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Yeni P.,Service des Maladies Infectieuses
Current HIV research | Year: 2010

Current HIV treatment guidelines emphasize the importance of using an active antiretroviral therapy regimen that produces full virologic suppression and immunologic competence, while at the same time providing patients with a favorable safety profile and limited risk for development of drug resistance. Etravirine (TMC125), a recently approved, non-nucleoside reverse transcriptase inhibitor (NNRTI), has shown durable, superior virologic efficacy over placebo in the Phase III, randomized, double-blind DUET trials in 1,203 treatment-experienced, NNRTI-resistant, HIV-1-infected patients. Statistical significance of responses with etravirine over placebo was maintained through Week 24, 48 and 96, regardless of baseline demographics, baseline disease characteristics or the background regimen used. Etravirine has demonstrated a favorable safety and tolerability profile; the incidence of treatment-emergent adverse events was comparable with placebo in the DUET trials, with the exception of rash. The tolerability profile of etravirine also appears to be favorable in terms of neuropsychiatric and hepatic side effects. The pharmacokinetic profile of twice-daily etravirine minimizes the potential for clinically relevant drug-drug interactions and allows for its use in combination with a wide range of other agents. In addition, etravirine has a high genetic barrier to the development of resistance, further enhancing potential benefit in patients infected with NNRTI-resistant virus. The clinical efficacy and favorable safety profile of etravirine, together with its pharmacokinetic profile and high genetic barrier to resistance, make it a valuable treatment option for a wide range of treatment-experienced HIV-1-infected patients.

Faye O.,Institute Pasteur Of Dakar | Boelle P.-Y.,French Institute of Health and Medical Research | Boelle P.-Y.,University Pierre and Marie Curie | Heleze E.,Ministry of Health | And 9 more authors.
The Lancet Infectious Diseases | Year: 2015

Background: An epidemic of Ebola virus disease of unprecedented size continues in parts of west Africa. For the first time, large urban centres such as Conakry, the capital of Guinea, are affected. We did an observational study of patients with Ebola virus disease in three regions of Guinea, including Conakry, aiming to map the routes of transmission and assess the effect of interventions. Methods: Between Feb 10, 2014, and Aug 25, 2014, we obtained data from the linelist of all confirmed and probable cases in Guinea (as of Sept 16, 2014), a laboratory database of information about patients, and interviews with patients and their families and neighbours. With this information, we mapped chains of transmission, identified which setting infections most probably originated from (community, hospitals, or funerals), and computed the context-specific and overall reproduction numbers. Findings: Of 193 confirmed and probable cases of Ebola virus disease reported in Conakry, Boffa, and Télimélé, 152 (79%) were positioned in chains of transmission. Health-care workers contributed little to transmission. In March, 2014, individuals with Ebola virus disease who were not health-care workers infected a mean of 2·3 people (95% CI 1·6-3·2): 1·4 (0·9-2·2) in the community, 0·4 (0·1-0·9) in hospitals, and 0·5 (0·2-1·0) at funerals. After the implementation of infection control in April, the reproduction number in hospitals and at funerals reduced to lower than 0·1. In the community, the reproduction number dropped by 50% for patients that were admitted to hospital, but remained unchanged for those that were not. In March, hospital transmissions constituted 35% (seven of 20) of all transmissions and funeral transmissions constituted 15% (three); but from April to the end of the study period, they constituted only 9% (11 of 128) and 4% (five), respectively. 82% (119 of 145) of transmission occurred in the community and 72% (105) between family members. Our simulations show that a 10% increase in hospital admissions could have reduced the length of chains by 26% (95% CI 4-45). Interpretation: In Conakry, interventions had the potential to stop the epidemic, but reintroductions of the disease and poor cooperation of a few families led to prolonged low-level spread, showing the challenges of Ebola virus disease control in large urban centres. Monitoring of chains of transmission is crucial to assess and optimise local control strategies for Ebola virus disease. Funding: Labex IBEID, Reacting, PREDEMICS, NIGMS MIDAS initiative, Institut Pasteur de Dakar. © 2015 Elsevier Ltd.

Minta D.K.,Service des Maladies Infectieuses
Médecine tropicale : revue du Corps de santé colonial | Year: 2011

Cryptococcal meningitis is the most common fatal central nervous system infection in AIDS patients in Sub-Saharan Africa. The purpose of this prospective study conducted from March 2003 to February 2004 in the internal medicine and infectious diseases departments of the Point G University Hospital Center was to investigate the clinical, prognostic and epidemiological profile of Cryptococcus neoformans infection in patients hospitalized for brain and meningeale infection (BMI). Diagnosis of neuromeningeal cryptococcosis (NMC) was based on positive identification of Cryptococcus by direct exam of the cebrospinal fluid (CSF) after India ink staining and/or culture on Sabouraud medium without actidione. During the study period, a total of 569 patients were hospitalized including 235 (41.3%) with HIV infection. Overall C. neoformans was identified in 14 patients. Median patient age was 39 +/- 8 years. There was a male preponderance with a sex ratio of 1.8 (9 men/5 women). Patients with BMI were HIV-positive in 85.7% of cases (n=12) and HIV-negative in 14.3% (n=2). The overall and HIV-specific prevalence of BMI was 2.5% and 5.1% respectively. The CD4 lymphocyte count was between I and 49 cells/mm3 in 64.3% of cases. The main clinical symptoms were cephalea in 85.7% of cases, altered consciousness in 50% and nausea/vomiting in 35.7%. Neurological manifestations (hemiparesis and cranial nerve deficit) were noted in 14.3%. HIV infection is the main purveyor of NMC in Mali. The actual incidence of cryptococcosis is unclear due to the poor sensitivity of diagnostic techniques. This study highlights diagnostic difficulties related to clinical polymorphism and poor technical facilities. Agglutination testing of blood and CSF is recommended, but mortality remains.

Tissot F.,Service des Maladies Infectieuses | Maillard M.H.,Service de Gastro enterologie et dHepatologie
Revue Medicale Suisse | Year: 2014

While metronidazole and vancomycin have been the only drug options to date for the treatment of C. difficile infection, new therapeutic approaches with promising results have recently emerged for the treatment of the first episode and relapses. Fidaxomicin is a new macrocyclic antibiotic more active against C. difficile and with a narrow spectrum allowing preservation of the intestinal microbiota. While having the same efficacy as vancomycin for the treatment of the first episode, this agent is associated with a lower rate of relapse. The highest relapse-free cure rate is achieved through fecal microbiota transplantation, which should be considered for patients with multiple relapses.

Giulieri S.,Service des Maladies Infectieuses
Revue Medicale Suisse | Year: 2014

C. difficile is transmitted in a faecal-oral mode and is widespread in hospital environment. Symptoms of Clostridial infection range from asymptomatic carriage to life-threatening toxic colitis. The treatment of a Clostridial infection is dependent on the seriousness of the symptoms. The diagnosis of the pathogen as well as the introduction of an efficient antibiotic therapy is crucial. Oral metronidazole is the gold standard in treatment of mild infection. Vancomycin should be introduced only in refractory cases or in particular situations. While there is a desire to avoid colectomy, inappropriate delay in a very ill patient can be fatal. Judgement on when to intervene is difficult and requires analysis of the factors which predict outcome with and without surgery. A total abdominal colectomy sparing the rectum with end ileostomy is the procedure of choice.

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