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Biomedical subjects

Vincent Foulongne

Publications and source records attributed to Vincent Foulongne.

14 recordsLinked to original sources
PubMed2006

Impact of suppressive herpes therapy on genital HIV-1 RNA among women taking antiretroviral therapy: a randomized controlled trial.

OBJECTIVE: To demonstrate a causal relationship between herpes simplex virus 2 (HSV-2) and increased genital HIV-1-RNA shedding in women on HAART. DESIGN: A randomized, double-blind, placebo-controlled trial of herpes-suppressive therapy (valacyclovir 500 mg twice a day) in HIV-1/HSV-2-infected women taking HAART in Burkina Faso. METHODS: Participants were followed for a total of 12 biweekly visits before and after randomization. The presence and frequency of genital and plasma HIV-1 RNA, and of genital HSV-2 were assessed using summary measures, adjusting for baseline values. Random effect linear regression models were used to assess the impact of treatment on genital and plasma viral loads among visits with detectable virus. RESULTS: Sixty women were enrolled into the trial. Their median CD4 lymphocyte count was 228 cells/mul, and 83% had undetectable plasma HIV-1 RNA at baseline. Valacyclovir reduced the proportion of visits with detectable genital HSV-2 DNA [odds ratio (OR) 0.37, 95% confidence interval (CI) 0.13, 1.05], but had no significant impact on the frequency (OR 0.90, 95% CI 0.31, 2.62) or quantity (reduction of 0.33 log copies/ml, 95% CI -0.81, 0.16) of genital HIV-1 RNA. However, according to pre-defined secondary analyses restricted to women who shed HIV-1 at least once in the baseline phase, valacyclovir reduced both the proportion of visits with detectable HIV-1 shedding (OR 0.27, 95% CI 0.07, 0.99) and the quantity of genital HIV-1 RNA during these visits (-0.71 log10 copies/ml, 95% CI -1.27, -0.14). CONCLUSION: HSV-2 facilitates residual genital HIV-1 replication among dually infected women taking HAART despite HIV-1 suppression at the systemic level.

Acyclovir↗
PubMed2006

Human metapneumovirus infection in young children hospitalized with respiratory tract disease.

BACKGROUND: Human metapneumovirus (hMPV) is a newly recognized pathogen associated with respiratory tract disease (RTD). OBJECTIVES: To evaluate the incidence of hMPV infection in children hospitalized with RTD and to analyze the virologic and clinical features of hMPV infection. STUDY DESIGN: All children younger than 5 years of age hospitalized for RTD were included in this 1-year prospective study. hMPV was detected in nasopharyngeal secretions by reverse transcription polymerase chain reaction. The hMPV F gene amplification products were sequenced, and a phylogenetic tree was constructed. Samples were also tested for other respiratory viruses by both direct immunofluorescence assay and virus culture. RESULTS: hMPV, detected in 50 of 589 (8.5%) children, represented the second leading cause of RTD after respiratory syncytial virus (RSV). Infections with hMPV occurred mainly between December and April. hMPV isolates clustered into the 4 subgroups (A1, A2, B1 and B2) currently recognized; the majority (72%) of hMPV isolates belonged to subgroup A1. Among the 35 children infected with hMPV alone, 23 (65.7%) had bronchiolitis, 5 (14.3%) had pneumonia, 2 (5.7%) had asthma exacerbation and 5 (14.3%) had a limited upper RTD. Fifteen (30%) of the hMPV-infected children were coinfected with RSV. As compared with children infected with hMPV or RSV alone, duration of hospitalization and requirement for supplemental oxygen were increased in the hMPV/RSV-coinfected children. CONCLUSIONS: hMPV is a frequent cause of RTD in young children. hMPV/RSV coinfection is frequent and could be more severe than a single hMPV or RSV infection.

Child, Preschool↗
PubMed2006

Comparison of the LCx human immunodeficiency virus (HIV) RNA quantitative, RealTime HIV, and COBAS AmpliPrep-COBAS TaqMan assays for quantitation of HIV type 1 RNA in plasma.

The LCx human immunodeficiency virus (HIV) RNA Quantitative, RealTime HIV, and COBAS AmpliPrep-COBAS TaqMan assays for HIV type 1 (HIV-1) were compared for their abilities to quantitate HIV-1 RNA in plasma. High degrees of correlation and agreement were observed between the assays. Differences in HIV-1 RNA levels according to HIV-1 subtypes did not reach statistical significance.

HIV Infections↗
PubMed2006

Human bocavirus in French children.

Human bocavirus (HBoV), a new member of the genus Bocavirus in the family Parvoviridae, has been recently associated with respiratory tract infections. We report the epidemiologic and clinical features observed from a 1-year retrospective study of HBoV infection in young children hospitalized with a respiratory tract infection.

Child, Preschool↗
PubMed2005

Quantitation of HIV-1 RNA in breast milk by real time PCR.

HIV-1 RNA in breast milk is a strong predictor of HIV-1 transmission through breastfeeding. In the present report, breast milk samples from HIV-1 uninfected donors were spiked with dilution of quantified culture supernatant from HIV-1(NDK) infected PBMC. Two RNA extraction techniques based on silica extraction, Nuclisens (BioMerieux) and Triazol (Qiagen), two techniques based on guanidine thiocynanate/chloroforme extraction, TRIzol (Life Technologie) and Amplicor HIV-1 Monitor (Roche Diagnostic Systems), and one technique based on electrostatic adsorption on iron oxide micro beads (Promega) were compared. HIV-1 RNA was quantitated by real time PCR (LTR gene) and Amplicor HIV-1 Monitor. Combining magnetic micro beads extraction and real time PCR quantitation allowed to correctly quantify breast milk HIV-1 RNA, with a difference between the expected and measured HIV-1 RNA levels always lower than 0.3 log copies/ml. The same combination was confirmed on 25 breast milk samples from HIV-1 infected women collected in Kwazulu-Natal, South Africa, by comparing measurements with those obtained by the Amplicor HIV-1 Monitor (r(2)=0.88). Nucleic acid extraction by magnetic micro beads followed by real time PCR is a reliable, sensitive, rapid and simple procedure to quantify HIV-1 RNA in breast milk and allows for PCR inhibitors found frequently in these samples.

Female↗
PubMed2005

Longitudinal assessment of HIV-1 and HSV-2 shedding in the genital tract of West African women.

Forty-two HSV-2-seropositive women, of whom 22 were HIV-1 seropositive, were followed up weekly for 3 weeks for assessment of HIV-1 and HSV-2 genital shedding in Bobo Dioulasso, Burkina Faso. HSV-2 DNA and HIV-1 RNA were quantitated in cervicovaginal lavages enriched with a cervical swabbing (eCVL) using real-time polymerase chain reaction. HIV-1 RNA shedding was detected in eCVL from 19 of 22 (86.4%) of the HIV-1-seropositive women and HSV-2 DNA was detected in eCVL from 12 of 42 (28.6%) of the women. Compared with the HIV-1-seronegative women, the HIV-1-seropositive women showed more persistent HSV-2 genital shedding and higher HSV-2 DNA loads in eCVL. This study showed that eCVL is a reliable sampling method for detecting both viruses. Three measurement points (at weekly intervals in this study) seem to adequately allow detection of most HIV-1 or HSV-2 genital shedders.

Adult↗
PubMed2004

[Human metapneumovirus pneumonia in an adult patient hospitalized for suspected severe acute respiratory syndrome (SARS)].

INTRODUCTION: Human metapneumovirus (hMPV) is a newly identified virus responsible for occasionally severe respiratory infections, mainly observed in children. OBSERVATION: A 59-year old man was hospitalised for respiratory problems and fever 3 days after his return from China during the epidemic of severe acute respiratory syndrome (SARS). Other than fever (>38 degrees C), the patient exhibited a dry cough, myalgias, arthralgias and mild lymphopenia and the chest radiography showed an opacity on the right lower lung. Conventional virological investigations remained negative. Detection of the novel SARS-associated coronavirus was negative but hMPV detection was positive. DISCUSSION: The present observation indicates that hMPV may cause respiratory symptoms mimicking initial manifestations of SARS in adults visiting epidemic countries. CONCLUSION: hMPV testing has clinical utility in adult patients with acute respiratory tract infection.

DNA, Viral↗
PubMed2003

Smooth and rough lipopolysaccharide phenotypes of Brucella induce different intracellular trafficking and cytokine/chemokine release in human monocytes.

Virulence of the intracellular pathogen Brucella for humans is mainly associated with its lipopolysaccharide (LPS) phenotype, with smooth LPS phenotypes generally being virulent and rough ones not. The reason for this association is not quite understood. We now demonstrate by flow cytometry, electron microscopy, and ELISA that human peripheral blood monocytes interact both quantitatively and qualitatively different with smooth and rough Brucella organisms in vitro. We confirm that considerably higher numbers of rough than smooth brucellae attach to and enter the monocytes in nonopsonic conditions; but only smooth brucellae replicate in the host cells. We show for the first time that rough brucellae induce higher amounts than smooth brucellae of several CXC (GRO-alpha, IL-8) and CC (MIP-1alpha, MIP-1beta, MCP-1, RANTES) chemokines, as well as pro- (IL-6, TNF-alpha) and anti-inflammatory (IL-10) cytokines released by challenged monocytes. Upon uptake, phagosomes containing rough brucellae develop selective fusion competence to form spacious communal compartments, whereas phagosomes containing smooth brucellae are nonfusiogenic. Collectively, our data suggest that rough brucellae attract and infect monocytes more effectively than smooth brucellae, but only smooth LPS phenotypes establish a specific host cell compartment permitting successful parasitism. These novel findings link the LPS phenotype of Brucella and its virulence for humans at the level of the infected host cells. Whether this is due to a direct effect of the LPS molecules or to upstream bacterial mechanisms remains to be established.

Brucella↗
PubMed2002

Type IV secretion and Brucella virulence.

The type IV secretion system, encoded by the virB region, is a key virulence factor for Brucella. The 12 genes of the region form an operon that is specifically induced by phagosome acidification in cells after phagocytosis. We speculate that the system serves to secrete unknown effector molecules, which allow Brucella to pervert the host cell endosomal pathways and to create a novel intracellular compartment in which it can replicate.

Animals↗
PubMed2002

The analysis of the intramacrophagic virulome of Brucella suis deciphers the environment encountered by the pathogen inside the macrophage host cell.

The pathogen Brucella suis resides and multiplies within a phagocytic vacuole of its host cell, the macrophage. The resulting complex relationship has been investigated by the analysis of the set of genes required for virulence, which we call intramacrophagic virulome. Ten thousand two hundred and seventy-two miniTn5 mutants of B. suis constitutively expressing gfp were screened by fluorescence microscopy for lack of intracellular multiplication in human macrophages. One hundred thirty-one such mutants affected in 59 different genes could be isolated, and a function was ascribed to 53 of them. We identified genes involved in (i) global adaptation to the intracellular environment, (ii) amino acid, and (iii) nucleotide synthesis, (iv) sugar metabolism, (v) oxidoreduction, (vi) nitrogen metabolism, (vii) regulation, (viii) disulphide bond formation, and (ix) lipopolysaccharide biosynthesis. Results led to the conclusion that the replicative compartment of B. suis is poor in nutrients and characterized by low oxygen tension, and that nitrate may be used for anaerobic respiration. Intramacrophagic virulome analysis hence allowed the description of the nature of the replicative vacuole of the pathogen in the macrophage and extended our understanding of the niche in which B. suis resides. We propose calling this specific compartment "brucellosome."

Adaptation, Physiological↗
PubMed2002

The Brucella suis virB operon is induced intracellularly in macrophages.

A type IV secretion system similar to the VirB system of the phytopathogen Agrobacterium tumefaciens is essential for the intracellular survival and multiplication of the mammalian pathogen Brucella. Reverse transcriptase-PCR showed that the 12 genes encoding the Brucella suis VirB system form an operon. Semiquantitative measurements of virB mRNA levels by slot blotting showed that transcription of the virB operon, but not the flanking genes, is regulated by environmental factors in vitro. Flow cytometry used to measure green fluorescent protein expression from the virB promoter confirmed the data from slot blots. Fluorescence-activated cell sorter analysis and fluorescence microscopy showed that the virB promoter is induced in macrophages within 3 h after infection. Induction only occurred once the bacteria were inside the cells, and phagosome acidification was shown to be the major signal inducing intracellular expression. Because phagosome acidification is essential for the intracellular multiplication of Brucella, we suggest that it is the signal that triggers the secretion of unknown effector molecules. These effector molecules play a role in the remodeling of the phagosome to create the unique intracellular compartment in which Brucella replicates.

Bacterial Proteins↗
PubMed2002

[Brucella at the dawn of the third milenium: genomic organization and pathogenesis].

Bacteria of the genus Brucella, responsible for brucellosis, are pathogenic for animals and occasionally for humans. The cost of this widespread zoonotic infection is still very high for the community. Over the last few years, there have been advances in two main domains. First, the Brucella genome has been shown to be complex, with two circular chromosomes. Second, recent data on the virulence of Brucella suggest common mechanisms shared with plant pathogens and endosymbionts of the alpha-proteobacteria. Understanding virulence will have practical repercussions in the realms of vaccine development and, perhaps, development of new antibiotics. Two complete Brucella genome sequences are now available and will be a gold mine of information to guide future research.

Animals↗
PubMed2002

Experimental application of the median-effect principle for in vitro quantification of the combined inhibitory activities of clavulanic acid and imipenem against IRT-4 beta-lactamase.

Inhibitor-resistant TEM beta-lactamases (IRT) have been identified in Enterobacteriaceae which, however, remained susceptible to cephalosporins. We evaluated the combined inhibitory activity of clavulanic acid and imipenem at ratios of 1:1 and 1:3 against IRT-4, using the median effect principle of Chou and Talalay. The combination of the two drugs, which produced a nearly additive effect, meant their concentrations could be lowered 1.3-4.9-fold, while maintaining a 50% inhibitory effect against the IRT-4 in comparison with each drug alone. From a therapeutic point of view, such a combination is not efficient but this method of Chou and Talalay, used for the first time to assay combined inhibitory activity of beta-lactamase inhibitors, could be used to evaluate new molecules and/or strategies to inactivate beta-lactamase.

Anti-Bacterial Agents↗