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Olson A.D.,French Institute of Health and Medical Research | Olson A.D.,University Pierre and Marie Curie | Guiguet M.,French Institute of Health and Medical Research | Guiguet M.,University Pierre and Marie Curie | And 10 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2014

Design: Rapid CD4 cell loss represents an HIV phenotype used to identify causal variants of accelerated disease progression. The optimal rate and threshold for identifying this extreme phenotype in recently infected individuals is unclear. Methods: Using a cohort of patients with known dates of HIV-1 seroconversion (SC), CASCADE (Concerted Action on SeroConversion on AIDS and Death in Europe), we identified proportions experiencing nadir CD4 cell levels within 1 year of SC, and assessed their mean AIDS-free survival time at 10-year follow-up and hazard of AIDS/death, compared with those whose CD4 remained >500 cells per cubic millimeter. Follow-up was censored at December 31, 1996 to avoid bias due to combination antiretroviral therapy initiation. Results: Of 4876 individuals, 2.8%, 7.3%, and 24.9% experienced 1 CD4 <100, 200, and 350 cells per cubic millimeter, respectively, within 1 year of SC. Minimum CD4 levels of 30, 166, 231, and 506 cells per cubic millimeter were experienced during this period by 1%, 5%, 10%, and 50% of individuals, respectively. Mean (95% confidence interval) AIDS-free survival at 10 years follow-up was 2.9 (2.3 to 3.6), 5.5 (5.0 to 6.1), 6.7 (6.5 to 7.0), 7.4 (7.2 to 7.6), and 8.1 (7.9 to 8.3), for those with minimum counts ≤100, 100-200, 200-350, 350-500, >500 cells per cubic millimeter, respectively. Using counts of >500 cells per cubic millimeter as reference, the hazard ratios (95% confidence interval) of AIDS/death were 15.0 (11.9 to 18.9), 3.6 (2.9 to 4.5), 2.1 (1.8 to 2.4), and 1.5 (1.3 to 1.7), respectively. The hazard ratio increased to 37.5 (26.5 to 53.1) when a minimum CD4 count <100 was confirmed within 1 year of SC. Conclusion: At least 1 CD4 ≤100 cells per cubic millimeter within the first year of SC identifies a rare group of individuals at high risk of disease progression and could form the basis for defining the rapid progressor phenotype. © 2014 by Lippincott Williams & Wilkins.


Gottenberg J.-E.,University of Strasbourg | Cinquetti G.,Service de Medecine Interne et Maladies Infectieuses | Larroche C.,Service de Medecine Interne | Combe B.,Montpellier University Hospital Center | And 26 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objectives: To evaluate the efficacy and safety of rituximab in patients with primary Sjögren's syndrome (pSS). Methods: The AutoImmune and Rituximab registry has included 86 patients with pSS treated with rituximab, prospectivey followed up every 6 months for 5 years. Results: Seventy-eight patients with pSS (11 men, 67 women), who already had at least one follow-up visit, were analysed. Median age was 59.8 years (29-83), median duration of disease was 11.9 years (3-32). Indications for treatment were systemic involvement for 74 patients and only severe glandular involvement in four patients. The median European Sjögren's Syndrome disease activity index (ESSDAI) was 11 (2-31). 17 patients were concomitantly treated with another immunosuppressant agent. Median follow-up was 34.9 months (6-81.4) (226 patient-years). Overall efficacy according to the treating physician was observed in 47 patients (60%) after the first cycle of rituximab. Median ESSDAI decreased from 11 (2-31) to 7.5 (0-26) (p<0.0001). Median dosage of corticosteroid decreased from 17.6 mg/day (3-60) to 10.8 mg/day (p=0.1). Forty-one patients were retreated with rituximab. Four infusion reactions and one delayed serum sickness-like disease resulted in rituximab discontinuation. Three serious infections (1.3/100 patient-years) and two cancer-related deaths occurred. Conclusions: In common practice, the use of rituximab in pSS is mostly restricted to patients with systemic involvement. This prospective study shows good efficacy and tolerance of rituximab in patients with pSS and systemic involvement.


PubMed | University of Tours, Service de parasitologie mycologie medecine tropicale, French Institute of Health and Medical Research, French National Institute for Agricultural Research and Service de medecine interne et maladies infectieuses
Type: Journal Article | Journal: Archives de pediatrie : organe officiel de la Societe francaise de pediatrie | Year: 2016

Intestinal parasitoses are very common infections in tropical areas. By contrast, they are rarely diagnosed in developed countries, and are mostly seen in specific populations.This analytical observational study was longitudinally performed in a French university hospital (2007-2011). It dealt with the study of gastrointestinal carriage of parasites in internationally adopted children. A standard stool examination was therefore systematically undertaken for every new immigrant. Association with risk factors was made by uni- and multivariate analysis.Overall, 69stool samples were analyzed. The proportion of positive samples was 78%. Protozoans, mainly Giardiaduodenalis, were more prevalent than helminths. In univariate analysis, a subjects low weight and height were significantly associated with intestinal parasite carriage. Amoebae were more frequent in older children and in children from Haiti, as confirmed by the trend observed in the multivariate analysis. Flagellates were seen more often in African children. Infections with multiple parasite species were observed in half of the study population, and were inversely correlated to increasing age.According to the results of this study, gastrointestinal parasites are still very frequent in stool samples from immigrant children. Since they are easy to transmit, the majority of infections were protozoan. The best antiparasitic strategy lies in: (a) the routine screening of stool from any immigrant child coming from endemic areas and (b) the use of antiparasitic treatment.


Frange P.,University of Paris Descartes | Chaix M.-L.,University of Paris Descartes | Raymond S.,French Institute of Health and Medical Research | Galimand J.,University of Paris Descartes | And 5 more authors.
Journal of Clinical Microbiology | Year: 2010

We used genotypic and phenotypic assays to estimate the frequency of X4/DM viruses in 131 patients infected with non-subtype-B viruses at the time of primary HIV-1 infection (PHI). All patients were enrolled in the French PRIMO Cohort from 1996 to 2007. Most strains belonged to CRF02-AG (51.1%) and subtype A (14.5%). Sixteen viruses (12.2%) were classified as CXCR4 tropic ("X4 strains") by the combined criteria of amino acids 11 and 25 of the V3 loop (11/25) and net charge rules and/or the SVMgeno2pheno 10% algorithm: 6 strains by the combined genotypic rule, 7 by the SVMgeno2pheno 10% algorithm, and 3, clustering in subtype D, by both algorithms. However, only one strain (0.8%), belonging to subtype A, was defined as a dual-tropic (DM) virus by the phenotypic assay. The 67 CRF02-AG strains included 2 classified as X4 strains by the combined genotypic rule (3%) and 2 others classified as X4 strains by SVMgeno2pheno 10% (3%), but none of these 4 strains was an X4 or DM strain according to the phenotypic assay. These results suggest that the cellular virus reservoir was established with X4 strains in very few non-subtype-B-infected patients at the time of PHI. Genotypic predictions can overestimate the proportion of non-subtype-B X4 viruses at PHI. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Gros H.,Service de medecine interne et maladies infectieuses | Aslangul E.,Service de medecine interne | Lesprit P.,Equipe transversale dinfectiologie | Mainardi J.-L.,University of Paris Descartes
Medecine et Maladies Infectieuses | Year: 2012

Objective: The study's objective was to describe the notification methods of positive blood cultures and analyse the impact of recommendations made by an infectious disease specialist on the appropriateness of antibiotherapy. Method: We included all patients with positive blood cultures, from 12 different hospitals (including six with mobile infectious disease teams: MIDT) during a seven-day period. Medical records were retrospectively analysed to determine the delivered antibiotic treatment and the notification method of positive blood culture. We considered that the antibiotic treatment was appropriate if the antibiotic was effective on the isolated bacterium, whatever its spectrum. We assessed the impact of recommendations on appropriateness of antibiotherapy. Results: One hundred and eighty-six patients were included. 44% (n= 86) were considered as contamination cases. In true infections (n=104), Staphylococcus aureus and enterobacteria accounted for 51% of isolated bacteria. The Medical Unit was notified of blood culture positivity the day of positivity in 98% of cases (n=182). Antibiotic recommendations were given on the same day in 71% of cases. The antibiotic treatment was appropriate if recommendations were given in 92% of bacteremia, and only in 79% in without any recommendations (P=0.1). Conclusion: Antibiotic treatment seems to be more appropriate when antibiotic recommendations are given. This suggests that the MIDT has a key role in improving antibiotic prescriptions, whether for effectiveness, cost, or bacterial ecology. © 2011 Elsevier Masson SAS.


PubMed | Service de biologie clinique, Service de pharmacie, Service de medecine interne et maladies infectieuses, University Pierre and Marie Curie and 2 more.
Type: Journal Article | Journal: Medecine et maladies infectieuses | Year: 2016

The emergence of bacterial resistance and the lack of new antibiotics in the pipeline represent a public health priority. Maximizing the quality of antibiotic prescriptions is therefore of major importance in terms of adequate preparation and administration modalities. Adequate preparation prevents the inactivation of antibiotics and is a prerequisite to maximizing their efficacy (taking into account the pharmacokinetic/pharmacodynamic relationship) and to minimizing their toxicity. Many antibiotic guidelines address the choice of drugs and treatment duration but none of them exclusively address preparation and administration modalities. These guidelines are based on the available literature and offer essential data for a proper antibiotic preparation and administration by physicians and nurses. They may lead to a better efficacy and to a reduced antibiotic resistance. Such guidelines also contribute to a proper use of drugs and improve the interaction between inpatient and outpatient care for a better overall management of patients.


Desoubeaux G.,Service de Parasitologie Mycologie Medecine tropicale | Desoubeaux G.,French Institute of Health and Medical Research | Maakaroun-Vermesse Z.,Service de Medecine Interne et Maladies Infectieuses | Lier C.,Service de Parasitologie Mycologie Medecine tropicale | And 8 more authors.
Transplant Infectious Disease | Year: 2013

We report the first successful use, to our knowledge, of fumagillin alone in a pediatric patient to cure intestinal microsporidiosis in a liver-kidney transplanted child. Detection of Enterocytozoon bieneusi in stool became negative from the first post-therapeutic control, while digestive symptoms disappeared in 4 days. During a 9-month follow-up, polymerase chain reaction and direct examinations remained negative for microsporidia in her feces. No major undesirable effects were noted during the anti-microsporidial therapy. © 2013 John Wiley & Sons A/S.


PubMed | National Reference Center for Pneumococci, French Institute of Health and Medical Research and Service de Medecine Interne et Maladies Infectieuses
Type: Journal Article | Journal: BMC medicine | Year: 2016

Pneumococcal meningitis (PM) is a major invasive pneumococcal disease. Two pneumococcal conjugate vaccines (PCVs) have been introduced in France: PCV7 was recommended in 2003 and replaced in 2010 by PCV13, which has six additional serotypes. The impact of introducing those vaccines on the evolution of PM case numbers and serotype distributions in France from 2001 to 2014 is assessed herein.Data on 5166 Streptococcus pneumoniae strains isolated from cerebrospinal fluid between 2001 and 2014 in the 22 regions of France were obtained from the National Reference Center for Pneumococci. The effects of the different vaccination campaigns were estimated using time series analyses through autoregressive moving-average models with exogenous variables (flu-like syndromes incidence) and intervention functions. Intervention functions used 11 dummy variables representing each post vaccine epidemiological period. The evolution of serotype distributions was assessed for the entire population and the two most exposed age groups (<5 and>64years old).For the first time since PCV7 introduction in 2003, total PM cases decreased significantly after starting PCV13 use: -7.1 (95% CI, -10.85 to -3.35) cases per month during 2013-2014, and was confirmed in children<5years old (-3.5; 95% CI, -4.81 to -2.13) and adults>64years old (-2.0; 95% CI, -3.36 to -0.57). During 2012-2014, different non-vaccine serotypes emerged: 12F, 24F in the entire population and children, 6C in the elderly; serotypes 3 and 19F persisted in the entire population.Unlike other European countries, the total PM cases in France declined only after introduction of PCV13. This suggests that vaccine pressure alone does not explain pneumococcal epidemiological changes and that other factors could play a role. Serotype distribution had changed substantially compared to the pre-vaccine era, as in other European countries, but very differently from the US. A highly reactive surveillance system is thus necessary not only to monitor evolutions due to vaccine pressure and to verify the local serotypic appropriateness of new higher-valent pneumococcal vaccines, but also to recognise and prevent unexpected changes due to other internal or external factors.


N'Guyen Y.,Service de Medecine Interne et Maladies Infectieuses | Baumard S.,Service de Medecine Interne et Maladies Infectieuses | Vernet-Garnier V.,Reims University Hospital Center | Batalla A.S.,Service de Medecine Interne et Maladies Infectieuses | And 3 more authors.
Scandinavian Journal of Infectious Diseases | Year: 2012

Background: We sought to determine the epidemiological patterns of Staphylococcus bacteraemia, with a focus on the proportion of coagulase-negative Staphylococcus (CoNS) as compared to Staphylococcus aureus bacteraemia, and the prognosis. Methods: All patients with significant Staphylococcus bacteraemia at the university hospital in Reims in 2008 were included in the study. Data were retrieved retrospectively from the patient records using a standardized case investigation form. Quantitative variables were compared using the MannWhitney U-test and qualitative variables were compared using Fisher's exact test or Pearson's Chi-square test, as appropriate. Bivariate logistic regression was performed on both S. aureus and CoNS bacteraemia. All variables with a p-value of < 0.15 were entered into a multiple logistic regression model. Results: CoNS represented 31.6% of all strains isolated. The methicillin resistance rate was higher in CoNS (66.1%) than in S. aureus (19.1%) (p < 0.0001). CoNS were more frequently associated with intravascular catheters and neoplastic disease, whereas S. aureus was associated with chronic renal failure (p < 0.0001) and diabetes mellitus (p = 0.004). Mortality was 30.7% for S. aureus and 19.6% for CoNS bacteraemia (p = 0.12). Methicillin resistance was not associated with mortality (p = 0.99). Factors independently associated with mortality in CoNS and S. aureus bacteraemia were age and acute renal failure. The presence of severe sepsis/septic shock was only associated with mortality in S. aureus bacteraemia. Conclusions: CoNS represent one third of Staphylococcus bacteraemia. The mortality difference between CoNS and S. aureus bacteraemia was not statistically significant. Acute renal failure is associated with mortality in both S. aureus and CoNS bacteraemia. © 2012 Informa Healthcare.


Lefebvre M.,Nantes University Hospital Center | Capito C.,Service de chirurgie pediatrique | Durant C.,Service de medecine interne | Hervier B.,Service de medecine interne | Grossi O.,Service de medecine interne et maladies infectieuses
Medecine et Maladies Infectieuses | Year: 2011

Tungiasis is the parasitic skin disease caused by the sand flea Tunga penetrans, also called the jigger flea, found in most intertropical countries. The contamination occurs when walking barefoot in the sand: adult females actively burrow the foot epidermis leading to self-limited lesions responsible for itching or pain. The diagnosis is made on clinical observation and history of travelling to an endemic country. The simple treatment is surgical extraction of the flea. © 2011 Elsevier Masson SAS.

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