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Background: Q fever is a worldwide zoonosis caused by Coxiella burnetii, which can be isolated from ticks. Reports of people with both Q fever and other tickborne diseases are rare. In this study, we describe 6 patients with Q fever who were infected with 1 of the following tickborne pathogens: Rickettsia conorii (2 patients), Rickettsia slovaca (2), Rickettsia africae (1), and Francisella tularensis (1)., Methods: Diagnoses were made on the basis of results of microimmunofluorescence assays for detection of C. burnetii, R. conorii, R. slovaca, R. africae, and F. tularensis antigens. Cross-adsorption studies and Western blots were used to confirm dual infections., Results: Among the 6 cases presented, 3 were probably due to a concomitant infection after a tick bite, whereas the remaining 3 were more likely consecutive infections., Conclusions: Because acute Q fever is often asymptomatic, we recommend that patients infected with the tickborne pathogens mentioned above also undergo routine testing for concurrent infections with C. burnetii.

Dengue fever (DF) is a mosquito-transmitted acute disease caused by any of four dengue flavivirus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) which is becoming a major public health problem in intertropical areas.1 DF is increasingly observed in febrile travelers returning from tropical areas,2 especially those returning from the Caribbean islands and Southeast Asia, but it is rarely diagnosed in travelers returning from Africa.3-8 Diagnosis is often serologic, and in most cases is not confirmed; virus isolation remains exceptional. In a retrospective study of 44 cases of imported DF diagnosed in France, we found that the epidemiologic, clinical and diagnostic characteristics of these cases were similar to those reported in other previous published studies; diagnosis was carried out with serology, and no virus isolation was reported. To draw the attention of physicians from nonendemic areas to the possible occurrence of dengue infection in febrile travelers from all tropical countries, including those in Africa, and to reinforce recommendations required to establish diagnosis with certainty, we report herein a prospective study from 1998-1999 which we compiled with our previously published data.

Background: Q fever is characterized by its clinical polymorphism; neurological involvement has occasionally been described. In the course of acute Q fever, neurological manifestations may include aseptic meningitis, encephalitis or encephalomyelitis, and peripheral neuropathy., Objective: To review and evaluate cases of acute Q fever with neurological symptoms diagnosed in our laboratory., Methods: A total of 1269 acute Q fever cases were recorded from January 1985 to January 2000 in our laboratory and were reviewed for neurological complications. Patients were considered to have acute Q fever when serological procedures showed Coxiella burnetii phase II titers of 1:200 or higher for IgG and 1:50 or higher for IgM. Those patients who underwent a lumbar puncture for cerebrospinal fluid analysis or who had abnormal neurological symptoms were selected for this study. We describe the clinical, epidemiological, and biological features of these cases. We also review the literature and compare our cases with those previously reported., Results: Among the 45 patients selected, 14 were excluded because they had normal cerebrospinal fluid and no neurological symptoms. Two were excluded because there were no clinical or epidemiological data. Three major clinical syndromes were observed: meningoencephalitis or encephalitis in 17 cases; meningitis in 8; and myelitis and peripheral neuropathy in 4. Encephalitic signs were not specific, but behavior or psychiatric disturbances were common., Conclusions: Q fever should be included in the differential diagnosis of acute neurological disease in a patient with a fever. Serological testing should be performed in cases of meningoencephalitis, lymphocytic meningitis, and peripheral neuropathy, including Guillain-Barré syndrome and myelitis.

Q fever is a zoonosis caused by Coxiella burnetii. The acute Q fever is usually characterized by a self-limited flu-like syndrome, fever, pneumonia and hepatitis. Symptoms of the chronic Q fever (evolution>3 months) mainly consist of endocarditis with negative culture. Focal neurological symptoms are rarely observed. Neurological symptoms of acute Q fever consist of meningitis or meningo-encephalitis. Neurological symptoms of chronic Q fever are cerebral embolisms from Coxiella burnetii infected heart valves. We herein report two patients with meningoencephalitis revealing acute Q fever.

Imported dengue is increasingly observed in non endemic countries. We report a retrospective study of 44 cases of dengue fever diagnosed in nine french university hospitals between 1994 and 1997. The patients were aged between 13 and 67 years. Most of them were tourists and had been traveling for a few weeks, in French West Indies and French Guyana (18), South-East Asia (10), India (7) or Polynesia (4). Only, two contracted the disease in Africa. The onset of symptoms preceded the return or followed it within 7 days. The most frequent clinical presentation was a febrile and painful syndrome. Cutaneous manifestations (rash or macular exanthem) were observed in 59% of cases, digestive symptoms in 50%, pharyngitis and/or cough in 25%, microadenopathy in 20%, moderate mucous haemorrhagic manifestations in 16% and neuropsychiatric manifestations in 14%. The common biological abnormalities were thrombocytopenia (84%), leukopenia (59%), and elevated transminases (57%). The diagnosis, orientated by negativity of malaria smears, the knowledge of an epidemic in the visited country, or occurrence of similar cases in the entourage, were argued by serological results: presence of anti-DEN IgM in 25 cases, serological conversion (anti- DEN IgG) in 7 cases or very high seropositivity (anti-DEN IgG > 1/1280) in 12 cases. No virus isolation was obtained.

Objective: To analyse retrospectively the clinical, biological and epidemiological features of cytomegalovirus (CMV) infection in the immunocompetent host., Patients and Methods: A retrospective study was conducted in 116 cases of CMV infection (74 inpatients, 42 out-patients) collected from 1981 to 1997 in a university hospital. Diagnostic was established on serological criteria in all cases., Results: Fever was observed in all cases but one (mean duration: 21 days). The most frequent symptoms were headache (51%) and myalgia (46%). Splenomegaly was the most frequent sign (36%). Pulmonary interstitial opacities on chest x-ray were found in 8.5% of patients. Pulmonary (1 case) and neurological (2 cases) complications occurred. Concomitant HIV primary infection was observed in 2 patients. Mononucleosis and ALAT and LDH elevations were observed in 95%, 85% and 95% of cases respectively. Viremia was positive in 79% (30/38). pp65 antigenemia was useful to establish the diagnosis in 9 patients. Antibiotics were prescribed in 46% before diagnosis was established., Conclusion: CMV infection in the immunocompetent host is a frequent and rarely complicated disease. pp65 antigenemia should be evaluated more in this setting. Most hospitalizations due to this affection could be avoided.

We report the first three documented cases of murine typhus imported into Europe from Indonesia, discuss clues for the diagnosis of the disease, and urge that murine fever be considered in the diagnosis of febrile disease in travelers.

25 HIV-infected antiretroviral-naive adults were included in a 24-week study to evaluate the efficacy and the tolerability of a zidovudine/didanosine combination therapy in which didanosine was administered once daily (200 mg if weight < 60 kg, 300 mg if weight > 60 kg) and zidovudine twice daily (500 mg/day if weight < 90 kg, 600 mg/day if weight > 90 kg). 5 patients discontinued their treatment early: 3 had poor compliance and 2 presented adverse events. Evaluation of treatment efficacy was based on CD4+ T cell enumeration and HIV RNA level quantitation in plasma (NASBA). Baseline values were 278 CD4+/mm3 and 5.42 log RNA copies/ml. Mean changes from baseline were +102 CD4+/mm3 and -2.14 log RNA copies/ml at week 8 and +156 CD4+/mm3 and -2.07 log RNA copies/ml at week 24. HIV RNA in plasma was lower than the detection limit (2.60 log RNA copies/ml) in 55% of patients at week 8 and in 30% at week 24. No major adverse events such as neuropathy or pancreatitis were observed. Once-daily administration of didanosine in combination with twice-daily administration of zidovudine is a well tolerated regimen that appears to be as effective ad the conventional zidovudine/didanosine combination regimen.

Genetic diversity of 160 Candida albicans isolates from the oral cavity of 16 HIV-infected adults prior to antifungal treatment was assessed using multilocus enzyme electrophoresis (10 C. albicans colonies were randomly chosen from each specimen culture). 20 electrophoretic types were distinguished from the analysis of 21 enzyme loci (10 were polymorphic). Five patients (31%) were found to be colonized by 2 or 3 genetically distinct strains. Nevertheless, in these five cases, one strain predominated (from 7 to 9 of the 10 colonies). Some HIV + patients with oral candidiasis appear to be simultaneously infected with several genetically different C. albicans strains before antifungal treatment.

Multilocus enzyme electrophoresis and in vitro susceptibility testing with a broth microdilution method were used to analyze Candida albicans strain diversity in four AIDS patients with recurrent oropharyngeal candidiasis who successively developed clinical resistance to fluconazole (FCZ) and itraconazole (ITZ). One to ten colonies per sample were randomly chosen from oral washings collected before the initial FCZ treatment and just before every other antifungal treatment; a total of 98 isolates were analyzed. Multilocus enzyme electrophoresis analysis revealed 14 different electrophoretic types (ETs). Statistical analysis of genetic distances showed that C. albicans isolates clustered into five subpopulations (I to V). In each subpopulation, isolates are closely related, and genetic distances between subpopulations I to IV are short. In contrast, subpopulation V, which contained isolates typed as ET8 and ET14, is strongly divergent from the others; these isolates may represent atypical C. albicans isolates. Only one patient was infected with a single strain during the course of azole therapy; for the three remaining patients, variants of the same strain and different strains were concurrently isolated. Clinical FCZ resistance was clearly correlated with in vitro data for three patients. Moreover, MICs of ITZ increased during FCZ therapy, and MICs of ITZ which were > or = 1.56 micrograms/ml were found when clinical ITZ resistance occurred; isolates from subpopulation V showed the highest MICs of ITZ. Because of the emergence of clinical ITZ resistance after clinical FCZ resistance, the feasibility of long-term azole therapy for mucosal candidiasis in AIDS patients is questioned.

Between 1989 and 1993, investigations by classical parasitological procedures of 139 HIV-infected adults living in visceral leishmaniasis (VL) endemic areas showed that 10 of them (7.2%) were positive for Leishmania (by stained smears and culture). In the same period we identified 15 VL cases in patients not infected with HIV. Thus, 40% (10/25) of our VL cases were associated with HIV infection.

To ascertain the population structure of Candida albicans, we have carried out a multilocus enzyme electrophoresis study based on the analysis of 21 gene loci. We have thus characterized 55 strains isolated one each from 55 human immunodeficiency virus-positive patients. There is considerable polymorphism among the strains. A population-genetic analysis indicates that the two fundamental consequences of sexual reproduction (i.e., segregation and recombination) are apparently absent in this population of C. albicans. The population structure of C. albicans appears to be clonal, a state of affairs that has important medical and biological consequences.

A French multicentre study was conducted in 15 Infectious Diseases departments; 347 cases of severe staphylococcal infections were collected during one year (October 1989 to October 1990): Two-hundred and fifty-eight strains were analysed with complementary bacteriological studies, including 62 strains of methicillin-resistant Staphylococcus aureus. Epidemiological, clinical and therapeutic aspects were investigated. Nosocomial infection was responsible for 90 percent of the cases, and previous antibiotic therapy was reported in 74 percent. An invasive procedure was incriminated in 43 patients (69 percent); intravenous catheter (38 percent), mechanical ventilation (31 percent), surgery (22 percent), prosthetic device (20 percent). Thirty-nine patients were treated with glycopeptides either alone or in combination with beta-lactams, aminoglycosides, fucidic acid, fosfomycin, rifampicin, quinolones or synergistines, showing the great diversity in the choice of antibiotics in methicillin-resistant S. aureus infections. More than 90 percent of these strains were resistant to gentamicin and quinolones, 80 percent of clindamycin and 70 percent to rifampicin. No resistance to glycopeptides (vancomycin or teicoplanin) was observed. Prognosis was severe, with a mortality rate of 35 percent, justifying educational and prophylactic measures in at risk medical departments.

In France, human brucellosis decreased significantly between the 70's (800 annual cases) and 1992 (102 cases), the result of the veterinary fight against animal disease. Bovin brucellosis is almost eradicated except into Massif Central, Pyrénées and Alpes, where goats and sheep are always responsible for the contamination of cows. B. melitensis 9/11 biovar 3 is the more frequent contaminant. Clinical features of human disease are unchanged but skeletal and visceral focalisations become less frequent than previously--Blood cultures--too often left--and seroagglutination remain classical means of diagnosis. I.I.F. and ELISA are more precise because recognition of specific IgM and IgA which are good evidence of recent or persistent infection. In vitro antibody production--assay (IVAP) is more sophistical; its value should be assessed. Today antibiotherapy for acute or subacute forms is based on associations: Tetracycline (2 g/d) or better Doxycycline (200 mg once daily for 45 d) are always associated with either Streptomycin (1 g daily for 21 days) or Rifampicin (900 mg once daily for 45 d). The first regimen is probably more efficient than the second one because relapses occur more often (5-10%) with Doxycycline-Rifampicin than with Doxycycline-Streptomycin (relapses: 4-5%). In pregnant women Cotrimoxazole-Rifampin is efficient enough and atoxic if the treatment is stopped 7 days before delivery. The same regimen is recommended in children less 8 years of age. Veterinary action should be going on in spite of its cost. Individual measures (gloves, antiseptic solution for shoes, boiled milk...) are always necessary. Specific immunization (vaccin Mérieux, France) often seems efficient despite a few light adverse effects; its use is recommended in farmers, veterinary and bacteriologic workers.

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.

We developed an assay to detect antibodies spontaneously secreted in vitro by peripheral blood mononuclear cells (PBMC) against Brucella spp. High levels of anti-Brucella immunoglobulin G (IgG) and/or IgM and/or IgA antibodies were detected in the cell supernatant solution of PBMC cultures for 12 patients suffering from acute or focalized brucellosis and for 5 patients recently vaccinated against brucellosis. This spontaneous in vitro antibody production disappeared 5 to 20 months after onset of clinical signs and 20 to 27 days after vaccination. The transient character of this anti-Brucella antibody production by PBMC is consistent with a temporary in vivo stimulation of the immune system by Brucella antigens. Detection of this secretion could improve the diagnosis of evolutive brucellosis.

This prospective study evaluated the in vitro susceptibility of Candida albicans isolates recovered from the oral cavity of AIDS/ARC patients before and during long-term therapy with fluconazole. Thirty adults (15 with ARC and 15 with AIDS) with a first episode of thrush candidiasis were given oral fluconazole (Triflucan 50 mg; one capsule daily) for at least three months. Fungal susceptibility testing was performed before treatment, after one month, and at last follow-up (range 3.5-12 months; mean 5.7 months). MICs were determined using the agar dilution method with casitone (Difco 259-01) as the test medium at pH 7.2-7.4. There were two initial clinical failures (one with high MICs before and under treatment and one with an intermediate MIC initially and a rise in MIC under fluconazole). Four patients developed a clinical relapse with no change in MICs (which were low or intermediate). In six patients, clinical symptoms resolved but carriage of C. albicans persisted (low MICs). In 18 patients, clinical resolution with eradication of C. albicans was achieved. These data suggest that (1) clinical failures may be associated with in vitro resistance; (2) relapses under fluconazole maintenance therapy may develop in patients with advanced HIV disease despite the lack of change in the susceptibility of strains.

In 5 acquired-immunodeficiency syndrome (AIDS) cases without peripheral neuropathy, we observed myogen clinical signs (diffuse amyotrophy of lower limbs or cramps) or an isolated increase in seric enzyme (LDH, CK). EMG abnormalities were observed in all cases: spontaneous activities (fibrillations and positive sharp waves) in 5 cases, myogenic signs in 2 case. Muscular biopsies were normal in 3 cases and showed myopathic changes in 1 case and polymyositis in another case. Antidystrophin and antilaminin antibodies reactions were altered in 1 case. The spontaneous activities together with these modifications could be in favour of a lesion at the membrane level.

Cefotiam (SCE 963), a new, broad-spectrum, third generation cephalosporin was used in the treatment of 136 patients suffering from respiratory tract infections, urinary tract infections, septicemia, meningitis, biliary tract infections and osteoarthritis infections. Cefotiam was administered in monotherapy to 98 patients at the mean posology of two grams per day (extreme doses: 1 to 6 g). The following clinical effectiveness was noted: 83 successes and 18 failures on 101 available clinical reports. The general, biological tolerance and renal tolerance was good in all patients.

One hundred one nosocomial septicemias (NS) were studied among 461 cases of septicemias (22%) collected by French Septicemia Expert System Group during 1985. The mean-age of the patients was 58 +/- 23 years while it was 56 +/- 23 years in the 360 community acquired septicemias (CAS). The source of septicemia was found more frequently in NS than in CAS (79/101 versus 223/360; p less than 0.002): mainly urinary tract and intravenous therapy in NS, urinary tract, gastrointestinal and biliary origin in CAS. Invasive procedures (except surgical procedures) were more frequent in NS than in CAS (13/101 vs 14/360; p less than 0.0001). Underlying diseases were more often associated with NS than with CAS (96/101 vs 276/360; p less than 0.0001). Many pathogens were involved in these NS but the frequency of S. aureus meti-S and meti-R, S. epidermidis, Enterobacter, Klebsiella, Serratia, Proteus indol + and Pseudomonas carbeni-R was significantly greater in NS than in CAS. There was no significant difference between NS and CAS for septic localizations, respiratory distress syndrome and septic shock. Two antibiotics (and possibly 3 antibiotics for polymicrobial septicemias) were more often used in NS than in CAS (61/101 vs 135/360; p = 0.002). If the duration of hospitalization was not significantly greater in NS than in CAS (26 +/- 29 days vs 23 +/- 33 days), the overall mortality was significantly more important (25.6% vs 14.9%; p less than 0.05).

Twenty nine patients with Rickettsiosis (Tick born fever, n: 22, Q fever, n: 7) has been treated with fluoroquinolones. These compounds was used alone n: 25 (Pefloxacin, n: 15; Ofloxacin, n: 10) or associated n: 4 (Pefloxacin + Rifampin). The general efficacy was excellent. Common Tick born fever and pulmonary forms of Q fever was fast cured. Severe Tick born fever (neurologic or polyvisceral forms, n: 5) and Q fever with long term hyperthermia, n: 4 cas always cured without complications but the time necessary to obtain apyrexia was often longer (6 cases).

The authors discuss the present value of rifampicin in the treatment of human brucellosis on the basis of: 1) a bacteriological study of 42 strains of Brucella spp. (MIC's of rifampicin, tetracyclin, doxycyclin, minocyclin and streptomycin; results of doxycyclin-rifampicin and doxycyclin-streptomycin combinations), and 2) a clinical study of 38 cases of brucellosis treated with rifampicin, including 25 acute septicemias and 13 osteo-arthritis. Satisfactory results were observed in 92% of the cases with rifampicin alone, but one cannot state that the benefits are significant.

Fifty one cases of Pseudomonas aeruginosa bacteriaemia observed during the last 12 years are reported. Thirty five patients were over fifty years old; 92 p. cent were admitted for several days and about 50 p. cent were in post-operative period. A previous antibiotherapy and an impaired status are promotive factors. The respiratory or peritoneal origins are the most frequent. All patients were feverish; 24 have had an infectious shock which was inaugural in 12 cases. Seven pneumonitis, 3 endocarditis, one pericarditis and 2 osteitis were observed. An ecthyma gangrenosum was noted in three patients. Mortality was 70 p. cent. Comparison between recovered and died patients improved bad prognosis of old age, post operative period, neoplasic, previous organica weakness and pulmonary or peritoneal origins. Used alone, colimycin has seemed to be more effective than aminosid antibiotics; but their association with betalactamins was better. An in vitro study of the susceptibility of 100 Pseudomonas aeruginosa strains has proved the interest of piperacillin and cefsulodin; azlocillin, cefoperazone and ceftriaxone are just less effective.

Pefloxacin was given as the single drug (except in one case) to twenty-seven patients with a variety of infections (bone and/or joint: 8; respiratory tract: 6; urinary tract: 5; bacteremia: 4; meninges: 3; other: 1). The following bacteria were isolated: P. aeruginosa: 11; Enterobacteriaceae: 10; Acinetobacter: 3; Staphylococci: 3 (including 2 methicillin-resistant strains), and Streptococcus faecalis: 2. Pefloxacin was given in a daily dosage of 800 mg in 20 patients and 1 200 to 1 600 mg in 7. All pathogens proved susceptible, in varying degrees. 21 patients recovered. Three incomplete results and three failures were observed. No significant side effects were recorded except for development of three mucosal candidiasis and two transient rashes. The authors put special emphasis on the value of pefloxacin in bone and meningeal infections.

Thirty-two patients were treated by ofloxacin on bacteriological documented infections. They were Enterobacterias: n = 15 (MIC less than or equal to 0.06 to 0.5 microgram/ml); Pseudomonas aeruginosa and Acinetobacter: n = 1 (MIC 0.5 and 4 micrograms/ml); Staphylococcus: n = 6 (MIC less than or equal to 0.06 to 4 micrograms/ml); Pneumococcus: n = 1; Mycoplasma: n = 1; Chlamydia psittaci: n = 2; Legionella pneumophila: n = 1; Rickettsias: n = 4 (three mediterranean fevers one query fever). Ofloxacin was given orally from 400 to 800 mg per day (5 to 15 mg/kg/day). It was used alone 26 times and on 6 occasions it was associated with rifampin on 6 staphylococcal infections. On 19 cases it was used after failure or intolerance of initial therapy. Thirty times it was the first antibiotic substance used. Results were good mainly: 1) on nine pneumonitis (enterobacterias: 4; Pneumococcus: 1; Mycoplasma: 1; Chlamydia: 2; Legionella: 1) during a mean duration of twenty days; 2) urinary infections (n:7) provoked by E. coli and Enterobacter cloacae (mean duration: 20 days); 3) 4 osteo-articular-infections (mean duration: 77 days); 4) Rickettsial infections (n:4) during a mean duration of 11 days. Results are particularly noteworthy because patients treated had severe infections: 12 bacteremias, 1 endocarditis and 1 purulent meningitis. None severe adverse effect was observed.