Fièvre jaune: nouvelles recommandations [Yellow fever: new recommendations].

Indication for yellow fever vaccination is not always easy to assess. The decision to immunize is not only based on the actual risk of the disease in a specific location, but also on public health considerations in the visited country (in order to respectively avoid epidemics in endemic countries or the introduction of the virus in zones where the vectors mosquitoes are present) and on travelers' risk factors for severe or even fatal vaccine adverse events. WHO has recently published new recommendations regarding vaccination against yellow fever after concluding that one dose of vaccine generates a life-long protection. This article tends to clarify the strategy to adopt in 2013 using cases frequently encountered in the practice of travel medicine.

Interprétation de la volémie dans l'insuffisance rénale aiguë [Interpretation of volemia in acute kidney injury].

Assessment of volume status is often challenging in daily clinical practice. One of the clinician's tasks is to prevent or to treat organ systems failures that arise from a mismatch between the transport of oxygen and metabolic needs. Renal failure is a frequently encountered in-hospital diagnosis that is known to alter significantly the prognosis. In patients with acute renal failure in particular, the consequences of an inadequate volume management further increase morbidity and mortality.

Infliximab for Crohn's disease in the Swiss IBD Cohort Study: clinical management and appropriateness.

OBJECTIVE: Antitumor necrosis factor a agents have significantly improved the management of Crohn's disease (CD), but not all patients benefit from this therapy. We used data from the Swiss Inflammatory Bowel Disease Cohort Study and predefined appropriateness criteria to examine the appropriateness of use of infliximab (IFX) in CD patients. METHODS: EPACT II (European Panel on the Appropriateness of CD Therapy, 2007; www.epact.ch) appropriateness criteria have been developed using a formal explicit panel process combining evidence from the published literature and expert opinion. Questionnaires relating to EPACT II criteria were used at enrollment and follow-up of all Swiss Inflammatory Bowel Disease Cohort Study patients. A step-by-step analysis of all possible indications for IFX therapy in a given patient allowed identification of the most appropriate indication and final classification in a single appropriateness category (appropriate, uncertain, inappropriate). RESULTS: Eight hundred and twenty-one CD patients were prospectively enrolled between November 2006 and March 2009. IFX was administered to 146 patients (18%) at enrollment and was most frequently used for complex fistulizing disease and for the maintenance of remission induced by biological therapy. IFX therapy was considered appropriate in 44%, uncertain in 44%, and inappropriate in 10% of patients. CONCLUSION: In this cohort, 9 out of 10 indications for IFX therapy were clinically generally acceptable (appropriate or uncertain) according to EPACT II criteria. Uncertain indications resulted mainly from the current more liberal use of IFX in clinical practice as compared with the EPACT II criteria.

Immunological and clinical consequences of treating a patient with natalizumab.

BACKGROUND: Long-term therapy with natalizumab increases the risk of progressive multifocal leukoencephalopathy (PML). OBJECTIVES: We present a patient study through therapy, the diagnosis of PML (after 29 infusions), plasma exchange (PE) and development of immune reconstitution inflammatory syndrome (IRIS). METHODS: Routine diagnostics, magnetic resonance imaging (MRI), immunological status (flow cytometry, T-cell migration assays and T-cell repertoire analysis), and brain biopsy with immunohistological analysis. RESULTS: CD49d decreased after 12 months of treatment. At PML diagnosis, CD49d expression and migratory capacity of T cells was low and peripheral T-cell receptor (TCR) complexity showed severe perturbations. The distribution of peripheral monocytes changed from CCR5+ to CCR7+. After PE some changes reverted: CD49d increased and overshot earliest levels, migratory capacities of T cells recovered and peripheral TCR complexity increased. With no clinical, routine laboratory or cerebrospinal fluid (CSF) changes, MRI 2 months after PE demonstrated progressive lesion development. Brain histopathology confirmed the presence of infiltrates indicative of IRIS without clinical signs, immunologically accompanied by CCR7/CCR5 recovery of peripheral monocytes. CONCLUSION: Natalizumab-associated immunological changes accompanying PML were reversible after PE; IRIS can occur very late, remain asymptomatic and be elusive to CSF analysis. Our study may provide insights into the changes under treatment with natalizumab associated with JC virus control.

A pilot study of delayed versus immediate serial casting after botulinum toxin injection for partially reducible spastic equinus.

BACKGROUND: Serial casting is often prescribed after botulinum toxin injections to improve joint ranges of motion and to potentiate the decrease in hypertonia. The aim of this study was to compare delayed versus immediate serial casting as an adjunct to botulinum toxin therapy for partially reducible spastic equinus. METHODS: Twelve children who presented spastic equinus associated with mild gastrosoleus contracture took part. Five of them had a diagnosis of spastic diplegia, whereas 7 had a diagnosis of congenital hemiplegia. Children were randomized to immediate serial casting (same day) or delayed serial casting (4 weeks later) after botulinum toxin injection to their gastrosolei. Casts were replaced weekly for 3 weeks. RESULTS: Three children complained of pain that required recasting in the immediate casting group versus none in the delayed casting group (P = 0.08). At 3 months, there was a 27-degree improvement in the fast dorsiflexion angle (Tardieu R1) in the delayed casting group versus 17 degrees in the immediate casting group (P = 0.029). At 6 months, a 19-degree improvement persisted in the delayed group compared with 11 degrees in the immediate group (P = 0.010). CONCLUSIONS: There is a clear benefit in delaying serial casting after the injection of botulinum toxin in the recurrence of spasticity at the gastrosoleus that may also offer an advantage regarding the incidence of painful episodes associated with casting. Most importantly, reducing the recurrence of spasticity by delayed serial casting may offer the possibility of decreasing the frequency of botulinum toxin reinjections.

OnabotulinumtoxinA and multiple sclerosis.

Lower urinary tract dysfunction is present in two of three patients with multiple sclerosis five years after the diagnosis. Most frequent symptoms are related to neurogenic detrusor overactivity, often associated with detrusor-sphincter dyssynergia. From the end of the 1990s, there is growing evidence that neurogenic detrusor overactivity can be effectively managed by intradetrusorial injections of botulinum toxin type A. This treatment has shown, in different randomised placebo-controlled trials, to be safe and effective on clinical and urodynamic parameters with significant improvement in quality of life. The median duration of effect is in mean nine months. The vast majority of studies have been conducted with onabotulinumtoxinA. The dose of onabotulinumtoxinA commonly used to treat neurogenic detrusor overactivity in patients with multiple sclerosis is 200 UI, even if in selected patients lower doses can be preferred. To be considered eligible for treatment, all patients should accept and be instructed to perform clean intermittent self-catheterisation, since the risk of increased post-void residual volume and/or urinary retention after injection is high, especially with 200 UI of onabotulinumtoxinA. However, quality of life and patient satisfaction seem not to be affected by the need of intermittent catheterisation. The risk of urinary infection after the procedure is to be kept in mind, mainly in patients with multiple sclerosis, so that adequate antibiotic prophylaxis is highly recommended.

Efficacies of moxifloxacin, ciprofloxacin, and vancomycin against experimental endocarditis due to methicillin-resistant Staphylococcus aureus expressing various degrees of ciprofloxacin resistance.

The new 8-methoxyquinolone moxifloxacin was tested against two ciprofloxacin-susceptible Staphylococcus aureus strains (strains P8 and COL) and two ciprofloxacin-resistant derivatives of strain P8 carrying a single grlA mutation (strain P8-4) and double grlA and gyrA mutations (strain P8-128). All strains were resistant to methicillin. The MICs of ciprofloxacin and moxifloxacin were 0.5 and 0.125 mg/liter, respectively, for P8; 0.25 and 0.125 mg/liter, respectively, for COL; 8 and 0.25 mg/liter, respectively, for P8-4; and >or=128 and 2 mg/liter, respectively, for P8-128. In vitro, the rate of spontaneous resistance of P8 and COL was 10(-7) on agar plates containing ciprofloxacin at two times the MIC, whereas it was <or=10(-10) on agar plates containing moxifloxacin at two times the MIC. Rats with experimental aortic endocarditis were treated with doses of drugs that simulate the kinetics in humans: moxifloxacin, 400 mg orally once a day; ciprofloxacin, 750 mg orally twice a day; or vancomycin, 1 g intravenously twice a day. Treatment was started either 12 or 24 h after infection and lasted for 3 days. Moxifloxacin treatment resulted in culture-negative vegetations in a total of 20 of 21 (95%) rats infected with P8, 10 of 11 (91%) rats infected with COL, and 19 of 24 (79%) rats infected with P8-4 (P < 0.05 compared to the results for the controls). In contrast, ciprofloxacin treatment sterilized zero of nine (0%) vegetations infected with first-level resistant mutant P8-4. Vancomycin sterilized only 8 of 15 (53%), 6 of 11 (54%), and 12 of 23 (52%) of the vegetations, respectively. No moxifloxacin-resistant derivative emerged among these organisms. However, moxifloxacin treatment of highly ciprofloxacin-resistant mutant P8-128 failed and selected for variants for which the MIC increased two times in 2 of 10 animals. Thus, while oral moxifloxacin might deserve consideration as treatment for staphylococcal infections in humans, caution related to its use against strains for which MICs are borderline is warranted.

Impact of single nucleotide polymorphisms and of clinical risk factors on new‐onset diabetes mellitus in HIV‐infected individuals.

BACKGROUND: Metabolic complications, including cardiovascular events and diabetes mellitus (DM), are a major long-term concern in human immunodeficiency virus (HIV)-infected individuals. Recent genome-wide association studies have reliably associated multiple single nucleotide polymorphisms (SNPs) to DM in the general population. METHODS: We evaluated the contribution of 22 SNPs identified in genome-wide association studies and of longitudinally measured clinical factors to DM. We genotyped all 94 white participants in the Swiss HIV Cohort Study who developed DM from 1 January 1999 through 31 August 2009 and 550 participants without DM. Analyses were based on 6054 person-years of follow-up and 13,922 measurements of plasma glucose. RESULTS: The contribution to DM risk explained by SNPs (14% of DM variability) was larger than the contribution to DM risk explained by current or cumulative exposure to different antiretroviral therapy combinations (3% of DM variability). Participants with the most unfavorable genetic score (representing 12% and 19% of the study population, respectively, when applying 2 different genetic scores) had incidence rate ratios for DM of 3.80 (95% confidence interval [CI], 2.05-7.06) and 2.74 (95% CI, 1.53-4.88), respectively, compared with participants with a favorable genetic score. However, addition of genetic data to clinical risk factors that included body mass index only slightly improved DM prediction. CONCLUSIONS: In white HIV-infected persons treated with antiretroviral therapy, the DM effect of genetic variants was larger than the potential toxic effects of antiretroviral therapy. SNPs contributed significantly to DM risk, but their addition to a clinical model improved DM prediction only slightly, similar to studies in the general population.

Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America.

Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document.

Levofloxacin versus ciprofloxacin, flucloxacillin, or vancomycin for treatment of experimental endocarditis due to methicillin-susceptible or -resistant Staphylococcus aureus.

Levofloxacin is the L isomer of ofloxacin, a racemic mixture in which the L stereochemical form carries the antimicrobial activity. Levofloxacin is more active than former quinolones against gram-positive bacteria, making it potentially useful against such pathogens. In this study, levofloxacin was compared to ciprofloxacin, flucloxacillin, and vancomycin for the treatment of experimental endocarditis due to two methicillin-susceptible Staphylococcus aureus (MSSA) and two methicillin-resistant S. aureus (MRSA) isolates. The four test organisms were susceptible to ciprofloxacin, the levofloxacin MICs for the organisms were low (0.12 to 0.25 mg/liter), and the organisms were killed in vitro by drug concentrations simulating both the peak and trough levels achieved in human serum (5 and 0.5 mg/liter, respectively) during levofloxacin therapy. Rats with aortic endocarditis were treated for 3 days. Antibiotics were injected with a programmable pump to simulate the kinetics of either levofloxacin (350 mg orally once a day), ciprofloxacin (750 mg orally twice a day), flucloxacillin (2 g intravenously four times a day), or vancomycin (1 g intravenously twice a day). Levofloxacin tended to be superior to ciprofloxacin in therapeutic experiments (P = 0.08). More importantly, levofloxacin did not select for resistance in the animals, in contrast to ciprofloxacin. The lower propensity of levofloxacin than ciprofloxacin to select for quinolone resistance was also clearly demonstrated in vitro. Finally, the effectiveness of this simulation of oral levofloxacin therapy was at least equivalent to that of standard treatment for MSSA or MRSA endocarditis with either flucloxacillin or vancomycin. This is noteworthy, because oral antibiotics are not expected to succeed in the treatment of severe staphylococcal infections. These good results obtained with animals suggest that levofloxacin might deserve consideration for further study in the treatment of infections due to ciprofloxacin-susceptible staphylococci in humans.

Peut-on traiter la maladie d'Alzheimer [Is there a treatment for Alzheimer's disease?].

Alzheimer's disease is a frequent neurodegenerative disease, which affects more than one third of elderly persons over 80 years. No curative treatment is currently available for this disease, but symptomatic treatments have produced significant improvements in patients' condition. Cholinesterase inhibitors should be prescribed for early and moderate stages and memantine for more severe stages of the disease. These drugs have an impact on cognitive performances, may delay functional decline and improve behaviour disturbances. From a preventive perspective, evidence of benefit from early management of vascular risk factors is accumulating. In the near future, the improved comprehension of the underlying mechanisms of Alzheimer's disease will hopefully bring new treatments, thats will delay or modify its course.

Prevenzione della malaria nei viaggiatori: quale antimalarico?: revisione Cochrane per il medico di famiglia.

Cet article présente les résultats de la revue systématique: Jacquerioz FA, Croft AM. Drugs for preventing malaria in travellers. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD006491. PMID: 19821371

Parenteral is more efficient than mucosal immunization to induce regression of human papillomavirus-associated genital tumors.

Cervical cancer is a public health concern as it represents the second cause of cancer death in women worldwide. High-risk human papillomaviruses (HPV) are the etiologic agents, and HPV E6 and/or E7 oncogene-specific therapeutic vaccines are under development to treat HPV-related lesions in women. Whether the use of mucosal routes of immunization may be preferable for inducing cell-mediated immune responses able to eradicate genital tumors is still debated because of the uniqueness of the female genital mucosa (GM) and the limited experimentation. Here, we compared the protective activity resulting from immunization of mice via intranasal (i.n.), intravaginal (IVAG) or subcutaneous (s.c.) routes with an adjuvanted HPV type 16 E7 polypeptide vaccine. Our data show that s.c. and i.n. immunizations elicited similar frequencies and avidity of TetE71CD81 and E7-specific Interferon-gamma-secreting cells in the GM, whereas slightly lower immune responses were induced by IVAG immunization. In a novel orthotopic murine model, both s.c. and i.n. immunizations allowed for complete long-term protection against genital E7-expressing tumor challenge. However, only s.c. immunization induced complete regression of already established genital tumors. This suggests that the higher E7-specific systemic response observed after s.c. immunization may contribute to the regression of growing genital tumors, whereas local immune responses may be sufficient to impede genital challenges. Thus, our data show that for an efficiently adjuvanted protein-based vaccine, parenteral vaccination route is superior to mucosal vaccination route for inducing regression of established genital tumors in a murine model of HPV-associated genital cancer.