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A growing literature shows an improvement of chronic hepatitis C virus (HCV)-related depression after successful treatment with direct-acting antivirals. However, depression after HCV cure remains insufficiently documented in people living with HIV (PLWH) and HCV, a population with specific mental health challenges. This study aimed to (i) document the prevalence of moderate-to-severe depression (PHQ-9 score ≥10) across different age classes in HCV-cured PLWH; (ii) identify associated socio-behavioral correlates.Descriptive analyses were performed on data collected during a cross-sectional survey (February 2018 - May 2019) nested in a prospective, multicenter cohort of individuals living with HIV and HCV (ANRS CO13 HEPAVIH). Socio-behavioral correlates of moderate-to-severe depression were identified using logistic regression.Among the 398 HCV-cured individuals in the study sample (median age [IQR]: 56 [53-59] years; 73.1% men), 23.9% presented with moderate-to-severe depression (PHQ-9 score ≥10). Depressive symptom prevalence rates were as follows: anhedonia: 52.3%; feeling 'down' or feelings of hopelessness: 48.3%; sleeping problems: 65.7%; lack of energy: 70.3%; eating disorders: 51.2%; lack of self-esteem: 34.3%; difficulty concentrating: 34.9%; sluggishness (in movement and voice) or restlessness: 24.6%; suicidal ideation: 17.1%. No significant difference was detected across age classes. Female sex, unhealthy alcohol use, sedentary lifestyle, and unhealthy eating behaviors were associated with increased odds of moderate-to-severe depression.Depressive symptoms were common in this sample of HCV-cured PLWH. Unlike findings for the French general population, the prevalence of depression did not decrease with age class. Mental health remains a key issue for HIV-HCV-coinfected individuals, even after HCV cure, especially in women and in individuals with unhealthy behaviors.Despite potential improvements in mental health after successful treatment with direct-acting antivirals, many people living with HIV (PLWH) and hepatitis C virus (HCV) - even in older age classes - still face depressive symptoms after HCV cure. In this population, women and people reporting unhealthy alcohol use, sedentary lifestyle, or unhealthy eating behaviors are more prone to report depressive symptoms after HCV cure. Mental health and lifestyle-related issues should be integrated in a global care model for PLWH living with or having a history of hepatitis C.

International audience; No abstract available

International audience; No abstract available

International audience; Essentials Risk factors of bleeding in adult immune thrombocytopenia are not known. This multicenter study assessed risk factors of bleeding at immune thrombocytopenia onset. Platelet count thresholds associated with bleeding were < 20 × 109 L-1 and < 10 × 109 L-1 . Exposure to anticoagulants was a major risk factor of severe bleeding.Summary: Background The aim of this cross-sectional study was to assess risk factors for bleeding in immune thrombocytopenia (ITP) adults, including the determination of platelet count thresholds. Methods We selected all newly diagnosed ITP adults included in the Cytopénies Auto-immunes Registre Midi-PyrénéEN (CARMEN) register and at the French referral center for autoimmune cytopenias. The frequencies of any bleeding, mucosal bleeding and severe bleeding (gastrointestinal, intracranial, or macroscopic hematuria) at ITP onset were assessed. Platelet count thresholds were assessed by the use of receiver operating characteristic curves. All potential risk factors were included in logistic regression models. Results Among the 302 patients, the frequencies of any, mucosal and severe bleeding were 57.9%, 30.1%, and 6.6%, respectively. The best discriminant threshold of platelet count for any bleeding was 20 × 109 L-1 . In multivariate analysis, factors associated with any bleeding were platelet count (< 10 × 109 L-1 versus ≥ 20 × 109 L-1 , odds ratio [OR] 48.2, 95% confidence interval [CI] 20.0-116.3; between 10 × 109 L-1 and 19 × 109 L-1 versus ≥ 20 × 109 L-1 , OR 5.2, 95% CI 2.3-11.6), female sex (OR 2.6, 95% CI 1.3-5.0), and exposure to non-steroidal anti-inflammatory drugs (NSAIDs) (OR 4.8, 95% CI 1.1-20.7). A low platelet count was also the main risk factor for mucosal bleeding. Exposure to anticoagulant drugs was associated with severe bleeding (OR 4.3, 95% CI 1.3-14.1). Conclusions Platelet counts of < 20 × 109 L-1 and < 10 × 109 L-1 were thresholds for major increased risks of any and mucosal bleeding. Platelet count, female sex and exposure to NSAIDs should be considered for assessment of the risk of any bleeding. Exposure to anticoagulant drugs was a major risk factor for severe bleeding.

Le paludisme est endemique au Cameroun et la communaute expatriee est donc naturellement concernee par le risque. De nombreuses etudes sont publiees sur le paludisme, mais peu concernent les expatries. L’objectif de cette etude etait de decrire les caracteristiques epidemiologiques et la prise en charge du paludisme a Plasmodium falciparum chez les expatries a Yaounde. Il s’agit d’une etude retrospective de tous les patients pris en charge pour un paludisme au Centre medico-social de l’ambassade de France a Yaounde en 2013. Cent trois cas de paludisme ont ete identifies, 32,7 % provenaient de la region peripherique de Yaounde, 25,2 % de la region cotiere et 20,4 % de Yaounde centre. Vingt-deux patients ont beneficie d’une hospitalisation, dont 6 en service de reanimation. Trois deces ont ete recenses durant la periode. Des formes graves de paludisme sont regulierement diagnostiquees a Yaounde dans la population expatriee et preferentiellement chez les sujets de plus de 50 ans residents en long sejour, moins attentifs aux mesures de prevention et de lutte antivectorielle. Ce travail confirme egalement la presence de paludisme urbain a Yaounde. Devant la meconnaissance du risque et la mauvaise observance des mesures de prophylaxies, il apparait important que les differentes chancelleries des pays du nord aient une action d’information specifique aupres de leurs ressortissants vivant en zone d’endemie.

International audience; Direct-Acting Antivirals (DAAs) opened a new era in HCV treatment. We report the impact of HCV treatment in French HIV-HCV coinfected patients. METHODS: All HIV-HCV patients from the Dat'AIDS cohort followed between 2012 and 2015 were included. HCV status was defined yearly as naive, spontaneous cure, sustained virological response (SVR12), failure or reinfection. RESULTS: Among 32,945 HIV-infected patients, 15.2% were positive for anti-HCV antibodies. From 2012 to 2015, HCV incidence rate increased from 0.35%PY to 0.69%PY in MSM, while median incidence was 0.08%PY in other patients. Median reinfection rate was 2.56%PY in MSM and 0.22%PY in other patients. HCV treatment initiation rate rose from 8.2% in 2012 to 29.6% (48.0% in pre-treated patients vs 22.6% in naïve patients). SVR12 rate increased from 68.7% to 95.2%. By the end of 2015, 62.7% of the patients were cured either spontaneously or following SVR. CONCLUSIONS: HCV treatment dramatically increased in HIV-HCV patients in France from 2012 to 2015 resulting in HCV cure in nearly two-thirds of the patients in this cohort. Combined with a declining HCV prevalence, the prevalence of active HCV infection among HIV patients will drastically decrease in the forthcoming years.

Introduction La tuberculose (TB) et le VIH sont des problemes de sante publique. Notre objectif est de decrire les aspects epidemiologiques, cliniques et evolutifs des patients co-infectes TB/VIH. Materiels et methodes Etude observationnelle, monocentrique, retrospective d’une cohorte de patients adultes co-infectes TB/VIH sur une periode de 39 mois. Resultats Entre le 01/01/2010 et le 31/03/2013, 5550 patients ont ete hospitalises dans le service des maladies infectieuses du CHU, parmi lesquels 717 (13 %) etaient co-infectes TB/VIH, soit une prevalence de la TB de 18 % dans la population infectee par le VIH. A l’inclusion, l’âge moyen des patients etait de 39 ans (± 9,6), le sex-ratio H/F etait de 0,8. Deux cent vingt-sept (31,7 %) se sont reveles infectes par le VIH lors du diagnostic de la TB, 490 (68,3 %) etaient deja connus VIH parmi lesquels 423 etaient sous traitement antiretroviral (ARV), dont 215 en echec de leur 1 re ligne, et 187 sous chimioprophylaxie par cotrimoxazole. Le taux median de LTCD4 ( n = 365, 50,9 %) etait de 94/mm 3 . Sur les 717 patients, 704 (98,2 %) etaient des nouveaux cas de TB ; 355 (50 %) avaient une TB extrapulmonaire, 213 (30 %) une TB pulmonaire, dont 150 BAAR+ et 149 (20 %) une TB disseminee. Les TB extrapulmonaires etaient ganglionnaires ( n = 212), neuromeningees ( n = 74), pleurales ( n = 42), peritoneales ( n = 36), pericardiques ( n = 9), osseuses ( n = 6), mammaire ( n = 1), renale ( n = 1). Le poids moyen etait de 50 kg (± 11). Les signes cliniques les plus frequents etaient : fievre (98 %), amaigrissement (71 %), toux chronique (59 %), adenopathies peripheriques (58 %), hemoptysie (23,6 %) et dyspnee (4,6 %). Les traitements de la TB et de l’infection VIH suivaient les recommandations de l’OMS. Chez les patients naifs, le traitement ARV (TDF + 3TC/FTC + EFV) a ete initie suivant le debut du traitement antituberculeux apres un delai moyen de 16 jours (± 2,3) et une mediane de 18 jours. Le traitement ARV n’a pu etre precise pour 91 % des patients pretraites. A M6, le taux de succes therapeutique regroupant les patients gueris (culture M5 negative) et les patients ayant dument complete le traitement anti-TB etait de 45,3 %, le taux de perdus de vue de 23,6 % et la mortalite de 31,1 %. Conclusion La prise en charge conjointe VIH/TB est confrontee a des difficultes logistiques et organisationnelles expliquant un taux de succes therapeutique encore faible. Une accessibilite plus precoce des patients aux structures de soins est indispensable pour reduire la mortalite.

International audience; The use of fluoroquinolone (FQ) as first line therapy for typhoid fever should be reconsidered because of the emergence of Salmonella Typhi and Paratyphi A strains with decreased susceptibility to FQ, mainly from Asia. Relapse can occur when ciprofloxacin MIC is over 0.12 mg/l, as illustrated by our case report. Azithromycin can be used successfully for patients infected with reduced ciprofloxacin susceptibility isolates. Literature review led us to suggest a new therapeutic strategy for uncomplicated typhoid fever, the antibiotic was chosen according to nalidixic acid susceptibility and ciprofloxacin MIC of the strain. High-dose intravenous ceftriaxone (4 g per day) is always efficient in first line therapy. Depending on FQ susceptibility testing results, it is relayed by oral therapy with a FQ (ciprofloxacin 500 mg bid for 7 days) if the isolate has maintained susceptibility, or azithromycin (1 g first day and 500 mg per day, 7 days) if the isolate is resistant to nalidixic acid or has a ciprofloxacin MIC superior to 0.12 mg/l.; La place des fluoroquinolones (FQ) dans le traitement de première intention des fièvres typhoïdes (FT) doit être remise en question du fait de l’émergence de souches de Salmonella enterica serovar Typhi et Paratyphi A de sensibilité diminuée aux FQ en provenance d’Asie du sud-est. Des rechutes peuvent survenir quand la CMI de la ciprofloxacine est supérieure ou égale à 0,125 mg/l, comme l’illustre le cas clinique que nous rapportons. L’azithromycine a une efficacité démontrée sur les souches de sensibilité diminuée à la ciprofloxacine. À partir d’une revue de la littérature, nous proposons un nouveau schéma thérapeutique des FT non compliquées, où l’antibiothérapie est guidée par la sensibilité à l’acide nalidixique et la CMI de la ciprofloxacine de la souche. La ceftriaxone intraveineuse à forte dose (4 g/24 h) est toujours efficace en première intention ; elle est initiée dans l’attente des données de sensibilité de la souche. Un relais par voie orale est pris avec une FQ (ciprofloxacine 500 mg deux fois par jour, sept jours) en cas de sensibilité conservée, ou l’azithromycine (1 g le premier jour, puis 500 mg par jour, sept jours) en cas de résistance à l’acide nalidixique ou de CMI de la ciprofloxacine supérieure ou égale à 0,125 mg/l.

Introduction Situe dans l’Ocean Indien, le departement de Mayotte est l’une des iles de l’archipel des Comores caracterise par une transmission endemique du paludisme. Grande Comore, Anjouan et Moheli constituent l’Union des comores (UC) ou le programme national de lutte contre le paludisme (PNLP) a permis le controle de la maladie. Mayotte est desormais en phase d’elimination du paludisme grâce au renforcement de la lutte antipaludique initie en 2001 mais le flux migratoire peut etre une menace de reintroduction pour le territoire. Notre objectif est d’evaluer la situation epidemiologique du paludisme de l’archipel des Comores et le risque de reintroduction a Mayotte via les cas importes. Materiels et methodes Nous avons collige les fiches de notification de cas de paludisme etablies de 2002 a 2017 par les medecins et biologistes de Mayotte. Etait considere comme « paludisme d’importation », tout cas chez une personne declarant avoir sejourne pendant la periode presumee de contamination dans une zone de transmission du paludisme exterieure a Mayotte. Les donnees de l’UC sont fournies par le PNLP et l’OMS. Resultats A Mayotte sur cette periode, 6569 cas de paludisme ont ete notifies dont 4808 autochtones (73 %) et 1761 importes (27 %). L’incidence des cas autochtones est passee de 10,3 ‰ en 2002 (1649 cas) a 0,04 ‰ en 2017 (9 cas). Alors que les importes ne representaient que 10 % des cas en 2002 (192 cas), la proportion atteint 80 % depuis 2013 (124 cas). Ces cas proviennent pour 75 % de l’UC, 17 % de Madagascar et 8 % d’Afrique subsaharienne. Pour l’UC entre 2010 et 2016, 169550 cas confirmes ont ete enregistres. L’incidence annuelle est passee de 49,7 ‰ en 2010 (36 538 cas) a 2,08 ‰ en 2016 (1657 cas) mais avec des progres variables selon les iles. Deux sont entrees en phase d’elimination avec une incidence inferieure a 1 ‰ : Anjouan depuis 2013 et Moheli depuis 2014. L’incidence est de 0,03 ‰ (10 cas) a Anjouan et 0,11 ‰ (6 cas) a Moheli en 2016. Toutefois, l’incidence demeure superieure a ce seuil en Grande Comore ; 4,05 ‰ (1641 cas). Les donnees provisoires de 2017 confirment la baisse de transmission a Anjouan et Moheli mais revelent une inquietante augmentation en Grande Comore (5000 cas). Conclusion Toute recrudescence du paludisme aux Comores menace Mayotte via les cas importes. L’elimination et la prevention de la reintroduction du paludisme a Mayotte ne peuvent que beneficier d’une cooperation technique regionale transfrontaliere avec les pays voisins dont l’UC. Une premiere reunion d’experts associant les partenaires regionaux a eu lieu fin 2017 a Mayotte afin d’apporter les bases d’une reflexion pertinente pour un programme inter-iles harmonise de lutte contre le paludisme.

Introduction There are insufficient data regarding the efficacy and safety of vaccination in patients with auto-immune disease (AID) and/or drug-related immune deficiency (DRID). The objective of this study was to obtain professional agreement on vaccine practices in these patients. Methods A Delphi survey was carried out with physicians recognised for their expertise in vaccinology and/or the caring for adult patients with AID and/or DRID. For each proposed vaccination practice, the experts’ opinion and level of agreement were evaluated. Results The proposals relating to patients with AID specified: the absence of risk of AID relapse following vaccination; the possibility of administering live virus vaccines (LVV) to patients not receiving immunosuppressants; the pertinence of determining protective antibody titre before vaccination; the absence of need for specific monitoring following the vaccination. The proposals relating to patients with DRID specified that a 3–6 month delay is needed between the end of these treatments and the vaccination with LVV. There is no contraindication to administering LVV in patients receiving systemic corticosteroids prescribed for less than two weeks, regardless of their dose, or at a daily dose not exceeding 10 mg of prednisone, if this involves prolonged treatment. Out of 14 proposals, the level of agreement between the experts was “very good” for eleven, and “good” for the remaining three. Conclusion Proposals for vaccine practices in patients with AID and/or DRID should aid with decision-making in daily medical practice and provide better vaccine coverage for these patients.

International audience; Background - Chronic kidney disease (CKD) is frequent in individuals infected with human immunodeficiency virus (HIV). Progression to end-stage renal disease can be slowed by appropriate medical management. Methods - To assess whether active promotion of guidelines improves CKD management, we conducted a cluster randomized controlled trial within the French Hospital Database on HIV (FHDH-ANRS CO4). We randomized 46 centers participating in the FHDH to either simple information on guideline availability or active promotion with a multifaceted and repeated intervention comprising reminders and audit feedback and targeting of local opinion leaders carried out between April 2009 and April 2010. Outcome measure was CKD management adequacy assessed before and 2 years after the beginning of the intervention in HIV-infected patients with moderate to severe CKD. CKD management was considered adequate in case of referral to a nephrologist or if proteinuria, blood pressure, low-density lipoprotein cholesterol level, and glycemia had been measured during the previous year and medications had been prescribed when necessary. Results - Three hundred six patients were enrolled, of whom 238 (78%) completed the 2 years of follow-up. During the study period, the percentage of patients receiving adequate CKD management improved from 64.1% to 70.4% (+6.3%) in the active arm and from 68.3% to 75.6% (+7.3%) in the control arm (adjusted mean difference, -0.7 percentage points [95% confidence interval: -9.2 to 7.9]; P = .95). The biggest impact of active promotion was on the management of proteinuria and blood pressure. Conclusions - Adequate compliance with CKD management guidelines improved slightly between 2009 and 2011, with no difference between the simple information and active promotion arms. Clinical trials registration - CCTIRS 10.150 and CNIL DR-2010-379.

Summary Background: Data about anti-malarial drugs prescription practices in Europe and the safety of imported malaria treatments are scanty. In 1999, a French consensus development conference published guidelines for the prevention and treatment of imported P. falciparum malaria. The impact of these guidelines has not been evaluated. Aim: To investigate the impact of these guidelines on the prescription of anti-malarials, and to evaluate the incidence of acute drug events (ADEs) leading to discontinuation of treatment. Design: Cross-sectional survey. Methods: Members of the medical staff in 14 French infectious and tropical disease wards completed a standardized form for each patient treated for imported malaria in 2001. A propensity score matching technique was used to estimate the risk of ADEs leading to discontinuation of the regimen. Results: In the 474 patients studied, quinine was the first-line anti-malarial most often prescribed. Only 3% of patients received halofantrine. Mefloquine was associated with a RR of 4.9 (95%CI 3.2–7.4, p50.00001) risk of discontinuation of treatment due to ADEs. Discussion: The very limited use of halofantrine indicates that the main practice recommendations of the guidelines have been taken into account. Mefloquine was associated with a substantial risk of discontinuing the treatment because of ADEs. This is a serious limitation for the use of mefloquine in the treatment of out-patients with imported malaria.

Resume Les virus de la fievre jaune, de la dengue, de l’encephalite japonaise, de l’infection a virus West Nile sont 4 arbovirus majeurs pour leur pouvoir epidemique. Malgre l’existence du vaccin amaril, la fievre jaune reste tres active en Afrique et en Amerique. L’insuffisance des couvertures vaccinales et les mouvements de populations expliquent la permanence des epidemies. La vaccination est indispensable pour les voyageurs qui se dirigent vers les zones d’endemie. La prevalence de la dengue a considerablement augmente dans les dernieres decennies. Le nombre de pays concernes par ses formes hemorragiques continue aussi a croitre. Elle est l’arbovirose la plus souvent observee chez les voyageurs. Tres repandue en Asie, l’encephalite japonaise peut etre prevenue par une vaccination specifique. Le developpement du tourisme vers ses regions d’endemie amene a s’interroger sur les risques encourus par les voyageurs et sur les mesures de prevention a leur proposer. Depuis 1999, le virus West Nile s’est implante en Amerique du nord. Il y a cause pendant l’ete 2002 la plus severe epidemie de virose West Nile jamais observee. Depuis une dizaine d’annees, l’expression clinique de la maladie s’est transformee. Initialement consideree comme une virose benigne, on sait maintenant qu’elle est capable de causer des formes neurologiques a forte letalite, en particulier chez les personnes âgees.

Los progresos terapeuticos realizados en los ultimos 30 anos en cancerologia, tecnicas de trasplante e inmunopatologia se han acompanado de un incremento importante de la cantidad de pacientes inmunodeprimidos, con frecuencia cronicos.

Malaria is an endemic disease in Cameroon. Expatriate population is also affected by malaria risk. Many studies are published on malaria, but few are focused on the expatriate population. The objective was to describe epidemiological characteristics andmanagement ofmalaria at Plasmodium falciparum in Yaounde expatriate population. This is a retrospective analysis of all patients treated at health center of the French Embassy in Yaounde in 2013 with a diagnosis of malaria. 103 cases were recruited. Out of them, 32.7% came from the outskirts of Yaounde, 25.2% from the coastal area of Cameroon, and 20.4% from the center of Yaounde. 22 patients were hospitalized, including 6 in Emergency department. 3 deaths were reported during this period. Severe malaria cases are regularly detected in expatriate population inYaounde and preferentially patients, who are over 50 years old, long stay residents in Cameroon and they paid less attention on prevention and vector control. This study confirms the presence of urban malaria in Yaounde and the need to adopt measures including prophylaxis. To the ignorance of risk and the poor adherence to prophylactic measures, it appears important that the various embassies in northern countries have specific information to their expatriates living in endemic areas.

The analytical variability of the new commercially available Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) assay, Amplicor HIV-1 Monitor, has been assessed to establish criteria for assessing the significance of HIV-1 RNA level measurements. Estimations of the standard deviations (SD) of log-copies in inter-assay (mean 0.09 log) and in inter-laboratory (mean 0.14 log) reproducibility experiments demonstrated that the assay can discriminate with 95% confidence between 3-fold (inter-assay) and 5-fold differences (inter-laboratory). The inter-lot reproducibility (mean 0.10 log) was similar to the inter-assay reproducibility. The HIV-1 RNA concentrations measured in plasma collected in potassium EDTA anticoagulant were slightly higher than those measured in plasma collected in sodium citrate. The HIV-1 RNA concentrations measured in sera were about 50% of the HIV-1 RNA concentrations measured in paired plasma samples. However, there was a strong correlation between these two measurements (P < 0.0001). The assay was used to measure viral RNA in the plasma of 50 HIV-1 positive individuals at different stages of infection. All the individuals had detectable HIV-1 RNA (300-957000 copies/ml). There was no correlation between HIV-1 RNA and Immune Complex Dissociated (ICD) p24 antigen, but HIV-1 RNA was correlated with CD4+ cell counts (P < 0.0001) and the clinical stage (P = 0.0042), with higher HIV-1 RNA concentrations in patients with a more advanced stage of the disease. The significant association of HIV-1 RNA with major markers of HIV infection and the reliability of this sensitive, easy-to-use RT-PCR assay indicate its suitability for use in clinical trials and suggest that this assay is appropriate for routine clinical applications.

Many HIV-infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti-HIV therapy. The aim of this study was to identify factors influencing guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients.Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir scoreF1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (800000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow-up and those who did not.In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17-4.81; P=0.017], whereas patients with children (OR 0.53; 95% CI 0.30-0.91; P=0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01-0.78; P=0.03) were less likely to be treated.Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti-HCV therapy in this population.

Resume Evaluer le statut immunologique des voyageurs avant leur depart, vis-a-vis de six maladies pouvant etre prevenues par une vaccination : tetanos, diphterie, poliomyelite, rougeole, hepatite A, hepatite B, afin de recommander les vaccinations les plus utiles. A l'occasion de leur passage dans 8 centres de vaccination anti-amarile francais, les participants ont redige un questionnaire et apres consentement ecrit, un echantillon de sang a ete preleve pour etude serologique. Entre juin et septembre 1992, 1263 sujets ont participe a l'etude, parmi lesquels 790 ont accepte de subir un prelevement sanguin. Les pourcentages des sujets immunises ont ete les suivants : rougeole : 699 (99,9 %); poliomyelite type 1 : 764 (96,7 %), type 2 : 756 (95,7 %), type 3 : 738 (93,4 %); tetanos : 764 (86,8 %); diphterie : (68 %); hepatite A : 420 (53,9 %); hepatite B : 93 (11,8 %). Chez le voyageur adulte francais les vaccinations contre l'hepatite B et la diphterie sont a recommander systematiquement s'ils se rendent en zone d'endemie. Pour l'hepatite A, un controle serologique (IgG) avant la vaccination est une alternative a la vaccination systematique chez le voyageur apres l'âge de 40 ans surtout s'il existe chez lui une notion de voyages anterieurs. Le taux de protection relativement faible contre le tetanos justifie un rappel antitetanique surtout chez les femmes, et/ou apres 40 ans. La vaccination anti-poliomyelitique dependra de l'anciennete du dernier rappel.

The aim of the study was to identify factors associated with a strictly undetectable viral load (VL) using a routine sensitive real-time polymerase chain reaction (RT-PCR) technology.From a large prospective cohort, 1392 patients with a VL50 HIV-1 RNA copies/mL while receiving a three-drug suppressive regimen for at least 1 year were included in a cross-sectional analysis. Patients were classified into three groups and compared by univariate and multivariate analysis: 479 patients with a strictly undetectable VL (group 1; 34%), 617 patients with detectable VL below the threshold of 20 copies/mL (group 2; 44%), and 296 patients with a VL of 20-50 copies/mL (group 3; 12%).Comparing groups 1 and 2, VL zenith5 log(10) copies/mL [odds ratio (OR) 1.51; 95% confidence interval (CI) 1.15-1.99; P=0.003], current CD4 T-cell count500 cells/μL (OR 1.44; 95% CI 1.08-1.92; P=0.01), and duration of viral suppression50 copies/mL longer than 2 years (OR 2.32; 95% CI 1.20-4.54; P=0.01) were associated with undetectable VL. Comparing groups 1 and 3, VL zenith5 log(10) copies/mL (OR 2.48; 95% CI 1.75-3.50; P0.001), duration of viral suppression50 copies/mL longer than 1 year (OR 3.33; 95% CI 1.66-6.66; P=0.0006), and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (OR 1.45; 95% CI 1.03-2.04; P=0.03) were associated with undetectable VL. No individual drug effect was found within NNRTI molecules.Longer duration of viral suppression50 copies/mL, lower viral load zenith and NNRTI-based regimen were independently associated with a strictly undetectable viral load. This routinely used RT-PCR assay may prove to be a valuable tool in further large-scale studies.

Heavily treatment-experienced patients with good virological control could be at risk of virological failure on switching to a new regimen if pre-existing drug resistance is not taken into account. We examined whether genotyping based on cellular HIV-1 DNA during controlled viraemia identifies resistance mutations detected in plasma HIV-1 RNA during treatment with previous antiretroviral regimens.All 169 patients enrolled in the Agence Nationale de Recherche sur le SIDA (ANRS) 138-intEgrase inhibitor MK_0518 to Avoid Subcutaneous Injections of EnfuviRtide (EASIER) trial had already received three antiretroviral drug classes [nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI)] and had plasma HIV-1 RNA400 copies/ml at baseline. The results of previous resistance genotyping of plasma HIV-1 RNA in individual patients were compared with those of resistance genotyping of whole-blood HIV-1 DNA at randomization.A median of 4 plasma RNA genotypes were available for the 169 patients. The median numbers of resistance mutations in HIV-1 RNA and DNA were, respectively, 5 and 4 for NRTIs, 2 and 1 for NNRTIs, and 10 and 8 for PIs. The difference was significant for all three drug classes (P=0.001). Resistance to at least one antiretroviral drug was detected exclusively in HIV-1 RNA or in DNA in 63% and 13% of patients for NRTI, 47% and 1% of patients for NNRTI, and 50% and 7% of patients for PI, respectively.This study shows that, among highly treatment-experienced patients on effective highly active antiretroviral therapy, resistance genotyping of HIV-1 DNA detects fewer resistance mutations than previous analyses of HIV-1 RNA. These results have implications for patient management and for the design of switch studies.

To assess the significance of increased levels of Oil Red O-positive macrophages (ORO-PM) in bronchoalveolar lavage fluids (BALFs) from HIV-positive patients.Cytological data for seventy BALF samples from 66 consecutive HIV-infected patients were analysed according to antiretroviral therapy regimen, presence of Pneumocystis jiroveci infection, blood CD4(+) T cell count, HIV-1 viral load and plasma lipid levels. Non-parametric tests were used to compare the values between groups.The percentages of ORO-PM were high in this group: 40% [6-80] (median [interquartile range]). They were positively correlated with the BALF total cell count, 21% [5-48.5] for300 cells/mm(3) and 60% [26.5-80] for300 cells/mm(3) (P0.01) but inversely correlated with the percentage of BALF lymphocytes, 50% [20-80] for15% lymphocytes and 11.5% [2-47] for ≥15% lymphocytes (P0.01). Antiretroviral therapy with or without protease inhibitors, plasma lipid levels, HIV-1 viral load, blood CD4(+) T cell count or presence of a Pneumocystis jiroveci infection were not correlated with the ORO-PM status.Significantly increased numbers of ORO-PM were correlated with high total cell counts and low lymphocyte counts in BALF, irrespective of disease activity or treatment. Extended work on a larger series of patients needs to be conducted.

Resume L'emergence de souches multiresistantes de Salmonella typhi a rendu necessaires de nouveaux schemas therapeutiques. Grâce a leurs proprietes antibacteriennes et pharmacocinetiques, les cephalosporines de troisieme generation ou les fluoroquinolones ont permis de reduire la duree du traitement. Dans les salmonelloses non typhoidiques, ces memes antibiotiques sont indiques dans les formes severes (terrain fragile, formes extra-digestives) avec peut-etre une place dans les enterocolites.

Materials and Methods A HIV-1 patient database was scanned in March 1998, and 750 patients were identified who had received HAART including indinavir. Of these, 28 cases had nephrolithiasis; and 85 asymptomatic indinavir-treated patients were randomly selected as controls. The characteristics of cases and controls were compared by analysis of variance for quantitative parameters and by Fisher's exact test for classes. Results We observed a significant increase in the incidence of nephrolithiasis in patients co-infected with HIV-1 and either hepatitis C virus (HCV) (HCV RNA-positive) or hepatitis B virus (HBV) (HBs antigen-positive) (odds ratio and 95% confidence intervals: 2.8 and 1.1–7.7), whereas no significant differences were demonstrated between cases and controls with regard to age (42.4±8.0 versus 39.8±9.8 years), sex (male patients 70.4 versus 74.1%), duration of HIV-1 infection (8.6±3.1 versus 7.7±4.0 years), duration of indinavir treatment (16.1±5.8 versus 14.1±5.4 months), AST increase ≥1.25 of normal (29.6 versus 25.9%), or ALT increase ≥1.25 of normal (33.3 versus 22.4%). In co-infected patients, ALT increase (≥1.25 of normal), but not AST increase, at the time of indinavir initiation was statistically related to the occurrence of nephrolithiasis. Conclusions We found a significant increase of nephrolithiasis incidence in patients co-infected with HIV-1 and HCV or HBV, which suggests that underlying multifactorial hepatic damage may limit liver catabolism of indinavir, and consequently increase its renal excretion and the risk of nephrolithiasis. Caution is therefore advised when initiating indinavir treatment in HIV patients with evidence of HBV or HCV infection.

The use of fluoroquinolone (FQ) as first line therapy for typhoid fever should be reconsidered because of the emergence of Salmonella Typhi and Paratyphi A strains with decreased susceptibility to FQ, mainly from Asia. Relapse can occur when ciprofloxacin MIC is over 0.12 mg/l, as illustrated by our case report. Azithromycin can be used successfully for patients infected with reduced ciprofloxacin susceptibility isolates. Literature review led us to suggest a new therapeutic strategy for uncomplicated typhoid fever, the antibiotic was chosen according to nalidixic acid susceptibility and ciprofloxacin MIC of the strain. High-dose intravenous ceftriaxone (4 g per day) is always efficient in first line therapy. Depending on FQ susceptibility testing results, it is relayed by oral therapy with a FQ (ciprofloxacin 500 mg bid for 7 days) if the isolate has maintained susceptibility, or azithromycin (1 g first day and 500 mg per day, 7 days) if the isolate is resistant to nalidixic acid or has a ciprofloxacin MIC superior to 0.12 mg/l.

Malaria and HIV are two major public health issues, especially in sub-Saharan Africa. HIV infection increases the incidence of clinical malaria, inversely correlated with the degree of immunodepression. The effect of malaria on HIV infection is not as well established. Malaria, when fever and parasitemia are high, may be associated with transient increases in HIV viral load. The effect of subclinical malaria on HIV viral load is uncertain. During pregnancy, placental malaria is associated with higher plasma and placental HIV viral loads, independently of the severity of immunodeficiency. However, the clinical impact of these transient increases of HIV viral load remains unknown. Although some data suggests that malaria might enhance sexual and mother-to-child transmissions, no clinical study has confirmed this. Nevertheless pregnant women and children with malaria-induced anemia are also exposed to HIV through blood transfusions. Integrated HIV and malaria control programs in the regions where both infections overlap are necessary.

Many great discoveries have been made by chance but some have been the result of human perseverance and ingenuity. A sterling example of the second case is quinquina that was discovered in Peru and is now produced in Java. Quinquina has gone through centuries without losing its medical efficacy that efficacy allowed the exploration and colonization of Africa and played a key role in the ability to conduct overseas military campaigns. Because of its strategic importance, it was a coveted resource. It led to the discovery of homeopathy and dyes, allowed the development of organic chemistry, and has been used to make alcoholic bitters and soft drinks.

Hyperreactive malarial splenomegaly (HMS) is the chronic stage of a long-term stimulation of the immune system secondary to plasmodial infections, more frequently in genetically predisposed patients. HMS is a leading cause of large tropical splenomegaly in endemic zones but has been described in immigrants from Africa and in some European expatriates living in endemic countries. Diagnostic criteria include: long-term stay in a endemic zone, often large splenomegaly, high IgM titer, high antiplasmodial antibody titer, regression by at least 40% of splenomegaly six months after curative antimalarial treatment. In tropical settings, B-cell lymphoma and splenic lymphoma are the main differential diagnoses, which may be identified by a clonality analysis. Recent studies suggest that HMS can be treated by a short-term antimalarial therapy as long as the patient resides out of a malarial endemic country.

Malaria and HIV are two major public health issues, especially in sub-Saharan Africa. The impact of HIV infection on malaria depends on the patient's immune status: immunodepression level but also immunity against Plasmodium. HIV infection increases the incidence of clinical malaria, inversely correlated with the degree of immunodepression, but the severity and mortality are increased only in areas of unstable malaria. In severe malaria the level of parasitemia is similar in HIV-positive and HIV-negative patients. During pregnancy, HIV infection increases the incidence of clinical malaria, maternal morbidity, and fetal and neonatal morbi-mortality. Sulfa-based therapies reduce the risk of malaria, most importantly in pregnancy. HIV infection increases the risk of treatment failure, mainly with sulfa-based therapies, due to re-infection or parasitic recrudescence. Further studies are needed to determine the pathophysiological interactions between HIV infection and malaria.

Babesia is one of the most ubiquitous and widespread blood parasite in the world based on numbers and distribution of species in animals. The clinical presentation may vary according to the incriminated species. In some states of the USA this kind of infection is endemic; the number of cases reported in Europe is inferior but more life-threatening. A better understanding of parasite specificities such as cycle and pathogenicity allowed to suggest treatment guidelines adapted to the different clinical and microbiological situations.

Severe malaria is associated with the failure of host defenses to control parasite replication, with the excessive secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), and with the sequestration of parasitized erythrocytes (PEs) in the microcirculation of vital organs. The scavenger receptor CD36, known as a major sequestration receptor, has also been identified as an important factor in mediating nonopsonic phagocytosis of PEs by monocytes and macrophages. The specific consequence of this phagocytosis is a decrease in parasite-induced TNF-alpha secretion. We evaluated the variations in CD36 level and in lipopolysaccharide (LPS)-induced TNF-alpha production in monocytes from Plasmodium falciparum-infected patients and in vitro in the presence of PEs. Both the monocytes from infected patients and from in vitro culture showed a decrease of CD36 expression and a reduced production of TNF-alpha induced by LPS. Using incubation assays with no contact between monocytes and PEs, or in the presence of a soluble supernatant obtained from the incubation of monocytes and PEs, this study shows that decreased CD36 expression was posttranscriptional and not directly related to PEs phagocytosis. In addition, these culture models suggest that the reduced capacity of TNF-alpha production occurred in 2 phases. The early phase (24 hr) appeared to be CD36 dependent and the second phase (48 hr) was due to a soluble factor produced by PEs. These observations suggest that the control of the TNF-alpha production in malaria by monocytes was not entirely dependent on the phagocytosis of PEs by CD36 and that soluble factors produced by PEs could play a role in this process.

The Nadis electronic medical patient record allows real time constitution of a database including the clinical, therapeutic, biological, and epidemiological features of HIV-positive patients.Data concerning HIV-infected patients followed-up in 6 French University Hospitals was collected. Data quality was assessed on a regular basis in each center.The 6 first University hospitals using Nadis agreed to group their data on March 15, 2004, concerning 6236 patients having consulted at least once in the previous year. Among these, 29% were female patients, 80% were under treatment on March 15, 2004, 9% were off treatment, 29% were co-infected by hepatitis B or C virus, 57% had an undetectable viral load, 15% of the treated patients were in a worrying immunovirological situation, 358 were diagnosed HIV-positive in 2003. 35% of these "new patients" were women, the mode of infection was sexual in 80%, 45% were under treatment on March 15, 04. This recent data allowed us to have an accurate assessment of this population's management in 2004.

The aim of this study was to define standard values for fat mass distribution by dual-energy X-ray absorptiometry in human immunodeficiency virus (HIV)-negative men and to analyze factors associated with lipodystrophy in HIV-infected men. Total-body composition was analyzed in 241 HIV-negative men (controls) and 162 HIV-infected men. We created a fat mass ratio (FMR) as the ratio of the percentage of the trunk fat mass to the percentage of the lower limbs fat mass. We defined the FMR standard values as the mean value+/-standard deviation. We compared body mass index (BMI), fat mass percentage (%FM), lean mass (LM), bone mineral density (BMD), and FMR between the control group and HIV-infected men, by age range, according to prescription of treatment and presence of clinical lipodystrophy. The FMR standard value is equal to 1.3+/-0.2. The FMR was higher in treated HIV-infected men with or without clinical lipodystrophy. The FMR was similar for naïve HIV-infected men and controls. It was positively correlated with age, cumulative time on treatment, zidovudine, stavudine, or indinavir. BMD and fat mass were lower for treated and naïve HIV-infected men than for HIV-negative men. The FMR seems to be a valuable index for measuring fat mass distribution. We defined FMR standard values from the largest group of HIV-negative men to our knowledge. Applying FMR to HIV patients could help physicians to diagnose lipodystrophy earlier.

This retrospective study analyses causes as well as clinical, immunological and virological consequences of antiretroviral treatment interruptions (Ti) of more than 30 days in HIV-1 infected adults.This causes were classified as related to drug toxicity, therapeutic or adherence failure. We studied therapeutic regimens before Ti and after treatment reinitiation (TR), clinical events related to Ti, CD4 cells and viral loads before Ti and at months 3, 6, 9, and 12 after TR.Out of 188 Ti analysed, 42.6% were related to therapeutic failure, 33.5% to drug toxicity, and 23.9% to adherence failure. Eight Aids defining clinical events were reported during Ti, in patients with low CD4 cells and high viral load (P0.05). Viral loads evolution after TR was better if Ti was related to treatment failure (P0.05), was prolonged (P0.05), and if CD4 cells were high before Ti and at TR (P0.05). Median CD4 cells was of 296/mm(3) at month 12 after TR vs 382 before Ti.Ti consequences are strongly related to CD4 cells, which decrease sharply during Ti, increasing Aids defining events probability. Prospective randomised clinical studies are needed to define usefulness of Ti.

Resume L'acquisition de resistance chez certaines especes bacteriennes comme Enterobacter cloacae ou Pseudomonas aeruginosa au cours du traitement par les plus recentes betalactamines et fluoro-quinolones est un fait bien etabli depuis les dernieres annees. Un modele de peritonite chez la souris a permis de quantifier cette emergence de resistance liee a la selection de variants resistants sous l'influence de divers regimes antibiotiques et de preciser le role des associations d'antibiotiques pour prevenir l'echec therapeutique.

Introduction – objectifs la frequence des endocardites associees aux spondylodiscites et leur pronostic sont mal connus. A partir d’une cohorte de 359 spondylodiscites a pyogenes nous presentons la prevalence des endocardites et son influence sur le pronostic. Materiels et methodes Nous presentons l’analyse des donnees issues d’un large essai multicentrique randomise comparant deux durees de traitement dans les spondylodiscites a pyogene documentee de l’adulte sans presence de materiel chez le patient non immunodeprime. Ont ete extrait les donnees sur les cas d’endocardites documentees et leur pronostic. Resultats 257 (71,6 %) patients ont beneficie d’une echographie cardiaque a la recherche d’une endocardite infectieuse ; 56 (22 %) avaient une endocardite, 51 classees comme certaine selon la classification de Duke et 5 comme probable. Les patients qui presentaient une endocardite etaient significativement plus âges (70,9 ans vs 59,3 ans) et etaient plus souvent immunodeprimes et/ou diabetiques (14,3 % vs 6,1 %). Ils presentaient, de maniere significative, plus souvent une bacteriemie objectivee (89,3 % vs 64,4 %), une localisation cervicale (25 % vs 13 %) et une infection a streptocoque (39,3 % vs13,9 %) que le reste de la population presentant une spondylodiscite a pyogene. La proportion d’echec en cas d’endocardite infectieuse n’est pas significativement differente meme s’il existe une tendance (16,1 % vs 7,8 %, p = 0,008) Conclusion Les patients presentant une spondylodsicite a pyogene doivent beneficier d’une echographie cardiaque a la recherche d’une endocardite infectieuse ce d’autant que le germe responsable est un streptocoque, que le patient est diabetique, a plus de 70 ans et qu’il existe une localisation cervicale afin de modifier l’antibiotherapie. Le pronostic ne semble pas modifier par cette atteinte associee mais ce resultat doit etre confirme par des donnees de plus grande ampleur.

Introduction – objectifs Decrire et analyser l’antibiotherapie prescrite pour traiter les spondylodiscites a pyogene au cours d’un grand essai national. Materiels et methodes Nous presentons l’analyse de l’antibiotherapie prescrite dans cette indication et renseignee de maniere prospective au cours d’un large essai multicentrique comparant deux durees de traitement dans les spondylodiscites a pyogene documentee de l’adulte sans presence de materiel chez le patient non immunodeprime. L’antibiotherapie a ete analysee en fonction du micro organisme responsable et de la presence d’une endocardite. Resultats L’antibiotherapie de 359 patients a ete revue. La population etait a 69 % masculine avec un âge moyen de 61 ans et 68 % des patients etaient bacteriemiques au diagnostic. Une endocardite etait diagnostiquee dans 22 % des cas et les principales bacteries responsables etaient Staphylococcus aureus (41 %), les staphylocoques a coagulase negative (15 %) et les streptocoques non enterocoque (18 %). Pas de difference significative de succes n’etait retrouvee que les patients soient traitees plus ou moins de 7 jours par voie parenterale. La rifampicine etait l’antibiotique le plus prescrit en cas d’infection a Staphylococcus aureus et significativement plus que pour les autres bacteries (87,6 % vs 49 %) comme les aminoglycosides (74,5 % vs 54,9 %) et les fluoroquinolones (83,4 % vs 43,2 %). Sur l’ensemble de la population etudiee, l’utilisation de la rifampicine ne modifiait pas significativement le pronostic (p = 0,0617). Vingt-neuf patients ont presente une intolerance aux antibiotiques mais aucun antibiotique ne presentait une toxicite significativement plus elevee que les autres. La vancomycine etait responsable de 21,1 % des effets indesirables. Conclusion La duree de l’antibiotherapie parenterale n’influe pas le pronostic. L’association la plus prescrite est fluoroquinolone et rifampicine avec un pronostic excellent.

Resume L'encephalite boutonneuse dont la survenue est favorisee par un terrain a risque represente un element de gravite dans l'infection a R. conorii. Nous rapportons un cas d'encephalite ayant complique l'evolution d'une Fievre Boutonneuse Mediterraneenne (FBM) en depit d'un traitement antibiotique precoce. Apres une phase de detresse respiratoire menacant immediatement le pronostic vital, l'evolution fut progressivement favorable jusqu'a guerison sans sequelle. Cette observation souligne l'importance d'une surveillance etroite des cas de FBM survenant sur un terrain a risque.

Trichinellosis is an uncommon condition that is nevertheless a continuing problem as shown by two recent outbreaks in our region. The clinical features are reviewed briefly. The physical and laboratory test findings in the 117 patients affected during the first outbreak (February 1998) are reported, as well as the methods used to treat these patients.

The in vitro susceptibility of chloroquine and the genomic profile of dihydrofolate reductase (DHFR) codon 108 was determined against african isolates of P. falciparum (Pf) from imported malaria cases without previous drug intake by an isotopic microtest or PCR + RFLP. Pf resistance to chloroquine or to the DHFR inhibitor was present in 49% and 46% of isolates, respectively. Pf drug resistance was more frequent in permanent than in seasonal malarial transmission areas and chloroquine plus DHFR resistance reached 28% in years 1995-97. Updating the guidelines for the prevention of malaria in travellers to Africa is necessary.