Purpose: Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. Methods: A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. Results: Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung.

We have evaluated the Platelia Aspergillus enzyme immunoassay for detection of galactomannan in bronchoalveolar lavage (BAL) specimens in solid organ transplant patients with aspergillosis. The precision and reproducibility in serum or BAL to which galactomannan was added were similar. Sensitivity was 81.8% in patients with aspergillosis, and specificity was 95.8% in lung transplant patients who underwent BAL for surveillance for infection or rejection. Among transplant controls, positive results were more common in patients (i) who underwent diagnostic BAL performed for evaluation of symptoms or chest computed tomographic abnormalities, (ii) who had undergone lung transplantation, or (iii) who were colonized with Aspergillus. Galactomannan testing in BAL is useful for diagnosis of aspergillosis in transplant patients. The significance of positive results in patients without confirmed aspergillosis requires further evaluation.Invasive aspergillosis (IA) is common in hematopoietic stem cell and solid organ transplant patients, and the diagnosis often is determined based on bronchoalveolar lavage (BAL) (11). Galactomannan (GM) antigenemia detection is a useful method for the early diagnosis of IA (7,11,12). Several studies in hematologic patients show that detection of Aspergillus GM in BAL can be a sensitive method for the diagnosis of IA. The sensitivity was 89% or higher, and the specificity was 87 to 100% (1, 9, 10). In two studies that compared BAL and serum, sensitivity was lower in serum than in BAL: 47% versus 100% (1) and 44% versus 89%, respectively (9). False-positive results occurred in patients receiving piperacillin-tazobactam, in whom antigenemia also was present (9). False-positive results have also been reported when Plasmalyte was used to perform BAL (4). Positive BAL results may eliminate the need for additional invasive procedures in some patients (10).We reported previously the detection of Aspergillus GM in BAL from solid organ transplant patients with IA (2, 6). We have further analyzed here those studies and provide additional support for use of BAL testing for diagnosis of IA, including a more detailed analysis of specificity, precision, and reproducibility. MATERIALS AND METHODSClinical materials. The BAL specimens from patients with IA (n ϭ 11) and controls (n ϭ 185) have been previously described (2, 6). Four patients had proven and seven had probable IA, according to published criteria (3). BAL specimens from which Aspergillus or other mold was isolated were considered to be colonized if the patient failed to meet these criteria (i.e., if cultures were not associated with a mold resembling Aspergillus by cytology or histopathology of lung tissue, were not obtained from a sterile site, or were not associated with compatible abnormalities on chest computed tomography [CT] if isolated from a nonsterile site) (5).Transplant controls included 119 lung transplant patients who underwent bronchoscopy to monitor for infection or rejection (surveillance BAL) and 66 patients with a variety of tra...

Despite shortcomings, cultures of blood and sterile sites remain the "gold standard" for diagnosing systemic candidiasis. Alternative diagnostic markers, including antibody detection, have been developed, but none are widely accepted. In this study, we used an enzyme-linked immunosorbent assay to measure serum antibody responses against 15 recombinant Candida albicans antigens among 60 patients with systemic candidiasis due to various Candida spp. and 24 uninfected controls. Mean immunoglobulin G (IgG) responses against all 15 antigens were significantly higher among patients with systemic candidiasis than among controls, whereas IgM responses were higher against only seven antigens. Using discriminant analysis that included IgG responses against the 15 antigens, we derived a mathematical prediction model that identified patients with systemic candidiasis with an error rate of 3.7%, a sensitivity of 96.6%, and a specificity of 95.6%. Furthermore, a prediction model using a subset of four antigens (SET1, ENO1, PGK1-2, and MUC1-2) identified through backward elimination and canonical correlation analyses performed as accurately as the full panel. Using the simplified model, we predicted systemic candidiasis in a separate test sample of 32 patients and controls with 100% sensitivity and 87.5% specificity. We also demonstrated that IgG titers against each of the four antigens included in the prediction model were significantly higher in convalescent-phase sera than in paired acutephase sera. Taken together, our findings suggest that IgG responses against a panel of candidal antigens might represent an accurate and early marker of systemic candidiasis, a hypothesis that should be tested in future trials.

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ObjectiveChina’s national hepatitis burden is high. This study aims to provide a detailed national-level description of the reported incidence of viral hepatitis in China during 2004–2016.DesignObservational study.SettingData were obtained from China’s National Notifiable Disease Reporting System, and changing trends were estimated by joinpoint regression analysis.ParticipantsIn this system, 16 927 233 reported viral hepatitis cases occurring during 2004–2016 were identified.Primary outcome measureIncidence rates per 100 000 person-years and changing trends were calculated.ResultsThere were 16 927 233 new cases of viral hepatitis reported in China from 2004 to 2016. Hepatitis B (HBV) (n=13 543 137, 80.00%) and hepatitis C (HCV) (n=1 844 882, 10.90%) accounted for >90% of the cases. The overall annual percent change (APC) in reported cases of viral hepatitis and HBV were 0.3%(95% CI −2.0 to 0.8, p=0.6) and −0.2% (95% CI −1.6 to 1.2, p=0.8), respectively, showing a stable trend. HBV rates were highest in the 20–29 year old age group and lowest in younger individuals, likely resulting from the universal HBV vaccination. The reported incidence of HCV and hepatitis E (HEV) showed increasing trends; the APCs were 14.5% (95% CI 13.1 to 15.9, p<0.05) and 4.7% (95% CI 2.8 to 6.7, p<0.05), respectively. The hepatitis A (HAV) reporting incidence decreased, and the APC was −13.1% (95% CI −15.1 to −11.0, p<0.05). There were marked differences in the reporting of hepatitis among provinces.ConclusionsHBV continues to constitute the majority of viral hepatitis cases in China. Over the entire study period, the HBV reporting incidence was stable, the HCV and HEV incidence increased and the HAV incidence decreased. There were significant interprovincial disparities in the burden of viral hepatitis, with higher rates in economically less-developed areas. Vaccination is important for viral hepatitis prevention and control.

Introduction Little is known about the incidence or significance of mould infections in the explanted lungs of lung transplant recipients. Method We reviewed the histopathology of the explanted lungs from 304 patients who underwent lung transplantation at our institution from 2005–07 and received alemtuzumab induction therapy and post-transplant voriconazole prophylaxis. Results Invasive mould infections were present in the explanted lungs of 5% (14/304) of patients, including chronic necrotizing pneumonias (n=7), mycetomas (4) and invasive fungal pneumonias (3). Only 21% (3/14) received immunosuppressive therapy within one year prior to lung transplantation, suggesting that lung damage itself predisposed patients to mould infections. The risk of mould infection was higher in patients with cystic fibrosis (11%, 4/35) than other underlying lung diseases (4%, 10/269). Pulmonary mould infections were not diagnosed or suspected in 57% (8/14) of patients. Despite secondary voriconazole prophylaxis, fungal infections developed in 43% (6/14) of patients with mould infections of the explanted lungs, compared to 14% (42/290) of patients without mould infections (p=0.01). Three patients developed invasive fungal infections while on voriconazole prophylaxis, and three developed fungal infections more than 8 months after the discontinuation of voriconazole. The mortality attributable to invasive fungal infections among patients with mould infections of the explanted lungs was 29% (4/14). Conclusion Invasive mould infections in the explanted lungs are often not recognized prior to lung transplantation and are associated with poor outcomes.

Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune-response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture-positive samples across the groups. Bayesian regression analysis identified non-culture-based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumoniacolonization comparisons. The dissimilar microbiomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases.