Galactomannan Test Research Articles

735. Trends and Cost Analysis of Aspergillus Galactomannan testing at a Tertiary Medical Center

Background Aspergillus is a fungus spread by inhalation of spores that can lead to invasive (IA), chronic, or allergic aspergillosis. Risk factors for IA include neutropenia, hematological malignancy, allogenic stem cell (HSCT) or solid organ transplant, severe immunodeficiency, or prolonged steroid use. An alternative to invasive tissue sampling, the serum Galactomannan (AGM) test detects a polysaccharide cell wall component of Aspergillus and can be used to determine a probable diagnosis of IA. Accuracy of AGM is related to disease burden and thus has the highest sensitivity and specificity in patients with hematologic malignancy or Hematopoietic stem cell transplantation (HSCT) at 70-82% and 86-92%, respectively. Studies have shown sensitivity to decline in other populations, with solid organ transplants as low as 20%.MethodsWe performed a retrospective study of all patients who received the AGM test at UMMC from January 3, 2013 to December 31, 2019. Patient Cohort Explorer was used to obtain de-identified patient data from EPIC. We obtained the number of encounters and patients on whom the AGM test was performed along with other variables. Billing offices provided the self-pay cost per AGM test.ResultsA total of 6,404 AGM tests were performed on 2,126 patients during 4,315 encounters in the study period. With a total of 499, 574, 984, 1140, 851, 1175 and 1181 tests done respectively from 2013 to 2019, a increasing trend was noted. The patients ages ranged from 1 to 89 with a median age of 52 years. A total of 3,055 tests were ordered in females, and 3,349 were ordered in males.At a cut off value (optical density index) of > 0.5, 183 AGM tests resulted positive in 108 patients and at a cut of > 1.0, 113 tests are positive in 70 patients. The rate of a positive AGM tests at > 0.5 was at 2.85% and at > 1.0 was at 1.76% over the study period. With the self-pay cost of each test at $134.54 in 2019 USD, the total cost of 6,404 tests was $861,594.16.ConclusionTo our knowledge this data set constitutes the largest sample size of AGM testing. From our data, it seems that the rate of ordering this test has increased yearly. Relatively low percentage of these tests are positive, suggesting that it is most likely a large amount of these tests could have been ordered inappropriately or in the wrong clinical context.Disclosures All Authors: No reported disclosures

1707. Clinical Profile of Human T-Lymphotropic Virus Type I Infection in Pediatric Population in a Referral Hospital in Colombia

BackgroundThe Human T-lymphotropic virus type 1 (HTLV-1), affects around ten to twenty million people worldwide, predominantly in intertropical regions (Africa, Japan, Melanesia, Australia, and South America Pacific Coast). The most common disorders associated are T-cell leukemia/lymphoma (ALT) and HTLV-1-associated myelopathy (HAM). Studies have reported other clinical manifestations in HTLV-1, still studies are needed in pediatric population to improve diagnosis and treatment of infected patients.MethodsDescriptive, retrospective cohort study, conducted in our referral pediatric hospital in Cali, Colombia. Included pediatric patients (1 to 18 years of age) diagnosed with HTLV-1 infection, between January 2017 to March 2020.ResultsTwelve patients were included, seven males and five females. Eleven patients were from and resided in the Colombian Pacific coast. Ten patients showed nutritional deficiencies.None showed clinical or laboratory signs of ALT, neither neurological symptoms or physical exam suggesting HAM. In terms of associated diseases and opportunistic infections, none had a positive HIV ELISA test, and stool tests were all negative for Strongiloydes. Four presented infective dermatitis, and two showed lesions suggesting scabies.Eight patients presented respiratory symptoms with chest CT scans showing signs of chronic inflammation, bronchiectasis, and subpleural bullae as the major findings. Additional tests were carried out in bronchoalveolar fluid, four had positive galactomannan test,suggesting pulmonary aspergillosis, two exhibited positive gene PCR testing for Mycobacterium tuberculosis.Regarding inflammatory diseases, one patient presented with symptoms of Inflammatory Bowl Disease, with biopsy confirming Crohn’s disease. Another patient presente abrupt vision loss, diagnosed with Vogt Koyanagi Hadara Syndrome after ophthalmological evaluation.Summary features HTLV-1 patients Ground-glass opacity diffusely distributed in both lungs with multiple bronchiectasis involving predominantly lung bases. Cystic images diffusely distributed in both lungs, some subpleural and other centrilobular. ConclusionIt is important to consider alternative manifestations of HTLV-1 infection in the pediatric population, including pulmonary disease, opportunistic co-infections, and inflammatory disorders. It is crucial to diagnose this disease in childhood to reach a better control of this neglected infection that affects predominantly vulnerable population in low-income countries.Disclosures All Authors: No reported disclosures

The values of (1,3)-β-D-glucan and galactomannan in cases of invasive fungal rhinosinusitis

ObjectiveThe purpose of the present study was to investigate the values of the serum (1,3)-β-D-glucan test (G test) alone, the galactomannan test (GM test) alone, and their combination in the diagnosis of invasive fungal rhinosinusitis (IFRS). MethodsThe present study retrospectively analysed the clinical data of 98 patients who were preliminarily diagnosed with “space-occupying lesions in nose”. Of these 98 patients, 88 received the G test, 55 received the GM test, and 45 received both. A pathology analysis was used as the gold standard to diagnose IFRS. All data were analysed using SPSS 19.0. ResultsThe sensitivities (Se) of the G and GM tests alone were 60.0% and 28.6%, respectively, whereas the specificities (Sp) were 92.3% and 93.8%, respectively. Moreover, the positive predictive values (PPV) of the G and GM tests alone were 50.0% and 40.0%, respectively, and the negative predictive values (NPV) were 94.7% and 90.0%, respectively. In addition, the diagnostic odds ratios (DOR) were 18.0 and 6.0, respectively, and the Kappa values were 0.48 (P < 0.05) and 0.25 (P > 0.05), respectively. When the G and GM tests were parallel combined, the Se was 66.7%, the Sp was 92.3%, the PPV was 57.1%, the NPV was 94.7%, the DOR was 24.0, and the Kappa value was 0.55 (P < 0.05). The present study was unable to evaluate the serial diagnosis due to the lack of patients testing positive. ConclusionsThe G/GM tests exhibited low Se and PPV when used to diagnose IFRS, while high Sp and NPV. Parallel diagnosis improved the diagnostic Se and DOR values.

COVID-19-Associated Invasive Aspergillosis: Data from the UK National Mycology Reference Laboratory.

COVID-19-associated pulmonary aspergillosis (CAPA) was recently reported as a potential infective complication affecting critically ill patients with acute respiratory distress syndrome following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with incidence rates varying from 8 to 33% depending on the study. However, definitive diagnosis of CAPA is challenging. Standardized diagnostic algorithms and definitions are lacking, clinicians are reticent to perform aerosol-generating bronchoalveolar lavages for galactomannan testing and microscopic and cultural examination, and questions surround the diagnostic sensitivity of different serum biomarkers. Between 11 March and 14 July 2020, the UK National Mycology Reference Laboratory received 1,267 serum and respiratory samples from 719 critically ill UK patients with COVID-19 and suspected pulmonary aspergillosis. The laboratory also received 46 isolates of Aspergillus fumigatus from COVID-19 patients (including three that exhibited environmental triazole resistance). Diagnostic tests performed included 1,000 (1-3)-β-d-glucan and 516 galactomannan tests on serum samples. The results of this extensive testing are presented here. For a subset of 61 patients, respiratory specimens (bronchoalveolar lavage specimens, tracheal aspirates, and sputum samples) in addition to serum samples were submitted and subjected to galactomannan testing, Aspergillus-specific PCR, and microscopy and culture. The incidence of probable/proven and possible CAPA in this subset of patients was approximately 5% and 15%, respectively. Overall, our results highlight the challenges in biomarker-driven diagnosis of CAPA, especially when only limited clinical samples are available for testing, and the importance of a multimodal diagnostic approach involving regular and repeat testing of both serum and respiratory samples.

The Aspergillus Lateral Flow Assay for the Diagnosis of Invasive Aspergillosis: an Update.

Purpose of ReviewTo review the data on the Aspergillus lateral flow assay for the diagnosis of invasive Aspergillosis.Recent FindingsAspergillus spp. cause a wide spectrum of disease with invasive aspergillosis (IA) as its most severe manifestation. Early and reliable diagnosis of disease is crucial to decrease associated morbidity and mortality, and enable prompt initiation of treatment for IA. Most recently, non-culture-based tests, such as Aspergillus galactomannan (GM), have been useful in early identification and treatment of patients with IA. However, cost, turnaround time, and variable performance indifferent populations at risk for IA remain significant drawbacks to the use of this test. Several diagnostic tests for IA have been developed, including the sōna Aspergillus GM Lateral flow assay (GM-LFA) rapid test.SummaryThe GM-LFA has shown excellent performance for the diagnosis of IA in patients with hematologic malignancy and may be a viable option for settings where ELISA GM testing is not feasible. Further evaluation of the GM-LFA in the non-hematology setting is ongoing, including in solid organ transplant recipients and patients in the intensive care unit.

Comparison of β-D-Glucan and Galactomannan in Serum for Detection of Invasive Aspergillosis: Retrospective Analysis with Focus on Early Diagnosis.

The early diagnosis of invasive aspergillosis (IA) relies mainly on computed tomography imaging and testing for fungal biomarkers such as galactomannan (GM). We compared an established ELISA for the detection of GM with a turbidimetric assay for detection of the panfungal biomarker β-D-glucan (BDG) for early diagnosis of IA. A total of 226 serum specimens from 47 proven and seven probable IA cases were analysed. Sensitivity was calculated for samples obtained closest to the day of IA-diagnosis (d0). Additional analyses were performed by including samples obtained during the presumed course of disease. Most IA cases involved the respiratory system (63%), and Aspergillus fumigatus was the most frequently isolated species (59%). For proven cases, sensitivity of BDG/GM analysis was 57%/40%. Including all samples dating from –6 to +1 weeks from d0 increased sensitivities to 74%/51%. Sensitivity of BDG testing was as high as or higher than GM testing for all subgroups and time intervals analysed. BDG testing was less specific (90–93%) than GM testing (99–100%). Combining BDG and GM testing resulted in sensitivity/specificity of 70%/91%. Often, BDG testing was positive before GM testing. Our study backs the use of BDG for diagnosis of suspected IA. We suggest combining BDG and GM to improve the overall sensitivity.

COVID-19 associated with pulmonary aspergillosis: A literature review.

Bacterial or virus co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in many studies, however, the knowledge on Aspergillus co-infection among patients with coronavirus disease 2019 (COVID-19) was limited. This literature review aims to explore and describe the updated information about COVID-19 associated with pulmonary aspergillosis. We found that Aspergillus spp. can cause co-infections in patients with COVID-19, especially in severe/critical illness. The incidence of IPA in COVID-19 ranged from 19.6% to 33.3%. Acute respiratory distress syndrome requiring mechanical ventilation was the common complications, and the overall mortality was high, which could be up to 64.7% (n = 22) in the pooled analysis of 34 reported cases. The conventional risk factors of invasive aspergillosis were not common among these specific populations. Fungus culture and galactomannan test, especially from respiratory specimens could help early diagnosis. Aspergillus fumigatus was the most common species causing co-infection in COVID-19 patients, followed by Aspergillus flavus. Although voriconazole is the recommended anti-Aspergillus agent and also the most commonly used antifungal agent, aspergillosis caused by azole-resistant Aspergillus is also possible. Additionally, voriconazole should be used carefully in the concern of complicated drug–drug interaction and enhancing cardiovascular toxicity on anti-SARS-CoV-2 agents. Finally, this review suggests that clinicians should keep alerting the possible occurrence of pulmonary aspergillosis in severe/critical COVID-19 patients, and aggressively microbiologic study in addition to SARS-CoV-2 via respiratory specimens should be indicated.

Role of Serum (1,3)-Β-D-Glucan to Screen for Pneumocystis Pneumonia in Kidney Transplant Recipients

BackgroundPneumocystis pneumonia is a common opportunistic infection in kidney transplant recipients caused by the ascomycetous fungi Pneumocystis jirovecii. Its clinical presentation of a progressive nonproductive cough, shortness of breath, and fever is nonspecific and often delays diagnosis and appropriate treatment. Moreover, the plain radiograph may show a spectrum of findings from normal to bilateral diffuse infiltrates. Detection of serum (1,3)-β-D-glucan along with consistent clinical findings can be used as early screening tools to diagnose and initiate treatment for Pneumocystis pneumonia pending confirmation by bronchoscopy. MethodsThis case series describes 6 kidney transplant recipients who were diagnosed as having Pneumocystis pneumonia. The baseline demographic variables, presenting symptoms, radiographic findings, laboratory findings including lactate dehydrogenase and serum (1,3)-β-D-glucan levels, bronchoscopy findings, and its timing in relation to a positive serum (1,3)-β-D-glucan test, and response to treatment were collected. ResultsAll 6 patients who completed the first 3 months of prophylaxis against Pneumocystis pneumonia with sulfamethoxazole-trimethoprim were diagnosed as having Pneumocystis pneumonia between 2 to 24 years post transplant. They initiated treatment early based on a positive serum (1,3)-β-D-glucan and negative Histoplasma antigen and serum galactomannan test with a presumptive diagnosis of Pneumocystis pneumonia, which was later confirmed with a positive polymerase chain reaction on bronchoalveolar lavage fluid. ConclusionsPneumocystis pneumonia is a common opportunistic fungal infection in immunosuppressed kidney transplant recipients, and use of serum (1,3)-β-D-glucan can be used as an initial screening test for its early diagnosis and treatment.

Isolation of Aspergillus spp. in respiratory samples of patients with COVID-19 in a Spanish Tertiary Care Hospital.

SummaryBackgroundInvasive pulmonary aspergillosis (IPA) is a complication of respiratory bacterial and viral infections such as coronavirus disease 2019 (COVID‐19).Patients/MethodsIn University Hospital La Paz (Madrid, Spain), we reviewed the clinical and demographic characteristics of 10 patients with positive severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) PCR and Aspergillus spp. isolate in respiratory samples. We also recovered results of galactomannan tests in serum and/or bronchoalveolar lavage (BAL) samples.ResultsEight male and two female from 51 to 76 years were recovered. They had reported risk factors to develop IPA (haematological malignancies, immunosuppression, diabetes, obesity, intensive care unit stay, among others). Azole susceptible Aspergillus fumigatus was isolated in nine patients and Aspergillus nidulans was isolated in one patient. Only one case was classified as probable aspergillosis, seven cases as putative aspergillosis, and two cases were not classifiable. Eight patients received antifungal treatment. Seven patients died (70%), two are still inpatient due to nosocomial infections and one was discharged referred to another institution.ConclusionsThis clinical entity has high mortality, and therefore, it should be performed surveillance with early galactomannan tests and cultures in respiratory samples in order to improve the outcome of the patients with this condition.

Performance of the Bronchoalveolar Lavage Fluid Aspergillus Galactomannan Lateral Flow Assay With Cube Reader for Diagnosis of Invasive Pulmonary Aspergillosis: A Multicenter Cohort Study.

The Aspergillus Galactomannan Lateral Flow Assay (LFA) is a rapid test for the diagnosis of invasive aspergillosis (IA) that has been almost exclusively evaluated in patients with hematologic malignancies. An automated digital cube reader that allows for quantification of results has recently been added to the test kits. We performed a retrospective multicenter study on bronchoalveolar lavage fluid (BALF) samples obtained from 296 patients with various underlying diseases (65% without underlying hematological malignancy) who had BALF galactomannan (GM) ordered between 2013 and 2019 at the University of California, San Diego, the Medical University of Graz, Austria, and the Mannheim University Hospital, Germany. Cases were classified as proven (n = 2), probable (n = 56), putative (n = 30), possible (n = 45), and no IA (n = 162). The LFA showed an area under the curve (AUC) of 0.865 (95% confidence interval [CI] .815-.916) for differentiating proven/probable or putative IA versus no IA, with a sensitivity of 74% and a specificity of 83% at an optical density index cutoff of 1.5. After exclusion of GM as mycological criterion for case classification, diagnostic performance of the LFA was highly similar to GM testing (AUC 0.892 vs 0.893, respectively). LFA performance was consistent across different patient cohorts and centers. In this multicenter study the LFA assay from BALF demonstrated good diagnostic performance for IA that was consistent across patient cohorts and locations. The LFA may serve a role as a rapid test that may replace conventional GM testing in settings where GM results are not rapidly available.

Overview on common fungal infections, recovered in Baghdad teaching hospitals in five years

Objective: To evaluate the burden of invasive fungal infections , recovered in a group of patients who were non responsive to antibiotic therapy and have been referred from some Iraqi hospitals in five years interval in a clinical and microbiological scope.&#x0D; Methods: &#x0D; Samples were collected during from the 25th of May 2012 to 5th of November 2017 enrolled 1444 Iraqi adult patients who referred by hematology-oncology unit, medical wards, bone marrow transplant unit and respiratory care unit with some other cases received from other hospitals in the capital Baghdad. samples from any infected sites were sent to the central medical mycology lab to identify the causative fungi using wet mount, direct examination, culture and sensitivity tests, biochemical and some serological examinations as galactomannan testing for invasive aspergillosis and PCR test to detect some pathological properties of a group of Aspergillus species.&#x0D; &#x0D; Results&#x0D; Although (26,6%) 387 samples revealed no fungal isolates most of them were of blood culture. The commonest fungus noticed in all samples was Cryptococcus neoformans in the first place 646 samples (38.63%), the next was Candida albicans and non albicans in 594 samples (35.52%).Aspergillus species in 252 samples (15.07%) ,Penicillium 27 samples (1.61%) ,Gieotrichum candidum15 samples (0.89),Zygomycetes and Rhizopus 20 (1.18% ),Trichosporon and Rhodotorula glutinis yeasts 14 )0.83%(, Sporothrixes schenkii 5(0.29%),2(0.11%) two cases of systemic mycosis one Histoplasma capsulatum and the other is Coccidiomycosis immitus .&#x0D; Conclusions: The incidence of fungal infection is greatly increased in Iraq in relation to global and local risk factors with tendency for multiple fungal isolates in one patient. represents a major health problem in a wide variety of disease conditions ranging from hematology oncology to uncontrolled diabetic cases. with high case of fatality among hematological malignancies with neutropenia.

COVID-19 Associated Pulmonary Aspergillosis (CAPA)-From Immunology to Treatment.

Like severe influenza, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome (ARDS) has emerged as an important disease that predisposes patients to secondary pulmonary aspergillosis, with 35 cases of COVID-19 associated pulmonary aspergillosis (CAPA) published until June 2020. The release of danger-associated molecular patterns during severe COVID-19 results in both pulmonary epithelial damage and inflammatory disease, which are predisposing risk factors for pulmonary aspergillosis. Moreover, collateral effects of host recognition pathways required for the activation of antiviral immunity may, paradoxically, contribute to a highly permissive inflammatory environment that favors fungal pathogenesis. Diagnosis of CAPA remains challenging, mainly because bronchoalveolar lavage fluid galactomannan testing and culture, which represent the most sensitive diagnostic tests for aspergillosis in the ICU, are hindered by the fact that bronchoscopies are rarely performed in COVID-19 patients due to the risk of disease transmission. Similarly, autopsies are rarely performed, which may result in an underestimation of the prevalence of CAPA. Finally, the treatment of CAPA is complicated by drug–drug interactions associated with broad spectrum azoles, renal tropism and damage caused by SARS-CoV-2, which may challenge the use of liposomal amphotericin B, as well as the emergence of azole-resistance. This clinical reality creates an urgency for new antifungal drugs currently in advanced clinical development with more promising pharmacokinetic and pharmacodynamic profiles.

Evaluating the use of a 22-pathogen TaqMan array card for rapid diagnosis of respiratory pathogens in intensive care.

Introduction. Pneumonia is highly prevalent in intensive care units (ICUs), with high associated mortality. Empirical treatment prioritizes breadth of coverage while awaiting laboratory diagnosis, often at the expense of antimicrobial stewardship. Microarrays use multiple parallel polymerase chain reactions to enable a rapid syndromic approach to laboratory diagnosis.Aim. To evaluate the clinical and laboratory implications of introducing a bespoke 22-pathogen TaqMan Array Card (TAC) for rapid pathogen detection in deep respiratory samples from adult ICUs.Methodology. TAC results from all ICU patients prospectively tested over a 9-month period at Cambridge's Clinical Microbiology and Public Health Laboratory were compared to those of corresponding conventional microbiological assays (culture-, PCR- or serology-based) in terms of result agreement and time-to-result availability. Clinical impact was assessed by retrospective review of medical records.Results. Seventy-one patients were included [45 (63 %) male, median age 59). Overall result agreement was 94 %, with TAC detecting more pathogens than conventional methods. TAC detected Streptococcus pneumoniae more readily than culture (7 vs 0 cases; P=0.02). TAC did not detect Aspergillus spp. in eight culture- or galactomannan-positive cases. The median turnaround time (1 day) was significantly shorter than that of bacterial/fungal culture, Pneumocystis jirovecii PCR and galactomannan testing (each 3 days; P<0.001), atypical bacteria serology (13 days; P<0.001) and Mycobacterium tuberculosis culture (46 days; P<0.001). Earlier result availability prompted discontinuation of unnecessary antimicrobials in 15/71 (21 %) cases, but had no bearing on patient isolation/deisolation.Conclusion. TAC provided greater overall yield of pathogen detection and faster turnaround times, permitting earlier discontinuation of unnecessary antimicrobials.

Serum galactomannan level for the diagnosis of invasive pulmonary aspergillosis in hospitalized patients with chronic obstructive pulmonary disease (COPD): Meta-analysis

Background: The serum galactomannan (GM) assay is used to diagnose invasive pulmonary aspergillosis (IPA). We conducted a meta-analysis to assess the overall accuracy of the serum GM test for detecting IPA in critically ill COPD patients. Methods: The web of science, Pubmed, Embase, China National Knowledge Infrastructure, WanFang, Weipu (VIP) Science China databases were searched for all the eligible studies, including randomized controlled trials and prospective studies up to February 2019. We selected and assessed articles that reported diagnostic data related to serum GM for diagnosis of invasive fungal disease in hospitalized COPD patients. Additionally, pooled sensitivity (SEN), specificity (SPE), true positive (TP), false positive (FP), true negative (TN), false negative (FN) were estimated for summarizing overall test performance. Results: Of 1104 articles screened, 14 studies were involved in the meta-analysis with 1127 patients in the COPD serum sample. The pooled serum GM assay results with cutoff value of 0.5 were as follows: DOR: 15 (95% CI, 6–38), sensitivity: 0.57 (95% CI, 0.37–0.75), specificity: 0.92 (95%,CI, 0.85–0.96), and the SROC was 0.89 (95% CI, 0.86–0.91). When the cutoff value was 1, the results were as follows: DOR: 33 (95% CI, 15–70), sensitivity: 0.57 (95% CI, 0.39–0.73), specificity: 0.96 (95% CI, 0.93–0.98), and SROC was 0.95 (95% CI, 0.92–0.96). Conclusion: Serum GM can be used to assist in diagnosis of IPA in critically ill COPD patients. When cutoff value was set as 1, serum GM had better diagnostic value compared to those with cutoff of 0.5.

Galactomannan detection in bronchoalveolar lavage fluids: A diagnostic approach for fungus ball in patients with pulmonary tuberculosis?

Several previous studies have shown cavitary lung lesions in old pulmonary tuberculosis (PTB) increase the risk of fungus ball. Detection of galactomannan (GM) in bronchoalveolar lavage (BAL) is also proposed as a diagnostic approach for the fungus ball. We evaluated the diagnosis of fungus balls and GM levels in BAL samples in PTB patients. A total of 110 PTB patients were evaluated for fungus ball during 2017-2019. The patients were evaluated for radiological, histopathological results and mycological findings of BAL including GM detection and culture. The sensitivity, specificity and positive and negative predictive value for GM test were calculated. The optimal cut-off for BAL GM testing was determined by receiver operating characteristic (ROC). Of 110 PTB patients, nine (8.18%) showed fungus ball, all with old PTB. The molecularly confirmed Aspergillus species were A. flavus, A. fumigatus and A. ochraceus. The sensitivity and specificity of BAL GM ≥ 0.5 in old PTB patients with fungus ball were 100%, 41.5%, respectively. The statistical analysis of the mean ± SEM of BAL GM levels was demonstrated a higher levels of GM in patients with fungus ball/aspergilloma compared to old PTB patients without fungus ball/aspergilloma. The optimal cut-off value for BAL GM was determined as 0.50 by ROC curve analysis. According to our results, we can recommend the detection of GM in BAL samples as a diagnostic approach for fungus ball in PTB patients.

Diagnosing COVID-19-associated pulmonary aspergillosis

There is increasing concern that patients with coronavirus disease 2019 (COVID-19) might be at risk of developing invasive pulmonary aspergillosis co-infection.1 In a cohort of 221 patients with COVID-19 in China, fungal infections were diagnosed in seven individuals, all of whom were admitted to the intensive care unit (ICU).2 However, causative fungal pathogens were not identified.2 Given that in China, galactomannan testing is rarely available,3 the real burden of invasive pulmonary aspergillosis in patients with COVID-19 requiring ICU admission is probably underestimated.

Potential value of serum Aspergillus IgG antibody detection in the diagnosis of invasive and chronic pulmonary aspergillosis in non-agranulocytic patients

BackgroundAt present, serum Aspergillus IgG and IgM antibody detection is mainly used in the diagnosis of chronic pulmonary aspergillosis (CPA), but its value in the diagnosis of invasive pulmonary aspergillosis (IPA) in non-agranulocytic patients is still unclear. IgM can be used as a marker of acute infection to help diagnose acute infection-related diseases. IgG is a marker of long-term infection and is used to assist in the diagnosis of pre-existing or chronic infection-related diseases. The aim of this study was to investigate and compare the value of serum Aspergillus IgG and IgM antibody detection in the diagnosis of IPA and CPA in non-agranulocytic patients.MethodsFifty-eight cases of pulmonary aspergillosis (37 IPA and 21 CPA cases), 15 cases of community-acquired bacterial pneumonia and 50 cases in the healthy control group were collected. The serum (1,3)-β-D-glucan test (G test) was performed with a chromogenic method, and the galactomannan test (GM test) and Aspergillus IgG and IgM antibody detection were performed by commercial enzyme-linked immunosorbent assay (ELISA) in all patients. The sensitivity and specificity, cut-off value and area under the curve (AUC) of Aspergillus IgG and IgM antibodies were further obtained by receiver operating characteristic (ROC) curves.ResultsThe positive rate of the G test, Aspergillus IgG antibody detection and the GM test also showed notable differences among the IPA, CPA, community-acquired bacterial pneumonia and healthy groups (P = 0.006, P < 0.001 and P = 0.217, respectively). Only the positive rate of the GM test showed a significant difference between the IPA and CPA groups (P = 0.04). ROC curves indicated that Aspergillus IgG antibody detection had a higher specificity in the IPA group than in the CPA group (0.952). The detection of Aspergillus IgG antibody can preferably distinguish IPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.923, specificity = 0.459, cut-off value = 134.46, AUC = 0.727). It can also distinguish CPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.952, specificity = 0.692, cut-off value = 75.46, AUC = 0.873).ConclusionsSerum Aspergillus IgG antibody detection may have certain clinical value in the diagnosis of IPA and CPA in non-agranulocytic patients.

Diagnostic Value of Galactomannan in Bronchoalveolar Lavage Fluid for Chronic Respiratory Disease with Pulmonary Aspergillosis.

The objective of this study was to explore the diagnostic value of the bronchoalveolar lavage fluid galactomannan (BALF GM) test for chronic respiratory disease with pulmonary aspergillosis and to establish the optimal cutoff value. Samples from a total of 309 chronic respiratory disease patients seen at the respiratory medicine department of Peking University Shenzhen Hospital from September 2016 to September 2019 were analyzed. According to the diagnostic criteria, we divided the patients into a case group (n = 79, comprising 25 proven cases and 54 probable cases) and a control group (n = 230). Bronchoalveolar lavage fluid was collected, and the BALF GM test results were analyzed. A nonparametric rank sum test showed that the mean rank of the case group was 255.30, which was higher than that of the control group (120.55). The Z-value was -11.567 (P = 0.000), indicating that the general distributions of BALF GM differed between the two groups. A BALF GM cutoff value of 0.88 showed the highest diagnostic efficacy for pulmonary aspergillosis. The sensitivity, specificity, positive predictive value, and negative predictive value were 77.2%, 93%, 79.2%, and 92.2%, respectively. As the cutoff value increased, the specificity and sensitivity of the BALF GM test increased and decreased, respectively. The BALF GM test can be used confirm the diagnosis of patients with pulmonary aspergillosis and chronic respiratory disease. The optimum BALF GM cutoff value is 0.88.

Pulmonary aspergillosis: a challenging condition in the whole world.

Dear Editor, We read the report of invasive aspergillosis in a 38-year-old male diagnosed with the Hodgkin lymphoma refractory to chemotherapy and autologous transplantation. Three months after the allogeneic HLA-matched stem cell transplantation, he evolved with infections by Clostridioides (Clostridium) difficile, adenovirus, and Aspergillus.1 The bacterial infection was treated during life, while both adenoviral enteritis and hepatitis and the severe invasive pulmonary aspergillosis had a postmortem diagnosis. The authors made clear a wide spectrum of complications related to Hodgkin lymphoma management as a whole and emphasized the role of the hidden opportunistic infections. They highlighted the limitations of current diagnostic tools for aspergillosis, including cultures in blood and aspirates, tissue sampling, as well as serum galactomannan test.1 The patient underwent the best care of modern medicine in a high-income country. However, worthy of note was the final seven days of a downhill clinical course, despite utilizing three antifungal medications - caspofungin, voriconazole, and posaconazole.1 In this setting, comments about diagnostic challenges seem appropriate in three Brazilian patients with pulmonary aspergillosis; two also had lung adenocarcinomas.2-4 These 76-year-old and 64-year-old males with right lung malignancies underwent a schedule of pemetrexed disodium, cisplatin, and dexamethasone for near one year. The management with voriconazole in both cases resulted in successful outcomes.2,3 The first one had accentuated lymphopenia, and chest imaging showed a cavity in a left lung nodule mimicking central necrosis within an implant of the lung adenocarcinoma, but qualitative PCR analysis and cultures obtained in aspirates revealed Aspergillus.2 The second with neutropenia lower than 500/mm3 had the diagnosis of aspergillosis by histopathology and culture of biopsy samples, as well as positive galactomannan test.3 The main initial concern, in this case, was about misdiagnosis involving most common agents of pneumonia and sepsis associated with febrile neutropenia in malignancies.3 The last case, but not the least, refers to a 76-year-old immunocompetent woman with bilateral bronchiectasis, multiple nodules, and a tree-in-bud image in the lung base.4 During the last four months, she utilized moxifloxacin, amoxicillin plus clavulanate, moxifloxacin, piperacillin, and tazobactam without significant clinical improvement. The major concerns, in this case, were pulmonary tuberculosis and scar cell carcinoma. Complementary exams showed neutrophilia, positive galactomannan test (0.7 index), and negative cultures for fungi in samples of the bronchoalveolar aspirate. Furthermore, the repeated galactomannan test was negative after the itraconazole administration, and the chest images of control revealed a decrease in the diameters of pulmonary nodules. The final diagnosis was chronic pulmonary aspergillosis responsive to itraconazole.4 The growing population pertaining to the oldest age groups, in addition to the increased number of patients submitted to organ transplantations, chemotherapy, and other immunosuppressive treatments, are predisposing to opportunist fungal infections. Due to nonspecific manifestations, these conditions are frequently underdiagnosed, misdiagnosed, or neglected and often related to late diagnosis and very poor outcomes. The current low rate of postmortem studies may cast doubt on the estimated prevalence of these infections, especially in low-income regions with limited diagnostic resources.

Risk factors of non-invasive ventilation failure in hematopoietic stem-cell transplantation patients with acute respiratory distress syndrome.

Background:Non-invasive ventilation (NIV) was one of the first-line ventilation supports for hematopoietic stem-cell transplantation (HSCT) patients with acute respiratory distress syndrome (ARDS). Successful NIV may avoid need for intubation. However, the influence NIV failure had on patients’ outcome and its risk factors were hardly known.Methods:In this retrospective observational study, we reported risk factors and incidence of NIV failure in HSCT patients who were admitted to the Intensive Care Unit (ICU) with a diagnosis of ARDS and supported with mechanical ventilation, in a 5-year period. Patient outcomes, such as ventilator-free days, ICU-free days, and ICU mortality were also reported.Results:Of all the 94 patients included, 70 patients were initially supported with NIV. NIV failure occurred in 44 (63%) patients. Male sex, elevated serum galactomannan (GM) test, (1-3)-β-D-glucan (BG) assay, or elevated serum creatinine level were risk factors for NIV failure. When compared with the NIV success group, failure of NIV was associated with much fewer ICU-free days (22 versus 0, p < 0.001, Cohen’s d = 0.62) and higher ICU mortality (9.5% versus 75.5%, p < 0.001, Pearson’s r = 0.75). There was no difference in ICU-free days, ventilator-free days and ICU mortality between NIV failure and initial invasive mechanical ventilation (IMV) groups. Patients who failed in NIV support had a higher ICU mortality (75.5%) than those who succeeded (9.5%).Conclusion:In a small cohort of HSCT patients with mainly moderate severity of ARDS, male patients with elevated serum GM/BG test or serum creatinine level had a higher risk of NIV failure. Both NIV failure and initial IMV groups were characterized by high mortality rate and extremely low ICU-free days and ventilator-free days; failure of NIV support may further aggravate patient prognosis. The reviews of this paper are available via the supplemental material section.