Hervé Tissot-Dupont

Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients

PURPOSE To determine incidence of non-AIDS-defining cancers (NADC) in HIV-infected patients before (P1) and during (P2) the use of highly active antiretroviral therapy (HAART) relative to that observed in the French general population (FGP) of the same age and sex. PATIENTS AND METHODS Sex- and age-adjusted NADC standardized incidence ratios (SIR), with FGP as reference, were estimated in 1992 to 1995 (P1) and in 1996 to 1999 (P2) in a French Hospital Database on HIV prospective hospital cohort study. RESULTS NADCs were diagnosed in 260 patients during P1 and 391 patients during P2 among the 77,025 patients included in the database between January 1, 1992, and December 31, 1999. Estimated incidence of all cancers was higher in HIV-infected men than in FGP during both periods (P1 SIR = 2.36 and P2 SIR = 1.91). No excess of cancers was observed among HIV-infected women in either period. Incidence of all cancers did not change from P1 to P2 in either sex (SIR = 0.96 for men and 1.00 for women). In contrast, incidence of Hodgkins disease (HD) was higher than in FGP in both sexes and both periods and increased in P2 as compared with P1; incidence of lung cancer was higher in both sexes during P2. CONCLUSION Relative to FGP, the overall incidence of NADCs was increased in HIV-infected men but not in women and did not differ between P1 and P2. Only HD was much more common in HIV infection, and the potential role of HAART on HD cannot be excluded.

Use of a mobile cart influenza program for vaccination of hospital employees.

OBJECTIVE Rates of annual influenza vaccination of healthcare workers (HCWs) remained low in our university hospital. This study was conducted to evaluate the impact of a mobile cart influenza vaccination program on HCW vaccination. METHODS From 2000 to 2002, the employee health service continued its annual influenza vaccination program and the mobile cart program was implemented throughout the institution. This program offered influenza vaccination to all employees directly on the units. Each employee completed a questionnaire. Vaccination rates were analyzed using the Mantel-Haenszel test. RESULTS The program proposed vaccination to 50% to 56% of the employees. Among the nonvaccinated employees, 52% to 53% agreed to be vaccinated. The compliance with vaccination varied from 61% to 77% among physicians and medical students and from 38% to 55% among nurses and other employees. Vaccination of the chief or associate professor of the unit was associated with a higher vaccination rate of the medical staff (P < .01). Altogether, the vaccination program led to an increase in influenza vaccination among employees from 6% in 1998 and 7% in 1999 before the mobile cart program to 32% in 2000, 35% in 2001, and 32% in 2002 (P < .001). CONCLUSIONS The mobile cart program was associated with a significantly increased vaccination acceptance. Our study was able to identify HCW groups for which the mobile cart was effective and highlight the role of the unit head in its success.

Cohort Profile: French hospital database on HIV (FHDH-ANRS CO4)

The French Hospital Database on HIV (FHDH) is a hospital-based multicentre open cohort with inclusions ongoing since 1989. The research objectives focus mainly on mid- and long-term clinical outcomes and therapeutic strategies, as well as severe AIDS and non-AIDS morbidities, and public health issues relative to HIV infection. FHDH also serves to describe HIV-infected patients receiving hospital care in France. FHDH includes data on more than 120,000 HIV-infected patients from 70 French general or university hospitals distributed throughout France. Patients are eligible for inclusion if they are infected by HIV-1 or HIV-2 and give their written informed consent. Standardized variables are collected at each outpatient visit or hospital admission during which a new clinical manifestation is diagnosed, a new treatment is prescribed or a change in biological markers is noted, and/or at least every 6 months. Since its inception, variables collected in FHDH include demographic characteristics, HIV-related biological markers, the date and type of AIDS and non AIDS-defining events, antiretroviral treatments and the date and causes of death, as reported in the medical records. Since 2005, data have also been collected on: co-infection with hepatitis B or C virus; alcohol and tobacco use; and non HIV-related biomarkers. Anyone can submit a research project by completing a standardized form available on the FHDH website (http://www.ccde.fr/_fold/fl-1385734776-429.pdf) or from the corresponding author, describing the context and objectives of the study. All projects are reviewed by the scientific committee.

Detection of Mycobacterium ulcerans DNA in the Environment, Ivory Coast

Background Ivory Coast is a West African country with the highest reported cases of Buruli ulcer, a disabling subcutaneous infection due to Mycobacterium ulcerans. However, the prevalence of environmental M. ulcerans is poorly known in this country. Methods We collected 496 environmental specimens consisting of soil (n = 100), stagnant water (n = 200), plants (n = 100) and animal feces (n = 96) in Ivory Coast over five months in the dry and wet seasons in regions which are free of Buruli ulcer (control group A; 250 specimens) and in regions where the Buruli ulcer is endemic (group B; 246 specimens). After appropriate total DNA extraction incorporating an internal control, the M. ulcerans IS2404 and KR-B gene were amplified by real-time PCR in samples. In parallel, a calibration curve was done for M. ulcerans Agy99 IS2404 and KR-B gene. Results Of 460 samples free of PCR inhibition, a positive real-time PCR detection of insertion sequence IS2404 and KR-B gene was observed in 1/230 specimens in control group A versus 9/230 specimens in group B (P = 0.02; Fisher exact test). Positive specimens comprised seven stagnant water specimens, two feces specimens confirmed to be of Thryonomys swinderianus (agouti) origin by real-time PCR of the cytb gene; and one soil specimen. Extrapolation from the calibration curves indicated low inoculums ranging from 1 to 102 mycobacteria/mL. Conclusion This study confirms the presence of M. ulcerans in the watery environment surrounding patients with Buruli ulcer in Ivory Coast. It suggests that the agouti, which is in close contacts with populations, could play a role in the environmental cycle of M. ulcerans, as previously suggested for the closely related possums in Australia.

Culturomics and Amplicon-based Metagenomic Approaches for the Study of Fungal Population in Human Gut Microbiota

Herein, the mycobiota was characterized in fecal samples from sick patients and healthy subjects, collected from different geographical locations and using both culturomics and amplicon-based metagenomics approaches. Using the culturomics approach, a total of 17,800 fungal colonies were isolated from 14 fecal samples, and resulted in the isolation of 41 fungal species, of which 10 species had not been previously reported in the human gut. Deep sequencing of fungal-directed ITS1 and ITS2 amplicons led to the detection of a total of 142 OTUs and 173 OTUs from the ITS1 and ITS2 regions, respectively. Ascomycota composed the largest fraction of the total OTUs analyzed (78.9% and 68.2% of the OTUs from the ITS1 and ITS2 regions, respectively), followed by Basidiomycota (16.9% and 30.1% of the OTUs from the ITS1 and ITS2 regions, respectively). Interestingly, the results demonstrate that the ITS1/ITS2 amplicon sequencing provides different information about gut fungal communities compared to culturomics, though both approaches complete each other in assessing fungal diversity in fecal samples. We also report higher fungal diversity and abundance in patients compared to healthy subjects. In conclusion, combining both culturomic and amplicon-based metagenomic approaches may be a novel strategy towards analyzing fungal compositions in the human gut.

Evaluation of empirical treatment for blood culture-negative endocarditis

Objectives Much progress has been made in understanding the main causes of blood culture-negative endocarditis (BCNE). Few studies concerning BCNE treatment (due to previous antibiotics used or fastidious pathogens) are available. We performed this study to evaluate the effectiveness of our therapeutic protocol in BCNE, based on compliance with the protocol, outcome and 1 year mortality. Patients and methods We collected prospectively and analysed retrospectively cases of BCNE between 2002 and 2014, using a simplified and standardized protocol developed by our multidisciplinary team. We apply two kinds of protocols to treat BCNE, which include only four intravenous antimicrobial agents: amoxicillin, vancomycin, gentamicin and amphotericin B. Results We had 177 patients with definite BCNE. There were 154 (87.0%) patients treated with both appropriate antimicrobial agents and appropriate duration of treatment. We analysed the causes of inappropriate treatment in 13 (7.3%) cases and inappropriate duration in 10 (5.6%) cases. The treatment changes were justified in all cases except one of discharge against medical advice. The fatality rate was 5.1% (nine cases) and all deaths occurred in the group of patients who were treated with appropriate treatment; however, four deaths were not attributable to empirical treatment failure. Concerning the other deaths, the lack of surgical management, in association with empirical treatment, could explain our protocols failure, such as poorly tolerated surgery. Conclusions Our protocol is efficient and our mortality rate was low, compared with the literature review. This may result from a strategy that uses a sampling procedure and a standardized protocol at the same time.

From Expert Protocols to Standardized Management of Infectious Diseases

We report here 4 examples of management of infectious diseases (IDs) at the University Hospital Institute Méditerranée Infection in Marseille, France, to illustrate the value of expert protocols feeding standardized management of IDs. First, we describe our experience on Q fever and Tropheryma whipplei infection management based on in vitro data and clinical outcome. Second, we describe our management-based approach for the treatment of infective endocarditis, leading to a strong reduction of mortality rate. Third, we report our use of fecal microbiota transplantation to face severe Clostridium difficile infections and to perform decolonization of patients colonized by emerging highly resistant bacteria. Finally, we present the standardized management of the main acute infections in patients admitted in the emergency department, promoting antibiotics by oral route, checking compliance with the protocol, and avoiding the unnecessary use of intravenous and urinary tract catheters. Overall, the standardization of the management is the keystone to reduce both mortality and morbidity related to IDs.

Evaluation of self-collected rectal swabs for the detection of bacteria responsible for sexually transmitted infections in a cohort of HIV-1-infected patients

Purpose. The standard approach to screening sexually transmitted infections (STIs) has often been restricted to urogenital specimens. Most current guidelines, however, also recommend testing extra‐genital sites, including rectal locations, because asymptomatic rectal carriage of pathogens has often been reported. The aim of our study was to evaluate self‐collected rectal swabs to screen bacterial STIs in HIV‐infected patients in Marseille, France. Methodology. Between January 2014 and December 2015, 118 HIV‐infected patients (93 males and 25 females) agreed to self‐sample anal swabs for detection of bacterial STI. Detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Mycoplasma genitalium and Haemophilus ducreyi was performed using in‐house qPCR assay. Results/Key findings. Bacterial STIs were found in 8% (9/118) of the patients. C. trachomatis was the most commonly detected bacterium (4.2%) followed by N. gonorrhoeae (2.5%), M. genitalium (1.7%) and T. pallidum (0.8%). All the positive patients were males. The rectal carriage of pathogenic bacteria was fortuitously discovered for seven men (78%) who did not present rectal signs of STIs and was suspected for two men who presented proctitis (22%). Conclusion. In conclusion, testing extra‐genital sites is crucial for the diagnosis of STIs in men and women presenting or not concomitant urogenital infections in order to detect asymptomatic carriage with the aim of controlling and preventing transmission to their sexual partners.

Antiphospholipid antibodies proposed in the diagnosis of infective endocarditis

Antiphospholipid antibodies (aPL) may occur alone or associated with other diseases. To evaluate aPL, tested as anticardiolipin antibodies (IgG aCL) in infective endocarditis (IE) diagnosis, we investigated their prevalence in a cohort of 651 patients with IE suspicion. aPL was significantly associated with definite IE versus IE-rejected patients. Their mean levels were significantly higher in patients with definite IE versus possible IE. When applied as Duke minor criterion, they were significantly more often positive, and at higher levels, in patients with definite IE than in patients with possible or rejected IE. aPL could be helpful in difficult cases of IE diagnosis.

Co-circulation of Plasmodium and Bacterial DNAs in Blood of Febrile and Afebrile Children from Urban and Rural Areas in Gabon.

Malaria is considered to be the most common etiology of fever in sub-Saharan Africa while bacteremias exist but are under assessed. This study aimed to assess bacteremias and malaria in children from urban and rural areas in Gabon. DNA extracts from blood samples of 410 febrile and 60 afebrile children were analyzed using quantitative polymerase chain reaction. Plasmodium spp. was the microorganism most frequently detected in febrile (78.8%, 323/410) and afebrile (13.3%, 8/60) children, (P < 0.001). DNA from one or several bacteria were detected in 15 febrile patients (3.7%) but not in the controls (P = 0.1). This DNA was more frequently detected as co-infections among febrile children tested positive for Plasmodium (4.6%, 15/323) than in those tested negative for Plasmodium (0%, 0/87; P = 0.04). The bacteria detected were Streptococcus pneumoniae 2.4% (10/410), Staphylococcus aureus 1.7% (7/410), Salmonella spp. 0.7% (3/410), Streptococcus pyogenes 0.2% (1/410) and Tropheryma whipplei 0.2% (1/410) only in febrile children. Coxiella burnetii, Borrelia spp., Bartonella spp., Leptospira spp., and Mycobacterium tuberculosis were not observed. This paper reports the first detection of bacteremia related to T. whipplei in Gabon and shows that malaria decreases in urban areas but not in rural areas. Co-infections in febrile patients are common, highlighting the need to improve fever management strategies in Gabon.