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Biomedical subjects

P Francioli

Publications and source records attributed to P Francioli.

At least 19 recordsLinked to original sources
PubMed2001

Genetic diversity of Pneumocystis carinii in HIV-positive and -negative patients as revealed by PCR-SSCP typing.

OBJECTIVE: To describe the epidemiology of severe Pneumocystis carinii pneumonia (PCP) in HIV-infected and non HIV-infected patients. METHODS: Bronchoalveolar lavage specimens from 212 European patients with PCP were typed using PCR--single strand conformation polymorphism analysis of four genomic regions of P. carinii f. sp. hominis. Demographic and clinical information was obtained from all patients. RESULTS: Twenty-three per cent of the patients were presumably infected with a single P. c. hominis type. The other patients presented with two (50%) or more (27%) types. Thirty-five genetically stable and ubiquitous P. c. hominis types were found. Their frequency ranged from 0.4% to 10% of all isolates, and up to 15% of those from a given hospital. There was no significant association between the P. c. hominis type or number of co-infecting types per patient and geographical location, year of collection, sex, age, or HIV status. No more than three patients infected with the same type were observed in the same hospital within the same 6 month period, and no epidemiological link between the cases was found. CONCLUSIONS: The broad diversity of types observed seems to indicate that multiple sources of the pathogen co-exist. There was no evidence that in our study population inter-human transmission played a significant role in the epidemiology of P. carinii.

Bronchoalveolar Lavage↗
PubMed2001

Community-acquired pneumonia. A prospective outpatient study.

We initiated a prospective study with a group of practitioners to assess the etiology, clinical presentation, and outcome of community-acquired pneumonia in patients diagnosed in the outpatient setting. All patients with signs and symptoms suggestive of pneumonia and an infiltrate on chest X-ray underwent an extensive standard workup and were followed over 4 weeks. Over a 4-year period, 184 patients were eligible, of whom 170 (age range, 15-96 yr; median, 43 yr) were included and analyzed. In 78 (46%), no etiologic agent could be demonstrated. In the remaining 92 patients, 107 etiologic agents were implicated: 43 were due to "pyogenic" bacteria (39 Streptococcus pneumoniae, 3 Haemophilus spp., 1 Streptococcus spp.), 39 were due to "atypical" bacteria (24 Mycoplasma pneumoniae, 9 Chlamydia pneumoniae, 4 Coxiella burnetii, 2 Legionella spp.), and 25 were due to viruses (20 influenza viruses and 5 other respiratory viruses). There were only a few statistically significant clinical differences between the different etiologic categories (higher age and comorbidities in viral or in episodes of undetermined etiology, higher neutrophil counts in "pyogenic" episodes, more frequent bilateral and interstitial infiltrates in viral episodes). There were 2 deaths, both in patients with advanced age (83 and 86 years old), and several comorbidities. Only 14 patients (8.2%) required hospitalization. In 6 patients (3.4%), the pneumonia episode uncovered a local neoplasia. This study shows that most cases of community-acquired pneumonia have a favorable outcome and can be successfully managed in an outpatient setting. Moreover, in the absence of rapid and reliable clinical or laboratory tests to establish a definite etiologic diagnosis at presentation, the spectrum of the etiologic agents suggest that initial antibiotic therapy should cover both S. pneumoniae and atypical bacteria, as well as possible influenza viruses during the epidemic season.

Adolescent↗
PubMed2001

Study of Staphylococcus aureus pathogenic genes by transfer and expression in the less virulent organism Streptococcus gordonii.

Because Staphylococcus aureus strains contain multiple virulence factors, studying their pathogenic role by single-gene inactivation generated equivocal results. To circumvent this problem, we have expressed specific S. aureus genes in the less virulent organism Streptococcus gordonii and tested the recombinants for a gain of function both in vitro and in vivo. Clumping factor A (ClfA) and coagulase were investigated. Both gene products were expressed functionally and with similar kinetics during growth by streptococci and staphylococci. ClfA-positive S. gordonii was more adherent to platelet-fibrin clots mimicking cardiac vegetations in vitro and more infective in rats with experimental endocarditis (P < 0.05). Moreover, deleting clfA from clfA-positive streptococcal transformants restored both the low in vitro adherence and the low in vivo infectivity of the parent. Coagulase-positive transformants, on the other hand, were neither more adherent nor more infective than the parent. Furthermore, coagulase did not increase the pathogenicity of clfA-positive streptococci when both clfA and coa genes were simultaneously expressed in an artificial minioperon in streptococci. These results definitively attribute a role for ClfA, but not coagulase, in S. aureus endovascular infections. This gain-of-function strategy might help solve the role of individual factors in the complex the S. aureus-host relationship.

Animals↗
PubMed2001

Reemergence of gentamicin-susceptible strains of methicillin-resistant Staphylococcus aureus in France: a phylogenetic approach.

The reemergence of gentamicin-susceptible (Gen(s)) methicillin-resistant Staphylococcus aureus (MRSA) isolates in France between 1992 and 1996 was investigated using a phylogenetic approach (multiprimer randomly amplified polymorphic DNA typing). Eighty-six percent (65 of 85) of the French strains were grouped into one phylogenetic cluster within which all but one Gen(s) strain were grouped into a subcluster. Thus, the reemergence of Gen(s) MRSA strains in France was likely due to the spread of one specific clone which belonged to a cluster comprising most French gentamicin-resistant (Gen(r)) strains. This suggests that the Gen(s) clone has emerged from a Gen(r) strain of this cluster.

Anti-Bacterial Agents↗
PubMed2001

[Surgical site infection surveillance: an effective preventive measure].

Surgical site infection (SSI) is a feared complication of any surgical procedure. Despite clear progresses during the last decades, recent studies (some from Switzerland) show that many patients still suffer from SSIs and that SSIs have a huge impact for patients and public health. Thus, the prevention of SSIs must constitute a priority of nosocomial infections control in hospitals. In addition to classical approaches focusing on skin preparation, antibiotic prophylaxis, asepsis, and operative environment, surveillance has proved effective in decreasing the incidence of SSIs. The present paper reviews the principles and the main components of an SSI surveillance program.

Cross Infection↗
PubMed2000

Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study.

BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent among HIV-1-infected individuals, but its contribution to the morbidity and mortality of coinfected patients who receive potent antiretroviral therapy is controversial. We used data from the ongoing Swiss HIV Cohort Study to analyse clinical progression of HIV-1, and the virological and immunological response to potent antiretroviral therapy in HIV-1-infected patients with or without concurrent HCV infection. METHODS: We analysed prospective data on survival, clinical disease progression, suppression of HIV-1 replication, CD4-cell recovery, and frequency of changes in antiretroviral therapy according to HCV status in 3111 patients starting potent antiretroviral therapy. RESULTS: 1157 patients (37.2%) were coinfected with HCV, 1015 of whom (87.7%) had a history of intravenous drug use. In multivariate Cox's regression, the probability of progression to a new AIDS-defining clinical event or to death was independently associated with HCV seropositivity (hazard ratio 1.7 [95% CI 1.26-2.30]), and with active intravenous drug use (1.38 [1.02-1.88]). Virological response to antiretroviral therapy and the probability of treatment change were not associated with HCV serostatus. In contrast, HCV seropositivity was associated with a smaller CD4-cell recovery (hazard ratio for a CD4-cell count increase of at least 50 cells/microL=0.79 [0.72-0.87]). INTERPRETATION: HCV and active intravenous drug use could be important factors in the morbidity and mortality among HIV-1-infected patients, possibly through impaired CD4-cell recovery in HCV seropositive patients receiving potent antiretroviral therapy. These findings are relevant for decisions about optimum timing for HCV treatment in the setting of HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed2000

[Epidemiology of Lyme borreliosis in French-speaking Switzerland].

The purpose of this study was to assess the number of cases and the clinical aspects of Lyme borreliosis in French-speaking Switzerland. From July 1996 to December 1997, all laboratories performing serological tests for Lyme borreliosis sent a questionnaire to the treating physicians whenever the tests were positive. In addition, the physicians who diagnosed a case on clinical grounds only were also asked to report these cases. During this period, 1460 positive serological tests were recorded among approximately 10,360 performed (14%). A total of 775 questionnaires were returned (53%). In 3/4 of the cases, the test was ordered because of an acute clinical manifestation or a tick bite. The rest related to chronic symptoms or follow-up. In 504 cases (65%), diagnosis was considered certain or probable. These were erythema migrans in 46%, clinical manifestations of stage II in 33% (26 facial palsy, 20 acute arthritis, 5 benign cutaneous lymphocytoma) and chronic symptoms in 21% (23 acrodermatitis, 26 neuropathies, and 8 arthritis). The adjusted incidence, estimated on the basis of the treating physician's place of residence, ranged from 9/100,000 in Valais to 95/100,000 in Neuchâtel. This study indicates that Lyme borreliosis is a diagnosis frequently looked for and established in French-speaking Switzerland. Although erythema migrans is the main clinical manifestation, symptoms of stage II and III indicate that Lyme borreliosis is also responsible for relatively major systemic morbidity.

Adolescent↗
PubMed2000

Clinical epidemiology and research on HIV infection in Switzerland: the Swiss HIV Cohort Study 1988-2000.

BACKGROUND AND OBJECTIVES: The Swiss HIV Cohort Study (SHCS) was initiated in 1988 and represented the main scientific component of the comprehensive response to the AIDS epidemic in Switzerland. It brought together physicians and scientists from five university hospitals (Basel, Berne, Geneva, Lausanne and Zurich) and two Cantonal hospitals (Lugano and St. Gallen). The objective of SHCS was, and still is, to produce rapid, high quality patient-oriented medical research in the field of HIV infection. METHODS: SHCS is a prospective population-based cohort study. Any HIV-infected person aged > or = 16 years is eligible to participate. Data collection and study procedures are standardised. Data quality and protocol monitoring are conducted at the coordination and data centre in Lausanne. Detailed information on demographics, income, mode of HIV acquisition, risk behaviours, clinical events, laboratory results, treatment and treatment tolerance is collected at registration and at 6-monthly intervals. RESULTS: Since 1996, 10,600 persons have been enrolled and the SHCS study population is considered fairly representative of the HIV-infected population in Switzerland, at least in terms of gender and mode of HIV acquisition. In 1999, 4600 patients were actively followed up and more than 70% of patients were receiving highly active antiretroviral therapy (HAART). As a consequence, mortality and the incidence of HIV-related opportunistic infections have decreased significantly in the recent past. Between 1996 and 2000, 91 original manuscripts have been published by SHCS scientists and physicians, almost exclusively in peer-reviewed journals. A wide range of scientific questions have been addressed, including HIV primary infection, the natural history of HIV infection, the clinical and biological impact of HAART, drug resistance, risk factors for disease evolution including the timing of treatment initiation, the role of CD4 receptors, the validity of HIV surveillance reports, determinants of treatment access and tolerance, clinical trials of new drug combinations, the interruption of prophylaxis following a favourable response to HAART and issues relating to quality of life and interaction between income, social level and disease evolution. CONCLUSION: The SHCS has had, and continues to have, a significant impact on medical practice, public health and research in Switzerland and beyond. It represents a network of excellence which has brought together and fostered intensive collaboration between physicians and institutions throughout this country and beyond. This was possible thanks to the support of the Federal Office of Public Health and the commitment of primary care physicians, researchers and patients. This project may be model for focused and prioritised multicentre and transdisciplinary research programmes.

AIDS-Related Opportunistic Infections↗
PubMed2000

Clinical features and analysis of the duration of colonisation during an outbreak of Salmonella braenderup gastroenteritis.

During an outbreak of acute Salmonella braenderup gastroenteritis we performed a standardised interview encompassing questions on clinical symptoms in 156 (127 adults and 29 children) of 215 identified patients. Sequential stool cultures were obtained for up to five months in these 156 cases. We restricted the analysis to the 122 patients with at least 3 or more available cultures. They were treated with a fluoroquinolone, trimethoprim-sulfamethoxazole, or not treated with antibiotics, according to the decision of the practitioners. For this reason, a randomised double blind study was not possible. Minimum inhibitory concentrations (MIC) of the prescribed drugs were measured for representative isolates before and after treatment. The most frequent symptoms were diarrhoea (98%) and abdominal pain (96%). Vomiting occurred in 43% of cases. Children were more severely ill. Seven weeks after acute gastroenteritis, stool cultures were still positive for salmonella in 71% of the 22 children and 30% of the 100 adults examined (p < 0.002). This rate decreased progressively in both groups to 5 and 3% respectively at 20 weeks (n.s.). Among adults, no significant difference in enteric carriage over time could be demonstrated between untreated patients and those treated with either a fluoroquinolone or trimethoprim-sulfamethoxazole. MIC for salmonella isolates remained unchanged after treatment. In a cohort of patients infected with a single strain of salmonella, fluoroquinolone therapy of acute gastroenteritis failed to influence the duration of enteric carriage, despite continuing susceptibility of the strain. In children, the rate of clearance of Salmonella braenderup from stool was statistically lower until the tenth week after the acute disease, but there was no further difference after 5 months.

Adult↗
PubMed2000

Preemptive treatment approach to cytomegalovirus (CMV) infection in solid organ transplant patients: relationship between compliance with the guidelines and prevention of CMV morbidity.

Cytomegalovirus (CMV) remains a major cause of morbidity in solid organ transplant patients. In order to reduce CMV morbidity, we designed a program of routine virological monitoring that included throat and urine CMV shell vial culture, along with peripheral blood leukocyte (PBL) shell vial quantitative culture for 12 weeks post-transplantation, as well as 8 weeks after treatment for acute rejection. The program also included preemptive ganciclovir treatment for those patients with the highest risk of developing CMV disease, i.e., with either high-level viremia (>10 infectious units [IU]/106 PBL) or low-level viremia (<10 IU/106 PBL) and either D+/R- CMV serostatus or treatment for graft rejection. During 1995-96, 90 solid organ transplant recipients (39 kidneys, 28 livers, and 23 hearts) were followed up. A total of 60 CMV infection episodes occurred in 45 patients. Seventeen episodes were symptomatic. Of 26 episodes managed according to the program, only 4 presented with CMV disease and none died. No patient treated preemptively for asymptomatic infection developed disease. In contrast, among 21 episodes managed in non-compliance with the program (i.e., the monitoring was not performed or preemptive treatment was not initiated despite a high risk of developing CMV disease), 12 episodes turned into symptomatic infection (P=0.0048 compared to patients treated preemptively), and 2 deaths possibly related to CMV were recorded. This difference could not be explained by an increased proportion of D+/R- patients or an increased incidence of rejection among patients with episodes treated in non-compliance with the program. Our data identify compliance with guidelines as an important factor in effectively reducing CMV morbidity through preemptive treatment, and suggest that the complexity of the preemptive approach may represent an important obstacle to the successful prevention of CMV morbidity by this approach in the regular healthcare setting.

Adolescent↗
PubMed2000

Outbreak of Salmonella braenderup gastroenteritis due to contaminated meat pies: clinical and molecular epidemiology.

OBJECTIVES: To determine the epidemiologic, clinical and molecular characteristics of an outbreak of severe gastroenteritis due to the ingestion of meat pies highly contaminated with Salmonella braenderup. METHODS: In October 1993, we observed an outbreak of Salmonella braenderup gastroenteritis that occurred in the Lausanne area, Canton de Vaud, Switzerland. Cultures of suspected food products, of samples at the incriminated food factory and from workers, as well as a case-control study, were used to determine the source of the epidemics. Ribotyping of representative Salmonella braenderup strains was performed to define the molecular epidemiology. The clinical characteristics of this infection were determined by using a standardized interview performed during and 6 months after the outbreak in 156 of 215 identified patients. RESULTS: The outbreak resulted from the ingestion of pies, heavily contaminated (> 106 CFU/g) with a strain of Salmonella braenderup. The contamination was due to mishandling and recycling of jelly poured on top of the products. According to its ribotype and plasmid characteristics, this strain had not been isolated previously in Switzerland. Ten of the 24 workers of the incriminated food factory were shedding the epidemic strain in their stools, and one of them reported gastroenteritis 3 weeks before the beginning of the outbreak. The estimated attack rate in the exposed population was 7.5%. The median incubation time was 18 h. Among 127 adult patients studied, 98% had diarrhea, 95% abdominal pain, 74% fever > or = 38.5 degrees C, 69% nausea and 35% vomiting. One patient developed prosthetic valve endocarditis, and one reactive arthritis. Long-term complications were not identified, although 12 patients complained of irritable bowel syndrome and 24 of unusual asthenia lasting for more than 6 weeks after infection. Children had more severe signs and symptoms compared to adults, and six of 29 needed hospitalization. CONCLUSIONS: This study showed that ingestion of food highly contaminated with Salmonella braenderup resulted in severe but typical gastroenteritis and indicated mishandling of food during manufacture as the cause of this outbreak.

Adult↗
PubMed2000

Methicillin-resistant Staphylococcus aureus: phylogenetic relatedness between European epidemic clones and Swiss sporadic strains.

We have compared the phylogenetic diversity of methicillin-resistant Staphylococcus aureus (MRSA) strains from Switzerland and their phylogenetic relationships with European epidemic clones, using multiprimer random amplification polymorphic DNA (RAPD). Strains included 24 European epidemic clones (59 strains), 66 sporadic strains isolated in Switzerland in 1996-1997, and 15 reference strains of five other Staphylococcus species. Similarity and clustering analysis with the Jaccard's coefficient showed that the maximum genetic distance between MRSA strains was 0.43, whereas the minimum genetic distance between the six Staphylococcus species was 0.97, indicating that the method permits phylogenetic hierarchization. The 24 MRSA clones reported to be epidemic in European countries during the 1990s were distributed into seven different genetic clusters with a maximum distance of 0.29 among them. This clustering pattern was confirmed by the analysis of a subset of MRSA strains by multilocus enzyme electrophoresis at 12 loci. Most of the sporadic Swiss strains were distributed into these seven different genetic clusters, together with the epidemic MRSA clones. This suggests that there is no phylogenetic cluster specific to epidemic clones of MRSA.

Clone Cells↗
PubMed2000

Expression of Staphylococcus aureus clumping factor A in Lactococcus lactis subsp. cremoris using a new shuttle vector.

Staphylococcus aureus harbors redundant adhesins mediating tissue colonization and infection. To evaluate their intrinsic role outside of the staphylococcal background, a system was designed to express them in Lactococcus lactis subsp. cremoris 1363. This bacterium is devoid of virulence factors and has a known genetic background. A new Escherichia coli-L. lactis shuttle and expression vector was constructed for this purpose. First, the high-copy-number lactococcal plasmid pIL253 was equipped with the oriColE1 origin, generating pOri253 that could replicate in E. coli. Second, the lactococcal promoters P23 or P59 were inserted at one end of the pOri253 multicloning site. Gene expression was assessed by a luciferase reporter system. The plasmid carrying P23 (named pOri23) expressed luciferase constitutively at a level 10,000 times greater than did the P59-containing plasmid. Transcription was absent in E. coli. The staphylococcal clumping factor A (clfA) gene was cloned into pOri23 and used as a model system. Lactococci carrying pOri23-clfA produced an unaltered and functional 130-kDa ClfA protein attached to their cell walls. This was indicated both by the presence of the protein in Western blots of solubilized cell walls and by the ability of ClfA-positive lactococci to clump in the presence of plasma. ClfA-positive lactococci had clumping titers (titer of 4,112) similar to those of S. aureus Newman in soluble fibrinogen and bound equally well to solid-phase fibrinogen. These experiments provide a new way to study individual staphylococcal pathogenic factors and might complement both classical knockout mutagenesis and modern in vivo expression technology and signature tag mutagenesis.

Bacterial Adhesion↗
PubMed2000

Contribution of clumping factor B to pathogenesis of experimental endocarditis due to Staphylococcus aureus.

Staphylococcus aureus Newman with an insertion mutation in clfB, the gene encoding clumping factor B, only marginally decreased infection rate (P>0.05) in rats with experimental endocarditis. In contrast, clfB complementation on a multicopy plasmid significantly increased infectivity (P<0.05) over the deleted mutants. Although clfB could affect endovascular infection, its importance in experimental endocarditis was limited.

Adhesins, Bacterial↗