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Type IVB secretion by intracellular pathogens.

A growing number of pathogens are being found to possess specialized secretion systems which they use in various ways to subvert host defenses. One class, called type IV, are defined as having homology to the conjugal transfer systems of naturally occurring plasmids. It has been proposed that pathogens with type IV secretion systems have acquired and adapted the conjugal transfer systems of plasmids and now use them to export toxins. Several well-characterized intracellular pathogens, including Legionella pneumophila, Coxiella burnetii, Brucella abortus, and Rickettsia prowazekii, contain type IV systems which are known or suspected to be of critical importance in their ability to cause disease. Specifically, these systems are believed to be the key factors determining intracellular fate, and thus the ability to replicate and cause disease.

Amino Acid Sequence↗

Clinical and pathologic changes in a guinea pig aerosol challenge model of acute Q fever.

Acute Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii and can manifest as a flu-like illness, pneumonia, or hepatitis. A need exists in Q fever research for animal models mimicking both the typical route of infection (inhalation) and the clinical illness seen in human cases of Q fever. A guinea pig aerosol challenge model was developed using C. burnetii Nine Mile phase I (RSA 493), administered using a specialized chamber designed to deliver droplet nuclei directly to the alveolar spaces. Guinea pigs were given 10(1) to 10(6) organisms and evaluated for 28 days postinfection. Clinical signs included fever, weight loss, respiratory difficulty, and death, with the degree and duration of response corresponding to the dose of organism delivered. Histopathologic evaluation of the lungs of animals infected with a high dose showed coalescing panleukocytic bronchointerstitial pneumonia at 7 days postinfection that resolved to multifocal lymphohistiocytic interstitial pneumonia by 28 days. Guinea pigs receiving a killed whole-cell vaccine prior to challenge with the highest dose of C. burnetii were protected against lethal infection and did not develop fever. Clinical signs and pathological changes noted for these guinea pigs were comparable to those seen in human acute Q fever, making this an accurate and valuable animal model of human disease.

Acute Disease↗

[Coxiella burnetti: serologic study on bovine from the community of Madrid].

Complement fixative antibodies are determined with regard to Coxiella burnetii in phase II, in 106 serum samples taken from cattle in the Madrid region. The overall prevalence of antibodies was 66.98% and 11.32% was high titer. The result obtained are compared with the results from other studies.

Animals↗

A survey of Q-fever in Sweden.

Coxiella burnetii, the etiological agent of Q-fever has recently been isolated from sheep in southern Sweden. In this region 24-30% of sheep farmers have been exposed to the organism as shown by serological measurements. In veterinarians, another group with high risk of exposure to C. burnetii, about 12% have antibodies to the bacteria. The seropositive veterinarians are scattered all over the country. In two non-risk groups, draftees and hospital employees, 5-7% were found to be positive. This survey showed that Q-fever is a domestic disease which is spread throughout Sweden.

Adolescent↗

Cure of Q fever pneumonia with moxifloxacin: case report.

In a 25-y-old hospitalized male, Coxiella burnetii pneumonia was confirmed serologically by enzyme-linked immunosorbent assay. Previous treatment with oral azithromycin was unsuccessful. In hospital the patient was treated with oral moxifloxacin for 10 d and was completely cured. To our knowledge, this is the first clinical report of Q fever pneumonia treated with moxifloxacin.

Adult↗

Evaluation of specificity of indirect enzyme-linked immunosorbent assay for diagnosis of human Q fever.

Ninety-five acute- and convalescent-phase serum specimens from 48 patients suspected of having rickettsial or Legionella infections were assayed for antibodies to Coxiella burnetii, the causative agent of Q fever. To evaluate the specificity of the indirect enzyme-linked immunosorbent assay (ELISA) for human Q fever, we compared the ELISA results with those of the indirect immunofluorescence antibody (IFA) test. The ELISA data were analyzed by two different criteria for a positive test. The first criterion for positive results by ELISA was based upon diagnostic titers established in a study of 150 subjects who had no demonstrable cellular or humoral immune responses to C. burnetii phase I or phase II whole cells or phase I lipopolysaccharide. The second criterion was based upon diagnostic antibody titers in a study of 51 subjects who had been diagnosed as having clinical Q fever and had fourfold or greater rises in humoral immune responses to C. burnetii phase I and phase II whole-cell antigens. A comparison of the ELISA and IFA test results of the 95 serum specimens indicated excellent agreement between the tests (Kappa = 92.9%; P < 0.05). None of the 38 patients whose etiologies were confirmed serologically as Legionnaires' disease or rickettsial diseases other than Q fever were classified as positive for C. burnetii by the ELISA. Only one patient identified by the IFA test as having Q fever was not scored positive by the ELISA. These results suggest that the ELISA is useful for epidemiologic screening and as a diagnostic test for human Q fever.

Acute Disease↗

[Splenic abscess caused by Coxiella burnetti in the absence of endocarditis].

INTRODUCTION: The most frequent clinical expression of chronic Q fever is culture-negative endocarditis. Other localizations are rare. EXEGESIS: We report a documented case of chronic Q fever that occurred in a 47-year-old immunocompetent man and was associated with spleen abscess, in the absence of detectable endocarditis. The spleen abscess was a complication of either a preexisting cyst or a calcified hematoma. Splenic infection with Coxiella burnetii was documented with cultures, polymerase chain reaction and immunohistochemistry. The outcome was favorable after splenectomy and a 21-month antibiotherapy. CONCLUSION: Chronic Q fever may develop in the absence of endocarditis, when a preexisting vascular lesion such as aortic aneurysm exists. A splenic cyst may have played a similar role for this patient.

Abscess↗

Safety and immunogenicity in human volunteers of a chloroform-methanol residue vaccine for Q fever.

Current Q fever vaccines, consisting of Formalin-inactivated phase I whole Coxiella burnetii, are highly efficacious in preventing disease in high-risk settings but are associated with a risk of unacceptable local reactions in previously immune individuals and require cumbersome preliminary immunologic evaluation of potential vaccinees. A vaccine prepared from the residue of chloroform-methanol extraction of phase I Henzerling strain C. burnetii (CMR) has been shown to be less reactogenic but still immunogenic and protective in small animals and sheep. In a placebo-controlled trial, we immunized 35 healthy adults unscreened for markers of prior C. burnetii immunity with a single subcutaneous CMR dose of 30, 60, 120, or 240 micrograms. None of those receiving the 30- or 60-micrograms CMR dose and none of the placebo recipients experienced any adverse effects. Five of 15 120-micrograms dose CMR recipients complained of transient discomfort in the inoculated arm; erythema or induration of > or = 100 mm2 was noted in three and four, respectively, and two had malaise and low-grade fever (< 101 degrees F, orally). No 240-micrograms dose vaccinee reported limb discomfort, but 7 of 10 had erythema and/or induration of > or = 100 mm2 (P < 0.001 versus placebo). Two reported malaise, and one had low-grade fever. All adverse effects were self-limited. Serum immunoglobulin M responses were optimally detected with CMR antigen and occurred in 50, 60, 73, and 90% of recipients of the 30-, 60-, 120-, and 240-micrograms doses, respectively; results with phase I whole-cell antigen were similar. Serum immunoglobulin G responses were best detected with phase II antigen and were seen in 20, 20, and 40% of those receiving the 60-, 120-, and 240-micrograms doses, respectively. Peripheral blood T-cell proliferative responses to C. burnetii recall antigens were transient and of low magnitude but were seen with CMR antigen in 33% of 120-micrograms dose recipients and 40% of 240-micrograms dose recipients. Data from this study and those from comparative-efficacy trials in primates should provide the basis for field trials of the CMR vaccine.

Antibodies, Bacterial↗

[Laboratory diagnosis of Q-fever with the indirect immunofluorescence test].

Q-Fever nowadays presents the most diffuse disease in the world, caused by the microorganisms from the family Risckettiacae. This disease is Coxiellae burnetii. The laboratory diagnosis of the Q-Fever can be stated either by the isolation of the causer from the patient material, either by the proving of the specifically antibodies. The serologic diagnostics presents the choile method in Q-Fever. The aim of this work is to illustrate the results of the detection of the serum in patients with the clinical symptoms at the infeçtion Coxiellom burnetii. We tested the sera of the patient from the region of the Federation Bosnia and Herzegovina, which arrived in our laboratory in the period of November 2000 till May 2001. From the total 174 prepared sera specific IgM of the antibodies we found in cases, and the specific IgG of the antibodies in 54 sera.

Antibodies, Bacterial↗

[Seropositivity against atypical pneumonia agents demonstrated in patients with community-acquired pneumonia].

The aim of this study was to investigate the IgG and IgM antibody positivities against atypical pneumonia agents in patients with community-acquired pneumonia (CAP), and to compare the results with the controls. The serum samples which were collected from 53 adult patients and 20 healthy donors have been investigated by a commercial indirect immunofluorescent assay (IFA, Pneumo-slide, Vircell SL, Spain) in which nine different antigens were fixed onto a slide. In both of the study groups. IgG and IgM seropositivities were detected in different rates against one or more etiologic agents. In the patient group. IgG and IgM positivity rates for the agents were as follows, respectively; 22.6% and 28.3% for Legionella pneumophila, 9.4% and 5.6% for Mycoplasma pneumoniae, 30.1% and 7.5% for Coxiella burnetii, 33.9% and 3.7% for Chlamydia pneumoniae, 28.3% and 0 for adenovirus, 71.6% and 1.8% for respiratory syncytial virus, 30.1% and 24.5% for influenza A virus, 35.8% and 7.5% for influenza B virus, 71.6% and 1.8% for parainfluenza viruses type 1-3. The rates of IgG positivities in the control group varied between 5-55% for all of the agents except M. pneumoniae and 3 of these controls were positive for L. pneumophila IgM, 3 were positive for C. pneumoniae IgM and one was positive for influenza A virus IgM. According to the statistical evaluation, there were no significant differences for IgM seropositivities to any of the agents, between the patient and control groups (p > 0.05). These results could be attributed to one or more of the following; a) none of these microorganisms were the primary etiologic agents, b) IgM positivities were the result of reinfections with these agents, c) longer duration of IgM antibodies after the acute infections. In terms of IgG positivities between the patient and control groups, only C. burnetii showed statistically significant difference (p = 0.029). Since the type of the pathogens causing CAP are of crucial importance both for the epidemiological purposes and for planning the empirical treatment strategies, more detailed multicenter studies should be performed in our country.

Adenoviridae↗

A seroepidemiological study of the risks of Q fever infection in Japanese veterinarians.

The causative agent of Q fever, a widespread zoonotic disease, is the bacteria Coxiella burnetii. Although cases of Q fever have been documented in countries throughout the world, the prevalence of the disease in Japan is not yet known. Q fever is a demonstrated occupational hazard to those employed in zoological professions, but the risk to Japanese veterinarians has not yet been quantified. In order to evaluate the risk to Japanese veterinarians, we performed a serological survey using serum samples from 267 veterinarians. Two control groups consisting of 352 medical workers and 2003 healthy blood donors were also evaluated. The antibody titers of the serum samples were measured by indirect immunofluorescence assay (IFA) using phase II C. burnetii Nine Mile strain as the antigen. The positive rate of IgG antibody was 13.5% in the veterinarians, which was higher than in the blood donors (3.6%, p < 0.001) and medical workers (5.1 %,p < 0.001). These findings suggest that Japanese veterinarians have a higher risk of infection by C. burnetii than other members of the Japanese population. An interesting finding of this study was that positive rates of IgG and IgM antibodies in the blood donor group were higher in younger individuals. The IgM antibody positive rate was the highest in females under 30 years old.

Antibodies, Bacterial↗

Corpuscular antigenic microarray for the serodiagnosis of blood culture-negative endocarditis.

Blood culture-negative endocarditis is due to fastidious bacteria, including Coxiella burnetii and Bartonella spp. Diagnosis of such infection relies on serology and microimmunofluorescence is therefore the reference method. We developed a multiplex serology test featuring automatic incubation and reading and incorporating internal controls. Preliminary results indicate that this new serologic test is valuable for the rapid, automated serological diagnosis of blood culture-negative endocarditis.

Antigens, Bacterial↗

[Q fever: not just in sheep].

Four patients, a woman aged 41 years and 3 men aged 12, 47 and 44 years, developed high fever after returning from a farm vacation in the Ardèche (France). They also suffered from severe headache, a painful tightness of the chest, abdominal pain or myalgia. Other symptoms were shivers, tiredness and a cough. While physical examination revealed few abnormalities, the chest X-ray in 3 patients showed an atypical pneumonia. One of these patients developed dural venous sinus thrombosis with increased intraspinal pressure. This patient also showed signs of a slight hepatitis. Serological investigation revealed that all 4 patients were suffering from acute Q fever, a zoonosis caused by the Coxiella burnetii bacterium. All 4 had been present at lambing and sheep-shearing. The patients with pneumonia were treated with antibiotics. All 4 patients recovered well. It is known that animal birth products in particular can contain large numbers of bacteria and therefore be highly infectious.

Acute Disease↗

Route of infection determines the clinical manifestations of acute Q fever.

In Nova Scotia the main manifestation of acute Q fever is pneumonia, while in France it is granulomatous hepatitis. To test the hypothesis that the route of infection is the major determinant of the manifestations of acute Q fever, 10 groups of 10- to 12-g female BALB/c mice (4 animals/group) were used. Five groups were inoculated intraperitoneally (ip) and 5 intranasally (inl) with Coxiella burnetii. Both routes of infection resulted in pneumonia. However, the inl route resulted in greater airway changes (on a numeric scale with 0 being no changes): 2.05 +/- 2.20 versus 0.60 +/- 0.83 (P < .002). The ip route resulted only in hepatosplenomegaly. It was concluded that the route of infection is one determinant of the manifestations of acute Q fever.

Animals↗

[Outbreak of Q fever and seroprevalence in a rural population from Soria Province].

BACKGROUND: The aim of this study was to describe an outbreak of acute fever in a rural town from Soria (Spain) in the spring of 1998 and to know the prevalence of IgG antibodies to Coxiella burnetii in this population. METHODS: 1. Outbreak of Q fever: epidemiological, clinical and analytical data were obtained by standardised questionnaire and the clinical records from all clinical cases. These cases were confirmed by complement fixation test.2. Seroprevalence: 253 sera were chosen by not probabilistic sampling of convenience of sera samples collected between 1 September 1996 and 28 February 1999. Were regarded as positive anti-phase II C. burnetii IgG titles by indirect inmunoflourescence assay equal or higher to 1/80. RESULTS: 1. A total of 14 cases of Q fever with a mean age of 21.5 +/-3.1 years were confirmed. 64% presented pneumonia and in 36% the symptoms were nonspecific. No patient had direct contact with animals but near to the town there were 4 flocks with 2,614 sheeps overall. 2. The seroprevalence was 60% (95% confidence interval: 54-66). The seroprevalence was not increased with the outbreak (p > 0.05). CONCLUSION: The high prevalence of antibodies to C. burnetii in this population shows that this area is hyperendemic for such infection, but generally is asymptomatic or clinical signs are extremely mild because no cases of Q fever had been reported in the years before. Probably indirect exposure to flocks of sheep was the source of infection and transmission mechanism airborne.

Adolescent↗

Acute Q fever pericarditis followed by chronic hepatitis in a two-year-old girl.

Acute Coxiella burnetii infection is most commonly a mild and self-limiting disease with fever, pneumonia and hepatitis. Endocarditis is the most frequent clinical presentation of chronic infection. We report a 2-year-old child with Q fever who presented with acute pericarditis and cardiac tamponade and who developed a chronic hepatic infection.

Anti-Bacterial Agents↗

A serologic survey for some bacterial and viral zoonoses in game animals in the Czech Republic.

Between 1986 and 1991, sera were collected from 33 roe deer (Capreolus capreolus), 24 red deer (Cervus elaphus), four fallow deer (Dama dama), two mouflon (Ovis musimon), 34 wild boars (Sus scrofa), and 48 hares (Lepus europaeus) shot in two areas of the Czech Republic. Collectively, the sera contained antibodies to Coxiella burnetii (prevalence of 12%), Francisella tularensis (4%), Brucella spp. (2%), Central European tick-borne encephalitis virus (8%), Tahyna (California serogroup) virus (36%), and Calovo (= Batai) virus (23%). We propose that these mammals may play a role in maintaining natural foci of Q-fever, Tahyna fever and Calovo virus infection.

Agglutination Tests↗

Evidence of rickettsial and leptospira infections in Andean northern Peru.

Between May and October 2002, a cluster of acute febrile illnesses occurred in the subtropical Andean foothills of Peru. Serologic evidence in villages where disease had been documented showed that the prevalence of IgM antibody to Leptospira ranged from 6% to 52%, that of IgM antibody to spotted fever group (SFG) rickettsia ranged from 10% to 19%, and that of IgM antibody to Coxiella burnetii from 1% to 15%. Measurement of IgG antibodies for SFG rickettsiae suggested that this disease was endemic. In contrast, IgG antibodies against C. burnetii were largely absent. In humans, microagglutination tests identified pathogenic variants of Leptospira. The presence of an SFG rickettsial infection was confirmed in four febrile patients following polymerase chain reaction and sequencing of the conserved 17-kD common antigen gene (htrA). Collectively, these analyses indicated that Rickettsia sp., C. burnetii, and Leptospira sp. were circulating in the region during the time of disease outbreak and implicate the involvement of an as yet undetermined SFG rickettsia in northwestern Peru.

Adolescent↗