[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.

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.

Feedback on difficulties raised by the interpretation of serological tests for the diagnosis of Lyme disease.

OBJECTIVES: We had for objectives: i) to evaluate the accuracy of serologic testing for Lyme borreliosis performed in a private medical laboratory (PML); ii) to evaluate the impact of these tests on the practices of infectious diseases specialists (IDS). PATIENTS AND METHOD: This study was performed in two steps: i) retrospective study of patients followed in a university hospital infectious diseases outpatient clinic for suspected Lyme borreliosis, tested (ELISA and Western blot) by both the PML and the National Reference Center (NRC); ii) national survey on IDS practices concerning patients consulting for suspected Lyme borreliosis. RESULTS: Between July 2008 and July 2011, 128 patients consulting for suspected Lyme borreliosis were tested by both laboratories. Serological tests came back positive in 91% of cases from the PML versus 8% of cases from the NRC. Lyme borreliosis was the IDS's final diagnosis for 3.6% of patients. The survey on practices revealed that: i) the modal duration of consultation for suspected Lyme borreliosis was 30-60 minutes; ii) for 33% of patients, serologic test results performed at the PML were the only reason to suspect Lyme borreliosis; iii) 60% of patients had no indication for antibiotics. CONCLUSION: The serological test performed in the PML were positive most of the time, but were not confirmed by tests performed at the NRC. This discrepancy lead to multiple and prolonged consultations in infectious diseases clinics, and discordance in the indications for antibiotics.

Mutations in SDCCAG8/NPHP10 Cause Bardet-Biedl Syndrome and Are Associated with Penetrant Renal Disease and Absent Polydactyly.

The ciliopathies are an expanding group of disorders caused by mutations in genes implicated in the biogenesis and function of primary cilia. Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by progressive retinal degeneration, obesity, polydactyly, cognitive impairment, kidney anomalies and hypogonadism. Mutations in SDCCAG8(NPHP10) were described recently in patients with nephronophthisis and retinal degeneration (Senior-Loken syndrome; SLS). Given the phenotypic and genetic overlap between known ciliopathy genes, we hypothesized that mutations in SDCCAG8 might also contribute alleles to more severe, multisystemic ciliopathies. We performed genetic and phenotypic analyses of 2 independent BBS cohorts. Subsequent to mutation screening, we made a detailed phenotypic analysis of 5 families mutated for SDCCAG8 (3 homozygous and 2 compound heterozygous mutations) and conducted statistical analyses across both cohorts to examine possible phenotype-genotype correlations with mutations at this locus. All patients with mutations in SDCCAG8 fulfilled the diagnostic criteria for BBS (retinal degeneration, obesity, cognitive defects, renal failure, hypogonadism). Interestingly, none of the patients with primary SDCCAG8 mutations had polydactyly, a frequent but not obligatory BBS feature. In contrast, the same patients displayed early-onset renal failure, obesity, as well as recurrent pulmonary and ENT infections. Comparison of the phenotypes of these families with our entire BBS cohort indicated that renal impairment and absent polydactyly correlated significantly with causal SDCCAG8 mutations. Thus, SDCCAG8 mutations are sufficient to cause BBS in 1-2% of our combined cohorts, and define this gene as the sixteenth BBS locus (BBS16). The absence of polydactyly and the concomitant, apparently fully penetrant association with early kidney failure represents the first significant genotype-phenotype correlation in BBS that potentially represents an indicator for phenotype-driven priority screening and informs specific patient management.

Hippocampal dysgenesis and variable neuropsychiatric phenotypes in patients with Bardet-Biedl syndrome underline complex CNS impact of primary cilia.

The Bardet-Biedl syndrome (BBS) is a rare ciliopathy clinically defined by the association of retinitis pigmentosa, polydactyly, obesity, kidney disease and cognitive impairment. The cognitive functioning, behavioral phenotype, prevalence of psychiatric diseases and memory performances of a cohort of 34 patients with BBS were evaluated and a systemic brain magnetic resonance imaging (MRI) was performed. The patients' cognitive functioning was of marked variable efficiency ranging from normal to disabling performances. Neuropsychological disorders such as slow thought process, attention difficulties and obsessive-compulsive traits were observed. Our main finding was hippocampal dysgenesis, diagnosed by MRI, found in 42.31% of the patients in this cohort. Moreover, we show that BBS proteins are expressed in the human hippocampus and in the human brain in the normal subject. Recent literature in the murine model shows that hippocampal neurogenesis, in particular in the adult mouse, requires an intact primary cilia. These results encourage us to further investigate the possible role of BBS proteins in the hippocampus and related central nervous system structures.

[Management of a scabies epidemic in the Strasbourg teaching hospital, France]. / Gestion d'une épidémie de gale aux Hôpitaux universitaires de Strasbourg.

CONTEXT: An outbreak of scabies occurred in the geriatric department of the Strasbourg University Hospital in September 2005. The index case presented with hyperkeratosic scabies, an extremely contagious form. The epidemic spread to several wards and pavilions and also contaminated healthcare staff and patient's families. OBJECTIVE: Our objective was to describe the outbreak, its progression, and the measures taken to eradicate it. METHODOLOGY: All healthcare workers, patients, and families affected in the outbreak were retrospectively studied, using medical prescriptions recorded by the hospital pharmacy, listings established by the occupational health department, and patient files. RESULTS: Two epidemic waves were recorded, between August 31 and December 16, 2005, affecting 51 patients and staff members in the geriatric department, with a total of 58 episodes of scabies, seven of which were recurrences. Three main measures were taken to eradicate the epidemic: setting up of "contact" isolation precautions, information for the affected individuals, and treatment of the infected patients associated to mass treatment of contact cases. The mass treatment was widely applied, involving 490 patients and 592 caregivers. All of these measures successfully curtailed the outbreak in 3 months. CONCLUSION: Rapid and radical action is essential to prevent extension of scabies within a community.

Osteosclerotic bone dysplasia in siblings with a Fam20C mutation.

Raine syndrome is an autosomal recessive disorder caused by mutations in the FAM20C gene. FAM20C codes for the human homolog of DMP4, a dentin matrix protein highly expressed in odontoblasts and moderately in bone. DMP4 is probably playing a role in the mineralization process. Since the first case reported in 1989 by Raine et al. 21 cases have been published delineating a phenotype which associates dysmorphic features, cerebral calcifications, choanal atresia or stenosis and thoracic/pulmonary hypoplasia. Kan and Kozlowski suggested the name of Raine syndrome to describe this new lethal osteosclerotic bone dysplasia. All the cases described were lethal during the neonatal period except for the last two reported patients aged 8 and 11 years who presented severe mental retardation. Here we describe two sisters, with an attenuated phenotype of Raine syndrome, who present an unexpectedly normal psychomotor development at ages 4 and 1, respectively. Identification of a homozygous mutation in the FAM20C gene confirmed the Raine syndrome diagnosis, thus contributing to the expansion of the Raine syndrome phenotype. This case report also prompted us to revisit the FAM20 gene classification and allowed us to highlight the ancestral status of Fam20C.

[Inadequate vaccination coverage in a French cohort of HIV positive patients]. / Insuffisance de couverture vaccinale d'une cohorte française de patients séropositifs VIH.

INTRODUCTION: HIV patients have a high rate of infectious complications. Vaccination, though less efficient in case of severe immunosuppression, can prevent some of these infections. Since 2006, new vaccine recommendations have been elaborated in France. We studied the vaccine status of HIV+ patients for influenza, Streptococcus pneumoniae, tetanus, and hepatitis A and B among an alsatian HIV+ population. PATIENTS AND METHODS: From August 20, 2007 to September 15, 2007, HIV patients of the Alsace HIV center (COREVIH) were included in a prospective study, screening demographic, medical, immunovirological, and vaccination data. RESULTS: Three hundred and thirty-one patients were included, 49% of whom were asymptomatic, 29% symptomatic without AIDS, 18% at AIDS stage, and no documentation for 4%. Seventy-one patients (21.4%) were vaccinated against influenza, 11 (3.3%) against Streptococcus pneumoniae, 34 against HAV (only 16.3% of patients with a negative test before), 120 against HBV (60% of patients with no serological markers before), and 186 (56.2%) against tetanus. The most frequent reasons for non-vaccination were non-proposal by physicians, lack of expected effectiveness, and fear of an immunovirological adverse effect. CONCLUSION: Vaccination coverage for recommended vaccines of HIV infected people remains at a low level and appears sometimes inferior to the rates reached among the general French population. It is necessary to inform prescribers and HIV positive patients about the interest of vaccination.

[Hereditary hemorragic telangiectasia and hepatic abcess]. / Maladie de Rendu-Osler et abcès hépatique.

We report the case of a 27-year-old man presenting with a hepatic abscess and hereditary hemorrhagic telangiectasia (HHT). The association between HHT and an infectious disease seemed to be induced by arteriovenous malformations and maybe also by a deficit of polymorphonuclear cells, a monocyte oxidative burst and phagocytosis. This diagnosis should be suggested in case of serious infections in young patients. Prevention is based on screening for and destroying infection, antibioprophylaxis and embolization of arteriovenous malformations.

Value of (18)F-FDG-PET/CT in patients with fever of unknown origin and unexplained prolonged inflammatory syndrome: a single centre analysis experience.

OBJECTIVE: The aim of our study was to evaluate the diagnostic contribution of (18)F-fluoro-deoxyglucose ((18)F-FDG)-positron emission tomography (PET)/computed tomography (CT) in patients with fever of unknown origin (FUO) or unexplained prolonged inflammatory syndrome (UPIS) in real life. PATIENTS AND METHODS: We performed a retrospective study including 14 patients with FUO or UPIS hospitalised in our institution (Strasbourg University Hospital, France) between January 2005 and July 2006. (18)F-FDG-PET/CT was considered helpful when abnormal results allowed an accurate diagnosis. RESULTS: (18)F-FDG-PET/CT was helpful in half the patients (7/14) for final diagnosis. A diagnosis was reached in 87.5% of the patients (7/8) with an abnormal (18)F-FDG-PET/CT but only in 50% of the patients (3/6) with a normal (18)F-FDG-PET/CT. Conventional chest and abdominal CT was performed in 13 patients before ordering (18)F-FDG-PET/CT. We considered that (18)F-FDG-PET/CT was essential to establish the final diagnosis in only 23% of the patients (3/13) since neither chest nor abdominal CT identified abnormalities consistent with the final diagnosis. However, among the three patients, two were diagnosed with large vessel vasculitis and one patient with local prosthetic infection. CONCLUSIONS: Our study supports the potential interest of (18)F-FDG-PET/CT in the diagnostic workup of FUO and UPIS as it helped establish a fine diagnosis in half of the cases. However, (18)F-FDG-PET/CT appeared to be essential to the final diagnosis in only 23% of the cases. In our opinion, this protocol should be performed as a second level test, especially when conventional CT is normal or is unable to discriminate between active and silent lesions.

Relevance of the antibody index to diagnose Lyme neuroborreliosis among seropositive patients.

BACKGROUND: No consensual criteria exist to diagnose neuroborreliosis. The intrathecal anti-Borrelia antibody index (AI) is a necessary criterion to diagnose neuroborreliosis in Europe, but not in the United States. Previous studies to determine the diagnostic value of the AI found a sensitivity ranging from 55% to 80%. However, these studies included only typical clinical cases of meningitis or meningoradiculitis, and none had a control group with CSF anti-Borrelia antibodies. METHODS: We studied a sample of 123 consecutive patients with clinical signs of neurologic involvement and CSF anti-Borrelia antibodies. We determined the AI for all patients and a final diagnosis was made. Patients were then divided into three groups (neuroborreliosis, possible neuroborreliosis, control). RESULTS: Thirty of the 40 patients with neuroborreliosis had a positive AI (AI sensitivity = 75%). Two of the 74 patients with another neurologic diagnosis had a positive AI (AI specificity = 97%). CONCLUSION: The antibody index has a very good specificity but only moderate sensitivity. Given the lack of consensual criteria for neuroborreliosis and the absence of a "gold standard" diagnostic test, we propose pragmatic diagnostic criteria for neuroborreliosis, namely the presence of four of the following five items: no past history of neuroborreliosis, positive CSF ELISA serology, positive anti-Borrelia antibody index, favorable outcome after specific antibiotic treatment, and no differential diagnosis. These new criteria will need to be tested in a larger, prospective cohort.

[Invasive Streptococcus agalactiae infections in non-pregnant adults]. / Les infections invasives à Streptococcus agalactiae chez l'adulte (femme enceinte exclue).

OBJECTIVES: Streptococcus agalactiae (Group B streptococcus) is a major cause of invasive diseases in non-pregnant adults, particularly in the elderly and those with underlying conditions. We describe these conditions and clinical characteristics of patients followed in our teaching hospital. METHODS: We retrospectively reviewed clinical records of 64 patients with S. agalactiae-related invasive infection, hospitalized between January 1997 and January 2006. RESULTS: The mean age of patients was 59 (+/-17 years). The H:F sex ratio was 1.06. At least one underlying condition was found in 90.6%. Diabetes mellitus (43.7%), peripheral vascular disease (34.4%), myocardial ischemia (20.3%) and malignant neoplasms (20.3%) were among the most frequent conditions. The mean index of comorbidity (Charlson) was 2.5 (+/-2). Common clinical manifestations included infection of the urinary tract (32.8%), skin and soft-tissue (25%), and osteoarthritis (21.9%). Bacteremia occurred in 31.2% with no identified source in 2 patients. During the first month, 2 cases of endocarditis, 1 case of meningitis, and 4 deaths occurred. CONCLUSION: We confirm the importance of underlying diseases in the emergence of S. agalactiae infections.