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Frontiers in Immunology 2023and are the common opportunistic pathogens in immunodeficient patients. There have been no reports of and coinfection in immunodeficient children. Signal transducer... (Review)
Review
and are the common opportunistic pathogens in immunodeficient patients. There have been no reports of and coinfection in immunodeficient children. Signal transducer and activator of transcription 1 () is a key transcription factor in immune responses. mutations are predominately associated with chronic mucocutaneous candidiasis and invasive mycosis. We report a 1-year-2-month-old boy diagnosed with severe laryngitis and pneumonia caused by and coinfection, which was confirmed by smear, culture, polymerase chain reaction and metagenome next-generation sequencing of bronchoalveolar lavage fluid. He has a known mutation at amino acid 274 in the coiled-coil domain of according to whole exome sequencing. Based on the pathogen results, itraconazole and trimethoprim-sulfamethoxazole were administered. This patient's condition improved, and he was discharged after two weeks of targeted therapy. In the one-year follow-up, the boy remained symptom-free without recurrence.
Topics: Male; Humans; Child; Infant; Pneumocystis carinii; Coinfection; Talaromyces; Mutation; STAT1 Transcription Factor
PubMed: 36891307
DOI: 10.3389/fimmu.2023.1103184 -
BMC Pulmonary Medicine Feb 2023Pneumocystis jirovecii pneumonia (PJP) is one of the most common opportunistic infections in immunocompromised patients. However, the accurate prediction of the...
BACKGROUND
Pneumocystis jirovecii pneumonia (PJP) is one of the most common opportunistic infections in immunocompromised patients. However, the accurate prediction of the development of PJP in non-HIV immunocompromised patients is still unclear.
METHODS
Non-HIV immunocompromised patients confirmed diagnosis of PJP by the clinical symptoms, chest computed tomography and etiological results of metagenomic next-generation sequencing (mNGS) were enrolled as observation group. Another group of matched non-HIV immunocompromised patients with non-PJP pneumonia were enrolled to control group. The risk factors for the development of PJP and the co-pathogens in the bronchoalveolar lavage fluid (BALF) detected by mNGS were analyzed. RESULTS: A total of 67 (33 PJP, 34 non-PJP) participants were enrolled from Fujian Provincial Hospital. The ages, males and underlying illnesses were not significantly different between the two groups. Compared to non-PJP patients, PJP patients were more tends to have the symptoms of fever and dyspnea. The LYM and ALB were significantly lower in PJP patients than in non-PJP patients. Conversely, LDH and serum BDG in PJP patients were significantly higher than in non-PJP controls. For immunological indicators, the levels of immunoglobulin A, G, M and complement C3, C4, the numbers of T, B, and NK cells, had no statistical difference between these two groups. Logistic multivariate analysis showed that concomitant use of corticosteroids and immunosuppressant (OR 14.146, P = 0.004) and the lymphocyte counts < 0.7 × 10/L (OR 6.882, P = 0.011) were risk factors for the development of PJP in non-HIV immunocompromised patients. 81.82% (27/33) and 64.71% (22/34) mixed infections were identified by mNGS in the PJP group and non-PJP group separately. CMV, EBV and Candida were the leading co-pathogens in PJP patients. The percentages of CMV and EBV identified by mNGS in PJP group were significantly higher than those in the control group(p < 0.005). CONCLUSIONS: Clinicians should pay close attention to the development of PJP in non-HIV immunocompromised patients who possess the risk factors of concomitant use of corticosteroids and immunosuppressant and the lymphocyte counts < 0.7 × 10/L. Prophylaxis for PJP cannot rely solely on CD4 T counts in non-HIV immunocompromised patients. Whether CMV infection increases the risk of PJP remains to be further investigated.
Topics: Male; Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Risk Factors; Cytomegalovirus Infections; Adrenal Cortex Hormones; Immunosuppressive Agents; Immunocompromised Host; High-Throughput Nucleotide Sequencing
PubMed: 36829171
DOI: 10.1186/s12890-022-02300-8 -
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 Nephrology Feb 2023One of the rare life-threatening fungal infections is pneumocystis pneumonia (PCP). Immunocompromised patients are the main vulnerable population. We investigate the...
PURPOSE
One of the rare life-threatening fungal infections is pneumocystis pneumonia (PCP). Immunocompromised patients are the main vulnerable population. We investigate the risk factors associated with the development of severe PCP infection with acute respiratory failure after kidney transplantation.
MATERIALS AND METHODS
This is a retrospective, single-center, case-control study. PCP patients who are kidney transplant recipients and required high-flow oxygen support or mechanical ventilation between March 2009 and February 2017 were included in the study. The comparison was conducted between the non-severe and severe PCP groups. To identify associated risk factors, we performed univariate and multivariate logistic regression.
RESULTS
Among the total 2,330 kidney transplant recipients, 50 patients (2.1%) were diagnosed with PCP. Of these, 27 patients (54.0%) had severe PCP and 7 patients (14.0%) died, all of them were severe PCP patients. In the severe PCP group, the time from transplantation to PCP diagnosis (23.4 ± 24.9 months vs. 13.7 ± 9.9 months, p = 0.090) was insignificantly faster than in the non-severe PCP group. According to multiple logistic regression analysis, the significant risk factors associated with severe PCP were as follows, age (odds ratios (OR) 1.07; 95% confidence intervals (CI): 1.01-1.13; p = 0.027), time from transplantation to PCP diagnosis (odds ratios (OR) 0.92; 95% confidence intervals (CI): 0.86-0.99; p = 0.024), lymphopenia (OR 6.48; 95% CI: 1.05-40.09; p = 0.044), and history of acute rejection within 1 year (OR 8.28; 95% CI: 1.29-53.20; p = 0.026).
CONCLUSION
Patients who have lymphopenia at the time of hospital admission or have been recently treated with acute rejection are more likely to progress to severe PCP, requiring intensive monitoring and aggressive treatment.
Topics: Humans; Pneumonia, Pneumocystis; Kidney Transplantation; Retrospective Studies; Case-Control Studies; Risk Factors; Transplant Recipients; Lymphopenia; Respiratory Insufficiency; Pneumocystis carinii
PubMed: 36759777
DOI: 10.1186/s12882-023-03071-y -
CytoJournal 2023Immunosuppressed individuals are more prone for opportunistic infections. pneumonia (PJP), previously known as pneumonia (PCP), is the most common opportunistic...
OBJECTIVES
Immunosuppressed individuals are more prone for opportunistic infections. pneumonia (PJP), previously known as pneumonia (PCP), is the most common opportunistic infection affecting people living with HIV. As PJP can cause life threatening serious infection to a patient, treatment should not be delayed for these cases. To study clinico-cytomorphological spectrum of PJP.
MATERIAL AND METHODS
We analysed the clinical and detailed cytological features of 15 patients with PJP who were diagnosed on examination of bronchoalveolar lavage (BAL) fluid.
RESULTS
The mean age of the patients was 38.4 years (range 13 - 61 years). A total of seven patients were HIV positive; five patients were post renal transplant, and one patient was a known case of acute leukaemia on immunosuppression. Presence of foamy alveolar casts (FACs) was the distinctive feature and was noted in 14 out of 15 cases. We detected 14 out of 15 cases accurately in BAL fluid cytology.
CONCLUSION
BAL cytology is one of the important modes of investigations which can detect PJP infection. The history of fever, cough, immunosuppression, bilateral haziness in the radiography of lung and the characteristic alveolar cast indicate the possibility of PJP infection. Cytology can provide early diagnosis and can reduce the mortality of immunocompromised patients.
PubMed: 36751555
DOI: 10.25259/Cytojournal_5_2022 -
Medicine Feb 2023Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human... (Review)
Review
RATIONALE
Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human immunodeficiency virus (HIV) infection, organ transplantation, leukemia, and immunosuppressive therapy. Here we describe the rare case of PCP in a non-HIV-infected diabetic patient and find possible reasons for the association through a literature review.
PATIENT CONCERNS
A 65-years-old male was admitted to our hospital due to a 10-year history of abnormal blood glucose levels and edema of both lower extremities for half a month. However, the patient developed a high fever and progressive dyspnea during hospitalization.
DIAGNOSES
The patient had elevated blood sugar levels, a low white blood cell count within normal limits, and severe lymphopenia. His blood G test and lactate dehydrogenase levels increased significantly. Multiple sputa and bronchoalveolar lavage fluid specimens for Pneumocystis jirovecii (PJ) nucleic acid detection were positive. Chest computed tomography scan demonstrated hazy patchy shadows in the lungs suspected to be pulmonary infections. No tumor, transplantation, or an autoimmune disease was found in the examinations. The patient was diagnosed with PCP finally.
INTERVENTIONS
A combination of oral trimethoprim-sulfamethoxazole and intravenous caspofungin was administered immediately against PJ. The patient was also treated with noninvasive ventilator-assisted ventilation, subcutaneous insulin, and hemodialysis therapy.
OUTCOMES
The patient was discharged home finally with a fair general condition and was followed up without respiratory symptoms.
LESSONS
The compromised immunity in HIV-negative patients with diabetes may be related to lymphocyte decrease and dysfunction, which may cause diabetic patients prone to PJ. Although PCP is rare in diabetes, it should be paid attention to the high rate of misdiagnosis and missed diagnosis.
Topics: Humans; Male; Aged; Pneumonia, Pneumocystis; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination; HIV Infections; Diabetes Mellitus
PubMed: 36749248
DOI: 10.1097/MD.0000000000032290 -
Frontiers in Pediatrics 2022Rituximab is emerging as a new steroid sparing agent in children with difficult-to-treat nephrotic syndrome due to its ability of depleting CD20-positive B cells....
Case Report: Successful treatment of severe pneumocystis carinii pneumonia in a case series of primary nephrotic syndrome after receiving anti-CD20 monoclonal antibody therapy.
Rituximab is emerging as a new steroid sparing agent in children with difficult-to-treat nephrotic syndrome due to its ability of depleting CD20-positive B cells. Life-threatening adverse events such as pneumocystis carinii pneumonia may occur even though it seems to be well tolerated. Since rituximab is wildly used in immune-mediated diseases, it is important to manage its severe adverse events. To explore the importance of early diagnosis and treatment of pneumocystis carinii pneumonia in children with primary nephrotic syndrome (PNS) after receiving rituximab therapy, we retrospectively analyzed the clinical data of PNS patients younger than 18 years old with pneumocystis carinii pneumonia who were hospitalized in our center. Clinical features and laboratory test results were retrieved from the electronic medical records. Severe pneumocystis carinii pneumonia occurred in one child with steroid resistant nephrotic syndrome and two with steroid dependent nephrotic syndrome patients after rituximab treatment. These patients were diagnosed in time by metagenomic next-generation sequencing (mNGS) for pathogen detection. Fortunately, all three patients survived after antifungal treatment and achieved complete remission eventually. In conclusion, early diagnosis by using mNGS and timely antifungal treatment is the key to successful management of pneumocystis carinii pneumonia in children with difficult-to-treat PNS.
PubMed: 36683820
DOI: 10.3389/fped.2022.1067634 -
MBio Feb 2023Pneumocystis jirovecii kills hundreds of thousands of immunocompromised patients each year. Yet many aspects of the biology of this obligate pathogen remain obscure...
Pneumocystis jirovecii kills hundreds of thousands of immunocompromised patients each year. Yet many aspects of the biology of this obligate pathogen remain obscure because it is not possible to culture the fungus independently of its host. Consequently, our understanding of Pneumocystis pathobiology is heavily reliant upon bioinformatic inferences. We have exploited a powerful combination of genomic and phylogenetic approaches to examine the evolution of transcription factors in Pneumocystis species. We selected protein families (Pfam families) that correspond to transcriptional regulators and used bioinformatic approaches to compare these families in the seven Pneumocystis species that have been sequenced to date with those from other yeasts, other human and plant pathogens, and other obligate parasites. Some Pfam families of transcription factors have undergone significant reduction during their evolution in the Pneumocystis genus, and other Pfam families have been lost or appear to be in the process of being lost. Meanwhile, other transcription factor families have been retained in Pneumocystis species, and some even appear to have undergone expansion. On this basis, Pneumocystis species seem to have retained transcriptional regulators that control chromosome maintenance, ribosomal gene regulation, RNA processing and modification, and respiration. Meanwhile, regulators that promote the assimilation of alternative carbon sources, amino acid, lipid, and sterol biosynthesis, and iron sensing and homeostasis appear to have been lost. Our analyses of transcription factor retention, loss, and gain provide important insights into the biology and lifestyle of Pneumocystis. Pneumocystis jirovecii is a major fungal pathogen of humans that infects healthy individuals, colonizing the lungs of infants. In immunocompromised and transplant patients, this fungus causes life-threatening pneumonia, and these Pneumocystis infections remain among the most common and serious infections in HIV/AIDS patients. Yet we remain remarkably ignorant about the biology and epidemiology of Pneumocystis due to the inability to culture this fungus . Our analyses of transcription factor retentions, losses, and gains in sequenced Pneumocystis species provide valuable new views of their specialized biology, suggesting the retention of many metabolic and stress regulators and the loss of others that are essential in free-living fungi. Given the lack of culture methods for Pneumocystis, this powerful bioinformatic approach has advanced our understanding of the lifestyle of and the nature of its dependence on the host for survival.
Topics: Humans; Pneumocystis; Phylogeny; Transcription Factors; Pneumonia, Pneumocystis; Pneumocystis carinii; Genomics; Life Style
PubMed: 36651897
DOI: 10.1128/mbio.02711-22 -
Annals of Clinical Microbiology and... Jan 2023The aim of this study was to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) for the diagnosis of Pneumocystis jirovecii Pneumonia (PCP) in...
OBJECTIVE
The aim of this study was to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) for the diagnosis of Pneumocystis jirovecii Pneumonia (PCP) in critically pediatric patients.
METHODS
Seventeen critically pediatric patients with PCP and sixty patients diagnosed with non-PCP pneumonia who were admitted in pediatric intensive care unit between June 2018 and July 2021 were enrolled. Conventional methods and mNGS for detecting Pneumocystis jirovecii (P. jirovecii) were compared. The patients' demographics, comorbidities, laboratory test results, antibiotic treatment response and 30 day mortality were analyzed.
RESULT
The mNGS showed a satisfying diagnostic performance with a sensitivity of 100% in detecting P. jirovecii compared with Gomori methenamine silver staining (5.9%), serum (1,3)-β-D-glucan (86.7%) and and LDH (55.6%). The diagnostic specificity of mNGS for PCP was higher than that of serum BDG (56.7%) and LDH (71.4%). In PCP group, over one thirds' cases had mixed infections. Compared with survivors, non-survivors had higher stringently mapped read numbers (SMRNs) in bronchoalveolar lavage fluid (BALF) sample (P < 0.05), suggesting SMRNs were closely associated with the severity of response. The detection for P. jirovecii by mNGS both in BALF and blood samples reached a concordance rate of 100%, and the SMRNs in the BALF were remarkably higher than that in blood samples. Initial antimicrobial treatment was modified in 88.2% of PCP patients based on the mNGS results.
CONCLUSION
The mNGS is a potential and efficient technology in diagnosing PCP and shows a satisfying performance in the detection of co-pathogens. Both blood and BALF samples for mNGS are suggested for the presumptive diagnosis of PCP.
Topics: Child; Humans; Bronchoalveolar Lavage Fluid; High-Throughput Nucleotide Sequencing; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 36647095
DOI: 10.1186/s12941-023-00555-5