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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 -
Arthritis & Rheumatology (Hoboken, N.J.) Nov 2023
Topics: Humans; Pneumonia, Pneumocystis; Rituximab; Cyclophosphamide; Risk Assessment
PubMed: 37192270
DOI: 10.1002/art.42562 -
Journal of Fungi (Basel, Switzerland) Sep 2023, a fungus causing severe pneumonia (PCP) in humans, has long been described as non-culturable. Only isolated short-term experiments with and a small number of...
, a fungus causing severe pneumonia (PCP) in humans, has long been described as non-culturable. Only isolated short-term experiments with and a small number of experiments involving animal-derived species have been published to date. However, culture conditions may differ significantly from those of animal-derived , as there are major genotypic and phenotypic differences between them. Establishing a well-performing cultivation is crucial to understanding PCP and its pathophysiological processes. The aim of this study, therefore, was to develop an axenic culture for . To identify promising approaches for cultivation, a literature survey encompassing animal-derived cultures was carried out. The variables identified, such as incubation time, pH value, vitamins, amino acids, and other components, were trialed and adjusted to find the optimum conditions for culture. This allowed us to develop a medium that produced a 42.6-fold increase in qPCR copy numbers after a 48-day culture. Growth was confirmed microscopically by the increasing number and size of actively growing clusters in the final medium, DMEM-O3. doubling time was 8.9 days (range 6.9 to 13.6 days). In conclusion, we successfully cultivated under optimized cell-free conditions in a 70-day long-term culture for the first time. However, further optimization of the culture conditions for this slow grower is indispensable.
PubMed: 37755011
DOI: 10.3390/jof9090903 -
Journal of Fungi (Basel, Switzerland) Jul 2023The increasing morbidity and mortality of life-threatening pneumonia (PCP) in immunocompromised people poses a global concern, prompting the World Health Organization... (Review)
Review
The increasing morbidity and mortality of life-threatening pneumonia (PCP) in immunocompromised people poses a global concern, prompting the World Health Organization to list it as one of the 19 priority invasive fungal diseases, calling for increased research and public health action. In response to this initiative, we provide this review on the epidemiology of PCP in non-HIV patients with various immunodeficient conditions, including the use of immunosuppressive agents, cancer therapies, solid organ and stem cell transplantation, autoimmune and inflammatory diseases, inherited or primary immunodeficiencies, and COVID-19. Special attention is given to the molecular epidemiology of PCP outbreaks in solid organ transplant recipients; the risk of PCP associated with the increasing use of immunodepleting monoclonal antibodies and a wide range of genetic defects causing primary immunodeficiency; the trend of concurrent infection of PCP in COVID-19; the prevalence of colonization; and the rising evidence supporting de novo infection rather than reactivation of latent infection in the pathogenesis of PCP. Additionally, we provide a concise discussion of the varying effects of different immunodeficient conditions on distinct components of the immune system. The objective of this review is to increase awareness and knowledge of PCP in non-HIV patients, thereby improving the early identification and treatment of patients susceptible to PCP.
PubMed: 37623583
DOI: 10.3390/jof9080812 -
Mycoses Jul 2023Invasive and superficial fungal infections are increasingly reported in Algeria, testifying to the increase in their frequency in parallel with the increase in risk...
INTRODUCTION
Invasive and superficial fungal infections are increasingly reported in Algeria, testifying to the increase in their frequency in parallel with the increase in risk factors and the availability of diagnostic means, at least in university hospitals (CHU). The latter, located in the major northern cities, are equipped with high-performance diagnostic tools compared to hospitals in the interior of the country.
METHODS
A comprehensive search of published and grey literature was undertaken. Prevalence and incidence of discrete fungal diseases were estimated using a deterministic modelling approach based on populations at risk. Population (2021) and major underlying disease risk groups were obtained from UNAIDS, WHO Tuberculosis and the international transplant registries as well as published data for asthma and COPD. The health service profile was summarised from national documentation.
RESULTS
Among the 43.6 million, including 12.9 million children, living in Algeria, the most prevalent fungal diseases are tinea capitis (>1.5 million), recurrent vaginal candidiasis (>500,000) and allergic fungal lung and sinus disorders (>110,000) and chronic pulmonary aspergillosis (>10,000). Life-threatening invasive fungal infection incidence includes 774 Pneumocystis pneumonia in AIDS, 361 cryptococcal meningitis, 2272 candidaemia and 2639 invasive aspergillosis cases. Fungal keratitis probably affects >6000 eyes each year.
CONCLUSIONS
Fungal infections are underestimated in Algeria because they are sought in patients with risk factors only after bacterial infections when they should be sought in parallel. The diagnosis is only accessible in hospitals in large cities and the work carried out in mycology is rarely published, making the estimation of the burden of these conditions difficult.
Topics: Child; Female; Humans; Algeria; Aspergillosis; Pneumonia, Pneumocystis; Invasive Fungal Infections; Prevalence; Incidence; Candidemia
PubMed: 37005355
DOI: 10.1111/myc.13585 -
Frontiers in Microbiology 2024species are pathogenic fungi known to cause pneumonia in immunocompromised mammals. They are obligate to their host, replicate extracellularly in lung alveoli and...
INTRODUCTION
species are pathogenic fungi known to cause pneumonia in immunocompromised mammals. They are obligate to their host, replicate extracellularly in lung alveoli and thrive in the copper-enriched environment of mammalian lungs. In this study, we investigated the proteome of , a model organism that infects mice, in the context of its copper sensing and tolerance.
METHODS AND RESULTS
The query for copper-associated annotations in FungiDB followed by a manual curation identified only 21 genes in , significantly fewer compared to other clinically relevant fungal pathogens or phylogenetically similar free-living fungi. We then employed instrumental analyses, including Size-Exclusion Chromatography Inductively Coupled Plasma Mass Spectrometry (SEC-ICP-MS), Immobilized Metal Affinity Chromatography (IMAC), and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), to isolate and identify copper-binding proteins from freshly extracted organisms, revealing 29 distinct cuproproteins. The RNA sequencing (RNA-seq) analysis of exposed to various CuSO concentrations at three temporal intervals (0.5, 2, and 5 h) indicated that significant gene expression changes occurred only under the highest CuSO concentration probed (100 μM) and the longest exposure duration (5 h). This stimulus led to the upregulation of 43 genes and downregulation of 27 genes compared to untreated controls. Quantitative PCR (qPCR) confirmed the expression of four out of eight selected upregulated genes, including three assumed transcription factors (PNEG_01236, PNEG_01675, and PNEG_01730) and a putative copper transporter (PNEG_02609). Notably, the three applied methodologies - homology-based annotation, SEC-ICP-MS/IMAC/LC-MS/MS, and RNA-seq - yielded largely distinct findings, with only four genes (PNEG_02587, PNEG_03319, PNEG_02584, and PNEG_02989) identified by both instrumental methods.
DISCUSSION
The insights contribute to the broader knowledge of copper homeostasis and provide novel facets of host-pathogen interactions for extracellular pathogens. We suggest that future studies of pathogenicity and copper stress survival should consider the entire spectrum of identified genes.
PubMed: 38812685
DOI: 10.3389/fmicb.2024.1383737 -
Infection and Drug Resistance 2023Metagenomic next-generation sequencing (mNGS) is a promising tool for improving antimicrobial therapy and infection control decision-making in complex infections....
BACKGROUND
Metagenomic next-generation sequencing (mNGS) is a promising tool for improving antimicrobial therapy and infection control decision-making in complex infections. Secondary infection surveillance using mNGS in COVID-19 patients has rarely been reported.
METHODS
Respiratory pathogen and antibiotic resistance prediction were evaluated by BALF mNGS for 192 hospitalized COVID-19 patients between December 2022 and February 2023.
RESULTS
Secondary infection was confirmed in 83.3% (160/192) of the COVID-19 patients, with bacterial infections (45%, 72/160) predominating, followed by mixed bacterial and fungal infections (20%, 32/160), and fungal infections (17.5%, 28/160). The incidence of bacterial or viral secondary infection was significantly higher in patients who were admitted to the ICU, received mechanical ventilation, or developed severe pneumonia (all p<0.05). (n=30, 8.4%) was the most prevalent pathogen associated with secondary infection followed by (n=29, 8.1%), (n=29, 8.1%), (n=27, 7.6%), (n=23, 6.4%), (n=20, 5.6%) and (n=14, 3.9%). The overall concordance between the resistance genes detected by mNGS and the reported phenotypic resistance in 69 samples containing five clinically important pathogens (ie, and ) that caused secondary infection was 85.5% (59/69).
CONCLUSION
mNGS can detect pathogens causing secondary infection and predict antimicrobial resistance for COVID19 patients. This is crucial for initiating targeted treatment and rapidly detect unsuspected spread of multidrug-resistant pathogens.
PubMed: 37795203
DOI: 10.2147/IDR.S424061 -
Journal of Molecular Medicine (Berlin,... Oct 2023The transcription factor GATA2 is involved in human diseases ranging from hematopoietic disorders, to cancer, to infectious diseases. GATA2 is one of six GATA-family... (Review)
Review
The transcription factor GATA2 is involved in human diseases ranging from hematopoietic disorders, to cancer, to infectious diseases. GATA2 is one of six GATA-family transcription factors that act as pioneering transcription factors which facilitate the opening of heterochromatin and the subsequent binding of other transcription factors to induce gene expression from previously inaccessible regions of the genome. Although GATA2 is essential for hematopoiesis and lymphangiogenesis, it is also expressed in other tissues such as the lung, prostate gland, gastrointestinal tract, central nervous system, placenta, fetal liver, and fetal heart. Gene or transcriptional abnormalities of GATA2 causes or predisposes patients to several diseases including the hematological cancers acute myeloid leukemia and acute lymphoblastic leukemia, the primary immunodeficiency MonoMAC syndrome, and to cancers of the lung, prostate, uterus, kidney, breast, gastric tract, and ovaries. Recent data has also linked GATA2 expression and mutations to responses to infectious diseases including SARS-CoV-2 and Pneumocystis carinii pneumonia, and to inflammatory disorders such as atherosclerosis. In this article we review the role of GATA2 in the etiology and progression of these various diseases.
PubMed: 37624387
DOI: 10.1007/s00109-023-02359-8