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Biomedical subjects

D Raoult

Publications and source records attributed to D Raoult.

At least 145 records · Page 8Linked to original sources

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↗

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↗

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↗

Nonculture Laboratory Methods for the Diagnosis of Infectious Endocarditis.

Over the past few years new techniques have been developed to improve the diagnosis of infectious diseases. However, despite the various available culture systems, culture-negative endocarditis currently represents a challenge for physicians. In our laboratory, in an effort to reduce the rate of endocarditis of unknown etiology, we have used several recent histologic, serologic, and molecular tests. We review the latest technical developments for the diagnosis of infectious endocarditis, including those that we are currently using.

Journal Article↗

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↗

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↗

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↗

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↗

Survey of three bacterial louse-associated diseases among rural Andean communities in Peru: prevalence of epidemic typhus, trench fever, and relapsing fever.

Typhus and other louse-transmitted bacterial infections in Peruvian sierra communities are known to occur but have not recently been assessed. In this study, 194 of 1,280 inhabitants of four villages in Calca Province in the Urubamba Valley were included. Thirty-nine (20%) of the 194 volunteers had antibodies to Rickettsia prowazekii, whereas 24 (12%) had antibodies to Bartonella quintana and 2 against Borrelia recurrentis. There was a significant correlation between the presence of infesting ectoparasites and antibodies to R. prowazekii, as well as between antibodies to R. prowazekii and ectoparasite infestation and fever in the previous 6 months. The proportion of inhabitants infested with ectoparasites was significantly higher in the highest-altitude village than in the other three villages. Two volunteers' antibody levels suggested a recent typhus infection, but only B. quintana DNA was amplified from lice. Epidemic typhus remains extant in the area, and B. quintana infections were encountered and documented for the first time in South America.

Adult↗

The body louse as a vector of reemerging human diseases.

The body louse, Pediculus humanus humanus, is a strict human parasite, living and multiplying in clothing. Louse infestation is associated with cold weather and a lack of hygiene. Three pathogenic bacteria are transmitted by the body louse. Borrelia recurrentis is a spirochete, the agent of relapsing fever, recently cultured on axenic medium. Historically, massive outbreaks have occurred in Eurasia and Africa, but currently the disease is found only in Ethiopia and neighboring countries. Bartonella quintana is now recognized as an agent of bacillary angiomatosis bacteremia, trench fever, endocarditis, and chronic lymphadenopathy among the homeless. Rickettsia prowazekii is the agent of epidemic typhus. The most recent outbreak (and the largest since World War II) was observed in Burundi. A small outbreak was also reported in Russia in 1997. Louse infestation appears to become more prevalent worldwide, associated with a decline in social and hygienic conditions provoked by civil unrest and economic instability.

Animals↗

Pigeon pneumonia in provence: a bird-borne Q fever outbreak.

Q fever is a widespread zoonosis caused by Coxiella burnetii, an obligate intracellular bacterium, which humans usually acquire through the inhalation of infected dust from subclinically infected mammals. Human infection commonly takes place when an infected mammal gives birth, since high concentrations of the organism are found in the products of conception. Worldwide, cattle, sheep, and goats are the most common reservoirs for C. burnetii. A few investigators have also reported parturient cats and dogs as the sources of human outbreaks of Q fever. During a 10-day period in May 1996, all five members of one family living on a farm in Provence, in the south of France, became ill with fever, general malaise, and cough. All of them had acute Q fever. An epidemiological investigation suggested that this outbreak resulted from exposure to contaminated pigeon feces and ticks.

Adult↗

Characterization of mutations in the rpoB gene in naturally rifampin-resistant Rickettsia species.

Rickettsiae are gram-negative, obligately intracellular bacteria responsible for arthropod-borne spotted fevers and typhus. Experimental studies have delineated a cluster of naturally rifampin-resistant spotted fever group species. We sequenced the 4, 122- to 4,125-bp RNA polymerase beta-subunit-encoding gene (rpoB) from typhus and spotted fever group representatives and obtained partial sequences for all naturally rifampin-resistant species. A single point mutation resulting in a phenylalanine-to-leucine change at position 973 of the Rickettsia conorii rpoB sequence and present in all the rifampin-resistant species was absent in all the rifampin-susceptible species. rpoB-based phylogenetic relationships among these rickettsial species yielded topologies which were in accordance with previously published phylogenies.

Antibiotics, Antitubercular↗

In vitro susceptibilities of four Bartonella bacilliformis strains to 30 antibiotic compounds.

We have evaluated for the first time in vitro antibiotic susceptibilities of four human strains of Bartonella bacilliformis, the agent of Carrion's disease. Our results show that B. bacilliformis, like other Bartonella species, is highly susceptible to antibiotics, including most beta-lactams, aminoglycosides, chloramphenicol, rifampin, macrolides, tetracyclines, cotrimoxazole, and fluoroquinolones.

Anti-Bacterial Agents↗

Predominant immunoglobulin A response to phase II antigen of Coxiella burnetii in acute Q fever.

Diagnosis of acute Q fever is usually confirmed by serology, on the basis of anti-phase II antigen immunoglobulin M (IgM) titers of >/=1:50 and IgG titers of >/=1:200. Phase I antibodies, especially IgG and IgA, are predominant in chronic forms of the disease. However, between January 1982 and June 1998, we observed anti-phase II antigen IgA titers of >/=1:200 as the sole or main antibody response in 10 of 1,034 (0.96%) patients with acute Q fever for whom information was available. In order to determine whether specific epidemiological or clinical factors were associated with these serological profiles, we conducted a retrospective case-control study that included completion of a standardized questionnaire, which was given to 40 matched controls who also suffered from acute Q fever. The mean age of patients with elevated phase II IgA titers was significantly higher than that usually observed for patients with acute Q fever (P = 0.026); the patients were also more likely than controls to live in rural areas (P = 0.026) and to have increased levels of transaminase in blood (P = 0.03). Elevated IgA titers are usually associated with chronic Q fever and are directed mainly at phase I antigens. Although the significance of our findings is unexplained, we herein emphasize the fact that IgA antibodies are not specific for chronic forms of Q fever and that they may occasionally be observed in patients with acute disease. Moreover, as such antibody profiles may not be determined by most laboratories, which test only for total antibody titers to phase I and II antigens, the three isotype-specific Ig titers should be determined as the first step in diagnosing Q fever.

Acute Disease↗

Diagnosis of rickettsial diseases using samples dried on blotting paper.

The use of filter paper is an inexpensive and convenient method for collecting, storing, and transporting blood samples for serological studies. In addition, samples occupy little space and can be readily transported without refrigeration. Rickettsial diseases often evolve according to an epidemic mode and are now considered reemerging diseases, especially in developing countries, under conditions where fieldwork could be difficult. The suitability of collecting whole-blood specimens on filter paper discs for rickettsial antibody assay was evaluated. Dried blood specimens from 64 individuals with antibodies to Coxiella burnetii, Bartonella quintana, or Rickettsia conorii were tested for rickettsial antibodies by microimmunofluorescence. Although occasional titers were 1 or 2 dilutions lower than those of tested serum samples, no statistically significant differences were observed. Among patients with negative serology, no false positives were found. This study demonstrated that the recovery of antibodies from finger-stick blood dried on filter paper after elution produces results comparable to those obtained by recovering antibodies from serum. Storing paper samples for 1 month at room temperature or at 4 degrees C did not significantly affect the level of antibodies recovered. This report shows the utility of this sample collection method in developing countries where refrigeration is not possible and venipuncture is problematic.

Antibodies, Bacterial↗