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BMJ Case Reports Jul 2023
Topics: Humans; Pneumonia, Pneumocystis
PubMed: 37479492
DOI: 10.1136/bcr-2023-255853 -
PLoS Pathogens Sep 2020
Review
Topics: Animals; Humans; Lung; Pneumocystis; Pneumonia, Pneumocystis; Species Specificity
PubMed: 32913371
DOI: 10.1371/journal.ppat.1008824 -
Frontiers in Immunology 2022is a ubiquitous fungal pathogen that causes pneumonia (PCP) and pulmonary sequelae in HIV-infected individuals and other immunocompromised populations. With the success...
INTRODUCTION
is a ubiquitous fungal pathogen that causes pneumonia (PCP) and pulmonary sequelae in HIV-infected individuals and other immunocompromised populations. With the success of anti-retroviral therapy for HIV-infected individuals the frequency of PCP in that population has decreased, however, PCP remains a significant cause of morbidity and mortality in individuals with hematologic and solid malignancies, and in individuals treated with immunosuppressive therapies for autoimmune diseases, and following bone marrow and solid organ transplantation. Despite the clinical need, there is no approved vaccine to prevent PCP in vulnerable populations. The ultimate goal of the field is to develop an effective vaccine that can overcome immune deficits in at risk populations and induce long-lasting protective immunity to . Toward this goal, our laboratory has established a model of PCP co-infection in simian immunodeficiency virus (SIV)-infected non-human primates (NHP) and identified a recombinant protein sub-unit vaccine, KEX1, that induces robust anti- immunity in immune-competent macaques that is durable and prevents PCP following simian immunodeficiency virus (SIV)-induced immunosuppression. Type I, or invariant natural killer T (iNKT) cells have the potential to provide B cell help under conditions of reduced CD4+ T cell help.
METHODS
In the present study, we used the SIV model of HIV infection to address whether therapeutic vaccination with the iNKT cell-activating adjuvant α-galactosylceramide (α-GC) and KEX1 (α-GC+KEX1) can effectively boost anti- humoral immunity following virus-induced immunosuppression.
RESULTS
Immunization of antigen-experienced NHPs with α-GC+KEX1 during the early chronic phase of SIV-infection significantly boosted anti- humoral immunity by increasing memory B cells and antibody titers, and enhanced titer durability during SIV-induced immunosuppression. This therapeutic vaccination strategy boosted anti- immune responses during SIV-infection and contributed to protection against co-infection in KEX1-vaccinated macaques.
CONCLUSION
These studies present a novel strategy for stimulating durable anti- humoral immunity in the context of complex, chronic SIV-induced immunosuppression and may be further applied to immunization of other immunosuppressed populations, and toward other common recall antigens.
Topics: Animals; HIV Infections; Pneumocystis; Pneumonia, Pneumocystis; Simian Acquired Immunodeficiency Syndrome; Coinfection; Simian Immunodeficiency Virus; Immunocompromised Host; Vaccines, Synthetic; Primates; Adjuvants, Immunologic; Macaca
PubMed: 36561749
DOI: 10.3389/fimmu.2022.1036658 -
Infectious Disease Clinics of North... Sep 2023Pneumocystis infection manifests predominantly as an interstitial pneumonia in immunocompromised patients. Diagnostic testing in the appropriate clinical context can be... (Review)
Review
Pneumocystis infection manifests predominantly as an interstitial pneumonia in immunocompromised patients. Diagnostic testing in the appropriate clinical context can be highly sensitive and specific and involves radiographic imaging, fungal biomarkers, nucleic acid amplification, histopathology, and lung fluid or tissue sampling. Trimethoprim-sulfamethoxazole remains the first-choice agent for treatment and prophylaxis. Investigation continues to promote a deeper understanding of the pathogen's ecology, epidemiology, host susceptibility, and optimal treatment and prevention strategies in solid organ transplant recipients.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Organ Transplantation; Trimethoprim, Sulfamethoxazole Drug Combination; Immunocompromised Host
PubMed: 37142510
DOI: 10.1016/j.idc.2023.03.005 -
Rheumatology (Oxford, England) Oct 2023To identify potential risk factors and prognostic factors of Pneumocystis jirovecii pneumonia (PJP) infection in anti-melanoma differentiation-associated gene 5...
OBJECTIVES
To identify potential risk factors and prognostic factors of Pneumocystis jirovecii pneumonia (PJP) infection in anti-melanoma differentiation-associated gene 5 antibody-positive DM (anti-MDA5+ DM) patients, and to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS).
METHODS
Anti-MDA5+ DM patients who underwent mNGS or real-time PCR for PJP detection were recruited. The potential risk factors for PJP occurrence and death were analysed via Logistic regression and Cox proportional hazards regression, respectively. The diagnostic efficacy of mNGS was compared with the conventional methods.
RESULTS
91 patients were enrolled and 44 were assigned to PJP+ group. The PJP detection rate was 48.4%. PJP often occurred in the first 3 months (68.2%) of the disease; this period also showed the highest mortality rate (20.5%). Fever and increased lactate dehydrogenase (LDH) were independent risk factors for PJP occurrence, while trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis was an independent protective factor (all P < 0.05). Older age and increased LDH were predictors for mortality in patients with anti-MDA5+ DM and PJP (all P < 0.05). In addition, we found that mNGS had a sensitivity of 100.0% and specificity of 90.0% in diagnosing PJP, with the highest area under the curve of 0.95 (P < 0.001).
CONCLUSION
PJP has high prevalence and mortality in anti-MDA5+ DM. It is crucial for clinicians to identify high-risk patients and promptly institute TMP/SMZ to prevent PJP. mNGS is the preferred approach for pathogen detection in anti-MDA5+ DM when PJP is suspected.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Prevalence; Dermatomyositis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 36734589
DOI: 10.1093/rheumatology/kead063 -
Frontiers in Cellular and Infection... 2022can result in a serious pulmonary infection, pneumonia, in immunocompetent hosts. The diagnosis of pneumonia has long been a major clinical concern, and there are...
BACKGROUND
can result in a serious pulmonary infection, pneumonia, in immunocompetent hosts. The diagnosis of pneumonia has long been a major clinical concern, and there are limitations with the currently utilized immunostaining and polymerase chain reaction diagnosis/detection technologies (, insufficient sensitivity and accuracy). Hence, we sought to establish a rapid and RNA-specific transcription mediated amplification and CRISPR/Cas13a-based diagnostics targeted -mitochondrial large subunit ribosomal RNA.
METHODS
The procedure of the diagnostics included amplification of the extracted RNA samples by transcription mediated amplification, followed by CRISPR/Cas13 detection, and ultimately, the judgment of the results after 30 minutes of fluorescence signal. Later, the diagnostic performance of the CRISPR/Cas13-based diagnostics were tested on the 62 surplus clinical samples.
RESULTS
This CRISPR/Cas13-based diagnostics achieved limits of detection of approximately 2 copies/µL transcribed RNA templates, with no cross reaction to other respiratory pathogens, including bacteria and fungi. Similar to in-house quantitative real-time polymerase chain reaction, CRISPR/Cas13-based diagnostics was still positive in 243-fold diluted bronchial alveolar lavage fluid. A preliminary evaluation of 62 surplus bronchial alveolar lavage fluid samples from patients suspected of pneumonia showed that CRISPR/Cas13-based diagnostics achieved a 78.9% sensitivity and a 97.7% specificity in the diagnosis of pneumonia.
CONCLUSION
Our study demonstrates that the CRISPR/Cas13-based diagnostics technique has good performance for the accurate and specific diagnosis of pneumonia.
Topics: CRISPR-Cas Systems; Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; RNA; Real-Time Polymerase Chain Reaction
PubMed: 35782118
DOI: 10.3389/fcimb.2022.904485 -
Journal of Mother and Child Jan 2021Pneumocystis carinii pneumonia is a common opportunistic respiratory infection among children with human immunodeficiency virus and a weakened immune system. The primary... (Review)
Review
Pneumocystis carinii pneumonia is a common opportunistic respiratory infection among children with human immunodeficiency virus and a weakened immune system. The primary infection in immunocompetent patients may be asymptomatic, whereas fever, shortness of breath, night sweats, nonproductive (dry) cough, pneumonia, progressive respiratory distress and apnea are cardinal symptoms of full-blown pneumocystis pneumonia. The diagnosis can be confirmed by histochemical staining of biological specimens or, recently, by polymerase chain reaction. International recommendations indicate that the drug of choice is the intravenously administered trimethoprim-sulfamethoxazole combination. Early diagnosis and appropriate treatment reduce the mortality of the disease. This article briefly highlights the epidemiology of Pneumocystis pneumonia, its diagnosis and therapeutic options in the pediatric population.
Topics: AIDS-Related Opportunistic Infections; Child; Humans; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 33759428
DOI: 10.34763/devperiodmed.20192303.159162 -
International Journal of Environmental... Mar 2022Pneumocystis is an atypical fungus that resides in the pulmonary parenchyma of many mammals, including humans and dogs. Immunocompetent human hosts are usually...
Pneumocystis is an atypical fungus that resides in the pulmonary parenchyma of many mammals, including humans and dogs. Immunocompetent human hosts are usually asymptomatically colonised or show subtle clinical signs, but some immunocompromised people can develop florid life-threatening Pneumocystis pneumonia (PCP). Since much less is known concerning Pneumocystis in dogs, we posit the question: can Pneumocystis colonization be present in dogs with inflammatory airway or lung disease caused by other pathogens or disease processes? In this study, Pneumocystis DNA was detected in bronchoalveolar lavage fluid (BALF) of 22/255 dogs (9%) with respiratory distress and/or chronic cough. Although young dogs (<1 year-of-age) and pedigree breeds were more often Pneumocystis-qPCR positive than older dogs and crossbreds, adult dogs with other infectious conditions and/or a history of therapy-resistant pulmonary disease could also be qPCR-positive, including two patients with suppression of the immune system. Absence of pathognomonic clinical or radiographic signs render it impossible to convincingly discriminate between overt PCP versus other lung/airway disease processes colonised by P. canis. It is possible that colonisation with P. canis might play a certain role as a co-pathogen in some canine patients with lower respiratory disease.
Topics: Animals; Bronchoalveolar Lavage Fluid; Dogs; Humans; Lung; Mammals; Plant Breeding; Pneumocystis; Pneumonia, Pneumocystis
PubMed: 35328882
DOI: 10.3390/ijerph19063192 -
Frontiers in Immunology 2023β-glucan is the most abundant polysaccharide in the cell wall of , which has attracted extensive attention because of its unique immunobiological characteristics.... (Review)
Review
β-glucan is the most abundant polysaccharide in the cell wall of , which has attracted extensive attention because of its unique immunobiological characteristics. β-glucan binds to various cell surface receptors, which produces an inflammatory response and accounts for its immune effects. A deeper comprehension of the processes by β-glucan recognizes its receptors, activates related signaling pathways, and regulates immunity as required. Such understanding will provide a basis for developing new therapies against . Herein, we briefly review the structural composition of β-glucans as a vital component of the cell wall, the host immunity mediated by β-glucans after their recognition, and discuss opportunities for the development of new strategies to combat .
Topics: Pneumocystis; beta-Glucans; Glucans; Pneumonia, Pneumocystis; Cell Wall
PubMed: 36845149
DOI: 10.3389/fimmu.2023.1094464 -
American Journal of Respiratory Cell... Jun 2020
Topics: Humans; Macrophage Activation; Pneumocystis; Pneumonia, Pneumocystis; Programmed Cell Death 1 Receptor; Th1 Cells
PubMed: 32109143
DOI: 10.1165/rcmb.2020-0051ED