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Biomedical subjects

J Barrat

Publications and source records attributed to J Barrat.

At least 19 recordsLinked to original sources

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.

Administration, Oral↗

Use of filter paper (FTA) technology for sampling, recovery and molecular characterisation of rabies viruses.

This study evaluates the feasibility of the use of the FTA Gene Guard System (a commercial product consisting of filter paper impregnated with patented chemicals supplied by the Whatman company) for the shipment, storage and detection of RNA rabies viruses by a simplified hemi-nested reverse transcriptase polymerase chain reaction. HnRT-PCR of the rabies virus nucleoprotein gene with specific primers showed that viral RNA extracted from crude infected tissues remained stable after fixation on the filter paper under diverse environmental conditions for at least 35 days. The sequence analysis of the products amplified from five out of the seven known genotypes of Lyssaviruses showed the stability of viral RNA viruses after fixation on the filter paper. Furthermore, the sensitivity of the hnRT-PCR following RNA fixation on the filter paper was equivalent to that of standard hnRT-PCR. In conclusion, the stability of viral RNA and the inactivation of infectivity make the FTA technology useful for the storage, transport, collection and subsequent molecular analysis of viral rabies RNA, facilitating epidemiological investigations in the field.

Animals↗

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.

Administration, Oral↗

Rabies diagnosis.

A reliable diagnosis of rabies can only be made based on laboratory examination of specimens collected from suspected animals. Without data from diagnostic tests, it is not possible to establish rabies control policies. These data are also necessary for evaluating the impact of control measures on the disease and to adapt veterinary and human health policies to the rabies situation. This paper presents the routine laboratory techniques for rabies diagnosis that are published and recommended by both the OIE and WHO and which form the basis of rabies surveillance. They are presented along with more recent techniques which have proved useful in epidemiological and phylogenetic studies. The first step in controlling a disease is to be able to identify it consistently. A reliable and sensitive diagnostic test is therefore essential for use in epidemiological studies and disease control. Reliable diagnosis is also needed by official medical and veterinary services to decide how to deal with infected humans or animals. Without knowing where rabies is present in a country, it is difficult to establish a solid, long-term control policy. A viral disease may be diagnosed on the basis of clinical signs or after laboratory examination. Clinical diagnosis is based on the observation of symptoms and on observation of specific or at least highly evocative signs. Laboratory tests reveal the presence of infection using either indirect or direct methods. The most frequently used indirect methods are based on serological testing. Direct methods aim to detect the virus itself, its proteins, genetic material or traces of its replication in tissues.

Animals↗

Means used for terrestrial rabies elimination in France and policy for rabies surveillance in case of re-emergence.

In France, the first case of wildlife rabies was detected in 1968, with the red fox (Vulpes vulpes) as reservoir and vector of terrestrial rabies. The last case was reported at the end of 1998. The maximum infected area amounted to 140,000 km2 in 1989 with a record number of 4,213 infected wild and domestic animals. The contaminated areas included various landscapes such as low populated farming areas and low mountainous areas as well as very densely populated areas and industrial areas contiguously urbanised. Oral vaccination of wildlife against rabies was implemented in 1986 and 1987 on limited areas treated by hand distribution and then helicopter distribution was implemented in 1988. The control of wildlife rabies was centralised at the country level in one institute for elaboration of baiting strategies, rabies surveillance network, laboratory investigations such as tetracycline and serological testing, vaccine titration and rabies diagnosis. Oral vaccination campaigns were organised in spring and in autumn by dropping annually 40 baits/km2. The following vaccine baits were used: SAD B19 from 1986 to 1992, SAG1/SAG2 from 1990 to 2003 and VRG from 1989 to 2003. A cost analysis study of the system of oral vaccination implemented in France demonstrated that it is beneficial compared to the traditional expenses of rabies control. Animal rabies prophylaxis has been progressively adapted to the disease free status of the country; the surveillance network for rabies is still working and an emergency procedure is in place in the event of a re-emergence of the disease in the context of high density fox populations.

Administration, Oral↗

First oral vaccination of wildlife against rabies in Estonia.

Estonia is a small country, with many islands, that covers a total area of 45,000 km2 in the Baltic region. Rabies is widely distributed all over the country, even on some islands. The disease is maintained by two species: red foxes and raccoon dogs. In 2003, 813 cases of rabies were recorded with 315 cases in foxes and 362 cases in raccoon dogs; since 2002 the latter species has had the highest level of rabies infection among all animal species in Estonia. The measure used to control rabies is vaccination of dogs and cats, as they are the source on infection of humans. In Spring 2004, a limited trial of oral vaccination of wildlife was conducted. The goal of this was to train the actors who will be implicated in larger future campaigns. This trial was conducted on Vormsi island (92 km2), located 10 km away from the west coast. Oral vaccination was performed manually over three days with SAG2 baits (Virbac company, France), by three teams.

Administration, Oral↗

Bat rabies surveillance in France, from 1989 through May 2005.

In France, the passive surveillance of lyssaviruses in bats started in 1989, with the first positive case found in the East of the country. In 2000, the French bat rabies surveillance network in France was improved on the basis of the one used for the surveillance of fox rabies. The objectives of this network are to improve bat rabies surveillance by increasing the number of specimens and to provide an estimation of rabies incidence in bat populations across the country. The surveillance network is principally constituted by the network of local Veterinary Services and by the National Bat Conservationists Network (French Society for the Study and Protection of Mammals). From 1989 to through 2004, 21 autochtonous rabies cases were diagnosed out of the 934 French bat cadavers found. The laboratory techniques used for diagnosis, recommended by WHO and OIE, were fluorescent antibody test (FAT), rabies tissue culture infection test (RTCIT) on murine neuroblastoma cells, and the mouse inoculation test (MIT). All 21 cases were diagnosed in serotine bats (Eptesicus serotinus) and were due to European bat lyssavirus type 1 (EBLV-1), genotype 5, infection.

Animals↗

Incidence and persistence of classical swine fever in free-ranging wild boar (Sus scrofa).

Although veterinary authorities aim to limit persistence of classical swine fever (CSF) in wild boar (Sus scrofa), to avoid potential transmission to pigs, factors influencing CSF transmission and persistence are not clearly understood. Here we analyse incidence and persistence in a CSF epidemic that occurred in the French Vosges Forest. Higher incidence was found in large forests compared to smaller isolated ones, being highest near the starting point of the epidemic, but poorly related to the local density. We hypothesize that the spatial and social structure of wild boar populations may be responsible for this variability of incidence over space. Persistence was highest near the starting point of the epidemic and where initial density was highest. We hypothesize that persistence was favoured by the abundance of young wild boar, itself encouraged by CSF. Our results allow us to propose management measures aimed at limiting CSF persistence.

Animal Husbandry↗

Genetic analysis of European bat lyssavirus type 1 isolates from France.

European bat lyssavirus type 1a (EBLV-1a) was first identified in central France from a serotine bat (Eptesicus serotinus) collected at the end of 2002. Rabies was diagnosed by reference rabies diagnosis methods and molecular tools. Phylogenetic analysis of 14 viral isolates obtained from French bats infected with EBLV-1 between 1989 and the end of 2002 against 47 nucleoprotein sequences showed a north-west to east distribution of EBLV-1a virus and a south to north distribution of EBLV-1b virus, isolates of which could be divided into two groups: group 1 in north-eastern France and group 2 in central and north-western France.

Animals↗

Development of a hemi-nested RT-PCR method for the specific determination of European Bat Lyssavirus 1. Comparison with other rabies diagnostic methods.

A simplified hemi-nested reverse transcriptase polymerase chain reaction (hnRT-PCR) has been developed to determine specifically the European Bat Lyssavirus 1 (EBLV-1) nucleoprotein gene. The specificity of this method was determined by using the seven genotypes of lyssavirus by RT-PCR, Southern blot and sequence analysis. Compared to the rabies diagnostic methods, the hnRT-PCR showed a higher sensitivity for the detection of small amounts of EBLV-1 virus. In view of these results, we suggest this new hnRT-PCR should be performed for the epidemiological survey of bat colonies, also providing rapid detection and genotyping of EBLV-1 until now encountered in all naturally infected bats in France.

Amino Acid Sequence↗

A dog rabies vaccination campaign in rural Africa: impact on the incidence of dog rabies and human dog-bite injuries.

Despite the availability of safe and effective rabies vaccines, the incidence of dog rabies has been increasing throughout much of sub-Saharan Africa. Here we describe a vaccination strategy that has resulted in successful control of rabies in a rural dog population of Northwestern Tanzania. From October 1996 to February 2001, four central-point dog vaccination campaigns were conducted in villages within Serengeti District with a mean interval between campaigns of 338, 319 and 456 days. Vaccination coverage of the dog population was estimated from household questionnaires as 64.5, 61.1, 70.6 and 73.7% following each of the four campaigns, respectively. The incidence of dog rabies declined significantly in Serengeti District falling by 70% after the first campaign and by 97% after the second campaign. Over the same period, the incidence of dog rabies did not differ significantly in unvaccinated control villages of Musoma District. The incidence of human bite injuries from suspected rabid dogs declined significantly in Serengeti District after dog vaccination but not in adjacent unvaccinated districts. Vaccination of 60-70% of dogs has been sufficient to control dog rabies in this area and to significantly reduce demand for human post-exposure rabies treatment. Dog-bite injuries can provide a valuable and accessible source of data for surveillance in countries where case incidence data are difficult to obtain.

Animals↗

Kinetics of humoral immune response after rabies VR-G oral vaccination of captive fox cubs (Vulpes vulpes) with or without maternally derived antibodies against the vaccine.

In western Europe during the spring, the largest proportion of fox populations are cubs and the key to successful rabies oral vaccination campaigns is cub vaccination. In this paper we report on studies of the serology of 93 fox (Vulpes vulpes) cubs born to unvaccinated and orally vaccinated captive vixens, some of which were orally vaccinated at 30 or at 90 days of age with the vaccinia recombinant vaccine (VR-G) that expresses the rabies virus glycoprotein. The duration of cub passively acquired antibody, the development of immune responses to oral vaccination at either 30 or 90 days of age, possible interference between passive and active immunity to such vaccination and resistance to a potentially lethal rabies challenge dose when five months old were measured. The study showed that rabies neutralising antibody can be passed to their cubs by vixens orally vaccinated with VR-G during pregnancy. Maternally derived antibody titres in cubs declined with time and disappeared by 45-75 days after birth. Thirty days old cubs serologically responded to oral vaccination. No interference between antibody of maternal origin and active immunity conferred by VR-G oral vaccination or between antibody of maternal origin and protection was observed. Thus, very young cub immunisation against rabies with VR-G per os is possible whatever the immune status of their mothers. Provided a vaccine-bait suitable for such young cubs exists, oral vaccination at den entrances with VR-G is a feasibility.

Administration, Oral↗

Humoral and cell-mediated immune responses of foxes (Vulpes vulpes) after experimental primary and secondary oral vaccination using SAG2 and V-RG vaccines.

Humoral and cell-mediated immune responses of 36 captive foxes to two oral vaccines against rabies currently used for foxes in Europe were studied. The Street Alabama Dufferin (SAD) mutant Gif (SAG2) vaccine has been selected by double mutation from the SAD virus. The vaccinia recombinant virus (V-RG) expresses the rabies glycoprotein. Both vaccines induce similar humoral and cell-mediated responses after primary and secondary oral administration. We observed a typical anamnestic response, although of a limited duration, after the booster vaccination. Therefore, our results suggested that two successive oral vaccination campaigns should not significantly improve the immunisation of foxes. Lymphocyte in vitro proliferative response to the SAD antigen highlighted the presence in blood of a T-cell specific memory 6 months after vaccination. The synthesis of several vulpine cytokines was detected in peripheral blood mononuclear cells (PBMC) stimulated by SAD antigen via reverse transcription polymerase chain amplification. The data showed a concomitant expression of interleukin (IL)-4 and interferon-gamma in PBMC of vaccinated foxes. No change was detected in the level of IL-2, IL-10 and IL-12 synthesis, whereas the pro-inflammatory cytokine tumour necrosis factor-alpha seemed involved in the activation of naive T lymphocytes.

Administration, Oral↗

A rabies serosurvey of domestic dogs in rural Tanzania: results of a rapid fluorescent focus inhibition test (RFFIT) and a liquid-phase blocking ELISA used in parallel.

During a serosurvey of domestic dogs in Tanzania, a rapid fluorescent focus inhibition test (RFFIT) and a liquid-phase blocking ELISA (LPBE) were used to measure rabies antibodies in vaccinated and unvaccinated dogs. Post-vaccination titres measured by LPBE correlated closely with those found by RFFIT. Of 567 unvaccinated dogs tested using the LPBE, 42 (7.4%) were seropositive, with titres exceeding 32. Of this group, 233 dogs were tested using the RFFIT and 115 (49.4%) were seropositive, with titres exceeding 0.5 IU/ml. Two lines of evidence pointed to the greater specificity of the LPBE when measuring rabies antibodies induced by natural infections: (a) no seropositive dogs were detected among the 162 unvaccinated dogs from the rabies-free island of Pemba, Tanzania, when using LPBE, whereas 15/145 (10.3%) dogs of the same group were seropositive using RFFIT; (b) among Tanzanian dogs there was a close association between the location of rabies cases and location of seropositive dogs when using LPBE, but not when using RFFIT. These results suggest that LPBE may be of value in rabies seroepidemiological studies and could be developed as a reference technique for the detection of rabies antibody in domestic dogs.

Animals↗

Effectiveness of SAG1 oral vaccine for the long-term protection of red foxes (Vulpes vulpes) against rabies.

Three groups of 10 foxes were vaccinated by the direct oral instillation of 2 ml of SAG1 rabies virus vaccine containing 10(6) MICLD50 (10(7) TCID50/ml) infectious viral particles/ml. SAG1 is a natural variant of the attenuated rabies vaccine strain SAD Bern and was selected in the presence of monoclonal antibodies. The strain is devoid of residual pathogenicity for the fox and the highly susceptible adult laboratory mouse by the oral, intramuscular and intracerebral routes. The foxes were challenged six, 12 and 18 months later with a virulent vulpine street rabies virus (GS 7-1-1). They all survived, whereas seven of eight unvaccinated control foxes died.

Administration, Oral↗

[Early debulking surgery after chemotherapy in advanced cancer of the ovary].

The main prognostic factor in advanced ovarian cancer is the volume of residual disease after the initial laparotomy. Early debulking surgery after several cycles of chemotherapy, before the emergence of resistant cell lines, could improve the prognosis of patients with bulky residual disease. This study concerns patients with advanced ovarian cancer entered into three prospective trials including IV cisplatin and anthracycline-based chemotherapy, early debulking surgery after three cycles of chemotherapy in case of initial residual disease superior 2 cm and intraperitoneal consolidation chemotherapy. Among 160 patients with stage III or IV, 80 (50%) had at least a residual tumor of more than 2 cm in diameter. Early debulking surgery was effectively performed in 54 patients (67.5%), leaving 39 patients with no residue over 2 cm. Twenty-one patients had no macroscopic residual disease. The median survival of all patients with initial residual disease over 2 cm was 23 months. Patients with no macroscopic residual disease at early debulking surgery had a median survival of 44 months. Early debulking surgery appears useful in advanced ovarian cancer with bulky residual disease. The objective of this operation is to achieve no macroscopic residual lesion.

Antineoplastic Agents↗

The relation of birth weight and gestational age to biological, occupational and socioeconomic factors.

The data of the 2,040 single births, born during 1987 at the "Saint Antoine" Hospital in Paris, were analysed in order to identify the impact of various biological, occupational, and socioeconomic factors on gestational age and birth weight. Birth weight is associated with the height of the mother and the weight gained during pregnancy. It is lower for mothers with preeclampsia during the current or previous pregnancies or with urogenital infections during the current pregnancy and for mothers with one or more induced abortions. Girls weigh less than boys. Parity has a positive relation to the baby's weight, while manual work seems to have a negative one. APGAR score and duration of the pregnancy are associated with the birth weight. Placenta previa, preeclampsia and urinary infections affect the gestational age. A short pause period in work is related to a shorter gestational age. Weight gain is associated with a prolonged duration of the pregnancy. Gestational age and birth weight are associated with the nationality of the mother, especially in some ethnic groups, and with marital status.

Birth Weight↗