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Epidemiology of diphtheria in the southwestern Indian Ocean is poorly documented. We analyzed 14 cases of infection with toxigenic Corynebacterium diphtheriae reported during 2007-2015 in Mayotte, a French department located in this region. Local control of diphtheria is needed to minimize the risk for importation of the bacterium into disease-free areas.

Background: The fetal heart at term is exposed to an increase in hemodynamic work as a consequence of fetal growth, increased circulating volume, and alteration in loading patterns due to maturational changes in fetoplacental circulation. The extent to which these cardiovascular changes influence human fetal and neonatal cardiac adaptation has not been fully elucidated. The aim of this study was to evaluate perinatal cardiovascular changes in ventricular geometry and myocardial performance in normal term fetuses., Methods: Prospective study of 108 uncomplicated pregnancies delivering at term. M-mode, two-dimensional or B-mode, pulsed wave Doppler, pulsed wave tissue Doppler, and two-dimensional speckle-tracking imaging were performed a few days before and within 24 hours of birth., Results: Analysis of paired fetal and neonatal echoes demonstrated significant perinatal changes (P < .0001 for all) in right ventricular (RV) and left ventricular (LV) geometry (RV/LV end-diastolic dimension ratio, 1.2 vs 0.8; RV sphericity index, 0.53 vs 0.40; LV sphericity index, 0.46 vs 0.49). There were corresponding significant (P < .001 for all) perinatal changes in global myocardial performance: LV myocardial performance index, 0.60 versus 0.47; RV myocardial performance index, 0.61 versus 0.42; systolic function: LV longitudinal systolic strain rate, -1.4/sec versus -1.0/sec; RV longitudinal systolic strain rate, -1.5/sec versus -1.0/sec; RV S', 5.3 cm/sec versus 6.5 cm/sec; and diastolic function: LV E'/A', 0.8 versus 1.1., Conclusions: The findings support the concept that the perinatal period is associated with major changes in fetal ventricular geometry and cardiac function in response to significant alterations in loading conditions. Improved knowledge of perinatal cardiac changes in normal fetuses could facilitate better understanding of cardiac adaptation in normal and pathological pregnancies., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Introduction: Several recent studies have identified a potential role for intrauterine Candida albicans in adverse pregnancy outcomes, including preterm birth. There is, however, a limited understanding of the impact of intrauterine candida infection on fetal well-being in early pregnancy. Using a sheep model of early pregnancy, the aims of this study were to determine (1) the ability of experimentally induced intrauterine C albicans to infect the fetus and (2) whether C albicans exposure in early pregnancy is associated with alterations in fetal cardiac function, as measured by spectral tissue Doppler imaging analysis of fetal cardiac function., Methods: Merino ewes carrying singleton pregnancies at 89 days' gestation (term is ∼150 days) received C albicans (n = 8) via ultrasound-guided intra-amniotic injection. Saline-exposed fetuses served as controls (n = 6). Spectral tissue Doppler imaging echocardiography and amniotic fluid collection were performed at baseline and 24 and 72 hours after intrauterine C albicans injection. Fetal tissues were collected at postmortem for analysis of infection and inflammation., Results: Relative to saline control, intrauterine C albicans infection resulted in pronounced increases in amniotic fluid tumor necrosis factor α (TNF-α; P < .05) and cytokine/chemokine messenger RNA (interleukin [IL] 1β, IL-6, TNF-α, and monocyte chemoattractant protein 1; P < .05) in the fetal myocardium, lung, skin, and liver at 72 and 96 hours postinfection. Spectral tissue Doppler imaging showed diastolic dysfunction at 24 hours and severe biventricular diastolic dysfunction 72 hours postinfection., Conclusion: Intrauterine C albicans infection in a sheep model of early pregnancy causes systemic fetal candidiasis, which is associated with a robust systemic inflammatory response and progressive cardiac dysfunction detectable by spectral tissue Doppler imaging.

Objective: To compare non-invasive hemodynamic measurements obtained in pregnant and postpartum women using two automated cardiac output monitors against those obtained by two-dimensional (2D) transthoracic echocardiography (TTE)., Methods: This was a cross-comparison study into which we recruited 114 healthy women, either with normal singleton pregnancy (across all three trimesters) or within 72 hours following delivery. Cardiac output estimations were obtained non-invasively using two different monitors, Ultrasound Cardiac Output Monitor (USCOM®, which uses continuous-wave Doppler analysis of transaortic blood flow) and Non-Invasive Cardiac Output Monitor (NICOM®, which uses thoracic bioreactance), and 2D-TTE. The performance of each monitor was assessed relative to that of TTE by calculating bias, precision, 95% limits of agreement and mean percentage difference (MPD). Intraobserver repeatability was assessed for both monitors and interobserver reproducibility was assessed for USCOM, NICOM being operator-independent., Results: Following exclusions due to poor-quality results of a monitor or TTE, or for medical reasons, our analysis included 98 women (29 in the first trimester, 25 in the second and 21 in the third, and 23 postpartum). For cardiac output estimation, when compared with TTE, USCOM had a bias ranging from 0.4 to 0.9 L/min. The MPD of USCOM was 29% in the third-trimester cohort. NICOM had a bias ranging from -1.0 to 0.6 L/min, with a MPD of 32% in the third-trimester group. There was limited agreement between the cardiac output monitors and TTE in the first and second trimesters, with a MPD of 38% for USCOM in both first and second trimesters, and 71% and 61% for NICOM in first and second trimesters, respectively. For cardiac output estimation using USCOM, we found excellent intraobserver repeatability (intraclass correlation coefficient (ICC), 0.97; 95% CI, 0.95-0.98) and interobserver reproducibility (ICC, 0.90; 95% CI, 0.81-0.94), and the repeatability for NICOM was comparable (ICC, 0.95; 95% CI, 0.93-0.97)., Conclusions: We found good agreement of both USCOM and NICOM when compared with 2D-TTE, specifically in the third trimester of pregnancy. Both devices had good intraobserver repeatability and either had good interobserver reproducibility or were operator-independent. Future studies should take into account the significant differences in the precise maternal hemodynamic values obtained by these devices, and consider developing device-specific reference ranges in pregnancy and the postpartum period. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: The objective of this study was to determine the prevalence and mechanisms of azithromycin resistance of Neisseria gonorrhoeae French isolates from 2013 to 2014., Methods: N. gonorrhoeae samples isolated in a network of laboratories were tested for susceptibility to azithromycin between April 2013 and March 2014. Fifty-four isolates that were non-susceptible to azithromycin and 18 susceptible isolates were characterized for molecular mechanisms of resistance by PCR/sequencing and genotyped using N. gonorrhoeae multiantigen sequence typing (NG-MAST)., Results: Among the 970 N. gonorrhoeae isolates, 54 (5.56%) were non-susceptible to azithromycin, 9 (1%) were resistant and 45 (4.6%) showed intermediate resistance. Azithromycin-non-susceptible isolates harboured a C2599T mutation in the rrl gene encoding the 23S rRNA alleles (5.5%), a C substitution in the mtrR promoter (5.5%), an A deletion in the mtrR promoter (53.7%) and mutations in the L4 ribosomal protein (14.8%) and in the MtrR repressor (25.9%). No isolates showed an L22 mutation or carried an erm, ere, mef(A)/(E) or mphA gene. Thirty different STs were highlighted using the NG-MAST technique. The predominant genogroups non-susceptible to azithromycin were G21 (31%), G1407 (20%) and G2400 (15%). Genogroup G2400 (15%) was revealed to be a novel cluster prevalent in the south of France and resistant to azithromycin, ciprofloxacin and tetracycline., Conclusions: Our study highlights that the prevalence of resistance of N. gonorrhoeae to azithromycin in France is low and essentially due to multiple genetic mutations. Its dissemination occurs through three major genogroups including a novel one in France (G2400)., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: HIV-infected patients with TB need simplified, effective and well-tolerated antiretroviral regimens., Methods: The French ANRS 129 BKVIR open trial evaluated the once-daily tenofovir DF/emtricitabine and efavirenz combination, started within 12 weeks after TB treatment initiation, in antiretroviral-naive HIV-1-infected patients. Success was defined as an HIV-1 RNA <50 copies/mL and TB cure at 48 weeks., Results: TB was confirmed microbiologically (90%) or histologically (10%) in 69 patients (71% male; median age 43 years; 54% born in Africa). The median time between TB treatment initiation and antiretroviral therapy was 8 weeks (range 1-22 weeks). At baseline, median HIV-1 RNA was 5.4 log10 copies/mL and median CD4 cell count 74 cells/mm(3). In the ITT analysis, combined success at week 48 was achieved in 57/69 patients (83%, 95% CI 74-92). Twelve patients did not achieve virological success, and TB was not cured in one of them. Among the 47 patients who fully adhered to the strategy, the success rate was 96% (95% CI 90-100) and was not affected by low rifampicin and isoniazid serum concentrations. Forty-nine serious adverse events were reported in 31 patients (45%), and 11 led to antiretroviral drug interruption. All adverse events resolved. The immune reconstitution inflammatory syndrome occurred in 23 patients (33%, 95% CI 22-44), and was associated with a low baseline BMI (P = 0.03) and a low haemoglobin level (P = 0.02)., Conclusion: These results support the use of tenofovir DF/emtricitabine and efavirenz combination therapy for HIV infection in patients with TB., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The worldwide antibiotic crisis has led to a renewed interest in phage therapy. Since time immemorial phages control bacterial populations on Earth. Potent lytic phages against bacterial pathogens can be isolated from the environment or selected from a collection in a matter of days. In addition, phages have the capacity to rapidly overcome bacterial resistances, which will inevitably emerge. To maximally exploit these advantage phages have over conventional drugs such as antibiotics, it is important that sustainable phage products are not submitted to the conventional long medicinal product development and licensing pathway. There is a need for an adapted framework, including realistic production and quality and safety requirements, that allows a timely supplying of phage therapy products for 'personalized therapy' or for public health or medical emergencies. This paper enumerates all phage therapy product related quality and safety risks known to the authors, as well as the tests that can be performed to minimize these risks, only to the extent needed to protect the patients and to allow and advance responsible phage therapy and research.

In March 2014, a person in their eighties who was diagnosed with extensive cellulitis due to toxigenic Corynebacterium ulcerans died from multiple organ failure. Environmental investigation also isolated C. ulcerans in biological samples from two stray cats in contact with the case. This finding provides further evidence that pets can carry toxigenic C. ulcerans and may be a source of the infection in humans.

Objective: Patients coinfected with HIV and Mycobacterium tuberculosis frequently experience a paradoxical worsening of tuberculosis (TB) symptoms early after the initiation of combination antiretroviral therapy (cART). This immune reconstitution inflammatory syndrome (TB-IRIS) can lead to significant morbidity and needs to be distinguished from TB recurrence due to ineffective treatment. We investigated whether plasma biomarkers could predict the occurrence of TB-IRIS., Design: ANRS 129 BKVIR is a single-arm multicentre trial that enrolled 69 cART-naïve HIV-1-infected patients treated for TB. The patients received once-daily tenofovir/emtricitabine/efavirenz first-line regimen. TB-IRIS cases (IRIS+) were validated by an Event Review Committee., Methods: A panel of 26 plasma biomarkers was monitored longitudinally for 24 weeks from cART initiation onward, using multiplexed assays and high-sensitivity ELISA. Statistical analyses of biomarkers were adjusted for test multiplicity., Results: One-third of patients (n=23) experienced TB-IRIS. The inflammatory cytokines and chemokines interleukin (IL)-6, IL-8, interferon-gamma-induced protein 10 (IP-10), and tumour necrosis factor-alpha (TNF-α) showed increased plasma levels at week 4 in IRIS-positive (IRIS+) patients (P<0.05 for each biomarker). The soluble IL-2 receptor sCD25, which is released upon CD4 T-cell activation, was significantly increased at week 0 in IRIS+ patients (P<0.05), and remained elevated throughout follow-up. IL-7, a key homeostatic cytokine for CD4 T-cells, showed a trend for higher values in the TB-IRIS group. Both sCD25 and IL-7 baseline levels were independently associated with a shorter time to TB-IRIS occurrence (P=0.005 and P=0.02, respectively)., Conclusion: These findings support a role for CD4 T-cell activation prior to massive inflammation in the development of TB-IRIS.

Background: Concurrent treatment of HIV and tuberculosis is complicated by drug interactions. We explored the safety and efficacy of raltegravir as an alternative to efavirenz for patients co-infected with HIV and tuberculosis., Methods: We did a multicentre, phase 2, non-comparative, open-label, randomised trial at eight sites in Brazil and France. Using a computer-generated randomisation sequence, we randomly allocated antiretroviral-naive adult patients with HIV-1 and tuberculosis (aged ≥18 years with a plasma HIV RNA concentration of >1000 copies per mL) to receive raltegravir 400 mg twice a day, raltegravir 800 mg twice daily, or efavirenz 600 mg once daily plus tenofovir and lamivudine (1:1:1; stratified by country). Patients began study treatment after the start of tuberculosis treatment. The primary endpoint was virological suppression at 24 weeks (HIV RNA <50 copies per mL) in all patients who received at least one dose of study drug (modified intention-to-treat analysis). We recorded death, study drug discontinuation, and loss to follow-up as failures to achieve the primary endpoint. We assessed safety in all patients who received study drugs. This study is registered in ClinicalTrials.gov, number NCT00822315., Findings: Between July 3, 2009, and June 6, 2011, we enrolled and randomly assigned treatment to 155 individuals; 153 (51 in each group) received at least one dose of the study drug and were included in the primary analysis. 133 patients (87%) completed follow-up at week 48. At week 24, virological suppression was achieved in 39 patients (76%, 95% CI 65-88) in the raltegravir 400 mg group, 40 patients (78%, 67-90) in the raltegravir 800 mg group, and 32 patients (63%, 49-76) in the efavirenz group. The adverse-event profile was much the same across the three groups. Three (6%) patients allocated to efavirenz and three (6%) patients allocated to raltegravir 800 mg twice daily discontinued the study drugs due to adverse events. Seven patients died during the study (one in the raltegravir 400 mg group, four in the raltegravir 800 mg group, and two in the efavirenz group): none of the deaths was deemed related to study treatment., Interpretation: Raltegravir 400 mg twice daily might be an alternative to efavirenz for the treatment of patients co-infected with HIV and tuberculosis., Funding: French National Agency for Research on AIDS and Viral Hepatitis (ANRS), Brazilian National STD/AIDS Program-Ministry of Health., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: Disseminated gonococcal infections (DGIs) are rare. We describe the characteristics of DGIs in France., Methods: This is a 3-year retrospective analysis of DGI cases collected through two networks of microbiologists and infectious disease specialists in France between 2009 and 2011. DGI was defined either by the isolation of Neisseria gonorrhoeae from blood and synovial fluid or by the existence of a clinical syndrome consistent with DGI and the isolation of N gonorrhoeae from any site. We describe the epidemiological, clinical and microbiological characteristics and outcomes of DGIs., Results: 21 patients (9 women, 12 men; 18-62 years old) were diagnosed with DGI. The number of DGI cases increased between 2009 and 2011. Two men who had sex with men were coinfected with HIV. We found 28 extragenital locations, including arthritis (14 cases), tenosynovitis (7), skin lesions (4), endocarditis (1), prostatitis (1) and pelvic inflammatory disease (1). Genital signs were present in five patients. The diagnosis was confirmed by cultures in 20 patients-blood (4), synovial fluid (11), genital (3), throat (1), urine (1)-and by molecular biology on a pharyngeal swab in 1 patient. Seven cases were resistant to fluoroquinolones. The patients were treated with ceftriaxone, associated with corticosteroids (two cases) and surgery (six cases). Four patients had joint sequelae., Conclusions: DGIs are increasing. Men seem to be at higher risk than women. Joint involvement was common. Microbiological diagnosis was based on culture, however molecular biology using pharyngeal swabs was helpful when cultures were negative.

The aim of this study was to evaluate to what extent travel-related factors may cause adherence failure to antiretroviral therapy (ART) in otherwise adherent migrants when traveling back to Africa. HIV-infected sub-Saharian migrants living in France with a plasma HIV viral load < 200 copies/mL, with no change in ART for ≥3 months and who were about to visit their native country for between 2 weeks and 6 months were enrolled for the study. Patients completed a self-administered adherence questionnaire both at enrollment and during the week following their return to France. Adherence failure occurred in 23 (11.5%) of 200 patients. Negative perception about ART effectiveness (adjusted odds ratio = 4.3; 95% confidence interval = 1.3-13.7), unexpected traumatic events during their stay in their native country (7.8; 2.3-26.1), and a prolongation of their stay (5.2; 1.4-20.4) were independently associated with a higher likelihood of adherence failure. Owning/renting one's house in France (0.30; 0.10-0.96), singlehood (0.23; 0.05-1.00), and HIV status disclosure (0.19; 0.05-0.76) were correlates of sustained adherence during traveling.

Background: In France, 1/3 HIV-infected patients is diagnosed at an advanced stage of the disease. We describe missed opportunities for earlier HIV testing in newly-HIV-diagnosed patients., Methods: Cross sectional study. Adults living in France for ≥1 year, diagnosed with HIV-infection ≤6 months earlier, were included from 06/2009 to 10/2010. We collected information on patient characteristics at diagnosis, history of HIV testing, contacts with healthcare settings, and occurrence of HIV-related events 3 years prior to HIV diagnosis. During these 3 years, we assessed whether or not HIV testing had been proposed by the healthcare provider upon first contact in patients notifying that they were MSM or had HIV-related conditions., Results: 1,008 newly HIV-diagnosed patients (mean age: 39 years; male: 79%; MSM: 53%; diagnosed with an AIDS-defining event: 16%). During the 3-year period prior to HIV diagnosis, 99% of participants had frequented a healthcare setting and 89% had seen a general practitioner at least once a year. During a contact with a healthcare setting, 91/191 MSM (48%) with no HIV-related conditions, said being MSM; 50 of these (55%) did not have any HIV test proposal. Only 21% (41/191) of overall MSM who visited a healthcare provider received a test proposal. Likewise, 299/364 patients (82%) who sought care for s had a missed opportunity for HIV testing., Conclusions: Under current screening policies, missed opportunities for HIV testing remain unacceptably high. This argues in favor of improving risk assessment, and HIV-related conditions recognition in all healthcare facilities.

Background: Chloroquine (CQ) was the main malaria therapy worldwide from the 1940s until the 1990s. Following the emergence of CQ-resistant Plasmodium falciparum, most African countries discontinued the use of CQ, and now promote artemisinin-based combination therapy as the first-line treatment. This change was generally initiated during the last decade in West and Central Africa. The aim of this study is to describe the changes in CQ susceptibility in this African region, using travellers returning from this region as a sentinel system., Methods: The study was conducted by the Malaria National Reference Centre, France. The database collated the pfcrtK76T molecular marker for CQ susceptibility and the in vitro response to CQ of parasites from travellers' isolates returning from Senegal, Mali, Ivory Coast or Cameroon. As a proxy of drug pressure, data regarding CQ intake in febrile children were collated for the study period. Logistic regression models were used to detect trends in the proportions of CQ resistant isolates., Results: A total of 2874 parasite isolates were genotyped between 2000-2011. The prevalence of the pfcrt76T mutant genotype significantly decreased for Senegal (from 78% to 47%), Ivory Coast (from 63% to 37%), Cameroon (from 90% to 59%) and remained stable for Mali. The geometric mean of the 50% inhibitory concentration (IC50) of CQ in vitro susceptibility and the proportion of resistant isolates (defining resistance as an IC50 value > 100 nM) significantly decreased for Senegal (from 86 nM (59%) to 39 nM (25%)), Mali (from 84 nM (50%) to 51 nM (31%)), Ivory Coast (from 75 nM (59%) to 29 nM (16%)) and Cameroon (from 181 nM (75%) to 51 nM (37%)). Both analyses (molecular and in vitro susceptibility) were performed for the 2004-2011 period, after the four countries had officially discontinued CQ and showed an accelerated decline of the resistant isolates for the four countries. Meanwhile, CQ use among children significantly deceased in this region (fixed effects slope = -0.3, p < 10-3)., Conclusions: An increase in CQ susceptibility following official withdrawal of the drug was observed in travellers returning from West and Central African countries. The same trends were observed for molecular and in vitro analysis between 2004-2011 and they correlated to the decrease of the drug pressure.

The Committee for the Prevention and Control of Influenza (Comité de lutte contre la Grippe - CLCG) is an advisory committee to the French Health Minister for a medical and scientific collective expertise on the measures to be implemented to control or to reduce the impact of an epidemic or a pandemic of influenza. Appointed by decree, the CLCG consists of ex-officio members; representatives of French Agencies strongly involved by influenza and qualified personalities, representing various fields of expertise. Collective expertise is based on consensus after thorough collective discussion. A notice is drafted in reply to every official question and passed on either to the Chief Medical Officer, or, when the question concerns vaccines, to the Technical Committee of the vaccinations for which the CLCG acted as a working group. The CLCG was extremely active throughout the pandemic. The objective of this article is to describe in a factual way its output throughout this period of sanitary crisis. This article presents and compare chronologically and in a factual way the state of the scientific knowledge about influenza due to the A(H1N1)pdm09 virus and the CLCG notices. Between the alert launched by the WHO the 24th of April and the 31st of December 2009, CLCG met on 40 occasions. Its work dealt in particular with patient care, recommendations on medical treatment (antivirals, seasonal and pandemic vaccines), and on virological diagnosis. Whatever the defects of its expertise delivered in a context of urgency, which was a difficult exercise, the CLCG fulfilled its advisory to the health authorities. However, the pandemic experience showed that this expertise must be improved by insuring the recognition and the visibility of the advisory committee and by defining their exact position in the chain of decision., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

In March 2011, a 40 year-old French man was diagnosed with diphtheria caused by toxigenic Corynebacterium diphtheriae. Fifty-three close contacts were identified from whom throat samples were analysed. C. diphtheriae was found only in the asymptomatic partner of the index case. The two cases had travelled in Spain during the incubation period of the index case. Investigation around the second case identified 13 new close contacts.None of them was found to be infected.

Mycobacterium marinum is the cause of opportunistic infections in man. Although its clinical presentation is usually cutaneous, osteoarticular infections are not rare and should be rapidly diagnosed. Orthopaedic surgeons may have to manage a patient with this mycobacterial infection and should be able to make this diagnosis based on information about the patient's history and clinical criteria. Lesions develop from a skin wound, with a single nodule or a bright purplish-red patch with papules; they also may be inflamed or may abscess. Secondary lesions may develop as the disease progresses. Aquatic exposure is the most important factor to look for. We report three cases of this infection with a delayed diagnosis. Response to treatment and an absence of complications are correlated with an early diagnosis., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Thanks to vaccination, diphtheria has almost disappeared in France. The case definition, used for mandatory notification, was expanded in 2003 to include toxin-producing strains of Corynebacterium ulcerans. We describe the epidemiology of diphtheria in France from 1990 to 2008. No cases occurred between 1990 and 2001. Since 2002, 19 cases have been reported: 4 cases due to Corynebacterium diphtheriae related to exposure in endemic countries, and 15 cases due to other corynebacteria, including 4 cases of pseudomembranous pharyngitis, mainly related to contact with domestic animals. High vaccination coverage in the population and sensitive surveillance need to be maintained. Moreover, control measures need to be adapted to the non-C. diphtheriae toxigenic species.

Elderly population increases in France. Myxovirus influenza affect each year 2 to 7 millions of persons. Younger are most frequently infected but rates of serious illness and death are highest among persons aged >65 years. Some clinical forms are misleading, because of associated underlying illness. Thus, rapid diagnostic test are important to take appropriate preventive measures. Annual vaccination is deeply recommended for older people, on the one hand for health care worker on the other hand.

Lyme disease is a bacterial infection caused by Borrelia burgdorferi, which is transmitted by infected ticks. The transmission depends on several factors, especially on the duration of the tick's presence in the host body (the nymph which is smaller than the adults and thus less visible, is in this case the most frequently involved) and on whether the tick is infected or not. The interpretation of results in the few available studies is made difficult by the lack of information obtained (due to difficulty to collect information and examination costs). The comparison is made even more difficult by the difference between Borrelia ticks species in various regions. Today, the best methods are preventive: protective clothing, tick repellents, checking and removal of ticks after a journey in an endemic zone, and in case of tick bite, regular examination of the bite site during the following weeks in order to initiate an early curative treatment if ECM is diagnosed. The currently available data seems to be insufficient to suggest systematic antimicrobial prophylaxis in case of tick bite.

The in vivo relevance of the paradoxical bactericidal effect (the Eagle effect) is not evident. We found in vitro a paradoxical bactericidal effect of amoxicillin on 2 strains of nontoxigenic Corynebacterium diphtheriae. Then, using an experimental rabbit model of endocarditis, we evaluated the in vivo relevance of this phenomenon. Rabbits were assigned to the following groups: no treatment (control group), continuous amoxicillin infusion simulating a dosage of 200 mg/kg/day in humans, and continuous amoxicillin infusion simulating a dosage of 20 mg/kg/day in humans. The low dosage (20 mg/kg/day) was significantly more effective than the high dosage (200 mg/kg/day) against both strains (P<.025), confirming the paradoxical bactericidal effect observed in vitro.

We conducted a 12-week, multicenter, randomized, double-blind, placebo-controlled trial of cetirizine to assess the ability of antihistamines to prevent nevirapine-associated rash in patients infected with human immunodeficiency virus type 1. Patients initiating treatment with nevirapine were randomized to receive either cetirizine, 10 mg q.d. (104 patients), or placebo (96 patients) during the first 6 weeks of therapy. Rash occurred in 22 (11%) of 200 patients; 10 (9.6%) were in the cetirizine group and 12 (12.5%) were in the placebo group (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.31-1.81; P=.5). Five of 22 rashes were cases of hypersensitivity syndrome. The rate of nevirapine discontinuation due to rash was similar in the 2 groups (7.7% and 6.25% in the cetirizine and placebo groups, respectively; P=.4). Multivariate analysis showed no treatment-group effect but indicated that age >40 years (OR, 3.83; 95% CI, 1.4-10.46; P=.008) was associated with an increased risk of rash. Cetirizine has no preventive effect on nevirapine-associated rash.

The mortality of non-toxigenic Corynebacterium diphtheriae endocarditis is high (27%). One explanation could be tolerance to amoxicillin. The aim of this work was to evaluate in vivo the tolerance phenomenon, in a rabbit endocarditis experimental model. Two strains of non-toxigenic Corynebacterium diphtheriae were compared: a tolerant one and a non-tolerant one. EACH ANIMAL WAS RANDOMLY ASSIGNED TO ONE OF THE FOLLOWING GROUPS: no treatment, continuous infusion of amoxicillin simulating 200 mg/kg/24 h in humans, or fractionated infusion of amoxicillin simulating 66 mg/kg/8 h in humans. Surviving bacteria were counted in vegetations after one or three days of treatment. The 24 h fractionated amoxicillin infusion was more efficacious on the non-tolerant strain than on the tolerant strain. On the tolerant strain, 24 h amoxicillin was more efficacious as a continuous infusion than as a fractionated one.

Background: Increased and premature T cell apoptosis is recognized as a feature of HIV infection, and its normalization during highly active antiretroviral therapy (HAART) is thought to contribute to quantitative CD4 T cell restoration., Design: Cross-sectional study of spontaneous, CD3- and CD95-mediated apoptosis in lymphocytes from 53 HIV-infected individuals taking HAART., Methods: Overnight stimulation of peripheral blood mononuclear cells (PBMC) with coated anti-CD3 or anti-CD95 monoclonal antibodies or incubation overnight in medium. Apoptosis in CD4 and CD8 T cells was measured by flow cytometry. For in vitro assay of antiretroviral drugs, normal PBMC were prestimulated with anti-CD3 monoclonal antibodies and apoptosis was induced by ligation of CD95. The expression of active caspase-8 and caspase-3 was examined by flow cytometry., Results: We report for the first time that important levels of T cell apoptosis may persist under HAART, in spite of a rise in CD4 T cells from baseline and a sustained suppression of plasmatic viral load. Spontaneous CD3- or CD95-induced apoptosis levels were inversely correlated with the in vivo number of CD4 T cells and the CD4/CD8 ratio, but not with the viral load or duration of antiretroviral therapy. Regimens including lamivudine are associated with persistent T cell apoptosis, particularly following CD95 ligation. Lamivudine was also found to stimulate in vitro CD95-induced apoptosis and caspase activation in pre-activated T lymphocytes from healthy donors., Conclusion: The immunomodulatory effect of lamivudine may be one of the contributing factor to increased levels of T cell apoptosis under HAART. The data suggest that there is a requirement for physiological apoptosis during HAART.

Highly-active antiretroviral therapy (HAART) has lead to a dramatic decrease in the morbidity of patients infected with the human immunodeficiency virus (HIV). However, metabolic side effects, including lipodystrophy-associated (LD-associated) dyslipidemia, have been reported in patients treated with antiretroviral therapy. This study was designed to determine whether successful HAART was responsible for a dysregulation in the homeostasis of tumor necrosis factor-alpha (TNF-alpha), a cytokine involved in lipid metabolism. Cytokine production was assessed at the single cell level by flow cytometry after a short-term stimulation of peripheral blood T cells from HIV-infected (HIV(+)) patients who were followed during 18 months of HAART. A dramatic polarization to TNF-alpha synthesis of both CD4 and CD8 T cells was observed in all patients. Because it was previously shown that TNF-alpha synthesis by T cells was highly controlled by apoptosis, concomitant synthesis of TNF-alpha and priming for apoptosis were also analyzed. The accumulation of T cells primed for TNF-alpha synthesis is related to their escape from activation-induced apoptosis, partly due to the cosynthesis of interleukin-2 (IL-2) and TNF-alpha. Interestingly, we observed that LD is associated with a more dramatic TNF-alpha dysregulation, and positive correlations were found between the absolute number of TNF-alpha CD8 T-cell precursors and lipid parameters usually altered in LD including cholesterol, triglycerides, and the atherogenic ratio apolipoprotein B (apoB)/apoA1. Observations from the study indicate that HAART dysregulates homeostasis of TNF-alpha synthesis and suggest that this proinflammatory response induced by efficient antiretroviral therapy is a risk factor of LD development in HIV(+) patients.

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.

Introduction: Diphtheria is a reemerging disease. Two epidemics recently occurred in Algeria and Independent States Community, not so far from Europe. Imported cases were diagnosed in contiguous European countries. This review focuses on the data obtained from these epidemics, with particular emphasis on new clinical forms of Corynebacterium diphtheriae infections. CURRENTS KNOWLEDGE AND KEY POINTS: Sore throat with membranes is no longer the only clinical feature of diphtheria. However, patients' management is identical, with combination of antibiotics, injection of specific antisera, and immunization of patients' close contacts and relatives. French and American sero-epidemiological studies showed that antibody levels does not provide protection, particularly in the elderly. Adult populations would therefore be at risk every 10 years. Recent advances in molecular biology led to the development of gene amplification with polymerase chain reaction, that may be used for the detection of the toxin gene. They also promoted epidemiological surveys of circulating strains via ribotyping. Although this technic evidenced predominant strains in the various countries, genotypes encountered during an epidemics may differ. Besides diphtheria which has apparently been eradicated in France, systemic infections with non-toxigenic strains of C diphtheriae, such as endocarditis, septicemia and arthritis, are evenly diagnosed., Future Prospects and Projects: A French national reference center for C diphtheriae has been recently created. This center collects most of the strains isolated in France, clinical data and assesses the toxigenicity of bacteria, allowing strict epidemiological survey.

A case of cotrimoxazole-induced meningoencephalitis in an HIV-infected patient without signs of AIDS is reported. The patient developed an apparently generalized seizure, of cotrimoxazole, 1 month after first taking a dose of this drug and a febrile coma after a second dose 3 weeks later. Lumbar puncture revealed eosinophilic aseptic meningitis. The patient quickly recovered without sequelae and was given antiretroviral therapy plus pentamidine aerosolized and pyrimethamine as prophylaxis for opportunistic infections. No other adverse effects were observed. The report describes the diagnosis of this case supported by a commentary, including a literature review.

Thirty-eight nontoxigenic strains of Corynebacterium diphtheriae isolated between 1987 and 1992 from clinical specimens of French patients were typed by biotyping, antibiograms, bacteriophage typing, ribotyping, and restriction analysis by pulsed-field gel electrophoresis (PFGE). Excellent correlation occurred between the genotypes defined by PFGE SfiI profiles or by ribotype BstEII profiles. Genotyping revealed seven genotype patterns among the 26 biotype mitis isolates, five among the nine biotype gravis isolates, and three among the three biotype belfanti isolates. Phage typing was nonreactive for nine of the 38 isolates. A combination of all the typing methods led to the identification of 19 different types of Corynebacterium diphtheriae.

Diphtheria is a disease with a long history that almost completely disappeared from developed countries. In addition, until 1987, systemic infections involving Corynebacterium diphtheriae were rare. However, in 1990, an epidemic occurred in Russia. These two circumstances have provided the stimulus to gain insight into the situation in France. In fact, between 1987 and 1993, a total of 59 C. diphtheriae strains were isolated. Epidemiological data were collected for patients from whom 40 strains were isolated from normally sterile sites, including 34 from blood cultures, and half of the bacteremic patients developed endocarditis. Osteoarticular involvement was noted in 11 of these 40 patients, including 5 bacteremic patients. The fatality rate following bacteremia was 36%, despite specific antibiotic treatment (beta-lactams and aminoglycosides). The mean age of the participants was 38 years, with half of the patients subsisting under low socioeconomic conditions and suffering from homelessness or alcoholism. Apparently, the skin turned out to be the major route of transmission in this reemerging disease. Eighty-eight percent of the isolates belonged to the C. diphtheriae biotype mitis. These were found predominantly in the Paris area, and most were of the same ribotype. Those isolates originating from the overseas territories (Guyana and New Caledonia) belonged to C. diphtheriae biotype gravis. No strains were positive for the tox gene by PCR. This study attests to the persistent circulation in France of C. diphtheriae in the form of systemic infections. The matter is especially significant since these strains are nontoxigenic and are of a unique ribotype. The strains are, however, sensitive to most antibiotics, although 20% are rifampin resistant.

Following the generalized vaccination of children, the European countries achieved the elimination of diphtheria. However the huge epidemic which rages since 1990 in the New Independent States of ex-URSS, culminating in 1994-1995 (with respectively 47,802 and 50,412 notified cases), has showed that diphtheria could be still threatening. A serosurvey was carried out in France on 1,025 adult patients attending the emergency wards of three hospitals, located in different parts of this country. This study showed the insufficient immunity of adults, for lack of a routine programme for revaccination: only half of them have antibodies assuring their protection. The antitoxic immunity decreases according to age. This decline is more marked in women than in men, most of them being reimmunized during the military service. These data confirm the alarming results of similar serosurveys performed in others industrialized countries. The present risk of importing diphtheria in these countries requires a strengthening of clinical and bacteriological surveillance of all cases of infections attributable to C. diphtheriae, and could justify a revaccination programme for adult population, including a regular booster, at 10 year-interval, of a reduced dose of diphtheria toxoid (d), and/or using the combined toxoid Td in the wounded, instead of tetanus toxoid alone.

The purpose of this epidemiologic retrospective is to recognize the endemic nature of Lyme borreliosis in 'Berry', region of France. Fifty-nine cases have been reported here during the past six years (1988-1994). An erythema migrans (EM), or a late manifestation concurrent with positive ELISA-test represents the main inclusion criterion (case definition used by the CDC). The results reveal a high incidence considering the limited information available in France. The farmer has been found to be mainly at risk, with EM being observed in 49% of cases. In general, late manifestations are rarely described. Peripheral neurological manifestations occur more frequently than those reported in the USA. The steps taken as a result of our study of Lyme disease are in accordance with the recommendations of the World Health Organization.

In human immunodeficiency virus type 1 (HIV)-1-infected Black people, the circulating p24 antigen is hidden frequently in immune complexes, because of high titers of serum anti-p24 antibodies. In order to evaluate the prognostic values for progression of free and dissociated serum p24 antigen in Black people, sera from 45 HIV-1-infected Black patients, all at non-AIDS stages, were evaluated prospectively for p24 antigen by several assays; circulating free p24 antigen was measured by immunocapture ELISA only (method 1) and with ELAST amplification (method 2), and dissociated p24 antigen determined after glycine-HCl pretreatment of serum, by immunocapture ELISA only (method 3) and with ELAST amplification (method 4). Serum CD4 and CD8 cell counts, beta 2-microglobulin, and total IgA were determined also at least twice a year. Clinical events for AIDS were those included in the 1986 CDC classification for HIV infection. At entry, p24 antigen was found in 3 (6.7%) patients by method 1, in 7 (15.6%) by method 2, in 14 (31.1%) by method 3, and in 22 (48.9%) by method 4. Methods 3 and 4 were more sensitive than method 1 (P < 0.001) and method 2 (P < 0.001). The mean follow-up was 30 months. The free symptom survival times (mean +/- SD months) were significantly lower in patients being p24 antigen positive by method 1 [(+) 33 +/- 27 vs. (-) 61 +/- 15, P = 0.03), but they were similar in patients positive and in those negative for p24 antigen determined by method 2 [(+) 71 +/- 17 vs. (-) 74 +/- 9, P = 0.54], method 3 [(+) 76 +/- 12 vs. (-) 69 +/- 13.2, P = 0.80], and method 4 [(+) 79 +/- 9 vs. (-) 63 +/- 7, P = 0.71]. At 24 months, p24 antigen positivity did not correlate either with CD4 or CD4/CD8 slops, nor with beta 2-microglobulin or IgA variations. By contrast, a CD4 cell count below 200/mm3 at entry was significantly associated with disease progression. In conclusion, dissociated p24 antigenemia does not appear as a useful surrogate marker for progression in HIV-1-infected Black people.

Corynebacterium diphtheriae is the causative agent of Diphtheria. This bacteria circulates throughout the world. Recently, two outbreaks occurred in New independent states (Russia, Ukraine...) and Algeria. Routine technics permit to study the strains of Corynebacterium diphtheriae : biotype, antibiotype, toxin gene detection. However, molecular biological tests (ribotyping, and pulsed field gel electrophoresis) are necessary to characterize these strains in the space and the time. The studies with international laboratories exchanges are recents and have permitted first results concerning the molecular epidemiology of C. diphtheriae strains.

Since children have been vaccinated routinely, diphtheria has been eliminated in most European states and the recent occurrence of a large epidemic in the Newly Independent States (NIS) of the former USSR was unexpected. The resurgence of diphtheria in th

Tuberculous splenic abscess is an exceptional disease with silent presentation in disseminated tuberculosis infection. Imaging procedures allow to suspect this diagnosis in case of multilocular nodules of the spleen, or unilocular pseudotumoral macronodule. We report three cases of tuberculous splenic abscesses in two patients with acquired immunodeficiency syndromes and one with polycythemia vera. Under antituberculous treatment, clinical evolution was good with regression of the radiological features.

We report the case of a 32-year-old Malian man with abdominal tuberculosis revealing acquired immunodeficiency syndrome. A gastroscopy was made for epigastric pain and showed caseum in a digestive fistula with acid fast bacilli. Mycobacterium tuberculosis infection was confirmed by sputum culture. An early antituberculous therapy was prescribed. Outcome was good with rapid fistula closing and slower mass diminution of the abdominal lymph nodes. This case report confirms nodal tuberculosis as a possible cause of digestive fistulae. Rapid endoscopic diagnosis of this tuberculous fistula led to diagnosis of acquired immunodeficiency syndrome and early adapted medical treatment without invasive diagnostic methods.