Immunogenicity and booster efficacy of pre-exposure rabies vaccination.

A multivariate analysis was used to identify factors influencing the immunogenicity of rabies vaccine and to assess the efficacy of booster injections in a cohort of 407 people monitored prospectively for 10 years after primary vaccination. Rabies vaccine (HDCV or PVRV) was injected by intramuscular route either on days 0 and 28 or on days 0, 7 and 28. All the participants received a booster injection on day 365. At the end of follow-up (year 10), 163 subjects had titers >0.5IU/ml (group A) and 59 subjects had titers <0.5IU/ml (group B: poor responders). The number of injections had a significant influence (P<0.001) on the magnitude of the serological response to rabies vaccine, but the type of vaccine and the potency of the batches did not (P=0.07 and P=0.06, respectively). The difference between GMTs on day 365 and day 379 was significantly lower in group B than in group A (13 and 50.70IU/ml, respectively; P<0.001). In conclusion, our study confirms that the rabies pre-exposure vaccination protocol of three intramuscular injections significantly decreases the proportion of poor responders at 10 years. Moreover, our findings indicate that a routine booster injection at 1 year could significantly increase the levels and duration of antibody titers.

[Laparoscopic diagnosis of stenosing eosinophilic jejuno-ileitis]. / Diagnostic coelioscopique d'une jéjuno-iléite sténosante à éosinophiles.

INTRODUCTION: Eosinophilic gastroenteritis of unknown origin could be isolated or integrated in idiopathic hypereosinophilic syndrome. Clinical expression is variable since the lesion may affect any area of the gastrointestinal tract and any layer of the wall. EXEGESIS: A 25-year-old male patient had digestive symptoms such as peritoneal, obstructive and diarrheal signs, associated with blood eosinophilia, giving evidence for eosinophilic jejuno-ileitis. Computer tomography revealed an extensive obstruction of the jejuno-ileum and thickening of the intestinal wall. The diagnosis was obtained using laparoscopy and controlled wedge biopsy, which showed a predominantly external infiltration of the intestinal wall by eosinophils. The disease evolution was favorable with corticosteroid therapy. CONCLUSION: Worrying and persistent digestive symptomatology, associated with blood eosinophilia, particularly when intestinal wall infiltration is revealed by computer tomography, should lead one to perform a laparoscopy to guide a surgical biopsy of the intestinal wall.

[Tick-born encephalitis]. / L'encéphalite virale à tiques.

INTRODUCTION: Tick-borne encephalitis (TBE), a disease contracted through tick bites, is caused by a Flavivirus. Its geographical distribution comes from the geographical distribution of the reservoir of infection--i.e., mainly the tiny mammals living in the forests and bushes. The endemic area spreads from the Rhine to the Urals, from Scandinavia to Italy and Greece. CURRENT KNOWLEDGE AND KEY POINTS: Symptoms usually evolve in three phases: at first a nonspecific phase with fever and myalgia, then an afebrile phase, and finally a phase with neurological manifestations, such as meningitis, meningoencephalitis and/or myelitis, and fever. Motor neurological sequelae are possible. The cases occurring in the East are characterized by their greater severity compared to those occurring in the West. The diagnosis, easily established given a history of a tick bite in an endemic area, is confirmed by the presence of specific IgM in the blood and/or cerebral spinal fluid. FUTURE PROSPECT AND PROJECTS: There is no specific treatment. Prevention consists of individual prophylactic measures (self-examination and systematic extraction of ticks after exposure, use of repellents), and in immunization. The vaccine, prepared from inactivated viruses, should be used for target populations, that is, for people exposed to tick bites during their professional or leisure outdoor activities.

Pre-exposure rabies vaccination: strategies and cost-minimization study.

An alternative strategy for pre-exposure rabies vaccination to the institutional recommendations of the World Health Organization and the Centers for Disease Control and Prevention is proposed based on recent long-term follow-up of post-vaccinal seroconversion rates. The alternative strategy uses the same primary series (i.e. vaccination in the deltoid area on D0, D7, and D28), but is completed by a scheduled booster vaccination at D365. The frequency of recommended subsequent booster injections depends on the serological test results obtained by a RFFIT on D379 and 3 years later. The objective of this study was to compare the efficiency of the two pre-exposure strategies. A cost-minimization analysis was carried out to compare the two rabies pre-exposure vaccination and serological test strategies based on the data from two published studies on the long-term evolution of the immunity achieved using the different recommendations. For a theoretically equivalent immunogenicity, the cost of the alternative strategy ranged from 1.7 to 5.2 times lower than that of the institutional recommendations. A sensitivity analysis confirmed the robustness of the results. The alternative strategy should be validated externally under field conditions. This approach would compare its real efficiency to the institutional recommendations.

[Rabies in France: an update]. / La rage en France: actualité.

INTRODUCTION: In 1996, rabies was responsible for more than 35,000 deaths worldwide. Three cases of human rabies that had been contracted abroad were diagnosed in France during the same year. Cases notified in 1997 followed exposure outside the country. Fox, bat, and dog rabies are reviewed on the basis of the latest epidemiological data obtained in France. CURRENT KNOWLEDGE AND KEY POINTS: Two cases of fox rabies diagnosed in 1998 occurred at the border between France and Germany, thus preventing five French departments bordering Germany from being officially declared rabies-free in 1999. The campaigns for oral immunization of foxes that are led since 1986 are responsible for the decrease in rabies incidence. Though not well known, bat rabies is a reality in France, involving either European virus strains (five cases all over the country) or African virus strains that are carried along by imported tropical bats. Dogs rabies is also today an imported disease. FUTURE PROSPECTS AND PROJECTS: The decrease in risk for rabies has resulted from the conjunction of multiple efforts: extensive programs aimed at oral vaccination of foxes in France and its neighboring countries, efficient epidemiological survey, sanitary controls at borders, ban on importing tropical bats. Furthermore, recommendations for preventive pre-exposure immunization have recently been changed, leading to modifications of the French licensing form.

Predictive factors for the neutralizing antibody response following pre-exposure rabies immunization: validation of a new booster dose strategy.

A prospective cohort of 312 subjects who received pre-exposure rabies immunization and who were monitored serologically with a 10-year follow-up was assessed using multivariate analysis. The aim was to propose a new booster dose strategy by identifying predictive factors for the durability of the neutralizing antibody response. Evaluation bore on several factors relating to: (1) demographic characteristics: age, gender; (2) vaccines: type of vaccine (HDCV or PVRV), injection regimen (D0-D28-D365 or D0-D7-D28-D365) and vaccine lots' antigenic potency; and (3) resulting antibody titers. Logistic regression analysis enabled the authors to establish a predictive model for immunized subjects' serological status at ten years' follow-up expressed as a P probability for seroreversion (antibody titer <0.5 IU/ml). Highly significant factors were the immunization regimen, the type of vaccine used and the antibody titer at D379. A P value <0.4 identified subjects as "good" responders who were sure to be have satisfactory antibody titers at 10 years and who required a single booster dose every 10 years. A P value >/=0.4 identified subjects as "poor" responders in whom a specific follow-up and booster dose strategy is proposed. This new immunization strategy could at least be applied to subjects with a frequent risk of exposure, as defined by institutional recommendations. This new immunization strategy should nevertheless undergo an external validation and a cost-effectiveness evaluation.

Antibody persistence following preexposure regimens of cell-culture rabies vaccines: 10-year follow-up and proposal for a new booster policy.

Subjects (n = 312) received either the human diploid cell rabies vaccine (HDCV) or the purified Vero cell rabies vaccine (PVRV) according to either two-injection (days 0 and 28) or three-injection (days 0, 7, and 28) primary regimens. They received a booster injection at 1 year. Rabies antibody levels were measured after the primary series and the booster and then each year for the next 10 years. The results confirm the superior long-term immunogenicity of the three-injection over the two-injection protocol. HDCV and PVRV in three doses were equally immunogenic. A booster injection at 1 year provides long-term seroconversion (titer > or = 0.5 IU/mL). Antibody titers 2 weeks after the 1-year booster allowed prediction of long-term immunity. Good responders, with titers > or = 30 IU/mL, were protected for at least 10 years. An algorithm for differentiation between good responders and poor responders with respect to vaccine booster strategies is proposed.

[Immunoprophylaxis of rabies: current recommendations]. / L'immuno-prophylaxie de la rage: actualisation des recommandations.

Pre-exposure rabies vaccination should comprise 3 injections (day 0, day 7, day 28) followed by boosters 1 year later then every 5 years. Populations who are particularly exposed due to occupation, regular contact with animals in endemic areas during leisure activities or holidays should be vaccinated, especially if access to post-exposure treatment is difficult. Post-exposure treatment should comprise 5 injections (day 0, day 3, day 7, day 14, day 28) which must be given with specific immunoglobulins on day 0 if there are penetrating wounds. In persons whose prior vaccination status is well-documented and correctly maintained, post-exposure treatment may be limited to 2 injections on day 0 and day 3. The vaccine is given is intramuscular injection in the deltoid region. Immunoglobulins are used at the dose of 20 IU/kg for human immunoglobulins and at 40 IU/kg for horse immunoglobulins. The injections are infiltrated around the lesions and the remaining quantity injected in the gluteus muscle. Seroconversion must be monitored by assaying neutralizing antibodies (titre > or = 0.5 IU/ml with the RFFI Test) in vaccinated populations who regularly exposed. Monitoring can also be useful after post-exposure treatment in certain specific cases (immunosuppressed subjects, treatment protocol incorrectly or incompletely applied). An antibody titre under 0.5 IU/ml requires an immediate vaccine injection.

[Granular-cell tumor: review of the literature apropos of a case of bronchial site]. / Tumeur à cellules granuleuses: revue de la littérature à propos d'une localisation bronchique.

Abrikossoff's tumor, also called granular cell tumor, is an uncommon condition, generally benign, which can affect every organ and specially skin and tongue. The authors report an observation of a bronchial tumor and review the literature. Possible relapse after treatment, locally or everywhere in the body, may occur as local or regional complication that may necessit heavy surgery. It appears that a benign tumor can have macroscopic and even microscopic aspect of malignancy, when real malignant tumors are extremely rare. Wide excision still remain current treatment of Abrikossoff's tumor. Endoscopic methods are an interessant and less invasive alternative to treat some deep tumors.

[Human periorbital dirofilariasis]. / Dirofilariose humaine periorbitaire.

We present the case of a 72 year-old-woman with recurrent periocular inflamatory mass caused by an infection with Dirofilaria repens. The zoonotic infection is spreading by mosquito vectors from dogs to humans. Residence in endemic areas (ex-USSR, Italy, Sri Lanka, Southeastern United States) should always be suspected in patients with this type of symptomatology. The treatment is curative by the extraction of the pseudotumoral mass.

[Brucellosis among occupationally exposed people: evaluation of immunological tests after vaccination]. / Brucellose en milieu professionnel exposé: évaluation des tests immunologiques après vaccination.

For the evaluation of immunological tests during an epidemiological survey and of vaccination with the PI brucellin vaccine, in an occupationally exposed environment, a sample group of 354 subjects was studied. The vaccinal strategy was based on the outcome of a skin test for hypersensitivity: the PS brucellin test. In this framework, the serological status and evolution of individuals with positive or negative reactions to this test were analysed. Sera were studied using the buffered antigen test, indirect fluorescence immunoassay and Wright's agglutination test, as well as by PACIA and ELISA techniques with assay of IgG, IgA and IgM antibodies. The PS test, which was pivotal in this study, was compared with the lymphoblastic transformation test. One prominent aspect of this evaluation was the establishment of conventional prognostic indices for the PS and serology. The PS is definitely shown to be a convenient, reliable tool for screening. Although it does not generate sensitivity it may modify the serological status of both positive and negative individuals.

[Pre-exposure rabies immunization in occupational exposed milieu. A 5-year prospective and comparative study of immunogenicity]. / Vaccination antirabique préventive en milieu professionnel exposé. Etude prospective et comparative d'immunogénicité sur 5 ans.

Pre-exposure rabies immunization has been the object of numerous immunogenicity studies with cultivated cell vaccines. Several primary immunizations and booster injection schedules have been suggested. The purpose of the present study was to compare simultaneously the immunogenicities of two vaccines at 5 years and those of two primary immunization schedules with a booster injection at 1 year. We compared the vaccine prepared from Vero cell cultures (PVRV) versus the reference vaccine prepared from human diploid cell culture (HDCV). We also compared primary immunization with 2 injections (on days 0 and 28) versus 3 injections (on days 0, 7 and 28). This phase IV study was prospective, randomized and conducted on open cohorts, according to a factorial plan defining four modalities (HDCV 2, HDCV 3, PVRV 2, PVRV 3). The study involved 312 volunteers of both sexes, aged from 15 to 65 years and exposed to rabies by their profession. The vaccines were injected intramuscularly in the deltoid region. Immunogenicity was evaluated by staged titering of neutralizing antibodies, using immunofluorescence. Seroprotection levels and mean geometrical means of titers were compared. The 3 injections schedule proved to be significantly superior to the 2 injections schedule. No difference could be clearly elicited between the two vaccines. The worst results were obtained with PVRV 2, with a 68.3 percent seroprotection rate at five years; with the other modalities this rate was 93.1 percent or more. We therefore recommend the following procedure: primary immunization by 3 injections, with a booster dose at 1 year, particularly when PVRV is used. It seems that the seroprotection obtained in this manner would make it possible to envisage a booster injection every 5 years.

[Brucella vaccination in professionally exposed subjects. Prospective study]. / Vaccination brucellique en milieu professionnel exposé. Etude prospective.

This prospective phase IV study on cohort concerns a vaccine made of the phenol-insoluble fraction of Brucella abortus biotype 1 (B19 strain). Three hundred and three professionally exposed subjects entered the study; 161 out of 182 subjects (88.5 percent) with negative response to an intradermal test for detection of previous contamination accepted to be vaccinated. Booster injections were given 18 and 36 months after vaccination. Local pain was observed after 45.2 percent of injections and moderate systemic reactions after 5 percent of injections. Seropositivity after primary vaccination reached 80 percent. The booster injection, justified by a major decrease of this rate after 18 months, gave exactly the same response of the thymo-independent type. This vaccinal schedule did not result in detectable hypersensitivity. The clinical effectiveness of the vaccine could not be evaluated accurately because of the insufficient number of subjects. The possibility of subclinical infection in vaccinated subjects calls for wider comparative studies of vaccinated versus non-vaccinated subjects.

Immunisation with canarypox virus expressing rabies glycoprotein.

Poxviruses have many useful features as vectors for genes that carry immunising antigens from other viruses, such as ease of production and induction of cellular and humoral immunity, but there is concern about the safety of vaccinia virus. We turned to an avian poxvirus (canarypox); this virus undergoes abortive replication in mammalian cells that enables presentation of early gene products to the immune system. Canarypox virus was used as a vector for the rabies glycoprotein G gene. The safety and efficacy of the recombinant (ALVAC-RG; vCP65) were tested in several animal species, then it was subjected to a phase 1 clinical trial. Twenty-five volunteers were randomly assigned to subcutaneous injections of the recombinant (three groups [A, B, and C] received two doses each of 10(3.5), 10(4.5), and 10(5.5) tissue-culture infectious doses50, respectively) or of human diploid cell culture vaccine (HDC; 6.52 international potency units per dose). 28 days after the second dose, all nine ALVAC-RG group-C subjects and two of three group-B subjects had rabies neutralising antibody concentrations of at least 0.5 IU/ml, the level associated with protection in animals. Although the geometric mean titre of these antibodies at that time was lower in group C than in the ten HDC recipients (4.4 [range 0.9-12.5] vs 11.5 [4.7-25.3] IU/ml), a single booster dose at 6 months induced a recall response in volunteers primed with either vaccine. Side-effects associated with ALVAC-RG were mild and of short duration and occurred at similar frequency to those of HDC vaccine. This study has shown the potential of non-replicating poxviruses as vectors for vaccination in human beings. Trials of canarypox-virus recombinants at higher doses and by other routes of administration are needed.

[Animal bites. Epidemiology and infection risks]. / Morsures d'animaux. Epidémiologie et risques infectieux.

A review of 5,116 cases of animal bites (587 of which were studied prospectively) has shed some light on their epidemiological aspects and on the risk of infection they carry. It has also led to a more objective assessment of the real effect of the therapeutic and prophylactic measures usually applied in such cases. The most frequent wounds are those of the hands and face, the former rising an infectious problem, the latter a predominantly cosmetic problem. The overall risk of infection is 30 per cent, but it is increased, notably as regards pasteurellosis, in the case of cat bite. Precise and simple rules concerning the prevention of this risk cannot easily be given, but it seems that the systematic antibiotic treatment initially prescribed has not clearly proved effective. Similarly, early sutures do not significantly increase the risk of infection.