Safety and immunogenicity of subcutaneous or intramuscular administration of a monovalent inactivated vaccine against Leptospira interrogans serogroup Icterohaemorrhagiae in healthy volunteers.

The safety and immunogenicity of a monovalent inactivated vaccine against Leptospira interrogans serogroup Icterohaemorrhagiae was evaluated in 84 volunteers according to the route of administration, i.e., subcutaneous (SC) or intramuscular (IM), in a double-blind randomised trial. The volunteers were randomised into four groups: SC vaccine; IM vaccine; SC placebo; and IM placebo. Primary vaccination comprised two injections on day 0 and day 14, with a booster after 6 months. A second booster was given 30 months after primary vaccination. Local reactions within 1 h of injections were rare, with no difference between vaccine groups. Local reactions within 3 h were more frequent after the second, third and fourth SC injections than after IM injections. Systemic reactions never occurred within 1 h of vaccination and were rare within 3 days; the rates were comparable for the different vaccine groups. Evolution of the antibody responses, as assessed by microscopic agglutination tests and specific IgG and IgM ELISAs, were similar for both injection routes. IgG seroconversion rates after the first booster were 97% (95% CI 80-100%) for the SC vaccine group, and 96% (95% CI 80-100%) for the IM vaccine group, and both reached 100% for IgG after the second booster. The safety and immunogenicity of the anti-leptospiral vaccine were both good. Monitoring of antibody levels established that a booster dose triggered a strong antibody response in fully vaccinated subjects at 30 months after primary vaccination.

Antibiotic susceptibility and genotypic characterization of Haemophilus influenzae strains isolated from nasopharyngeal specimens from children in day-care centers in eastern France.

OBJECTIVE: To determine the overall carriage rate for Haemophilus influenzae in young children in day-care centers, the frequency of resistance to various classes of antibiotic, and the clonal relationship between isolates of the various resistant phenotypes. METHODS: Nasopharyngeal (NP) specimens were obtained and cultured on chocolate agar with bacitracin. Antibiotic susceptibility testing and serotyping were performed for all isolates. The genetic polymorphism of ampicillin-susceptible and beta-lactamase-producing isolates was studied by pulsed-field gel electrophoresis using SmaI. RESULTS: Of the 596 NP secretion cultures, 152 (25.5%) were positive for H. influenzae. Sixty-four (42.1%) isolates produced beta-lactamase and two (1.3%) were ampicillin resistant but did not produce beta-lactamase. We were unable to serotype 150 isolates; one isolate belonged to capsular serotype e and one to serotype f. Forty-six major DNA patterns were identified among 76 randomized isolates. beta-lactamase producing isolates more frequently showed EP than ampicillin-susceptible isolates P < 10(-4). The frequency of isolates with EP was significantly lower in day-care centers attended by less than 20 children than in those attended by more than 20 children (P = 0.020). CONCLUSIONS: Resistance due to beta-lactamase production has disseminated in some day-care centers, mostly by person-to-person spread but also via the possible conjugal transfer of large plasmids between strains. The size of day-care centers may affect the risk of transmission.

Systemic cat scratch disease: hepatic and splenic involvement about 3 pediatric cases.

Numerous diseases can lead to multinodular lesions of liver and spleen; surgical biopsy can be required for the etiologic diagnosis. Among these diseases, systemic cat scratch disease has been recently described. Macroscopical appearance of the lesions is evocative and must be known by surgeons. Three children with systemic cat scratch disease involving liver and spleen are reported.

[Treatment of human alveolar echinococcosis with flubendazole. Clinical, morphological and immunological study]. / Traitement de l'échinococcose alvéolaire humaine par le flubendazole. Etude clinique, morphologique et immunologique.

Flubendazole has been given at a daily dosage of 50 mg/kg for 16 months (extremes 10 and 24 months) to 10 patients with hepatic alveolar echinococcosis. Clinical, morphological and immunological evaluations have been performed every 2 months during the treatment, and in 6 patients after discontinuation of the drug for 24 months. Jaundice persisted or occurred in 7 patients; infectious complications were observed in 4 patients; portal hypertension appeared in 5 patients; metastatic spread was suspected in 2 patients. Subjective improvement and weight gain were reported by 6 patients during the first 4 months of treatment. Severe complications occurring during the period of FZ therapy or within 2 months after withdrawal of the drug led to surgery in 6 patients, and death occurred in 3 cases. These observations demonstrate the inefficacy of FZ in this series of 10 patients with alveolar echinococcosis, possibly related to the extremely poor bioavailability of FZ. Higher plasma concentrations obtained with mebendazole and albendazole could explain the better efficacy of these two drugs despite their similar chemical structures and experimental toxicity upon larval cestodes.

[Ecthyma gangrenosum caused by Pseudomonas stutzeri with bacteraemia and systemic vascularitis]. / Ecthyma gangrenosum avec septicémie à Pseudomonas stutzeri s'accompagnant d'une vascularite systémique.

INTRODUCTION: Ecthyma gangrenosum is a cutaneous manifestation of Pseudomonas infections. This condition may be associated with bacteraemia but can also occur in the absence of bacteraemia. EXEGESIS: The authors report the case of a 66-year-old woman presented with necrotic ulcerations on the face associated with fever, arthralgia, myalgia, fatigue and neutropenia. Blood cultures and skin cultures were positive for Pseudomonas stutzeri. Her condition improved under appropriate antibiotic therapy. However, the patient further developed clinical and biological symptoms of systemic vasculitis and mixed cryoglubulinemia. Complete healing was finally obtained after a course of corticosteroids. CONCLUSION: Ecthyma gangrenosum should be suspected in people who have typical clinical presentation. This disease could sometimes be associated with systemic vasculitis.

[1977 mortality rate in HIV-infected patients presenting with hepatitis C cirrhosis. Results of the GERMIVC multicenter survey conducted in French departments of internal medicine or infectious disease]. / Mortalité par cirrhose virale C chez les patients infectés par le VIH dans les services de médecine interne et de pathologie infectieuse en 1997. Enquête multicentrique GERMIVIC. (Groupe d'étude sur le virus C). (Société nationale française de médecine interne). (Société de pathologie Infectieuse de langue française).

PURPOSE: Hepatitis C (HCV) has a high prevalence (10-30%) among human immunodeficiency virus (HIV)-infected patients. However, little information is available regarding the impact of hepatitis C on survival. The objective of our study was to determine the incidence of hepatitis C-related deaths in HIV-HCV co-infected patients. METHODS: The study was a retrospective (1-year), multicenter cohort survey conducted in 63 departments of either internal medicine or infectious diseases in France. It included 26,497 HIV-infected patients, of whom 4,465 (16.8%) presented coinfection due to the hepatitis C virus. The following parameters were studied for the year 1997: total number of deaths, number of deaths related to either AIDS, cirrhosis, hepatocellular carcinoma, or other causes. RESULTS: Among the 26,497 patients, 543 deaths (incidence: 2%) were observed in 1997; 543 deaths were due to AIDS (incidence: 1.7%), 36 to cirrhosis and/or hepatocellular carcinoma (incidence: 0.13%), and 48 (incidence: 0.18%) to another cause. In the subgroup including 4,465 HIV-HCV-coinfected patients, 29 deaths (incidence: 0.64%) were due to either HCV-related cirrhosis or hepatocellular carcinoma. These results were compared with those of a previous similar survey conducted in 1995, before the era of highly active antiretroviral therapy. The only significant difference is the dramatic regression of deaths due to AIDS. CONCLUSION: The impact of hepatitis C virus on the mortality among HIV-infected patients whose follow-up took place in departments of either internal medicine or infectious diseases in France was very low in 1997. The expected increase in the life span in these patients could modify these results in the future, due to recent improvements in the HIV infection treatment.

[Splenic infarction in Plasmodium falciparum malarial attack]. / Infarctus splénique au cours d'un accès palustre a Plasmodium falciparum.

Splenic infarct during P. falciparum malaria is rare but well known. We report one case where ultrasonography and computed tomography suggested the diagnostic, showing respectively in splenic parenchyma a peripheral hypoechoic lesion and a low attenuation lesion. Diagnostic was confirmed by spontaneous regression during following days. We shall encounter more frequently than nowadays this rare entity due to expanding tourism and P. falciparum resistance.

[Critical analysis of antibiotic treatment of acute gastroenteritis in infants and young children]. / Analyse critique de la prescription des antibiotiques au cours des gastroentérites aiguës du nourrisson et du petit enfant.

BACKGROUND: Antibiotics are usually not recommended in the management of acute gastroenteritis (AGE) in infants. Our study aimed at testing whether our practice was in adequacy with this recommendation. METHODS: We reviewed the files of infants hospitalized for AGE from January 1999 to June 2000. They were sorted into three categories: 1) primary community-acquired AGE; 2) secondary community-acquired AGE; and 3) miscellaneous. Only the cases of primitive AGE were retained for this study in which we compared the characteristics of the patients treated to those who were not given antibiotic treatment. RESULTS: On the 149 analysed cases, Rotavirus was identified in stools in 94 cases and stool culture was positive in 18 cases. Antibiotics were given to 10% of cases. Treated vs. untreated patients were significantly different for body temperature on admission, maximal body temperature and CRP. CONCLUSION: Recommendation not to give antibiotic to infants with AGE was followed in 90% of the cases managed in our department. Antibiotic prescription was dictated by clinical or laboratory signs of severity.

[Intracamera penetration of ofloxacin in man]. / La pénétration intracamérulaire de l'ofloxacine chez l'homme.

The authors have studied the penetration of Ofloxacin in the aqueous humour in 30 patients (30 eyes). Six hours after a single oral dose of 200 mg, the concentration in the anterior chamber reached 0.6 microgram/ml which is 23% of the average serum level. It is over the minimal inhibitory concentration necessary for many bacterial agents found in endophthalmitis (except Streptococcus) because the MIC of Ofloxacin are the lowest among quinolones. Side effects and association with other antibiotics are precise.

[A little known cause of persistent fever and granulomatous hepatitis in children: cat scratch disease]. / Une cause peu connue de fièvre prolongée et d'hépatite granulomateuse chez l'enfant: la maladie des griffes du chat.

BACKGROUND: Extensive hepatic and splenic involvement in cat-scratch disease has rarely been reported. CASE REPORT: A 2 1/2 year-old boy suffered for 2 weeks from high-grade fever, abdominal pain and alteration of his general condition. Ultrasonography revealed multiple hypoechogenic nodules in liver and spleen. The CT scan also showed hypodense lesions. An open liver biopsy was performed 5 weeks after the onset of illness. Histopathology of a resected nodule demonstrated neutrophilic granulomatous inflammation with central abscess formation. Recent cat exposure, suppurated epitrochlear lymph node 15 days before admission were also consistent with cat-scratch disease which was confirmed by elevated anti-Rochalimaea antibody titers. Follow-up showed complete resolution of all hepatic and splenic lesions within 6 months and emergence of splenic calcifications. CONCLUSION: Cat-scratch disease should be considered in the diagnosis of fever of unknown origin and hepatosplenic abscesses in children.

[Intracameral penetration of pefloxacine in man]. / La pénétration intracamérulaire de la péfloxacine chez l'homme.

Authors have studied the intraocular penetration of a new antibiotic, pefloxacin in 35 patients (35 eyes). This study emphasizes the three main qualities of this recent quinolone in ophthalmology: wide spectrum adequate for the most pathogens commonly found in endophthalmitis. Very large penetration in the aqueous humour flow with an average level of 0.95 mu/ml, which is over the minimal inhibitory concentration for many bacterial infections and is equal to 25% of average serum level.

[Allergic bronchopulmonary aspergillosis and cystic fibrosis. 2 case reports in adults]. / Aspergillose bronchopulmonaire allergique et mucoviscidose. A propos de deux cas d'association chez l'adulte.

The authors report two cases of allergic bronchopulmonary aspergillosis complicating cystic fibrosis in adults: respectively an acute and an exacerbation stage. Association cystic fibrosis-allergic bronchopulmonary aspergillosis is not uncommon and should be considered in all patients with cystic fibrosis especially with atopic disorders. These two cases are a reminder of the diagnosis criteria (clinical, radiologic and biological) and treatment.

[Behcet disease with cardiac and pulmonary manifestations]. / Maladie de Behçet avec manifestations cardiaques et pulmonaires.

BACKGROUND: Behçet's disease is a multisystem illness rarely including cardiac involvement. We report a case characterized by a mural cardiac mass in the right ventricle. CASE REPORT: A 14-year-old boy presented with a full set of symptoms leading to the diagnosis of Behçet's disease. Echocardiography revealed a 60/120 mm mass in the right ventricle. With anticoagulation therapy, prednisone and cyclophosphamide, the cardiac lesion progressively resolved. DISCUSSION: This observation is exceptional because cardiac mas is rarely described in Behçet's disease. Surgical exploration, which is usually indicated to exclude malignant process, is not necessary in such cases.

[Skin manifestations of Still's disease in adults. Apropos of 4 cases]. / Manifestations cutanées de la maladie de Still de l'adulte. A propos de 4 observations.

The authors report four new cases of Still's disease in adult. Each time, the clinical picture associated the following triad: fever, joint involvement and skin rashes. The latter consisted in non-pruritic but sensitive maculo-papular and disseminated lesions, the mean course of which lasted 24 to 48 hours and were readily accompanied by the two other components of the basic clinical triad. Laboratory investigations were non-specific but constantly included a polymorphonuclear leucocytosis and a raised ESR, the mean value of which reached 80 mm in the 1st hour. Antinuclear factors were not demonstrated, but circulating immune complexes were found on several occasions in three out of the four reported cases. Histopathological changes observed were those of a superficial and mid cutis edema, associated with a diffuse or perivascular infiltrate in which either mononuclears or polymorphonuclears were prominent. Dermal vessels involvement appeared rather weak, including swelling of the walls by edema with focal fibrinoid necrosis. Direct immunofluorescence showed mainly IgG, IgA and C3 vascular deposits. Based on these data, an immune pathology is discussed, besides the more classic infections pathogenesis.

[Haemorrhagic oedema acute in neonatal skin. Immunological and ultrastructural examination (author's transl)]. / Cedème aigu hémorragique du nourrisson. Données immunologiques et ultrastructurales.

There are three reports on acute haemorrhagic oedema of the skin of infants, an illness which English-speaking authors do not individualize but only regard as a clinical variety of Henoch-Schönlein purpura. Yet the features of the disease, as described in children under two years of age, are very characteristic. --Clinical feature is the sudden appearance of oedemas on face and limbs and of cocarde-like purpura with an occasional temperature. --Histological feature is the presence of leukocytoclastic vasculitis. --Immunologically the disease is characterized by the deposit of immune complexes. --Ultrastructural examination confirms the presence of leukocytoclastic vasculitis accompanied by deposit of immune complexes and of platelets. These three reports enable the authors to study the nosological aspects of the illness among the varieties of allergic vasculitis.

[Pseudomonas aeruginosa infection in cystic fibrosis: predominance of a single strain and the influence of antibiotic therapy and the environment]. / Infection à bacille pyocyanique au cours de la mucoviscidose: prédominance d'un clone, influence des antibiotiques et de l'environnement.

We analysed the implantation pattern and persistence of Pseudomonas aeruginosa in the tracheobronchial tracts of patients with cystic fibrosis, and investigated the relation of this bacterium with the environment and antibiotic therapy. We used four different techniques to ensure the precise and detailed identification of isolates. In particular, chromosomal differences were assessed by pulsed field electrophoresis (pulsotype determination). Sputum samples were collected from 8 patients, from 6 to 22 years-old, over a period of 19 to 24 months. Only a single strain was isolated from samples from each five patients taken at different times, and there was a predominant strain in the samples from two others. Patient 8, aged 14, was free of infection throughout the study. None of the infections was eradicated by antibiotic therapy (an association of two antibiotics for 15 days at one or two months interval). The strains isolated from two patients became resistant to imipenem: 3 out of the 4 resistant strains were the result of mutation in the resident, susceptible strain. Swabs were taken from the environments of infected patients and were tested for P. aeruginosa: this bacteria was found in three sites, and two of these contained an isolate with the same pulsotype as the strain responsible for the infection, whereas no P. aeruginosa was detected in the environment of an uninfected patient. The detailed and accurate identification of the isolates (by pulsotyping) enabled us--to show that each infected patient was infected by a single or predominant strain,--to investigate the relationship of these strains with those in the environment and the effects of antibiotic therapy.

[Leptospiroses]. / Leptospiroses.

Leptospirosis is a worldwide zoonosis, that is most frequently encountered in tropical and subtropical areas. In France, during the last years, its incidence has increased. Epidemiology is conditioned by a wide animal reservoir. Important clinical polymorphism makes diagnosis difficult. Laboratory abnormalities such as increased serum C-reactive protein and triglycerides and suggestive. Early diagnosis is now possible by using polymerase chain reaction methods. Early treatment with an aminopenicillin can improve prognosis which remains poor, especially in case of renal or pulmonary involvement. Pathophysiology of the disease still needs to be thoroughly studied.

Leptospirosis in Franche-Comté (FRANCE): clinical, biological, and therapeutic data.

OBJECTIVES AND METHOD: We report the patient data in 77 cases of leptospirosis confirmed by PCR and/or serology (micro-agglutination), observed between 1994 and 2008 at the Besançon teaching hospital. Our aim was to compare the epidemiological, clinical, biological, and therapeutic characteristics of leptospirosis in the Franche-Comté region, to those reported in other regions. RESULTS: The median age was 42years and 95% were male patients. Leptospirosis acquisition was likely related to aquatic leisure activities (50.6%), professional exposure (28.6%), building maintenance works (11.7%), or unknown (9.1%). Forty-eight cases were uncomplicated and 29 were severe presentations of leptospirosis. Among severe cases, eight patients had to be managed in an intensive care unit, and one patient died. L. grippotyphosa and L. icterohaemorrhagiae were the main serogroups involved. Age above 50years and serogroup L. icterohaemorrhagiae were positively associated with clinical severity. The outcome was favorable for 15 patients treated with ceftriaxone for less than 7days. CONCLUSIONS: We recommended conducting clinical trials aiming at validating short courses of ceftriaxone to treat leptospirosis.

Synthetic peptide issued from Hap1/LipL32 for new early serodiagnosis of human leptospirosis.

Leptospirosis is a worldwide zoonosis. Today, serological diagnosis is generally assessed by MAT. We performed ELISA with a synthetic peptide derived from Hap1/lipL32 which is a protein expressed only by pathogenic Leptospira. Repeatability and thresholds were defined with 85 controls sera and 119 hospitalized leptospirosis. The PP-ELISA repeatability and IgM/IgG cut-off values were based on control sera. For these cut-off values, we observed the IgM-PP-ELISA specificity of 89%, whereas it was 100% for the IgG. Then, we compared PP-ELISA and standard MAT results for leptospirosis patients. The concordance rate for IgM-PP-ELISA and MAT was low (43%), whereas it was 85% for IgG-PP-ELISA and MAT. During the first 5 days after hospitalization, PP-ELISA gave positive results in 13 out of 16 patients (81%) whereas 8 out of 14 patients (57%) were positive to MAT. ELISA using Hap1/lipL 32-derived synthetic peptide PP is an earlier serological diagnosis of human leptospirosis than MAT.