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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 -
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 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 -
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 -
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 -
MBio May 2018species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable Human... (Comparative Study)
Comparative Study
species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable Human infections present major challenges because of a limited therapeutic arsenal and the rise of drug resistance. To investigate the diversity and demographic history of natural populations of infecting humans, rats, and mice, we performed whole-genome and large-scale multilocus sequencing of infected tissues collected in various geographic locations. Here, we detected reduced levels of recombination and variations in historical demography, which shape the global population structures. We report estimates of evolutionary rates, levels of genetic diversity, and population sizes. Molecular clock estimates indicate that species diverged before their hosts, while the asynchronous timing of population declines suggests host shifts. Our results have uncovered complex patterns of genetic variation influenced by multiple factors that shaped the adaptation of populations during their spread across mammals. Understanding how natural pathogen populations evolve and identifying the determinants of genetic variation are central issues in evolutionary biology. , a fungal pathogen which infects mammals exclusively, provides opportunities to explore these issues. In humans, can cause a life-threatening pneumonia in immunosuppressed individuals. In analysis of different species infecting humans, rats, and mice, we found that there are high infection rates and that natural populations maintain a high level of genetic variation despite low levels of recombination. We found no evidence of population structuring by geography. Our comparisons of the times of divergence of these species to their respective hosts suggest that may have undergone recent host shifts. The results demonstrate that strains are widely disseminated geographically and provide a new understanding of the evolution of these pathogens.
Topics: Animals; Genetic Variation; Genomics; Humans; Mice; Phylogeny; Pneumocystis; Pneumonia, Pneumocystis; Rats; Rats, Sprague-Dawley; Recombination, Genetic; Rodent Diseases
PubMed: 29739910
DOI: 10.1128/mBio.00381-18 -
Pulmonology 2020
Topics: Humans; Immunocompromised Host; Pneumonia, Pneumocystis
PubMed: 31744754
DOI: 10.1016/j.pulmoe.2019.10.005 -
Frontiers in Cellular and Infection... 2021Differentiating infection from colonisation is crucial for appropriate therapy administration. In this study, we evaluated the performance of bronchoalveolar lavage...
BACKGROUND
Differentiating infection from colonisation is crucial for appropriate therapy administration. In this study, we evaluated the performance of bronchoalveolar lavage fluid (BAL) metagenomic next-generation sequencing (mNGS) and serum 1,3-β-D-glucan (BDG) tests in differentiating colonisation and infection with
METHODS
From January 2018 to March 2021, 47 patients were enrolled in this study at the Hunan Provincial People's Hospital. The final diagnosis was used as a reference, and cases were classified into the pneumonia (PJP) group or the colonisation (PJC) group. Clinical data were recorded. The performances of mNGS and BDG were compared.
RESULT
The fungal load significantly differed between patients with PJP and PJC, with median reads of 3,215.79 ± 1,797 . 5.61 ± 0.88 in the PJP and PJC groups, respectively ( < 0.0001). BDG also significantly differed between the two groups, with a median titre of 233.60 ± 39.65 pg/ml in the PJP group and 68.48 ± 19.21 pg/ml in the PJC group ( 0.0006). The area under the curve was 0.973 (95%CI: 0.868-1.007) for mNGS of the BAL and 0.879 (95%CI: 0.769-0.989) for the serum BDG. The optimal threshold value for discriminating infection from colonisation appeared to be 14 reads (sensitivity, 83.3%; specificity, 95.7%; positive likelihood ratio, 19.2) and BDG = 88.6 pg/ml (sensitivity, 79.2%; specificity, 92.9%; positive likelihood ratio, 18.2). No correlation between mNGS reads and the BDG titre was found in mNGS-positive patients ( = 0.0076, = 0.583). The levels of lactate dehydrogenase and C-reactive protein were significantly higher in the PJP group than in the PJC group.
CONCLUSION
BAL mNGS and serum BDG are useful adjunct tests that can assist with differentiating between colonisation and infection of .
Topics: Bronchoalveolar Lavage Fluid; Diagnosis, Differential; Glucans; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Proteoglycans; Sensitivity and Specificity; beta-Glucans
PubMed: 35004353
DOI: 10.3389/fcimb.2021.784236 -
MBio Jul 2019The genus encompasses fungal species that colonize mammals' lungs with host specificity. Should the host immune system weaken, the fungal species can cause severe...
The genus encompasses fungal species that colonize mammals' lungs with host specificity. Should the host immune system weaken, the fungal species can cause severe pneumonia. The life cycle of these pathogens is poorly known, mainly because an culture method has not been established. Both asexual and sexual cycles would occur. Trophic cells, the predominant forms during infection, could multiply asexually but also enter into a sexual cycle. Comparative genomics revealed a single mating type locus, including plus and minus genes, suggesting that primary homothallism involving self-fertility of each strain is the mode of reproduction of species. We identified and analyzed the expression of the and genes encoding the receptors for plus and minus pheromones using reverse transcriptase PCR, in both infected mice and bronchoalveolar lavage fluid samples from patients with pneumonia. Both receptors were most often concomitantly expressed during infection, revealing that both pheromone-receptor systems are involved in the sexual cycle. The transcripts were subject to alternative splicing. Using immunostaining, we investigated the presence of the pheromone receptors at the surfaces of cells from a patient. The staining tools were first assessed in displaying the receptors at their cellular surface. Both receptors were present at the surfaces of the vast majority of the cells that were likely trophic forms. The receptors might have a role in mate recognition and/or postfertilization events. Their presence at the cell surface might facilitate outbreeding versus inbreeding of self-fertile strains. The fungi belonging to the genus may cause severe pneumonia in immunocompromised humans, a disease that can be fatal if not treated. This disease is nowadays one of the most frequent invasive fungal infections worldwide. Whole-genome sequencing revealed that the sexuality of these fungi involves a single partner that can self-fertilize. Here, we report that two receptors recognizing specifically excreted pheromones are involved in this self-fertility within infected human lungs. Using fluorescent antibodies binding specifically to these receptors, we observed that most often, the fungal cells display both receptors at their surface. These pheromone-receptor systems might play a role in mate recognition and/or postfertilization events. They constitute an integral part of the obligate sexuality within human lungs, a cycle that is necessary for the dissemination of the fungus to new individuals.
Topics: Animals; Bronchoalveolar Lavage Fluid; DNA, Fungal; Gene Expression; Genes, Fungal; Genes, Mating Type, Fungal; Genomics; Humans; Immunoenzyme Techniques; Mice; Pneumocystis; Pneumonia, Pneumocystis; Receptors, Pheromone; Staining and Labeling
PubMed: 31289178
DOI: 10.1128/mBio.01145-19 -
Cellular Microbiology Oct 2020Caspase recruitment domains-containing protein 9 (CARD9) is an adaptor molecule critical for key signalling pathways initiated through C-type lectin receptors (CLRs)....
Caspase recruitment domains-containing protein 9 (CARD9) is an adaptor molecule critical for key signalling pathways initiated through C-type lectin receptors (CLRs). Previous studies demonstrated that Pneumocystis organisms are recognised through a variety of CLRs. However, the role of the downstream CARD9 adaptor signalling protein in host defence against Pneumocystis infection remains to be elucidated. Herein, we analysed the role of CARD9 in host defence against Pneumocystis both in CD4-depleted CARD9 and immunocompetent hosts. Card9 gene-disrupted (CARD9 ) mice were more susceptible to Pneumocystis, as evidenced by reduced fungal clearance in infected lungs compared to wild-type (WT) infected mice. Our data suggests that this defect was due to impaired proinflammatory responses. Furthermore, CARD9 macrophages were severely compromised in their ability to differentiate and express M1 and M2 macrophage polarisation markers, to enhanced mRNA expression for Dectin-1 and Mincle, and most importantly, to kill Pneumocystis in vitro. Remarkably, compared to WT mice, and despite markedly increased organism burdens, CARD9 animals did not exhibit worsened survival during pneumocystis pneumonia (PCP), perhaps related to decreased lung injury due to altered influx of inflammatory cells and decreased levels of proinflammatory cytokines in response to the organism. Finally, although innate phase cytokines were impaired in the CARD9 animals during PCP, T-helper cell cytokines were normal in immunocompetent CARD9 animals infected with Pneumocystis. Taken together, our data demonstrate that CARD9 has a critical function in innate immune responses against Pneumocystis.
Topics: Animals; CARD Signaling Adaptor Proteins; Cell Differentiation; Colony Count, Microbial; Cytokines; Immunocompromised Host; Lectins, C-Type; Lung; Macrophages, Alveolar; Membrane Proteins; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Peroxidase; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis; Rats; T-Lymphocytes, Helper-Inducer; Tumor Necrosis Factor-alpha
PubMed: 32548948
DOI: 10.1111/cmi.13235