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Transplant Infectious Disease : An... Oct 2018In at risk populations, Pneumocystis pneumonia (PCP) may occur as a solitary event as well as in a cluster- or outbreak setting due to interpatient transmission of... (Review)
Review
In at risk populations, Pneumocystis pneumonia (PCP) may occur as a solitary event as well as in a cluster- or outbreak setting due to interpatient transmission of Pneumocystis jirovecii. Despite the data and insights obtained from studies of outbreaks of PCP, the development and implementation of comprehensive recommendations for the prevention of healthcare related transmission of P. jirovecii have been delayed. Both optimization of chemoprophylaxis strategies as well as combination with prudent use of isolation precautions are warranted to achieve this goal. The rationale of the available measures for the prevention of PCP should be viewed in the context of what is currently known about the complex biology and epidemiology of P. jirovecii. From there, phased but practical prevention strategies can be deducted to balance the efforts, costs and negative consequences of chemoprophylaxis and isolation precautions with the beneficial effect of preventing healthcare related transmission of P. jirovecii and development of PCP.
Topics: Antibiotic Prophylaxis; Cross Infection; Disease Outbreaks; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Risk Factors
PubMed: 29873156
DOI: 10.1111/tid.12942 -
International Journal of Molecular... Jun 2022The genus is an opportunistic fungal pathogen that infects patients with AIDS and immunocompromised individuals. The study of this fungus has been hampered due to the...
The genus is an opportunistic fungal pathogen that infects patients with AIDS and immunocompromised individuals. The study of this fungus has been hampered due to the inability to grow it in a (defined media/pure) culture. However, the use of modern molecular techniques and genomic analysis has helped researchers to understand its complex cell biology. The transcriptional process in the genus has not been studied yet, although it is assumed that it has conventional transcriptional machinery. In this work, we have characterized the function of the RNA polymerase II (RNAPII) general transcription factor TFIIB from using the phylogenetically related biological model . The results of this work show that TFIIB is able to replace the essential function of TFIIB both in in vivo and in vitro assays. The strain harboring the TFIIB grew slower than the parental wild-type strain in complete media and in minimal media. The cells carrying out the TFIIB are larger than the wild-type cells, indicating that the TFIIB gene replacement confers a phenotype, most likely due to defects in transcription. TFIIB forms very weak complexes with TATA-binding protein on a TATA box promoter but it is able to form stable complexes in vitro when TFIIF/RNAPII are added. TFIIB can also replace the transcriptional function of TFIIB in an in vitro assay. The transcription start sites (TSS) of the endogenous gene do not change when TFIIB replaces TFIIB, and neither does the TSS of the gene, although this last gene is poorly transcribed in vivo in the presence of TFIIB. Since transcription by RNA polymerase II in is poorly understood, the results described in this study are promising and indicate that TFIIB from can replace the transcriptional functions of TFIIB, although the cells expressing the TFIIB show an altered phenotype. However, performing studies using a heterologous approach, like this one, could be relevant to understanding the basic molecular processes of such as transcription and replication.
Topics: Humans; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; RNA Polymerase II; Schizosaccharomyces; Schizosaccharomyces pombe Proteins; Transcription Factor TFIIB; Transcription, Genetic
PubMed: 35743306
DOI: 10.3390/ijms23126865 -
Transplantation Proceedings Nov 2014Pneumocystis jirovecii is a fungus that causes pneumonia in immunocompromised patients, such as liver transplant recipients. (Review)
Review
BACKGROUND
Pneumocystis jirovecii is a fungus that causes pneumonia in immunocompromised patients, such as liver transplant recipients.
METHODS
We searched the Medline database in September 2013 for articles referring to infections from P. jirovecii in liver transplant recipients, using the terms "liver transplantation" and "pneumocystis." Our search yielded 60 articles, 35 of which were used for our review.
RESULTS
P. jirovecii pneumonia (PJP) has an incidence of 1%-11% in liver transplant recipients without prophylaxis and mortality rates of 7%-88%. Most cases occur within the first 7 months after transplantation. When prophylactic treatment with oral trimethoprim-sulfamethoxazole is used, its incidence is only 0%-3%. The duration of its use varies from 3 months to 1 year after the liver transplantation.
CONCLUSIONS
PJP has relatively high incidence and high mortality rates in liver transplant recipients without prophylactic treatment, which diminishes or even eliminates its occurrence. Therefore, oral trimethoprim-sulfamethoxazole should be used as prophylaxis for 1 year after the liver transplantation in this population.
Topics: Anti-Bacterial Agents; Global Health; Humans; Immunocompromised Host; Incidence; Liver Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Transplant Recipients
PubMed: 25420860
DOI: 10.1016/j.transproceed.2014.09.156 -
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 -
Microbiology and Immunology May 2022Pneumocystis spp. interacts with epithelial cells in the alveolar spaces of the lung. It is thought that the binding of Pneumocystis to host cell epithelium is needed...
Gene expression in lung epithelial cells following interaction with Pneumocystis carinii and its specific life forms yields insights into host gene responses to infection.
Pneumocystis spp. interacts with epithelial cells in the alveolar spaces of the lung. It is thought that the binding of Pneumocystis to host cell epithelium is needed for life cycle completion and proliferation. The effect of this interaction on lung epithelial cells has previously shown that the trophic form of this organism greatly inhibits p34 activity, a serine/threonine kinase required for transition from the G to M phase in the cell cycle. To gain further insight into the host response during Pneumocystis pneumonia infection, we used microarray technology to profile epithelial cell (A549) gene expression patterns following Pneumocystis carinii interaction. Furthermore, we isolated separate populations of cyst and trophic forms of P. carinii, which were then applied to the lung epithelial cells. Differential expression of genes involved in various cellular functions dependent on the specific P. carinii life form in contact with the A549 cell was identified. The reliability of our data was further confirmed by Northern blot analysis on a number of selected upregulated or downregulated transcripts. The transcriptional response to P. carinii was dominated by cytokines, apoptotic, and antiapoptosis-related genes. These results reveal several previously unknown effects of P. carinii on the lung epithelial cell and provide insight into the complex interactions of host and pathogen.
Topics: Epithelial Cells; Gene Expression; Lung; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; Reproducibility of Results
PubMed: 35229348
DOI: 10.1111/1348-0421.12972 -
Medical Mycology Dec 2021Pneumocystis jirovecii is associated with non-noxious colonization or severe pneumonia in immunocompromised hosts. Epidemiological investigations have been hampered by...
UNLABELLED
Pneumocystis jirovecii is associated with non-noxious colonization or severe pneumonia in immunocompromised hosts. Epidemiological investigations have been hampered by the lack of a standardized typing scheme. Thus, only partial molecular data on Spanish P. jirovecii cases are available. Recently, a new ISHAM consensus multilocus sequence typing scheme (MLST) targeting β-TUB, mt26S, CYB, and SOD with a publicly accessible database has been launched to overcome this problem. The molecular epidemiology of P. jirovecii from immunocompromised patients either colonized (n = 50) or having pneumonia (n = 36) seen between 2014 and 2018 at a single center in Barcelona, Spain, was studied. The new ISHAM consensus MSLT scheme was used to investigate the local epidemiology and identify possible unnoticed outbreaks. Mutations in the DHPS gene, not included in the scheme but giving information about potential sulfa treatment failure, were also studied. The study assigned 32 sequence types (ST) to 72.2% pneumonia and 56% colonization cases. The most frequent STs were ST21 (18.5%), ST22 (14.8%), and ST37(14.8%). For non-unique STs, ST3, ST30 and ST31 were found only in pneumonia cases, whereas ST27 was associated exclusively to colonizations. Despite 38 patients sharing similar STs, only two were involved in a potential cross transmission event. No DHPS mutations were identified. The new consensus typing scheme was useful to ascertain the molecular epidemiology of P. jirovecii in our center revealing a high genetic diversity and the potential association of specific STs to colonization and pneumonia cases.
LAY SUMMARY
A newly described MLST scheme aims at providing a standardized tool to study and compare Pneumocystis jirovecii epidemiology. A high diversity among P. jirovecii isolates from patients in Barcelona, Spain, and a potential association between specific STs and infection/colonization were identified.
Topics: Animals; Multilocus Sequence Typing; Mutation; Pneumocystis carinii; Pneumonia, Pneumocystis; Tertiary Care Centers
PubMed: 34698858
DOI: 10.1093/mmy/myab065 -
Microbial Pathogenesis Jul 2019The present study was aimed to synthesize and evaluate tetrazoles of baicalin against Pneumocystis carinii pneumonia in the rat model. Among the seven synthesized...
The present study was aimed to synthesize and evaluate tetrazoles of baicalin against Pneumocystis carinii pneumonia in the rat model. Among the seven synthesized baicalin tetrazoles, one with trifloromethyl group in the aromatic ring was found to be most potent during the initial study. The mechanism of preventive effect of most potent compound 4c against Pneumocystis carinii pneumonia was investigated in detail. The compound 4c decreased the parasitic load by almost 99% in the rats. It significantly (P < 0.05) decreased mortality rate of the rats, prevented pulmonary tissue damage and aggregation of inflammatory cytokines. In Pneumocystis carinii infected rats compound 4c treatment inhibited production of interleukin-18, interleukin-1β and TNF-α significantly (P < 0.05) in the BALF and pulmonary tissues. Treatment of the pneumocystis carinii-infected rats with compound 4c inhibited up-regulation of mRNA expression corresponding NLRP3, ASC and caspase-1. The compound 4c treatment of the pneumocystis carinii-infected rats significantly (P < 0.02) suppressed the level of NLRP3 and ASC proteins. Moreover, the enhancement of caspase-1 activation by pneumocystis carinii-infection in rats was also suppressed by compound 4c. The results from present study demonstrate that compound 4c protects pneumocystis carinii induced pneumonia through suppression of inflammatory cytokines and NLRP3 activation. Therefore, compound 4c can be of therapeutic importance for the treatment of pneumocystis carinii induced pneumonia.
Topics: Animals; Anti-Inflammatory Agents; Antifungal Agents; Bronchoalveolar Lavage Fluid; CARD Signaling Adaptor Proteins; Caspase 1; Cytokines; Disease Models, Animal; Flavonoids; Immunocompromised Host; Interleukin-18; Interleukin-1beta; Lung; Mortality; NLR Family, Pyrin Domain-Containing 3 Protein; Pneumocystis carinii; Pneumonia, Pneumocystis; RNA, Messenger; Rats; Tetrazoles; Tumor Necrosis Factor-alpha
PubMed: 31002962
DOI: 10.1016/j.micpath.2019.04.027 -
Internal and Emergency Medicine Sep 2023The diagnosis of Pneumocystis jirovecii pneumonia (PCP) in patients presenting with severe pneumonia is challenging and delays in treatment were associated with worse... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The diagnosis of Pneumocystis jirovecii pneumonia (PCP) in patients presenting with severe pneumonia is challenging and delays in treatment were associated with worse prognosis. This study aimed to develop a rapid, easily available, noninvasive machine learning diagnostic model for PCP among patients with severe pneumonia.
METHODS
A retrospective study was performed in West China Hospital among consecutive patients with severe pneumonia who had undergone bronchoalveolar lavage for etiological evaluation between October 2010 and April 2021. Factors associated with PCP were identified and four diagnostic models were established using machine learning algorithms including Logistic Regression, eXtreme Gradient Boosting, Random Forest (RF) and LightGBM. The performance of these models were evaluated by the area under the receiver operating characteristic curve (AUC).
RESULTS
Ultimately, 704 patients were enrolled and randomly divided into a training set (n = 564) and a testing set (n = 140). Four factors were ultimately selected to establish the model including neutrophil, globulin, β-D-glucan and ground glass opacity. The RF model exhibited the greatest diagnostic performance with an AUC of 0.907. The calibration curve and decision curve analysis also demonstrated its accuracy and applicability.
CONCLUSIONS
We constructed a PCP diagnostic model in patients with severe pneumonia using four easily available and noninvasive clinical indicators. With satisfying diagnostic performance and good clinical practicability, this model may help clinicians to make early diagnosis of PCP, reduce the delays of treatment and improve the prognosis among these patients.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Retrospective Studies; beta-Glucans; Bronchoalveolar Lavage
PubMed: 37530943
DOI: 10.1007/s11739-023-03353-1 -
Zhonghua Jie He He Hu Xi Za Zhi =... Sep 2022To describe the underlying diseases, microbiologic examination and severity of hospitalized patients with pneumonia (PJP) in a tertiary Chinese hospital. We conducted...
To describe the underlying diseases, microbiologic examination and severity of hospitalized patients with pneumonia (PJP) in a tertiary Chinese hospital. We conducted a retrospective analysis of 485 identified PJP patients who were admitted to our hospital between January 2013 and December 2021. Among the 485 enrolled PJP cases, there were 237 males and 248 females, aging (53.3±16.2) years (range from 14 y to 88 y). They were divided into 8 subgroups with variable underlying diseases. There were 209 cases with connective tissue diseases(CTD), 27 cases with non-hematologic malignancies, 38 cases with hematologic malignancies, 81 cases with kidney diseases, 33 cases with idiopathic interstitial pneumonia(IIP), 30 cases infected with human immunodeficiency virus (HIV), and 42 cases with miscellaneous underlying diseases. In the CTD group, there was more females than males, while male patients were predominant in both the malignant and the HIV groups. The was identified in 44.95%(218/485) sputum samples and 92.01%(265/288) bronchoscopic samples. asci were observed at direct microscopic examination with Grocott's methenamine silver stain in 4.95%(24/485)sputum samples and 9.72%(28/288)bronchoscopic samples. DNA fragments were identified by PCR analysis in 43.09%(209/485)sputum samples and 90.63%(261/288)bronchoscopic samples. Among the 8 groups, cytomegaviremia and respiratory failure were most common in the HIV-infected PJP group, but the rates of mechanic ventilation, intensive care unit (ICU) admission and death were the lowest. There were less PJP patients in the IIP group (IIP-PJP) who received mechanic ventilation and admitted to ICU than the other groups except HIV-infected PJP group. However, the mortality rate was highest for the IIP-PJP group. CTD was the most common predisposed underlying disease for our enrolled PJP cases. Cytomegaviremia and respiratory failure were common in HIV-infected PJP patients, but the prognosis of HIV-PJP was slightly better than the others. The disease was more severe, rapidly progressive and fatal in the IIP-PJP group.
Topics: Female; HIV Infections; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Respiratory Insufficiency; Retrospective Studies
PubMed: 36097925
DOI: 10.3760/cma.j.cn112147-20220303-00170 -
BMJ Case Reports May 2024A male patient in his 40s who had been unwell for months with fever of unknown origin and clinicopathological features suspicious for haemophagocytic lymphohistiocytosis...
A male patient in his 40s who had been unwell for months with fever of unknown origin and clinicopathological features suspicious for haemophagocytic lymphohistiocytosis presented to hospital with worsening subacute shortness of breath. CT pulmonary angiogram demonstrated ground glass changes involving all lung lobes with an apicobasal gradient. These changes, combined with long-term steroid exposure for granulomatous hepatitis without pneumocystis prophylaxis, raised concern for pneumocystis jirovecii pneumonia (PJP). A subsequent bronchoscopic lavage specimen was positive on PCR for PJP and the patient was started on appropriate therapy. Clinical and radiological changes initially improved but after completion of therapy, symptoms and radiological abnormalities returned. Retreatment with second-line treatment resulted again in initial improvement followed by relapse with acute deterioration. Further investigations for an alternate diagnosis were made, with a surgical lung biopsy performed finally revealing immunosuppression-related Epstein-Barr virus positive large B cell lymphoma with lymphomatoid granulomatosis of grade 3 pattern.
Topics: Humans; Lymphomatoid Granulomatosis; Male; Diagnosis, Differential; Adult; Pneumonia, Pneumocystis; Pneumocystis carinii; Tomography, X-Ray Computed; Lung
PubMed: 38821563
DOI: 10.1136/bcr-2024-259969