detected after mice were treated with caspofungin, a β-1,3-glucan synthase inhibitor that is known to reduce the number of cysts. Thus, Eng is a cyst-specific protein that may play a role in Msg variant expression in Pneumocystis.
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evolving health effects of Pneumocystis one hundred years of progress in diagnosis and treatment
JAMA, 2009Co-Authors: Joseph A Kovacs, Henry MasurAbstract:2009 marks the 100th anniversary of the first description of Pneumocystis, an organism that was ignored for much of its first 50 years but that has subsequently been recognized as an important pathogen of immunocompromised patients, especially patients infected with human immunodeficiency virus (HIV). We present a patient with chronic lymphocytic leukemia who died from Pneumocystis pneumonia (PCP) despite appropriate anti-Pneumocystis therapy. Although substantial advances in diagnosis, treatment, and prevention of PCP have decreased its frequency and improved prognosis, PCP continues to be seen in both HIV-infected patients and patients receiving immunosuppressive medications. Pneumocystis species comprise a family of fungi, each of which appears to be able to infect only 1 host species. Pneumocystis has a worldwide distribution. Immunocompetent hosts clear infection without obvious clinical consequences. Pneumocystis has been identified in patients with other diseases such as chronic obstructive pulmonary disease, although its clinical impact is uncertain. Immunocompromised patients develop disease as a consequence of reinfection and possibly reactivation of latent infection. In patients with HIV infection, the CD4 count is predictive of the risk for developing PCP, but such reliable markers are not available for other immunocompromised populations. In the majority of patients with PCP, multiple Pneumocystis strains can be identified using recently developed typing techniques. Because Pneumocystis cannot be cultured, diagnosis relies on detection of the organism by colorimetric or immunofluorescent stains or by polymerase chain reaction. Trimethoprim-sulfamethoxazole is the preferred drug regimen for both treatment and prevention of PCP, although a number of alternatives are also available. Corticosteroids are an important adjunct for hypoxemic patients.
Geetha Kutty - One of the best experts on this subject based on the ideXlab platform.
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characterization of Pneumocystis murina bgl2 an endo β 1 3 glucanase and glucanosyltransferase
The Journal of Infectious Diseases, 2019Co-Authors: Geetha Kutty, Sally A Davis, Kaitlynn N Schuck, Mya Masterson, Honghui Wang, Yueqin Liu, Joseph A KovacsAbstract:Glucan is the major cell wall component of Pneumocystis cysts. In the current study, we have characterized Pneumocystis Bgl2 (EC 3.2.1.58), an enzyme with glucanosyltransferase and β-1,3 endoglucanase activity in other fungi. Pneumocystis murina, Pneumocystis carinii, and Pneumocystis jirovecii bgl2 complementary DNA sequences encode proteins of 437, 447, and 408 amino acids, respectively. Recombinant P. murina Bgl2 expressed in COS-1 cells demonstrated β-glucanase activity, as shown by degradation of the cell wall of Pneumocystis cysts. It also cleaved reduced laminaripentaose and transferred oligosaccharides, resulting in polymers of 6 and 7 glucan residues, demonstrating glucanosyltransferase activity. Surprisingly, confocal immunofluorescence analysis of P. murina-infected mouse lung sections using an antibody against recombinant Bgl2 showed that the native protein is localized primarily to the trophic form of Pneumocystis in both untreated mice and mice treated with caspofungin, an antifungal drug that inhibits β-1,3-glucan synthase. Thus, like other fungi, Bgl2 of Pneumocystis has both endoglucanase and glucanosyltransferase activities. Given that it is expressed primarily in trophic forms, further studies are needed to better understand its role in the biology of Pneumocystis.
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β glucans are masked but contribute to pulmonary inflammation during Pneumocystis pneumonia
The Journal of Infectious Diseases, 2016Co-Authors: Geetha Kutty, Sally A Davis, Gabriela A Ferreyra, Ju Qiu, Dawei Huang, Monica Sassi, Lisa R Bishop, Grace Handley, Brad T Sherman, Richard A LempickiAbstract: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.
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genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts
Nature Communications, 2016Co-Authors: Zehua Chen, Geetha Kutty, Dawei Huang, Lisa R Bishop, Honghui Wang, Mayumi Ishihara, Amr Abouelleil, Emma Davey, Rebecca DengAbstract:Pneumocystis jirovecii is a major cause of life-threatening pneumonia in immunosuppressed patients including transplant recipients and those with HIV/AIDS, yet surprisingly little is known about the biology of this fungal pathogen. Here we report near complete genome assemblies for three Pneumocystis species that infect humans, rats and mice. Pneumocystis genomes are highly compact relative to other fungi, with substantial reductions of ribosomal RNA genes, transporters, transcription factors and many metabolic pathways, but contain expansions of surface proteins, especially a unique and complex surface glycoprotein superfamily, as well as proteases and RNA processing proteins. Unexpectedly, the key fungal cell wall components chitin and outer chain N-mannans are absent, based on genome content and experimental validation. Our findings suggest that Pneumocystis has developed unique mechanisms of adaptation to life exclusively in mammalian hosts, including dependence on the lungs for gas and nutrients and highly efficient strategies to escape both host innate and acquired immune defenses.
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Pneumocystis Encodes a Functional Endo-β-1,3-glucanase That is Expressed Exclusively in Cysts
The Journal of infectious diseases, 2014Co-Authors: Geetha Kutty, A. Sally Davis, Jeffery K. Taubenberger, Joseph A KovacsAbstract:β-1,3-glucan is a major cell wall component of Pneumocystis cysts. We have characterized endo-β-1,3-glucanase (Eng) from 3 species of Pneumocystis. The gene eng is a single-copy gene that encodes a protein containing 786 amino acids in P. carinii and P. murina, and 788 amino acids in P. jirovecii, including a signal peptide for the former 2 but not the latter. Recombinant Eng expressed in Escherichia coli was able to solubilize the major surface glycoprotein of Pneumocystis, thus potentially facilitating switching of the expressed major surface glycoprotein (Msg) variant. Confocal immunofluorescence analysis of P. murina–infected mouse lung sections localized Eng exclusively to the cyst form of Pneumocystis. No Eng was detected after mice were treated with caspofungin, a β-1,3-glucan synthase inhibitor that is known to reduce the number of cysts. Thus, Eng is a cyst-specific protein that may play a role in Msg variant expression in Pneumocystis.
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outbreaks of Pneumocystis pneumonia in 2 renal transplant centers linked to a single strain of Pneumocystis implications for transmission and virulence
Clinical Infectious Diseases, 2012Co-Authors: Monica Sassi, Geetha Kutty, Nicolas J Mueller, Chiara Ripamonti, Hirohisa Yazaki, Charles Huber, Emile Gogineni, Shinichi Oka, Norihiko Goto, Thomas FehrAbstract:Pneumocystis jirovecii continues to be an important, often fatal, cause of Pneumocystis pneumonia (PCP) in a wide spectrum of immunosuppressed patients including patients with human immunodeficiency virus (HIV) infection and patients who have received human stem cell or solid organ transplants [1, 2]. Although prophylaxis has been very effective in preventing PCP in HIV infection, identification of patients who are at risk for PCP and thus suitable candidates for prophylaxis in non-HIV populations can be more difficult. Notable outbreaks of PCP have occurred, especially in renal transplant patients over the past 2 decades, primarily from centers in Europe and Japan [3–9]. Renal transplant patients in the recent era may well have been susceptible to PCP because of inconsistent use of anti-Pneumocystis prophylaxis at many centers in the context of changing immunosuppressive regimens. However, the dramatic occurrence of clusters that are geographically and temporally distinct suggests that special circumstances may exist where renal transplant patients are uniquely susceptible to infection, possibly due to epidemiologic factors, such as dedicated clinics for transplant patients, or to a unique, potentially more virulent strain of Pneumocystis. We have recently developed a typing technique using restriction fragment length polymorphism (RFLP) analysis that has allowed us to demonstrate substantial diversity among Pneumocystis isolates, both in HIV-infected and uninfected patients [10]. A remarkable feature of our studies is the tremendous variability seen in the RFLP patterns: no 2 patients with sporadic cases of PCP showed the same pattern, suggesting that each case was caused by a unique strain of Pneumocystis. However, in contrast to this experience with sporadic cases, using this technique we were able to confirm that an outbreak of PCP in Germany in 2006 was caused by a single Pneumocystis strain [7, 10]. These studies support the high discriminatory power of this typing technique. The availability of samples from additional outbreaks in renal transplant centers in Zurich, Switzerland (2006–2007) [5], and Nagoya, Japan (2004–2008) [8], provided an opportunity to study strain differences among patients and centers and to compare strains causing disease within Europe with those outside of Europe.
Alison Morris - One of the best experts on this subject based on the ideXlab platform.
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Pneumocystis jirovecii colonization is associated with enhanced th1 inflammatory gene expression in lungs of humans with chronic obstructive pulmonary disease
Microbiology and Immunology, 2014Co-Authors: Meghan Fitzpatrick, Karen A Norris, John Tedrow, Maria E Hillenbrand, Lorrie Lucht, Thomas J Richards, Yingze Zhang, Frank C Sciurba, Naftali Kaminski, Alison MorrisAbstract:Chronic obstructive pulmonary disease (COPD) is a complex disease, the pathogenesis of which remains incompletely understood. Colonization with Pneumocystis jirovecii may play a role in COPD pathogenesis; however, the mechanisms by which such colonization contributes to COPD are unknown. The objective of this study was to determine lung gene expression profiles associated with Pneumocystis colonization in patients with COPD to identify potential key pathways involved in disease pathogenesis. Using COPD lung tissue samples made available through the Lung Tissue Research Consortium (LTRC), Pneumocystis colonization status was determined by nested PCR. Microarray gene expression profiles were performed for each sample and the profiles of colonized and non-colonized samples compared. Overall, 18 participants (8.5%) were Pneumocystis-colonized. Pneumocystis colonization was associated with fold increase in expression of four closely related genes: INF-γ and the three chemokine ligands CXCL9, CXCL10, and CXCL11. These ligands are chemoattractants for the common cognate receptor CXCR3, which is predominantly expressed on activated Th1 T-lymphocytes. Although these ligand-receptor pairs have previously been implicated in COPD pathogenesis, few initiators of ligand expression and subsequent lymphocyte trafficking have been identified: our findings implicate Pneumocystis as a potential trigger. The finding of upregulation of these inflammatory genes in the setting of Pneumocystis colonization sheds light on infectious-immune relationships in COPD.
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relationship of Pneumocystis jiroveci humoral immunity to prevention of colonization and chronic obstructive pulmonary disease in a primate model of hiv infection
Infection and Immunity, 2010Co-Authors: Heather M Kling, Alison Morris, Timothy W Shipley, Sangita Patil, Jan Kristoff, Marianne A Bryan, Ronald C Montelaro, Karen A NorrisAbstract:Pulmonary colonization by the opportunistic pathogen Pneumocystis jiroveci is common in HIV+ subjects and has been associated with development of chronic obstructive pulmonary disease (COPD). Host and environmental factors associated with colonization susceptibility are undefined. Using a simian-human immunodeficiency virus (SHIV) model of HIV infection, the immunologic parameters associated with natural Pneumocystis jiroveci transmission were evaluated. SHIV-infected macaques were exposed to P. jiroveci by cohousing with immunosuppressed, P. jiroveci-colonized macaques in two independent experiments. Serial plasma and bronchoalveolar lavage (BAL) fluid samples were examined for changes in antibody titers to recombinant Pneumocystis-kexin protein (KEX1) and evidence of Pneumocystis colonization by nested PCR of BAL fluid. In experiment 1, 10 of 14 monkeys became Pneumocystis colonized (Pc+) by 8 weeks post-SHIV infection, while 4 animals remained Pneumocystis colonization negative (Pc−) throughout the study. In experiment 2, 11 of 17 animals became Pneumocystis colonized by 16 weeks post-SHIV infection, while 6 monkeys remained Pc−. Baseline plasma KEX1-IgG titers were significantly higher in monkeys that remained Pc−, compared to Pc+ monkeys, in experiments 1 (P = 0.013) and 2 (P = 0.022). Pc− monkeys had greater percentages of Pneumocystis-specific memory B cells after SHIV infection compared to Pc+ monkeys (P = 0.037). After SHIV infection, Pc+ monkeys developed progressive obstructive pulmonary disease, whereas Pc− monkeys maintained normal lung function throughout the study. These results demonstrate a correlation between the KEX1 humoral response and the prevention of Pneumocystis colonization and obstructive lung disease in the SHIV model. In addition, these results indicate that an effective Pneumocystis-specific memory B-cell response is maintained despite progressive loss of CD4+ T cells during SHIV infection.
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persistent Pneumocystis colonization leads to the development of chronic obstructive pulmonary disease in a nonhuman primate model of aids
The Journal of Infectious Diseases, 2010Co-Authors: Timothy W Shipley, Alison Morris, Heather M Kling, Sangita Patil, Jan Kristoff, Frank C Sciurba, Siobhan Guyach, Jessica Murphy, Xiuping Shao, Robert M RogersAbstract:Human immunodeficiency virus (HIV)-infected patients are at increased risk for development of pulmonary complications, including chronic obstructive pulmonary disease (COPD). Inflammation associated with subclinical infection has been postulated to promote COPD. Persistence of Pneumocystis is associated with HIV infection and COPD, although a causal relationship has not been established. We used a simian/human immunodeficiency virus model of HIV infection to study pulmonary effects of Pneumocystis colonization. Simian/human immunodeficiency virus-infected/Pneumocystis-colonized monkeys developed progressive obstructive pulmonary disease characterized by increased emphysematous tissue and bronchial-associated lymphoid tissue. Increased levels of T helper type 2 cytokines and proinflammatory mediators in bronchoalveolar lavage fluid coincided with Pneumocystis colonization and a decline in pulmonary function. These results support the concept that an infectious agent contributes to the development of HIV-associated lung disease and suggest that Pneumocystis colonization may be a risk factor for the development of HIV-associated COPD. Furthermore, this model allows examination of early host responses important to disease progression, thus identifying potential therapeutic targets for COPD.
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Pneumocystis colonisation is common among hospitalised hiv infected patients with non Pneumocystis pneumonia
Thorax, 2008Co-Authors: J L Davis, Alison Morris, David A Welsh, Charles B Beard, Jeffrey L Jones, Gena G Lawrence, Melissa Fox, Kristina Crothers, D Charbonnet, Alexandra SwartzmanAbstract:Background: When Pneumocystis DNA is recovered from respiratory specimens of patients without Pneumocystis pneumonia (PCP), patients are said to be colonised with Pneumocystis , although the significance of this state is unknown. Understanding risk factors for and outcomes of colonisation may provide insights into the life cycle and transmission dynamics of Pneumocystis jirovecii . Methods: We performed a cross sectional study of the prevalence and clinical predictors of Pneumocystis colonisation in 172 HIV infected, PCP negative inpatients undergoing diagnostic evaluation of 183 episodes of pneumonia at either the Medical Center of Louisiana at New Orleans between 2003 and 2005 or San Francisco General Hospital between 2000 and 2005. DNA was extracted from sputum and bronchoalveolar lavage specimens and amplified using a nested PCR assay at the mitochondrial large subunit (18S) ribosomal RNA locus. Colonisation was deemed present if Pneumocystis DNA was identified by both gel electrophoresis and direct DNA sequencing. Results: 68% (117/172) of all patients were colonised with Pneumocystis . No strong associations with colonisation were identified for any demographic factors. Among clinical factors, having a CD4+ T cell count ⩽50 cells/μl (unadjusted OR 2.4, 95% CI 1.09 to 5.48; p = 0.031) and using PCP prophylaxis (unadjusted OR 0.55, 95% CI 0.29 to 1.07; p = 0.077) were associated with Pneumocystis colonisation, although the latter association may have been due to chance. After adjustment for CD4+ T cell count, use of PCP prophylaxis was associated with a decreased odds of colonisation (adjusted OR 0.45, 95% CI 0.21 to 0.98; p = 0.045). 11 patients who were colonised were subsequently readmitted for evaluation of a second episode of pneumonia; three were found to be colonised again, but none had PCP. Conclusions: The majority of hospitalised HIV infected patients with non-PCP pneumonia are colonised with Pneumocystis . Failure to use co-trimoxazole prophylaxis and severe immunosuppression are associated with an increase in the odds of colonisation. Pneumocystis colonisation among hospitalised patients does not commonly lead to PCP.
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epidemiology and clinical significance of Pneumocystis colonization
The Journal of Infectious Diseases, 2008Co-Authors: Alison Morris, Kamyar Afshar, Laurence HuangAbstract:particularly those with HIV infection.Pneumocystis colonization—that is, detection of the organism or its DNA, without signs or symptoms of pneumonia— has recently been described, and accumulating evidence suggests that it may be an important clinical phenomenon. Sensitive molecular techniques such as polymerase chain reaction are frequently used to identify Pneumocystis colonization. Low levels of Pneumocystis in the lungs may stimulate pulmonary inflammation and may play a role in the development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss evidence for the occurrence of Pneumocystis colonization in animals as well as the epidemiology and risk factors for Pneumocystis colonization in various human populations. We also evaluate the clinical significance ofPneumocystis colonization and its relationship to lung disease. Pneumocystis jirovecii, previously known as Pneumocystis carinii f. sp. hominis, has long been recognized as a cause of opportunisticinfectionsinthelowerrespiratory tract.Individualswithweakenedimmune systems, especially those with AIDS, are most commonly affected. Pneumocystis may also be present in the respiratory tract when clinical pneumonia is absent. The detection of Pneumocystis in individuals without signs and symptoms of Pneumocystis pneumonia (PCP) has been defined as colonization. Other terms that have been used include “carriage” and “subclinical infection.” Although Pneumocystis can be visualized in respiratory specimens by microscopic examination usingtraditionalstainingmethods,itsdetectioninindividualswithoutpneumonia oftenrequiresuseofpolymerasechainreaction (PCR). The clinical significance of Pneumocystis colonization is not yet fully understood, but it may be important for several reasons. Individuals colonized withPneumocystismaybeatriskofdevelopmentofPCPormaytransmitPneumocystis to others. In individuals receiving long-term anti-Pneumocystis prophylaxis, colonization may lead to the selection of mutations that have been associated with drug resistance. Furthermore, the presence of Pneumocystis in the lungs, even at low levels, may stimulate a host inflammatory response that leads to lung damage and may play a role in the progression of lung diseases such as chronic obstructive pulmonary disease (COPD). In the present review, we will describe techniques to detectPneumocystiscolonization and will discuss its effects in animals. The epidemiology of Pneumocystis colonization in humans will be summarized, along with the risk factors associated with it. Finally, its clinical significance will be discussed.
Laurence Huang - One of the best experts on this subject based on the ideXlab platform.
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Pneumocystis pneumonia associated with human immunodeficiency virus
Clinics in Chest Medicine, 2013Co-Authors: R F Miller, Laurence Huang, Peter D. WalzerAbstract:Pneumocystis pneumonia (PCP) is caused by the yeastlike fungus Pneumocystis. Despite the widespread availability of specific anti-Pneumocystis prophylaxis and of combination antiretroviral therapy (ART), PCP remains a common AIDS-defining presentation. PCP is increasingly recognized among persons living in Africa. Pneumocystis cannot be cultured and bronchoalveolar lavage is the gold standard diagnostic test to diagnose PCP. Use of adjunctive biomarkers for diagnosis requires further evaluation. Trimethoprim-sulfamethoxazole remains the preferred first-line treatment regimen. In the era of ART, mortality from PCP is approximately 10% to 12%. The optimal time to start ART in a patient with PCP remains uncertain.
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epidemiology and clinical significance of Pneumocystis colonization
The Journal of Infectious Diseases, 2008Co-Authors: Alison Morris, Kamyar Afshar, Laurence HuangAbstract:particularly those with HIV infection.Pneumocystis colonization—that is, detection of the organism or its DNA, without signs or symptoms of pneumonia— has recently been described, and accumulating evidence suggests that it may be an important clinical phenomenon. Sensitive molecular techniques such as polymerase chain reaction are frequently used to identify Pneumocystis colonization. Low levels of Pneumocystis in the lungs may stimulate pulmonary inflammation and may play a role in the development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss evidence for the occurrence of Pneumocystis colonization in animals as well as the epidemiology and risk factors for Pneumocystis colonization in various human populations. We also evaluate the clinical significance ofPneumocystis colonization and its relationship to lung disease. Pneumocystis jirovecii, previously known as Pneumocystis carinii f. sp. hominis, has long been recognized as a cause of opportunisticinfectionsinthelowerrespiratory tract.Individualswithweakenedimmune systems, especially those with AIDS, are most commonly affected. Pneumocystis may also be present in the respiratory tract when clinical pneumonia is absent. The detection of Pneumocystis in individuals without signs and symptoms of Pneumocystis pneumonia (PCP) has been defined as colonization. Other terms that have been used include “carriage” and “subclinical infection.” Although Pneumocystis can be visualized in respiratory specimens by microscopic examination usingtraditionalstainingmethods,itsdetectioninindividualswithoutpneumonia oftenrequiresuseofpolymerasechainreaction (PCR). The clinical significance of Pneumocystis colonization is not yet fully understood, but it may be important for several reasons. Individuals colonized withPneumocystismaybeatriskofdevelopmentofPCPormaytransmitPneumocystis to others. In individuals receiving long-term anti-Pneumocystis prophylaxis, colonization may lead to the selection of mutations that have been associated with drug resistance. Furthermore, the presence of Pneumocystis in the lungs, even at low levels, may stimulate a host inflammatory response that leads to lung damage and may play a role in the progression of lung diseases such as chronic obstructive pulmonary disease (COPD). In the present review, we will describe techniques to detectPneumocystiscolonization and will discuss its effects in animals. The epidemiology of Pneumocystis colonization in humans will be summarized, along with the risk factors associated with it. Finally, its clinical significance will be discussed.
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epidemiology and clinical significance of Pneumocystis colonization
The Journal of Infectious Diseases, 2008Co-Authors: Alison Morris, Kamyar Afshar, Kenneth Wei, Laurence HuangAbstract:Pneumocystis pneumonia has long been recognized as a cause of morbidity and mortality in immunocompromised populations, particularly those with HIV infection. Pneumocystis colonization-that is, detection of the organism or its DNA, without signs or symptoms of pneumonia-has recently been described, and accumulating evidence suggests that it may be an important clinical phenomenon. Sensitive molecular techniques such as polymerase chain reaction are frequently used to identify Pneumocystis colonization. Low levels of Pneumocystis in the lungs may stimulate pulmonary inflammation and may play a role in the development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss evidence for the occurrence of Pneumocystis colonization in animals as well as the epidemiology and risk factors for Pneumocystis colonization in various human populations. We also evaluate the clinical significance of Pneumocystis colonization and its relationship to lung disease.
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an official ats workshop summary recent advances and future directions in Pneumocystis pneumonia pcp
Proceedings of the American Thoracic Society, 2006Co-Authors: Laurence Huang, Andrew H Limper, Alison Morris, James M BeckAbstract:Pneumocystis pneumonia (PCP) is a major cause of morbidity and mortality among immunocompromised persons, and it remains a leading acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in human immunodeficiency virus (HIV)-infected individuals throughout the world. Pneumocystis has proven difficult to study, in part due to the lack of a reliable culture system for the organism. With the development of molecular techniques, significant advances in our understanding of the organism and the disease have been made over the past several years. These advances include an improved understanding of host-organism interactions and host defense, the development of noninvasive polymerase chain reaction (PCR)-based diagnostic assays, and the emerging data regarding the possible development of trimethoprim-sulfamethoxazole-resistant Pneumocystis. In addition, the recognition that patients without PCP may nevertheless be carriers of or colonized with Pneumocystis, and observations that suggest a role for Pneumocystis in the progression of pulmonary disease, combine to signal the need for a comprehensive and accessible review. In May 2005, the American Thoracic Society sponsored a one-day workshop, "Recent Advances and Future Directions in Pneumocystis Pneumonia (PCP)," which brought together 45 Pneumocystis researchers. The workshop included 21 presentations on diverse topics, which are summarized in this report. The workshop participants identified priorities for future research, which are summarized in this document.
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an official ats workshop summary recent advances and future directions in Pneumocystis pneumonia pcp
Proceedings of the American Thoracic Society, 2006Co-Authors: Laurence Huang, Alison Morris, Andrew Harold Limper, James M BeckAbstract:Pneumocystis pneumonia (PCP) is a major cause of morbidity and mortality among immunocompromised persons, and it remains a leading acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in human immunodeficiency virus (HIV)-infected individuals throughout the world. Pneumocystis has proven difficult to study, in part due to the lack of a reliable culture system for the organism. With the development of molecular techniques, significant advances in our understanding of the organism and the disease have been made over the past several years. These advances include an improved understanding of host–organism interactions and host defense, the development of noninvasive polymerase chain reaction (PCR)-based diagnostic assays, and the emerging data regarding the possible development of trimethoprim-sulfamethoxazole–resistant Pneumocystis. In addition, the recognition that patients without PCP may nevertheless be carriers of or colonized with Pneumocystis, and observations that suggest a rol...
Stephane Bretagne - One of the best experts on this subject based on the ideXlab platform.
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association between circulating dna serum 1 3 β d glucan and pulmonary fungal burden in Pneumocystis pneumonia
Clinical Infectious Diseases, 2012Co-Authors: Jeanmarc Costa, Francoise Botterel, Odile Cabaret, F Foulet, Catherine Cordonnier, Stephane BretagneAbstract:Circulating Pneumocystis jirovecii DNA and (1→3)-β-d-glucan determined in 70 serum samples from immunocompromised patients were compared to fungal load in bronchoalveolar lavage fluids assessed using quantitative polymerase chain reaction. Both serum biomarkers are influenced by pulmonary fungal load, which should be taken into account when diagnosing Pneumocystis infection.