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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 -
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 -
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 -
Annals of Clinical Microbiology and... Nov 2023The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected...
OBJECTIVE
The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results.
METHODS
This was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort.
RESULTS
Two hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4 T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG.
CONCLUSIONS
Serum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Glucans; Retrospective Studies; beta-Glucans; Lung Neoplasms; HIV Infections; Lung Diseases, Interstitial
PubMed: 37986091
DOI: 10.1186/s12941-023-00650-7 -
Indian Journal of Nuclear Medicine :... 2022Fever or pyrexia of unknown origin (PUO) is commonly defined as body temperature higher than 38.3°C on several occasions for a period of at least 3 weeks with uncertain...
Fever or pyrexia of unknown origin (PUO) is commonly defined as body temperature higher than 38.3°C on several occasions for a period of at least 3 weeks with uncertain diagnosis after initial routine obligatory investigations. In most cases of PUO, there is an uncommon presentation of a common disease which includes infection, noninfectious inflammatory diseases, malignancy, and miscellaneous causes. We present an interesting case of a 48-year-old man with PUO, who is a known case of multiple myeloma on immunosuppressive therapy, where 18F-fluorodeoxyglucose positron emission tomography-computed tomography was able to detect occult cause of infective etiology.
PubMed: 35982811
DOI: 10.4103/ijnm.ijnm_140_21 -
The Journal of Infectious Diseases May 2022We describe the prevalence of Pneumocystis jirovecii in mother-infant pairs of very low birth weight newborns <32 weeks gestation. Molecular and microscopic methods were...
We describe the prevalence of Pneumocystis jirovecii in mother-infant pairs of very low birth weight newborns <32 weeks gestation. Molecular and microscopic methods were used for detection of P. jirovecii in patients' specimens. Pneumocystis DNA was detected in 8 nasopharyngeal aspirates (14%) of 56 newborns and in 7 oral washes (21%) of 34 mothers. Pneumocystis detection immediately after birth suggests the possibility of its transplacental transmission. Compared to noncolonized infants, more frequent occurrence of bronchopulmonary dysplasia was seen in colonized infants (P = .02), suggesting a potential clinical importance of this pathogen in abnormal lung development.
Topics: Gestational Age; Humans; Infant; Infant, Newborn; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; Respiratory Distress Syndrome
PubMed: 33857302
DOI: 10.1093/infdis/jiab209 -
Seminars in Arthritis and Rheumatism Dec 2022Objective No guidelines exist for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in patients with systemic lupus erythematosus (SLE). Limited data are available on...
Objective No guidelines exist for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in patients with systemic lupus erythematosus (SLE). Limited data are available on incidence of PJP infection and use of PJP prophylaxis. Using a real-world, electronic health record (EHR) cohort, we investigated the frequency of PJP infections as well as patient and provider factors that impacted use and type of PJP prophylaxis. Methods In a large, de-identified EHR, we identified possible SLE patients using a previously validated algorithm. PJP ICD-9 or ICD-10-CM billing codes and PJP keywords were used to identify possible PJP cases within this SLE cohort. We assessed for PJP prophylaxis prescribing in all SLE patients using keywords and reviewing medication lists for prophylactic agents. Chart review was used to confirm cases of SLE, PJP, and PJP prophylaxis and to obtain data on demographics, comorbidities, and immunosuppressants. Results Of 977 SLE patients, there were only four with confirmed PJP infection. Two of these patients had concurrent Acquired Immunodeficiency Syndrome, and none were on prophylaxis. Of 977 SLE patients, 132 (14%) were prescribed PJP prophylaxis. Of 617 SLE patients ever prescribed immunosuppressants, 128 (21%) were prescribed PJP prophylaxis. Sulfonamides were the most common prophylaxis prescribed (69%), and possible adverse events were documented in 22 out of 117 instances of being placed on a sulfonamide. Patients of younger age, Black race, nephritis, and renal transplant, and on chronic glucocorticoids were all more likely to have PJP prophylaxis prescribed. Patients who were on transplant induction medications, calcineurin/mTOR inhibitors, cyclophosphamide, and mycophenolate mofetil all were more likely to be prescribed PJP prophylaxis compared to other immunosuppressants. Conclusion PJP is a rare diagnosis among SLE patients, and prior studies may even overestimate its prevalence. PJP prophylaxis was less common in our cohort than previously described. Adverse events related to sulfonamides used for PJP prophylaxis were relatively rare with lower rates than previously reported. Our study demonstrates real-world PJP prophylaxis prescribing patterns in a large cohort of SLE patients.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Electronic Health Records; Lupus Erythematosus, Systemic; Immunosuppressive Agents; Sulfonamides; Retrospective Studies
PubMed: 36279805
DOI: 10.1016/j.semarthrit.2022.152106 -
Annals of Clinical Microbiology and... Jun 2021Pneumocystis jirovecii and Aspergillus fumigatus, are opportunistic pathogenic fungus that has a major impact on mortality in patients with systemic lupus erythematosus....
Rapid and precise diagnosis of pneumonia coinfected by Pneumocystis jirovecii and Aspergillus fumigatus assisted by next-generation sequencing in a patient with systemic lupus erythematosus: a case report.
BACKGROUND
Pneumocystis jirovecii and Aspergillus fumigatus, are opportunistic pathogenic fungus that has a major impact on mortality in patients with systemic lupus erythematosus. With the potential to invade multiple organs, early and accurate diagnosis is essential to the survival of SLE patients, establishing an early diagnosis of the infection, especially coinfection by Pneumocystis jirovecii and Aspergillus fumigatus, still remains a great challenge.
CASE PRESENTATION
In this case, we reported that the application of next -generation sequencing in diagnosing Pneumocystis jirovecii and Aspergillus fumigatus coinfection in a Chinese girl with systemic lupus erythematosus (SLE). Voriconazole was used to treat pulmonary aspergillosis, besides sulfamethoxazole and trimethoprim (SMZ-TMP), and caspofungin acetate to treat Pneumocystis jirovecii infection for 6 days. On Day 10 of admission, her chest radiograph displayed obvious absorption of bilateral lung inflammation though the circumstance of repeated fever had not improved. Unfortunately, the patient discharged from the hospital since the financial burden, and during the follow-up, it was documented the patient died within one week after discharge.
CONCLUSIONS
This successful application of the next generation sequencing assisting the rapid diagnosis of Pneumocystis jirovecii and Aspergillus fumigatus coinfection provides a new perspective in the clinical approach against the systematic fungi infections and highlights the potential of this technique in rapid etiological diagnosis.
Topics: Adolescent; Aspergillus fumigatus; Caspofungin; Coinfection; Female; High-Throughput Nucleotide Sequencing; Humans; Lupus Erythematosus, Systemic; Opportunistic Infections; Pneumocystis carinii; Pneumonia; Sulfamethoxazole; Trimethoprim; Voriconazole
PubMed: 34174895
DOI: 10.1186/s12941-021-00448-5 -
MBio Mar 2020Environmental exposure has a significant impact on human health. While some airborne fungi can cause life-threatening infections, the impact of environment on fungal...
Environmental exposure has a significant impact on human health. While some airborne fungi can cause life-threatening infections, the impact of environment on fungal spore dispersal and transmission is poorly understood. The democratization of shotgun metagenomics allows us to explore important questions about fungal propagation. We focus on , a genus of host-specific fungi that infect mammals via airborne particles. In humans, causes lethal infections in immunocompromised patients if untreated, although its environmental reservoir and transmission route remain unclear. Here, we attempt to clarify, by analyzing human exposome metagenomic data sets, whether humans are exposed to different species present in the air but only cells are able to replicate or whether they are selectively exposed to Our analysis supports the latter hypothesis, which is consistent with a local transmission model. These data also suggest that healthy carriers are a major driver for the transmission.
Topics: Air Microbiology; DNA, Fungal; Environmental Exposure; Humans; Immunocompromised Host; Metagenomics; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 32156824
DOI: 10.1128/mBio.03138-19 -
BMC Infectious Diseases Jan 2021Pneumocystis pneumonia (PCP) is a fatal infectious disease caused by Pneumocystis jirovecii (PJP). The major factor relevant to morbidity and mortality seems to be the...
BACKGROUND
Pneumocystis pneumonia (PCP) is a fatal infectious disease caused by Pneumocystis jirovecii (PJP). The major factor relevant to morbidity and mortality seems to be the host inflammatory reaction. The objective of this study was to evaluate the role of IL-2, IL-4, IL-10, and IL-13 cytokine mRNA expression among suspected P. jirovecii infection.
METHODS
This was a cross-sectional analytical study undertaken in Aseer region, Saudi Arabia. One hundred suspected PCP cases and 100 healthy controls were included in the study. Basic clinical manifestations, radiological findings, microbiological and immunological findings were extracted from the hospital records from January 2019 to August 2019, Pneumocystis detection was done by immune-fluorescent staining (IFAT, Gomorimethanamine silver staining (GMSS), Giemsa staining, Toluidine blue O (TBO), and Pneumocystis RT-PCR.
RESULTS
Increased more than 5 fold, 3 fold, 4 fold, and 7 fold of IL-2, IL-4, IL-10, and IL-13 mRNA expression were observed in PCP cases compared to controls. Higher expression of IL-2 mRNA was connected with crept, wheezing and chest X-ray findings like central perihilar infiltrate, patchy infiltrate, consolidation, hilar lymphadenopathy, pneumothorax, pleural effusion which showed higher expression compared to counterpart (p< 0.0001). Higher expression of IL-4 mRNA was found to be significantly associated with weight loss (p=0.002), dyspnea (p=0.003), crept (p=0.01), and chest X-ray findings (p< 0.0001). Significantly increased expression of IL-10 mRNA was observed to be associated with weight loss, dyspnea, night sweats, wheezing, and different findings of chest X-ray compared to their counterparts, whereas, IL-13 mRNA was observed in cases with fever. Suspected cases of PCP confirmed positive by IFTA with higher IL-2, IL-4, and IL-10 mRNA expression compared to negative cases. RT-PCR confirmed PCP cases had significantly higher expression of IL-2, IL-4, and IL-10 as well as IL-13 mRNA compared to negative cases. Positive detected cases by GMSS showed higher IL-2, IL-10 mRNA expression, while Giemsa showed only higher IL-4 mRNA expression compared to negative cases.
CONCLUSION
Confirmed cases of P. jirovecii showed higher IL-2, IL-4, IL-10, and IL-13 mRNA expression comparatively to negative cases. Increased expression of cytokines may be indicative of infection severity and could help in patients' management.
Topics: Adult; Azure Stains; Case-Control Studies; Cross-Sectional Studies; Cytokines; Female; Fluorescent Antibody Technique; Gene Expression; Humans; Interleukin-10; Interleukin-13; Interleukin-2; Interleukin-4; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; RNA, Messenger; Saudi Arabia; Tolonium Chloride
PubMed: 33413198
DOI: 10.1186/s12879-020-05729-6