BACKGROUND: Pneumocystis jirovecii is the most emerging life-threating health problem that causes acute and fatal pneumonia infection. It is rare and more contagious for patients with leukemia and immune-deficiency disorders. Until now there is no treatment available for this infection therefore, it is needed to develop any treatment against this pathogen.
METHODS: In this work, we used comparative proteomics, robust immune-informatics, and reverse vaccinology to create an mRNA vaccine against Pneumocystis jirovecii by targeting outer and transmembrane proteins. Using a comparative subtractive proteomic analysis of two Pneumocystis jirovecii proteomes, a distinct non-redundant Pneumocystis jirovecii (strain SE8) proteome was chosen. Seven Pneumocystis jirovecii transmembrane proteins were chosen from this proteome based on hydrophilicity, essentiality, virulence, antigenicity, pathway interaction, protein-protein network analysis, and allergenicity.
OBJECTIVE: The reverse vaccinology approach was used to predict the immunogenic and antigenic epitopes of major histocompatibility complex (MHC) I, II and B-cells from the selected proteins on the basis of their antigenicity, toxicity and allergenicity. These immunogenic epitopes were linked together to construct the mRNA-based vaccine. To enhance the immunogenicity, suitable adjuvant, linkers (GPGPG, KK, and CYY), and PRDRE sequences were used.
RESULTS: Through predictive modeling and confirmation via the Ramachandran plot, we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct\'s immunogenicity (GRAVY index: -0.271, instability index: 39.53, antigenicity: 1.0428). The physiochemical profiling of vaccine construct was predicted it an antigenic, efficient, and potential vaccine. Notably, strong interactions were observed between the vaccine construct and TLR-3/TLR-4 (-1301.7 kcal/mol-1 and -1374.7 kcal/mol-1).
CONCLUSIONS: The results predicted that mRNA-based vaccines trigger a cellular and humoral immune response, making the vaccine potential candidate against Pneumocystis jirovecii and it is more suitable for in-vitro analysis and validation to prove its effectiveness.

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UNASSIGNED: Compared with Human Immunodeficiency Virus (HIV) patients, non-HIV patients with Pneumocystis pneumonia (PCP) have more rapid onset, more rapid progression, and higher mortality.
UNASSIGNED: To investigate the predictive value of variables obtained upon hospital admission for in-hospital death and 90-day outcomes in non-HIV-PCP patients with respiratory failure (RF).
UNASSIGNED: This was a single center retrospective study in a tertiary care institution over 15 years. It included all adults inpatients (≥18 years old) with laboratory confirmed non-HIV-PCP with RF who were discharged or died from Peking University First Hospital between April 1st, 2007 and November 1st, 2022. Epidemiological, clinical, laboratory, imaging and outcome data were collected from patient records.
UNASSIGNED: In this study, a total of 146 non-HIV-PCP patients with RF were included. There were 57 patients (39%) died during hospitalization, 44 patients (53%) died in Intensive care unit (ICU). A total of 137 patients completed 90 days of follow-up, of which 58 (42.3%) died. The multivariable regression analysis revealed that a CD8+ T cell count <115/μl (P=0.009), bronchoalveolar lavage fluid (BALF)-neutrophil percentage ≥50% (P=0.047), the time from corticosteroids withdrawal to symptom onset ≤5 days (P=0.012), and the time from visit to initiation of sulfonamides ≥2 days (P=0.011) were independent risk factors for in-hospital death. Furthermore, a CD8+ T cell count < 115/μl (P=0.001) and the time from visit to initiation of sulfonamides therapy ≥2 days (P=0.033) was independently associated with 90-day all-cause death.
UNASSIGNED: A low CD8+ T cell count in peripheral blood, a high percentage of BALF-neutrophils, a short time from corticosteroids withdrawal to symptom onset, and a long time from visit to initiation of sulfonamides are associated with poor prognosis in non-HIV-PCP patients with RF.

暂无摘要。

BACKGROUND: Metagenomic next-generation sequencing (mNGS) excels in diagnosis of infection pathogens. We aimed to evaluate the performance of mNGS for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-HIV infected children.
METHODS: Totally 36 PJP children and 61 non-PJP children admitted to the pediatric intensive care unit from March 2018 to December 2021 were retrospectively enrolled. Clinical features of PJP children were summarized. 1,3-β-D glucan (BDG) test and bronchoalveolar lavage fluid (BALF) mNGS were used for evaluation of PJP diagnostic performance. Antimicrobial management modifications for PJP children after the mNGS results were also reviewed.
RESULTS: Pneumocystis jirovecii was detected in all PJP children by mNGS (36/36), and the sensitivity of mNGS was 100% (95% confidence interval [CI]: 90.26-100%). The sensitivity of BDG was 57.58% (95% CI: 39.22-74.52%). Of the 26 (72.2%) PJP patients with mixed infection, twenty-four (66.7%) were detected by BALF-mNGS. Thirteen patients (36.1%) had their antimicrobial management adjusted according to the mNGS results. Thirty-six PJP children included 17 (47.2%) primary immunodeficiency and 19 (52.8%) secondary immunodeficiency, of whom 19 (52.8%) survived and 17 (47.2%) died. Compared to survival subgroup, non-survival subgroup had a higher rate of primary immunodeficiency (64.7% vs. 31.6%, P = 0.047), younger age (7 months vs. 39 months, P = 0.011), lower body weight (8.0 kg vs. 12.0 kg, P = 0.022), and lower T lymphocyte counts.
CONCLUSIONS: The mortality rate of PJP in immunosuppressed children without HIV infection is high and early diagnosis is challenging. BALF-mNGS could help identify PJP and guide clinical management.

BACKGROUND: Kidney transplantation has emerged as the most effective treatment for patients with uremia. Advances in immunosuppressant medications have significantly reduced the risk of rejection. However, a notable increase in opportunistic infections, such as Pneumocystis jirovecii pneumonia (PJP), demands special attention in clinical practice. Our study aims to evaluate risk factors and identify predictive markers associated with PJP in kidney transplantation recipients.
METHODS: We conducted a case-control study (1:2 ratio) involving kidney transplant recipients with and without PJP, matched based on the same surgical date. The study was carried out at Zhongnan Hospital of Wuhan University, China.
RESULTS: Ninety-three participants were enrolled at Zhongnan Hospital of Wuhan University, comprising 31 with PJP and 62 without PJP. All patients tested negative for HIV. Our findings indicate that PJP patients exhibited lower levels of serum albumin (P = 0.001), reduced counts of total and CD3+ (P < 0.001), CD4+ (P = 0.001), and CD8+ T lymphocytes (P < 0.001), and a lower rate of prophylactic trimethoprim-sulfamethoxazole (TMP-SMZ) usage compared to non-PJP patients (P = 0.02). Conversely, urea levels in PJP patients were significantly higher than in non-PJP controls (P < 0.001). We developed a model combining CD8+ T cell count (< 241.11/μL, P < 0.001) and ALB levels (< 35.2 g/L, P = 0.003), which demonstrated excellent discriminatory power in distinguishing PJP from non-PJP cases, with an area under the curve (AUC) of 0. 920 (95% CI, 0.856-0.989).
CONCLUSIONS: Our study suggests that a baseline CD8+ T cell count (< 241.11/μL) and serum ALB levels (< 35.2 g/L) offer robust predictive value for the occurrence of PJP infections in kidney transplant recipients.

This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%-30%, while in studies of persons without HIV, mortality ranged from 4% to 76%. Risk factors for disease principally include immunosuppression from HIV, but other types of immunosuppression are increasingly recognised, including solid organ and haematopoietic stem cell transplantation, autoimmune and inflammatory disease, and chemotherapy for cancer. Although prophylaxis is available and generally effective, burdensome side effects may lead to discontinuation. After a period of decline associated with improvement in access to HIV treatment, new risk groups of immunosuppressed patients with PJP are increasingly identified, including solid organ transplant patients.

Persistent inflammatory damage and suppressed immune function play a crucial role in the pathogenesis and progression of the pneumocystis jirovecii pneumonia (PjP). Therefore, we aimed to investigate the correlation between the combined immune and inflammatory indicator: the neutrophil-to-lymphocyte ratio (NLR) and prognosis of non-human immunodeficiency virus (non-HIV) PjP.In the retrospective analysis conducted in ICUs at Beijing Chao-Yang Hospital, we examined data from 157 patients diagnosed with non-HIV PjP. Our findings reveal a concerning hospital mortality rate of 43.3%, with the 28-day mortality rate reaching 47.8%.Through multivariable logistic and Cox regression analyses, we established a significant association between elevated NLR levels and hospital mortality (adjusted odd ratio, 1.025; 95% CI, 1.008-1.043; p = 0.004) or 28-day mortality (adjusted hazard ratio, 1.026; 95% CI, 1.008-1.045; p = 0.005). Specifically, patients with an NLR exceeding 20.3 demonstrated markedly lower overall survival rates, underscoring the biomarker\'s predictive value for both hospital and 28-day mortality.In conclusion, non-HIV PjP patients in the ICU still have a high rate of mortality and a poor short-term prognosis after discharge. A high level of NLR was associated with an increased risk of hospital mortality and 28-day mortality.

BACKGROUND: This meta-analysis examines the comparative diagnostic performance of polymerase chain reaction (PCR) for the diagnosis of Pneumocystis pneumonia (PCP) on different respiratory tract samples, in both human immunodeficiency virus (HIV) and non-HIV populations.
METHODS: A total of 55 articles met inclusion criteria, including 11 434 PCR assays on respiratory specimens from 7835 patients at risk of PCP. QUADAS-2 tool indicated low risk of bias across all studies. Using a bivariate and random-effects meta-regression analysis, the diagnostic performance of PCR against the European Organisation for Research and Treatment of Cancer-Mycoses Study Group definition of proven PCP was examined.
RESULTS: Quantitative PCR (qPCR) on bronchoalveolar lavage fluid provided the highest pooled sensitivity of 98.7% (95% confidence interval [CI], 96.8%-99.5%), adequate specificity of 89.3% (95% CI, 84.4%-92.7%), negative likelihood ratio (LR-) of 0.014, and positive likelihood ratio (LR+) of 9.19. qPCR on induced sputum provided similarly high sensitivity of 99.0% (95% CI, 94.4%-99.3%) but a reduced specificity of 81.5% (95% CI, 72.1%-88.3%), LR- of 0.024, and LR+ of 5.30. qPCR on upper respiratory tract samples provided lower sensitivity of 89.2% (95% CI, 71.0%-96.5%), high specificity of 90.5% (95% CI, 80.9%-95.5%), LR- of 0.120, and LR+ of 9.34. There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients.
CONCLUSIONS: On deeper respiratory tract specimens, PCR negativity can be used to confidently exclude PCP, but PCR positivity will likely require clinical interpretation to distinguish between colonization and active infection, partially dependent on the strength of the PCR signal (indicative of fungal burden), the specimen type, and patient population tested.

BACKGROUND: Kidney transplant recipients (KTRs) are at an elevated risk of progressing to severe infections upon contracting COVID-19. We conducted a study on risk factors and multi-pathogen infections in KTRs with SARS-CoV-2 Omicron variant.
METHODS: KTRs were subjected to a thorough etiological evaluation. Whenever feasible, they were also provided with bronchoscopy and bronchoalveolar lavage to enable metagenomic next-generation sequencing (mNGS), ideally within a 48-hour window post-admission. We performed a retrospective analysis for pathogens and risk factors of KTRs with the COVID-19 virus variant Omicron.
RESULTS: We included thirty patients in our study, with sixteen exhibiting single infection of COVID-19 and fourteen experiencing co-infections, predominantly with Pneumocystis jirovecii. Notably, patients with severe cases demonstrated significantly elevated levels of C-reactive protein (CRP) and interleukin-6 compared to those with moderate cases (P < 0.05). Furthermore, individuals whose conditions progressed had markedly higher baseline serum creatinine levels than those without such progression (P < 0.05). The presence of heart failure, acute exacerbation of renal dysfunction, and a history of opportunistic infections were significantly associated with a higher likelihood of deterioration and hospital admission due to the SARS-CoV-2 Omicron variant, as compared to the control group (P < 0.05). In subsequent follow-up analysis, the all-cause rehospitalization rate was observed to be 21.4%, with Pneumocystis jirovecii infection accounting for half of these cases.
CONCLUSIONS: Among KTRs, a significant coinfection rate of 47% was observed, with Pneumocystis jirovecii emerging as the predominant pathogen in these cases. The development of heart failure, acute exacerbation of chronic renal dysfunction, and a prior history of opportunistic infections have been identified as potential risk factors that may contribute to clinical deterioration in KTRs. Additionally, Pneumocystis jirovecii infection has been established as a critical factor influencing the rate of all-cause rehospitalization within this patient population.