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Clinical Microbiology and Infection :... Aug 2023Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in patients without HIV infection. In contrast to PCP in patients infected with HIV, diagnosis is often... (Review)
Review
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) incidence is increasing in patients without HIV infection. In contrast to PCP in patients infected with HIV, diagnosis is often delayed and illness is associated with increased mortality.
OBJECTIVES
To provide a comprehensive review of clinical presentation, risk factors, diagnostic strategies, and treatment options for PCP in patients without HIV infection.
SOURCES
Web-based literature review on PCP for trials, meta-analyses, and systematic reviews using PubMed. The restriction to the English language was applied.
CONTENT
Common underlying conditions in patients without HIV infection having PCP are haematological malignancies, autoimmune and inflammatory diseases, solid organ or haematopoietic stem cell transplant, and previous corticosteroid exposure. New risk groups include patients receiving monoclonal antibodies and immunomodulating therapies. Patients without HIV infection who have PCP present with rapid onset and progression of pneumonia, increased duration of hospitalization and a significantly higher mortality rate than patients infected with HIV. PCP is diagnosed by a combination of clinical symptoms and radiological as well as mycological features. Results of immunofluorescence microscopy from bronchoalveolar lavage, PCR testing, and computed tomography imaging as well as the evaluation of clinical presentation are required. The established treatment regime consists of trimethoprim and sulfamethoxazole.
IMPLICATIONS
Although the number of patients with immunosuppression due to causes different from HIV is increasing, a simultaneous rise in PCP incidence is observed. In the group of patients without HIV infection, rapid onset of symptoms, a more complex course, and a high mortality rate are recorded. Therefore, the time to diagnosis must be as short as possible to initiate effective therapy promptly. This review aims to raise awareness of PCP in an increasingly affected at-risk group and provides clinicians with a practical guide for efficient diagnosis and targeted therapy. Furthermore, it intends to display current inadequacies in research on the topic of PCP.
Topics: Humans; HIV Infections; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Bronchoalveolar Lavage; Pneumocystis carinii
PubMed: 37086781
DOI: 10.1016/j.cmi.2023.04.015 -
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 -
Trends in Microbiology Dec 2020
Topics: Genome, Fungal; Humans; Lung; Pneumocystis Infections; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 33171104
DOI: 10.1016/j.tim.2020.03.006 -
Pediatrics in Review Dec 2023
Topics: Humans; Pneumonia, Pneumocystis; Pneumonia
PubMed: 38036438
DOI: 10.1542/pir.2022-005516 -
Mycopathologia Oct 2020Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity in immunocompromised patients, with a higher mortality in non-HIV than in HIV patients. P.... (Review)
Review
Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity in immunocompromised patients, with a higher mortality in non-HIV than in HIV patients. P. jirovecii is one of the rare transmissible pathogenic fungi and the only one that depends fully on the host to survive and proliferate. Transmissibility among humans is one of the main specificities of P. jirovecii. Hence, the description of multiple outbreaks raises questions regarding preventive care management of the disease, especially in the non-HIV population. Indeed, chemoprophylaxis is well codified in HIV patients but there is a trend for modifications of the recommendations in the non-HIV population. In this review, we aim to discuss the mode of transmission of P. jirovecii, identify published outbreaks of PCP and describe molecular tools available to study these outbreaks. Finally, we discuss public health and infection control implications of PCP outbreaks in hospital setting for in- and outpatients.
Topics: Chemoprevention; Cross Infection; Disease Outbreaks; HIV Infections; Humans; Immunocompromised Host; Infection Control; Mycological Typing Techniques; Pneumocystis carinii; Pneumonia, Pneumocystis; Public Health; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 31782069
DOI: 10.1007/s11046-019-00408-w -
The New England Journal of Medicine Mar 2021
Topics: AIDS-Related Opportunistic Infections; Acute Kidney Injury; Adult; Anti-Bacterial Agents; Crystallization; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination; Urinalysis; Urine
PubMed: 33734650
DOI: 10.1056/NEJMicm2028020 -
Methods in Molecular Biology (Clifton,... 2023Pneumocystis jirovecii causes pneumonia in immunocompromised patients. A major challenge in drug susceptibility testing and in understanding host/pathogen interactions... (Review)
Review
Pneumocystis jirovecii causes pneumonia in immunocompromised patients. A major challenge in drug susceptibility testing and in understanding host/pathogen interactions is that Pneumocystis spp. are not viable in vitro. Continuous culture of the organism is not currently available, and therefore, developing new drug targets is very limited. Due to this limitation, mouse models of Pneumocystis pneumonia have proven to be an invaluable resource to researchers. In this chapter, we provide an overview of selected methods used in mouse models of infection including, in vivo Pneumocystis murina propagation, routes of transmission, genetic mouse models available, a P. murina life form-specific model, a mouse model of PCP immune reconstitution inflammatory syndrome (IRIS), and the experimental parameters associated with these models.
Topics: Animals; Mice; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 37145284
DOI: 10.1007/978-1-0716-3199-7_13 -
Respiratory Investigation Jul 2022While Pneumocystis jirovecii pneumonia (PCP) can occur in immunocompromised patients with HIV infection, the prognosis of non-HIV PCP is still poor, showing a high... (Review)
Review
While Pneumocystis jirovecii pneumonia (PCP) can occur in immunocompromised patients with HIV infection, the prognosis of non-HIV PCP is still poor, showing a high mortality rate of 30%-75%. The pathophysiological mechanism of non-HIV PCP is quite different from that of HIV-PCP. Aging, underlying disease, dysbiotic gut microbiome, and Th1 predominance, leads to macrophagic polarization shifting from M2 to M1. These cause dysregulation in the host immunity against P. jirovecii, resulting in severe lung injury and a high mortality rate among non-HIV PCP patients. This review describes poor prognostic factors, an issue of predictive values used for general pneumonia practice, and new aspects, including the dysbiosis of the gut microbiome and macrophagic polarization in the treatment of non-HIV PCP.
Topics: HIV Infections; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Prognosis
PubMed: 35501264
DOI: 10.1016/j.resinv.2022.04.002 -
Pulmonology 2022
Topics: Acrylamides; Aniline Compounds; Humans; Indoles; Leukopenia; Lymphopenia; Pneumonia, Pneumocystis; Pyrimidines
PubMed: 35701337
DOI: 10.1016/j.pulmoe.2022.04.005 -
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