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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 -
Mycoses Sep 2022The diagnostic accuracy of immunoassays versus immunoprecipitation methods for detecting A.fumigatus-specific IgG in patients with allergic bronchopulmonary... (Meta-Analysis)
Meta-Analysis
Comparative diagnostic accuracy of immunoprecipitation versus immunoassay methods for detecting Aspergillus fumigatus-specific IgG in allergic bronchopulmonary aspergillosis: A systematic review and meta-analysis.
BACKGROUND
The diagnostic accuracy of immunoassays versus immunoprecipitation methods for detecting A.fumigatus-specific IgG in patients with allergic bronchopulmonary aspergillosis (ABPA) complicating asthma remains unclear.
METHODS
We performed a systematic review to identify studies describing both the methods in the same ABPA subjects. We assessed study quality using the QUADAS-2 tool. We derived the relative sensitivity and specificity using the HSROC meta-regression model. We calculated the number-needed-to-test using an immunoassay to detect one additional positive test in ABPA.
RESULTS
Our search yielded 20 studies (796 ABPA and 929 controls). The studies had a high risk of bias. The summary estimates for sensitivity and specificity of immunoprecipitation methods were 68.6% (95% CI, 48.4-83.5) and 93.8% (95% CI, 83.6-97.8), respectively, while for immunoassays they were 85.2% (95% CI, 73.3-92.3) and 84.6% (95% CI, 76.0-90.5), respectively. The relative sensitivity and specificity of immunoassays compared to immunoprecipitation tests were 1.29 (95% CI, 1.1-1.6) and 0.91 (95% CI, 0.85-0.97), respectively. The automated immunoassays (1.77; 95% CI, 1.1-2.8) had better relative sensitivity than the manual (1.1; 95% CI, 1.02-1.18) assays compared to immunoprecipitation. The relative specificity of manual immunoassays (0.95; 95% CI, 0.91-0.99) was significantly lower, while that of automated (0.88; 95% CI, 0.77-1.0) assays was lower but not statistically different. One additional positive result was detected for every six (95% CI, 5-7) tests performed with immunoassay (versus immunoprecipitation).
CONCLUSION
Compared to immunoprecipiation methods, automated immunoassays have higher sensitivity and similar specificity, manual immunoassays have higher sensitivity and lower specificity, while automated immunoassays have higher sensitivity and similar specificity for detecting A.fumigatus-IgG in patients with ABPA. [www.crd.york.ac.uk/prospero/display_record.php?RecordID=309864].
Topics: Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Humans; Immunoassay; Immunoglobulin G; Immunoprecipitation
PubMed: 35757847
DOI: 10.1111/myc.13488 -
Microbial Pathogenesis Dec 2018The co-colonization prevalence of P. aeruginosa and A. fumigatus in cystic fibrosis (CF) has been inconsistently reported. The purpose of this systematic review and... (Meta-Analysis)
Meta-Analysis
PURPOSE
The co-colonization prevalence of P. aeruginosa and A. fumigatus in cystic fibrosis (CF) has been inconsistently reported. The purpose of this systematic review and meta-analysis was to estimate the overall co-colonization prevalence of P. aeruginosa and A. fumigatus in CF.
METHODS
The Embase, PubMed and Web of Science databases were systematically searched for studies reporting the co-colonization prevalence of P. aeruginosa and A. fumigatus in CF. The co-colonization prevalence of two pathogenic microorganisms in the individual studies was assessed by calculating the proportion and 95% confidence interval (CI). The random effects model was used to calculate the pooled prevalence. The I test was used to assess statistical heterogeneity. The funnel plot and two statistical methods were used to assess publication bias.
RESULTS
Twenty-three eligible studies were included in this analysis. The pooled co-colonization prevalence of P. aeruginosa and A. fumigatus in CF patients was 15.8% (95% CI: 9.9-21.8). The co-colonization prevalence of P. aeruginosa and A. fumigatus chronic colonization was lower than that of intermittent colonization, higher in sputum cultures than in bronchoalveolar lavage (BAL) cultures, and lower in children than in adults. There was a statistically significant difference in co-colonization prevalence among studies from different decades, but the prevalence was similar in different geographical regions and with different study types.
CONCLUSIONS
The co-colonization prevalence of P. aeruginosa and A. fumigatus in the lower respiratory tract of CF patients was high. The anti-infective treatment in exacerbation of CF should be considered to cover the two pathogenic microorganisms simultaneously. Large-scale research is still needed to obtain more accurate co-colonization data.
Topics: Aspergillus fumigatus; Coinfection; Cystic Fibrosis; Humans; Prevalence; Pseudomonas Infections; Pseudomonas aeruginosa; Pulmonary Aspergillosis
PubMed: 30217514
DOI: 10.1016/j.micpath.2018.09.010 -
Microbial Pathogenesis Apr 2020Progress of the disease and prolonged treatment with antibiotics or immunosuppressive agents makes tuberculosis patients susceptible to fungal infections. This study... (Meta-Analysis)
Meta-Analysis Review
Progress of the disease and prolonged treatment with antibiotics or immunosuppressive agents makes tuberculosis patients susceptible to fungal infections. This study aimed to determine the prevalence of pulmonary Aspergillus coinfection among patients with pulmonary tuberculosis in Asia and Africa. The present review of cross-sectional studies was conducted on the prevalence of pulmonary Aspergillus coinfection among patients with pulmonary tuberculosis according to the PRISMA Protocol. Literatures published online in English from January 2001 to March 2019 via key databases such as Web of Science, MEDLINE, PubMed, Scopus, and Cochrane Library were searched. The used MeSH and non-MeSH keywords were; "pulmonary fungal", "pulmonary coinfection", OR "Pulmonary mycosis", "pulmonary fungal infections/agents", OR "Polymicrobial infection", OR "Secondary infection", OR "Mixed infections", "pulmonary aspergillosis", "fungi coinfection", "Fungal co-colonization", AND "pulmonary tuberculosis", OR "pulmonary TB", AND "Asia" AND "Africa". Finally, data analyzed using Comprehensive Meta-Analysis software (CMA). The combined Aspergillus coinfection among patients with pulmonary tuberculosis was 15.4% (95% CI: 11.4-20.5), Q = 105.8 and Z = 9.57 in Asia and Africa. The most frequency of Aspergillus spp. was related to A. fumigatus with a combined prevalence of 57.6%. Most of the studies included in the present review showed a higher Aspergillus coinfection in the age group of 40 years and higher. Also, the existence of a correlation between increasing age and Aspergillus coinfection was reported (p < 0.05). The present review showed a high combined Aspergillus coinfection among patients with pulmonary tuberculosis in Asia and Africa. Also, amongst the Aspergillus spp., the most frequent was related to A. fumigatus.
Topics: Africa; Age Factors; Asia; Aspergillus; Aspergillus fumigatus; Coinfection; Cross-Sectional Studies; Humans; Prevalence; Pulmonary Aspergillosis; Risk Factors; Tuberculosis, Pulmonary
PubMed: 32006637
DOI: 10.1016/j.micpath.2020.104018 -
The Journal of Allergy and Clinical... Jun 2023The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in asthmatic patients remains unclear and is likely different across geographic locales.
BACKGROUND
The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in asthmatic patients remains unclear and is likely different across geographic locales.
OBJECTIVE
To systematically review the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in adults with bronchial asthma.
METHODS
We searched the PubMed and Embase databases for studies reporting the prevalence of AS or ABPA in at least 50 asthmatic subjects. The primary outcome was to assess the prevalence of ABPA. The secondary outcome was to evaluate the prevalence of AS in asthma and that of ABPA in asthma with AS. We pooled the prevalence estimates using a random-effects model and examined the factors influencing the prevalence using multivariate meta-regression.
RESULTS
Of the 11,801 records retrieved, 86 studies with 25,770 asthmatic subjects met the inclusion criteria. Most of the studies were from tertiary care centers. The pooled prevalence of ABPA in asthma (47 studies; 9822 asthmatic subjects) was 11.3% (95% CI, 8.7-14.2). The pooled prevalence of AS in asthma (73 studies; 23,003 asthmatic subjects) was 25.1% (95% CI, 20.5-30.0), whereas the prevalence of ABPA in AS (36 studies; 2954 asthmatic subjects) was 37.0% (95% CI, 27.9-46.6). Multivariate meta-regression identified studies published from India (odds ratio, 1.11; 95% CI, 1.01-1.23) as the only factor associated with higher ABPA prevalence. There was presence of significant statistical heterogeneity and publication bias.
CONCLUSIONS
We found a high prevalence of ABPA in adult asthmatic subjects, underscoring the need for screening for ABPA in all asthmatic subjects seeking tertiary care.
Topics: Adult; Humans; Aspergillosis, Allergic Bronchopulmonary; Prevalence; Asthma; Aspergillus; India; Aspergillus fumigatus
PubMed: 37088374
DOI: 10.1016/j.jaip.2023.04.009 -
Therapeutic Advances in Infectious... 2024, a widespread fungus in the natural environment, poses a significant threat to human health by entering the human body the airways and causing a disease called... (Review)
Review
BACKGROUND
, a widespread fungus in the natural environment, poses a significant threat to human health by entering the human body the airways and causing a disease called aspergillosis. This study comprehensively analyzed data on aspergillosis in published articles from mainland China to investigate the prevalence of , and risk factors, mortality rate, and underlying condition associated with aspergillosis.
METHODS
Published articles were retrieved from Google Scholar, PubMed, and Science Direct online search engines. In the 101 analyzed studies, 3558 isolates were meticulously collected and classified. GraphPad Prism 8 was used to statistically examine the epidemiology and clinical characteristics of aspergillosis.
RESULTS
was prominently reported ( = 2679, 75.14%), followed by ( = 437, 12.25%), ( = 219, 6.14%), and ( = 119, 3.33%). Of a total of 9810 patients, 7513 probable cases accounted for the highest number, followed by confirmed cases ( = 1956) and possible cases ( = 341). In patients, cough emerged as the most common complaint ( = 1819, 18.54%), followed by asthma ( = 1029, 10.48%) and fever (1024, 10.44%). Of total studies, invasive pulmonary aspergillosis (IPA) was reported in 47 (45.53%) studies, exhibiting an increased prevalence in Beijing ( = 12, 25.53%), Guangdong ( = 7, 14.89%), and Shanghai ( = 6, 12.76%). Chronic pulmonary aspergillosis (CPA) was reported in 14 (13.86%) studies. Among the total of 14 studies, the occurrence of CPA was 5 (35.71%) in Beijing and 3 (21.42%) in Shanghai. Allergic bronchopulmonary aspergillosis (ABPA), was reported at a lower frequency ( = 8, 7.92%), Guangdong recorded a relatively high number ( = 3, 37.5%), followed by Beijing ( = 2, 25.0%), and Shanghai ( = 1, 12.5%). Percentage of death reported: IPA had the highest rate ( = 447, 68.87%), followed by CPA ( = 181, 27.88%) and ABPA ( = 14, 2.15%). Among the aspergillosis patients, 6220 had underlying conditions, including chronic lung disease ( = 3765, 60.53%), previous tuberculosis ( = 416, 6.68%), and organ transplant or organ failure ( = 648, 10.41%). Aspergillosis was also found in patients using corticosteroid therapy ( = 622, 10.0%).
CONCLUSION
This review sheds light on the prevalence patterns of species, risk factors of aspergillosis, and gaps in surveillance that could be helpful for the control and treatment of aspergillosis and guide the researchers in future studies.
REGISTRATION
This systematic review was prospectively registered on PROSPERO: Registration ID CRD42023476870.
PubMed: 38835831
DOI: 10.1177/20499361241252537 -
The Cochrane Database of Systematic... Sep 2022Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of... (Review)
Review
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, and their many side effects are well-documented. A group of compounds, the azoles, have activity against A fumigatus, and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been used in aerosolised form to treat invasive infection with A fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review.
OBJECTIVES
The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); and 2. do not have unacceptable adverse effects. If benefit was demonstrated, we planned to assess the optimal type, duration, and dose of antifungal therapy.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, and abstract books of conference proceedings. Date of the most recent search of the Group's Trials Register was 28 September 2021. We searched ongoing trials registries, most recently on 11 March 2022. Earlier, we also approached pharmaceutical companies regarding possible unpublished trials.
SELECTION CRITERIA
Published or unpublished randomised controlled trials, in which antifungal treatments were compared to either placebo or no treatment, or where different doses of the same treatment were used in the treatment of ABPA in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
The searches identified six trials; none of which met the inclusion criteria for the review.
MAIN RESULTS
We included no completed randomised controlled trials. There is currently one ongoing trial, which we may find eligible for a future update.
AUTHORS' CONCLUSIONS
At present, there are no randomised controlled trials that evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although one trial is currently ongoing. Trials with clear outcome measures are needed to properly evaluate the use of corticosteroids in people with ABPA and cystic fibrosis.
Topics: Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Cystic Fibrosis; Humans; Itraconazole
PubMed: 36053129
DOI: 10.1002/14651858.CD002204.pub5 -
Medical Mycology Jun 2024Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In...
Recognizing the growing global burden of fungal infections, the World Health Organization established a process to develop a priority list of fungal pathogens (FPPL). In this systematic review, we aimed to evaluate the epidemiology and impact of invasive infections caused by Aspergillus fumigatus to inform the first FPPL. The pre-specified criteria of mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence were used to search for relevant articles between 1 January 2016 and 10 June 2021. Overall, 49 studies were eligible for inclusion. Azole antifungal susceptibility varied according to geographical regions. Voriconazole susceptibility rates of 22.2% were reported from the Netherlands, whereas in Brazil, Korea, India, China, and the UK, voriconazole susceptibility rates were 76%, 94.7%, 96.9%, 98.6%, and 99.7%, respectively. Cross-resistance was common with 85%, 92.8%, and 100% of voriconazole-resistant A. fumigatus isolates also resistant to itraconazole, posaconazole, and isavuconazole, respectively. The incidence of invasive aspergillosis (IA) in patients with acute leukemia was estimated at 5.84/100 patients. Six-week mortality rates in IA cases ranged from 31% to 36%. Azole resistance and hematological malignancy were poor prognostic factors. Twelve-week mortality rates were significantly higher in voriconazole-resistant than in voriconazole-susceptible IA cases (12/22 [54.5%] vs. 27/88 [30.7%]; P = .035), and hematology patients with IA had significantly higher mortality rates compared with solid-malignancy cases who had IA (65/217 [30%] vs. 14/78 [18%]; P = .04). Carefully designed surveillance studies linking laboratory and clinical data are required to better inform future FPPL.
Topics: Humans; Aspergillus fumigatus; Antifungal Agents; Aspergillosis; World Health Organization; Drug Resistance, Fungal; Voriconazole; Incidence; Microbial Sensitivity Tests; Invasive Fungal Infections; Risk Factors
PubMed: 38935907
DOI: 10.1093/mmy/myad129 -
Clinical and Experimental Allergy :... Sep 2018The role of recombinant A. fumigatus (rAsp) antigens in the diagnosis of allergic bronchopulmonary aspergillosis (ABPA) has not been systematically evaluated. Herein,... (Meta-Analysis)
Meta-Analysis
Utility of recombinant Aspergillus fumigatus antigens in the diagnosis of allergic bronchopulmonary aspergillosis: A systematic review and diagnostic test accuracy meta-analysis.
BACKGROUND
The role of recombinant A. fumigatus (rAsp) antigens in the diagnosis of allergic bronchopulmonary aspergillosis (ABPA) has not been systematically evaluated. Herein, we evaluate the utility of recombinant A. fumigatus (rAsp) antigens in diagnosing ABPA.
METHODS
We systematically reviewed the PubMed, EmBase and Scopus databases for studies evaluating rAsp antigens in ABPA. The QUADAS-2 tool and the GRADE approach were used to assess the risk of bias and the quality of evidence, respectively. The diagnostic performance of IgE or skin test against rAsp f1, f2, f3, f4, f6 and their combination was evaluated separately for ABPA complicating asthma or cystic fibrosis (CF), using an HSROC model. The reference standard for diagnosing ABPA was the composite (clinical, radiological, immunological) criteria.
RESULTS
Our search yielded 26 studies (n = 1694) and 17 studies (n = 1131) for inclusion in the systematic review and meta-analysis, respectively. In asthmatics, the pooled sensitivity for diagnosing ABPA was best for IgE against a combination of rAsp f1 or f3 (96.7%; 95% confidence interval [CI], 87.6-99.2). The pooled specificity for diagnosing ABPA was highest (99.2%; 95% CI, 88.2-99.9) for IgE against a combination of f4 or f6. In CF patients, the pooled sensitivity of rAsp f1 or f3 was 93.3% (95% CI, 55.2-99.9) while the pooled specificity of rAsp f4 or f6 was 93.9% (95% CI, 68.8-99.9). The quality of evidence was low as per the GRADE approach.
CONCLUSIONS
A combination of IgE against rAsp antigens (f1, f2, f3, f4 and f6) is likely to be helpful in the diagnosis of ABPA.
Topics: Animals; Antibodies, Fungal; Antigens, Fungal; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Humans; Immunoassay; Immunoglobulin E; Recombinant Proteins; Reproducibility of Results
PubMed: 29927507
DOI: 10.1111/cea.13216 -
Transplantation Reviews (Orlando, Fla.) Jan 2022Infective endocarditis (IE) is a rare but potentially fatal complication following heart transplantation (HTx). There is a lack of literature regarding the patterns and... (Review)
Review
PURPOSE
Infective endocarditis (IE) is a rare but potentially fatal complication following heart transplantation (HTx). There is a lack of literature regarding the patterns and clinical course of IE development following HTx. We sought to pool the existing data in regards to defining characteristics, management options, and outcomes of IE following HTx.
METHODS
An electronic search of Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Ovid Medline, and the Scopus databases were performed to identify all articles in the English literature that report IE following HTx in adult patients. Patient-level data were extracted and analyzed.
RESULTS
Systematic search yielded 57 patients from 32 articles. Median patient age was 52 [IQR 43, 59] and 75% of patients (43/57) were male. Median time to IE presentation post-HTx was 8.4 [IQR 3.0, 35.8] months. IE of the mitral valve was observed in 36.8% (21/57) of patients, followed by mural IE in 24.6% (14/57), and tricuspid valve IE in 21.1% (12/57). The most common organisms were Staphylococcus aureus in 26.3% (15/57), Aspergillus fumigatus in 19.3% (11/57), Enterococcus faecalis in 12.3% (7/57), and an undetermined or unspecified organism in 14.0% (8/57) patients. Overall case fatality was 44.6% (25/56). Fungal IE was associated with a significantly higher case fatality 75.0% (9/12) than that of bacterial IE 36.1% (13/36) (p = 0.02). Surgical management of post-HTx IE was observed in 35.1% (20/57) of patients. This included valve surgery for 70.0% (14/20), including the mitral valve in 50.0% (7/14), aortic valve in 35.7% (5/14), and the tricuspid valve in 14.3% (2/14) of patients.
CONCLUSION
In addition to bacterial organisms, fungi also represent a frequent cause of IE in post-HTx patients. Overall HTx patient survival in the setting of IE is poor and may be worse if caused by A. fumigatus.
Topics: Adult; Endocarditis; Endocarditis, Bacterial; Heart Transplantation; Humans; Male; Staphylococcal Infections; Staphylococcus aureus
PubMed: 34826752
DOI: 10.1016/j.trre.2021.100672