Human Tularemia Epididymo-Orchitis Caused by Francisella tularensis Subspecies holartica, Austria.

A previously healthy man in Austria had tularemia epididymo-orchitis develop, leading to unilateral orchiectomy. Francisella tularensis subspecies holartica was detected by 16S rRNA gene sequencing analysis of inflamed granulomatous testicular tissue. Clinicians should suspect F. tularensis as a rare etiologic microorganism in epididymo-orchitis patients with relevant risk factors.

Pathogen Detection by Metagenomic Next-Generation Sequencing During Neutropenic Fever in Patients With Hematological Malignancies.

Background: Febrile neutropenia (FN) after chemotherapy is a major cause of morbidity during cancer treatment. The performance of metagenomic next-generation sequencing (mNGS) of circulating cell-free deoxyribonucleic acid from plasma may be superior to blood culture (BC) diagnostics for identification of causative pathogens. The aim of this study was to validate mNGS (DISQVER test) for the detection of pathogens in hematologic patients with FN. Methods: We collected paired whole blood specimens from central venous catheter and peripheral vein during FN for BC and mNGS testing. We repeated paired sampling at the earliest after 3 days of fever, which was defined as 1 FN episode. All clinical data were retrospectively reviewed by an infectious disease expert panel. We calculated percent positive agreement (PPA), percent negative agreement (PNA), percent overall agreement (POA), and sensitivity and specificity. Results: We analyzed a total of 98 unselected FN episodes in 61 patients who developed predominantly FN after conditioning therapy for allogeneic (n = 22) or autologous (n = 21) hematopoietic stem cell transplantation. Success rate of mNGS was 99% (97 of 98). Positivity rate of mNGS was 43% (42 of 97) overall and 32% (31 of 97) excluding viruses compared to 14% (14 of 98) in BC. The PPA, PNA, and POA between mNGS and BC were 84.6% (95% confidence interval [CI], 54.6% to 98.1%), 63.1% (95% CI, 51.9% to 73.4%), and 66% (95% CI, 55.7% to 75.3%), respectively. Sensitivity for bacteria or fungi was 40% (95% CI, 28.0% to 52.9%) and 18.5% (95% CI, 9.9% to 30.0%), respectively. Conclusions: Pathogen detection by mNGS (DISQVER) during unselected FN episodes shows 2-fold higher sensitivity and a broader pathogen spectrum than BC.

Performance of the Euroimmun Aspergillus Antigen ELISA for the Diagnosis of Invasive Pulmonary Aspergillosis in Bronchoalveolar Lavage Fluid.

Invasive pulmonary aspergillosis (IPA) is a life-threatening disease that affects mainly immunocompromised hosts. Galactomannan testing from serum and bronchoalveolar lavage fluid (BALF) represents a cornerstone in diagnosing the disease. Here, we evaluated the diagnostic performance of the novel Aspergillus-specific galactomannoprotein (GP) enzyme-linked immunosorbent assay (ELISA; Euroimmun Medizinische Labordiagnostika) compared with the established Platelia Aspergillus GM ELISA (GM; Bio-Rad Laboratories) for the detection of Aspergillus antigen in BALF. Using the GP ELISA, we retrospectively tested 115 BALF samples from 115 patients with clinical suspicion of IPA and GM analysis ordered in clinical routine. Spearman's correlation statistics and receiver operating characteristics (ROC) curve analysis were performed. Optimal cutoff values were determined using Youden's index. Of 115 patients, 1 patient fulfilled criteria for proven IPA, 42 for probable IPA, 15 for putative IPA, 10 for possible IPA, and 47 did not meet criteria for IPA. Sensitivities and specificities for differentiating proven/probable/putative versus no IPA (possible excluded) were 74% and 96% for BALF GP and 90% and 96% for BALF GM at the manufacturer-recommended cutoffs. Using the calculated optimal cutoff value of 12 pg/mL, sensitivity and specificity of the BALF GP were 90% and 96%, respectively. ROC curve analysis showed an area under the curve (AUC) of 0.959 (95% confidence interval [CI] of 0.923 to 0.995) for the GP ELISA and an AUC of 0.960 (95% CI of 0.921 to 0.999) for the GM ELISA for differentiating proven/probable/putative IPA versus no IPA. Spearman's correlation analysis showed a strong correlation between the ELISAs (rho = 0.809, P < 0.0001). The GP ELISA demonstrated strong correlation and test performance similar to that of the GM ELISA and could serve as an alternative test for BALF from patients at risk for IPA.