Biomedical subjects

Frédéric Lucht

Publications and source records attributed to Frédéric Lucht.

13 recordsLinked to original sources

PubMed2006

Analysis of polymorphism in the protease and reverse transcriptase genes of HIV type 1 CRF02-AG subtypes from drug-naive patients from Saint-Etienne, France.

SUMMARY: : The proportion of non-B HIV-1 variants is increasing in Western Europe. The impact of the high polymorphism in the protease and reverse transcriptase genes, as recently described for CRF02-AG isolates of African origin, on antiretroviral resistance is still disputed. We first examined the polymorphism of these genes in CRF02-AG strains recovered from drug-naive patients followed at the University Hospital of Saint-Etienne in France, most of these of French origin and harboring a clonal strain as elicited by phylogenic analysis. The first plasma sample detected positive from 31 CRF02-AG and 23 B strains was used to compare sequences with their respective subtype consensus strain. The overall number of mutations was dramatically higher for CRF02-AG strains than for B strains in both protease and reverse transcriptase genes (P < 0.0001 and 0.009, respectively). In addition, no statistically significant difference in the number of therapeutic failures, mean CD4 cell count, and viral load was observed between 22 and 45 patients infected with CRF02-AG or B strains, respectively, during a mean treatment period of 25.5 months. Even if no striking antiretroviral failure linked to this polymorphism was observed during short-term follow-up, its impact on long-term therapy will have to be extensively evaluated in patients infected by non-B HIV-1 variants.

Adult↗

PubMed2006

Amount of seminal IL-1beta positively correlates to HIV-1 load in the semen of infected patients.

BACKGROUND: Cytokines present in the sperm could influence the heterosexual transmission of HIV by modulating viral titers and influencing the early immune response in the vaginal mucosa. OBJECTIVES: To assess the relation between cytokine concentrations and HIV status in the seminal plasma. STUDY DESIGN: Twenty-five HIV positive subjects were tested for cytokine content and HIV-1 load in seminal and blood plasma through a cross-sectional study. RESULTS: HIV positive subjects exhibited a significantly higher amount of seminal IL-1beta as compared to a group of 33 HIV negative controls. In HIV positive subjects, amounts of IL-1beta and HIV-1 RNA in semen were significantly correlated and a trend for correlation was found between seminal IL-1beta and blood HIV-1 RNA. Amount of seminal IL-1beta was significantly lower in patients under HAART, according to the decrease of their viral loads in blood and semen. CONCLUSIONS: Considering that IL-1beta is known to enhance viral replication and to promote immune response, its dosage in semen could represent an interesting marker for identifying patients at high risk for HIV heterosexual transmission.

Adult↗

PubMed2006

Bacterial contamination of nonsterile disposable gloves before use.

BACKGROUND: After Bacillus cereus recovery in opened boxes of disposable gloves, the bacteriological contamination of disposable nonsterile gloves kept stored in native packages was investigated prospectively. METHODS: Thirty-six commercially available nonsterile nonpowdered disposable gloves made of latex, vinyl, or nitrile were cultured. RESULTS: A large variety of spore-forming and non-spore-forming bacteria was recovered, including Bacillus cereus and Clostridium perfringens. CONCLUSION: This finding must be taken into consideration for care involving gloves in very immunocompromised patients.

Bacillus cereus↗

PubMed2005

Lymphangitis-associated rickettsiosis, a new rickettsiosis caused by Rickettsia sibirica mongolotimonae: seven new cases and review of the literature.

BACKGROUND: Rickettsia sibirica mongolotimonae has been found in Hyalomma ticks in Inner Mongolia (in China) and Niger and in humans in France and South Africa. To date, only 3 cases of human infection have been reported. METHODS: Patients received a diagnosis of R. sibirica mongolotimonae infection on the basis of culture and/or PCR results plus serological test results. RESULTS: From January 2000 to June 2004, R. sibirica mongolotimonae infection was diagnosed in 7 patients. In 3 patients, the bacterium was cultivated from the inoculation eschar. The other 4 patients had cases that were diagnosed with use of PCR of samples obtained from the eschar (2 patients) or blood (2 patients), plus specific Western blot before (2 patients) and after (2 patients) cross-adsorption. The clinical presentation included fever (temperature, >38.5 degrees C), a maculopapular rash, and > or =1 inoculation eschar in 6 patients, enlarged regional lymph nodes in 4 patients, and lymphangitis in 3 patients. On the basis of the study of 9 cases, R. sibirica mongolotimonae infection differed from other tick-borne rickettsioses in the Mediterranean area in the following ways: it involved a specific incidence in the spring, the presence of 2 eschars in 2 (22%) of the patients, the presence of a draining lymph node in 5 (55%) of the patients, and lymphangitis expanding from the inoculation eschar to the draining node in 4 (44%) of the patients. The most recent patient in our series received a clinical diagnosis on the basis of such findings. All patients recovered without any sequelae. CONCLUSIONS: We propose that this new rickettsiosis be named "lymphangitis-associated rickettsiosis." Lymphangitis-associated rickettsiosis should be considered in the differential diagnosis of tick-borne rickettsioses in Europe, Africa, and Asia.

Adult↗

PubMed2005

Depletion in antibodies targeted to the HR2 region of HIV-1 glycoprotein gp41 in sera of HIV-1-seropositive patients treated with T20.

The anti-HIV drug T20 is a synthetic peptide derived from the HR2 region of HIV-1 gp41. T20 contains the sequence ELDKWA, which binds the broadly neutralizing antibody 2F5. Using plates coated with T20 or with synthetic peptides and recombinant proteins representing gp120 or gp41 domains, this study investigated by enzyme-linked immunosorbent assay the levels of antibodies directed to the gp160 molecule in patients treated with T20. Analysis of sera obtained before and after administration of T20 indicated that the levels of antibodies directed to T20, to MBP44, a maltose binding protein representing the HR2 region, and to 4765, a synthetic peptide containing the sequence ELDKWA, fell following administration of T20, while the levels of antibodies directed to other regions of gp41 ectodomain and to gp120 remained stable. The decline observed was independent of the viral load and of the total IgG concentration. Follow-up studies with sera obtained from HIV-1-seropositive patients naive to T20 indicated no decline in the level of antibodies directed to HR2 and other regions of gp160. Analysis of sera obtained from a patient after 2 months of T20 treatment interruption showed a level of antibodies to the HR2 region similar to that measured before administration of T20. The addition of increasing amounts of T20 to sera from T20-naive patients decreased the level of serum antibodies against peptide 4765, T20, and MBP44. The observation of antibody depletion by T20 suggests that anti-gp41 antibodies may interfere with T20 treatment by forming T20-antibody complexes.

Adult↗

PubMed2004

Isotype profiles of anti-gp160 antibodies from HIV-infected patients in plasma and culture supernatants.

We studied isotype profiles of anti-HIV antibodies (Ab) in HIV-1-infected African patients with high viral loads and major B cell dysfunction. We focussed on IgG1, IgG3, and IgA as these classes and subclasses tend to support neutralizing functions against HIV. Total IgG1, IgG3 and IgA were detected in the plasma of both HIV-1-infected and HIV-negative African individuals, but there was significantly more IgG3, a rare subclass, in HIV-1-infected patients (P < 0.05). Anti-HIV-gp160 specific antibodies were detected in sera from nearly all HIV-1-infected individuals tested, but not in HIV- individuals: 10/10, 9/10 and 8/10 individuals displayed specific IgG1, IgG3 and IgA, respectively. In the corresponding PBMC cultures carried out in the presence of IL-10 and IL-2, there was specific IgG1 and IgA in 5/10, and 3/10, respectively, but no IgG3 was detected. When HAART-treated European HIV-infected PBMC cultures were tested using the same protocol, specific IgG3 was detected in 4/10 cultures, and was unaffected by the addition of soluble CD40L molecules. The present study thus shows that, despite lymph node disorganization in HIV-infected drug-naïve Africans, these individuals retain the ability to produce HIV-specific IgG1, IgG3 and IgA. However, the specific mechanisms controlling the selective production of IgG3, probably the most potent subclass and a potential target of immuno-intervention, warrants further investigation.

Adult↗

PubMed2004

Detection of IgA inhibiting the interaction between gp120 and soluble CD4 receptor in serum and saliva of HIV-1-infected patients.

OBJECTIVE: To evaluate the presence of IgA directed to the CD4-binding domain of gp120 and to a conserved region of gp41 (the Kennedy epitope) in serum and parotid saliva of HIV-1-seropositive patients. METHODS: IgA were separated from IgG by anion-exchange chromatography and protein G treatment. The reactivity of IgA was tested against peptides and fusion proteins of the maltose-binding protein (MBP) and the CD4-binding site (MBP24) and MBP and the Kennedy epitope (MBP42). The capacity of serum and saliva IgA to interfere with the gp120-soluble CD4 (sCD4) interaction was examined. IgA were also purified by affinity chromatography using the MBP proteins adsorbed to a resin. RESULTS: Peptides representing the CD4-binding domain and the Kennedy epitope were recognized by serum and saliva IgA of HIV-1-seropositive patients. Of the sera and saliva samples tested, 6/26 serum IgA and 5/25 saliva IgA inhibited the gp120-sCD4 interaction by approximately 50%. The gp120-sCD4 interaction was inhibited by MBP24 affinity-purified IgA but not by MBP42 affinity-purified IgA. CONCLUSION: Immunogens capable of eliciting IgA antibodies that inhibit gp120-CD4 binding might be efficiently used in vaccine to prevent mucosal transmission of HIV-1.

Antibodies, Viral↗

PubMed2004

Identification of germinal center B cells in blood from HIV-infected drug-naive individuals in Central Africa.

To better understand the pathophysiology of B cell populations-the precursors of antibody secreting cells-during chronic human immunodeficiency virus (HIV) infection, we examined the phenotype of circulating B cells in newly diagnosed Africans. We found that all African individuals displayed low levels of naive B cells and of memory-type CD27+ B cells, and high levels of differentiated B cells. On the other hand, HIV-infected African patients had a population of germinal center B cells (i.e. CD20+, sIgM-, sIgD+, CD77+, CD138(+/-)), which are generally restricted to lymph nodes and do not circulate unless the lymph node architecture is altered. The first observations could be linked to the tropical environment whereas the presence of germinal center B cells may be attributable to chronic exposure to HIV as it is not observed in HIV-negative African controls and HAART treated HIV-infected Europeans. It may impact the management of HIV infection in countries with limited access to HIV drugs and urges consideration for implementation of therapeutic vaccines.

Adult↗

PubMed2004

Specific antibody production by blood B cells is retained in late stage drug-naïve HIV-infected Africans.

Unseparated peripheral blood mononuclear cells (PBMCs) obtained from drug-naïve African individuals living in a context of multi-infections and presenting with high viral load (VL), were cultured in vitro and tested for their ability to produce antibodies (Abs) reacting with HIV-1 antigens. Within these PBMCs, circulating B cells were differentiated in vitro and produced IgG Abs against not only ENV, but also GAG and POL proteins. Under similar experimental conditions, HAART treated patients produced Abs to ENV proteins only. The in vitro antibody production by drug-naïve individuals' PBMCs depended on exogenous cytokines (IL-2 and IL-10) but neither on the re-stimulation of reactive cells in cultures by purified HIV-1-gp160 antigen nor on the re-engagement of CD40 surface molecules. Further, it was not abrogated by the addition of various monoclonal Abs (mAbs) to co-stimulatory molecules. This suggests that the in vitro antibody production by drug-naïve individuals' PBMCs resulted from the maturation of already envelope and core antigen-primed, differentiated B cells, presumably pre-plasma cells, which are not known to circulate at homeostasy. As in vitro produced Abs retained the capacity of binding antigen and forming complexes, this study provides pre-clinical support for functional humoral responses despite major HIV- and other tropical pathogen-induced B cell perturbations.

Adolescent↗

PubMed2004

Comparison between real-time PCR, conventional PCR and different staining techniques for diagnosing Pneumocystis jiroveci pneumonia from bronchoalveolar lavage specimens.

Between January 2002 and July 2003, 173 bronchoalveolar lavage (BAL) specimens from 150 patients (19 HIV-infected and 131 non-HIV-infected patients) were evaluated for identification of Pneumocystis jiroveci (formerly known as Pneumocystis carinii f. sp. hominis) using staining techniques, conventional PCR (mtLSUrRNA gene) and real-time PCR (MSG gene). Test results were compared to Pneumocystis pneumonia (PCP) confirmed by typical clinical findings and response to treatment. Sensitivity and specificity of the techniques were 60 and 100% for staining (where either one or both techniques were positive), 100 and 87.0% for conventional PCR and 100 and 84.9 % for real-time PCR, respectively. The use of a concentration of 10(3) copies of DNA per capillary of BAL as a cut-off (determined by real-time PCR) increased specificity from 84.9 to 98.6% without reducing the sensitivity of the technique. This technique is rapid (<3 h) and therefore of major interest in differentiating between asymptomatic carriage and PCP. A BAL specimen with <10(3) copies per capillary of Pneumocystis-specific DNA is more likely to indicate a chronic carrier state, but in such cases follow-up is required to ensure that the patient is not in the early stage of an active PCP.

AIDS-Related Opportunistic Infections↗

PubMed2003

[Streptococcus suis bacteremia].

INTRODUCTION: Streptococcus suis infection is recognised despite it rareness as a zoonotic occupational disease in humans, and is often associated with meningitis, more rarely with bacteremia. OBSERVATION: A Streptococcus suis bacteremia occurred in a hunter and was complicated by septic shock with disseminated intravascular coagulation, rhabdomyolysis and purpura fulminans. Contamination had occurred through inoculation of a cut on the thumb when the hunter was slaughtering a wild boar. The blood cultures isolated Streptococcus suis. The patient died 36 hours after admission, despite intensive care and adapted antibiotic treatment with penicillin A and macrolide. CONCLUSION: Streptococcus suis bacteremia are uncommon but serious in humans. Despite adapted treatment, evolution may be fatal, so their conditions of occurrence must be well known by hunters and practitioners.

Anti-Bacterial Agents↗

PubMed2003

Implication of a healthcare worker with chronic skin disease in the transmission of an epidemic strain of methicillin-resistant Staphylococcus aureus in a pediatric intensive care unit.

This outbreak of colonization of neonates in a 10-bed pediatric intensive care unit illustrates the probable role of a healthcare worker (HCW) in the transmission of methicillin-resistant Staphylococcus aureus, despite good hygienic practices. It raises the issue of preventive exclusion of HCWs affected by chronic skin disease from high-risk units.

Child↗

PubMed1998

Nosocomial legionellosis outbreak over a three-year period: investigation and control.

OBJECTIVE: To investigate the epidemiologic relatedness of nosocomial infections due to Legionella pneumophila serogroup 1 diagnosed between 1992 and 1994 in six immunocompromised patients of the same hospital and to describe the measures which were developed to control the outbreak. METHODS: Legionella strains isolated from patients and from potable hot water were compared using three typing methods: monoclonal antibody analysis, arbitrarily primed PCR and ribotyping. RESULTS: Environmental investigations revealed the presence of high levels of L. pneumophila serogroup 1 in hot water. The typing methods gave concordant results for demonstrating (1) the persistence of an epidemic strain of L. pneumophila serogroup 1 in the major water distribution circuit of the hospital over a 3-year period, and (2) the identity between patients' and environmental strains. Five of the six patients were probably infected via aerosols of hot tap water following inappropriate therapeutic procedures. Repetitive heat flushings associated with regular bacteriologic surveillance allowed correct disinfection of the water distribution systems. Specific recommendations concerning aerosol delivery and oxygen therapy were implemented in order to prevent further nosocomial legionellosis. CONCLUSIONS: The same strain of L. pneumophila had been able to colonize the main water circuit of the hospital for at least 3 years; the relatedness between clinical and environmental strains was easily confirmed by the use of molecular markers.

Journal Article↗