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Journal de Mycologie Medicale Jun 2024With increasing concern about the negative health impact of fungal disease, there is a need to survey what is and is not known about the epidemiology of these infections... (Review)
Review
With increasing concern about the negative health impact of fungal disease, there is a need to survey what is and is not known about the epidemiology of these infections in Tunisia. We have estimated the incidence and prevalence of the most serious fungal diseases in Tunisia for the first time. Using published literature from Tunisia, or if absent other countries, we have estimated the burden of life-threatening fungal infections and those causing significant morbidity, using deterministic modeling, based on populations at greatest risk. An estimated 250,494 (2.12% of the Tunisian population) are affected by a serious fungal disease annually. Invasive and chronic pulmonary aspergillosis are relatively common with 708 and 2090 patients affected, partly linked to the prevalence of chronic obstructive pulmonary disease (COPD). Fungal asthma (allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization) have an estimated prevalence of 38,264 (5.8% of the adult asthma population). Fungal keratitis probably affects 1,761 eyes annually, often leading to uniocular blindness. Candidaemia and Candida peritonitis probably affect at least 680 people annually, with a high mortality. Recurrent vulvovaginal candidiasis probably affects over 200,000 women. While fungal diseases are regularly diagnosed in Tunisia, epidemiological studies with denominators are uncommon. Some fungal diseases are poorly addressed with the current diagnostic portfolio, and surveillance is lacking. Studies on these diseases and the implementation of a national program of surveillance are required.
Topics: Humans; Tunisia; Prevalence; Incidence; Female; Mycoses; Male; Adult; Asthma; Middle Aged; Pulmonary Disease, Chronic Obstructive; Adolescent; Aged; Candidiasis, Vulvovaginal; Young Adult; Child; Keratitis; Aspergillosis, Allergic Bronchopulmonary; Candidemia; Pulmonary Aspergillosis; Child, Preschool
PubMed: 38604083
DOI: 10.1016/j.mycmed.2024.101479 -
Cancer Science Jul 2023Glioma-initiating cells, which comprise a heterogeneous population of glioblastomas, contribute to resistance against aggressive chemoradiotherapy. Using drug...
Glioma-initiating cells, which comprise a heterogeneous population of glioblastomas, contribute to resistance against aggressive chemoradiotherapy. Using drug reposition, we investigated a therapeutic drug for glioma-initiating cells. Drug screening was undertaken to select candidate agents that inhibit proliferation of two different glioma-initiating cells lines. The alteration of proliferation and stemness of the two glioma-initiating cell lines, and proliferation, migration, cell cycle, and survival of these two differentiated glioma-initiating cell lines and three different glioblastoma cell lines treated with the candidate agent were evaluated. We also used a xenograft glioma mouse model to evaluate anticancer effects of treated glioma cell lines. Among the 1301 agents, pentamidine-an antibiotic for Pneumocystis jirovecii-emerged as a successful antiglioma agent. Pentamidine treatment suppressed proliferation and stemness in glioma-initiating cell lines. Proliferation and migration were inhibited in all differentiated glioma-initiating cells and glioblastoma cell lines, with cell cycle arrest and caspase-dependent apoptosis induction. The in vivo study reproduced the same findings as the in vitro studies. Pentamidine showed a stronger antiproliferative effect on glioma-initiating cells than on differentiated cells. Western blot analysis revealed pentamidine inhibited phosphorylation of signal transducer and activator of transcription 3 in all cell lines, whereas Akt expression was suppressed in glioma-initiating cells but not in differentiated lines. In the present study, we identified pentamidine as a potential therapeutic drug for glioma. Pentamidine could be promising for the treatment of glioblastomas by targeting both glioma-initiating cells and differentiated cells through its multifaceted antiglioma effects.
Topics: Humans; Mice; Animals; Glioblastoma; Pentamidine; Brain Neoplasms; Cell Proliferation; Cell Line, Tumor; Glioma; Apoptosis; Xenograft Model Antitumor Assays
PubMed: 37142416
DOI: 10.1111/cas.15827 -
Infectious Diseases and Therapy Aug 2023Unbiased metagenomic next-generation sequencing (mNGS) has been used for infection diagnosis. In this study, we explored the clinical diagnosis value of mNGS for...
Metagenomic Next-Generation Sequencing for Pathogens in Bronchoalveolar Lavage Fluid Improves the Survival of Patients with Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation.
INTRODUCTION
Unbiased metagenomic next-generation sequencing (mNGS) has been used for infection diagnosis. In this study, we explored the clinical diagnosis value of mNGS for pulmonary complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
METHODS
From August 2019 to June 2021, a prospective study was performed to comparatively analyze the pathogenic results of mNGS and conventional tests for bronchoalveolar lavage fluid (BALF) from 134 cases involving 101 patients with pulmonary complications after allo-HSCT.
RESULTS
More pathogens were identified by mNGS than with conventional tests (226 vs 120). For bacteria, the diagnostic sensitivity (P = 0.144) and specificity (P = 0.687) were similar between the two methods. For fungus except Pneumocystis jirovecii (PJ), conventional tests had a significantly higher sensitivity (P = 0.013) with a similarly high specificity (P = 0.109). The sensitivities for bacteria and fungi could be increased with the combination of the two methods. As for PJ, both the sensitivity (100%) and specificity (99.12%) of mNGS were very high. For viruses, the sensitivity of mNGS was significantly higher (P = 0.021) and the negative predictive value (NPV) was 95.74% (84.27-99.26%). Pulmonary infection complications accounted for 90.30% and bacterium was the most common pathogen whether in single infection (63.43%) or mixed infection (81.08%). The 6-month overall survival (OS) of 88.89% in the early group (mNGS ≤ 7 days) was significantly higher than that of 65.52% (HR 0.287, 95% CI 0.101-0.819, P = 0.006) in the late group (mNGS > 7 days).
CONCLUSIONS
mNGS for BALF could facilitate accurate and fast diagnosis for pulmonary complications. Early mNGS could improve the prognosis of patients with pulmonary complications after allo-HSCT.
TRIAL REGISTRATION
ClinicalTrials.gov identifier, NCT04051372.
PubMed: 37541984
DOI: 10.1007/s40121-023-00850-w -
BMC Infectious Diseases Nov 2023Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to...
OBJECTIVE
Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj.
METHODS
A total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed.
RESULTS
Pj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support.
CONCLUSION
The scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent.
Topics: Humans; Pneumonia, Pneumocystis; Retrospective Studies; DNA Copy Number Variations; Bronchoalveolar Lavage Fluid; Polymerase Chain Reaction; Pneumocystis; Respiratory Distress Syndrome; Pneumocystis carinii
PubMed: 38012564
DOI: 10.1186/s12879-023-08580-7 -
Annals of Clinical Microbiology and... Nov 2023The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected...
OBJECTIVE
The current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results.
METHODS
This was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort.
RESULTS
Two hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4 T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG.
CONCLUSIONS
Serum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Glucans; Retrospective Studies; beta-Glucans; Lung Neoplasms; HIV Infections; Lung Diseases, Interstitial
PubMed: 37986091
DOI: 10.1186/s12941-023-00650-7 -
Heliyon Jun 2024We present an AIDS patient coinfected with nontuberculous mycobacteria, and COVID-19, who finally recovered from the coinfection. The 36-year-old man had two...
We present an AIDS patient coinfected with nontuberculous mycobacteria, and COVID-19, who finally recovered from the coinfection. The 36-year-old man had two hospitalizations. In the first hospitalization, the patient was diagnosed with , HIV, and COVID-19 quickly and accurately, and the corresponding treatment worked well. The second hospitalization can be divided into four stages: (1) Persistent fever period; (2) Persistent fever and Pulmonary Progression; (3) ICU period; and (4) Pneumothorax period. During the second hospitalization, the diagnosis of Mycobacterium colombiense was hard because the NGS, acid-fast bacilli, and culture of vomit, sputum, and bronchoalveolar lavage fluid were all negative. Still, we detected acid-fast bacilli in the blood mycobacterium culture. In conclusion, we report a severe pneumonia AIDS patient coinfected with , COVID-19, and Mycobacterium colombiense who finally recovered from the disease. Nontuberculous mycobacteria infection is common in HIV patients, but bronchoalveolar lavage fluid NGS cannot identify nontuberculous mycobacteria in our report. Traditional blood culture was useful in detecting acid-fast bacilli in our study and then detecting the pathogens with NGS. Combining traditional microbial culture and emerging rapid NGS methods is more conducive to clinical diagnosis and treatment.
PubMed: 38867990
DOI: 10.1016/j.heliyon.2024.e31729 -
Emerging Infectious Diseases Jul 2023Hospitalizations involving fungal infections increased 8.5% each year in the United States during 2019-2021. During 2020-2021, patients hospitalized with...
Hospitalizations involving fungal infections increased 8.5% each year in the United States during 2019-2021. During 2020-2021, patients hospitalized with COVID-19-associated fungal infections had higher (48.5%) in-hospital mortality rates than those with non-COVID-19-associated fungal infections (12.3%). Improved fungal disease surveillance is needed, particularly during respiratory virus pandemics.
Topics: Humans; United States; Pandemics; Aspergillosis; Histoplasmosis; Coccidioidomycosis; Blastomycosis; Mucormycosis; Cryptococcosis; Nocardia Infections; Actinomycosis; COVID-19; Mycoses
PubMed: 37347805
DOI: 10.3201/eid2907.221771 -
Annals of Clinical Microbiology and... Jan 2024Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary...
BACKGROUND
Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary colonization in individuals with mild immunosuppression or impaired respiratory function. PCP and Cytomegalovirus (CMV) co-infections have been widely described whereas those involving other Herpesviruses (HVs) such as Epstein-Barr virus (EBV), Herpes simplex virus type 1 and type 2 (HSV-1 and -2), and Varicella zoster virus (VZV) remain scarce. To date, no data are available concerning HVs co-infections in P. jirovecii colonization.
METHODS
Our main objective was to evaluate the frequency of HVs in bronchoalveolar lavage fluid (BALF) samples from patients with PCP or with pulmonary colonization. The secondary objective was to assess the relationship between HVs and the mortality rate in PCP patients. A retrospective single-center study over a seven-year period was conducted. All patients with P. jirovecii detected using PCR in a BALF sample and for whom a PCR assay for HVs detection was performed were included in the study.
RESULTS
One hundred and twenty-five patients were included, corresponding to 77 patients with PCP and 48 colonized patients. At least one HV was detected in 54/77 (70.1%) PCP patients and in 28/48 (58.3%) colonized patients. EBV was the most frequent in both groups. Furthermore, the 30-day survival rate in PCP patients was significantly lower with [EBV + CMV] co-infection than that with EBV co-infection, [EBV + HSV-1] co-infection and without HV co-infection.
CONCLUSION
Our results show that the frequency of HV, alone or in combination is similar in PCP and colonization. They also suggest that [EBV + CMV] detection in BALF samples from PCP patients is associated with an increased mortality rate, underlying the significance to detect HVs in the course of PCP.
Topics: Humans; Pneumocystis carinii; Retrospective Studies; Pneumonia, Pneumocystis; Coinfection; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Herpesviridae; Cytomegalovirus Infections
PubMed: 38245721
DOI: 10.1186/s12941-023-00663-2 -
World Journal of Clinical Cases Aug 2023Anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5 Ab) dermatomyositis complicated with rapidly progressive interstitial lung disease...
Treatment of refractory anti-melanoma differentiation-associated gene 5 anbibody-positive dermatomyositis complicated by rapidly progressing interstitial pulmonary disease: Two case reports.
BACKGROUND
Anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5 Ab) dermatomyositis complicated with rapidly progressive interstitial lung disease (anti-MDA5 Ab DM-RP-ILD) has an unclear underlying mechanism with no recommended unified treatment plan. Herein, one of the cases that we report (Case 2) was successfully treated with tocilizumab despite having lung infection.
CASE SUMMARY
Case 1 was a 30-year-old woman who was admitted due to recurrent rash for 5 mo, fever and cough for 1 mo, and chest tightness for 3 d. She was diagnosed with non-myopathic dermatomyositis (anti-MDA5 Ab) and interstitial pneumonia, and was treated with the combination of hormone therapy and cyclophosphamide followed by oral tacrolimus. Case 2 was a 31-year-old man admitted due to systemic rash accompanied by muscle weakness of limbs for more than 1 mo, and chest tightness and dry cough for 4 d. He was diagnosed with dermatomyositis (anti-MDA5 Ab) and acute interstitial pneumonia with and infections and was treated with hormone therapy (without cyclophosphamide) and the combination of tocilizumab and tacrolimus. The condition of both patients eventually improved and they were discharged and showed clinically stable condition at the latest follow-up.
CONCLUSION
Tocilizumab could be a salvage treatment for patients with anti-MDA5 Ab DM-RP-ILD who are refractory to intensive immunosuppression.
PubMed: 37621599
DOI: 10.12998/wjcc.v11.i22.5351 -
Pathogens (Basel, Switzerland) Oct 2023Post-transplant pneumonia (PcP) is an uncommon but increasingly reported disease among solid organ transplantation (SOT) recipients, associated with significant... (Review)
Review
Post-transplant pneumonia (PcP) is an uncommon but increasingly reported disease among solid organ transplantation (SOT) recipients, associated with significant morbidity and mortality. Although the introduction of PcP prophylaxis has reduced its overall incidence, its prevalence continues to be high, especially during the second year after transplant, the period following prophylaxis discontinuation. We recently described two cases of PcP occurring more than one year after heart transplantation (HT) in patients who were no longer receiving PcP prophylaxis according to the local protocol. In both cases, the disease was diagnosed following the diagnosis of a viral illness, resulting in a significantly increased risk for PcP. While current heart transplantation guidelines recommend prophylaxis for up to 6-12 months after transplantation, after that period they only suggest an extended prophylaxis regimen in high-risk patients. Recent studies have identified several new risk factors that may be linked to an increased risk of PcP infection, including medication regimens and patient characteristics. Similarly, the indication for PcP prophylaxis in non-HIV patients has been expanded in relation to the introduction of new medications and therapeutic regimens for immune-mediated diseases. In our experience, the first patient was successfully treated with non-invasive ventilation, while the second required tracheal intubation, invasive ventilation, and extracorporeal CO2 removal due to severe respiratory failure. The aim of this double case report is to review the current timing of PcP prophylaxis after HT, the specific potential risk factors for PcP after HT, and the determinants of a prompt diagnosis and therapeutic approach in critically ill patients. We will also present a possible proposal for future investigations on indications for long-term prophylaxis.
PubMed: 37887781
DOI: 10.3390/pathogens12101265