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Influence of etiology on the functional result of aortic valve replacement.

The functional result of aortic valve replacement has been assessed in patients treated for isolated aortic incompetence. Using maximal oxygen uptake as an index of myocardial function, a significant difference (p less than .05) exists between the patients who had Q fever endocarditis on the one hand and those who had bacterial endocarditis or rheumatic fever on the other hand. We believe that permanent myocardial damage occurs as a result of bacterial endocarditis and rheumatic fever but because of the biological properties of Coxiella burnetii the myocardium is spared in Q fever endocarditis.

Aortic Valve↗

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↗

A prospective study of viral and mycoplasma infections in chronic inflammatory bowel disease.

Seventy-two children with chronic inflammatory bowel disease were investigated for infections with various viruses and Mycoplasma pneumoniae, Chlamydia psittaci, and Coxiella burnetii to determine whether these pathogens are associated with acute onset exacerbations. Altogether 54 infections were identified serologically, of which 23 (42.6%) were associated with exacerbations. This corresponded to 24.2% of the recorded exacerbations during the study period. The respiratory pathogens accounted for 59.3% of the infections and 43.8% of these were associated with gastrointestinal symptoms. This is consistent with the observation that up to 40% of the exacerbations were associated with symptoms of antecedent or concurrent infection, most commonly involving the respiratory tract. Rubella virus, Epstein-Barr virus, and adenovirus were associated with acute exacerbations in 5 children. Thus, common pathogens were frequently associated with exacerbations and account for a large proportion of the commonly reported symptoms of a concurrent infection. The possible causal relationship between these pathogens and exacerbation of inflammatory bowel disease is discussed. Reactivation of latent herpesviruses was identified in 4 children with active disease and indicates that the converse relationship may also occur.

Acute Disease↗

Prospective study of aetiology and outcome of adult lower-respiratory-tract infections in the community.

Community-acquired adult lower-respiratory-tract infections (LRTI) are generally thought to be caused by atypical and viral infections. We have studied 480 adults presenting to a single general practice with community-acquired LRTI between November, 1990, and December, 1991. The overall incidence was 44 cases per 1000 population per year; the incidence was 2-4 times higher in people aged 60 and over than in those aged less than 50. 206 patients were studied in detail; among this group 91 (44%) had 113 pathogens identified. There were 92 bacteria (Streptococcus pneumoniae in 62 and Haemophilus influenzae in 16), 19 viruses (influenza virus in 12), and only 2 atypical pathogens (Mycoplasma pneumoniae and Coxiella burnetii). Pneumococcal infection was common in people who were 60 or older, those who had underlying chronic disease, or people with both features. There was moderate morbidity in terms of time in bed, time to return to normal activities, and days off work. 25% of patients returned for a second consultation with the general practitioner, in most because of unsatisfactory clinical progress. Community-acquired LRTI are very common, and the range of causative pathogens is similar to that for community-acquired pneumonia. Existing management strategies seem inadequate.

Adolescent↗

Pneumonia. Patient profiles, choice of empiric therapy, and the place of third-generation cephalosporins.

Choosing appropriate antimicrobial therapy for patients with pneumonia requires knowledge of the etiologic agents seen in specific kinds of patients at specific times and places. For community-acquired pneumonia, there is an important difference in the agents seen in the normal and the compromised host. The normal host most often presents with viral, mycoplasmal, or pneumococcal pneumonia. The exact place of Chlamydia pneumoniae is still under study. A normal host who aspirates is at risk of anaerobic pneumonia. Normal hosts with influenza may acquire superinfection with Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus. Under specific epidemiologic conditions, community-acquired pneumonia may be due to Legionella species, Yersinia pestis, Francisella tularensis, Coxiella burnetii, Chlamydia psittaci, a mycotic agent, or tuberculosis. Patients with chronic bronchitis and emphysema are predisposed to H. influenzae, Moraxella catarrhalis, and S. pneumoniae infections. HIV-infected patients are likely to have Pneumocystis carinii pneumonia and pneumonia due to cytomegalovirus, S. pneumoniae, and H. influenzae. Patients with diabetes, nursing-home patients, hospitalized patients, immuno-compromised patients, and patients with recent antibiotic therapy are predisposed to pneumonia due to Gram-negative aerobic bacilli of enteric and environmental origin. Initial therapy should be directed at the likely organism or organisms based on hospital susceptibility surveillance. In the normal host with community-acquired pneumonia, the therapy will often be penicillin G or erythromycin. In the patient predisposed to Gram-negative pneumonia, a third-generation cephalosporin with or without an aminoglycoside is the usual choice.

Cephalosporins↗

Chloroquine does not enhance the activity of clarithromycin against multiplication of Mycobacterium avium within human macrophages.

SETTING: Chloroquine, an alkalinizing lysosomotropic agent, enhances the intracellular activity of antibiotics against Mycobacterium tuberculosis or Coxiella burnetii. OBJECTIVE: To determine if chloroquine modifies the activity of clarithromycin, less effective at acidic pH, against intracellular Mycobacterium avium. DESIGN: The activity of clarithromycin (4 micrograms/ml) against the MO-1 strain of M. avium was evaluated within human macrophages in presence of chloroquine (5 micrograms/ml). The minimal inhibitory concentration of clarithromycin for the strain was 2 micrograms/ml. RESULTS: While clarithromycin alone did decrease the intracellular infection at day 7 of culture (P < 0.01), chloroquine alone did not impede the intracellular growth of M. avium, and did not enhance the activity of clarithromycin. CONCLUSION: Chloroquine should not improve clarithromycin treatment against M. avium infection.

Cells, Cultured↗

Psoas abscess: An unusual manifestation of Q fever.

Q fever may lead to serious complications in chronically infected patients. We report two cases of psoas abscess due to Coxiella burnetii associated with lumbar osteomyelitis secondary to an aortic aneurysmal infection. Diagnosis was based on serology, and PCR detected C. burnetii DNA in an abscess sample.

Journal Article↗

Chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is thought to have a worldwide prevalence of 0.4-1% with approximately 240,000 patients in the UK. Diagnosis is based on clinical criteria and critically depends on exclusion of other physical and psychiatric diseases. Studies of pathogenesis have revealed immune system abnormalities and chronic immune activation, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, brain abnormalities, evidence of emotional stress (comprising host aspects) and evidence of exogenous insults, for example, various microbial infections (Epstein-Barr virus, enteroviruses, parvovirus B19, Coxiella burnetii and Chlamydia pneumoniae), vaccinations and exposure to organophosphate chemicals and other toxins (comprising environmental aspects). Emotional stress appears to be very important as it reduces the ability of the immune system to clear infections, it's presence has been shown to determine whether or not an individual develops symptoms upon virus infection, and it leads to activation of the HPA axis. But, emotional stress is distinct from depression, the presence of which precludes a diagnosis of CFS. There is no specific treatment for CFS other than the much underutilised approach of specific treatment of virus infections. Current priorities are to understand the molecular pathogenesis of disease in terms of human and virus gene expression, to develop a diagnostic test based on protein biomarkers, and to develop specific curative treatments.

Diagnosis, Differential↗

[Infections associated to severe thrombotic events and antiphospholipid antibodies].

The authors present 2 cases of infections in which the presence of antiphospholipid antibodies (APL), anticardiolipin and anti-beta2-GP1, was associated to the occurrence of significant thrombotic events: 1) a 55-year-old male patient whose serology (indirect immunofluorescence) revealed Coxiella burnetii infection (phase 2 antigens) with IgG at 1,600 and IgM at 50 (significant titer: IgG>or=200 and IgM>or=50); 2) and a 20-year-old male patient with a CMV infection confirmed by serology (IgG: 44 U/ml, significant threshold 6, IgM: 2.1 U/ml, significant threshold 0.9).

Adult↗

Ambulatory patients with community-acquired pneumonia: the frequency of atypical agents and clinical course.

OBJECTIVES: To determine the etiology of community-acquired pneumonia in patients treated in an ambulatory setting, using serological methods, and to compare presenting symptoms, radiographic manifestations, and clinical outcomes of patients with pneumonia of "atypical" and undetermined etiology. PATIENTS AND METHODS: This prospective cohort study was conducted in emergency room and outpatient facilities of Victoria General Hospital, Halifax, Nova Scotia, and in offices of participating family doctors based in Halifax. One hundred forty-nine adults with acute onset of one or more symptoms or signs suggestive of pneumonia and radiographic evidence of pneumonia who provided informed consent were enrolled. Patients known to be HIV positive or who had been discharged from a hospital within the previous 10 days were ineligible for enrollment. Demographic features and clinical data were collected by direct patient interview and chart review by trained research nurses. Outcome measures included quantitative evaluation of pneumonia-specific symptoms, and responses to the Short Form 36 Health Survey at presentation and at 30 days after presentation. Information was also collected on each patient's health prior to pneumonia, as well as the time until each patient's self-reported return to work and to usual activities. The etiology of pneumonia was determined by testing acute and convalescent serum samples for antibodies to Legionella pneumophila serogroup 1, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci, Coxiella burnetii, adenovirus, respiratory syncytia virus, influenza viruses A and B, and parainfluenza viruses 1, 2, 3. RESULTS: The study population consisted of 149 patients, 54 (36%) of whom were men, with a mean age (+/- SD) of 41 +/- 15 years. An etiological diagnosis was made in 74 (49.7%) patients using serological methods. Etiological agents included M pneumoniae 34 (22.8%); C pneumoniae 16 (10.7%); M pneumoniae and C pneumoniae 5 (3.4%); C burnetii 4 (2.7%); influenza A virus 4 (2.7%); and other agents 6% (7.4%). Three patients (2%) had a conventional bacterial etiology, and 72 patients (48.3%) had pneumonia of undetermined etiology. Patients with pneumonia of known (atypical) and undetermined etiology were similar in terms of age, gender, race, education, employment, and comorbidity. Despite a higher proportion of patients with pneumonia of known etiology reporting sweats, chills, and headache at presentation, the two groups were similar for symptom severity and bother. The patients with pneumonia of undetermined etiology were more likely to have multilobar pneumonia (P < 0.02). Both patients with atypical pneumonia and those with pneumonia of undetermined etiology suffered severe deterioration of physical functioning with a marked but incomplete recovery at 30 days. Those with atypical pneumonia had higher physical functioning and general mental health scores at 30 days. CONCLUSIONS: Nearly half the cases of ambulatory community-acquired pneumonia are due to "atypical" agents. It is not possible to reliably distinguish patients with atypical pneumonia from those with pneumonia of undetermined etiology by clinical features at baseline. The outcomes in terms of resolution of symptoms, functional status, return to work, and return to usual activities are essentially similar in the two groups.

Adult↗

Unusual aspects of acute Q fever-associated hepatitis.

We describe a 37-year-old farmer with a 3-week history of fevers and hepatitis, in whom Q fever was diagnosed. The diagnosis was based on the findings of characteristic "ring" granulomas on a bone marrow biopsy specimen and confirmed by complement-fixation antibody tests to Coxiella burnetii. Unusual aspects of this case included (1) relatively low complement-fixation antibody titers, (2) prolonged prothrombin time, (3) false-positive results of a serologic test for the human immunodeficiency virus (HIV), and (4) ring granulomas that progressed to atypical granulomas in biopsy specimens.

Adult↗

[Prospective study of 221 community acquired pneumonias followed up in an outpatient clinic. Etiology and clinical-radiological progression].

BACKGROUND: All the community acquired pneumonia followed up in an outpatient clinic were prospectively studied in order to determine: etiology, clinical-radiological characteristics and its progression with diagnostic and therapeutic protocols. PATIENTS AND METHOD: We arranged clinical evaluation protocols, etiological diagnosis by means of serology (in the first visit and three weeks later); and when necessary, by means of fiberbronchoscopy (protected microbiological brush), as well as clinical and radiological progression (up to three visits) after empirical treatment. RESULTS: Initially, 240 patients were included, of which 221 were fully followed up. Etiological diagnosis was obtained in 86 patients (39%). The bacteria most frequently isolated was Coxiella burnetii (12.2%), followed up Mycoplasma pneumoniae and Legionella pneumophila. Two cases of Strepcococus pneumoniae were diagnosed. The most frequent radiological onset was alveolar infiltrate (86%). The initial empiric treatment were macrolids (71%) or second generation cephalosporines (22%). Most patients presented a favourable clinical and radiological progression. Only 2 patients needed admission to the hospital (< 1%). CONCLUSIONS: In community acquired pneumonias studied in our outpatient clinic we found a high number of "atypical" agents. Treatment with macrolids or second generation cephalosporines are appropriate for these patients.

Adolescent↗

[Community acquired pneumonia in patients older than 60 years. Incidence of atypical agents and clinical-radiological progression].

BACKGROUND: Seventy five patients older than 60 years with a community acquired pneumonia followed up in an outpatient clinic, were prospectively studied in order to determine the incidence of atypical agents, clinical-radiological characteristics, progression and the differences with pneumonia in younger patients. METHOD: Clinical-radiological evaluation protocols were activated in the first visit and in two subsequent controls. Etiological diagnosis was made by means of serology (in the first visit and three weeks later). RESULTS: Initially, 85 patients older than 60 years were included of which 75 non hospitalized were fully followed up. Also, in the comparative study, 216 outpatient clinic patients 60 years old or younger were followed up during the same period. In the first group the frequency of atypical agents was 33.3%. The most frequently isolated bacteria was Coxiella burnetii (13.3%)followed by virus and Legionella pneumophila. No case of Mycoplasma pneumoniae was diagnosed. The most frequent radiological onset was alveolar infiltrate (85%). The comparative study between the two populations (older or younger than 60 years), found few clinical differences (dyspnea more frequent in older,feverish chill in younger) and auscultation (crackles more frequent in older). We did not find differences remaining clinical-radiological or laboratory data. Most patients presented a favourable clinical and radiological progression. Only 2 patients needed hospital admission (2.7%). CONCLUSIONS: In outpatient clinic patients older than 60 years with community acquired pneumonia a high number of atypical agents have been found. The clinical-radiological evolution was satisfactory for most of them. Age was not a decisive element in determining hospital admissions.

Adolescent↗

[Etiology of community-acquired pneumonia in ambulatory patients. Usefulness of a diagnostic investigation protocol using detection of Streptococcus pneumoniae and Legionella pneumophila antigens in urine samples].

BACKGROUND: To determine the etiology of community-acquired pneumonia (CAP) in ambulatory patients and to assess the efficiency of a diagnostic protocol by using tests to detect bacterial antigens in urine samples. PATIENTS AND METHOD: One-year prospective study that included blood and sputum cultures, serologic studies, and detection of Legionella pneumophila and Streptococcus pneumoniae urinary antigens. RESULTS: 49 patients were recruited and an etiological diagnosis was attained in 34 (69%). Microorganisms most frequently isolated were S. pneumoniae (12 cases), Mycoplasma pneumoniae (7), Haemophilus influenzae (4), respiratory viruses (4) and Coxiella burnetii (3 cases). CONCLUSIONS: By means of a non-invasive protocol with urinary antigen tests, a microbial etiology can be established in two thirds of patients with mild CAP. S. pneumoniae is the main cause of mild CAP.

Adolescent↗

Is Bell's palsy a reactivation of varicella zoster virus?

Despite various pointers to an infectious aetiology, the cause of Bell's palsy remains obscure. We examined paired sera from 62 patients with facial palsy and 50 age and sex matched contemporaneous controls. Significantly more patients than controls had IgM antibodies by ELISA to varicella zoster virus (56.5% vs. 20%, P = 0.0001) and herpes simplex virus (41.9% vs. 18%, P = 0.006). Additionally, significantly more patients than controls were positive for CF antibody to varicella zoster virus (14.5% vs. 0%, P = 0.004) but not to herpes simplex or cytomegalovirus. Significantly more controls than patients (54% vs. 25.8%, P = 0.002) had no evidence of antigenic stimulation by any of the herpesvirus group. No significant difference between patients and controls in seropositivity by IgM ELISA to cytomegalovirus. Epstein-Barr virus and IFA for human herpes virus 6 was found. Furthermore, there was no significant difference between the two groups as to evidence of recent infection by the following agents: rubella virus and Borrelia burgdorferi by IgM ELISA, influenza A. influenza B, adenovirus, respiratory syncytial virus, mumps and measles. Mycoplasma pneumoniae, Coxiella burnetii and chlamydia spp. by complement fixation test. The first reported case of clinically and serologically proven Mycoplasma pneumoniae pneumonia associated with Bell's palsy is described. The rate of complete recovery at 6-8 weeks after onset was not significantly different in patients who were given steroids compared to those who were not. Ear related symptoms were the most common, occurring in 12 of 65 cases, but only three (4.6%) had clinical shingles (vesicles in ear).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Q fever in pregnancy.

We describe a case of acute symptomatic infection with Coxiella burnetii acquired between the 16th and 28th week of pregnancy. Oral ciprofloxacin therapy was started on diagnosis, at the 28th week of pregnancy, but symptoms were unabated after 3 weeks treatment, suggesting persisting infection of the products of conception. Caesarean section was therefore performed at 32 weeks gestation when a healthy infant was delivered, and subsequent investigations showed no evidence of transplacental spread of infection. Infection control measures were applied at the time of delivery to minimize the risk of infection to obstetricians and midwives from potentially infectious products of conception.

Adult↗

Glomerular nephropathy associated with chronic Q fever.

Of three patients with Coxiella burnetii endocarditis, two developed focal segmental proliferative glomerulonephritis (GN), and the third developed diffuse intracapillary proliferative glomerulonephritis. In one case, a good therapeutic response was followed by partial remission of the renal alterations, but 10 months later there were clinical and histological signs of active glomerular nephropathy, suggesting that the antigenic stimulus persisted. In another case, poor evolution of the infection was accompanied by clinically and histologically aggressive glomerular nephropathy, and advanced renal failure. The third patient, who had diffuse proliferative glomerulonephritis, underwent renal biopsy earlier than the other two cases, and the behavior of the nephropathy has not been aggressive to date. Immunohistopathologic study revealed a diffuse granular deposit of IgM and C3 in all three cases; the first two also presented a discrete linear IgG deposit in the capillary loops. Attempts to identify C burnetii antigen at the glomerular level by immunohistologic techniques failed in two patients. The literature on the association of chronic Q fever with glomerulonephritis is briefly reviewed.

Adult↗

Identification and characterization of the dnaA upstream region of Thermus thermophilus.

The gene order in the dnaA region of Thermus thermophilus was determined. Previously, we showed that the putative oriC of T. thermophilus is located in the dnaA-dnaN intergenic region. In the 4 kb region upstream of the dnaA gene four ORFs were found, all orientated in the same direction which is opposite to that of dnaA. The ORFs were identified as T. thermophilus homologs of gidA, gidB, soj and spo0J of Bacillus subtilis. The gene order spo0J-soj-gidB-gidA-dnaA-dnaN resembles that of B. subtilis, Pseudomonas putida, Coxiella burnetii, Streptomyces coelicolor, Mycobacterium leprae, and Mycobacterium tuberculosis. We identified the transcriptional start point of the dnaA gene. The -10 region shows significant homology to the Escherichia coli -10 consensus sequence. The putative -35 region shows homology neither to the E. coli -35 consensus sequence nor to known -35 sequences of T. thermophilus. There are no DnaA boxes in the promoter region, and consequently dnaA transcription is not repressed by DnaA protein in vitro, i.e. the dnaA gene of T. thermophilus is not autoregulated.

Bacterial Proteins↗