Browsing by Author "Denning, David W."

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    Access to the World Health Organization-recommended essential diagnostics for invasive fungal infections in critical care and cancer patients in Africa: A diagnostic survey
    (Journal of Infection and Public Health, 2023-08-16) Tufa, Tafese Beyene; Bongomin, Felix; Fathallah, Akila; Luísa S.M., Ana; Hashad f, Rola; Soussi Abdallaoui g, Maha; Ahmed Nail h, Abdelsalam; Adetona Fayemiwo, Samuel; Penney, Richard O.S.; Orefuwa, Emma; Denning, David W.
    Background: Invasive fungal infections (IFIs) contribute to significant morbidity and mortality among patients with haemato-oncological conditions, seriously ill hospitalised patients and those in intensive care (ICU). We surveyed for the World Health Organization-recommended essential diagnostic tests for IFIs in these risk groups in Africa. Methods: The Global Action For Fungal Infections (GAFFI) evaluated the different levels of access to both diagnostics for IFIs for populations in Africa, with the aim of building a comparative dataset and a publicly available interactive map. Data was collected through a validated questionnaire administered to a country leader in relevant topics (i.e., HIV, laboratory coordination) and/or Ministry of Health representatives and followed up with 2 rounds of validation by video calls, and later confirmation by email of findings. Results: Initial data was collected from 48 African countries covering 99.65 % of the population.Conventional diagnostics such as blood cultures, direct microscopy and histopathology were often used for diagnosis of IFIs in more than half of the facilities. Bronchoscopy was rarely done or not done in 20 countries (population 649 million). In over 40 African countries (population > 850 million), Aspergillus antigen testing was never performed in either the public or private sectors. Computed tomography (CT) imaging is routinely used in 27 (56 %) of countries in the public sector and 21 44 %) in the private sector. However, magnetic resonance imaging remains relatively uncommon in most African countries. Conclusions: There are critical gaps in the availability of essential diagnostics for IFIs in Africa, particularly Aspergillus antigen testing and modern medical imaging modalities. Early diagnosis and commencement of targeted therapy of IFIs are critical for optimal outcomes from complex cancer therapies
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    Impact of high baseline Aspergillus-specific IgG levels on weight and quality-of-life outcomes of patients with chronic pulmonary aspergillosis
    (Medical Mycology, 2020-04-02) Bongomin, Felix; Garcez, Tomaz; Denning, David W.
    This study aimed to evaluate the impact of quantitative baseline Aspergillus-specific immunoglobulin G (IgG) serum levels on weight changes of patients with chronic pulmonary aspergillosis (CPA) under antifungal treatment. We retrospectively reviewed data of patients diagnosed with CPA between April 2015 and March 2018 at the National Aspergillosis Centre (Manchester, UK). All patients were on continued antifungal treat ment for 12 months. Data on Aspergillus-specific IgG levels, St George’s quality of life (SGQoL) variables and weight at baseline, 6 months and 12 months were extracted. We defined a high serum Aspergillus-specific IgG as ≥ 200 mg/l (Group A) and low level < 200 mg/l (Group B). Forty-nine patients (37 male; 12 female), median age 65 years (range: 29–86) were studied. Overall, 33% (n = 16) of the patients were in Group A. The baseline characteristics between the two groups were similar. The median Charlson comorbidity index was 4 (range: 0–5) and 3 (range: 0–9) for Group A and Group B, respectively (P = .543). There was a sustained decline in median Aspergillus IgG levels from baseline, through 6 month to 12 months of continues therapy from 170 (range: 20–1110) to 121 (range: 20–1126), and finally 107 (15–937) mg/l, respectively (P < .001). Group A patients gained more weight at 6 months (9/15 [60%] vs. 7/33 [21%], P = .012) and at 12 months of treatment (9/15 [60%] vs. 7/33 [22%]), and more patients in Group B lost weight ((13/33 [41%] vs. 1/15 [7%]), P = .015). However, there was no difference in QoL outcomes across groups at 6 (P = .3) and 12 (P = .7) months. A very high Aspergillus IgG may confer a higher likelihood of weight gain as a key, objective marker of clinical response, if patients can tolerate 12 months of antifungal therapy.
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    Innate and Adaptive Immune Defects in Chronic Pulmonary Aspergillosis
    (Journal of Fungi, 2017-05-29) Bongomin, Felix; Harris, Chris; Foden, Philip; Kosmidis, Chris; Denning, David W.
    We evaluated the expression of biomarkers of innate and adaptive immune response in correlation with underlying conditions in 144 patients with chronic pulmonary aspergillosis (CPA). Patients with complete medical and radiological records, white cell counts, and a complete panel of CD3, CD4, CD8, CD19, and CD56 lymphocyte subsets were included. Eighty-four (58%) patients had lymphopenia. Six (4%) patients had lymphopenia in all five CD variables. There were 62 (43%) patients with low CD56 and 62 (43%) patients with low CD19. Ten (7%) patients had isolated CD19 lymphopenia, 18 (13%) had isolated CD56 lymphopenia, and 15 (10%) had combined CD19 and CD56 lymphopenia only. Forty-eight (33%) patients had low CD3 and 46 (32%) had low CD8 counts. Twenty-five (17%) patients had low CD4, 15 (10%) of whom had absolute CD4 counts <200/μL. Multivariable logistic regression showed associations between: low CD19 and pulmonary sarcoidosis (Odds Ratio (OR), 5.53; 95% Confidence Interval (CI), 1.43–21.33; p = 0.013), and emphysema (OR, 4.58; 95% CI; 1.36–15.38; p = 0.014), low CD56 and no bronchiectasis (OR, 0.27; 95% CI, 0.10–0.77; p = 0.014), low CD3 and both multicavitary CPA disease (OR, 2.95; 95% CI, 1.30–6.72; p = 0.010) and pulmonary sarcoidosis (OR, 4.94; 95% CI, 1.39–17.57; p = 0.014). Several subtle immune defects are found in CPA.
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    Isolated renal and urinary tract aspergillosis: a systematic review
    (Sage Publications, 2023-11-16) Bongomin, Felix; Ekeng, Bassey E.; Mushi, Martha F.; Kibone, Winnie; Olum, Ronald; Meya, David B.; Hamer, Davidson H.; Denning, David W.; Morgan, Bethan
    Abstract 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 August2023 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 46years. 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. Aspergillus fumigatus (42.9%), Aspergillus flavus (9.9%), and Aspergillus niger/glaucus (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 (p=0.739) or nephrectomy status (p=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.
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    Prevalence of chronic pulmonary aspergillosis along the continuum of pulmonary tuberculosis care: A protocol for a living systematic review and meta-analysis
    (PLOS ONE, 2023-12-15) Bongomin, Felix; Olum, Ronald; Kibone, Winnie; Namusobya, Martha; Rhijn, Norman van; Denning, David W.
    Introduction Chronic pulmonary aspergillosis (CPA) is a debilitating disease estimated to affect over 3million people worldwide. Pulmonary tuberculosis (PTB) is the most significant risk factor for CPA. However, the true burden of CPA at the time of PTB diagnosis, during, and after PTB treatment remains unknown. In this paper, we present a protocol for a living systematic review aimed at estimating the current burden of CPA along the continuum of PTB care. Materials and methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines to formulate this protocol, which is registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023453900). We will identify primary literature through various electronic databases, including CINAHL, Ovid MEDLINE, MEDLINE (PubMed), EMBASE, Google Scholar, Cochrane Database of Systematic Reviews, and African Journal Online. The search will encompass articles from inception to December 31st, 2023, using medical subject heading search terms "pulmonary tuberculosis" AND "chronic pulmonary aspergillosis". Two reviewers will independently assess titles, abstracts, and full texts for eligibility using the Covidence web-based software.The eligible studies will comprise original observational research that reports on the prevalence of CPA diagnosed in individuals with PTB, based on established criteria, without language or geographic restriction. We intend to exclude single case reports and case series with fewer than 10 participants, as well as review articles, guidelines, and letters to the editors. Cochrane Risk of Bias Tools (ROB2 and ROBINS-I) will used to assess study quality and risk of bias and the quality of the evidence will be rated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool. Our data syntheses will encompass meta-analysis and meta-regression, conducted using STATA version 18 and R- Studio version 4.0.2. This systematic review will be updated every 3–5years as more data emerges. Conclusions The findings of this proposed systematic review will summarize the available evidence on the occurrence of CPA, at the time of PTB diagnosis, during and after PTB treatment. The study results have the potential to guide healthcare policies regarding screening for CPA,enhance clinical decision-making, and catalyse further research into understanding the interplay between PTB and CPA. By shedding light on the current burden of CPA along the continuum of PTB care, we aspire to contribute to the betterment of patient care, disease management, and global health outcomes.