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Biomedical subjects

D Raoult

Publications and source records attributed to D Raoult.

At least 19 recordsLinked to original sources
PubMed1999

Subversion of monocyte functions by coxiella burnetii: impairment of the cross-talk between alphavbeta3 integrin and CR3.

Several intracellular pathogens exploit macrophages as a niche for survival and replication. The success of this strategy requires the subversion or the avoidance of microbicidal functions of macrophages. Coxiella burnetii, the agent of Q fever, is a strictly intracellular bacterium that multiplies in myeloid cells. The survival of C. burnetii may depend on the selective use of macrophage receptors. Virulent C. burnetii organisms were poorly internalized but survived successfully in human monocytes, whereas avirulent variants were efficiently phagocytosed but were also rapidly eliminated. The uptake of avirulent organisms was mediated by leukocyte response integrin (alphavbeta3 integrin) and CR3 (alphaMbeta2 integrin), as demonstrated by using specific Abs and RGD sequence-containing peptides. The phagocytic efficiency of CR3 depends on its activation via alphavbeta3 integrin and integrin-associated protein. Indeed, CR3-mediated phagocytosis of avirulent C. burnetii was abrogated in macrophages from integrin-associated protein-/- mice. In contrast, the internalization of virulent C. burnetii organisms involved the engagement of alphavbeta3 integrin but not that of CR3. The pretreatment of monocytes with virulent C. burnetii organisms prevented the CR3-mediated phagocytosis of zymosan particles and CR3 activation assessed by the expression of the 24 neo-epitope. We conclude that the virulence of C. burnetii is associated with the engagement of alphavbeta3 integrin and the impairment of CR3 activity, which probably results from uncoupling alphavbeta3 integrin from integrin-associated protein. This study describes a strategy not previously reported of phagocytosis modulation by intracellular pathogens.

Antigens, CD↗
PubMed1999

Intraspecies diversity of Coxiella burnetii as revealed by com1 and mucZ sequence comparison.

Coxiella burnetii is classified within the gamma subgroup of the Proteobacteria. All strains tested to date have an identical 16S rRNA sequence but 20 different genotypes have been determined by pulsed field gel electrophoresis (PFGE). In this study, intraspecies genetic diversity was investigated by sequence comparison of 715 bp of the Com1 encoding gene (com1) and 774 bp of the MucZ encoding gene (mucZ) in 37 strains isolated from animals and humans with acute or chronic Q fever in Europe, North America and Africa. Five and four groups were established from sequence analysis of com1 and mucZ, respectively. Neither relation of the defined groups to geographical distribution of the isolates was noted nor relation to disease form (acute/chronic). The same isolates were grouped together regardless of the gene being investigated. Comparison of the five proposed groups to previous groups, yielded after digestion by NotI PFGE, allowed for an intermediate classification of C. burnetii isolates between those obtained by using 16S rDNA (one group) and PFGE (20 groups).

Animals↗
PubMed1999

[African Rickettsia infections].

EPIDEMIOLOGY: African rickettsiasis is transmitted by Rickettsia africae, a cattle tick. Amblyomma spp. is an emerging rickettsiasis in sub-sehalian Afric described in 1992. Seroepidemiology studies conducted in Africa show that it is probably the most widespread rickettsiasis in the sorld. In addition, the development of tourist activities in southern African countries has led to an increase in the number of reported cases in subjects returning from endemic areas. A high serprevalence of anti R. africae anticodies has been recently reported in the guadeloupe (French East Indies) population as well as one documented infection. CLINIC: The clinical expression of African tick rickettsiasis includes fevder, headache, inoculation scar, locoredgional node enlargement, and an inconsistent sometimes vesicular rash. The diagnosis is made on the basis of serological findings and cross absorption of anti R. africae and R. conorii antibodies and/or isolation or gene amplification of R. africae from inoculation scar biopsies.

Africa↗
PubMed1999

Hyperendemic focus of Q fever related to sheep and wind.

Q fever is a worldwide zoonosis which is caused by Coxiella burnetii and presents as both acute or chronic cases. The disease can be transmitted from animal reservoirs to humans by the inhalation of infected aerosols. The authors investigated the epidemiology of Q fever in the Bouches-du-Rhône district of southern France. The study area was centered around the small town of Martigues near the cities of Marseille and Aix-en-Provence, where the incidence of the disease seemed higher than in neighboring areas. Epidemiologic data included sheep breeding and wind. Between 1990 and 1995, Q fever was diagnosed in 289 patients, leading to an incidence rate of 35.4 per 100,000 in the study area (range: 6-132), compared with 6.6 in the area of Marseille, and 11.4 in the area of Aix-en-Provence. There was a graphical and statistical relation between the sheep densities, the incidence of the disease, and the strong, local wind known as the Mistral, which blows from the northwest. Although Coxiella burnetii transmission is multifactorial, we may speculate that the high endemicity in the study area is related to a contamination by aerosols because the Mistral blows through the local steppe where 70,000 sheep are bred. This public health problem requires further studies in order to confirm this hypothesis, and to identify more individual and preventable risk factors.

Adolescent↗
PubMed1999

Determination of the genome size of Ehrlichia spp., using pulsed field gel electrophoresis.

Ehrlichiae are obligatory intracellular, Gram-negative bacteria which belong to the alpha subclass of the phylum Proteobacteria and are responsible for infectious diseases of humans. Little is known about genetics and genomic organization of Ehrlichia spp. The genome sizes of four representatives of the genus Ehrlichia were determined for the first time by pulsed field gel electrophoresis. The sizes for E. sennetsu, E. risticii, E. chaffeensis (strain Arkansas and strain 91HE17), and the HGE agent were 878.5 kb, 880.3 kb, 1225.8 kb, 1262.3 kb and 1494 kb respectively.

Animals↗
PubMed1999

[Bartonella infection in humans].

BARTONELLA BACILLIFORMIS: Among the 3 species of Bartonella known to be human pathogens, B. bacilliformis causes Carriun's disease, which manifests an acute phase (Oroya fever) and a chronic phase marked by benign skin eruption with wart like macules of vascular origin. Until 1993, B. bacilliformis was considered to be the only species in Bartonella genus. In 1993, species formally in the Rochalimaea genus were designated as Bartonella species. BARTONELLA QUINTANA: This species causes trench fever. It is also the causal agent in cases of bacillary angiomatosis, septicemia, endocarditis with negative blood cultures, and chronic nodal infections, particularly in immunosuppressed patients. Trench fever is transmitted by body lice and is becoming more prevalent, particularly in the homeless. BARTONELLA HENSELAE: This agent causes bacillary angiomatosis, visceral peliosis, septicemia, endocarditis and cat-scratch disease. Transmitted by cats, and perhaps by lice, cat-scratch disease is one of the most frequent zoonoses. OTHER SPECIES: The spectrum of Bartonella infections has continued to widen these last 5 years. The role of B. elizabethae and C. clarridgeiae as human pathogens remains to be defined [abstract corrected]

Bartonella Infections↗
PubMed1999

IFN-gamma-mediated control of Coxiella burnetii survival in monocytes: the role of cell apoptosis and TNF.

The treatment of infectious diseases caused by intracellular bacteria, such as Q fever, may benefit from cytokines acting on macrophages. Monocytic THP-1 cells were infected with Coxiella burnetii, the etiological agent of Q fever, and then treated with IFN-gamma. While C. burnetii multiplied in untreated monocytes, IFN-gamma reduced bacterial viability after 24 h of treatment and reached maximum inhibition after 96 h. IFN-gamma also affected the viability of infected cells. Cell death resulted from apoptosis; occurring 24 h after the addition of IFN-gamma, it reached a maximum after 48 h and was followed by necrosis. Reactive oxygen intermediates were not required for C. burnetii killing, since monocytes from patients with chronic granulomatous disease were microbicidal in response to IFN-gamma. The role of cytokines was also investigated. IFN-gamma elicited a moderate release of IL-1beta in infected monocytes. Moreover, the IL-1 receptor antagonist did not affect C. burnetii survival, suggesting that IL-1beta was not involved in the bacterial killing induced by IFN-gamma. TNF was involved in IFN-gamma-induced killing of C. burnetii and cell death. IFN-gamma induced mRNA expression and sustained secretion of TNF. Neutralizing Abs to TNF as well as Abs directed against TNF receptors I and II, significantly prevented IFN-gamma-dependent killing of C. burnetii and cell death. These results suggest that IFN-gamma promotes the killing of C. burnetii in monocytes through an apoptotic mechanism mediated in part by TNF.

Animals↗
PubMed1999

Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydroxychloroquine.

BACKGROUND: Q fever endocarditis, caused by Coxiella burnetii, is fatal in 25% to 60% of patients. Currently, treatment with a long-term tetracycline and quinolone regimen for at least 4 years is recommended, although relapses are frequent. METHODS: Between January 1987 and December 1997, the reference treatment of Q fever endocarditis was compared with one of doxycycline and hydroxychloroquine sulfate. Patients were treated by conventional therapy until May 1991 and then by the new regimen. Microimmunofluorescence was used for antibody-level determination for diagnosis and follow-up. RESULTS: Thirty-five patients were included in the study, 26 males and 9 females. Of 14 patients treated with a doxycycline and quinolone combination, 1 died, 7 relapsed (3 were re-treated and 4 switched to the new regimen), 1 is still being treated, and 5 were considered cured using this regimen only. The mean duration of therapy for cure in this group was 55 months (median, 60 months). Twenty-one patients received the doxycycline and hydroxychloroquine regimen: 1 patient died of a surgical complication, 2 are still being treated, 17 were cured, and 1 is currently being evaluated. Two patients treated for 12 months but none of the patients treated for longer than 18 months relapsed. The mean duration of treatment in this group was 31 months (median, 26 months). No significant differences were observed between the 2 regimens in terms of death, valve surgery, or tolerance. The mortality rate for both regimens in this study was 5%. CONCLUSION: Prescription of the doxycycline and hydroxychloroquine combination for at least 18 months allows shortening of the duration of therapy and reduction in the number of relapses.

Adult↗
PubMed1999

Chronic Bartonella quintana bacteremia in homeless patients.

BACKGROUND: Infection with Bartonella quintana can cause trench fever, endocarditis, bacillary angiomatosis, and peliosis. An outbreak of bacteremia due to B. quintana has been reported among homeless people in Seattle, and the seroprevalence is high among homeless people in both the United States and Europe. Body lice are known to be the vectors of B. quintana. METHODS: We studied all the homeless people who presented in 1997 to the emergency departments of the University Hospital, Marseilles, France. Blood was collected for microimmunofluorescence testing for antibodies against B. quintana and for culture of the bacterium. Body lice were collected and analyzed by the polymerase chain reaction and sequencing of a portion of the citrate synthase gene of B. quintana. RESULTS: In 10 of 71 homeless patients (14 percent), blood cultures were positive for B. quintana, and 21 of the patients (30 percent) had high titers of antibody against the organism. A total of 17 patients (24 percent) had evidence of recent infection (bacteremia or seroconversion). Tests of lice from 3 of the 15 patients from whom they were collected were positive for B. quintana. The homeless people with B. quintana bacteremia were more likely to have been exposed to lice (P=0.002), were more likely to have headaches (P=0.03) and severe leg pain (P<0.001), and had lower platelet counts (P=0.006) than the homeless people who were seronegative for B. quintana and did not have bacteremia; 8 of the 10 patients with bacteremia were afebrile. Five patients had chronic bacteremia, as indicated by positive blood cultures over a period of several weeks. CONCLUSIONS: In an outbreak of urban trench fever among homeless people in Marseilles, B. quintana infections were associated with body lice in patients with nonspecific symptoms or no symptoms.

Adult↗
PubMed1999

Value and limitations of the Duke criteria for the diagnosis of infective endocarditis.

OBJECTIVES: The purpose of this study was to assess the value and limitations of Duke criteria for the diagnosis of infective endocarditis (IE). BACKGROUND: Duke criteria have been shown to be more sensitive in diagnosing IE than the von Reyn criteria, but the diagnosis of IE remains difficult in some patients. METHODS: Both classifications were applied in 93 consecutive patients with pathologically proven IE. Blood cultures, and transthoracic and transesophageal echocardiography were performed in all patients. RESULTS: Sensitivities for the diagnosis of IE were 56% and 76% for von Reyn and Duke criteria, respectively. Fifty-two patients were correctly classified as "probable IE" by von Reyn and "definite IE" by Duke criteria (group 1). However, discrepancies were observed in 41 patients. Eleven patients (group 2) were misclassified as "rejected" by von Reyn, but were "definite IE" by Duke criteria; this difference could be explained by negative blood cultures and positive echocardiogram in all patients. In eight patients (group 3), the diagnosis of IE was "possible" by von Reyn but "definite" by Duke criteria. This difference was essentially explained by the failure of the von Reyn classification to consider echocardiographic abnormalities as major criteria. Twenty-two patients (group 4) were misclassified as possible IE using Duke criteria, being false negative of this classification. Echocardiographic major criteria were present in 19 patients, but blood cultures were negative in 21 patients. The cause of negative blood cultures was prior antibiotic therapy in 11 patients and Q-fever endocarditis diagnosed by positive serology in three cases. CONCLUSIONS: Twenty-four percent of patients with proved IE remain misclassified as "possible IE" despite the use of Duke criteria, especially in cases of culture-negative and Q-fever IE. Increasing the diagnostic value of echographic criteria in patients with prior antibiotic therapy and typical echocardiographic findings and considering the serologic diagnosis of Q fever as a major criterion would further improve the clinical diagnosis of IE.

Bacteria↗
PubMed1999

Circulating cytokine balance and activation markers of leucocytes in Q fever.

As Q fever is associated with an inflammatory syndrome, we determined circulating levels of inflammatory cytokines, cytokine antagonists, and activation markers of leucocytes in patients with acute Q fever and Q fever endocarditis. Tumour necrosis factor (TNF) and IL-6, but not IL-1beta, were markedly increased compared with controls. Cytokine antagonists and activation markers of leucocytes were profoundly different in acute and chronic Q fever. IL-1 receptor antagonist and TNF receptor type II were significantly increased in patients with acute Q fever, suggesting a shift of cytokine balance towards cytokine antagonists. The activation marker of B cells, sCD23, was significantly increased in Q fever endocarditis compared with controls and patients with acute Q fever. In a 2-year follow-up study of patients with Q fever endocarditis, sCD23 and specific IgG levels slowly decreased in patients whose symptoms resolved, but remained high in those who required prolonged treatment.

Adult↗
PubMed1999

African tick-bite fever imported into Norway: presentation of 8 cases.

We report on 8 Norwegian travellers to Southern Africa with African tick-bite fever (ATBF), a recently described spotted fever group rickettsiosis. All patients had acute flu-like symptoms and developed I or multiple inoculation eschars. The patients were treated with either doxycycline or ciprofloxacin, and all recovered. The diagnosis of ATBF was confirmed by the detection of specific IgM antibodies to Rickettsia africae by microimmunofluoroscence in convalescent-phase serum samples.

Antibodies, Bacterial↗
PubMed1999

Coxiella burnetii pericarditis: report of 15 cases and review.

Q fever is characterized by its clinical polymorphism, and pericarditis associated with Q fever has occasionally been described. Herein we report 15 cases of Coxiella burnetii pericarditis, 9 from our data bank and 6 encountered within the past 12 months. Three patients presented with life-threatening tamponade. We compare our cases with the 18 previously reported and with 60 Q fever-matched controls at our center. This study showed that Q fever pericarditis can present as acute as well as chronic disease; we describe relapse after 6 months in association with a serological profile compatible with the chronic form of disease (phase I C. burnetii IgG titer of > or = 800). Discriminant factors among patients and controls are age of > 52 years (adjusted odds ratio [OR], 5.66), the occurrence of general symptoms such as arthralgias or myalgias (adjusted OR, 6.54), and a normal erythrocyte sedimentation rate (adjusted OR, 16.37). No specific symptoms or underlying cardiac predispositions are observed.

Adolescent↗