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Expert Review of Respiratory Medicine 2022is an opportunistic, human-specific fungus that causes pneumonia (PCP). PCP symptoms are nonspecific. A patient with and another lung infection faces a diagnostic... (Review)
Review
INTRODUCTION
is an opportunistic, human-specific fungus that causes pneumonia (PCP). PCP symptoms are nonspecific. A patient with and another lung infection faces a diagnostic challenge. It may be difficult to determine which of these agents is responsible for the clinical symptoms, preventing effective treatment. Diagnostic and treatment efforts have been made more difficult by the rising frequency with which coronavirus 2019 (COVID-19) and PCP co-occur.
AREAS COVERED
Herein, we provide a comprehensive review of clinical and pharmacological recommendations along with a literature review of PCP in immunocompromised patients focusing on HIV-uninfected patients.
EXPERT OPINION
PCP may be masked by identifying co-existing pathogens that are not necessarily responsible for the observed infection. Patients with severe form COVID-19 should be examined for underlying immunodeficiency, and co-infections must be considered as co-infection with may worsen COVID-19's severity and fatality. PCP should be investigated in patients with PCP risk factors who come with pneumonia and suggestive radiographic symptoms but have not previously received PCP prophylaxis. PCP prophylaxis should be explored in individuals with various conditions that impair the immune system, depending on their PCP risk.
Topics: Humans; Pneumonia, Pneumocystis; COVID-19; Pneumocystis carinii; Immunocompromised Host; HIV Infections
PubMed: 36440485
DOI: 10.1080/17476348.2022.2152332 -
Frontiers in Cellular and Infection... 2020pneumonia (PCP) is an AIDS-defining illness. In patients with HIV, the benefit of PCP prophylaxis is well-defined when the CD4 T-cell count decreases below 200...
pneumonia (PCP) is an AIDS-defining illness. In patients with HIV, the benefit of PCP prophylaxis is well-defined when the CD4 T-cell count decreases below 200 cells/μL. In other immunocompromised patients, the value of PCP prophylaxis is not always as well-established. This study aimed to describe the epidemiology of PCP in recent years and assess how many patients with PCP did or did not receive prophylaxis in the month preceding the infection. A multicenter retrospective study was performed in 3 tertiary care hospital. A list of patients that underwent broncho-alveolar lavage sampling and (PJ) PCR testing was retrieved from the microbiology laboratories. An in-house PJ quantitative PCR (qPCR) was used in each center. A cycle threshold (Ct) value of ≤ 28.5-30 was considered a probable PCP. For patients with a positive PJ qPCR but above this threshold, a predefined case definition of possible PCP was defined as a qPCR Ct value ≤ 34-35 and both of the following criteria: 1. Clinical and radiological features compatible with PCP and 2. The patient died or received PCP therapy and survived. Patient files from those with a qPCR Ct value ≤ 35 were reviewed to determine whether the patient fulfilled the case definition and if PCP prophylaxis had been used in the weeks preceding the PCP. Disease-specific guidelines, as well as hospital-wide guidelines, were used to evaluate if prophylaxis could be considered indicated. From 2012 to 2018, 482 BAL samples were tested. Two hundred and four had a qPCR Ct value ≤ 35 and were further evaluated: 90 fulfilled the definition of probable and 63 of possible PCP while the remaining 51 were considered colonized. Seventy-four percentages of the patients with PCP were HIV-negative. Only 11 (7%) of the 153 patients had received prophylaxis, despite that in 133 (87%) cases prophylaxis was indicated according to guidelines. In regions where HIV testing and treatment is available without restrictions, PCP is mainly diagnosed in non-HIV immunocompromised patients. More than four out of five patients with PCP had not received prophylaxis. Strategies to improve awareness of antimicrobial prophylaxis guidelines in immunocompromised patients are urgently needed.
Topics: Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Real-Time Polymerase Chain Reaction; Retrospective Studies
PubMed: 32500040
DOI: 10.3389/fcimb.2020.00224 -
Der Internist Jul 2019Pneumocystis jirovecii pneumonia (PcP) has for many years been reported mostly in human immunodeficiency virus-infected patients. Increasingly, it also affects other... (Review)
Review
Pneumocystis jirovecii pneumonia (PcP) has for many years been reported mostly in human immunodeficiency virus-infected patients. Increasingly, it also affects other immunocompromised patients, e.g. after organ or allogeneic stem cell/bone marrow transplantation, patients with hematologic malignancies or autoimmune diseases. The diagnosis of PcP relies on a critical evaluation of clinical symptoms, risk factors, radiologic features and microbiological tests. High dose cotrimoxazole is the most effective therapeutic option. Rapid initiation is essential, since mortality is especially high in patients admitted to intensive care with respiratory failure. This article reviews the current epidemiology of PcP and highlights the diagnostic and therapeutic options. Recommendations for primary and secondary prophylaxis are summarized.
Topics: Anti-Bacterial Agents; HIV Infections; Humans; Immunocompromised Host; Opportunistic Infections; Pneumocystis Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 31089770
DOI: 10.1007/s00108-019-0616-5 -
Frontiers in Immunology 2024Clinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of...
OBJECTIVE
Clinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of patients with MDA5+ DM, identify disease endotypes related to the heterogeneous manifestations and prognosis, and guide individualized therapy regimen.
METHODS
This inpatient cohort included 123 patients with MDA5+ DM. Unsupervised hierarchical clustering analysis was used to derive disease endotypes from the circulating immune cell profiles on admission. Clinical symptoms, laboratory test results, inpatient treatments, and disease outcomes were then analyzed among the identified endotypes.
RESULTS
Three disease endotypes in MDA5+ DM were identified from peripheral immune cell profiles. Endotype1 had the highest percentages of CD4 T cells and monocytes, and the lowest percentage of neutrophils; Endotype2 had the highest percentage of B cells; Endotype3 had the highest percentage of CD8 T cells and NK cells. Clinical and prognostic heterogeneity of the endotypes were revealed. Endotype1 had the lowest 3-month mortality with the high incidence of periungual capillary changes. Endotype2 and Endotype3 had higher prevalence of rapidly progressive interstitial lung disease (RPILD) and mortality at 3 months than Endotype1. Meanwhile, Endotype3 had higher pneumocystis jiroveci and CMV viremia cases with significantly elevated of activated CD8 T cells and multiple cytokines than Endotype1.
CONCLUSION
Clustering analysis of peripheral immune cell profiles identified three different endotypes in MDA5+ dermatomyositis. Endotpye2 and 3 showed higher RPILD, 3-month mortality, pneumocystis jiroveci and CMV viremia.
Topics: Humans; Interferon-Induced Helicase, IFIH1; Dermatomyositis; CD8-Positive T-Lymphocytes; Viremia; Lung Diseases, Interstitial; Cytomegalovirus Infections
PubMed: 38533498
DOI: 10.3389/fimmu.2024.1349611 -
Antimicrobial Agents and Chemotherapy Mar 2024cyst life forms contain abundant β-glucan carbohydrates, synthesized using β-1,3 and β-1,6 glucan synthase enzymes and the donor uridine diphosphate (UDP)-glucose....
cyst life forms contain abundant β-glucan carbohydrates, synthesized using β-1,3 and β-1,6 glucan synthase enzymes and the donor uridine diphosphate (UDP)-glucose. In yeast, phosphoglucomutase (PGM) plays a crucial role in carbohydrate metabolism by interconverting glucose 1-phosphate and glucose 6-phosphate, a vital step in UDP pools for β-glucan cell wall formation. This pathway has not yet been defined in . Herein, we surveyed the and genomes, which predicted a homolog of the major PGM enzyme. Furthermore, we show that PjPgm2p and PmPgm2p function similarly to the yeast counterpart. When both homologs are heterologously expressed in cells, both genes can restore growth and sedimentation rates to wild-type levels. Additionally, we demonstrate that yeast cell lysates expressing the two transcripts individually can restore PGM activities significantly altered in the yeast strain. The addition of lithium, a competitive inhibitor of yeast PGM activity, significantly reduces PGM activity. Next, we tested the effects of lithium on viability and found the compound displays significant anti- activity. Finally, we demonstrate that a para-aryl derivative (ISFP10) with known inhibitory activity against the PGM protein and exhibiting 50-fold selectivity over the human PGM enzyme homolog can also significantly reduce Pmpgm2 activity . Collectively, our data genetically and functionally validate phosphoglucomutases in both and and suggest the potential of this protein as a selective therapeutic target for individuals with pneumonia.
Topics: Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Phosphoglucomutase; Saccharomyces cerevisiae; Lithium; Pneumocystis; beta-Glucans; Phosphates; Glucose; Uridine Diphosphate
PubMed: 38259086
DOI: 10.1128/aac.00756-23 -
Medical Mycology Dec 2023Bronchoalveolar lavage fluid (BALF) is a standard respiratory sample for diagnosing invasive fungal diseases like Pneumocystis pneumonia (PCP) and invasive pulmonary... (Observational Study)
Observational Study
Bronchial aspirate obtained during bronchoscopy yields increased fungal load compared to bronchoalveolar lavage fluid in patients at risk of invasive aspergillosis and Pneumocystis pneumonia.
Bronchoalveolar lavage fluid (BALF) is a standard respiratory sample for diagnosing invasive fungal diseases like Pneumocystis pneumonia (PCP) and invasive pulmonary aspergillosis (IPA). However, procedural variations exist across medical centers and wards. This study aimed to compare the diagnostic potential of BALF and bronchial aspirate (BA) obtained during bronchoscopy in 173 patients suspected of fungal infections. A prospective observational study was conducted from April 2020 to November 2021. BALF and BA were collected during bronchoscopy and subjected to direct examination, fungal culture, Aspergillus fumigatus qPCR (AfqPCR), and Pneumocystis jirovecii qPCR (PjqPCR). Galactomannan detection was performed on BALF. Patients were classified based on established European Organization for Research and Treatment of Cancer (EORTC) criteria. Out of 173 patients, 75 tested positive for at least one test in BA or BALF. For Aspergillus, proportion of positive AfqPCR (14.5% vs. 9.2%; P < 0.0001) and fungal loads (Cq of 31.3 vs. 32.8; P = 0.0018) were significantly higher in BA compared to BALF. For Pneumocystis, fungal loads by PjqPCR was also higher in BA compared to BALF (Cq of 34.2 vs. 35.7; P = 0.003). BA only detected A. fumigatus and P. jirovecii in 12 (42.9%) and 8 (19.5%) patients, respectively. BA obtained during a BAL procedure can be a suitable sample type for increased detection of P. jirovecii and A. fumigatus by qPCR. The use of BA in diagnostic algorithms requires further investigation in prospective studies.
Topics: Humans; Bronchoalveolar Lavage Fluid; Pneumonia, Pneumocystis; Bronchoscopy; Prospective Studies; Sensitivity and Specificity; Aspergillosis; Invasive Pulmonary Aspergillosis; Pneumocystis carinii; Mannans
PubMed: 37996394
DOI: 10.1093/mmy/myad120 -
Frontiers in Cellular and Infection... 2020pneumonia (PCP) remains the most frequent AIDS-defining illness in developed countries. This infection also occurs in non-AIDS immunosuppressed patients, e.g., those... (Review)
Review
pneumonia (PCP) remains the most frequent AIDS-defining illness in developed countries. This infection also occurs in non-AIDS immunosuppressed patients, e.g., those who have undergone an organ transplantation. Moreover, mild infections related to low pulmonary fungal burden, frequently designated as pulmonary colonization, occurs in patients with chronic pulmonary diseases, e.g., cystic fibrosis (CF). Indeed, this autosomal recessive disorder alters mucociliary clearance leading to bacterial and fungal colonization of the airways. This mini-review compiles and discusses available information on and CF. It highlights significant differences in the prevalence of pulmonary colonization in European and Brazilian CF patients. It also describes the microbiota associated with in CF patients colonized by . Furthermore, we have described genomic diversity in colonized CF patients. In addition of pulmonary colonization, it appears that PCP can occur in CF patients specifically after lung transplantation, thus requiring preventive strategies. In other respects, primary infection is a worldwide phenomenon occurring in non-immunosuppressed infants within their first months. The primary infection is mostly asymptomatic but it can also present as a benign self-limiting infection. It probably occurs in the same manner in CF infants. Nonetheless, two cases of severe primary infection mimicking PCP in CF infants have been reported, the genetic disease appearing in these circumstances as a risk factor of PCP while the host-pathogen interaction in older children and adults with pulmonary colonization remains to be clarified.
Topics: Adult; Brazil; Child; Cystic Fibrosis; Humans; Infant; Lung; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 33117730
DOI: 10.3389/fcimb.2020.571253 -
Journal of Medical Microbiology Jun 2023C-type lectin receptors (CLRs) are prominently expressed on myeloid cells where they perform multiple functions including serving as pattern recognition receptors...
C-type lectin receptors (CLRs) are prominently expressed on myeloid cells where they perform multiple functions including serving as pattern recognition receptors (PRRs) to drive innate as well as adaptive immunity to pathogens. Depending on the presence of a tyrosine-based signalling motif, CLR-microbial pathogen engagement may result in either anti- or pro-inflammatory signalling. In this manuscript, we report our laboratory study of two novel CLRs that recognize cell wall homogenates (CWH) and a purified cell wall fraction (CWF). To study the potential of newly generated hFc-CLR fusions on binding to CWHs and CWFs and subsequent downstream inflammatory signalling analysis. Newly generated hFc-CLR fusion CLEC4A and CLEC12B were screened against CWHs and CWFs preparations via modified ELISA. Immunofluorescence assay (IFA) was utilized to visualize hFc-CLR fusion binding against intact fixed fungal life forms to verify results. Quantitative PCR (q-PCR) analysis of lung mRNA from the mouse immunosuppressed Pneumocystis pneumonia (PCP) model versus uninfected mice was employed to detect possible changes in the respective and transcripts. Lastly, siRNA technology of both CLRs was conducted to determine effects on downstream inflammatory events in mouse macrophages stimulated in the presence of CWFs. We determined that both CLEC4A and CLEC12B hFc-CLRs displayed significant binding with CWHs and CWFs. Binding events showed significant binding to both curdlan and laminarin, both polysaccharides containing β-(1,3) glucans as well as -acetylglucosamine (GlcNAc) residues and modest yet non-significant binding to the negative control carbohydrate dextran. IFA with both CLR hFc-fusions against whole life forms corroborated these findings. Lastly, we surveyed the mRNA expression profiles of both CLRs tested above in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model and determined that both CLRs were significantly up regulated during infection. Lastly, siRNA of both CLRs in the mouse RAW macrophage cell line was conducted and results demonstrated that silencing of resulted in no significant changes in TNF-alpha generation in CWF stimulated macrophages. On the contrary, silencing of CLR resulted in significant decreases in TNF-alpha in RAW cells stimulated with the same CWF. The data presented here provide new members of the CLRs family recognizing . Future studies using CLEC4A and/or CLEC12B deficient mice in the PCP mouse model should provide further insights into the host immunological response to .
Topics: Mice; Animals; Lectins, C-Type; Pneumonia, Pneumocystis; Tumor Necrosis Factor-alpha; Pneumocystis; Cell Wall; RNA, Small Interfering; RNA, Messenger
PubMed: 37294293
DOI: 10.1099/jmm.0.001714 -
Pharmacotherapy Nov 2022Patients with inflammatory bowel disease (IBD) are at increased risk of developing Pneumocystis jirovecii pneumonia (PJP) than the general population. Many medications... (Review)
Review
Patients with inflammatory bowel disease (IBD) are at increased risk of developing Pneumocystis jirovecii pneumonia (PJP) than the general population. Many medications utilized for the treatment of IBD affect the immune system, potentially further increasing the risk of PJP. Recommendations for prophylaxis against PJP in this patient population are based upon limited evidence, and risk factors for PJP development are not well-agreed upon. The purpose of this systematic review was to consolidate and evaluate the evidence for PJP prophylaxis in patients with IBD. An electronic literature search was performed, and 29 studies were included in the review, of which 24 were case reports or case series. Combined data from five cohort studies showed an absolute risk of developing PJP to be 0.07%. The majority of patients who developed PJP were receiving corticosteroids at the time of diagnosis (76%). The number of concomitant immunosuppressants received at time of PJP diagnosis varied from one to four. All studies reporting treatment of PJP utilized sulfamethoxazole-trimethoprim. Of the 27 studies reporting mortality data, 19% of patients died. Given the lack of conclusive data regarding risk factors for PJP development and the overall low incidence of PJP in patients with IBD, it is recommended to assess the patient's risk on a case-by-case basis to determine whether PJP prophylaxis is warranted.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination; Inflammatory Bowel Diseases; Immunosuppressive Agents
PubMed: 36222368
DOI: 10.1002/phar.2733 -
The Korean Journal of Parasitology Oct 2022This study determined the recent status and trend of Pneumocystis jirovecii pneumonia (PcP) in the non-human immunodeficiency virus (HIV) (non-HIV-PcP) and HIV (HIV-PcP)...
This study determined the recent status and trend of Pneumocystis jirovecii pneumonia (PcP) in the non-human immunodeficiency virus (HIV) (non-HIV-PcP) and HIV (HIV-PcP) infected populations using data from the Health Insurance Review & Assessment Service (HIRA) and the Korea Disease Control and Prevention Agency (KDCA). SaTScan and Joinpoint were used for statistical analyses. Non-HIV-PcP cases showed an upward trend during the study period from 2010 to 2021, with the largest number in 2021 (551 cases). The upward trend was similar until 2020 after adjusting for the population. Seoul had the highest number of cases (1,597) in the non-HIV-PcP group, which was the same after adjusting for the population (162 cases/1,000,000). It was followed by Jeju-do (89 cases/1,000,000). The most likely cluster (MLC) for the non-HIV-PCP group was Seoul (Relative Risk (RR)=4.59, Log Likelihood Ratio (LLR)=825.531), followed by Jeju-do (RR=1.59, LLR=5.431). An upward trend was observed among the non-HIV-PcP group in the Jeju-do/Jeollanam-do/Jeollabuk-do/Gyeongsangnam-do/Busan/Daejeon/Daegu/Ulsan joint cluster (29.02%, LLR=11.638, P<0.001) located in the southern part of Korea. Both women and men in the non-HIV groups showed an overall upward trend of PcP during the study period. Men in the 60-69 age group had the highest annual percentage change (APC 41.8) during 2014-2019. In contrast, the HIV groups showed a falling trend of PcP recently. Men in the 60-69 age group had the most decrease (APC -17.6) during 2018-2021. This study provides an analytic basis for health measures and a nationwide epidemiological surveillance system for the management of PcP.
Topics: Female; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; HIV Infections; Risk; Republic of Korea
PubMed: 36320109
DOI: 10.3347/kjp.2022.60.5.327