The authors report the general epidemiologic features of Mediterranean spotted fever (MSF) in the Marseille area (South France). Age was a risk factor, increasing after 50 years, and annual incidence seemed positively correlated with the average temperature of the preceding year and negatively correlated with the number of days with frost of the preceding year. However, correlations were not significant.

Adolescent↗

PubMed1992

Clinicoepidemiological study of murine typhus on the Greek island of Evia.

Cases of murine typhus were described in Chalkis, capital town of the island Evia in Greece. In the present work a prospective study on murine typhus was carried out in Chalkis General Hospital in 1985, is presented. During this year 49 cases, serologically confirmed using indirect fluorescence assay, were diagnosed. Signs and symptoms of the patients as well as preliminary epidemiological data are reported in this paper.

Adolescent↗

PubMed1992

Epidemiologic features and clinical presentation of acute Q fever in hospitalized patients: 323 French cases.

PURPOSE: To contribute to the knowledge of epidemiologic and clinical features of patients hospitalized with Q fever in France. METHODS: We conducted a retrospective analysis of 22,496 sera submitted between 1982 and 1990 to the French National Reference Center for Rickettsial Diseases (NRC). The diagnosis of acute Q fever was based on an IgG titer greater than or equal to 1:200 and an IgM titer greater than or equal to 1:25 against phase II Coxiella burnetii antigen on an indirect immunofluorescence test (IFA). Fifteen cases prior to 1985 were diagnosed on the basis of a complement fixation titer greater than or equal to 1:8. A serosurvey of blood donors from Marseille was also conducted in 1988 on 924 sera, using IFA with a cutoff titer of 1:25. RESULTS: The serosurvey conducted in 1988 showed a seroprevalence of 4.03%, without age or sex prediction. The incidence rate of acute Q fever detection at the NRC was 0.58 per 100,000 inhabitants over the 9-year period. Three hundred twenty-three clinical cases were diagnosed, rising from 1 in 1982 to 107 in 1990. In patients hospitalized for acute Q fever, there was a significantly higher sex ratio of males to females (2.3), which, coupled with the age distribution, indicated that elder males, who are overrepresented due to our recruitment bias, are more susceptible to C. burnetii infections. The mean age of the patients was 45.5 years, while the risk was increased in the 30 to 39 age group as well as in the 60 to 69 age group. Usual epidemiologic risk factors were found in 20.1% of the cases. Hepatitis (61.9%) was a more common clinical presentation in our patients with Q fever than pneumonia (45.8%). This might reflect differences in strains of C. burnetii or the biology of the host. However, French farmers and stock breeders commonly drink unpasteurized raw milk from their cattle, which might indicate a relationship between hepatitis and infection via the digestive tract. CONCLUSION: Our results indicate that many cases of acute Q fever are undiagnosed. A greater awareness of the disease and more extensive serologic testing of patients with symptoms compatible with Q fever may improve the situation.

Acute Disease↗

PubMed1992

Rhodococcus equi infection in patients with AIDS.

Rhodococcus equi is an emerging opportunistic pathogen of HIV-I infected patients. It is an aerobic, Gram-positive coryneform bacterium which acts as a facultative intracellular micro-organism, multiplying in the phagosome of macrophages. Eighteen cases of R. equi infection in HIV-I positive patients have now been reported. Sixteen of these had pneumonia, of which 12 had cavitating lung lesions. A history of contact with farm animals, which are the primary hosts of R. equi, was found in only three patients. There was a delay in establishing a definite diagnosis in most cases as this depended upon the isolation of R. equi from sputum, bronchoalveolar lavage fluid, or blood. Treatment included surgical resection in five patients and erythromycin with a second antibiotic in 13 cases, but II of the 18 patients died from the infection. In this report we describe our experience of R. equi pneumonia in two AIDS patients and review the published cases of the disease in man.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Rickettsial infections of the central nervous system.

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Central Nervous System Diseases↗

PubMed1992

Spotless boutonneuse fever.

Mediterranean spotted fever is endemic in southern France, especially during summer. Clinical diagnosis is generally based upon the presence of a febrile eruption with or without the typical tache noire. Usual laboratory findings, which include thrombocytopenia, elevated levels of hepatic enzymes, and hyponatremia, are not specific to the disease. The diagnosis may be confirmed serologically by obtaining specific western immunoblot results and by isolation of Rickettsia conorii from blood culture with use of the shell vial cell culture technique. We report here the first documented case of spotless boutonneuse fever.

Adult↗

PubMed1992

Acute and chronic Q fever in patients with cancer.

Q fever is caused by Coxiella burnetii, a strictly intracellular bacterium that lives within the phagolysosome of infected cells. We report here five cases of Q fever in patients with cancer. Three of them had a solid tumor, one had a B cell lymphoma, and one had chronic myeloid leukemia. One patient had acute Q fever, and the four others had chronic Q fever endocarditis. Two patients with endocarditis had no previous history of valvulopathy. C. burnetii was isolated from the valves of two patients. One of the patients with endocarditis died. Patients with cancer who have unexplained fever and live in areas in which C. burnetii is endemic should undergo serological testing for infection with this microorganism.

Acute Disease↗

PubMed1992

Astrakhan fever rickettsia is identical to Israel tick typhus rickettsia, a genotype of the Rickettsia conorii complex.

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Animals↗

PubMed1992

Diagnosis of Mediterranean spotted fever by indirect immunofluorescence of Rickettsia conorii in circulating endothelial cells isolated with monoclonal antibody-coated immunomagnetic beads.

Rickettsia conorii, an obligate intracellular bacterium that infects vascular endothelial cells, is the etiologic agent of Mediterranean spotted fever (MSF). A new procedure using indirect immunofluorescence was used to directly detect R. conorii in circulating endothelial cells (CEC). CEC were separated from other blood components by using anti-endothelial cell monoclonal antibody-coated magnetic beads. An anti-R. conorii polyclonal rabbit antiserum was used to stain rickettsiae. The entire procedure took 3 h. R. conorii was detected in CEC from 9 of 12 patients ultimately confirmed as having MSF. Among the patients, 5 with R. conorii isolated by centrifugation-shell vial assay were also positive by the new technique. None of 3 patients whose diagnosis was other than MSF had R. conorii detected in CEC. The procedure may be helpful for rapid diagnosis of MSF and may lead to new technical approaches for the diagnosis of infectious diseases caused by intracellular pathogenic microorganisms.

Adult↗

PubMed1992

Phagolysosomal alkalinization and the bactericidal effect of antibiotics: the Coxiella burnetii paradigm.

Most infections due to intracellular bacteria respond poorly to antibiotic treatment. The chemical conditions within the subcellular site of bacteria may change antibiotic activity. Coxiella burnetii multiplies within phagolysosomes. The antimicrobial activity of antibiotics combined with the lysosomotropic agents amantadine (1 microgram/mL), chloroquine (1 microgram/mL), and ammonium chloride (1 mg/mL), which alkalinized Coxiella burnetii-containing phagolysosomes from pH 4.8 to 5.3, 5.7, and 6.8, respectively, was evaluated. Percentages of residual viable bacteria (RVB) in cell cultures were significantly reduced after exposure to combinations of doxycycline (4 micrograms/mL) with amantadine (RVB = 18.2% +/- 8.7%, P < .05), chloroquine (RVB = 0.64% +/- 0.38%, P < .01), or ammonium chloride (RVB = 0.29% +/- 0.17%, P < .01); the same was seen with pefloxacin (1 microgram/mL) with chloroquine (RVB = 27.6% +/- 10.8%, P < .05) or ammonium chloride (RVB = 3.72% +/- 1.1%, P < .05). Such bactericidal activity correlated with increased phagolysosomal pH, as determined by Pearson's correlation coefficient, suggesting that phagolysosomal alkalinization is critical for the bactericidal effect of antibiotics.

Amantadine↗

PubMed1992

Chlamydial endocarditis: a report on ten cases.

Over the period 1983-1990, 10 cases of infective native-valve endocarditis as a result of Chlamydia were seen. All patients were men, with a mean age of 42 years, and none had a history of exposure to Chlamydia psittaci. Symptoms, such as weight loss and anorexia, with fever in eight cases, had persisted for at least 2 months before admission. Haemodynamic failure was present in seven patients, and neurological signs in four. The aortic valve was involved in seven cases, the mitral valve in one and both valves in two. Vegetations, often fingerlike, were observed by echocardiography in nine cases. All patients required valve replacement, and three died in the year following diagnosis. Blood cultures were consistently negative in all cases, and no antibiotics had been given before admission. Significant titres of complement fixing anti-chlamydial antibodies were present in six cases, and micro-immunofluorescence using the three chlamydial species showed cross-reacting antibodies in all nine cases studied, with transient IgM positivity in six cases. Histologically, the leaflets were fibrosed and infiltrated by large macrophages containing dark red granules after Machiavello staining. These granules were specifically stained by immunofluorescence using monoclonal antibody to Chlamydia common antigen, but not by that specific for C. pneumoniae. No organisms were seen after Gram staining, and no positive chlamydial immunofluorescence was seen on sections of valves from patients with staphylococcal or streptococcal endocarditis.

Adult↗

PubMed1992

Susceptibility of Rickettsia conorii, R. rickettsii, and Coxiella burnetii to PD 127,391, PD 131,628, pefloxacin, ofloxacin, and ciprofloxacin.

Plaque formation and dye uptake assays were used to measure the MICs of PD 127,391 and PD 131,628 against Rickettsia species. The MICs of PD 127,391 were 0.25 microgram/ml for Rickettsia rickettsii and 0.125 to 0.25 microgram/ml for Rickettsia conorii. The MICs of PD 131,628 were 0.25 to 0.5 microgram/ml for R. rickettsii and 0.5 microgram/ml for R. conorii. As determined by the shell vial technique, 15 strains of Coxiella burnetii were susceptible to PD 127,391 and PD 131,628 (MIC, < or = 1 microgram/ml), while one strain of C. burnetii (MP10) was of intermediate susceptibility.

Anti-Infective Agents↗

PubMed1992

In vitro antibiotic susceptibility of the newly recognized agent of ehrlichiosis in humans, Ehrlichia chaffeensis.

Ehrlichiosis in humans, a rickettsial disease recently discovered in the United States, is generally treated successfully with tetracyclines; however treatment with these agents is usually avoided with children and pregnant women. The in vitro susceptibility of Ehrlichia chaffeensis, the agent of human ehrlichiosis in the United States, was assessed by a quantitative evaluation of infected DH82 cells cultivated in 96-well microtiter plates in the presence of different concentrations of selected antibiotics. Extracellular MICs and MBCs were evaluated after 72 h of exposure to the antibiotics. Doxycycline and rifampin were found to exert rapidly bactericidal effects, with MBCs in the extracellular culture medium of less than 0.5 and 0.125 microgram/ml, respectively. E. chaffeensis was resistant to chloramphenicol, ciprofloxacin, erythromycin, co-trimoxazole, penicillin, and gentamicin, which had MICs greater than 16, 4, 8, 4, 40, and 32 micrograms/ml, respectively. These observations are consistent with the finding that human ehrlichiosis appears to respond to tetracycline therapy, which has been the therapy of first choice. Further clinical investigations are necessary to evaluate the role of rifampin in the treatment of human ehrlichiosis, especially in children.

Anti-Bacterial Agents↗

PubMed1992

von Willebrand factor release and thrombomodulin and tissue factor expression in Rickettsia conorii-infected endothelial cells.

Mediterranean spotted fever, a tick-borne rickettsiosis caused by Rickettsia conorii, may lead to small-vessel or deep-vein thrombosis. In order to evaluate the role of endothelial cell alteration in this lesion, we infected human endothelial cells derived from umbilical veins with R. conorii. We report the induction of two previously unreported prothrombotic mechanisms in rickettsial disease: (i) a progressive decline in thrombomodulin antigen and (ii) early expression of tissue factor, and, as described for R. rickettsii infection, later release of von Willebrand factor from Weibel-Palade bodies. Thrombomodulin expression in infected endothelial cells, measured by the thrombin-dependent activation of protein C or flow cytometric analysis, decreased steadily between 4 and 24 h after inoculation with rickettsiae. R. conorii infection induced tissue factor expression, measured by clotting assay and flow cytometric analysis, which was detectable 2 h postinoculation, reached its maximum 4 h postinoculation, and progressively decreased thereafter. Infection resulted in a relatively late release of von Willebrand factor antigen into the culture medium. A double-label immunofluorescence assay for the simultaneous evaluation of von Willebrand factor and R. conorii showed that the depletion of cytoplasmic von Willebrand factor stored in Weibel-Palade bodies was due to a direct effect of the intracellular R. conorii. These disturbances of endothelial function observed with R. conorii-infected cells may provide a paradigm for the elucidation of thrombotic pathobiology with Mediterranean spotted fever.

Cells, Cultured↗