A case of Pneumocystis jirovecii pneumonia in a patient with acquired immune deficiency syndrome who showed eosinophilia and an increased serum TARC/CCL17 level

Pneumocystis jirovecii pneumonia (PCP) in patients with acquired immune deficiency syndrome (AIDS) shows eosinophilic pneumonia like condition. The detailed mechanisms how AIDS-associated PCP causes eosinophilic pneumonia has not been elucidated, but it has been suggested that beta-D-glucan, a major component of Pneumocystis jirovecii, and T helper type 2 immunity may be involved in the mechanism of eosinophilia in the lung. We experienced the case who developed an eosinophilic pneumonia-like condition in a patient with AIDS-associated PCP, whose clinical course indicated the importance of TARC/CCL17 but not IL-4 and IL-5 as involved in eosinophilia caused by HIV and Pneumocystis jirovecii infection.

Pneumocystis jirovecii Pneumonia in Patients with Rheumatic Diseases: Risk Assessment and Prophylaxis

Pneumocystis jirovecii pneumonia (PJP) is an uncommon opportunistic infection in patients with rheumatic diseases with high mortality. Unlike other non-HIV conditions, international guideline for PJP prophylaxis in rheumatic diseases is currently lacking. Recent evidence regarding the risk of PJP and effectiveness of prophylaxis has been accumulating. This Review provides an update on the information about risk factors associated with PJP in patients with rheumatic diseases based on rheumatic diagnoses, use of immunosuppressive agents and other disease-related factors. The second part of the article summarizes evidence regarding the effectiveness of PJP prophylaxis by considering both disease-related and therapy-related factors. Finally, the Review outlined the currently available disease-specific recommendations and local guidelines, and appreciate the factors that influence physicians’ decision.

SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression

Intra-host evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in cases with persistent coronavirus disease 2019 (COVID-19). In this study, we describe a severely immunosuppressed individual with HIV-1/SARS-CoV-2 coinfection with a long-term course of SARS-CoV-2 infection. A 28-year-old man was diagnosed with HIV-1 infection (CD4+ count: 3 cells/µL nd 563000 HIV-1 RNA copies/mL) and simultaneous Pneumocystis jirovecii pneumonia, disseminated Mycobacterium avium complex infection and SARS-CoV-2 infection. SARS-CoV-2 real-time reverse transcription polymerase chain reaction positivity from nasopharyngeal samples was prolonged for 15 weeks. SARS-CoV-2 was identified as variant Alpha (PANGO lineage B.1.1.7) with mutation S:E484K. Spike-specific T-cell response was similar to HIV-negative controls although enriched in IL-2, and showed disproportionately increased immunological exhaustion marker levels. Despite persistent SARS-CoV-2 infection, adaptive intra-host SARS-CoV-2 evolution, was not identified. Spike-specific T-cell response protected against a severe COVID-19 outcome and the increased immunological exhaustion marker levels might have favoured SARS-CoV-2 persistence.

Clinical impact of pneumothorax in patients with Pneumocystis jirovecii pneumonia and respiratory failure in an HIV-negative cohort

Background Pneumocystis jirovecii pneumonia (PCP) with acute respiratory failure can result in development of pneumothorax during treatment. This study aimed to identify the incidence and related factors of pneumothorax in patients with PCP and acute respiratory failure and to analyze their prognosis. Methods We retrospectively reviewed the occurrence of pneumothorax, including clinical characteristics and results of other examinations, in 119 non-human immunodeficiency virus patients with PCP and respiratory failure requiring mechanical ventilator treatment in a medical intensive care unit (ICU) at a tertiary-care center between July 2016 and April 2019. Results During follow up duration, twenty-two patients (18.5%) developed pneumothorax during ventilator treatment, with 45 (37.8%) eventually requiring a tracheostomy due to weaning failure. Cytomegalovirus co-infection (odds ratio 13.9; p = 0.013) was related with occurrence of pneumothorax in multivariate analysis. And development of pneumothorax was not associated with need for tracheostomy and mortality. Furthermore, analysis of survivor after 28 days in ICU, patients without pneumothorax were significantly more successful in weaning from mechanical ventilator than the patients with pneumothorax (44% vs. 13.3%, p = 0.037). PCP patients without pneumothorax showed successful home discharges compared to those who without pneumothorax (p = 0.010). Conclusions The development of pneumothorax increased in PCP patient with cytomegalovirus co-infection, pneumothorax might have difficulty in and prolonged weaning from mechanical ventilators, which clinicians should be aware of when planning treatment for such patients.

Clinical characteristics of patients with acquired immunodeficiency syndrome having respiratory symptoms as the initial manifestations: A retrospective study

The aim of the study was to investigate clinical features of patients with AIDS having respiratory symptoms as initial manifestations and help in the early diagnosis. Eighty-eight patients admitted to the Shanghai Pulmonary Hospital were included in the study. General data, clinical manifestations, laboratory tests, chest computed tomography (CT) imaging features, treatments, and prognosis were analyzed. Peripheral leukopenia, lymphopenia, hypoxemia, and reduced percentage of CD4+ T lymphocytes were found in 25.6%, 43.6%, 27.5%, and 94.9% of the patients, respectively. Pneumocystis jirovecii pneumonia (PCP) was the most frequent cause of opportunistic pulmonary infection. Patients with PCP had more bilateral lung involvement and ground-glass shadow in CT manifestations. A follow-up of the 43 patients transferred to the Public Health Center showed improvement in 27 (62.8%), stabilization in 4 (9.3%), worsening in 1 (2.3%), and death in 11 (25.6%) patients. Detailed medical history recording, screening of human immunodeficiency virus antibody, and flow cytometry would improve the diagnostic efficiency of AIDS in patients with diffuse ground-glass shadow in chest CT. Early and empirical treatment could improve the prognosis.

Pneumocystis pneumonia and rheumatic disease: diagnostic potential of circulating microbial cell-free DNA sequencing

Objectives This study aimed to explore the clinical utility of circulating microbial cell-free DNA (cfDNA) sequencing as a non-invasive approach for diagnosing Pneumocystis jirovecii pneumonia (PJP) in immunocompromised patients with rheumatic disease (RD). Methods The study included 72 RD patients with suspected lung infections admitted to Renji hospital. Eighteen individuals were diagnosed with PJP, and 54 patients without PJP were enrolled as control group. All patients had undergone pulmonary computed tomography scans, and blood and respiratory tract specimens had been subjected to metagenomic next-generation sequencing (mNGS) and conventional microbiological tests. The clinical and laboratory parameters were collected and efficacy of circulating microbial cfDNA of PJP was evaluated. Results Of the 18 patients with PJP, the average age was 53.0 years and the median time between RD diagnosis and PJP presentation was 126 days (IQR 84.0–176.3). Low circulating CD4+ cell counts and a lack of PJP prophylaxis were observed in the patients. Metagenomic NGS of circulating microbial cfDNA was performed in 69 patients including 15 cases with PJP and 54 controls. Twelve (80%) of 15 analysed blood samples contained Pneumocystis jirovecii (PJ) sequences in PJP group with PJ not detected among controls. There was a significant difference between PJP and non-PJP groups (p < 0.001) with a sensitivity of 83.3% and specificity of 100% when using plasma cfDNA sequencing. Higher β-D-glucan levels were found in patients with positive results for PJ in plasma cfDNA sequencing. Conclusion Metagenomic NGS of circulating microbial cfDNA is a potential tool for diagnosing PJP in RD patients.

Clinical Performance of BAL Metagenomic Next-Generation Sequence and Serum (1,3)-β-D-Glucan for Differential Diagnosis of Pneumocystis jirovecii Pneumonia and Pneumocystis jirovecii Colonisation

BackgroundDifferentiating Pneumocystis jirovecii 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 P. jirovecii.MethodsFrom 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 P. jirovecii pneumonia (PJP) group or the P. jirovecii colonisation (PJC) group. Clinical data were recorded. The performances of mNGS and BDG were compared.ResultThe fungal load significantly differed between patients with PJP and PJC, with median reads of 3,215.79 ± 1,797 vs. 5.61 ± 0.88 in the PJP and PJC groups, respectively (P < 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 (P = 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 P. jirovecii 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 (r2 = 0.0076, P = 0.583). The levels of lactate dehydrogenase and C-reactive protein were significantly higher in the PJP group than in the PJC group.ConclusionBAL mNGS and serum BDG are useful adjunct tests that can assist with differentiating between colonisation and infection of P. jirovecii.

Current State of Carbohydrate Recognition and C-Type Lectin Receptors in Pneumocystis Innate Immunity

Pneumocystis jirovecii is one of the most common fungal pathogens in immunocompromised individuals. Pneumocystis jirovecii pneumonia (PJP) causes a significant host immune response that is driven greatly by the organism’s cell wall components including β-glucans and major surface glycoprotein (Msg). These ligands interact with a number of C-type lectin receptors (CLRs) leading to downstream activation of proinflammatory signaling pathways. This minireview provides a brief overview summarizing known CLR/Pneumocystis interactions.