-
Medical Mycology Nov 2020Pneumocystis jirovecii can cause life-threatening pneumonia in immunocompromised patients. Traditional diagnostic testing has relied on staining and direct visualization... (Review)
Review
Pneumocystis jirovecii can cause life-threatening pneumonia in immunocompromised patients. Traditional diagnostic testing has relied on staining and direct visualization of the life-forms in bronchoalveolar lavage fluid. This method has proven insensitive, and invasive procedures may be needed to obtain adequate samples. Molecular methods of detection such as polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), and antibody-antigen assays have been developed in an effort to solve these problems. These techniques are very sensitive and have the potential to detect Pneumocystis life-forms in noninvasive samples such as sputum, oral washes, nasopharyngeal aspirates, and serum. This review evaluates 100 studies that compare use of various diagnostic tests for Pneumocystis jirovecii pneumonia (PCP) in patient samples. Novel diagnostic methods have been widely used in the research setting but have faced barriers to clinical implementation including: interpretation of low fungal burdens, standardization of techniques, integration into resource-poor settings, poor understanding of the impact of host factors, geographic variations in the organism, heterogeneity of studies, and limited clinician recognition of PCP. Addressing these barriers will require identification of phenotypes that progress to PCP and diagnostic cut-offs for colonization, generation of life-form specific markers, comparison of commercial PCR assays, investigation of cost-effective point of care options, evaluation of host factors such as HIV status that may impact diagnosis, and identification of markers of genetic diversity that may be useful in diagnostic panels. Performing high-quality studies and educating physicians will be crucial to improve the rates of diagnosis of PCP and ultimately to improve patient outcomes.
Topics: Humans; Immunoassay; Immunocompromised Host; Microbiological Techniques; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Sensitivity and Specificity; Specimen Handling; Staining and Labeling
PubMed: 32400869
DOI: 10.1093/mmy/myaa024 -
Cold Spring Harbor Perspectives in... Nov 2014Since its initial misidentification as a trypanosome some 100 years ago, Pneumocystis has remained recalcitrant to study. Although we have learned much, we still do not... (Review)
Review
Since its initial misidentification as a trypanosome some 100 years ago, Pneumocystis has remained recalcitrant to study. Although we have learned much, we still do not have definitive answers to such basic questions as, where is the reservoir of infection, how does Pneumocystis reproduce, what is the mechanism of infection, and are there true species of Pneumocystis? The goal of this review is to provide the reader the most up to date information available about the biology of Pneumocystis and the disease it produces.
Topics: Humans; Pneumocystis; Pneumocystis Infections; Pneumonia, Pneumocystis; Virulence Factors
PubMed: 25367973
DOI: 10.1101/cshperspect.a019828 -
Clinical Microbiology and Infection :... Sep 2020Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring semi-invasive respiratory sampling. The serum 1,3-β-D-glucan (BDG) assay has been proposed as a minimally invasive test for the presumptive diagnosis of PJP.
METHOD
We carried out a systematic review and meta-analysis using articles in the English language published between January 1960 and September 2019. We estimated the pooled sensitivity and specificity of BDG testing using a bivariate random effects approach and compared test performance in human immunodeficiency virus (HIV) and non-HIV subgroups with meta-regression. Data from the pooled sensitivity and specificity were transformed to generate pre- and post-test probability curves.
RESULTS
Twenty-three studies were included. The pooled sensitivity and specificity of serum BDG testing for PJP were 91% (95%CI 87-94%) and 79% (95%CI 72-84%) respectively. The sensitivity in patients with HIV was better than in patients without (94%, 95%CI 91-96%) versus 86% (95%CI 78-91%) (p 0.02), with comparable specificity (83%, 95%CI 69-92% versus 83%, 95%CI 72-90%) (p 0.10). A negative BDG was only associated with a low post-test probability of PJP (≤5%) when the pre-test probability was low to intermediate (≤20% in non-HIV and ≤50% in HIV).
CONCLUSIONS
Among patients with a higher likelihood of PJP, the pooled sensitivity of BDG is insufficient to exclude infection. Similarly, for most cases, the pooled specificity is inadequate to diagnose PJP. Understanding the performance of BDG in the population being investigated is therefore essential to optimal clinical decision-making.
Topics: Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Sensitivity and Specificity; Serologic Tests; beta-Glucans
PubMed: 32479781
DOI: 10.1016/j.cmi.2020.05.024 -
MBio Feb 2023Pneumocystis jirovecii kills hundreds of thousands of immunocompromised patients each year. Yet many aspects of the biology of this obligate pathogen remain obscure...
Pneumocystis jirovecii kills hundreds of thousands of immunocompromised patients each year. Yet many aspects of the biology of this obligate pathogen remain obscure because it is not possible to culture the fungus independently of its host. Consequently, our understanding of Pneumocystis pathobiology is heavily reliant upon bioinformatic inferences. We have exploited a powerful combination of genomic and phylogenetic approaches to examine the evolution of transcription factors in Pneumocystis species. We selected protein families (Pfam families) that correspond to transcriptional regulators and used bioinformatic approaches to compare these families in the seven Pneumocystis species that have been sequenced to date with those from other yeasts, other human and plant pathogens, and other obligate parasites. Some Pfam families of transcription factors have undergone significant reduction during their evolution in the Pneumocystis genus, and other Pfam families have been lost or appear to be in the process of being lost. Meanwhile, other transcription factor families have been retained in Pneumocystis species, and some even appear to have undergone expansion. On this basis, Pneumocystis species seem to have retained transcriptional regulators that control chromosome maintenance, ribosomal gene regulation, RNA processing and modification, and respiration. Meanwhile, regulators that promote the assimilation of alternative carbon sources, amino acid, lipid, and sterol biosynthesis, and iron sensing and homeostasis appear to have been lost. Our analyses of transcription factor retention, loss, and gain provide important insights into the biology and lifestyle of Pneumocystis. Pneumocystis jirovecii is a major fungal pathogen of humans that infects healthy individuals, colonizing the lungs of infants. In immunocompromised and transplant patients, this fungus causes life-threatening pneumonia, and these Pneumocystis infections remain among the most common and serious infections in HIV/AIDS patients. Yet we remain remarkably ignorant about the biology and epidemiology of Pneumocystis due to the inability to culture this fungus . Our analyses of transcription factor retentions, losses, and gains in sequenced Pneumocystis species provide valuable new views of their specialized biology, suggesting the retention of many metabolic and stress regulators and the loss of others that are essential in free-living fungi. Given the lack of culture methods for Pneumocystis, this powerful bioinformatic approach has advanced our understanding of the lifestyle of and the nature of its dependence on the host for survival.
Topics: Humans; Pneumocystis; Phylogeny; Transcription Factors; Pneumonia, Pneumocystis; Pneumocystis carinii; Genomics; Life Style
PubMed: 36651897
DOI: 10.1128/mbio.02711-22 -
Clinical Microbiology Reviews Apr 2012Although the incidence of Pneumocystis pneumonia (PCP) has decreased since the introduction of combination antiretroviral therapy, it remains an important cause of... (Review)
Review
Although the incidence of Pneumocystis pneumonia (PCP) has decreased since the introduction of combination antiretroviral therapy, it remains an important cause of disease in both HIV-infected and non-HIV-infected immunosuppressed populations. The epidemiology of PCP has shifted over the course of the HIV epidemic both from changes in HIV and PCP treatment and prevention and from changes in critical care medicine. Although less common in non-HIV-infected immunosuppressed patients, PCP is now more frequently seen due to the increasing numbers of organ transplants and development of novel immunotherapies. New diagnostic and treatment modalities are under investigation. The immune response is critical in preventing this disease but also results in lung damage, and future work may offer potential areas for vaccine development or immunomodulatory therapy. Colonization with Pneumocystis is an area of increasing clinical and research interest and may be important in development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss current clinical and research topics in the study of Pneumocystis and highlight areas for future research.
Topics: Carrier State; HIV Infections; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 22491773
DOI: 10.1128/CMR.00013-12 -
Chest Jun 2024Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical... (Observational Study)
Observational Study
BACKGROUND
Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated.
RESEARCH QUESTION
Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease?
STUDY DESIGN AND METHODS
In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to the European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality.
RESULTS
Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95% CI, 2.16-14.1; P < .001), IMIDs (OR, 2.19; 95% CI, 1.05-4.60; P = .037), long-term corticosteroid exposure (OR, 2.07; 95% CI, 1.03-4.31; P = .045), cysts in sputum/BAL smears (OR, 1.92; 95% CI, 1.02-3.62; P = .043), and SOFA score at admission (OR, 1.58; 95% CI, 1.39-1.82; P < .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95% CI, 1.03-2.71; P = .035), especially for a prednisone daily dose ≥ 10 mg (OR, 1.80; 95% CI, 1.14-2.85; P = .010).
INTERPRETATION
Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs.
Topics: Humans; Pneumonia, Pneumocystis; Male; Female; Retrospective Studies; Middle Aged; Prognosis; Aged; Pneumocystis carinii; Immunocompromised Host; Risk Factors
PubMed: 38215935
DOI: 10.1016/j.chest.2024.01.015 -
Frontiers in Cellular and Infection... 2022can result in a serious pulmonary infection, pneumonia, in immunocompetent hosts. The diagnosis of pneumonia has long been a major clinical concern, and there are...
BACKGROUND
can result in a serious pulmonary infection, pneumonia, in immunocompetent hosts. The diagnosis of pneumonia has long been a major clinical concern, and there are limitations with the currently utilized immunostaining and polymerase chain reaction diagnosis/detection technologies (, insufficient sensitivity and accuracy). Hence, we sought to establish a rapid and RNA-specific transcription mediated amplification and CRISPR/Cas13a-based diagnostics targeted -mitochondrial large subunit ribosomal RNA.
METHODS
The procedure of the diagnostics included amplification of the extracted RNA samples by transcription mediated amplification, followed by CRISPR/Cas13 detection, and ultimately, the judgment of the results after 30 minutes of fluorescence signal. Later, the diagnostic performance of the CRISPR/Cas13-based diagnostics were tested on the 62 surplus clinical samples.
RESULTS
This CRISPR/Cas13-based diagnostics achieved limits of detection of approximately 2 copies/µL transcribed RNA templates, with no cross reaction to other respiratory pathogens, including bacteria and fungi. Similar to in-house quantitative real-time polymerase chain reaction, CRISPR/Cas13-based diagnostics was still positive in 243-fold diluted bronchial alveolar lavage fluid. A preliminary evaluation of 62 surplus bronchial alveolar lavage fluid samples from patients suspected of pneumonia showed that CRISPR/Cas13-based diagnostics achieved a 78.9% sensitivity and a 97.7% specificity in the diagnosis of pneumonia.
CONCLUSION
Our study demonstrates that the CRISPR/Cas13-based diagnostics technique has good performance for the accurate and specific diagnosis of pneumonia.
Topics: CRISPR-Cas Systems; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; RNA; Real-Time Polymerase Chain Reaction
PubMed: 35782118
DOI: 10.3389/fcimb.2022.904485 -
Therapeutic Advances in Respiratory... Feb 2011Pneumocystis is an opportunistic fungal pathogen that causes an often-lethal pneumonia in immunocompromised hosts. Although the organism was discovered in the early... (Review)
Review
Pneumocystis is an opportunistic fungal pathogen that causes an often-lethal pneumonia in immunocompromised hosts. Although the organism was discovered in the early 1900s, the first cases of Pneumocystis pneumonia in humans were initially recognized in Central Europe after the Second World War in premature and malnourished infants. This unusual lung infection was known as plasma cellular interstitial pneumonitis of the newborn, and was characterized by severe respiratory distress and cyanosis with little or no fever and no pathognomic physical signs. At that time, only anecdotal cases were reported in adults and usually these patients had a baseline malignancy that led to a malnourished state. In the 1960-1970s additional cases were described in adults and children with hematological malignancies, but Pneumocystis pneumonia was still considered a rare disease. However, in the 1980s, with the onset of the HIV epidemic, Pneumocystis prevalence increased dramatically and became widely recognized as an opportunistic infection that caused potentially life-treating pneumonia in patients with impaired immunity. During this time period, prophylaxis against this organism was more generally instituted in high-risk patients. In the 1990s, with widespread use of prophylaxis and the initiation of highly active antiretroviral therapy (HAART) in the treatment of HIV-infected patients, the number of cases in this specific population decreased. However, Pneumocystis pneumonia still remains an important cause of severe pneumonia in patients with HIV infection and is still considered a principal AIDS-defining illness. Despite the decreased number of cases among HIV-infected patients over the past decade, Pneumocystis pneumonia continues to be a serious problem in immunodeficient patients with other immunosuppressive conditions. This is mostly due to increased use of immunosuppressive medications to treat patients with autoimmune diseases, following bone marrow and solid organ transplantation, and in patients with hematological and solid malignancies. Patients with hematologic disorders and solid organ and hematopoietic stem cell transplantation are currently the most vulnerable groups at risk for developing this infection. However, any patient with an impaired immunity, such as those receiving moderate doses of oral steroids for greater than 4 weeks or those receiving other immunosuppressive medications are at also at significant risk.
Topics: AIDS-Related Opportunistic Infections; Humans; Pneumocystis; Pneumonia, Pneumocystis; Risk Factors
PubMed: 20736243
DOI: 10.1177/1753465810380102 -
PLoS Pathogens Sep 2020
Review
Topics: Animals; Humans; Lung; Pneumocystis; Pneumonia, Pneumocystis; Species Specificity
PubMed: 32913371
DOI: 10.1371/journal.ppat.1008824 -
PLoS Pathogens Dec 2018
Review
Topics: Animals; Cell Proliferation; Humans; Life Cycle Stages; Pneumocystis; Pneumonia, Pneumocystis; Reproduction, Asexual
PubMed: 30521646
DOI: 10.1371/journal.ppat.1007409