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.

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.

[Risk factors for Abacavir-induced hypersensibility syndrome in the "real world"]. / Facteurs de risque de syndrome d'hypersensibilité à l'Abacavir en pratique clinique de routine.

UNLABELLED: Abacavir (ABC) is a generally well-tolerated NRTI. However, up to 5% of patients may develop hypersensitivity syndrome (HSS) within the first weeks of treatment. The objectives of this study were to describe the side effects of ABC, to evaluate the incidence of the ABC-HSS, and to identify the risk factors of HSS after first exposure to ABC in a cohort of patients followed up in a university HIV clinic. METHODS: The charts of all HIV-infected patients who started ABC between February 1998 and May 2002 were reviewed. HSS was defined as the onset, within 8 weeks of ABC initiation, of either a skin rash associated with at least one of the following symptoms (fever, gastrointestinal symptoms, respiratory symptoms, myalgia, malaise) or at least three of the above symptoms in the absence of rash. A multivariate logistic regression analysis was performed to identify risk factors of HSS. RESULTS: Of the 191 patients studied (134 M, 57 F, mean age 39 years), 53 (27.8%) presented with manifestations that were regarded as potential side-effects of ABC. Ten (5.2%) developed HSS, none of whom died. Two factors were independently associated with an increased risk of HSS: history of allergy to nevirapine (OR 8.1, 95% CI 1.6-40.5, p = 0.02), and being naïve to ART (OR 5.8, 95% CI 1.2-28.5, p = 0.04). CONCLUSION: This study "in the real world" confirms that the incidence of ABC-induced HSS is of about 5%. It also confirms that HSS occurs more frequently in patients with a history of allergy to nevirapine and in ART-naïve patients.

[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.

[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.

Evaluation of vancomycin use in a large university-affiliated hospital in eastern France in 1999.

OBJECTIVE: In 1999, we conducted a retrospective drug utilization review to determine the volume and pattern of vancomycin use in a university-affiliated hospital in eastern France. METHODS: Total vancomycin use was determined and expressed as vancomycin courses per 100 admitted patients and defined daily doses (DDD) of vancomycin per 100 patient-days. The indication for vancomycin use was classified as appropriate or inappropriate according to the guidelines issues by the HICPAC. RESULTS: A total of 311 vancomycin courses were given, as 2098 DDD, giving crude incidences of 1.17 courses per 100 admitted patients and of 1.19 defined daily doses per 100 patient-days. The frequency of appropriate courses was 66.7%. Of the 63 inappropriate courses of vancomycin, 39.7% and 28.6% were empiric therapy for nosocomial and community-acquired infections, respectively, 20.6% and 6.3% were specific therapy for nosocomial and community-acquired infections, respectively, and 4.7% were prophylactic. CONCLUSIONS: This study shows that vancomycin use in our hospital resulted in a lower selection pressure than has been reported for US university-affiliated hospitals and that comprehensive programs to improve use of vancomycin are needed in our institution.

[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.

Validation of a diagnosis model for differentiating bacterial from viral meningitis in infants and children under 3.5 years of age.

The aim of this study was to validate, in a population of infants and children under 3.5 years of age, a diagnosis model that provides a figure for the probability of bacterial meningitis (pABM), based on four parameters collected at the time of the first lumbar tap: the cerebrospinal fluid (CSF) protein level, CSF polymorphonuclear cell count, blood glucose level, and leucocyte count. The best cut-off value for distinguishing between bacterial and viral meningitis was previously found to be 0.1, since 99% of meningitides associated with pABM<0.1 were viral. The charts of 103 consecutive children aged 0.1-3.5 years who had been hospitalised for acute meningitis were reviewed. Each case was sorted into the following three categories for aetiology: bacterial (positive CSF culture, n=48); viral (negative CSF culture and no other aetiology, and no antibiotic treatment after diagnosis, n=36); and undetermined (fitting neither of the first two definitions, n=19). After computation of pABM values in each case, the predictive values of the model were calculated for different pABM cut-off values. The results confirmed that the best cut-off pABM value was 0.1, for which the positive and negative predictive values in this model were 96% and 97%, respectively. Only one case of bacterial meningitis (lumbar tap performed early in an infant with meningococcal purpura fulminans with negative CSF culture) was associated with a pABM value of <0.1. This model is quite reliable for differentiating between bacterial and viral meningitis in children under 3.5 years of age, and it may enable physicians to withhold antibiotics in cases of meningitis of uncertain aetiology.

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.

[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.

[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.

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.

[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.