Probabilistic classification of anti-SARS-CoV-2 antibody responses improves seroprevalence estimates.

Objectives: Population-level measures of seropositivity are critical for understanding the epidemiology of an emerging pathogen, yet most antibody tests apply a strict cutoff for seropositivity that is not learnt in a data-driven manner, leading to uncertainty when classifying low-titer responses. To improve upon this, we evaluated cutoff-independent methods for their ability to assign likelihood of SARS-CoV-2 seropositivity to individual samples. Methods: Using robust ELISAs based on SARS-CoV-2 spike (S) and the receptor-binding domain (RBD), we profiled antibody responses in a group of SARS-CoV-2 PCR+ individuals (n = 138). Using these data, we trained probabilistic learners to assign likelihood of seropositivity to test samples of unknown serostatus (n = 5100), identifying a support vector machines-linear discriminant analysis learner (SVM-LDA) suited for this purpose. Results: In the training data from confirmed ancestral SARS-CoV-2 infections, 99% of participants had detectable anti-S and -RBD IgG in the circulation, with titers differing > 1000-fold between persons. In data of otherwise healthy individuals, 7.2% (n = 367) of samples were of uncertain serostatus, with values in the range of 3-6SD from the mean of pre-pandemic negative controls (n = 595). In contrast, SVM-LDA classified 6.4% (n = 328) of test samples as having a high likelihood (> 99% chance) of past infection, 4.5% (n = 230) to have a 50-99% likelihood, and 4.0% (n = 203) to have a 10-49% likelihood. As different probabilistic approaches were more consistent with each other than conventional SD-based methods, such tools allow for more statistically-sound seropositivity estimates in large cohorts. Conclusion: Probabilistic antibody testing frameworks can improve seropositivity estimates in populations with large titer variability.

99mTc-HMPAO-WBC SPECT/CT versus 18F-FDG-WBC PET/CT in chronic prosthetic joint infection: a pilot study.

PURPOSE: The aim of this study was to compare 99mTc-HMPAO-WBC-SPECT/CT combined with 99mTc-nanocollloid SPECT/CT and 18F-FDG-WBC-PET/CT combined with 99mTc-Nanocollloid SPECT/CT for the diagnosis and treatment evaluation of chronic prosthetic joint infection (PJI). METHODS: Patients with suspected chronic PJI were examined with 99mTc-HMPAO-WBC SPECT/CT, 18F-FDG-WBC PET/CT, and 99mTc-nanocolloid SPECT/CT (to visualize bone marrow). The location and patterns of uptake were noted and compared between the two leukocyte examinations. Both leukocyte examinations were evaluated visually for infection. The PET examinations were also evaluated semiquantitatively. Chronic PJI was verified clinically by microbial culture and successfully treated PJI was confirmed by 12 months symptom-free follow-up after cessation of antibiotics. RESULTS: Nineteen patients were included with 10 hip prostheses and nine knee prostheses. Fourteen were diagnosed with chronic PJI and five with successfully treated PJI. The sensitivity of visual evaluation of 99mTc-WBC-HMPAO SPECT/CT for all joints was 0.31 and for 18F-FDG-WBC PET/CT 0.38. The specificity was 0.80 and 0.83, respectively. All patients with a true-positive SPECT examination had a false-negative PET examination and vice versa. Semiquantitative evaluation of the hips gave an area under the curve of 0.905 using the iliac crest as the background. Semiquantitative evaluation of the knees did not produce significant results. CONCLUSION: This pilot study showed no difference in the sensitivity or specificity of 99mTc-HMPAO-WBC SPECT/CT and 18F-FDG-WBC PET/CT when combined with 99mTc-nanocollloid SPECT/CT in the diagnosis or treatment evaluation of suspected late chronic PJI.

Dual-tracer approach vs. dual time-point approach in leukocyte scintigraphy in treatment evaluation of persistent chronic prosthetic joint infection.

BACKGROUND: Both dual time-point 99mTc-hexamethylpropylene amine oxime (HMPAO)-leukocyte scintigraphy and dual-tracer 99mTc-HMPAO-leukocyte scintigraphy (with the addition of 99mTc-nanocolloid bone marrow scintigraphy) have been used to diagnose prosthetic joint infection (PJI). A treatment evaluation of persistent PJI using these imaging protocols has yet to be presented. OBJECTIVE: The purpose of this study was to compare the accuracy of dual time-point 99mTc-HMPAO-leukocyte scintigraphy to the dual-tracer alternative of single time-point 99mTc-HMPAO-leukocyte scintigraphy or single-photon emission computed tomography/computed tomography (SPECT/CT) combined with a 99mTc-nanocolloid bone marrow scintigraphy or SPECT/CT, for treatment evaluation of PJI. MATERIAL AND METHODS: Thirty-one PJI patients under antibiotic treatment were included in this retrospective study. Examinations were organized into three settings. Setting one used dual time-point approach with delayed (2 h) and late (24 h) planar 99mTc-HMPAO-leukocyte scintigraphy, including both visual and semiquantitative analysis. Setting two used delayed (2 h) planar 99mTc-HMPAO-leukocyte scintigraphy combined with 99mTc-nanocolloid bone marrow scintigraphy and for setting three SPECT/CT replaced planar imaging. RESULTS: Accuracy was 0.68 for visual evaluation and 0.55 for semiquantitative evaluation of setting one; 0.71 for setting two; and 0.68 for setting three. Sensitivity was 0.54 for visual evaluation and 0.31 for semiquantitative evaluation of setting one; 0.38 for setting two; and 0.46 for setting three. Specificity was 0.78 for visual evaluation and 0.72 for semiquantitative evaluation of setting one; 0.94 for setting two; and 0.83 for setting three. CONCLUSION: No significant difference in accuracy, sensitivity, or specificity between the approaches for treatment evaluation of suspected persistent PJI in the hip or knee was observed.

Is 99mTc-HMPAO-leukocyte imaging an accurate method in evaluating therapy result in prosthetic joint infection and diagnosing suspected chronic prosthetic joint infection?

BACKGROUND: To investigate the sensitivity and specificity of 99mTc-HMPAO-leukocyte imaging in evaluating therapy result in patients with prosthetic joint infection (PJI) and in diagnosing suspected chronic PJI. METHODS: Sixty-two patients (63 joints) with microbiologically verified PJI were examined by leukocyte imaging to evaluate therapy result during or at the end of antibiotic treatment or if the patient had a chronic PJI after treatment. Group 1 consisted of 49 patients with on-going or within less than 14 days of ending antibiotic treatment examined to evaluate response. Group 2 consisted of 13 patients examined after completed treatment on suspicion of chronic PJI with no or recently initiated renewed antibiotic treatment. This study applied a combination of different imaging approaches of 99mTc-HMPAO-leukocyte scintigraphy: delayed and late planar images, bone marrow imaging and SPECT/CT imaging. All joints were examined with at least two of the approaches and 53 joints with all three approaches. The report was based on the combined results of the approaches used. A chronic PJI was confirmed with a positive microbiological culture. A cured infection was confirmed with either a negative culture or at least 24 months antibiotic-free follow-up with no relapse. RESULTS: In the therapy evaluation group sensitivity was 0.57 and specificity was 0.81. In the suspected chronic infection group sensitivity was 1.00 and specificity 0.91. CONCLUSIONS: 99mTc-HMPAO-leukocyte imaging appears to be an accurate method to diagnose or exclude chronic PJI, but cannot be recommended for therapy evaluation of PJI in patients with on-going antibiotic treatment.

Secondary bacterial infections in patients with seasonal influenza A and pandemic H1N1.

The aim of the present study is to analyse the secondary bacterial infections in a large group of patients with seasonal influenza A and influenza A(H1N1) pdm09. Patients diagnosed with seasonal influenza A and influenza A(H1N1) pdm09 between 2005 and 2009 were enrolled in the study. Data was retrieved from medical records and laboratory information systems (LIS). In total, 1094 patients with laboratory confirmed influenza were studied. There were 352 patients with seasonal influenza A and 742 patients with influenza A(H1N1) pdm09. The patients with influenza A were older and had higher comorbidity than patients with influenza A(H1N1) pdm09 (P < 0.001 and P < 0.05, resp.). Hospital admission was higher in influenza A group (P = 0.01). In contrast, ICU admission was higher in patients with influenza A(H1N1) pdm09 than influenza A patients (P < 0.05). There were higher numbers of bacterial samples taken and culture positivity in patients with influenza A than patients with influenza A(H1N1) pdm09 (P < 0.0001 and P = 0.01, resp.). In both groups, the majority of the patients with positive bacterial cultures had underlying diseases. The present study shows that the patient characteristics and the frequency of secondary bacterial infections were different in patients with seasonal influenza A and in patients with influenza A(H1N1) pdm09.