Spinal cord involvement in progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infectious demyelinating disease of the central nervous system caused by JC polyomavirus predominantly affecting immunocompromised individuals. Nowadays, HIV, hematological malignancies and iatrogenic immune suppression account for most PML cases. For unknown reasons, spinal cord is classically protected from PML lesions. Here, we report the course of a patient harboring spinal cord lesions in the context of PML with immune reconstitution inflammatory syndrome and review the eight other cases reported in the literature so far. Then, we discuss the evolving spectrum of PML over recent years, potentially making its diagnosis more challenging.

[Evaluation of the knowledge on alveolar echinococcosis among general practitioners in the province of Liege : impact of a formative intervention]. / Évaluation des connaissances de l'échinococcose alvéolaire réalisée auprès des médecins généralistes de la Province de Liège : impact d'une intervention formative.

Alveolar echinococcosis is an indigenouszoonosis caused by the growth of the larval stage of a small tapeworm, Echinococcus multilocularis. Despite a low incidence in Belgium, with about 10 cases on average recorded per year, this parasitosis poses a real public health problem because it often remains difficult to diagnose and is potentially fatal in the absence of treatment. General practitioners are on the frontline, but they do not always know enough about the disease, which causes a delay in the diagnosis and impacts the prognosis. The present study aims to assess the level of knowledge of alveolar echinococcosis among general practitioners in the province of Liège via a questionnaire, on the one hand, and to increase their level of knowledge via a formative intervention using a video capsule, on the other hand. We have performed a randomized controlled experimental study, which showed that general practitioners in the province of Liège have limited knowledge on alveolar echinococcosis. This mainly concerns symptomatology, diagnostic tools and treatment. The formative intervention carried out allowed increasing their level of knowledge about this disease.

L'échinococcose alvéolaire est une zoonose autochtone provoquée par le développement tissulaire de la larve d'un petit ténia, Echinoccocus multilocularis. Malgré une faible incidence en Belgique, avec une moyenne de 10 cas recensés par an, cette parasitose pose un réel problème de santé publique car elle reste souvent difficile à diagnostiquer et potentiellement mortelle en l'absence de traitement. Les médecins généralistes sont en première ligne, mais ils ne connaissent pas toujours suffisamment la maladie, ce qui retarde le diagnostic et compromet le pronostic. La présente étude visait à évaluer les connaissances à propos de l'échinococcose alvéolaire des médecins généralistes de la province de Liège via un questionnaire approprié et à accroître leur niveau de connaissance via une intervention formative sous forme de capsule vidéo. Nous avons réalisé une étude à visée expérimentale randomisée contrôlée qui a montré que les médecins généralistes de la province de Liège ont des connaissances partielles sur la symptomatologie, les outils de diagnostic et le traitement. L'intervention formative réalisée a permis d'augmenter leur niveau de connaissances à propos de cette maladie.

Transmission of SARS-CoV-2 After COVID-19 Screening and Mitigation Measures for Primary School Children Attending School in Liège, Belgium.

Importance: Recent data suggest a relatively low incidence of COVID-19 among children. The possible role that children attending primary school may play in the transmission of SARS-CoV-2 remains poorly understood. Objective: To gain a better understanding of the possible role of children in the transmission of SARS-CoV-2. Design, Setting, and Participants: This prospective cohort study was conducted from September 21 to December 31, 2020, in a primary school in Liège, Belgium, among a volunteer sample of 181 children, parents, and school employees. Exposures: Participants were tested for SARS-CoV-2 infection once a week for 15 weeks through throat washing, performed with 5 mL of saline and collected in a sterile tube after approximately 30 seconds of gargling. Quantitative reverse transcription-polymerase chain reaction was performed to detect SARS-CoV-2 infection. Main Outcomes and Measures: In case of test positivity, participants were asked to complete a questionnaire aimed at determining the timing of symptom onset and symptom duration. SARS-CoV-2 genetic sequencing was also performed. Confirmed cases were linked based on available information on known contacts and viral sequences. Results: A total of 181 individuals participated in this study, including 63 children (34 girls [54.0%]; mean [SD] age, 8.6 [1.9] years [range, 5-13 years]) and 118 adults (75 women [63.6%]; mean [SD] age, 42.5 [5.7] years [range, 30-59 years]). Forty-five individuals (24.9%) tested positive: 13 children (20.6%; 95% CI, 10.6%-30.6%) and 32 adults (27.1%; 95% CI, 19.1%-35.7%) (P = .34). Children were more often asymptomatic compared with adults (6 [46.2%; 95% CI, 19.1%-73.3%] vs 4 of 31 [12.9%; 95% CI, 1.3%-24.5%]; P = .04). The median duration of symptoms was shorter in children than in adults (0.00 days [IQR, 0.00-1.00 days] vs 15.00 days [IQR, 7.00-22.00 days]). A reconstruction of the outbreak revealed that most transmission events occurred between teachers and between children within the school. Of the observed household transmission events, most seemed to have originated from a child or teacher who acquired the infection at school. Conclusions and Relevance: Despite the implementation of several mitigation measures, the incidence of COVID-19 among children attending primary school in this study was comparable to that observed among teachers and parents. Transmission tree reconstruction suggests that most transmission events originated from within the school. Additional measures should be considered to reduce the transmission of SARS-CoV-2 at school, including intensified testing.

Evolution of Drug Interactions With Antiretroviral Medication in People With HIV.

BACKGROUND: Polypharmacy and drug interactions are important issues for HIV-infected individuals. The number and nature of those interactions are continuously evolving with the use of new antiretroviral drugs and the aging of HIV-infected individuals. We aimed to analyze this evolution over time. METHODS: This retrospective cohort study was conducted in the University Hospital of Liège (Belgium). Treatments of HIV-infected outpatients attending Liège University Hospital were collected and analyzed in 2012 and 2016. The University of Liverpool HIV drug interactions database was used to determine drug interactions. RESULTS: We included 1038 patients in 2016, of whom 78% had 1 comedication. Polypharmacy was seen in 20% of the cohort. Four percent of the patients presented red flag interactions, and 38% had orange flag interactions. Nonantiretroviral (non-ARV) therapeutic classes involved in drug interactions were mostly cardiovascular and central nervous system drugs. They were followed by hormone drugs and dietary supplements for orange flag interactions. Two factors significantly contributed to both red and orange flag interactions: the number of non-ARV comedications and protease inhibitor-based ARV regimens. The proportion of patients with red or orange flag interactions remained stable from 2012 to 2016. CONCLUSIONS: This study highlights the persistence of an alarming number of contraindicated drug interactions and a high prevalence of potential drug interactions over time. Identification, prevention, and management of drug interactions remain a key priority in HIV care.

Recurrence of visceral and muco-cutaneous leishmaniasis in a patient under immunosuppressive therapy.

BACKGROUND: Leishmaniasis is a protozoan disease caused by parasites of the genus Leishmania, transmitted to humans by sandflies. The diagnosis of leishmaniasis is often challenging as it mimics many other infectious or malignant diseases. The disease can present in three ways: cutaneous, mucocutaneous, or visceral leishmaniasis, which rarely occur together or consecutively. CASE PRESENTATION: The patient was a 52 years old immunosuppressed Belgian woman with a long history of severe rheumatoid arthritis. She underwent bone marrow biopsy to explore thrombocytopenia. Diagnosis of visceral leishmaniasis was made by identification of Leishman Donovan (LD) bodies in macrophages. Treatment with liposomal amphotericin B was successful. She later developed cutaneous leishmaniasis treated with amphotericin B lipid complex. She next presented with relapsing cutaneous lesions followed by rapidly progressing lymphadenopathies. Biopsy confirmed the diagnosis of leishmaniasis. Treatments by miltefosine, amphotericin B, N-methyl-glucamine antimoniate were subsequently initiated. She later presented a recurrent bone marrow involvement treated with intramuscular paromomycin and miltefosine. She died two years later from leukemia. At the time of death, she presented with a mucosal destruction of the nose. A Leishmania-specific PCR (Polymerase Chain Reaction) identified L. infantum as etiological agent. CONCLUSIONS: Clinicians should be aware of the potential concomitant or sequential involvement of multiple anatomic localizations of Leishmania in immunosuppressed patients.

One-stage exchange arthroplasty for chronic periprosthetic hip infection: results of a large prospective cohort study.

BACKGROUND: Exchange arthroplasty of one or two stages is required for the treatment of chronic periprosthetic joint infections. Two-stage exchange is costly and has high morbidity with limited patient mobility between procedures. One-stage exchange has been promoted by several European teams as the preferred alternative. The aim of this study was to prospectively analyze the outcome of patients with a periprosthetic hip infection treated with one-stage exchange arthroplasty. METHODS: We performed a prospective cohort study in a French referral center for osteoarticular infections including all periprosthetic hip infections treated with one-stage exchange arthroplasty from November 2002 to March 2010. Direct exchange was performed in chronic periprosthetic hip infection with no or minor bone loss and preoperative identification of a microorganism from joint fluid aspirate. No antibiotic-loaded bone cement was used. Antibiotic therapy was administered for twelve weeks: intravenously for four to six weeks, followed by an oral regimen for six to eight weeks. Follow-up was a minimum of two years. The following events were noted: relapse, new infection, joint revision for mechanical reasons, and periprosthetic hip infection-related and unrelated deaths. RESULTS: One hundred and fifty-seven patients with periprosthetic hip infections with a median infection duration of 258 days (interquartile range, 120 to 551 days) prior to our index surgical procedure for infection were included. Periprosthetic hip infection occurred in ninety-nine cases of primary hip arthroplasty, twenty-seven cases of revision arthroplasty, and thirty-one cases in which the periprosthetic hip infection had been treated previously. A difficult-to-treat organism was isolated in fifty-nine cases (38%). After a median follow-up of 41.6 months (interquartile range, 28.1 to 66.9 months), two relapses, six new infections, nine revisions for mechanical reasons, two related deaths, and nineteen unrelated deaths occurred. CONCLUSIONS: One-stage exchange arthroplasty is an effective surgical procedure in patients with periprosthetic hip infection who have good bone quality. Precise identification of the microorganism(s) and prolonged administration of appropriate intravenous antibiotic therapy are key factors for successful treatment.

Monitoring the one year postoperative infection rate after primary total hip replacement.

PURPOSE: Infection of a total hip replacement is potentially a devastating complication. Statistical process control methods have been generating interest as a means of improving the quality of healthcare, and we report our experience with the implementation of such a method to monitor the one year infection rate after primary total hip replacement. METHOD: Infection was defined as the growth of the same organism in cultures of at least two aspirates or intra-operative specimens, or growth of one pathogen in a patient with local signs of infection such as erythema, abscess or draining sinus tract. The cumulative summation test (CUSUM test) was used to continuously monitor the one year postoperative infection rate. The target performance was 0.5% and the test was set to detect twice that rate. RESULTS: Over the three year study period, 2006 primary total hip replacements were performed. Infection developed within one year after surgery in eight (0.4%) hips. The CUSUM test generated no alarms during the study period, indicating that there was no evidence that the process was out of control. CONCLUSION: The one year infection rate after primary total hip replacement was in control. The CUSUM test is a useful method to continuously ensure that performance is maintained at an adequate level.

Autoimmune angioneurotic edema in a patient with Helicobacter pylori infection.

Association of acquired autoimmune angioneurotic edema with other diseases is increasing. However, the precise mechanism by which antibodies to C1-esterase inhibitor (C1-INH) are produced, is not elucidated. We describe a patient with IgA antibodies against C1-INH without other autoimmune markers. Our patient had gastritis and Helicobacter pylori infection, proven by biopsy. This case suggests that H. pylori infection can act as triggering factor for acquired autoimmune angioneurotic edema.

Dislocation after total hip arthroplasty using Hueter anterior approach.

A prospective study including 1764 hips has been carried out to evaluate the frequency of dislocation while using the Hueter anterior approach and the correlated factors. The dislocation group was compared with the patients without dislocation. We observed 27 dislocations (1.5%). The dislocation rate when using 28 mm head diameter was 0.5%. Two patients underwent a revision for recurrent dislocations. Correlated factors for dislocation were male sex, high body mass index, etiology of osteonecrosis, low head diameter, high bleeding, and low postoperative ROM. Dislocation risk while using Hueter approach is one of the lowest in the literature. The main disadvantages are the necessity for a specific orthopedic table and a more difficult exposure of the femur.

Downregulation of CD94/NKG2A inhibitory receptors on CD8+ T cells in HIV infection is more pronounced in subjects with detected viral load than in their aviraemic counterparts.

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated CD8+ T lymphocytes. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In this study, CD94/NKG2A receptor expression on CD8+ T lymphocytes and NK cells was assessed in 46 HIV-1-infected patients (24 viraemic, 22 aviraemic) and 10 healthy volunteers. The percentage of CD8+ T lymphocytes expressing the CD94/NKG2A inhibitory heterodimer was very significantly decreased in HIV-1-infected patients in comparison with non-infected controls. Within the HIV infected patients, the proportion of CD8+ T lymphocytes and NK cells expressing CD94/NKG2A was higher in subjects with undetectable viral loads in comparison with their viraemic counterparts. No significant difference was detected in the proportion of CD8+ T lymphocytes expressing the activatory CD94/NKG2C heterodimer between the HIV-1 infected patients and the healthy donors, nor between the vireamic and avireamic HIV-1 infected patients. In conclusion, chronic stimulation with HIV antigens in viraemic patients leads to a decreased rather than increased CD94/NKG2A expression on CD8+ T lymphocytes and NK cells.

Phase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults.

Two double-blind randomised controlled studies (phase I and I/II) were performed to assess for the first time the safety and immunogenicity of a recombinant subunit gp350 Epstein-Barr virus (EBV) vaccine in 148 healthy adult volunteers. All candidate vaccine formulations had a good safety profile and were well tolerated, with the incidence of solicited and unsolicited symptoms within a clinically acceptable range. One serious adverse event was reported in the phase I trial which was considered to be of suspected relationship to vaccination. The gp350 vaccine formulations were immunogenic and induced gp350-specific antibody responses (including neutralising antibodies).

Propionibacterium acnes: an agent of prosthetic joint infection and colonization.

BACKGROUND: Prosthetic joint infection (PJI) can present a diagnostic challenge, especially with slow-growing and poorly virulent bacteria. OBJECTIVE: To describe the epidemiological, clinical and biological characteristics of Propionibacterium acnes PJI, their treatments and outcomes and compare 2 clinical pictures (according to the time PJI symptoms appeared after the index operation: < or = 2 years, > 2 years). METHODS: We conducted a cohort study on P. acnes PJI. Diagnosis was based on > or = 2 positive cultures of intraoperative specimens taken during revision arthroplasties for infection or presumed aseptic loosening. RESULTS: Fifty patients with prosthetic hip (34), knee (10) or shoulder (6) infections were included and analyzed according to their symptom-free interval: < or = 2 years for 35 and > 2 years for 15 (mean interval: 11+/-6 years). The numbers of previous prostheses (p=0.04) were higher for the shorter-interval group, which had more frequent signs of infection (p=0.004). These findings suggest infection in most of the patients whose PJI symptoms appeared: < or = 2 years after the index operation, and colonization in the majority of those whose symptoms appeared > 2 years after index surgery. Treatment combining exchange arthroplasty with prolonged intravenous antibiotics was successful for 92% of the patients. CONCLUSION: P. acnes can cause different types of PJI: late chronic infections, colonization of loosened prostheses and, exceptionally, acute postoperative infections.

Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults.

BACKGROUND: To date, there is no commercially available vaccine to prevent infectious mononucleosis, a disease frequently induced by Epstein-Barr virus (EBV) infection in adolescents or adults devoid of preexisting immunity to the virus. METHODS: A total of 181 EBV-seronegative, healthy, young adult volunteers were randomized in a double-blind fashion to receive either placebo or a recombinant EBV subunit glycoprotein 350 (gp350)/aluminum hydroxide and 3-O-desacyl-4'-monophosphoryl lipid A (AS04) candidate vaccine in a 3-dose regimen. RESULTS: The vaccine had demonstrable efficacy (mean efficacy rate, 78.0% [95% confidence interval {CI}, 1.0%-96.0%]) in preventing the development of infectious mononucleosis induced by EBV infection, but it had no efficacy in preventing asymptomatic EBV infection. One month after receipt of the final dose of gp350 vaccine, 98.7% of subjects showed seroconversion to anti-gp350 antibodies (95% CI, 85.5%-97.9%), and they remained anti-gp350 antibody positive for >18 months. Furthermore, there were no concerns regarding the safety or reactogenicity of the gp350/AS04 vaccine. CONCLUSION: These data support the clinical feasibility of using an EBV vaccine to prevent infectious mononucleosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00430534.

Contribution of routine joint aspiration to the diagnosis of infection before hip revision surgery.

OBJECTIVES: To define the sensitivity and specificity of routine preoperative hip aspiration for diagnosing hip prosthesis infection (HPI) and to separately analyze subgroups with and without a clinical suspicion of HPI before aspiration. METHODS: From June 1994 to June 1997, all patients scheduled for hip revision surgery underwent aspiration of the hip under image intensifier guidance. Microbiological results were compared between these preoperative specimens and the intraoperative specimens. The reason for surgery was either a clinical suspicion of HPI or pain suggesting loosening. RESULTS: The study patients had had multiple surgical procedures. HPI was suspected clinically in 39.4% of cases. Of the 109 patients who underwent aspiration, 54 had true-negative results, nine had false-negative results, and 44 had true-positive results (there were no false-positive results), yielding a sensitivity of 83% and a specificity of 100%. Diagnostic efficiency was 91.6%, positive predictive value was 100%, and negative predictive value was 85.7%. In the subset of 43 patients with a clinical suspicion of HPI, aspiration identified all the causative organisms in 60.5% of cases. Of the 66 patients with no clinical suspicion of HPI, 12 had HPI, and aspiration provided the diagnosis preoperatively in seven of these patients, radically changing their management plans. Restricting routine aspiration to patients whose prosthesis had been implanted within the last 5 years or whose erythrocyte sedimentation rate (ESR) was above 30 mm/h would not have modified our findings. CONCLUSIONS: Hip aspiration before revision surgery for pain is effective in detecting HPI, which can simulate aseptic loosening. However, this investigation may be noncontributive in patients who have had their prosthesis for more than 5 years and whose ESR is less than 30 mm/h.