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Mycoses Mar 2022The landscape of fungal endocarditis (FE) has constantly been evolving in the last few decades. Despite the advancement in diagnostic methods and the introduction of... (Review)
Review
The landscape of fungal endocarditis (FE) has constantly been evolving in the last few decades. Despite the advancement in diagnostic methods and the introduction of newer antifungals, mortality remains high in FE. This systematic review aimed to evaluate the epidemiology, clinical features, diagnostic and therapeutic interventions in patients with FE. We also aim to examine the aforementioned factors as a determinant of mortality in FE. A literature search was performed in PubMed, Google Scholar and Scopus, and all patients ≥18 years with proven fungal endocarditis were included. A total of 220 articles (250 patients) were included in the final analysis. Candida was the commonest aetiology (49.6%), followed by Aspergillus (30%) and Scedosporium species (3.2%). The proportion of prosthetic valve endocarditis (PVE) and intravenous drug users was 35.2% and 16%, respectively. The overall mortality rate was 40%. On multivariate analysis, Aspergillus endocarditis (HR 3.7, 95% CI 1.4-9.7; p = .009) and immunocompromised state (HR 2.8, 95% CI 1.24-6.3; p = .013) were independently associated with mortality. Patients treated with surgery along antifungals had better survival (HR 0.20, 95% CI 0.09-0.42; p < .001) compared to those treated with antifungals alone. Recurrence of FE was reported in 10.4% of patients. In conclusion, FE carries significant mortality, particularly in immunodeficient and Aspergillus endocarditis. We advocate the use of surgery combined with antifungals to improve clinical outcomes.
Topics: Endocarditis; Endocarditis, Bacterial; Heart Valve Prosthesis; Humans; Prosthesis-Related Infections; Risk Factors; Treatment Outcome
PubMed: 34787939
DOI: 10.1111/myc.13398 -
Therapeutic Advances in Urology 2023Aspergillosis localized to the kidneys and the urinary tract is uncommon. We conducted a comprehensive systematic review to evaluate risk factors and clinical outcomes... (Review)
Review
BACKGROUND
Aspergillosis localized to the kidneys and the urinary tract is uncommon. We conducted a comprehensive systematic review to evaluate risk factors and clinical outcomes of patients with isolated renal and genito-urinary tract aspergillosis.
METHODS
We systematically searched Medline, CINAHL, Embase, African Journal Online, Google Scholar, and the Cochrane Library, covering the period from inception to August 2023 using the key terms 'renal' OR 'kidney*' OR 'prostate' OR 'urinary bladder' OR 'urinary tract*AND 'aspergillosis' OR 'aspergillus' OR 'aspergilloma' OR 'mycetoma'. We included single case reports or case series. Review articles, guidelines, meta-analyses, animal studies, protocols, and cases of genitourinary and /or renal aspergillosis occurring as a part of disseminated disease were excluded.
RESULTS
We identified 91 renal and urinary aspergillosis cases extracted from 76 publications spanning 1925-2023. Among the participants, 79 (86.8%) were male, with a median age of 46 years. Predominantly, presentations consisted of isolated renal infections (74 instances, 81.3%), followed by prostate (5 cases, 5.5%), and bladder (7 cases, 7.7%) involvement. (42.9%), (9.9%), and (1.1% each) were isolated. Underlying risk factors included diabetes mellitus (29.7%), HIV (12.1%), haematological malignancies (11%), and liver cirrhosis (8.8%), while common symptoms encompassed flank pain (36.3%), fever (33%), and lower urinary tract symptoms (20.9%). An autopsy was conducted in 8.8% of cases. Diagnostic work-up involved histopathology (70.5%), renal CT scans and urine microscopy and culture (52.6% each), and abdominal ultrasound (17.9%). Treatments included amphotericin B (34 cases, 37.4%) and azole-based regimens (29 cases, 31.9%). Nephrectomy was performed in 16 of 78 renal cases (20.5%). All-cause mortality was 24.4% (19 cases). No significant mortality rate difference was observed among antifungal regimens ( = 0.739) or nephrectomy status ( = 0.8).
CONCLUSION
Renal and urinary aspergillosis is an important cause of morbidity and mortality, particularly in immunocompromised and people with diabetes mellitus. While varied treatment strategies were observed, mortality rates showed no significant differences based on treatments or nephrectomy status. Further research is needed to refine diagnostics, optimize treatments, and enhance awareness among clinicians for early detection and management.
PROSPERO REGISTRATION NUMBER
CRD42023430959.
PubMed: 38130371
DOI: 10.1177/17562872231218621 -
Scientific Reports May 2023This systematic review and meta-analysis aimed to comprehensively evaluate the factors associated with mortality and progressive disease in NTM-LD patients. We conducted... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis aimed to comprehensively evaluate the factors associated with mortality and progressive disease in NTM-LD patients. We conducted a literature search to identify the eligible studies, dated between January 1, 2007, and April 12, 2021. Forty-one studies with total 10,452 patients were included. The overall all-cause mortality rate was 20% (95% CI 17-24%). The overall rates of clinical and radiographic progressive disease were 46% (95% CI 39-53%) and 43% (95% CI 31-55%), respectively. Older age, male sex, history of TB, diabetes, chronic heart disease, malignancy, systemic immunosuppression, chronic liver disease, presence of cavity, consolidative radiologic features, acid-fast bacillus (AFB) smear positivity, hypoalbuminemia, anemia, increasing platelet count, high CRP, and high ESR were significantly associated with increased all-cause mortality, whereas increasing body mass index (BMI), hemoptysis, and treatment with rifamycin regimen (in M. xenopi) were significantly associated with decreased all-cause mortality in multivariable analysis. History of TB, Aspergillus co-infection, cough, increased sputum, weight loss, presence of cavity, and AFB smear positivity were significantly associated with increased clinical progression with treatment, while older age and low BMI were significantly associated with decreased clinical progression in multivariable analysis. Older age, interstitial lung disease, presence of cavity, consolidative radiologic feature, anemia, high CRP, and leukocytosis were significantly associated with increased radiographic progression after adjusting for covariates. Older age, history of tuberculosis, presence of cavity, consolidative radiologic features, AFB smear positivity, anemia, and high C-reactive protein were common significant factors associated with the all-cause mortality and clinical or radiographic progressive disease of NTM-LD. These factors are thought to directly affect NTM-LD related mortality. The future prediction models for the prognosis of NTM-LD should be established considering these factors.
Topics: Humans; Male; Retrospective Studies; Mycobacterium Infections, Nontuberculous; Lung Diseases; Pneumonia; Disease Progression
PubMed: 37147519
DOI: 10.1038/s41598-023-34576-z -
Mycoses Jul 2021We performed this study to provide the latest evidence of the diagnostic accuracy of all Aspergillus antibodies for chronic pulmonary aspergillosis (CPA). In this... (Meta-Analysis)
Meta-Analysis Review
We performed this study to provide the latest evidence of the diagnostic accuracy of all Aspergillus antibodies for chronic pulmonary aspergillosis (CPA). In this meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and other databases, until 19 March 2020, for studies that examined the diagnostic accuracy of each Aspergillus-specific antibody for CPA and assessed the risk of bias using the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. We integrated the results using a hierarchical summary receiver operating characteristic (HSROC) model and calculated the point estimates of specificity with sensitivity fixed at 0.90 using the HSROC curve. We identified 32 published and one unpublished studies, including 75 studies on five antibody test types: 18 of precipitin test (2810 participants), 46 of IgG (8197), three of IgA (283), six of IgM (733) and two of combined IgG and IgM (IgG + IgM) (920). The results of specificity with sensitivity fixed at 0.90 were as follows: precipitin test, 0.93 (95% credible intervals: 0.86, 1.00); IgG, 0.90 (0.86, 0.95); IgA, 0.74 (0.00, 1.00); IgM, 0.50 (0.37, 0.53); IgG + IgM, 0.47 (0.00, 1.00). However, the precipitin test showed imprecision and instability in the sensitivity analysis. Most studies had a high risk of bias due to the case-control design. Although there is lack of applicability for malignancy or immunosuppressive patients, our study suggests a preference for IgG over other antibody tests in CPA screening. Particularly, IgG should be used as an adjunct when ruling out CPA.
Topics: Antibodies, Fungal; Aspergillus; Chronic Disease; Diagnostic Tests, Routine; Enzyme-Linked Immunosorbent Assay; Immunocompromised Host; Immunoglobulin G; Immunologic Tests; Pulmonary Aspergillosis; ROC Curve; Sensitivity and Specificity
PubMed: 33594774
DOI: 10.1111/myc.13253 -
Lung India : Official Organ of Indian... 2023The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in Indian asthmatic patients remains unknown. We systematically reviewed the literature for estimating...
BACKGROUND
The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in Indian asthmatic patients remains unknown. We systematically reviewed the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in Indian subjects with bronchial asthma.
METHODS
We searched the PubMed and Embase databases for studies from India reporting the prevalence of AS or ABPA in at least 50 asthmatics. The primary outcome of our study was to assess the prevalence of ABPA. The secondary outcomes were to evaluate the prevalence of AS in asthma and ABPA in Aspergillus-sensitized asthma. We pooled the prevalence estimates using a random effects model and examined the factors influencing the prevalence using multivariate meta-regression.
RESULTS
Of the 8,383 records retrieved, 34 studies with 14,580 asthmatics met the inclusion criteria. All the studies were from tertiary centers. The pooled prevalence of ABPA in asthmatics (26 studies; 5,554 asthmatics) was 16.2% [95% confidence interval (CI), 12.5-20.4]. The pooled prevalence of AS in asthma (29 studies; 13,405 asthmatics) was 30.9% (95% CI, 25.3-36.6), while the prevalence of ABPA in AS (20 studies; 1,493 asthmatics) was 48.2% (95% CI, 39.6-56.8). Meta-regression identified studies published after 2009 (OR 1.14; 95% CI, 1.02-1.28) and studies with severe asthmatics (OR 1.12; 95% CI, 1.00-1.26) as the only factors associated with higher ABPA prevalence.
CONCLUSIONS
There is a high prevalence of ABPA in Indian asthmatic subjects at tertiary centers, underscoring the need for screening all asthmatic subjects in special asthma and chest clinics for ABPA.
PubMed: 37961961
DOI: 10.4103/lungindia.lungindia_69_23 -
Medical Mycology Aug 2022Emergence of triazole resistance has been observed in Aspergillus fumigatus over the past decade including Africa. This review summarizes the current published data on...
UNLABELLED
Emergence of triazole resistance has been observed in Aspergillus fumigatus over the past decade including Africa. This review summarizes the current published data on the epidemiology and reported mechanisms of triazole-resistant Aspergillus fumigatus (TRAF) in both environmental and clinical isolates from Africa. Searches on databases Medline, PubMed, HINARI, Science Direct, Scopus and Google Scholar on triazole resistance published between 2000 and 2021 from Africa were performed. Isolate source, antifungal susceptibility using internationally recognized methods, cyp51A mechanism of resistance and genotype were collected. Eleven published African studies were found that fitted the search criteria; these were subsequently analyzed. In total this constituted of 1686 environmental and 46 clinical samples. A TRAF prevalence of 17.1% (66/387) and 1.3% (5/387) was found in respectively environmental and clinical settings in African studies. Resistant to itraconazole, voriconazole, and posaconazole was documented. Most of the triazole-resistant isolates (30/71, 42.25%) were found to possess the TR34/L98H mutation in the cyp51A-gene; fewer with TR46/Y121F/T289A (n = 8), F46Y/M172V/E427K (n = 1), G54E (n = 13), and M172V (n = 1) mutations. African isolates with the TR34/L98H, TR46/Y121F/T289A and the G54E mutations were closely related and could be grouped in one of two clusters (cluster-B), whereas the cyp51A-M172V mutation clustered with most cyp51A-WT strains (cluster-A). A single case from Kenya shows that TR34/L98H from environmental and clinical isolates are closely related. Our findings highlight that triazole resistance in environmental and clinical A. fumigatus is a cause for concern in a number of African countries. There is need for epidemiological surveillance to determine the true burden of the problem in Africa.
LAY SUMMARY
Emergence of triazole resistance has been observed in Aspergillus fumigatus. TRAF was found from environmental (17.1%) and clinical (1.3%) settings in Africa. We highlighted that triazole resistance in environmental and clinical A. fumigatus is a cause for concern in a number of African countries.
Topics: Animals; Antifungal Agents; Aspergillus fumigatus; Azoles; Drug Resistance, Fungal; Fungal Proteins; Microbial Sensitivity Tests; Triazoles
PubMed: 35906879
DOI: 10.1093/mmy/myac059 -
Porto Biomedical Journal 2021A systematic review of published studies focused on the association between hypersensitivity pneumonitis (HP) and fungi exposure was conducted on PubMed, following... (Review)
Review
A systematic review of published studies focused on the association between hypersensitivity pneumonitis (HP) and fungi exposure was conducted on PubMed, following PRISMA guidelines for systematic reviews. A total of 14 studies met the inclusion criteria but only 6 of these studies were eligible, as the remaining 8 represented case reports that were separately included for further discussion. HP is an interstitial lung disease (ILD) characterized by a hypersensitization response to inhalable antigens and represents 1.5% to 12% of all ILD in the European population. Several fungi species that populate the indoor environment have been associated with the incidence of HP upon cumulative exposure, with spp and spp being the fungi species most frequently associated with the onset of disease. Although some studies have shown that avoiding exposure to causative HP fungi tends to improve patients' symptoms, other studies were unable to identify the source of sensitization. More microbial exposure studies are needed to properly estimate the risk of HP development in the built environment.
PubMed: 33532658
DOI: 10.1097/j.pbj.0000000000000117 -
Journal de Mycologie Medicale Mar 2023Invasive aspergillosis (IA) affects more than 300,000 people annually worldwide with a case fatality rate reaching 80%. However, in Africa despite the presence of risk... (Review)
Review
Invasive aspergillosis (IA) affects more than 300,000 people annually worldwide with a case fatality rate reaching 80%. However, in Africa despite the presence of risk factors for the development of IA, the burden of these fungal infections remained unknown. This systematic review aimed to update the available information on the epidemiology and the therapeutic management of IA in Africa. The published papers were systematically searched on major medical databases from September 20 to October 10, 2021. The list of references of eligible articles and the Google scholar database were also checked in order to search for possible eligible articles. Results were reported following the Preferred Reporting Items for Systematic and Meta-analyses (PRISMA) guidelines. The search yielded 1864 articles of which 29 met the inclusion criteria. This systematic review showed the existence of IA in Africa. The prevalence of IA can reach 27% with a fatality rate of more than 60%. The most common clinical form of IA found was invasive pulmonary aspergillosis. The main predisposing conditions identified were neutropenia, HIV/AIDS, renal transplant recipients, and renal failure. Aspergillus section Flavi and Nigri were the main Aspergillus species identified and Aspergillus section Fumigati was uncommon. The main management strategy for IA cases was to start antifungal therapy only after a failure of broad-spectrum antibiotic therapy. This review provided evidence of the existence of invasive aspergillosis in Africa and especially a high rate of undiagnosed invasive aspergillosis cases.
Topics: Humans; Antifungal Agents; Aspergillosis; Invasive Pulmonary Aspergillosis; Aspergillus; Invasive Fungal Infections; Risk Factors; Africa
PubMed: 36265260
DOI: 10.1016/j.mycmed.2022.101328 -
Microorganisms Jul 2023Fungal osteomyelitis is considered a rare disease, and the published literature mainly comprises case reports, case series and narrative reviews. A systematic review was... (Review)
Review
Fungal osteomyelitis is considered a rare disease, and the published literature mainly comprises case reports, case series and narrative reviews. A systematic review was undertaken to provide a practice-based global perspective on this disease, focusing on epidemiology and treatment strategies. We searched MEDLINE, EMBASE and Cochrane Library between the 3rd and 8th of March 2023 using a predefined search string. We included studies with at least one patient with a diagnosis of fungal osteomyelitis published before the 1st of January 2023. We included all study designs except for reviews, and we excluded non-English languages and grey literature. After exclusion, 678 studies, mostly case reports, were included. Descriptive analysis was performed on 1072 patients. The most common aetiological agent was (26.5%), followed by (20.7%) and (16.8%), and the bones most frequently involved were the vertebrae. We described the characteristics of patients divided by site of infection, and we found that diabetes mellitus, disseminated fungal infection, surgery and local lesion were major risk factors. We also successfully associated duration of treatment with outcome. We provided a general overview of this rare disease, and we highlighted the need for high-quality investigations on the subject.
PubMed: 37513000
DOI: 10.3390/microorganisms11071828 -
Medical Mycology May 2021Fungal infections are one of the most prevalent diseases in the world and there is a lack of new antifungal drug development for these diseases. We conducted a...
Fungal infections are one of the most prevalent diseases in the world and there is a lack of new antifungal drug development for these diseases. We conducted a systematic review of the literature regarding the in vitro antifungal activity of the organoselenium compounds ebselen (Eb) and diphenyl diselenide [(PhSe)2]. A systematic review was carried out based on the search for articles with data concerning Minimal Inhibitory Concentration (MIC) values, indexed in international databases and published until August 2020. A total of 2337 articles were found, and, according to the inclusion and exclusion criteria used, 22 articles were included in the study. Inhibitory activity against 96% (200/208) and 95% (312/328) of the pathogenic fungi tested was described for Eb and [(PhSe)2], respectively. Including in these 536 fungal isolates tested, organoselenium activity was highlighted against Candida spp., Cryptococcus ssp., Trichosporon spp., Aspergillus spp., Fusarium spp., Pythium spp., and Sporothrix spp., with MIC values lower than 64 μg/mL. In conclusion, Eb and [(PhSe)2] have a broad spectrum of in vitro inhibitory antifungal activity. These data added with other pharmacological properties of these organoselenium compounds suggest that both compounds are potential future antifungal drugs. Whether MICs toward the upper end of the ranges described here are compatible with efficacious therapy, and whether they may achieve such end as a result of the favorable non-antimicrobial effects of selenium on the host, requires more in vivo testing.
Topics: Animals; Antifungal Agents; Benzene Derivatives; Drug Synergism; Fungi; Humans; Isoindoles; Microbial Sensitivity Tests; Mycoses; Organoselenium Compounds
PubMed: 33421963
DOI: 10.1093/mmy/myaa115