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Mycology 2024Pulmonary invasive fungal infection in immunocompromised hosts is difficult to diagnose, and current tools for diagnosis or monitoring of response to antifungal...
Pulmonary invasive fungal infection in immunocompromised hosts is difficult to diagnose, and current tools for diagnosis or monitoring of response to antifungal treatments have inherent limitations. Droplet digital PCR (ddPCR) has emerged as a promising tool for pulmonary pathogen detection with high sensitivity. This study presents a novel ddPCR panel for rapid and sensitive identification of pulmonary fungal pathogens. First, a ddPCR method for detecting three fungal genera, including , , and , was established and evaluated. Then, the clinical validation performance of ddPCR was compared with that of qPCR using 170 specimens, and the 6 specimens with inconsistent results were further verified by metagenomics next-generation sequencing, which yielded results consistent with the ddPCR findings. Finally, the area under the ROC curve (AUC) was used to evaluate the efficiency of ddPCR. While the qPCR identified 16 (9.41%) cases of and 6 (3.53%) cases of , ddPCR detected 20 (11.76%) cases and 8 (4.71%) cases. The AUC for , , and was 0.974, 0.998, and 0.975, respectively. These findings demonstrated that the ddPCR assay is a highly sensitive method for identifying pathogens responsible for invasive fungal pulmonary infections, and is a promising tool for early diagnosis. .
PubMed: 38558836
DOI: 10.1080/21501203.2023.2296941 -
Viruses Feb 2024The frequency of respiratory viruses in people living with HIV (PLHIV) and their impact on lung function remain unclear. We aimed to determine the frequency of...
The frequency of respiratory viruses in people living with HIV (PLHIV) and their impact on lung function remain unclear. We aimed to determine the frequency of respiratory viruses in bronchoalveolar lavage and induced sputum samples in PLHIV and correlate their presence with lung function. A prospective cohort of adults hospitalized in Medellín between September 2016 and December 2018 included three groups: group 1 = people diagnosed with HIV and a diagnosis of community-acquired pneumonia (CAP), group 2 = HIV, and group 3 = CAP. People were followed up with at months 1, 6, and 12. Clinical, microbiological, and spirometric data were collected. Respiratory viruses were detected by multiplex RT-PCR. Sixty-five patients were included. At least 1 respiratory virus was identified in 51.9%, 45.1%, and 57.1% of groups 1, 2 and 3, respectively. Among these, 89% of respiratory viruses were detected with another pathogen, mainly (40.7%) and (22.2%). The most frequent respiratory virus was rhinovirus (24/65, 37%). On admission, 30.4% of group 1, 16.6% of group 2, and 50% of group 3 had airflow limitation, with alteration in forced expiratory volume at first second in both groups with pneumonia compared to HIV. Respiratory viruses are frequent in people diagnosed with HIV, generally coexisting with other pathogens. Pulmonary function on admission was affected in patients with pneumonia, improving significantly in the 1st, 6th, and 12th months after CAP onset.
Topics: Adult; Humans; Prospective Studies; Follow-Up Studies; Pneumonia; Viruses; Lung; HIV Infections
PubMed: 38543710
DOI: 10.3390/v16030344 -
International Journal of Molecular... Mar 2024Inflammation and mucus production are prevalent characteristics of chronic respiratory conditions, such as asthma and chronic chronic obstructive pulmonary disease...
Inflammation and mucus production are prevalent characteristics of chronic respiratory conditions, such as asthma and chronic chronic obstructive pulmonary disease (COPD). Biological co-factors, including bacteria, viruses, and fungi, may exacerbate these diseases by activating various pathways associated with airway diseases. An example is the fungus , which is linked to severe COPD in human patients. Recent evidence has demonstrated that significantly enhanced inflammation and mucus hypersecretion in a rat model of elastase-induced COPD. The present study specifically aims to investigate two additional aspects associated with the pathology induced by infection: inflammation and collagen deposition around airways. To this end, the focus was to investigate the role of the IL-1β pro-inflammatory pathway during infection in COPD rats. Several airway pathology-related features, such as inflammation, mucus hypersecretion, and fibrosis, were evaluated using histological and molecular techniques. COPD animals infected with exhibited elevated inflammation levels, including a synergistic increase in IL-1β and Cox-2. Furthermore, protein levels of the IL-1β-dependent transcription factor cAMP response element-binding (CREB) showed a synergistic elevation of their phosphorylated version in the lungs of COPD animals infected with , while mucus levels were notably higher in the airways of COPD-infected animals. Interestingly, a CREB responsive element (CRE) was identified in the Muc5b promoter. The presence of CREB in the Muc5b promoter was synergistically increased in COPD animals infected with compared to other experimental groups. Finally, an increment of deposited collagen was identified surrounding the airways of COPD animals infected with compared with the other experimental animal groups and correlated with the increase of mRNA levels. These findings emphasize the role of as a potential biological co-factor in chronic respiratory diseases like COPD or asthma, warranting new perspectives in the treatment of chronic respiratory diseases.
Topics: Humans; Rats; Animals; Pneumocystis; Pancreatic Elastase; Pulmonary Disease, Chronic Obstructive; Lung; Asthma; Pneumonia, Pneumocystis; Mucus; Inflammation; Collagen
PubMed: 38542124
DOI: 10.3390/ijms25063150 -
Journal of Fungi (Basel, Switzerland) Mar 2024Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to and other opportunistic respiratory...
Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to and other opportunistic respiratory pathogens. Certain breeds, such as the Cavalier King Charles Spaniel, are over-represented for pneumonia (PCP), suggesting the presence of a primary immunodeficiency in the breed. Here, we report the discovery of a nonsense variant in three Cavalier King Charles Spaniel dogs with either PCP (n = 2) or refractory pneumonia (n = 1). encodes a protein that plays critical roles in T-cell activation and other aspects of immune function. Deleterious variants have recently been reported in human patients with PCP and other recurrent pneumonias. In addition to opportunistic respiratory infection, the affected dogs also exhibited other clinical manifestations of CARMIL2 deficiencies that have been reported in humans, including early-onset gastrointestinal disease, allergic skin disease, mucocutaneous lesions, abscesses, autoimmune disorders, and gastrointestinal parasitism. This discovery highlights the potential utility of a natural canine model in identifying and studying primary immunodeficiencies in patients affected by PCP.
PubMed: 38535207
DOI: 10.3390/jof10030198 -
Frontiers in Immunology 2024Clinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of...
OBJECTIVE
Clinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of patients with MDA5+ DM, identify disease endotypes related to the heterogeneous manifestations and prognosis, and guide individualized therapy regimen.
METHODS
This inpatient cohort included 123 patients with MDA5+ DM. Unsupervised hierarchical clustering analysis was used to derive disease endotypes from the circulating immune cell profiles on admission. Clinical symptoms, laboratory test results, inpatient treatments, and disease outcomes were then analyzed among the identified endotypes.
RESULTS
Three disease endotypes in MDA5+ DM were identified from peripheral immune cell profiles. Endotype1 had the highest percentages of CD4 T cells and monocytes, and the lowest percentage of neutrophils; Endotype2 had the highest percentage of B cells; Endotype3 had the highest percentage of CD8 T cells and NK cells. Clinical and prognostic heterogeneity of the endotypes were revealed. Endotype1 had the lowest 3-month mortality with the high incidence of periungual capillary changes. Endotype2 and Endotype3 had higher prevalence of rapidly progressive interstitial lung disease (RPILD) and mortality at 3 months than Endotype1. Meanwhile, Endotype3 had higher pneumocystis jiroveci and CMV viremia cases with significantly elevated of activated CD8 T cells and multiple cytokines than Endotype1.
CONCLUSION
Clustering analysis of peripheral immune cell profiles identified three different endotypes in MDA5+ dermatomyositis. Endotpye2 and 3 showed higher RPILD, 3-month mortality, pneumocystis jiroveci and CMV viremia.
Topics: Humans; Interferon-Induced Helicase, IFIH1; Dermatomyositis; CD8-Positive T-Lymphocytes; Viremia; Lung Diseases, Interstitial; Cytomegalovirus Infections
PubMed: 38533498
DOI: 10.3389/fimmu.2024.1349611 -
Medical Mycology Case Reports Mar 2024is a type of endophytic fungus that parasitizes monocotyledonous plants. Cases of humans and other mammals being infected by are very rare around the world. We report...
is a type of endophytic fungus that parasitizes monocotyledonous plants. Cases of humans and other mammals being infected by are very rare around the world. We report the first case of subcutaneous mycosis caused by in China. A kidney transplant recipient was admitted for pneumonia and subsequently developed left calf redness and swelling due to a infection. The patient was treated with sulfamethoxazole and voriconazole and underwent five surgical debridements and vacuum sealing drainage (VSD) applications with the left leg. The patient was eventually cured and discharged from the hospital.
PubMed: 38533460
DOI: 10.1016/j.mmcr.2023.100620 -
Frontiers in Cellular and Infection... 2024Talaromycosis is a serious opportunistic infectious disease caused by , which mostly occurs in immunocompromised patients. The disease is mainly prevalent in tropical... (Review)
Review
BACKGROUND
Talaromycosis is a serious opportunistic infectious disease caused by , which mostly occurs in immunocompromised patients. The disease is mainly prevalent in tropical countries and regions of Southeast Asia and South Asia, but non-endemic areas also have patients with Talaromycosis. The disease has no characteristic clinical manifestations and is difficult to diagnose. Delayed diagnosis often leads to death.
CASE PRESENTATION
Both patients had cellular immunodeficiency. Case 1 had a history of acquired immune deficiency syndrome, and case 2 had a history of renal transplantation and glucose-6-phosphate dehydrogenase deficiency. They all had fever, anemia, fatigue, and skin lesions. Case 1 had gastrointestinal bleeding, enlarged lymph nodes, and hepatosplenomegaly. Case 2 had cough and dyspnea. Both patients had thrombocytopenia and hypoalbuminemia; an increased neutrophil ratio, procalcitonin, and C-reactive protein; and abnormal liver function and coagulation dysfunction. Case 1 sputum culture, blood culture, and bronchoalveolar lavage fluid were positive for . was detected in the blood culture of case 2, with infection of and . Chest computed tomography scan mainly showed pulmonary exudative lesions. Although these two patients were actively treated, they died of poor efficacy.
CONCLUSION
Talaromycosis has an insidious onset, long course, atypical clinical symptoms, imaging performance and laboratory results, difficult diagnosis, and high mortality. Therefore, it is important to promptly consider and treat Talaromycosis in immunocompromised patients upon infection in order to reduce mortality.
Topics: Humans; Mycoses; Tomography, X-Ray Computed; Acquired Immunodeficiency Syndrome; Liver Diseases; Antifungal Agents
PubMed: 38533387
DOI: 10.3389/fcimb.2024.1347677 -
British Journal of Haematology Jun 2024Pneumocystis jirovecii can cause life-threatening pneumonia (PjP), and patients with haematological malignancies are at high risk of this infection. Prophylactic... (Randomized Controlled Trial)
Randomized Controlled Trial
Pneumocystis jirovecii can cause life-threatening pneumonia (PjP), and patients with haematological malignancies are at high risk of this infection. Prophylactic measures have significantly decreased morbidity and mortality, but there is a paucity of contemporary data on the incidence and clinical course of PjP in well-defined and homogenous patient populations, such as children suffering from acute lymphoblastic leukaemia (ALL). In the multi-international trial AIEOP-BFM ALL2009, PjP was diagnosed in six children (incidence 1/1000) and was associated with insufficient prophylaxis in five of them. Although none of the patients died of PjP, the long-term impact of the infection is unclear.
Topics: Humans; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Child; Pneumocystis carinii; Male; Female; Child, Preschool; Antineoplastic Combined Chemotherapy Protocols; Adolescent; Incidence
PubMed: 38527954
DOI: 10.1111/bjh.19382 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Jan 2024To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic...
To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared. A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, =0.001) and similar to that of qPCR (91.6%, =1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods (=0.008) . mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.
Topics: Humans; Pneumonia, Pneumocystis; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Hematopoietic Stem Cell Transplantation; High-Throughput Nucleotide Sequencing; Sensitivity and Specificity; Retrospective Studies; Pneumonia
PubMed: 38527840
DOI: 10.3760/cma.j.cn121090-20230928-00147 -
PloS One 2024The epidemiology of Human Immunodeficiency Virus (HIV)-associated pneumocystosis (HAP) is poorly described on a worldwide scale. We searched related databases between... (Meta-Analysis)
Meta-Analysis
The epidemiology of Human Immunodeficiency Virus (HIV)-associated pneumocystosis (HAP) is poorly described on a worldwide scale. We searched related databases between January 2000 and December 2022 for studies reporting HAP. Meta-analysis was performed using StatsDirect (version 2.7.9) and STATA (version 17) according to the random-effects model for DerSimonian and Laird method and metan and metaprop commands, respectively. Twenty-nine studies with 38554 HIV-positive, 79893 HIV-negative, and 4044 HAP populations were included. The pooled prevalence of HAP was 35.4% (95% CI 23.8 to 47.9). In contrast, the pooled prevalence of PCP among HIV-negative patients was 10.16% (95% CI 2 to 25.3). HIV-positive patients are almost 12 times more susceptible to PCP than the HIV-negative population (OR: 11.710; 95% CI: 5.420 to 25.297). The mortality among HAP patients was 52% higher than non-PCP patients (OR 1.522; 95% CI 0.959 to 2.416). HIV-positive men had a 7% higher chance rate for PCP than women (OR 1.073; 95% CI 0.674 to 1.706). Prophylactic (OR: 6.191; 95% CI: 0.945 to 40.545) and antiretroviral therapy (OR 3.356; 95% CI 0.785 to 14.349) were used in HAP patients six and three times more than HIV-positive PCP-negatives, respectively. The control and management strategies should revise and updated by health policy-makers on a worldwide scale. Finally, for better management and understanding of the epidemiology and characteristics of this coinfection, designing further studies is recommended.
Topics: Male; Humans; Female; HIV; Pneumonia, Pneumocystis; Prevalence; HIV Infections; HIV Seropositivity
PubMed: 38526997
DOI: 10.1371/journal.pone.0297619