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Revista Da Sociedade Brasileira de... 2023
Topics: Humans; Pneumonia, Pneumocystis; Risk Factors; Adrenal Cortex Hormones; Pneumocystis carinii
PubMed: 36820664
DOI: 10.1590/0037-8682-0553-2022 -
BMC Infectious Diseases Jul 2019Pneumocystis jirovecii pneumonia (PCP) is one of the most common HIV-related opportunistic infections. The diagnosis of PCP is based on analyses from respiratory tract...
Serum-based diagnosis of Pneumocystis pneumonia by detection of Pneumocystis jirovecii DNA and 1,3-β-D-glucan in HIV-infected patients: a retrospective case control study.
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is one of the most common HIV-related opportunistic infections. The diagnosis of PCP is based on analyses from respiratory tract specimens which may require the invasive procedure of a diagnostic bronchoscopy. The objective of this study was to evaluate the diagnostic potential of Pneumocystis jirovecii PCR in serum combined with the 1,3-β-D-glucan (betaglucan) test for the diagnosis of PCP in HIV-infected patients.
METHODS
This was a retrospective case-control study including serum samples from 26 HIV-infected patients with PCP collected within 5 days prior to the start of PCP treatment, 21 HIV-infected control subjects matched by blood CD4 cell counts, and 18 blood donors. The serum samples were analyzed for Pneumocystis jirovecii PCR and betaglucan. The reference standard for PCP was based on previously described microbiological and clinical criteria.
RESULTS
All patients with PCP had detectabe Pneumocystis jirovecii DNA in serum yielding a sensitivity for the Pneumocystis jirovecii PCR assay in serum of 100%. All blood donors had negative Pneumocystis PCR in serum. The specificity when testing HIV-infected patients was 71%, but with a PCR Cycle threshold (Ct) value of 34 as cut-off the specificity was 90%. At a putative pretest probaility of 20%, the negative and positive predictive value for the Pneumocystis PCR assay in serum was 0.99 and 0.71, respectively. Betaglucan with cut-off level 200 pg/ml combined with a positive Pneumocystis jirovecii PCR result had sensitivity and specificity of 92 and 90%, respectively. The concentration of Pneumocystis jirovecii DNA in serum samples, expressed by the PCR Ct values, correlated inversely to the betaglucan levels in serum.
CONCLUSION
In this case-control study including 70% of all HIV-infected patients with PCP treated at Sahlgrenska University Hospital during a time period of 13 years, Pneumocystis PCR analysis on serum samples had a very high sensitivity and negative predictive value for the diagnosis of PCP in HIV-infected patients. A serum-based diagnostic procedure either based on Pneumocystis jirovecii PCR alone or in combination with betaglucan analysis may thus be feasible and would facilitate the care of HIV-infected patients with suspected PCP.
Topics: AIDS-Related Opportunistic Infections; Adolescent; Adult; Aged; Blood Donors; Case-Control Studies; DNA, Fungal; Female; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Retrospective Studies; Sensitivity and Specificity; beta-Glucans
PubMed: 31337356
DOI: 10.1186/s12879-019-4289-4 -
BMC Infectious Diseases Nov 2023Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to...
OBJECTIVE
Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj.
METHODS
A total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed.
RESULTS
Pj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support.
CONCLUSION
The scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent.
Topics: Humans; Pneumonia, Pneumocystis; Retrospective Studies; DNA Copy Number Variations; Bronchoalveolar Lavage Fluid; Polymerase Chain Reaction; Pneumocystis; Respiratory Distress Syndrome; Pneumocystis carinii
PubMed: 38012564
DOI: 10.1186/s12879-023-08580-7 -
Current Opinion in Microbiology Dec 2017Pneumocystis jirovecii causes clinical pneumonia in immunocompromised hosts. Despite this, the inability to cultivate this organism in vitro has likely hindered the... (Review)
Review
Pneumocystis jirovecii causes clinical pneumonia in immunocompromised hosts. Despite this, the inability to cultivate this organism in vitro has likely hindered the field in ascertaining the true impact of Pneumocystis in human infection. However the recent release of the genome as well as in advances in understanding host genetics, and other risk factors for infection and robust experimental models of disease have shed new light on the impact of this fungal pathogen as to better define populations at risk. This review will highlight these recent advances as well as highlight future needed areas of research.
Topics: Animals; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 29136537
DOI: 10.1016/j.mib.2017.10.019 -
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 -
International Journal of Infectious... Sep 2022To investigate the clinical outcomes and risk factors of mortality in patients with rheumatic diseases complicated by Pneumocystis pneumonia (PCP).
OBJECTIVES
To investigate the clinical outcomes and risk factors of mortality in patients with rheumatic diseases complicated by Pneumocystis pneumonia (PCP).
METHODS
Between November 2015 and April 2021, patients with rheumatic diseases with PCP in a tertiary referral hospital were retrospectively enrolled. The diagnosis of PCP requires the fulfillment of clinical, radiographic, and microbiological criteria. Factors associated with in-hospital, 30-day, and 90-day mortality were evaluated.
RESULTS
A total of 128 patients with rheumatic diseases who had a positive quantitative polymerase chain reaction assay for Pneumocystis jirovecii were screened, and 72 patients were included in the final analysis. The median (interquartile range [IQR]) pneumonia severity index (PSI) was 101.5 (77.0-132.0). The median (IQR) adjunctive corticosteroid dosage was 0.6 (0.4-0.9) mg/kg/day prednisolone equivalent. The receiver operating characteristic curve analysis showed that the optimal cutoff point of median adjunctive corticosteroid dosage was 0.6 mg/kg/day to predict in-hospital, 30-day, and 90-day mortality. In the multivariable logistic regression analysis, median adjunctive corticosteroid dosage ≥0.6 mg/kg/day and PSI >90 were independent factors of in-hospital, 30-day, and 90-day mortality.
CONCLUSION
A median adjunctive corticosteroid dosage of ≥0.6 mg/kg/day might be associated with mortality in patients with rheumatic diseases complicated by PCP.
Topics: Adrenal Cortex Hormones; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Rheumatic Diseases
PubMed: 35918031
DOI: 10.1016/j.ijid.2022.07.070 -
Infection Dec 2021Pneumocystis jirovecii (P. jirovecii) is increasingly identified on lower respiratory tract specimens of COVID-19 patients. Our narrative review aims to determine... (Review)
Review
BACKGROUND
Pneumocystis jirovecii (P. jirovecii) is increasingly identified on lower respiratory tract specimens of COVID-19 patients. Our narrative review aims to determine whether the diagnosis of pneumocystis jirovecii pneumonia (PJP) in COVID-19 patients represents coinfection or colonization based on the evidence available in the literature. We also discuss the decision to treat COVID-19 patients with coinfection by PJP.
METHODS
A literature search was performed through the Pubmed and Web of Science databases from inception to March 10, 2021.
RESULTS
We identified 12 COVID-19 patients suspected to have PJP coinfection. All patients were critically ill and required mechanical ventilation. Many were immunosuppressed from HIV or long-term corticosteroids and other immunosuppressive agents. In both the HIV and non-HIV groups, severe lymphocytopenia was encountered with absolute lymphocyte and CD4+T cell count less than 900 and 200 cells/mm, respectively. The time to PJP diagnosis from the initial presentation was 7.8 (range 2-21) days. Serum lactate dehydrogenase and beta-D-glucan were elevated in those coinfected with PJP. All patients were treated with anti-PJP therapy, predominantly sulfamethoxazole-trimethoprim with corticosteroids. The overall mortality rate was 41.6%, and comparable for both HIV and non-HIV groups.
CONCLUSION
As the current evidence is restricted to case reports, the true incidence, risk factors, and prognosis of COVID-19 patients with PJP coinfections cannot be accurately determined. Comorbidities of poorly controlled HIV with lymphocytopenia and multiple immunosuppressive therapies are likely predisposing factors for PJP coinfection.
Topics: COVID-19; Coinfection; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; SARS-CoV-2
PubMed: 34059997
DOI: 10.1007/s15010-021-01630-9 -
Annals of Clinical Microbiology and... Jan 2024Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary...
BACKGROUND
Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary colonization in individuals with mild immunosuppression or impaired respiratory function. PCP and Cytomegalovirus (CMV) co-infections have been widely described whereas those involving other Herpesviruses (HVs) such as Epstein-Barr virus (EBV), Herpes simplex virus type 1 and type 2 (HSV-1 and -2), and Varicella zoster virus (VZV) remain scarce. To date, no data are available concerning HVs co-infections in P. jirovecii colonization.
METHODS
Our main objective was to evaluate the frequency of HVs in bronchoalveolar lavage fluid (BALF) samples from patients with PCP or with pulmonary colonization. The secondary objective was to assess the relationship between HVs and the mortality rate in PCP patients. A retrospective single-center study over a seven-year period was conducted. All patients with P. jirovecii detected using PCR in a BALF sample and for whom a PCR assay for HVs detection was performed were included in the study.
RESULTS
One hundred and twenty-five patients were included, corresponding to 77 patients with PCP and 48 colonized patients. At least one HV was detected in 54/77 (70.1%) PCP patients and in 28/48 (58.3%) colonized patients. EBV was the most frequent in both groups. Furthermore, the 30-day survival rate in PCP patients was significantly lower with [EBV + CMV] co-infection than that with EBV co-infection, [EBV + HSV-1] co-infection and without HV co-infection.
CONCLUSION
Our results show that the frequency of HV, alone or in combination is similar in PCP and colonization. They also suggest that [EBV + CMV] detection in BALF samples from PCP patients is associated with an increased mortality rate, underlying the significance to detect HVs in the course of PCP.
Topics: Humans; Pneumocystis carinii; Retrospective Studies; Pneumonia, Pneumocystis; Coinfection; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Herpesviridae; Cytomegalovirus Infections
PubMed: 38245721
DOI: 10.1186/s12941-023-00663-2 -
JCI Insight Jan 2021Pneumocystis is an important opportunistic fungus that causes pneumonia in children and immunocompromised individuals. Recent genomic data show that divergence of major...
Pneumocystis is an important opportunistic fungus that causes pneumonia in children and immunocompromised individuals. Recent genomic data show that divergence of major surface glycoproteins may confer speciation and host range selectivity. On the other hand, immune clearance between mice and humans is well correlated. Thus, we hypothesized that humanize mice may provide information about human immune responses involved in controlling Pneumocystis infection. CD34-engrafted huNOG-EXL mice controlled fungal burdens to a greater extent than nonengrafted mice. Moreover, engrafted mice generated fungal-specific IgM. Fungal control was associated with a transcriptional signature that was enriched for genes associated with nonopsonic recognition of trophs (CD209) and asci (CLEC7A). These same genes were downregulated in CD4-deficient mice as well as twins with bare lymphocyte syndrome with Pneumocystis pneumonia.
Topics: Animals; Antibodies, Fungal; Antigens, CD34; Cell Adhesion Molecules; Disease Models, Animal; Female; Gene Expression; Hematopoietic Stem Cell Transplantation; Heterografts; Host Microbial Interactions; Host Specificity; Humans; Immunoglobulin G; Immunoglobulin M; Lectins, C-Type; Lung; Mice; Mice, Transgenic; Pneumocystis; Pneumonia, Pneumocystis; Receptors, Cell Surface; Species Specificity
PubMed: 33491669
DOI: 10.1172/jci.insight.139573 -
Clinical Infectious Diseases : An... Mar 2021Pneumocystis jirovecii pneumonia (PCP) causes substantive morbidity in immunocompromised patients. The EORTC/MSGERC convened an expert group to elaborate consensus...
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) causes substantive morbidity in immunocompromised patients. The EORTC/MSGERC convened an expert group to elaborate consensus definitions for Pneumocystis disease for the purpose of interventional clinical trials and epidemiological studies and evaluation of diagnostic tests.
METHODS
Definitions were based on the triad of host factors, clinical-radiologic features, and mycologic tests with categorization into probable and proven Pneumocystis disease, and to be applicable to immunocompromised adults and children without human immunodeficiency virus (HIV). Definitions were formulated and their criteria debated and adjusted after public consultation. The definitions were published within the 2019 update of the EORTC/MSGERC Consensus Definitions of Invasive Fungal Disease. Here we detail the scientific rationale behind the disease definitions.
RESULTS
The diagnosis of proven PCP is based on clinical and radiologic criteria plus demonstration of P. jirovecii by microscopy using conventional or immunofluorescence staining in tissue or respiratory tract specimens. Probable PCP is defined by the presence of appropriate host factors and clinical-radiologic criteria, plus amplification of P. jirovecii DNA by quantitative real-time polymerase chain reaction (PCR) in respiratory specimens and/or detection of β-d-glucan in serum provided that another invasive fungal disease and a false-positive result can be ruled out. Extrapulmonary Pneumocystis disease requires demonstration of the organism in affected tissue by microscopy and, preferably, PCR.
CONCLUSIONS
These updated definitions of Pneumocystis diseases should prove applicable in clinical, diagnostic, and epidemiologic research in a broad range of immunocompromised patients without HIV.
Topics: Adult; Child; Diagnostic Tests, Routine; HIV; HIV Infections; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Sensitivity and Specificity
PubMed: 33709126
DOI: 10.1093/cid/ciaa1805