A case series study of an innovative community-based brief psychological model for men in suicidal crisis.

OBJECTIVES: To conduct a 1-year evaluation of James' Place, a suicidal crisis centre delivering a clinical intervention in a community setting. DESIGN: A case series study, following men entering the service during the first year of operation. PARTICIPANTS: Men experiencing a suicidal crisis referred to the service (N = 265), with N = 176 going on to engage in therapy. INTERVENTION: The James' Place Model is a therapeutic intervention offered to men who are in a suicidal crisis. Trained therapists provide a range of therapeutic approaches and interventions, focusing on decreasing suicidal distress and supporting men to develop resilience and coping strategies. MAIN OUTCOME MEASURES: CORE-34 Clinical Outcome Measure (CORE-OM). RESULTS: For all subscales of the CORE-OM there was a significant reduction in mean scores between assessment and discharge (p < 0.001), with all outcomes demonstrating a large effect size. All reductions illustrated a clinically significant change or a reliable change. CONCLUSIONS: Our results support the use of the James' Place Model for men in suicidal distress to aid in potentially preventing suicides in this high-risk group of the population.HighlightsEvaluates a brief psychological clinical intervention delivered in the community.Model effectively reduces suicide risk and findings can inform future services.Accessed men receiving an innovative intervention at the time of suicidal crisis.

Clinical management and humoral immune responses to rabies post-exposure prophylaxis among three patients who received solid organs from a donor with rabies.

BACKGROUND: The rabies virus causes a fatal encephalitis and can be transmitted through organ transplantation. In 2013, a man developed rabies 18 months after receiving a kidney from a donor with rabies, who was not known to have been infected when the organs were procured. Three additional persons who received organs from the same donor (liver, kidney, heart), all of whom were not vaccinated for rabies before transplantation, received rabies post-exposure prophylaxis (PEP) with rabies immune globulin and 5 doses of rabies vaccine as soon as the diagnosis of rabies was made in the donor (18 months after their transplant surgeries). We describe their clinical management. METHODS: As the 3 recipients were all on immunosuppressive medications, post-vaccination serologic testing was performed using the rapid fluorescent focus inhibition test to measure rabies virus neutralizing antibodies (RVNAs). An acceptable antibody response to administration of rabies vaccine was defined as detection of RVNAs at a concentration ≥0.1 IU/mL from a serum specimen collected ≥7 days after the fifth vaccine dose. RESULTS: All 3 recipients demonstrated an acceptable antibody response despite their immunosuppressed states. More than 36 months have passed since their transplant surgeries, and all 3 recipients have no evidence of rabies. CONCLUSIONS: The survival of 3 previously unvaccinated recipients of solid organs from a donor with rabies is unexpected. Although the precise factors that led to their survival remain unclear, our data suggest that PEP can possibly enhance transplant safety in settings in which donors are retrospectively diagnosed with rabies.

DNA immunization protects nonhuman primates against rabies virus.

More than 40,000 people die annually from rabies worldwide. Most of these fatalities occur in developing countries, where rabies is endemic, public health resources are inadequate and there is limited access to preventive treatment. Because of the high cost of vaccines derived from cell culture, many countries still use vaccines produced in sheep, goat or suckling mouse brain. The stability and low cost for mass production of DNA vaccines would make them ideal for use in developing countries. To investigate the potential of DNA vaccines for rabies immunization in humans, we vaccinated Macaca fascicularis (Cynomolgus) monkeys with DNA encoding the glycoprotein of the challenge virus standard rabies virus, or with a human diploid cell vaccine (HDCV). The monkeys then were challenged with a non-passaged rabies virus. DNA or HDCV vaccination elicited comparable primary and anamnestic neutralizing antibody responses. All ten vaccinated monkeys (DNA or HDCV) survived a rabies virus challenge, whereas monkeys vaccinated with only the DNA vector developed rabies. Furthermore, serum samples from DNA- or HDCV-vaccinated monkeys neutralized a global spectrum of rabies virus variants in vitro. This study shows that DNA immunization elicits protective immunity in nonhuman primates against lethal challenge with a human viral pathogen of the central nervous system. Our findings indicate that DNA vaccines may have a promising future in human rabies immunization.

World Rabies Day: focusing attention on a neglected disease.

Rabies kills 55,000 people every year mainly in Africa and Asia, despite being entirely preventable through vaccination and prompt medical treatment. Spurred on by this statistic, the first ever World Rabies Day will be held on September 8 in order to raise global awareness of rabies prevention and control. The driving force behind the initiative is the Alliance for Rabies Control, a charity formed in 2006 by a group of researchers and professionals committed to eradicating rabies. To mark the event, The Veterinary Record has commissioned experts in the field of rabies control to discuss what veterinary surgeons have done and can do to tackle this devastating disease. The message that emerges is that veterinary surgeons, in close collaboration with the medical profession, have a vital role to play. In the first article, Deborah Briggs from Kansas State University and Cathleen Hanlon from the Centers for Disease Control and Prevention in the USA describe the impetus behind the day, who is supporting it and what it hopes to achieve. Articles on the following pages describe other veterinary contributions to this field.

Control and prevention of rabies in animals: paradigm shifts.

Animal management is the keystone of any modern programme for the prevention and control of rabies. Historically, "animal control" for local elimination of disease was largely equated with population reduction. However, with relatively few exceptions, culling alone has not led to effective control of rabies. In most documented examples of effective control of rabies in the 20th century, an integrated management approach was used that included public education, responsible stewardship of animal populations, manipulation of the population carrying capacity of the local habitat, and vaccination strategies. Globally, the greatest burden on human health that is attributable to this zoonosis is caused by uncontrolled rabies in dogs. Where political willingness, biomedical infrastructure, and economic stability permit the sustained use of control measures (e.g. stray animal removal and mandatory parenteral vaccination), canine rabies has been significantly suppressed and even eliminated over large geographical areas. Examples include many island nations, most of North America, Europe, and increasingly in South America. Despite the effectiveness of such proven control techniques, however, their implementation in parts of Asia, Africa, and elsewhere has been limited, primarily because of a lack of dedicated resources and intersectoral cooperation, and also because of the burden of high-density populations of dogs. Implementation is often complicated by cultural and social factors, e.g. reluctance to cull apparently ownerless, nuisance animals that are suspected to have been exposed to rabies, partly on the basis of religious beliefs). Attempts to modify animal fertility (such as the encouragement of voluntary spay-neuter programmes or individual chemical contraception, and the extension of such actions to animals in the community) may provide ancillary support in line with other traditional methods of control of canine rabies. With the identification of complex situations in which wildlife rabies persists despite the elimination of canine rabies, e.g. in North America and Europe, cats can pose a significant public health risk requiring consideration of alternative approaches. In any model system, the threat of translocation of infected animals, unintentional or otherwise, provides a strong rationale for the creation of barriers to prevent reintroduction or exacerbation of the disease, and the maintenance of a minimum body of expertise related to surveillance, diagnosis, and the enactment of mitigating measures. While control activities have traditionally focused upon certain Carnivora species, bats represent another worldwide rabies reservoir. Indiscriminate killing of bats and destruction of roosts was once the norm, but such activities are not sanctioned by reputable organizations today. Even vampire bats, responsible for substantial effects on health and agricultural losses in the New World (Mexico to Argentina), should be targeted only by specific control applications, rather than by more widespread, unconventional, non-specific methodology. Bats should be excluded from human living quarters. Implementing measures to prevent bats from gaining access to homes should occur at an appropriate time when the bats are absent, especially to avoid sealing the non-flying young within a building. Although great progress has been made during the past four decades in the induction of herd immunity among free-ranging carnivores via oral vaccination against rabies, similar novel solutions have not been readily applied to bat populations. Given these challenges, new paradigm shifts are eagerly anticipated as additional biotechnological applications (including contraceptives and anticoagulants) are developed to deal with domestic animals and wildlife.

Biomarkers for Success: Using Neuroimaging to Predict Relapse and Develop Brain Stimulation Treatments for Cocaine-Dependent Individuals.

Cocaine dependence is one of the most difficult substance use disorders to treat. While the powerful effects of cocaine use on behavior were documented in the 19th century, it was not until the late 20th century that we realized cocaine use was affecting brain tissue and function. Following a brief introduction (Section 1), this chapter will summarize our current knowledge regarding alterations in neural circuit function typically observed in chronic cocaine users (Section 2) and highlight an emerging body of literature which suggests that pretreatment limbic circuit activity may be a reliable predictor of clinical outcomes among individuals seeking treatment for cocaine (Section 3). Finally, as the field of addiction research strives to translate this neuroimaging data into something clinically meaningful, we will highlight several new brain stimulation approaches which utilize functional brain imaging data to design noninvasive brain stimulation interventions for individuals seeking treatment for substance dependence disorders (Section 4).

Current recommendations for the prophylaxis and treatment of rabies.

Once onset of clinical rabies develops in an individual, death is inevitable. Thus, it is imperative that, for persons exposed or potentially exposed to rabies virus, prophylaxis must be instituted as soon as possible following the exposure. Local wound management is an essential part of postexposure rabies prophylaxis. Exposed persons should receive a recommended series of a tissue culture or cell culture origin vaccine. The number of doses and route of vaccination differ in various regions of the world and are discussed in the text. The administration of a rabies immune globulin is generally recommended in conjunction with the first dose of the rabies vaccine. Nerve tissue origin vaccines, although used extensively in some parts of the world, are not recommended if cell or tissue culture vaccines are available. Decision trees are presented in the text to aid in determining if rabies vaccine is necessary following a known or presumed exposure to the virus, along with a table outlining the various rabies vaccines available in the World. Rabies pre-exposure immunisation is recommended for those individuals at risk of exposure to the virus. Pre-exposure prophylaxis consists of 3 doses of an approved rabies vaccine administered either intramuscularly or intradermally on days 0, 7, and 21 or 28 with periodic booster doses or titre determination depending on the level of risk of potential exposure to the virus.

Cholecystopleural fistula with cholelithiasis presenting as a right pleural effusion.

At autopsy, multiple gallstones were recovered from the right pleural space of an elderly patient who presented with a massive right pleural effusion and septic shock. The mechanisms of gallstone migration and fistula formation between the gallbladder and right pleural space are described. Despite atypical presentations, gallbladder disease remains an important differential consideration of right pleural effusion in the elderly.

Prevalence of psammoma bodies in meninges and choroid plexuses of raccoons (Procyon lotor) from Parramore Island, Virginia.

Microscopic evidence of multifocal mineralizations (psammoma bodies) were seen in brains of 33/53 (62%) raccoons (Procyon lotor) necropsied on Parramore Island, Virginia. Most mineralized foci had concentric laminations and were present in small capillaries of meninges of the brain (15/33), in choroid plexus (3/33), or at both these sites (13/33). In 2 raccoons, the lesions were confined to the meninges of the proximal cervical spinal cord. In most cases, the affected vessels appeared to have been completely occluded. However, no evidence of ischemic changes in the brain parenchyma was seen, and none of the raccoons had abnormal neurologic signs prior to euthanasia. The condition appears to be a common incidental histopathologic finding in raccoons from the eastern United States. Although the exact cause of this condition is not known, a primary vascular insult with resultant dystrophic mineralization of the affected vessels is suspected.

Oral vaccination of wildlife against rabies: opportunities and challenges in prevention and control.

Rabies is an acute, progressive, fatal encephalitis caused by viruses in the Family Rhabdoviridae, Genus Lyssavirus. Rabies virus is the representative member of the group. Warm-blooded vertebrates are susceptible to experimental infection, but major primary hosts for disease perpetuation encompass bats and mammalian carnivores. The dog is the global reservoir, and important wild carnivores include foxes, raccoons, skunks, and mongoose, among others. Traditionally, reliance upon long-term, widespread, government-supported programmes aimed at population reduction of animals at risk has been unsuccessful as the sole means of rabies control, based in part upon economical, ecological and ethical grounds. In contrast, immunization of domestic dogs with traditional veterinary vaccines by the parenteral route led to the virtual extinction of canine-transmitted rabies in developed countries. Taken from this basic concept of applied herd immunity, the idea of wildlife vaccination was conceived during the 1960s, and modified-live rabies viruses were used for the experimental oral vaccination of carnivores by the 1970s. The development of safe and effective rabies virus vaccines applied in attractive baits resulted in the first field trials in Switzerland in 1978. Thereafter, technical improvements occurred in vaccine quality and production, including the design of recombinant viruses, as well as in the ease of mass distribution of millions of edible baits over large geographical areas. Over the past few decades, extensive oral vaccination programmes focusing upon the red fox, using hand and aerial distribution of vaccine-laden baits, have resulted in the virtual disappearance of rabies in Western Europe. The same dramatic observation held true for southern Ontario. During the 1990s in the United States, oral vaccination programmes concentrated upon raccoons, grey foxes, and coyotes, with similar success. For example, raccoon rabies has not spread west of the current focus in the eastern states, grey fox rabies is contained in west central Texas, and no recent cases of rabies have been reported from coyotes away from the Mexican border for several years. Despite the progress observed and the absence of substantive adverse environmental or health effects, oral vaccination is not a panacea, and should be viewed as an important adjunct to traditional prevention and control techniques in human and veterinary medicine. Local outbreak suppression of rabies among free-ranging wildlife is documented, and regional elimination of particular virus variants among specific, targeted carnivore hosts is demonstrable, but true disease eradication is not achievable at the present time by current techniques. For example, no practical vaccination methods have been designed for bats. Although lyssaviruses appear in relative compartmentalization between the Chiroptera and Carnivora, major spillover events have been detected from bats to carnivores, and phylogenetic analyses suggest a historical basis for extant viral origins due to interactions between these taxa. Thus, bio-political considerations aside, the possibility for pathogen emergence resulting from transmission by rabid bats with subsequent perpetuation among other animals cannot be discounted easily on any continent, with the possible exception of Antarctica. Clearly, given their biodiversity, distribution, and abundance, novel methods would be necessary to consider meaningful control of rabies in these unique volant mammals. Newer approaches in biotechnology may be envisaged some day for eventual extension to bats, as well as more widespread application to global canine rabies remediation in developing countries.

A vaccinia-vectored rabies vaccine field trial: ante- and post-mortem biomarkers.

During the field safety evaluation of a vaccinia-rabies glycoprotein recombinant virus vaccine for wildlife, two biomarkers were used to identify potential contact with vaccine-laden baits. Tetracycline, a commonly used and reliable calciphilic tissue marker, was included in a fish-meal polymer bait matrix and was evaluated from post-mortem bone samples. Additionally, an ante-mortem marker was needed to identify, for prospective study, raccoons which had contacted baits and thus, potentially, vaccine. Sulfadimethoxine (SDM) was included in an attractant slurry surrounding the bait, as a novel short-term seromarker. Preliminary laboratory studies in raccoons demonstrated SDM residues for up to one week following ingestion of a single 250 mg dose. During the first six days after bait distribution, 49 individual raccoons were live-trapped in the vaccination area. SDM was detectable in 38 of 49 (77.5%) serum samples. Similarly, 47 of 56 (83.9%) bone samples from raccoons collected in the vaccination area throughout the twelve-month study were tetracycline-positive. Conversely, none of the serum samples (n = 12) from the first six days of the trial nor any of the bone samples (n = 34) from raccoons in the surveillance area were biomarker-positive.

Cerebrospinal fluid analysis of rabid and vaccinia-rabies glycoprotein recombinant, orally vaccinated raccoons (Procyon lotor).

Cerebrospinal fluid obtained from clinically normal free-ranging raccoons was analyzed and compared with CSF obtained from raccoons vaccinated orally with vaccinia-rabies glycoprotein (V-RG) recombinant virus vaccine and subsequently challenged peripherally with street rabies virus, and CSF from naive, rabies virus challenge-exposed control raccoons. Significant differences were not found in CSF of free-ranging or V-RG recombinant virus vaccine recipient raccoons, and there was no evidence of CNS invasion by V-RG virus. The CSF of naive, rabies challenge-exposed control raccoons contained high numbers of lymphocytes and monocytes, compatible with rabies virus encephalitis. Although V-RG orally vaccinated challenge-exposed raccoons were protected from lethal rabies virus infection, a mild lymphocytic pleocytosis was evident at 90 days after challenge exposure.

Lymphosarcoma in a raccoon (Procyon lotor).

A case of lymphosarcoma in a captive adult female raccoon (Procyon lotor) from northeastern Pennsylvania (USA) was observed in 1991. Prior to its death the raccoon had lost weight. At necropsy the carcass was in poor body condition and had pale mucous membranes. The thoracic and abdominal lymph nodes were enlarged, soft, and pale tan. Microscopically, there was effacement of normal lymph node architecture by sheets of mononuclear cells. These were well-differentiated small lymphocytes with distinct cell borders. Nuclei of these cells were darkly stained and mitotic figures were frequently seen. Similar but lesser numbers of neoplastic cells were seen in the parenchyma of liver, spleen, and the pancreas. Since the neoplasm involved several organs, we propose that the condition was of multicentric origin. Gross lesions, histopathologic findings and the organs involved differed from a previously described case of lymphosarcoma in a raccoon.

First report of a Demodex sp. in raccoons (Procyon lotor).

Demodex spp. mites were seen in skin sections of 5 of 53 raccoons (Procyon lotor) necropsied on Parramore Island, Virginia (USA). In all infections, mites were present in the skin over the lower legs; in one raccoon they also were located in a follicle of a vibrissa. None of the raccoons had Demodex-related gross lesions. Histopathologically, minimal lesions were seen in the affected follicles. This is the first documentation of Demodex spp. in raccoons.

Lung lesions in an opossum (Didelphis virginiana) associated with Capillaria didelphis.

An opossum (Didelphis virginiana) live-trapped on Parramore Island, Virginia was infected with the lung parasite Capillaria didelphis. Lung lesions associated with this parasite were extensive and consisted of numerous areas with central necrosis deep within the parenchyma. Necrotic foci were present around airways and consisted of a mixture of inflammatory cells and cellular debris, adult nematodes and many bipolar eggs. This parasite causes severe verminous pneumonia in the opossum.

Notoedric acariasis in the porcupine (Erethizon dorsatum).

Six of 16 porcupines (Erethizon dorsatum) live-trapped in Sullivan County, Pennsylvania were infested with the mite Notoedres douglasi. Alopecia was evident in the ventral inguinal area and the infested skin was thickened, wrinkled and had multifocal areas of extensive hyperkeratosis. Microscopically the skin lesions consisted of extensive acanthosis and hyperkeratosis with variable cellular infiltrate in the dermis. Mites were seen in tunnels in the hyperkeratotic skin sections. This is the first report of notoedric acariasis in the porcupine.

Pancreatic duct hyperplasia in a raccoon (Procyon lotor) caused by Atriotaenia procyonis.

A raccoon (Procyon lotor) live-trapped in Philadelphia, Pennsylvania was heavily infected with the tapeworm Atriotaenia procyonis. Histopathologic examination of the duodenum revealed this tapeworm attached to the mucosa; the mucosa was mildly hyperplastic without a significant inflammatory infiltrate. This tapeworm was seen also within the proximal pancreatic duct and histopathologic lesions associated with its presence consisted of marked hyperplasia of mucosal cells, causing the formation of an extensive papillary projection into the duct lumen. Inflammatory cellular reaction was minimal, consisting primarily of lymphocytes, and was seen in the mucosa and submucosa of the duct. The presence of A. procyonis in the pancreas of this raccoon is considered to be an aberrant location for this parasite and has not been reported previously.

First North American field release of a vaccinia-rabies glycoprotein recombinant virus.

Following nearly 10 yr of extensive laboratory evaluation, a vaccinia-rabies glycoprotein (V-RG) vaccine was the first recombinant virus to undergo limited North American field release on 20 August 1990. The free-ranging raccoon population on Parramore Island (Virginia, USA) was exposed to a high density (10 baits/ha) of vaccine-laden baits distributed on a 300 ha vaccination area. An annual total of 887 raccoons were live-trapped for sedation, physical examination and blood collection for rabies antibody determination; there was no evidence of adverse effects or lesions due to the vaccine. Age and sex distributions, mean body weights, and live-capture histories of raccoons from the vaccination and non-baited control areas were compared. There were no statistically significant differences in survivorship between the baited and non-baited areas, nor between rabies antibody-positive and antibody-negative raccoons from the vaccination area. There was no trend in field mortality that suggested an association with either tetracycline or sulfadimethoxine, used as biomakers, or with vaccine contact determined by antibody status. No gross or histopathologic lesions due to the vaccine were demonstrated among a subsample of live-trapped raccoons collected for gross necropsy, biomarker analysis, histopathologic examination, and V-RG virus isolation attempts. Recovery of V-RG virus was limited to the tonsils of two biomarker-positive, clinically healthy raccoons collected from the vaccination area for postmortem examination on days 2 and 4 following bait distribution. These data reinforce the extensive body of safety data on the V-RG virus and extend it to include field evaluation where vaccine is offered free-choice in abundance, in baits designed to attract free-ranging raccoons, in a relatively simple ecosystem.

Dirofilaria immitis in a raccoon (Procyon lotor).

A single juvenile male raccoon (Procyon lotor) was found naturally infected with Dirofilaria immitis. Two immature female worms were found in the heart of this raccoon at necropsy. Lesions attributable to the presence of these parasites were not found. Histopathologic examination of various tissues did not reveal any microfilariae. The raccoon may serve as an aberrant definitive host for this parasite, however, patent infections have not been reported.

Phagicola angrense (Digenea: Heterophyidae) as a cause of enteritis in a raccoon (Procyon lotor).

Numerous Phagicola angrense were associated with enteritis in a single male juvenile raccoon (Procyon lotor) live-trapped on Parramore Island, Virginia (USA). The raccoon was weak, ataxic and had melenic soft feces. The carcass was emaciated, pale and had ascites. Mesenteric vessels appeared prominent and the stomach and the intestines contained fetid bloody material. The small intestinal mucosa contained three locally extensive sites of necrosis. Histopathologically, there were numerous small digeneans both attached to the mucosa and free within the lumen. Digeneans were usually found deep within the crypts where the epithelium was markedly attenuated and devoid of epithelial cells at the point of parasite attachment. In the lamina propria there were areas of acute hemorrhage and infiltration with plasma cells and eosinophils. This appears to be the first record of severe enteritis in the raccoon caused by this digenean.