Changing profile of encephalitis: Results of a 4-year study in France.

CONTEXT: In 2007, we performed a nationwide prospective study to assess the epidemiology of encephalitis in France. We aimed to evaluate epidemiological changes 10years later. METHODS: We performed a 4-year prospective cohort study in France (ENCEIF) from 2016 to 2019. Medical history, comorbidities, as well as clinical, biological, imaging, and demographic data were collected. For the comparison analysis, we selected similar data from adult patients enrolled in the 2007 study. We used Stata statistical software, version 15 (Stata Corp). Indicative variable distributions were compared using Pearson's Chi2 test, and means were compared using Student's t-test for continuous variables. RESULTS: We analyzed 494 cases from 62 hospitals. A causative agent was identified in 65.7% of cases. Viruses represented 81.8% of causative agents, Herpesviridae being the most frequent (63.6%). Arboviruses accounted for 10.8%. Bacteria and parasites were responsible for respectively 14.8% and 1.2% of documented cases. Zoonotic infections represented 21% of cases. When comparing ENCEIF with the 2007 cohort (222 adults patients from 59 hospitals), a higher proportion of etiologies were obtained in 2016-2019 (66% vs. 53%). Between 2007 and 2016-2019, the proportions of Herpes simplex virus and Listeria encephalitis cases remained similar, but the proportion of tuberculosis cases decreased (P=0.0001), while tick-borne encephalitis virus (P=0.01) and VZV cases (P=0.03) increased. In the 2016-2019 study, 32 causative agents were identified, whereas only 17 were identified in the 2007 study. CONCLUSION: Our results emphasize the need to regularly perform such studies to monitor the evolution of infectious encephalitis and to adapt guidelines.

Microscopic detection of bacillus Calmette-Guérin mycobacteria in bladder biopsy using fluorescence in situ hybridization: Détection microscopique des Bacilles biliés de Calmette et Guérin (BCG) dans une biopsie vésicale par hybridation in situ en fluorescence.

Intravesical instillation of Bacilli Calmette Guérin (BCG) as a superficial bladder cancer treatment is generally well tolerated, but local or systemic complications may occur, some of which may be life-threatening. Following the suspicion of post-BCG cystitis in a 72-year-old man with a history of urothelial carcinoma treated by intravesical BCG instillation, we used fluorescence in situ hybridization (FISH) targeting the rpoB gene of the Mycobacterium tuberculosis complex to detect Mycobacterium bovis BCG in paraffin-embedded bladder biopsy sections. FISH yielded specific detection of BCG mycobacteria in the bladder biopsy section, appearing as red-fluorescent bacilli. Treatment with rifampicin, ethambutol and isoniazid is then initiated in combination with corticosteroid therapy.

Factors associated with treatment failure after advice from infectious disease specialists.

OBJECTIVE: Risk factors associated with treatment failure after the infectious disease specialist's (IDS) advice remain unknown. We aimed to identify these risk factors. METHODS: We included patients hospitalized in our tertiary care center who consulted an infectious disease specialist between January 2013 and April 2015. Treatment failure was defined by a composite criterion: signs of sepsis beyond Day 3, ICU admission, or death. Treatment success was defined by the patient's sustained clinical improvement. RESULTS: A total of 240 IDS recommendations were made. Diagnosis was changed for 64 patients (26.7%) and 50 patients experienced treatment failure after the IDS advice. In multivariate analysis, compliance with the IDS advice was associated with a higher rate of success (OR=0.09, 95%CI [0.01-0.67]). Variables associated with treatment failure in the multivariate analysis were Charlson comorbidity score at admission (OR=1.24, 95%CI [1.03-1.50]), a history of infection or colonization with multidrug-resistant bacteria (OR=8.27, 95%CI [1.37-49.80]), and deterioration of the patient's status three days after the IDS advice (OR=12.50, 95%CI [3.16-49.46]). CONCLUSION: Reassessing IDS recommendations could be interesting for specific patients to further adapt and improve them.

[Multidrug-resistant tuberculosis: A management problem that weighs heavily on the University Hospitals of Strasbourg]. / Tuberculose multirésistante : une prise en charge qui pèse lourd aux hôpitaux universitaires de Strasbourg.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem with great regional disparities. The aim of this study was to describe the epidemiological, clinical, and therapeutics aspects of MDR-TB in Alsace, France. PATIENTS AND METHODS: A 10 years retrospective study, conducted for the years 2006 to 2016, of all MDR-TB cases diagnosed in Alsace and particularly in Strasbourg University Hospitals. RESULTS: We included 22 patients with MDR-TB of whom 90% originated from Eastern Europe, 13.6% had extensively-resistant strains, and 41% reported previously treated tuberculosis. Clinically, 86,4% had a pulmonary form of tuberculosis. The mean length of antibiotic treatment was 21 months with several changes of drugs because of severe side effects. The mean follow-up was 48 months, during which time 2 patients were lost from contact and the 20 remaining patients were cured. CONCLUSIONS: Management of MDR-TB is a real social and medical challenge. Our study shows that the therapeutic protocols used in the management of these patients lead to an unusually high rate of success despite the occurrence of several, sometimes severe, side effects.

[Mesenteric lymph node cavitation in celiac disease: Report of four cases and literature review]. / Le syndrome de cavitation ganglionnaire mésentérique, complication rare de la maladie cœliaque de l'adulte : à propos de quatre cas et revue de la littérature.

INTRODUCTION: Mesenteric lymph node cavitation is an exceptional complication of celiac disease. We report four original observations of this syndrome, completed by a literature review. DISCUSSION: The analysis of 38 cases showed that this complication occurred exclusively in adults, with a mean age at diagnosis of 54 years. It revealed the celiac disease in the majority of cases. Hyposplenism was almost systematically associated. The risk of lymphoma appeared higher, especially enteropathy-associated T-cell lymphoma. The prognosis was poor with nearly 50% mortality and seemed related to the clinical response to the gluten-free diet. CONCLUSION: The severity of this complication deserves to be known and should lead to its research in celiac patients, especially in cases diagnosed in adulthood or in case of refractory disease.

Bacillus Calmette-Guerin infection following intravesical instillation: Does the strain matter?

PURPOSE: Intravesical BCG is the standard treatment of non-muscle invasive bladder cancer. No difference has yet been reported in the safety profiles of the various BCG strains. METHODS: A nationwide multidisciplinary retrospective survey was conducted between January 2013 and December 2016 to identify cases of BCG infection and differentiate them based on the type of BCG strain used. RESULTS: Forty patients were identified (BCG RIVM 28; other strains 8; unknown 4). Patients treated with BCG RIVM were less severely ill, with fewer occurrences of septic shock (3.6% vs. 50%, P=0.003) and ICU admission (7.1% vs. 62.5%, P=0.003). A higher frequency of pulmonary miliaries (71.4% vs. 12.5%, P=0.005) but lower transaminase levels (mean AST 65 vs. 264 U/L, P=0.001) were observed in these patients. No difference in terms of recovery was reported. CONCLUSION: The type of BCG strain could correlate with the frequency and severity of subsequent BCG infections.

Correction to: Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

In the original version of this article, Mustafa Sunbul was not included in the list of authors for this article. The name has been added accordingly.

18F-FDG PET/CT for invasive fungal infection in immunocompromised patients.

BACKGROUND: Opportunistic invasive fungal infections (IFIs) comprise a heterogeneous spectrum of pathogens, whose early diagnosis remains challenging. Candida spp. and Aspergillus spp, the most frequent pathogens in immunocompromised patients, frequently affect lungs, liver, bone and skin. AIM: To evaluate the impact of 18F-FDG PET/CT in the management of immunocompromised patients with IFI. DESIGN: A single-center retrospective study included 51 immunocompromised patients with IFI diagnosis undergoing 83 18F-FDG PET/CTs. METHODS: Twenty-nine 18F-FDG PET/CTs were performed for primary work-up in 29 treatment-naïve patients. Fifty-four PET/CTs were performed during follow-up to confirm IFI suspicion in 22 patients who had anti-fungal drug therapy before PET/CT. When available, histological and/or microbiological criteria were used to assess IFI diagnosis. RESULTS: Aspergillus spp. and Candida spp. were the most frequent microorganisms responsible for IFI in our population. 18F-FDG PET/CT sensitivity, specificity, positive and negative predictive values, and global accuracy were 93%, 81%, 95%, 72% and 90%, respectively. 18F-FDG PET/CT influenced the diagnostic work-up at primary staging in 16/29 patients (55%) by assessing the extent of infection and targeting the diagnostic procedure. 18F-FDG PET/CT results during treatment induced anti-fungal drugs dosage increase and/or new drugs addition in 8/54 cases (15%) and contributed to the reduction of anti-fungal drugs dosage or treatment withdraws in 17 cases (31%). CONCLUSIONS: We recommend the utilization of 18F-FDG PET/CT to improve the primary staging work-up of immunocompromised patients with IFI and to assess treatment effectiveness or disease relapse. Both 18F-FDG PET/CT and conventional imaging should be integrated into a well-defined imaging diagnostic algorithm considering the clinical context and both strengths and limitations of each diagnostic modality.

Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter Infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

Cryptococcal meningitis (CM) is mostly seen in immunocompromised patients, particularly human immunodeficiency virus (HIV)-positive patients, but CM may also occur in apparently immunocompetent individuals. Outcome analyses have been performed in such patients but, due to the high prevalence of HIV infection worldwide, CM patients today may be admitted to hospitals with unknown HIV status, particularly in underdeveloped countries. The objective of this multicenter study was to analyze all types of CM cases in an aggregate cohort to disclose unfavorable outcomes. We retrospectively reviewed the hospitalized CM patients from 2000 to 2015 in 26 medical centers from 11 countries. Demographics, clinical, microbiological, radiological, therapeutic data, and outcomes were included. Death, neurological sequelae, or relapse were unfavorable outcomes. Seventy (43.8%) out of 160 study cases were identified as unfavorable and 104 (65%) were HIV infected. On multivariate analysis, the higher Glasgow Coma Scale (GCS) scores (p = 0.021), cerebrospinal fluid (CSF) leukocyte counts > 20 (p = 0.038), and higher CSF glucose levels (p = 0.048) were associated with favorable outcomes. On the other hand, malignancy (p = 0.026) was associated with poor outcomes. Although all CM patients require prompt and rational fungal management, those with significant risks for poor outcomes need to be closely monitored.

[Neurosyphilis: A retrospective study of 13 cases at Strasbourg University Hospital]. / La neurosyphilis, étude rétrospective de 13 cas survenus aux hôpitaux universitaires de Strasbourg.

OBJECTIVE: After a decade of constant decline, the number of syphilis cases has been steadily increasing since the 2000s, particularly in HIV infected patients. Neurosyphilis is a rare manifestation of this sexually transmitted disease for which we performed a retrospective study and analyzed clinical manifestations. PATIENTS AND METHODS: We reviewed retrospectively all the neurosyphilis cases admitted to Strasbourg University Hospital between 2004 and 2014. We included and analyzed 13 patients admitted during this period who met the diagnostic criteria for neurosyphilis. RESULTS: Nine of 13 patients had isolated visual manifestations; three (23.1%) experienced posterior uveitis, two (15.4%), panuveitis, and 4 (30.8%) had papillitis. Out of five patients (38.5%) who were HIV positive, three (60%) had a CD4 cell count above 400/mm3 at the time of diagnosis of neurosyphilis. All patients received parenteral penicillin G or cephalosporin, and 5/13 (38.5%) received systemic corticotherapy. CONCLUSION: Ophthalmologists appear as key players in the identification, management and follow-up of neurosyphilis, since ocular findings are key diagnostic features in these patients.

The burden and epidemiology of community-acquired central nervous system infections: a multinational study.

Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012 and 2014. A total of 2583 patients with CA-CNS infections were included from 37 referral centers in 20 countries. Of these, 477 (18.5%) patients survived with sequelae and 227 (8.8%) died, and 1879 (72.7%) patients were discharged with complete cure. The most frequent infecting pathogens in this study were Streptococcus pneumoniae (n = 206, 8%) and Mycobacterium tuberculosis (n = 152, 5.9%). Varicella zoster virus and Listeria were other common pathogens in the elderly. Although staphylococci and Listeria resulted in frequent infections in immunocompromised patients, cryptococci were leading pathogens in human immunodeficiency virus (HIV)-positive individuals. Among the patients with any proven etiology, 96 (8.9%) patients presented with clinical features of a chronic CNS disease. Neurosyphilis, neurobrucellosis, neuroborreliosis, and CNS tuberculosis had a predilection to present chronic courses. Listeria monocytogenes, Staphylococcus aureus, M. tuberculosis, and S. pneumoniae were the most fatal forms, while sequelae were significantly higher for herpes simplex virus type 1 (p < 0.05 for all). Tackling the high burden of CNS infections globally can only be achieved with effective pneumococcal immunization and strategies to eliminate tuberculosis, and more must be done to improve diagnostic capacity.

[Systemic lupus erythematosus and lymphopenia: Clinical and pathophysiological features]. / Lupus érythémateux systémique et lymphopénie : aspects cliniques et physiopathologiques.

Lymphopenia is frequent in systemic lupus erythematosus (SLE) and profound (<500/mm3) in 10% of cases. T lymphocytes, especially CD4+, are more affected than B cells. The pathophysiological mechanisms are complex, involving lymphocytotoxic antibodies, excess of apoptosis, increased susceptibility of T cells to complement mediated cytolysis, as well as lymphopoiesis impairment and lymphocyte sequestration. Lymphopenia in SLE is independent from other cytopenia and immunosuppressive drug regiments, and associated with disease activity, risk of flare and damage scores. Infectious risk is mostly bacterial, and lymphopenia <1 G/L is an independent risk factor for severe bacterial infections occurrence. The T cellular deficiency is associated with less control of viral replication, but severe and symptomatic infections are scarce. Although exceptional in SLE, pneumocystis is more severe than in HIV+ patients, and risk of progressive multifocal leukoencephalopathy seems increased compared to other rheumatic diseases. To date, there are no specific recommendations for management of SLE with lymphopenia. Infectious prophylaxis should remain exceptional and discussed on a case by case basis. Further studies are needed to assess the clinical characteristics and outcomes of patients with SLE and profound lymphopenia (<500/mm3), which are probably a subset of SLE with primary immunodeficiency and require specific management.

VISLISI trial, a prospective clinical study allowing identification of a new metalloprotease and putative virulence factor from Staphylococcus lugdunensis.

OBJECTIVE: Staphylococcus lugdunensis is a coagulase-negative staphylococcus that displays an unusually high virulence rate close to that of Staphylococcus aureus. It also shares phenotypic properties with S. aureus and several studies found putative virulence factors. The objective of the study was to describe the clinical manifestations of S. lugdunensis infections and investigate putative virulence factors. METHOD: We conducted a prospective study from November 2013 to March 2016 at the University Hospital of Strasbourg. Putative virulence factors were investigated by clumping factor detection, screening for proteolytic activity, and sequence analysis using tandem nano-liquid chromatography-mass spectrometry. RESULTS: In total, 347 positive samples for S. lugdunensis were collected, of which 129 (37.2%) were from confirmed cases of S. lugdunensis infection. Eighty-one of these 129 patients were included in the study. Bone and prosthetic joints (PJI) were the most frequent sites of infection (n=28; 34.6%) followed by skin and soft tissues (n=23; 28.4%). We identified and purified a novel protease secreted by 50 samples (61.7%), most frequently associated with samples from deep infections and PJI (pr 0.97 and pr 0.91, respectively). Protease peptide sequencing by nano-liquid chromatography-mass spectrometry revealed a novel protease bearing 62.42% identity with ShpI, a metalloprotease secreted by Staphylococcus hyicus. CONCLUSION: This study confirms the pathogenicity of S. lugdunensis, particularly in bone and PJI. We also identified a novel metalloprotease called lugdulysin that may contribute to virulence.