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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 -
RoFo : Fortschritte Auf Dem Gebiete Der... Nov 2021Clinical signs and symptoms related to invasive fungal disease are nonspecific and need to be followed up by appropriate diagnostic procedures. The goal of this study...
Radiological CT Patterns and Distribution of Invasive Pulmonary Aspergillus, Non-Aspergillus, Cryptococcus and Pneumocystis Jirovecii Mold Infections - A Multicenter Study.
PURPOSE
Clinical signs and symptoms related to invasive fungal disease are nonspecific and need to be followed up by appropriate diagnostic procedures. The goal of this study was to analyze CT imaging patterns in invasive fungal infections and their correlation with the immune status and clinical outcome.
MATERIALS AND METHODS
We performed a retrospective multicenter study including 85 consecutive patients with invasive pulmonary fungal infection (2011-2014). Lung patterns on computed tomography (CT) scans were classified according to the Fleischner Society glossary. The patients were grouped according to immune status (neutropenia, steroid therapy, organ transplant recipient, and other cause) and outcome (positive outcome, progressive disease, and death). The Chi square test or Fisher exact test was used. Bonferroni correction was applied.
RESULTS
The total number of patients with invasive Aspergillus and non-Aspergillus infection (IANA), Pneumocystis jirovecii pneumonia (PCP), and Cryptococcus (CRY) was 60, 22, and 3, respectively. Patients with IANA demonstrated significantly more nodules (93 % vs. 59 %, p = 0.001), significantly fewer ground glass opacities (58 % vs. 96 %, p = 0.005), and significantly fewer positive lymph nodes (5 % vs. 41 %, p < 0.001) than patients with PCP. All patients with PCP and CRY had a favorable outcome. Patients with IANA and an adverse outcome demonstrated significantly more nodules with halo sign than patients with IANA and a favorable outcome (42.5 % vs. 15.9 %, p < 0.0001). Interestingly, patients with IANA and a favorable outcome had a higher prevalence of pulmonary infarction than patients with an adverse outcome (8 % vs. 1 %, p = 0.047). Patients with neutropenia showed significantly more consolidations (66 %) than organ transplant recipients (27 %, p = 0.045).
CONCLUSION
Patients with IANA showed a higher prevalence of nodules and a lower prevalence of ground glass opacities than patients with PCP. In patients with IANA, nodules with halo sign were associated with an adverse outcome. Patients with neutropenia showed generally more consolidations, but the consolidations were not associated with an adverse outcome.
KEY POINTS
· Nodules, ground glass opacities, and consolidations are common CT findings in all invasive pulmonary fungal infections.. · There is no pattern that is unique for one specific pathogen, although nodules are more predominant in IANA and Cryptococcus, and ground glass opacities are more predominant in PCP patients.. · Immune status had an impact on CT findings in fungal pneumonia with less consolidation in patients after organ transplantation compared to patients with neutropenia.. · Nodules with a halo sign are associated with a worse outcome..
CITATION FORMAT
· Obmann VC, Bickel F, Hosek N et al. Radiological CT Patterns and Distribution of Invasive Pulmonary Aspergillus, Non-Aspergillus, Cryptococcus and Pneumocystis Jirovecii Mold Infections - A Multicenter Study. Fortschr Röntgenstr 2021; 193: 1304 - 1314.
Topics: Aspergillus; Cryptococcus; Humans; Lung; Pneumocystis carinii; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 34034346
DOI: 10.1055/a-1482-8336 -
The Journal of Infectious Diseases Sep 2020Pneumocystis major surface glycoprotein (Msg) is a 120-kD surface protein complex on the organism with importance in adhesion and immune recognition. In this study, we...
BACKGROUND
Pneumocystis major surface glycoprotein (Msg) is a 120-kD surface protein complex on the organism with importance in adhesion and immune recognition. In this study, we show that Msg significantly impairs tumor necrosis factor (TNF)-α secretion by macrophages induced by Saccharomyces cerevisiae and Pneumocystis carinii (Pc) β-glucans.
METHODS
Major surface glycoprotein was shown to greatly reduce β-glucan-induced Dectin-1 immunoreceptor tyrosine-based activating motif (ITAM) phosphorylation. Major surface glycoprotein also down regulated Dectin-1 receptor messenger ribonucleic acid (mRNA) expression in the macrophages. It is interesting that Msg incubation with macrophages resulted in significant mRNA upregulation of both C-type lectin receptors (CLR) Mincle and MCL in Msg protein presence alone but to even greater amounts in the presence of Pc β-glucan.
RESULTS
The silencing of MCL and Mincle resulted in TNF-α secretions similar to that of macrophages treated with Pneumocystis β-glucan alone, which is suggestive of an inhibitory role for these 2 CLRs in Msg-suppressive effects on host cell immune response.
CONCLUSIONS
Taken together, these data indicate that the Pneumocystis Msg surface protein complex can act to suppress host macrophage inflammatory responses to the proinflammatory β -glucan components of the organisms.
Topics: Animals; Fungal Proteins; Lectins, C-Type; Macrophages; Membrane Glycoproteins; Mice; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; RAW 264.7 Cells; RNA, Messenger; Saccharomyces cerevisiae; Tumor Necrosis Factor-alpha; beta-Glucans
PubMed: 32363390
DOI: 10.1093/infdis/jiaa218 -
Advanced Drug Delivery Reviews May 2015The treatment of infection typically involves administration of antibiotics by a systemic route, such as intravenous or oral. However, pulmonary infections can also be... (Review)
Review
The treatment of infection typically involves administration of antibiotics by a systemic route, such as intravenous or oral. However, pulmonary infections can also be approached by inhalation of antibiotics as the infection is more directly accessible via the airways, making inhalation delivery essentially topical administration. This approach offers deposition of high antimicrobial concentrations directly at the site of infection but with a potentially reduced systemic exposure. This review covers the evidence for aerosolized antibiotics for the treatment of a number of conditions such as cystic fibrosis (CF), where it has become the standard of care for chronic infection, as well as non-CF bronchiectasis, non-tuberculous mycobacteria, and ventilator-associated infection where such therapy does not have an approved indication but has been used with increasing frequency.
Topics: Administration, Inhalation; Aerosols; Anti-Bacterial Agents; Cystic Fibrosis; Humans; Mycobacterium Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 25453268
DOI: 10.1016/j.addr.2014.10.009 -
MBio Jan 2015Pneumocystis species are fungal parasites of mammal lungs showing host specificity. Pneumocystis jirovecii colonizes humans and causes severe pneumonia in... (Comparative Study)
Comparative Study
UNLABELLED
Pneumocystis species are fungal parasites of mammal lungs showing host specificity. Pneumocystis jirovecii colonizes humans and causes severe pneumonia in immunosuppressed individuals. In the absence of in vitro cultures, the life cycle of these fungi remains poorly known. Sexual reproduction probably occurs, but the system of this process and the mating type (MAT) genes involved are not characterized. In the present study, we used comparative genomics to investigate the issue in P. jirovecii and Pneumocystis carinii, the species infecting rats, as well as in their relative Taphrina deformans. We searched sex-related genes using 103 sequences from the relative Schizosaccharomyces pombe as queries. Genes homologous to several sex-related role categories were identified in all species investigated, further supporting sexuality in these organisms. Extensive in silico searches identified only three putative MAT genes in each species investigated (matMc, matMi, and matPi). In P. jirovecii, these genes clustered on the same contig, proving their contiguity in the genome. This organization seems compatible neither with heterothallism, because two different MAT loci on separate DNA molecules would have been detected, nor with secondary homothallism, because the latter involves generally more MAT genes. Consistently, we did not detect cis-acting sequences for mating type switching in secondary homothallism, and PCR revealed identical MAT genes in P. jirovecii isolates from six patients. A strong synteny of the genomic region surrounding the putative MAT genes exists between the two Pneumocystis species. Our results suggest the hypothesis that primary homothallism is the system of reproduction of Pneumocystis species and T. deformans.
IMPORTANCE
Sexual reproduction among fungi can involve a single partner (homothallism) or two compatible partners (heterothallism). We investigated the issue in three pathogenic fungal relatives: Pneumocystis jirovecii, which causes severe pneumonia in immunocompromised humans; Pneumocystis carinii, which infects rats; and the plant pathogen Taphrina deformans. The nature, the number, and the organization within the genome of the genes involved in sexual reproduction were determined. The three species appeared to harbor a single genomic region gathering only three genes involved in sexual differentiation, an organization which is compatible with sexual reproduction involving a single partner. These findings illuminate the strategy adopted by fungal pathogens to infect their hosts.
Topics: Fungal Proteins; Genes, Mating Type, Fungal; Genome, Fungal; Genomics; Humans; Pneumocystis; Pneumocystis Infections; Synteny
PubMed: 25587012
DOI: 10.1128/mBio.02250-14 -
Polish Journal of Microbiology Feb 2022is an opportunistic fungus that can cause severe and potentially fatal pneumonia (PCP) in immunodeficient patients. In this study, we investigated the genetic...
is an opportunistic fungus that can cause severe and potentially fatal pneumonia (PCP) in immunodeficient patients. In this study, we investigated the genetic polymorphisms of at eight different loci, including six nuclear genes (ITS, 26S rRNA, , , and β-Tub) and two mitochondrial genes (mtLSU-rRNA and ) in three PCP cases, including two patients with HIV infection and one without HIV infection in Shanxi Province, P.R. China. The gene targets were amplified by PCR followed by sequencing of plasmid clones. The HIV-negative patient showed a coinfection with two genotypes of at six of the eight loci sequenced. Of the two HIV-positive patients, one showed a coinfection with two genotypes of at the same two of the six loci as in the HIV-negative patient, while the other showed a single infection at all eight loci sequenced. None of the three drug target genes ( and ) showed mutations known to be potentially associated with drug resistance. This is the first report of genetic polymorphisms of in PCP patients in Shanxi Province, China. Our findings expand our understanding of the genetic diversity of in China.
Topics: AIDS-Related Opportunistic Infections; China; Coinfection; HIV Infections; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymorphism, Genetic
PubMed: 35635165
DOI: 10.33073/pjm-2022-002 -
Antimicrobial Agents and Chemotherapy Nov 2018The impact of pneumonia (PcP) on morbidity and mortality remains substantial for immunocompromised individuals, including those afflicted by HIV infection, organ...
The impact of pneumonia (PcP) on morbidity and mortality remains substantial for immunocompromised individuals, including those afflicted by HIV infection, organ transplantation, cancer, autoimmune diseases, or subject to chemotherapy or corticosteroid-based therapies. Previous work from our group has shown that repurposing antimalarial compounds for PcP holds promise for treatment of this opportunistic infection. Following our previous discovery of chloroquine analogues with dual-stage antimalarial action both and , we now report the potent action of these compounds on Identification of chloroquine analogues as anti-PcP leads is an unprecedented finding.
Topics: A549 Cells; Antimalarials; Cell Line, Tumor; Chloroquine; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 30201816
DOI: 10.1128/AAC.00983-18 -
Medical Mycology Feb 2020Data on features of Pneumocystis primary infection in infancy are still fragmented. To study Pneumocystis primary infection, 192 infants who were monitored for acute...
Data on features of Pneumocystis primary infection in infancy are still fragmented. To study Pneumocystis primary infection, 192 infants who were monitored for acute pulmonary disease or fever over a 40-month period were retrospectively investigated. P. jirovecii detection on archival nasopharyngeal aspirates was performed using a qPCR assay. Factors associated with P. jirovecii were assessed using univariate and multivariate analyses. P. jirovecii genotypes in infants and a control group of adults contemporaneously diagnosed with Pneumocystis pneumonia were identified using unilocus, bilocus, and multilocus sequence typing (MLST). P. jirovecii was detected in 35 infants (18.2%). The univariate analysis pointed out four factors: viral infection (P = .035, OR [IC 95], 2.2 [1.1-4.7]), lower respiratory tract infection (P = .032, OR [IC 95], 2.5 [1.1-5.9]), absence of hospital discharge after birth (P = .003, OR (IC 95), 0.1 (0.02-0.5]), and the 63-189-day group (P < .001, OR [IC 95], 42.2 [5.4-332]). The multivariate analysis confirmed these two latter factors (P = .02, OR [IC 95], 0.1 [0.02-0.72]; P = .005, OR [IC 95], 11.5 [2.1-63.5]). Thus, P. jirovecii acquisition mostly takes place in the community. A comparison of these data with those of previously published studies showed that median and interquartile range of positive-infant ages were close to those observed in Chile, Denmark, and Peru, highlighting similar characteristics. Common unilocus or bilocus genotypes were identified in infants and adults, whereas no MLST genotypes were shared. Therefore, a common reservoir made up of infected infants and adults is still hypothetical. Finally, primary infection is a worldwide phenomenon occurring at the same time in childhood regardless of geographical location, rather than an incidental event.
Topics: Adult; Aged; Aged, 80 and over; Child, Preschool; Chile; DNA, Fungal; Denmark; Female; France; Genotype; Humans; Infant; Infant, Newborn; Male; Middle Aged; Multilocus Sequence Typing; Mycological Typing Techniques; Nasopharynx; Peru; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies
PubMed: 31127850
DOI: 10.1093/mmy/myz040 -
Journal of Clinical and Diagnostic... Feb 2017Opportunistic pneumonias are a major cause of mortality and morbidity in Human Immunodeficiency Virus (HIV) reactive patients. Despite the significant role that fungi...
INTRODUCTION
Opportunistic pneumonias are a major cause of mortality and morbidity in Human Immunodeficiency Virus (HIV) reactive patients. Despite the significant role that fungi play in causation of this opportunistic mycoses, very few Indian studies have attempted to investigate the burden and aetiological spectrum of HIV/AIDS-associated fungal pneumonias.
AIM
To document the prevalence of fungal aetiology in HIV/AIDS-related opportunistic pneumonias in an Indian setting; and to elucidate the various fungal opportunists responsible for the same.
MATERIALS AND METHODS
The present study was a prospective, cross-sectional analysis conducted at Maulana Azad Medical College and associated Lok Nayak Hospital, New Delhi from October 2008 to September 2011. Expectorated sputa were collected from 71 HIV reactive patients with a clinical diagnosis of pneumonia and subjected to direct microscopic examination employing Gram stain, 10% KOH wet mount and India ink preparation. In addition, direct immunofluorescence of sputum samples was performed for detection of cysts and trophozoites of . Also, each sputum sample was inoculated in duplicate onto Sabouraud Dextrose Agar (SDA) for culture. A blood sample was drawn from each patient and a battery of serological tests was performed, including Cryptococcal Antigen Latex Agglutination System (CALAS) for detection of cryptococcal capsular polysaccharide antigen; Platelia™ EIA for detection of galactomannan antigen; SERION ELISA for detection of C antigen and Histoplasma DxSelect™ for detecting antibodies to species. Descriptive statistics were employed to depict results as proportions and figures. Further, arithmetic mean and standard deviation were calculated for central tendencies and median for non-normal/skewed distributions.
RESULTS
A definite fungal aetiology was established in 25 (35.2%) of 71 HIV reactive patients with pneumonic involvement. Of these, sputa of 21 patients yielded single fungal isolates, while mixed fungal isolates were reported in four patients. was the predominant fungal pathogen isolated in our study and was reported in 14 (19.7%) patients. Pulmonary aspergillosis was reported in 7 (9.9%) patients, with (4), (2) and (1) being the commonly recovered species. Candida pneumonia was documented in 6 (8.5%) patients and the species isolated included in four, in one and in one of these six patients respectively. Pulmonary cryptococcosis was diagnosed in 2 (2.8%) patients; a coexisting cryptococcal meningitis was documented in one of them. Furthermore, antibodies against species were detected in 21 (29.6%) cases suggesting its possible aetiological role.
CONCLUSION
Fungal opportunistic pneumonias are common in HIV reactive patients in Indian setting and warrant a prompt and accurate diagnostic evaluation in the form of a combination of microbiological, serological and histopathological techniques, for an effective prophylactic and therapeutic management.
PubMed: 28384860
DOI: 10.7860/JCDR/2017/24219.9277 -
Annals of Palliative Medicine Jul 2021Acute fibrinous and organizing pneumonia (AFOP) is an unusual pathological pattern which is characterized by intra-alveolar deposition of fibrin (fibrin ball) and...
Acute fibrinous and organizing pneumonia (AFOP) is an unusual pathological pattern which is characterized by intra-alveolar deposition of fibrin (fibrin ball) and organizing pneumonia in a scattered distribution, and the pathological diagnosis plays an irreplaceable role in the diagnosis. Most Patients cannot confirm etiology, till now, known etiology included connective tissue disease, infection, environmental and occupational exposure, drugs, organ transplant, and tumor. It can be divided into acute and subacute subtype according to the extent of progress. The most common symptoms of AFOP were fever, cough, and dyspnea. Bilateral consolidations and ground-glass opacities (GGO) usually can be seen on chest CT images. At present, the treatment protocol for AFOP has not reached a consensus Glucocorticoid, immunosuppressants, stem cell transplantation or lung transplantation may contribute to improved clinical outcome. Here, we report a case of AFOP with myelodysplastic syndrome and pneumocystis jiroveci pneumonia (PJP). After treatments of glucocorticoid, immunosuppressant, chemotherapy, antibiotics and blood transfusion, the patient's clinical symptoms, peripheral blood test, and imaging findings were obviously improved. In this case, we consider the AFOP was caused by MDS and the immunodeficiency after chemotherapy lead to secondary PJP. This typical case highlights the importance of appropriate therapy for coexisted diseases of those patients with refractory AFOP.
Topics: Cough; Glucocorticoids; Humans; Myelodysplastic Syndromes; Pneumocystis carinii; Pneumonia
PubMed: 33894702
DOI: 10.21037/apm-20-2344