-
Journal de Mycologie Medicale Mar 2022To provide original data on Pneumocystis primary infection in non-immunosuppressed infants from Peru.
OBJECTIVES
To provide original data on Pneumocystis primary infection in non-immunosuppressed infants from Peru.
METHODS
A cross sectional study was performed. Infants less than seven months old, without any underlying medical conditions attending the "well baby" outpatient clinic at one hospital in Lima, Peru were prospectively enrolled during a 15-month period from November 2016 to February 2018. All had a nasopharyngeal aspirate (NPA) for detection of P. jirovecii DNA using a PCR assay, regardless of respiratory symptoms. P. jirovecii DNA detection was considered to represent pulmonary colonization contemporaneous with Pneumocystis primary infection. Associations between infants' clinical and demographic characteristics and results of P. jirovecii DNA detection were analyzed.
RESULTS
P. jirovecii DNA was detected in 45 of 146 infants (30.8%) and detection was not associated with concurrent respiratory symptoms in 40 of 45 infants. Infants with P. jirovecii had a lower mean age when compared to infants not colonized (p <0.05). The highest frequency of P. jirovecii was observed in 2-3-month-old infants (p < 0.01) and in the cooler winter and spring seasons (p <0.01). Multivariable analysis showed that infants living in a home with ≤ 1 bedroom were more likely to be colonized; Odds Ratio =3.03 (95%CI 1.31-7.00; p = 0.01).
CONCLUSION
Pneumocystis primary infection in this single site in Lima, Peru, was most frequently observed in 2-3-month-old infants, in winter and spring seasons, and with higher detection rates being associated with household conditions favoring close inter-individual contacts and potential transmission of P. jirovecii.
Topics: Cross-Sectional Studies; Humans; Infant; Peru; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 34598108
DOI: 10.1016/j.mycmed.2021.101202 -
Mikrobiyoloji Bulteni Apr 2015Pneumocystis pneumonia (PCP) is a potentially life-threatening infection for the immunocompromized patients. However, Pneumocystis jirovecii colonization can also be...
Pneumocystis pneumonia (PCP) is a potentially life-threatening infection for the immunocompromized patients. However, Pneumocystis jirovecii colonization can also be detected in healthy individuals and in patients with various underlying lung diseases. The aim of this study was to evaluate the immunocompetent and iatrogenically immunosuppressed patients in terms of PCP and P.jirovecii colonization. A total of 92 patients (66 male, 26 female; age range: 18-93 years, median: 58.5) who underwent bronchoscopy due to various pulmonary symptoms between January 2011-April 2014, were included in the study. Of these patients, 65 were under immunosuppressive therapy (38 were treated with anti-cancer drugs, 15 with anti-rejection/immunomodulatory drugs and 12 with corticosteroids), while 27 were immunocompetent. Bronchoalveolar lavage (BAL) fluids were evaluated for the presence of P.jirovecii mitochondrial gene coding ribosomal large subunit (mtLSUrRNA) with nested PCR (nPCR) method. All of the samples were also examined by Giemsa and Gomori's methenamine silver (GMG) staining methods. P.jirovecii DNA was detected in 31 (33.7%) out of 92 BAL samples by nPCR. Although six immunosuppressed patients were positive in the first round of amplification, 26 of 65 (40%) immunosuppressed and five of 27 (18.5%) immunocompetent patients were positive with nPCR. P.jirovecii cysts and trophozoites were detected in only five (16.1%) of the 31 nPCR positive samples. The probability of being immunosuppressive among nPCR positive cases was statistically higher than nPCR negative cases (χ²= 3.940; p= 0.047). This difference was more significant in organ transplant recipients and patients under anti-rejection/immunomodulatory treatment (χ²= 6.715, p= 0.01; χ²= 5.550, p= 0.018, respectively). When clinical, laboratory and radiological findings of nPCR positive patients were considered, five patients (2 kidney transplant, 1 bone marrow transplant, 1 interstitial lung disease and 1 lung cancer case) in immunosuppressed group were interpreted as "definite PCP" and eight patients (2 kidney transplant, 1 leukemia, 1 connective tissue disease, 1 Wegener's granulomatosus, 2 rheumatoid arthritis and 1 lung cancer case) were interpreted as "probable PCP". Other 18 (19.6%) nPCR positive patients, of them 13 were immunosuppressive and five were immunocompetent, were considered as "P.jirovecii colonization". The colonization rate was determined as 50% (13/26) in immunosuppressive patients, and was mostly detected in patients with hematological malignancies (4/13), followed by patients with solid tumors (3/13) and organ transplantations (3/13). On the other hand, all of the nPCR positive immunocompetent patients (5/5) were evaluated as colonization. In this study significant data was obtained about P.jirovecii epidemiology in our country. Our results also showed that iatrogenically immunosuppressed patients are under risk of PCP and nPCR method is more sensitive than conventional PCR and classical staining methods in the diagnosis of these patients.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bronchoalveolar Lavage Fluid; DNA, Bacterial; Female; Humans; Immunocompetence; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Turkey; Young Adult
PubMed: 26167822
DOI: 10.5578/mb.9344 -
Infection and Immunity Apr 2017pneumonia (PcP) is a life-threatening infection that affects immunocompromised individuals. Nearly half of all PcP cases occur in those prescribed effective...
pneumonia (PcP) is a life-threatening infection that affects immunocompromised individuals. Nearly half of all PcP cases occur in those prescribed effective chemoprophylaxis, suggesting that additional preventive methods are needed. To this end, we have identified a unique mouse surface protein, designated cross-reactive antigen 1 (Pca1), as a potential vaccine candidate. Mice were immunized with a recombinant fusion protein containing Pca1. Subsequently, CD4 T cells were depleted, and the mice were exposed to Pca1 immunization completely protected nearly all mice, similar to immunization with whole organisms. In contrast, all immunized negative-control mice developed PcP. Unexpectedly, Pca1 immunization generated cross-reactive antibody that recognized and Potential orthologs of Pca1 have been identified in Such cross-reactivity is rare, and our findings suggest that Pca1 is a conserved antigen and potential vaccine target. The evaluation of Pca1-elicited antibodies in the prevention of PcP in humans deserves further investigation.
Topics: Animals; Antibodies, Fungal; Antibody Specificity; Antigens, Fungal; Cross Reactions; Fungal Proteins; Fungal Vaccines; Immunization; Mice; Pneumocystis; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 28031260
DOI: 10.1128/IAI.00850-16 -
PloS One 2021Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP...
OBJECTIVE
Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP.
METHODS
We retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC).
RESULTS
The IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016).
CONCLUSIONS
Patients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.
Topics: Aged; Female; Hospital Mortality; Humans; Immunocompromised Host; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prognosis; Proportional Hazards Models; Republic of Korea; Retrospective Studies
PubMed: 33539407
DOI: 10.1371/journal.pone.0246296 -
MSphere May 2021Prior work has shown that parenterally administered anti-CD20 (5D2) inhibits CD4 T cell priming in response to challenge with and predisposes to pneumonia. In this...
Prior work has shown that parenterally administered anti-CD20 (5D2) inhibits CD4 T cell priming in response to challenge with and predisposes to pneumonia. In this study, we investigated the effect of subcutaneous anti-CD20 antibody and infection. In mice with primary infection, anti-CD20 antibody treatment depleted both CD19 and CD27 CD19 cells but not T cells in the lung at days 14 and 28 after inoculation. Although anti-CD20 antibody treatment impaired fungal clearance at day 14 postinfection, fungal burden in the lungs was substantially reduced at day 28 in both depleted and control mice in the low-dose group. Subcutaneous anti-CD20 antibody treatment did not alter antigen-specific serum immunoglobulin levels in mice compared with control mice, and there were no significant differences in the numbers of lung gamma interferon-positive (IFN-γ) CD4, interleukin 4-positive (IL-4) CD4, IL-5 CD4, and IL-17A CD4 cells between depleted and control mice after infection. In mice with secondary infection, the lung fungal burden was comparable between depleted and control mice 14 days after reinfection. Low-dose subcutaneous anti-CD20 antibody treatment may delay fungal clearance, but it did not impair the ability of the host to clear infection, irrespective of primary or secondary infection. Anti-CD20 antibody therapy is used for both cancer and autoimmune disease but has been shown to be associated with pneumonia in humans. This study shows that low-dose subcutaneous anti-CD20 can modulate B cell populations without grossly perturbing fungal immunity against lung infection.
Topics: Animals; Antibodies, Monoclonal; Antigens, CD20; B-Lymphocytes; Injections, Subcutaneous; Lung; Lymphocyte Depletion; Mice; Mice, Inbred C57BL; Pneumocystis; Pneumonia, Pneumocystis
PubMed: 33952667
DOI: 10.1128/mSphere.01144-20 -
Clinical Infectious Diseases : An... Jan 2013Pneumocystis without obvious accompanying pathology is occasionally reported in autopsied infant lungs. Its prevalence and significance are unknown. Interestingly, this...
BACKGROUND
Pneumocystis without obvious accompanying pathology is occasionally reported in autopsied infant lungs. Its prevalence and significance are unknown. Interestingly, this mild infection induces a strong activation of mucus secretion-related genes in young immunocompetent rodents that has not been explored in infants. Excess mucus is induced by multiple airway offenders through nonspecific pathways and would explain a cofactor role of Pneumocystis in respiratory disease. We undertook characterization of the prevalence of Pneumocystis and associated mucus in infant lungs.
METHODS
Samples from 128 infants (mean age, 101 days) who died suddenly and unexpectedly in Santiago during 1999-2004 were examined for Pneumocystis using nested polymerase chain reaction (nPCR) amplification of the P. jirovecii mtLSU ribosomal RNA gene and immunofluorescence microscopy (IF). Pneumocystis-negative infants 28 days and older and their age-closest positives were studied for MUC5AC expression and Pneumocystis burden by Western blot and quantitative PCR, respectively.
RESULTS
Pneumocystis DNA was detected by nPCR in 105 of the 128 infants (82.0%) and Pneumocystis organisms were visualized by IF in 99 (94.3%) of the DNA-positive infants. The infection was commonest at 3-4 months with 40 of 41 (97.6%) infants of that age testing positive. MUC5AC was significantly increased in Pneumocystis-positive tissue specimens (P = .013). Death was unexplained in 113 (88.3%) infants; Pneumocystis was detected in 95 (84.0%) of them vs 10 of 15 (66.7%) with explained death (P = .28).
CONCLUSIONS
A highly focal Pneumocystis infection associated to increased mucus expression is almost universally present in the lungs of infants dying unexpectedly in the community regardless of autopsy diagnosis.
Topics: Autopsy; Colony Count, Microbial; DNA, Fungal; Female; Humans; Infant; Infant, Newborn; Lung; Male; Microscopy; Mucin 5AC; Mucus; Nucleic Acid Amplification Techniques; Pneumocystis; Pneumonia, Pneumocystis; Prevalence; Sensitivity and Specificity; Sudden Infant Death
PubMed: 23074306
DOI: 10.1093/cid/cis870 -
Microbiology Spectrum Sep 2021Pneumocystis jirovecii is a threat to iatrogenically immunosuppressed individuals, a heterogeneous population at rapid growth. We assessed the ability of an in-house...
Pneumocystis jirovecii is a threat to iatrogenically immunosuppressed individuals, a heterogeneous population at rapid growth. We assessed the ability of an in-house semiquantitative real-time PCR assay to discriminate Pneumocystis pneumonia (PCP) from colonization and identified risk factors for infection in these patients. Retrospectively, 242 PCR-positive patients were compared according to PCP status, including strata by immunosuppressive conditions, human immunodeficiency virus (HIV) infection excluded. Associations between host characteristics and cycle threshold () values, semiquantitative real-time PCR correlates of fungal loads in lower respiratory tract specimens, were investigated. values differed significantly according to PCP status. Overall, a value of 36 allowed differentiation between PCP and colonization with sensitivity and specificity of 71.3% and 77.1%, respectively. A value of less than 31 confirmed PCP, whereas no value permitted exclusion. A considerable diversity was uncovered; solid organ transplant (SOT) recipients had significantly higher fungal loads than patients with hematological malignancies. In SOT recipients, a cutoff value of 36 resulted in sensitivity and specificity of 95.0% and 83.3%, respectively. In patients with hematological malignancies, a higher cutoff value of 37 improved sensitivity to 88.5% but reduced specificity to 66.7%. For other conditions, assay validity appeared inferior. Corticosteroid usage was an independent predictor of PCP in a multivariable analysis and was associated with higher fungal loads at PCP expression. Semiquantitative real-time PCR improves differentiation between PCP and colonization in immunocompromised HIV-negative individuals with acute respiratory syndromes. However, heterogeneity in disease evolution requires separate cutoff values across intrinsic and iatrogenic predisposition for predicting non-HIV PCP. Pneumocystis jirovecii is potentially life threatening to an increasing number of individuals with compromised immune systems. This microorganism can cause severe pneumonia in susceptible hosts, including patients with cancer and autoimmune diseases and people undergoing solid organ transplantation. Together, these patients constitute an ever-diverse population. In this paper, we demonstrate that the heterogeneity herein has important implications for how we diagnose and assess the risk of Pneumocystis pneumonia (PCP). Specifically, low loads of microorganisms are sufficient to cause infection in patients with blood cancer compared to those in solid organ recipients. With this new insight into host versus biology, clinicians can manage patients at risk of PCP more accurately. As a result, we take a significant step toward offering precision medicine to a vulnerable patient population. One the one hand, these patients have propensity for adverse effects from antimicrobial treatment. On the other hand, this population is susceptible to life-threatening infections, including PCP.
Topics: Aged; Female; Humans; Immunocompromised Host; Male; Middle Aged; Molecular Diagnostic Techniques; Pneumocystis carinii; Pneumonia, Pneumocystis; Real-Time Polymerase Chain Reaction; Retrospective Studies; Sensitivity and Specificity
PubMed: 34346746
DOI: 10.1128/Spectrum.00026-21 -
Mikrobiyoloji Bulteni Oct 2020Pneumocystis jirovecii is an atypical fungus that causes P.jirovecii pneumonia (PCP) in immunocompromised patients. Currently, while the incidence of AIDS-related PCP is...
Pneumocystis jirovecii is an atypical fungus that causes P.jirovecii pneumonia (PCP) in immunocompromised patients. Currently, while the incidence of AIDS-related PCP is decreasing, PCP has become more common in HIV-negative immunosuppressive patients as a result of increased diseases requiring immunosuppressive therapy. In this study, it was aimed to investigate PCP and colonizations by microscopy, polymerase chain reaction (PCR) and Krebs von den Lungen-6 (KL-6) tests in symptomatic immunosuppressive inpatients with the sign of radiologically atypical pneumonia in Mersin University Hospital. A total of 96 patients, between August 2016 and February 2018 were included in the study. Seventy two (75%) of the 96 patients were under immunosuppressive therapy. P.jirovecii was investigated in the respiratory tract samples [sputum (n= 88), tracheal aspirate (n= 6) and bronchoalveolar lavage (n= 2)] by mtLSUrRNA nested PCR and microscopic staining methods [immunofluorescence assay (IFA), Toluidine Blue O (TBO)], and KL-6 levels were tested in serum samples. P.jirovecii was detected in 16 (16.7%) samples by PCR, in five (5.2%) samples by IFA, in three (3.1%) samples by TBO stain method. When IFA was taken as a reference test, sensitivity and specificity of TBO and PCR were calculated as 60% and 100%; 100% and 87.9%, respectively. In P.jirovecii PCR positive patients, the distribution of underlying diseases; cancer (n= 6), hematological malignancy (n= 3), HIV/AIDS (n= 3), COPD (n= 2), and interstitial lung disease (n= 2) were found as 11 (68.75%) of the 16 positive patients, received immunosuppressive therapy (HIV positive non-Hodgkin lymphoma); of the 3 (18.75%) patients of were immunocompetent, and only 2 (12.5%) were HIV/AIDS. Five of the 16 PCR positive the patients that have positive microscopic examination were definited PCP [HIV/AIDS (n= 3), lung cancer (n= 1), interstitial lung disease (n= 1)]; three patients were PCR positive and microscopy negative probable PCP [multiple myeloma (n= 1), interstitial lung disease (n= 1), cholangiocellular carcinoma (n= 1)] and eight other patients were identified as colonized. In the study, when the frequency of the detection of P.jirovecii was evaluated according to the underlying diseases, it was found statistically significantly higher only in HIV/AIDS patients (p= 0.012). When KL-6 was evaluated among the patients defined as PCP/possible PCP and colonization, sensitivity and specificity were determined as 62.5% and 75%, respectively. As a result, nested PCR method was found as sensitive and successful for the detection of P.jirovecii from sputum samples. KL-6 test was not found sufficient for the differentiation of colonization and the infection in PCR positive patients. The results obtained in the study showed that PCP should be on the differential diagnosis list according to the immune status and the clinical features of the inpatients. More researchs are required with more patients to achieve for detailed reliable results in these groups. In addition, molecular epidemiological studies related to genotyping and resistance against anti-PCP drugs are needed to understand P.jirovecii infections in our region and country.
Topics: Bronchoalveolar Lavage Fluid; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Sputum
PubMed: 33107287
DOI: 10.5578/mb.69853 -
Thorax Jul 1982
Review
Topics: Homosexuality; Humans; Immune Tolerance; Male; Pneumocystis; Pneumonia, Pneumocystis; Sarcoma, Kaposi; Skin Neoplasms; Syndrome
PubMed: 6753225
DOI: 10.1136/thx.37.7.481 -
Journal of Clinical Microbiology Jan 1999The detection of Pneumocystis carinii DNA in blood by PCR could be useful for studying the natural history of pneumocystosis and could also be a noninvasive diagnostic... (Review)
Review
The detection of Pneumocystis carinii DNA in blood by PCR could be useful for studying the natural history of pneumocystosis and could also be a noninvasive diagnostic method. The results of previous studies are nevertheless conflicting. In our study, we compared three commercially available DNA extraction kits (GeneReleaser, QIAamp Tissue Kit, and ReadyAmp Genomic DNA Purification System) and proteinase K and proteinase K-phenol-chloroform treatments for the extraction of P. carinii DNA from dilutions of a P. carinii f. sp. hominis cyst suspension mixed with human whole blood. A rapid and simple nested PCR protocol which amplifies a portion of the mitochondrial large-subunit rRNA gene was applied to all the extraction products. The QIAmp Tissue Kit was the most effective kit for the isolation of amplification-ready P. carinii DNA and was used with nested PCR for the testing of whole-blood specimens from 35 immunocompetent control patients and 84 human immunodeficiency virus (HIV)-infected patients investigated for pulmonary disease and/or fever. In HIV-infected patients, P. carinii DNA was detected by nested PCR in blood samples from 3 of 14 patients with microscopically proven P. carinii pneumonia, 7 of 22 patients who were considered to be colonized with P. carinii, and 9 of 48 patients who were neither infected nor colonized with P. carinii. P. carinii DNA was not detected in blood specimens from the 35 immunocompetent patients. P. carinii DNA in blood might represent viable P. carinii organisms or DNA complexes released from pulmonary phagocytes. In conclusion, P. carinii DNA may be detected in whole blood from HIV-infected patients, but the nature and the meaning of the circulating form of P. carinii remain to be established.
Topics: AIDS-Related Opportunistic Infections; DNA, Fungal; Humans; Immunocompetence; Microbiological Techniques; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction
PubMed: 9854076
DOI: 10.1128/JCM.37.1.127-131.1999