Epidemiological aspects of healthcare-associated infections and microbial genomics.

Hospital-acquired infections (HAIs) are a cause of continuously increasing morbidity and mortality. Most of these infections are caused by a limited set of bacterial species, which share the capability to efficiently spread from patient to patient and to easily acquire antibiotic resistance determinants. This renders correct and rapid species identification and antibiotic susceptibility testing (AST) important and underscores the relevance of bacterial epidemiological typing. The latter is needed for the sensitive detection and exact tracing of nosocomial spread of these potentially multidrug-resistant microorganisms (MDRO). Many microbial typing technologies have been developed and put to some level of executive practice, but it seems that the continued evolution in methodology has currently reached an apex: there is likely to be scientific and practical consensus on the ultimate typing potential of bacterial whole-genome sequencing (WGS). The possibility to perform pan-genomic nucleotide-to-nucleotide comparisons between strains belonging to a single species and to detect even minute changes in nucleotide order will identify closely related organisms, while upon accumulation of such mutations, independent descend can be assumed. Calibration of difference levels [i.e. number of single nucleotide polymorphisms (SNPs)] into categories of inter-strain relatedness needs to be performed in order to generate robust, portable typing schemes. Here, we will briefly discuss the state of affairs regarding bacterial epidemiology based upon WGS, its relatedness with the nomenclature of former typing approaches and the continuing need for a global typing language.

[Vaccinations of the traveller]. / Vaccinations du voyageur.

Travelers' immunization has 2 aims: for the traveler, to prevent the risk of contracting an endemic disease during his stay abroad; for the community to prevent the risk of importing an infectious agent yet unknown in the country. Travelling offers an opportunity to update routine immunizations: tetanus, diphtheria, poliomyelitis, hepatitis B; for young people: measles and rubella; for elderly people: influenza. Two vaccinations are compulsory: yellow fever for travelers to tropical Africa and Amazonian forest; meningococcus A + C for Mecca pilgrims. Other vaccines are recommended for travelers to specific areas: typhoid fever, hepatitis A, cholera in countries with poor hygiene; rabies for exposed travelers (expatriates, trekkers...); Japanese encephalitis for persons spending a month or longer in rural agricultural areas during the monsoon season; tickborne encephalitis for persons visiting forested areas of central Europe from may to september. Yet, most of travelers' diseases such as malaria cannot be prevented by vaccination and appropriate preventive measures (chemoprophylaxis and protection against insects) should be taken.

Immunogenicity and safety in adults of a new chromatographically purified Vero-cell rabies vaccine (CPRV): a randomized, double-blind trial with purified Vero-cell rabies vaccine (PVRV).

Recent improvements in chromatographic purification procedures have made it possible to develop a new chromatographically purified rabies vaccine (CPRV) by further purifying the current rabies vaccine prepared from Vero-cell culture (Verorab; Pasteur Mérieux Connaught). The immunogenicity and safety of primary immunization, followed by a booster at one year, with CPRV was compared to that of the purified Vero cell vaccine (PVRV) in a randomized, double-blind study carried out at four veterinary schools in France. A total of 330 healthy, male and female, first-year veterinary students, aged at least 18 years and who required pre-exposure rabies prophylaxis, were enrolled in this study. Included subjects were randomly assigned either CPRV (n = 163) or PVRV (n = 167) to be given as a primary immunization series of three intramuscular injections (D0, D7, D28), followed by a booster after 1 year (D365). Blood samples for serological analysis were taken at D0 (before first injection), D28, D42, D180, D365 (before booster) and D379. All subjects developed a strong immune response to the primary series, and at D42, all subjects had seroconverted for rabies neutralizing antibody (serum titre > or = 0.5 IU/ml). The rabies virus-neutralizing antibody GMT value at D42 in the CPRV group (23.0 IU/ml) was non-inferior to that in the PVRV group (29.6 IU/ml), according to a one-sided non-inferiority test. While antibody titres tended to decrease over the period of follow-up, at D365 (before booster), 97.5% subjects in the CPRV group and 98.8% of subjects in the PVRV group remained seroconverted. After booster, although the rabies antibody GMT value in the CPRV group was lower than that in the PVRV group, all subjects in both groups were seroconverted, and the difference is probably not clinically important. The incidence of local and systemic reactions tended to decrease with each dose during the primary immunization series, followed by a slight increase after booster (significant time-effect in an exploratory logistic regression analysis). Although mild or moderate local reactions tended to be more frequent after injection with CPRV compared to PVRV, systemic reactions were reported less often (significant group-effects in exploratory logistic regression analyses). One serious adverse event possibly related to vaccine occurred during this study (severe asthenia after the third dose of PVRV). This comparative study in healthy young adults demonstrates that the new chromatographically purified rabies vaccine is as immunogenic as PVRV, and seems to be associated with fewer systemic reactions.

RU 41 740 (Biostim) and IL-4, or IL-13, have opposite effects on CD14, CD23, HLA-DR and HLA-DQ on monocytes.

RU 41 740 (Biostim) is a glycoprotein extract obtained from Klebsiella pneumoniae. Its immunostimulating properties on monocytes have been established in vivo and in vitro. To confirm its spectrum of action at molecular level we studied its role on the modulation of four molecules involved in antigen presentation (HLA-DR, HLA-DQ), uptake of endotoxin (CD14) and activation (CD23). These four molecules are known to be modulated by interleukins IL-4 and IL-13. We found that HLA-DR, HLA-DQ, CD14 and CD23 were differentially regulated by biostim and IL-4 or IL-13. Surprisingly, Biostim inhibited the IL-4 or IL-13-induced expression of CD23, HLA-DQ and HLA-DR, while it did not have any action on these molecules by itself. We therefore hypothesize that Biostim, through the action on its receptor, could interact with the IL-4 receptor and IL-13 receptor and/or inhibit the IL-4 and IL-13 receptor transducing signal.

A 3-week hepatitis B vaccination schedule provides rapid and persistent protective immunity: a multicenter, randomized trial comparing accelerated and classic vaccination schedules.

Hepatitis B (HB) vaccinations given once weekly for 3 weeks can provide early seroprotection. This study compared immune responses induced by the accelerated (A; days 0, 10, 21) and classic (C; days 0, 28, 56) HB vaccination schedules. Two hundred seventy healthy subjects (95 men, 175 women) with a mean age of 23.8 years received 3 doses of GenHevac B, a recombinant vaccine produced in mammalian cells. The subjects were randomly assigned to schedules A or C. A booster dose was given 1 year later. One month after the third dose, 70% (schedule A) and 92% (schedule C) of the subjects were seroprotected and 100% (A) and 99% (C) had developed anti-pre-S2 antibodies. Before booster injections, 93% (A) and 95% (C) of the subjects were seroprotected, and 1 month after the booster, almost all subjects were seroprotected. A 3-week HB vaccination schedule with GenHevac B can confer early protective immunity lasting up to 1 year.

Three-week hepatitis B vaccination provides protective immunity.

To determine whether a 3-week hepatitis B (HB) vaccination could achieve protective immunity, 89 healthy non-immunized young adults received three doses of 20 micrograms each of HBs antigen (GenHevac B, Pasteur) and were randomly assigned to schedule A (n = 44): two doses at day 0, one dose at day 21; or schedule B (n = 45): one dose at days 0, 10 and 21. Seroprotection rates (anti-HBs > or = 10 mIU ml-1) for groups A and B respectively were: 23 and 40% at day 21; and 77 and 91% at day 82 (not significant). Anti-HBs geometric mean titres were higher in group B than in group A (p < 0.05) at days 21 (6.4 versus 3.8) and 82 (77.6 versus 33.5). One year after primary vaccination, the seroprotection rate remained as high as 90% in the vaccinees of group B; after boosting all vaccinees had protective levels of anti-HBs antibodies. Thus 3-week HB vaccination with GenHevac B allowed early and durable protective immunity.

[Real information needs of the traveller before his departure. Results of a survey by questionnaire]. / Les besoins réels en information du voyageur avant son départ. Résultats d'une enquête par questionnaire. Société française de la Médecine des Voyages.

This study is based upon 727 questionnaires completed by French travellers 10 days after intercontinental travel. The response rate was 40%. Two out of 5 travellers had generally mild health problems: fever (12%), diarrhoea (36%). Forty-six of them took drugs, which they had brought with them during their travel. Ten per cent had a satisfactory visit to a local physician. Medical informations given before departure appears to be sufficient, useful and relevant in more than 90% of cases. The traveller would like to receive them from his own physician or from vaccination centers. Other informations as insurance, assistance, administration, finances, appeared to have been incorrectly perceived by 20% of the travellers. The travel agent is the one who should provide adequate information. The traveller, in general, plans to do more travelling for his own well being if not for his work. Would not the bigger risk for him be "not to travel at all".

[Development and trends from 1986 to 1993 of the attitude of intercontinental travellers on departure from France, with respect to malaria prophylaxis]. / Evolution et tendances de 1986 a 1993 de l'attitude des voyageurs intercontinentaux au départ de France, vis-a-vis de la prophylaxie du paludisme.

Simultaneously to information campaigns on malaria prevention in France, 5 successive surveys were performed from 1986 to 1993 on the knowledge and attitudes of travellers regarding malaria prevention. French travellers (principally towards Sub Saharan Africa) know the risk of malaria and the measures of prevention (96%). Chimioprophylaxis using chloroquine has been progressively replaced by mefloquine and then by the association mefloquine-proguanil; 25% of travellers know mosquito prevention measures (repellents and impregnated bed nets) and 27% know the stand-by treatment. Passive attitude of travellers has been modified (in part due to their education) and tend to emphasize today their own responsibility.