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Indian Journal of Pediatrics Aug 2023
Topics: Humans; Pneumocystis carinii; SARS-CoV-2; Coinfection; X-Linked Combined Immunodeficiency Diseases; COVID-19; Pneumonia, Pneumocystis
PubMed: 37249831
DOI: 10.1007/s12098-023-04661-2 -
Infection, Genetics and Evolution :... Nov 2019To investigate the genetic polymorphisms of mitochondrial large ribosomal subunit (mtLSU)-rRNA, dihydrofolate reductase (DHFR), dihydropteroate synthase (DHPS),...
OBJECTIVE
To investigate the genetic polymorphisms of mitochondrial large ribosomal subunit (mtLSU)-rRNA, dihydrofolate reductase (DHFR), dihydropteroate synthase (DHPS), cytochrome b (CYB), and superoxide dismutase (SOD) genes and its correlation with clinical outcomes of Pneumocystis jirovecii pneumonia in acquired immune deficiency(AIDS) patients.
METHODS
Eighty AIDS patients with P. jirovecii pneumonia that were admitted to our hospital from 2016 to 2018 were included in this study. Their demographic information and clinical data were collected, as well as corresponding saliva specimens for PCR and sequencing of mtLSU-rRNA, DHFR, DHPS, CYB, and SOD genes to analyze genetic polymorphisms, different polymorphic combinations, and clinical outcomes.
RESULTS
Of the 80 saliva specimens, mtLSU-rRNA was successfully amplified and sequenced in 30 cases; CYB was successfully amplified and sequenced in 26 cases; and SOD, DHFR, and DHPS were successfully amplified and sequenced in 18 cases. These results indicate that The mtLSU-rRNA, CYB, and SOD genes were highly polymorphic. mt85T and CYB1 were the variants dominantly detected at the mtLSU-rRNA and CYB loci, respectively. The SOD1 and SOD2 variants (each in 50% of the cases) were detected at the SOD locus. Among the 18 cases that were successfully amplified and sequenced for DHFR and DHPS, three DHFR nonsense mutations and no DHPS mutation were observed. The mt85C, CYB1, SOD1, and DHFR312T genes harbored common polymorphisms (n = 4; 22.22%) and the mt85T, CYB1, SOD1, DHFR312T genes were associated with poor clinical outcomes.
CONCLUSION
The types of genetic polymorphisms and polymorphic combinations of mtLSU-rRNA, DHFR, DHPS, CYB, and SOD in P. jirovecii were related to the clinical outcomes of patients with P. jirovecii pneumonia in Zhejiang Province, China.
Topics: Acquired Immunodeficiency Syndrome; Adult; China; Female; Genes, Fungal; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Polymorphism, Genetic
PubMed: 31284044
DOI: 10.1016/j.meegid.2019.103955 -
Immunity, Inflammation and Disease Jan 2022Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in organ transplant recipients that may be prevented by antibiotic prophylaxis. We aimed to...
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in organ transplant recipients that may be prevented by antibiotic prophylaxis. We aimed to investigate the incidence rate (IR) of PCP and the related hospitalization and mortality rates in liver transplant recipients in an era of routine prophylaxis.
METHODS
We included all adult liver transplant recipients transplanted at Rigshospitalet between January 1, 2011 and October 1, 2019. Microbiology data were obtained from the Danish Microbiology Database (MiBa), a national database containing all data from all Departments of Clinical Microbiology in Denmark receiving samples from both hospitals and general practices. According to local guidelines, PCP prophylaxis was initiated 1 week posttransplantation and discontinued after 6 months or sooner in patients experiencing side effects.
RESULTS
We included 343 liver transplant recipients with 1153 person-years of follow-up (PYFU), of which 269 (78%) received PCP prophylaxis during the first 6 months posttransplantation. Seven (2%) recipients were diagnosed with PCP during follow-up. In the first 6 months posttransplantation and in 269 transplant recipients who received prophylaxis there were zero PCP events while the IR was 32 (95% confidence interval [CI] 2.9-148) per 1000 PYFU in 74 recipient who did not receive prophylaxis. During 7th to 12th month posttransplantation the IR was 20 (95% CI: 5.5-53) per 1000 PYFU. All seven (100%) recipients diagnosed with PCP were hospitalized, however none died.
CONCLUSIONS
PCP was not detected in liver transplant recipients while on prophylaxis. Though, it worth mentioning that two out of the seven PCP patients received high-dose prednisolone before the PCP event. All liver transplant recipients with PCP were hospitalized, but none died. Randomized clinical trials to determine the optimal duration of prophylaxis are warranted.
Topics: Adult; Antibiotic Prophylaxis; Humans; Liver Transplantation; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 34713963
DOI: 10.1002/iid3.546 -
Frontiers in Cellular and Infection... 2023Pneumonia are the leading cause of death worldwide, and antibiotic treatment remains fundamental. However, conventional sputum smears or cultures are still inefficient...
INTRODUCTION
Pneumonia are the leading cause of death worldwide, and antibiotic treatment remains fundamental. However, conventional sputum smears or cultures are still inefficient for obtaining pathogenic microorganisms.Metagenomic next-generation sequencing (mNGS) has shown great value in nucleic acid detection, however, the NGS results for lower respiratory tract microorganisms are still poorly studied.
METHODS
This study dealt with investigating the efficacy of mNGS in detecting pathogens in the lower respiratory tract of patients with pulmonary infections. A total of 112 patients admitted at the First Affiliated Hospital of Zhengzhou University between April 30, 2018, and June 30, 2020, were enrolled in this retrospective study. The bronchoalveolar lavage fluid (BALF) was obtained from lower respiratory tract from each patient. Routine methods (bacterial smear and culture) and mNGS were employed for the identification of pathogenic microorganisms in BALF.
RESULTS
The average patient age was 53.0 years, with 94.6% (106/112) obtaining pathogenic microorganism results. The total mNGS detection rate of pathogenic microorganisms significantly surpassed conventional methods (93.7% vs. 32.1%, P < 0.05). Notably, 75% of patients (84/112) were found to have bacteria by mNGS, but only 28.6% (32/112) were found to have bacteria by conventional approaches. The most commonly detected bacteria included (19.6%), (17.9%), (14.3%), (12.5%), (12.5%), and (11.6%). In 29.5% (33/112) of patients, fungi were identified using mNGS, including 23 cases of (20.5%), 18 of (16.1%), and 10 of (8.9%). However, only 7.1 % (8/112) of individuals were found to have fungi when conventional procedures were used. The mNGS detection rate of viruses was significantly higher than the conventional method rate (43.8% vs. 0.9%, P < 0.05). The most commonly detected viruses included Epstein-Barr virus (15.2%), cytomegalovirus (13.4%), circovirus (8.9%), human coronavirus (4.5%), and rhinovirus (4.5%). Only 29.4% (33/112) of patients were positive, whereas 5.4% (6/112) of patients were negative for both detection methods as shown by Kappa analysis, indicating poor consistency between the two methods (P = 0.340; Kappa analysis).
CONCLUSION
Significant benefits of mNGS have been shown in the detection of pathogenic microorganisms in patients with pulmonary infection. For those with suboptimal therapeutic responses, mNGS can provide an etiological basis, aiding in precise anti-infective treatment.
Topics: Humans; Middle Aged; Retrospective Studies; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Pneumonia; High-Throughput Nucleotide Sequencing; Respiratory System
PubMed: 38264726
DOI: 10.3389/fcimb.2023.1291980 -
Microbiology Spectrum Feb 2024spp. are host obligate fungal pathogens that can cause severe pneumonia in mammals and rely heavily on their host for essential nutrients. The lack of a sustainable...
spp. are host obligate fungal pathogens that can cause severe pneumonia in mammals and rely heavily on their host for essential nutrients. The lack of a sustainable culture system poses challenges in understanding their metabolism, and the acquisition of essential nutrients from host lungs remains unexplored. Transmission electron micrographs show that extracellular vesicles (EVs) are found near spp. within the lung. We hypothesized that EVs transport essential nutrients to the fungi during infection. To investigate this, EVs from - and -infected rodents were biochemically and functionally characterized. These EVs contained host proteins involved in cellular, metabolic, and immune processes as well as proteins with homologs found in other fungal EV proteomes, indicating that may release EVs. Notably, EV uptake by indicated their potential involvement in nutrient acquisition and a possibility for using engineered EVs for efficient therapeutic delivery. However, EVs added to did not show increased growth or viability, implying that additional nutrients or factors are necessary to support their metabolic requirements. Exposure of macrophages to EVs increased proinflammatory cytokine levels but did not affect macrophages' ability to kill or phagocytose . These findings provide vital insights into and host EV interactions, yet the mechanisms underlying 's survival in the lung remain uncertain. These studies are the first to isolate, characterize, and functionally assess EVs from -infected rodents, promising to enhance our understanding of host-pathogen dynamics and therapeutic potential.IMPORTANCE spp. are fungal pathogens that can cause severe pneumonia in mammals, relying heavily on the host for essential nutrients. The absence of an culture system poses challenges in understanding their metabolism, and the acquisition of vital nutrients from host lungs remains unexplored. Extracellular vesicles (EVs) are found near spp., and it is hypothesized that these vesicles transport nutrients to the pathogenic fungi. proteins within the EVs showed homology to other fungal EV proteomes, suggesting that spp. release EVs. While EVs did not significantly enhance growth , displayed active uptake of these vesicles. Moreover, EVs induced proinflammatory cytokine production in macrophages without compromising their ability to combat . These findings provide valuable insights into EV dynamics during host-pathogen interactions in pneumonia. However, the precise underlying mechanisms remain uncertain. This research also raises the potential for engineered EVs in therapeutic applications.
Topics: Rats; Animals; Pneumocystis carinii; Proteome; Pneumonia, Pneumocystis; Pneumocystis; Macrophages; Mammals; Cytokines; Extracellular Vesicles
PubMed: 38236033
DOI: 10.1128/spectrum.03653-23 -
Arthritis Research & Therapy Sep 2021Idiopathic inflammatory myopathies (IIM) are associated with a significantly higher risk of opportunistic infections including Pneumocystis jirovecii pneumonia (PJP), a...
BACKGROUND
Idiopathic inflammatory myopathies (IIM) are associated with a significantly higher risk of opportunistic infections including Pneumocystis jirovecii pneumonia (PJP), a potentially fatal opportunistic infection. However, no prior studies have evaluated PJP infection in subtypes of IIM.
OBJECTIVES
To investigate the prevalence and mortality rate of PJP infection in subgroups of IIM patients stratified according to myopathy-specific antibodies.
METHODS
In the first part of the study, 463 consecutive patients with IIM were prospectively followed for a period of at least 1 year to analyze the incidence of PJP. In the second part of the study, we enrolled 30 consecutive PJP patients with any rheumatic disease in order to identify the mortality rate and risk factors by Cox regression analysis. The Kaplan-Meier method with log-rank testing was used to assess differences in survival.
RESULTS
The prevalence of PJP in IIM patients was found to be 3.0/100 person-years, while in MDA5 DM patients it was 7.5/100 person-years and in MDA5 IIM patients 0.7/100 person-years (P < 0.05). PJP typically occurred in the first 2 months in the case of MDA5 DM patients who had a significant decrease in their CD4 T cell counts and lymphocyte counts (P < 0.05). In PJP patients, 3-month mortality was higher for MDA5 DM patients than in those with other rheumatic diseases (83.3% vs 38.9%, P < 0.05). Alarmingly, MDA5 DM patients seemed not to benefit from prompt anti-PJP treatment, unlike patients with other rheumatic diseases whose survival improved when anti-PJP treatment was started within 6 days (P < 0.05).
CONCLUSION
PJP has an alarming high incidence and mortality in MDA5 DM patients. Timely treatment for PJP seems not to improve the prognosis of patients with this particular subtype. Hence, there remains a crucial unmet need to develop PJP prophylaxis for MDA5 DM patients.
Topics: Dermatomyositis; Humans; Incidence; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies
PubMed: 34481528
DOI: 10.1186/s13075-021-02606-8 -
Infection and Immunity Jan 2020The inflammatory response to the fungus plays a central role in the respiratory failure associated with pneumonia. To help ameliorate the inflammatory response,...
The inflammatory response to the fungus plays a central role in the respiratory failure associated with pneumonia. To help ameliorate the inflammatory response, corticosteroids are used as an adjuvant to standard antimicrobial therapy. Corticosteroids, however, can have a wide range of effects (including deleterious effects) on the host immune response. To date, pathogen-specific antibody therapy has primarily been developed for both its direct antimicrobial activity (e.g., toxin and viral neutralization) and its ability to enhance the antimicrobial activity of the host immune response via effector cells, like macrophages and neutrophils. In this issue of , Hoy et al. (Z. Hoy, T. W. Wright, M. Elliott, J. Malone, et al., Infect Immun 88:e00640-19, 2020, https://doi.org/10.1128/IAI.00640-19) report on a surprising application of -specific antibody therapy in treating disease by decreasing the inflammatory response. This effect appears to occur as a result of an enhanced phagocytic activity within the lung and an associated alteration in the macrophage phenotype. This study adds insight into our understanding of antibody activity and highlights the possibility of using antibody therapy to limit inflammation for other infectious diseases in which inflammatory damage plays a significant role in disease pathogenesis.
Topics: Anti-Inflammatory Agents; Humans; Immunotherapy; Pneumocystis; Pneumonia, Pneumocystis; Sulfasalazine
PubMed: 31712268
DOI: 10.1128/IAI.00844-19 -
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 -
HIV Medicine Apr 2021Pneumocystis jirovecii pneumonia (PCP) is an opportunistic fungal infection with high morbidity and mortality among people living with HIV. Upper respiratory tract (URT)...
OBJECTIVES
Pneumocystis jirovecii pneumonia (PCP) is an opportunistic fungal infection with high morbidity and mortality among people living with HIV. Upper respiratory tract (URT) swabs are routinely taken for testing viral and bacterial pathogens when patients present with respiratory symptoms in our hospital. We conducted a pilot service improvement project to explore the utility of URT swabs for PCP diagnosis using in-house real-time polymerase chain reaction (PCR).
METHODS
Ten URT swab samples obtained from HIV-positive patients with PCP and a positive PCP PCR (AusDiagnostics) from lower respiratory tract (LRT) samples were retrospectively identified. Nine HIV-positive patients with a negative PCR for PCP from LRT samples were identified. Stored aliquots of DNA extracted from these samples were retrieved and tested by an in-house real-time PCR for the presence of PCP DNA. Among PCP-positive cases, URT swabs collected after PCP treatment initiation were excluded from the study.
RESULTS
In all, 10 URT samples from PCP-positive patients and nine URT samples from PCP-negative patients were tested for PCP by real-time PCR. Eighteen out of 19 URT sample had a concordant result with the LRT samples. The sensitivity and specificity for URT sample PCR were 90% [confidence interval (CI): 55.50-99.75%] and 100% (CI: 66.37-100%). The positive predictive value was 100% and the negative predictive value was 90.9% (CI: 60.90-98.47%).
CONCLUSIONS
Upper respiratory tract swab can reliably detect PCP DNA on real-time PCR among people living with HIV with PCP.
Topics: HIV Infections; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Real-Time Polymerase Chain Reaction; Respiratory System; Retrospective Studies; Sensitivity and Specificity
PubMed: 33230932
DOI: 10.1111/hiv.13014 -
International Journal of Infectious... Sep 2019Histoplasma capsulatum and Pneumocystis jirovecii are respiratory fungal pathogens that principally cause pulmonary disease. Coinfection with both pathogens is scarcely...
BACKGROUND
Histoplasma capsulatum and Pneumocystis jirovecii are respiratory fungal pathogens that principally cause pulmonary disease. Coinfection with both pathogens is scarcely reported. This study detected this coinfection using specific molecular methods for each fungus in the bronchoalveolar lavage (BAL) of patients from a tertiary care hospital.
MATERIALS AND METHODS
BAL samples from 289 hospitalized patients were screened by PCR with specific markers for H. capsulatum (Hcp100) and P. jirovecii (mtLSUrRNA and mtSSUrRNA). The presence of these pathogens was confirmed by the generated sequences for each marker. The clinical and laboratory data for the patients were analyzed using statistical software.
RESULTS
The PCR findings separated three groups of patients, where the first was represented by 60 (20.8%) histoplasmosis patients, the second by 45 (15.6%) patients with pneumocystosis, and the last group by 12 (4.2%) patients with coinfection. High similarity among the generated sequences of each species was demonstrated by BLASTn and neighbor-joining algorithms. The estimated prevalence of H. capsulatum and P. jirovecii coinfection was higher in HIV patients.
Topics: Adult; Aged; Bronchoalveolar Lavage; Coinfection; Female; HIV Infections; Histoplasma; Histoplasmosis; Humans; Male; Mexico; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Tertiary Care Centers
PubMed: 31207386
DOI: 10.1016/j.ijid.2019.06.010