Multivariate analysis of the immune response to different rabies vaccines.

In a previous study, we proposed as an alternative to the use of animals in infectious challenge studies, a new approach describing the vaccine-induced immune response through the multivariate analysis of a defined set of immune parameters characterizing the B and T immune responses. This multivariate analysis, i.e. immune fingerprint, was evaluated first to assess the impact of minor changes in well characterized vaccines. The approach showed promising results in the assessment of the compatibility between two licensed vaccines. In the present study, the immune fingerprint was used to compare adjuvants with the various immunological parameters of the immune fingerprint as well as to assess the ability of this approach to discriminate different Rabies vaccine formulations in dogs. RABISIN® was the reference vaccine, adjuvanted with aluminum hydroxide. An exploratory factor analysis was used to analyse the covariance structure of the immunological data. Significant differences were observed between groups. RABISIN and a linear polyacrylate (SPA09) adjuvanted vaccine performed better than chitosan adjuvanted ones, both for humoral and cell immune responses. This study showed that the immune fingerprint approach can be used to screen vaccine formulations. It provides additional information compared to classical vaccination and infectious challenge efficacy study.

[Antimalarial drug retinopathy]. / Rétinopathie sévère aux antipaludéens de synthèse.

INTRODUCTION: Antimalarial drugs are largely used for the treatment of various systemic diseases. They can cause toxic retinopathy, which can lead to blindness. OBSERVATION: We report the case of a 32-year-old male with a systemic lupus erythematosus treated with hydroxychloroquine 400mg per day and then chloroquine 300mg per day during 8 and 9years respectively. Eighteen months after his latest visual examination, the patient experienced bilateral vision loss. Fundus examination revealed a bull's eye maculopathy. Additional tests including multifocal electroretinogram showed severe bilateral functional impairment in the parafoveal area leading to diagnosis of severe toxic retinopathy induced by antimalarial drugs. DISCUSSION: In 2016, the American Academy of Ophthalmology revised the previous 2011 recommendations concerning early retinal toxicity screening strategy which should be first based on both automated 10-2 visual fields and spectral-domain optical coherence tomography (SD OCT). Multifocal electroretinogram can be more helpful for diagnostic confirmation rather than screening. Although these recommendations are essential, they are not well known in clinical practice.

The obesity supine death syndrome (OSDS).

The obesity supine death syndrome refers to a catastrophic cascade of cardiorespiratory complications resulting from the supine positioning of a morbidly obese subject which can ultimately lead to death. It was first described in 1977 in two massively obese patients who were forced to lie down for medical procedures. But surprisingly, despite the current worldwide epidemic of obesity, very few cases have been reported yet. It can be assumed that the syndrome is poorly recognized in clinical practice and may participate in the high rate of unexplained death in morbidly obese patients. Based on the previously published cases and on those we met, this review aims at helping clinicians to early detect at-risk patients, to correctly diagnose this dramatic syndrome and to understand the underlying pathophysiology. More importantly, the main objective is to convince the attending clinicians that they have to do everything in their power to prevent obesity supine death syndrome occurrence by maintaining morbidly obese patients in the sitting or upright position whenever possible. When the syndrome unfortunately occurs, the best therapeutic approach is based on the immediate return to sitting position.

Evaluation of an ELISA to detect rabies antibodies in orally vaccinated foxes and raccoon dogs sampled in the field.

The assessment of the efficacy of oral vaccination in wildlife is based on detection in the teeth of a biomarker (tetracycline) which is incorporated in the vaccine bait, and the quantification of rabies antibodies. A blocking ELISA was evaluated and compared with the FAVN test and a validated in-house ELISA, using sera from foxes and raccoon dogs collected following oral vaccination campaigns in France and Estonia. Specificity reached 100% in sera from naïve animals. A high concordance (95%) was observed between the BioPro ELISA and the FAVN test, which was similar in sera from red foxes and raccoon dogs. Concordance between the BioPro ELISA and the in-house ELISA reached 96.5% for sera from red foxes. The agreement with tetracycline results was excellent in the fox for both the BioPro ELISA (95.9%) and the FAVN test (91.8%). Concordance was slightly lower in the raccoon dog, with a value of 82.8% for the BioPro ELISA and 78.4% for the FAVN test. Rabies antibodies were detected with the BioPro ELISA in animals vaccinated with different types of vaccines and in highly haemolysed sera. The BioPro ELISA is a valuable test to assess the efficacy of oral vaccination in foxes and raccoon dogs.

Experimental evaluation of personal protection devices against graphite nanoaerosols: fibrous filter media, masks, protective clothing, and gloves.

In this study, different conventional personal protection devices (fibrous filters, cartridges for respirators, protective clothing, and gloves) well qualified for micron particles were tested with graphite nanoparticles ranging from 10 to 100 nm (electrical mobility diameter). For this purpose, two specific test benches were designed: one for filter-based devices which are tested under a controlled air flow and other for gloves and protective clothing based on the "through diffusion method." The penetration versus particle size shows for most tested filter media the behavior predicted by the theoretical Brownian capture: penetration decreases when particle diameter decreases. No thermal rebound was detected until 10 nm for graphite nanoparticles. Protective clothes were tested by two methods and same trends were obtained. Nonwoven fabrics (air-tight materials) are much more efficient against nanoparticles than cotton and paper. Gloves tested by "through diffusion technique," in static condition seem to efficiently protect against graphite nanoparticles in spite of their important porosity.

Onset and duration of protective immunity against clinical disease and renal carriage in dogs provided by a bi-valent inactivated leptospirosis vaccine.

Protection against clinical disease and prevention of the renal carrier state remain the key objectives of vaccination against leptospirosis in the dog. In the present paper, groups of dogs were vaccinated twice with a commercial bacterin (EURICAN L) containing Leptospira interrogans serovars icterohaemorrhagiae and canicola and challenged with heterologous representatives of both serovars at 2 weeks (onset of immunity) or 14 months (duration of immunity) after the second vaccination. Control dogs were not vaccinated against leptospirosis and kept with the vaccinated dogs. The challenges, irrespective of the serovar, reliably produced clinical signs consistent with Leptospira infection in the control pups with up to 60% mortality. As expected clinical disease in the adult controls was less severe, but we were able to induce morbidity and mortality as well. Under these extreme challenge conditions, clinical signs in the vaccinated dogs were rare, and when observed, mild and transient in nature. Following experimental infection, 100% of the control pups and 83% of the adult controls became renal carriers. Despite the heavy challenges, none of the 18 vaccinated puppies (onset of immunity studies) and only 2 out of the 16 vaccinated adult dogs (duration of immunity studies) developed a renal carrier state. These results show that a primary course of two doses of EURICAN L provided quick onset and long-term protection against both clinical leptospirosis and the renal carrier stage. This vaccine should provide veterinarians with a powerful tool to prevent clinical disease in dogs and zoonotic transmission of leptospirosis to humans.

Onset of immunity in kittens after vaccination with a non-adjuvanted vaccine against feline panleucopenia, feline calicivirus and feline herpesvirus.

The induction of a quick onset of immunity against feline parvovirus (FPV), feline herpesvirus (FHV) and feline calicivirus (FCV) is critical both in young kittens after the decline of maternal antibodies and in cats at high risk of exposure. The onset of immunity for the core components was evaluated in 8-9 week old specific pathogen free kittens by challenge 1 week after vaccination with a combined modified live (FPV, FHV) and inactivated (FCV) vaccine. The protection obtained 1 week after vaccination was compared to that obtained when the challenge was performed 3-4 weeks after vaccination. The protocol consisted of a single injection for vaccination against FPV and two injections 4 weeks apart for FHV and FCV. At 1 week after vaccination, the kittens showed no FPV-induced clinical signs or leukopenia following challenge, and after FCV and FHV challenges the clinical score was significantly lower in vaccinated animals than in controls. Interestingly, the relative efficacy of the vaccination was comparable whether the animals were challenged 1 week or 3-4 weeks after vaccination, indicating that the onset of protection occurred within 7 days of vaccination. Following the 1-week challenge, excretion of FPV, FHV and FCV was significantly reduced in vaccinated cats compared to control kittens, confirming the onset of immunity within 7 days of vaccination.

Comparison of antibody responses after vaccination with two inactivated rabies vaccines.

Thirty laboratory dogs were randomly assigned to two groups (A and B) of 15 dogs and subcutaneously vaccinated with a single dose of one of two commercially available monovalent inactivated rabies vaccines: RABISIN (Merial, France) (group A) and NOBIVAC Rabies (Intervet International) (group B). Rabies antibodies were measured over a period of 4 months using the fluorescent antibody virus neutralization (FAVN) test. The two vaccines performed differently in terms of magnitude and persistence of rabies antibodies titers in dogs. Two weeks after vaccination, average rabies antibody titers peaked at 2.53 IU/mL (range, 0.17-13.77 IU/mL) and 1.26 IU/mL (range, 0.50-4.56 IU/mL) in groups A and B dogs, respectively. The average FAVN antibody titres against rabies on D28, D56, D84, D112 and D120 were significantly higher in group A than in group B. Although all dogs from group B serologically responded to vaccination, the proportion of dogs with antibody titres >or=0.5 IU/mL dropped significantly after D28 and was statistically significantly lower on D56, D84 and D112 compared to group A dogs. In conclusion, in the context of international trade, the choice of the vaccine and the timing of blood tests are critical factors in achieving successful serological test results after rabies vaccination. RABISIN induces high and sustained antibody titres against rabies, increasing the flexibility for the time of blood sampling after primo-vaccination.

Efficacy and bait acceptance of vaccinia vectored rabies glycoprotein vaccine in captive foxes (Vulpes vulpes), raccoon dogs (Nyctereutes procyonoides) and dogs (Canis familiaris).

The red fox, dog, and raccoon dog are known to play a major role in the global epidemiology of rabies. These three canid species were used to compare the appetency and efficacy of two commercial bait formats, each containing a single dose of vaccinia-rabies glycoprotein (V-RG) vaccine. Square and rectangular RABORAL V-RG baits were fed to individual caged animal, and results were evaluated using three parameters: bait consumption, induction of rabies virus neutralizing antibodies and protection after a virulent rabies challenge. The rectangular and square RABORAL V-RG baits were found to deliver the oral rabies vaccine in a similar manner to all three species resulting in acceptable seroconversion and effective protection levels after the rabies challenge. Appetency of each bait type was measured by bait consumption and found to be similar for both RABORAL V-RG bait formats in the fox and dog. The square RABORAL V-RG bait, however, was consumed more effectively than the rectangular RABORAL V-RG bait by the raccoon dog.

New steps in the control of canine rabies in India.

In India, about 20,000 people die of rabies every year. The dog is the main reservoir and transmitter of the disease. A pilot rabies control programme was launched in five Indian federal states in February, 2007. This initiative is led by the Animal Welfare Board of India (AWBI) federating many animal welfare organizations and the Ministry of Agriculture. It aims at creating a "Rabies Free India." The programme combines parenteral vaccination of accessible owned and stray dogs, spaying/neutering followed by parenteral vaccination and oral vaccination of inaccessible dogs. The freeze-dried vaccine SAG2, including the bait casing, was registered in India following successful evaluation of vaccine-bait safety and efficacy (by survival after virulent challenge) in captive Indian stray dogs in the Bhopal High Security Animal Disease Laboratory. Furthermore, bait acceptance was tested under both experimental and field conditions.

Efficacy of a square presentation of V-RG vaccine baits in red fox, domestic dog and raccoon dog.

Oral vaccination programmes conducted in rabies infected countries from Eastern Europe and Eurasia should not be restricted to foxes but should target other major rabies vectors such as dogs and raccoon dogs as well. The objective of this experimental trial was to assess the protection induced by the vaccine by challenging these different species, which had been previously vaccinated intramuscularly with the square V-RG baits (produced in the US). Different parameters were evaluated such as attractiveness of the baits and induction of neutralising antibodies as an indicator for immunogenicity and protection after rabies challenge. The acceptability of the square bait was satisfactory in dogs, foxes and raccoon dogs, confirming previous laboratory and field studies conducted with the rectangular baits. Only one vaccinated dog out of nine seroconverted after vaccination and among them one dog died of rabies. Eight of ten vaccinated foxes seroconverted after vaccination and survived the rabies challenge. All vaccinated raccoon dogs seroconverted after challenge and all survived the challenge. These trials demonstrated that the square presentation of the V-RG vaccine was attractive, immunogenic and efficacious.

Rabies in Estonia: situation before and after the first campaigns of oral vaccination of wildlife with SAG2 vaccine bait.

Despite the extermination of stray animals and the compulsory vaccination of companion animals, rabies has been widely distributed over Estonia for more than 30 years. The red fox and the raccoon dog are the rabies virus reservoirs. Through a PHARE project, successive oral vaccination campaigns, using Rabidog SAG2 baits, were implemented in the autumn of 2005 in North Estonia, and in the spring and autumn 2006 throughout the whole territory. After the autumn 2005 campaign, 73.5% of the raccoon dogs and foxes were positive for the tetracycline biomarker. After the campaigns of 2006, the seroconversion rate for rabies virus was 64% in both species. After the vaccination campaigns of 2005 and 2006, the incidence of rabies cases dramatically decreased. Of the 97 cases diagnosed in the whole of Estonia until the end of May 2006, 16 cases (16.5%) occurred within the vaccinated area. Only 17 cases were diagnosed between 1 June and 31 December 2006. In 2007, by the end of May, only two rabies cases have been registered.

The safety and efficacy of the oral rabies vaccine SAG2 in Indian stray dogs.

India is one of the countries with the highest prevalence of human rabies throughout the world. Dogs are primarily responsible for rabies transmission. Among them, stray dogs play a major role in that country. Parenteral vaccination programmes are insufficient to eliminate rabies partly due to difficulties in establishing satisfactory immunisation coverage in the dog population in view of the high proportion of stray dogs. Oral vaccination may be a useful adjunct to parenteral vaccination by increasing dog vaccination coverage. Safety, immunogenicity and efficacy of Rabidog SAG2 bait were evaluated in Indian stray dogs in captivity. Safety of SAG2 was demonstrated by the absence of adverse clinical sign, salivary excretion and absence of replication of the vaccine strain in brain and salivary glands of 21 vaccinated dogs, even when immunodepressed. Efficacy was shown 109 days post-vaccination after challenge with a highly virulent street rabies virus which killed all five controls whereas all nine vaccinated dogs survived, despite the fact that only five out of nine had seroconverted before challenge.

Safety and efficacy of the oral rabies vaccine SAG2 in raccoon dogs.

Oral vaccination programmes in several rabies-infected countries from Northern and Eastern Europe should not be restricted to foxes but should target raccoon dogs as well. The safety, immunogenicity and efficacy of Rabigen SAG2 bait was evaluated in raccoon dogs. Safety of SAG2 was demonstrated after direct instillation (n = 5) or ingestion of a bait (n = 5) using a quantity of virus at least 10 times superior to the field dose. All animals seroconverted and remained healthy. Raccoon dogs were vaccinated by SAG2 bait ingestion and unvaccinated raccoon dogs were kept as controls. More than 6 months after oral vaccination, all animals were challenged with a highly virulent street rabies virus. All 28 vaccinated animals developed high rabies neutralizing antibody titres. After virulent challenge, all 11 controls succumbed to rabies, whereas all 28 vaccinates survived.

[Influenza vaccination among health-care workers. Vaccination rates in universitary hospital of Besançon, winter 2003-2004]. / La vaccination antigrippale du personnel hospitalier. Enquête de prévalence au CHU de Besançon, hiver 2003-2004.

BACKGROUND: Influenza vaccination reduces the mortality of the patients when the vaccination rates of healthcare workers is important. PURPOSE AND METHOD OF THE STUDY: To investigate the vaccination rates at the Universitary Hospital of Besançon by anonymous questionnaire. RESULTS: Three thousand hundred seventy-seven answers were analyzed (228 men and 1145 women). Two hundred seventy-seven persons declared receiving the vaccine (20.1%) corresponding to sixty-three men (27.6%) and two hundred thirteen women (18.6%) (P = 0.001). The average age of the healthcare workers vaccined was of 38.9+/-11 years. Among most than 50 years, 34% was vaccined. Among the doctors, 40.5% were vaccined against 20.6% of the nurses. In the services of geriatrics, 78.5% of the staff was vaccined. CONCLUSIONS: Our results indicate a weak rate of influenza vaccination in our establishment and a misunderstanding of the character nosocomial of the influenza among the nurse.

Efficacy of a canarypox virus-vectored vaccine against feline leukaemia.

Canarypox virus recombinant vaccines have a unique efficacy and safety profile for the vaccinated host because the canarypox virus is non-replicative in mammalian hosts. After the vaccination of a mammalian species, recombinant canarypox viruses express the inserted genes but cannot multiply in the host. They stimulate a strong immune response in the absence of any virus amplification in the host or any viral spread into the environment. A new canarypox-based recombinant vaccine is the canarypox-feline leukaemia virus (FeLV) vaccine (EURIFEL FeLV; Merial) that expresses the FeLV env and gag protective genes. This paper describes experiments which demonstrate that it is effective against any oronasal FeLV challenge. The protection was shown to be solid against an oronasal challenge one year after the initial vaccination, and was effective against a very severe 'in-contact' challenge. Furthermore, the canarypox virus-FeLV vaccine was effective without an adjuvant.

Seroprevalence of canine herpesvirus-1 in the Belgian dog population in 2000.

Canine herpesvirus-1 (CHV-1) is known to be associated with fertility and fecundity disorders as well as neonatal mortality in puppies of less than 3 weeks of age. The virus is presumed to be enzootic in dogs all over the world and recent studies in several European countries suggest a high seroprevalence among the dog population. In the year 2000, a total of 647 Belgian canine sera from 102 privately owned patients and 545 breeding dogs were analysed with an enzyme-linked immunosorbent assay (ELISA). Furthermore 77 of the samples were submitted to two serum neutralization (SN) tests for comparison. An overall CHV-1 seroprevalence of 45.75% was observed in the Belgian dog population. No significant differences could be observed based on breeding status, reason for consultation or sex. The correlation between the ELISA and both SN tests appeared to be moderate with a significantly greater sensitivity of the ELISA. This study also demonstrated that the CHV-1 seroprevalence in the Belgian dog population is similar to that in other recently investigated European countries and that the incidence in breeding units is not necessarily higher than in non-breeding dogs.

Spontaneous programmed cell death (PCD) process of lymphocytes of FIV-infected cats: cellular targets and modulation.

Unstimulated lymphocytes from FIV-infected cats undergo spontaneous apoptosis in vitro as indicated by internucleosomal DNA fragmentation and hypodiploid DNA content of nuclei. Unlike what is reported in HIV-infected individuals, we observed that cell death of cat lymphocytes was inhibited by activation. Spontaneous apoptosis was reduced by the addition of cat serum and after activation by phorbol ester (PMA), superantigens (SEB, SEA), and to a lesser extent by mitogens such as concanavalin A and pokeweed mitogen. In contrast, apoptosis of lymphocytes from FIV-infected, but not from control cats was increased in the presence of calcium ionophore (ionomycin). Analysis of the phenotype of cells undergoing apoptosis revealed that cell death is not restricted to a cell subpopulation but involved all lymphocyte subsets. These data suggest that the mature lymphocytes of FIV-infected cats appear programmed to die by apoptosis unless rescued by specific agents, such as protein kinase C activators or mitogens.

Spontaneous programmed cell death (PCD) process of lymphocytes of FIV-infected cats: pharmacological modulation in vitro.

We previously reported that unstimulated lymphocytes in culture from FIV-infected cats undergo spontaneous apoptosis in vitro as indicated by internucleosomal DNA fragmentation and hypodiploid DNA content of nuclei. Unlike what is reported in HIV-infected individuals, we observed that cell death of cat lymphocytes was inhibited by activation. Spontaneous apoptosis was reduced by the addition of cat serum, interleukins [interleukin (IL)1, Il2, IL6 and interferon-gamma (IFN gamma)] and after activation by phorbol ester [phorbol myristyl acetate (PMA)], superantigens [staphylococcal enterotoxin B (SEB), staphylococcal enterotoxin A (SEA)], and to a lesser extent by mitogens such as Concanavalin A and pokeweed mitogen, IN contrast, apoptosis of lymphocytes from FIV-infected, but not from control cats was increased in the presence of calcium ionophore (ionomycin). In this study, we studied the spontaneous programmed cell death (PCD)-inducing pathways, and the mechanisms of action of PMA, SEB and SEA. Spontaneous lymphocyte apoptosis of FIV-infected cats was inhibited by cycloheximide, ZnSO4 and N-acetyl-cystein. The preventive effect of SEB and SEA was inhibited by actinomycin, but not by inhibitors of kinases. Calyculin, an inhibitor of phosphatase, had no effect either on spontaneous apoptosis, or on the action of PMA, SEB and SEA. Ionomycin-induced apoptosis was found sensitive to PMA and cytokines. In FIV-infected cats, these data suggest that the mature lymphocytes appear programmed to die by apoptosis, unless rescued by specific agents, such as protein kinase C activators or growth factors, and that spontaneous PCD seems to be dependent of de nove protein synthesis (see effect of cycloheximide). The effects of PMA, SEB and SEA are probably mediated by de novo proteins which for PMA, undergo a phosphorylation involving serine-threonine and/or tyrosine groups. Our data suggest a clear difference between lymphocytes from FIV-infected cats and lymphocytes from HIV-infected humans, with regard to their metabolic regulations.