Lessons for rabies control and elimination programmes: a decade of One Health experience from Bali, Indonesia.

Since the emergence of rabies on Bali, Indonesia, in 2008, the Indonesian Government and other stakeholders have implemented disease control and prevention activities with the aim of re-securing Bali's freedom from dog-mediated rabies. The authors report on the lessons learned during these efforts, and their applicability to other regions where canine rabies is endemic, as well as to rabies-free populations that are at risk from incursions. To eliminate rabies from Bali will require time and commitment, as well as a combination of approaches employing the principle of One Health. Efforts should be directed towards well-coordinated, highcoverage, annual dog vaccination campaigns using high-quality vaccines, and enhanced surveillance focused on investigations of biting animals. Bali, an island, is an ideal target for achieving freedom from rabies, but the logistics of vaccinating its very large, free-roaming dog population are challenging. Lessons can be drawn from Bali for other large and dense dog populations, where dog management and rabies control appear difficult. Well-trained teams with nets can rapidly catch and vaccinate large numbers of dogs where central-point vaccination is insufficient, and post vaccination surveys of collared dogs can be used to evaluate coverage and target supplementary vaccination. However, careful planning is required to ensure that all communities are reached during such campaigns and that sufficient vaccine is available over the following years. Effective communication strategies are needed to coordinate intersectoral activities, and to keep communities engaged, particularly during the 'end game', when the risk of rabies appears only minimal. An effective One Health approach to eliminate rabies requires long-term planning, multisectoral communication and coordination, and sustained effort, using tried and tested methods.

Suite à l'émergence de la rage à Bali (Indonésie) en 2008, le gouvernement indonésien et d'autre parties prenantes ont introduit des mesures de contrôle et de prévention de la maladie afin de sécuriser le statut précédemment indemne de Bali au regard de la rage transmise par les chiens. Les auteurs font le point sur les enseignements tirés de cette expérience et évaluent sa pertinence pour d'autres régions, par exemple celles où la rage canine est endémique ou qui possèdent des populations indemnes de rage mais exposées au risque d'une incursion du virus. L'élimination de la rage à Bali est une entreprise qui prendra du temps et exigera une grande détermination ainsi que le recours combiné à diverses méthodes suivant les principes Une seule santé. Les efforts devront s'orienter vers des campagnes annuelles de vaccination des chiens, qu'il faudra coordonner avec soin en assurant une couverture élevée et en faisant appel à des vaccins de haute qualité, et vers une surveillance accrue avec notamment l'investigation de tout chien responsable de morsure. De par son insularité, Bali constitue un territoire idéal pour réussir l'élimination totale de la rage, mais la logistique requise pour la vaccination est lourde, en plus du défi majeur que posent les effectifs importants de chiens errants. Les leçons tirées de l'expérience de Bali peuvent se révéler fructueuses dans d'autres régions dotées de populations canines denses et nombreuses et où les opérations de gestion de ces populations et de lutte contre la rage se présentent sous un jour peu favorable. Dans les contextes où il n'y a pas suffisamment de centres de vaccination, les chiens peuvent être capturés et vaccinés en grand nombre par des équipes bien entraînées et disposant de filets, tandis que le suivi post-vaccinal des chiens enregistrés offre un bon moyen d'évaluer la couverture vaccinale et de cibler les besoins supplémentaires. Il est essentiel de bien planifier ces campagnes afin de s'assurer qu'elles ont touché toutes les communautés et que les stocks de vaccins sont suffisants pour les années à venir. Des stratégies efficaces de communication sont nécessaires pour coordonner les activités intersectorielles et pour maintenir le niveau de motivation des communautés, en particulier en fin de campagne car les risques de rage sont alors perçus comme étant minimes. Pour être efficace, une approche Une seule santé d'élimination de la rage requiert une planification sur le long terme, une communication multisectorielle et des efforts de longue haleine recourant à des méthodes éprouvées.

Desde que en 2008 la rabia hizo su aparición en Bali (Indonesia), el Gobierno del país y otras partes interesadas han llevado a cabo una serie de actividades de control y prevención de la enfermedad con el objetivo de devolver a la isla la condición de «libre de la rabia transmitida por perros¼. Los autores dan cuenta de las enseñanzas extraídas de esta labor y examinan la viabilidad de aplicarlas a otras regiones donde la rabia canina es endémica, así como a poblaciones libres de rabia que corren peligro de sufrir incursiones de la enfermedad. Para eliminar la rabia de Bali hará falta tiempo y dedicación, así como una combinación de métodos regida por los principios de Una sola salud. Convendría centrar el trabajo en campañas anuales de vacunación de perros bien coordinadas, de amplia cobertura y realizadas con vacunas de gran calidad, que se acompañen de una vigilancia más intensa centrada en la investigación de los casos de animales mordedores. Por su condición insular, Bali ofrece condiciones idóneas para lograr la eliminación de la rabia, pero la logística de las vacunaciones es muy aparatosa y las poblaciones de perros vagabundos plantean grandes problemas. De la experiencia balinesa cabe extraer enseñanzas útiles para otras zonas que albergan poblaciones de perros amplias y densas, donde la gestión de estas poblaciones y la lucha antirrábica parecen resultar dificultosas. Allí donde la vacunación centralizada no baste, cabe desplegar equipos bien formados y provistos de redes que puedan capturar y vacunar rápidamente a un gran número de perros, empleando después, eventualmente, estudios posvacunales de los perros con collar identificativo para evaluar la cobertura y seleccionar objetivos de vacunación complementaria. Sin embargo, para llegar a todas las comunidades en el curso de tales campañas y tener la seguridad de disponer de un suministro suficiente de vacunas en los años subsiguientes hace falta una minuciosa planificación. Se necesitan asimismo dispositivos eficaces de comunicación para coordinar las actividades intersectoriales, y también hay que mantener movilizadas a las comunidades, especialmente en la fase final, cuando el riesgo de rabia parece ser mínimo. Todo método eficaz de eliminación de la rabia que parta de los postulados de Una sola salud exige planificación a largo plazo, comunicación y coordinación multisectoriales y una labor sostenida, con empleo de métodos de probada y contrastada eficacia.

Changes in the regulation and activity of glutathione redox system, and lipid peroxidation processes in short-term aflatoxin B1 exposure in liver of laying hens.

The purpose of this study was to investigate the short-term (48 hr) effects of feeding aflatoxin contaminated diet (170.3 µg/kg AFB1) in 49-week-old laying hens. Liver samples were taken at 12-hr intervals. Feed intake, body weight, absolute and relative liver weight were the same in groups. However, there was no feed intake during both dark periods (between 12nd to 24th and 36th to 48th hours of the experiment); therefore, aflatoxin intake was also negligible. Markers of initial phase of lipid peroxidation, conjugated dienes and trienes did not change as effect of aflatoxin, but terminal marker, malondialdehyde content was significantly higher at 12 hr as effect of aflatoxin. No significant difference was found in reduced glutathione concentration and glutathione peroxidase activity between the groups. Expression of glutathione peroxidase 4 gene (GPX4) was significantly reduced due to aflatoxin treatment at 12 and 24 hr, but induced later, while glutathione reductase gene (GSR) expression was significantly lower at 24 hr and glutathione synthetase gene (GSS) in aflatoxin-treated group at 12 hr. The results suggest that aflatoxin induced oxygen-free radical formation, but it did not reach critical level during this short period of time to cause activation of the expression of glutathione system.

Effect of nano-sized, elemental selenium supplement on the proteome of chicken liver.

The nano-sized (100-500 nm) selenium has higher bioavailability and relatively lower toxicity compared to other selenium forms. The objective of the present study was to compare liver proteome profiles of broiler chicken fed with control diet without Se supplementation and diet supplemented with nano-Se with 4.25 mg/kg DM. Differential proteome analyses were performed by two-dimensional gel electrophoresis (2D-PAGE) followed by tryptic digestion and protein identification by liquid chromatography-mass spectrometry (LC-MS). Seven hundred and eight spots were detected, and 18 protein spots showed significant difference in their intensity (p < 0.05) between the two groups. In response to nano-Se supplementation, the expression of 8 proteins was higher, and 5 proteins were lower in nano-Se supplemented group compared to control group. The functions of the differentially expressed proteins indicate that the high dose of selenium supplementation induced a dietary stress. Selenium supplementation may influence the metabolism of fatty acids and carbohydrates and antioxidant system, and increase the quantity of cytoskeletal actin and the expression of actin regulatory protein as well.

Short-term effects of T-2 toxin exposure on some lipid peroxide and glutathione redox parameters of broiler chickens.

The purpose of this study was to investigate the short-term effects of T-2 toxin exposure (3.09 mg/kg feed) on lipid peroxidation and glutathione redox system of broiler chicken. A total of 54 Cobb 500 cockerels were randomly distributed to two experimental groups at 21 days of age. Samples (blood plasma, red blood cell, liver, kidney and spleen) were collected every 12 h during a 48-h period. The results showed that the initial phase of lipid peroxidation, as measured by conjugated dienes and trienes in the liver, was continuously, but not significantly higher in T-2 toxin-dosed birds than in control birds. The termination phase of lipid peroxidation, as measured by malondialdehyde, was significantly higher in liver and kidney as a result of T-2 toxin exposure at the end of the experimental period (48th hour). The glutathione redox system activated shortly after starting the T-2 toxin exposure, which is supported by the significantly higher concentration of reduced glutathione and glutathione peroxidase activity in blood plasma at 24 and 48 h, in liver at 12, 24 and 36 h, and in kidney and spleen at 24 h. These results suggest that T-2 toxin, or its metabolites, may be involved in the generation of reactive oxygen substances which causes an increase in lipid peroxidation, and consequently activates the glutathione redox system, namely synthesis of reduced glutathione and glutathione peroxidase.

Bovine rabies in Turkey: patterns of infection and implications for costs and control.

The incidence of rabies in livestock is an important factor for estimating the economic impact of the disease, but obtaining reliable data is hindered by inadequate surveillance. In order to understand the contribution of livestock rabies to the overall burden of disease, the rabies incidence in cattle was investigated in detail for Turkey between 2008 and 2011. Data were compiled on cattle numbers, samples submitted for rabies diagnosis, vaccinated animals and positive rabies cases in animals for seven regions in Turkey. Rabies incidence in cattle fluctuated annually and differed between regions from 0·10 to 3·87 cases/100 000 animals. The positive influence of compensation schemes was observed. Livestock losses were conservatively estimated at around $250 000 international dollars per annum, although in areas where compensation schemes are not operating this could be an underestimate of the economic burden. Vaccination of cattle remains an option for disease prevention, although oral rabies vaccination through aerially distributed baits should be implemented to prevent the further spread of fox-mediated rabies, which could result in much greater economic costs.

Integrating the surveillance of animal health, foodborne pathogens and foodborne diseases in developing and in-transition countries.

Animal diseases, foodborne pathogens and foodborne diseases have enormous impacts upon the health and livelihoods of producers and consumers in developing and in-transition countries. Unfortunately, the capacity for effective surveillance of infectious disease threats is often limited in these countries, leading to chronic under-reporting. This further contributes towards underestimating the effects of these diseases and an inability to implement effective control measures. However, innovative communications and diagnostic tools, as well as new analytical approaches and close cooperation within and between the animal and human health sectors, can be used to improve the coverage, quality and speed of reporting, as well as to generate more comprehensive estimates of the disease burden. These approaches can help to tackle endemic diseases and build essential surveillance capacities to address changing disease threats in the future.

Detection of a rare CDKN2A intronic mutation in a Hungarian melanoma-prone family and its role in splicing regulation.

BACKGROUND: The major locus for melanoma predisposition is the cell cycle regulatory CDKN2A gene on chromosome 9p21. However, the frequency of germline coding mutations of the CDKN2A gene is lower than expected in melanoma-prone families linked to chromosome 9p21. OBJECTIVES: To investigate whether the rare IVS1+37 G/C intronic mutation of the CDKN2A gene, recently identified in a Hungarian melanoma-prone family, influences mRNA splicing regulation. METHODS: CDKN2A minigenes containing the wild-type and the mutant intronic sequence were created and transfected into HeLa cells with the aim of studying the mRNA transcripts. RESULTS: The results revealed the emergence of a differential splicing pattern from the wild-type and the mutant minigene, suggesting that this mutation may alter the splicing of CDKN2A primary mRNA and therefore might have a pathogenetic role in familial melanoma. CONCLUSIONS: We believe that these results confirm the importance of the identification and characterization of CDKN2A intronic mutations with a view to improving our understanding of the pathogenesis, and explain why the frequency of germline coding mutations of the CDKN2A gene is lower than expected in melanoma-prone families linked to chromosome 9p21.

Negative allometry of docosahexaenoic acid in the fowl lung and pulmonary surfactant phospholipids.

In a recent study (Comp. Biochem. Physiol. B. (2010)155: 301-308) we reported that the fatty acids (FA) of the avian (7 species) total lung phospholipids (PL) (i.e. lung parenchyma and surfactant together) provide allometric properties. To test whether this allometric scaling also occurs in either of the above components, in six gallinaceous species, in a body weight range from 150 g (Japanese quail, Coturnix coturnix japonica) to 19 kg (turkey, Meleagris gallopavo) the PL FA composition (mol%) was determined in the pulmonary surfactant, in native and in thoroughly lavaged lungs (referred to as lung parenchyma). In all three components docosahexaenoic acid (DHA) showed significant and negative allometric scaling (B = -0.056, -0.17 and -0.1, respectively). Surfactant PLs provided further negative allometry for palmitic acid and the opposite was found for palmitoleate and arachidonate. In the lung parenchymal PLs increasing body weight was matched with shorter chain FAs (average FA chain length) and competing n6 and n3 end-product fatty acids (positive allometry for arachidonic acid and negative for DHA). Negative allometric scaling was found for the tissue malondialdehyde concentration in the native and lavaged lungs (B = -0.1582 and -0.1594, respectively). In these tissues strong correlation was found between the MDA concentration and DHA proportion (r = 0.439 and 0.679, respectively), denoting the role of DHA in shaping the allometric properties and influencing the extent of in vivo lipid peroxidation of membrane lipids in fowl lungs.

Effect of dietary fatty acid pattern on growth, body fat composition and antioxidant parameters in broilers.

The effects of dietary fat supplementation on performance, fatty acid (FA) composition of tissues and antioxidant defence system of broilers were studied. Male broilers were placed in 20 floor pens (60 broilers per pen). The broilers were fed by diets with added different energy sources: lard (L); sunflower oil (SFO); soybean oil (SBO); and linseed oil (LSO). The treatments did not modify significantly growth performance and feed intake of the broilers. There was no effect of dietary FA pattern on reduced glutathione level and glutathione peroxidase activity of plasma, erythrocyte and liver samples. However, higher PUFA content of the diet resulted in a significant increase in malondialdehyde level of erythrocytes and liver. The broilers fed LSO diet more effectively maintained their antioxidant status with enhanced plasma radical scavenger capacity. FA composition in tissues reflected the FA pattern of the diets, although proportion of FAs with four or more double bonds was metabolic specific. LSO diet increased the level of C18:3, C20:5 and C22:6 in tissue lipids in relation to L, SFO and SBO diets. Significantly increased plasma radical scavenging capacity in concert with the enhanced C20:5 and C22:6 proportion in liver and muscle during LSO feeding indicate metabolic changes to counteract the oxidative injury. This may be related to the compounds produced after different biochemical pathways of n-6 and n-3 FAs.

Effects of ochratoxin A on some production traits, lipid peroxide and glutathione redox status of weaned piglets.

The effect of feeding ochratoxin A (OTA) contaminated diet (379.6 and 338.1 microg/kg in starter and grower diets) on production traits, lipid peroxidation and some parameters of the glutathione redox system were investigated in weaned piglets over a seven-week period. Feed intake and feed conversion ratio (FCR) did not differ significantly, but in the first phase (0-28 days) the daily weight gain was significantly lower in the piglets fed the OTA-contaminated diet. Lipid peroxidation, as measured by the amount of malondialdehyde, glutathione content and glutathione peroxidase activity, did not change significantly in the blood plasma and red blood cell haemolysate in the OTA-loaded group, while malondialdehyde content increased significantly in the liver and markedly but not significantly in the kidney of piglets fed OTA-contaminated feed. Glutathione content did not differ significantly in the studied organs of the two groups while glutathione peroxidase activity of the OTA-loaded animals was significantly lower both in the liver and in the kidney. The results suggest that the use of feed-stuffs contaminated with low levels of OTA for seven weeks did not cause marked differences in the production traits or in lipid peroxidation and amount or activity of the glutathione redox system in the blood plasma, red blood cells and kidney, while significant changes occurred in the liver homogenate.

Effect of feeding T-2 toxin contaminated feed on the utilisation of vitamin E in chickens.

The purpose of the present study was to investigate the effect of experimental T-2 toxin load (2.35 mg/kg of feed) and vitamin E supply in the drinking water (10.5 mg/bird/day) on vitamin E levels of the blood plasma and liver in broiler chickens in a 14-day experiment. It was found that T-2 toxin load did not influence vitamin E content of the blood plasma except at day 3 after the toxin load when a moderate increase was detected in plasma vitamin E. No significant changes were found in vitamin E content of the liver. The simultaneous use of high-dose vitamin E supplementation and T-2 toxin load caused a significantly higher plasma vitamin E content but the changes were less expressed in the group subjected to T-2 toxin load. Vitamin E supply also resulted in a marked and significant increase in vitamin E concentrations of the liver on days 3 and 7 even in the T-2 loaded group, but this concentration significantly decreased thereafter. The results show that T-2 contamination of the diet has an adverse effect on the utilisation of vitamin E in broiler chickens.

Investigation of lipid peroxide and glutathione redox status of chicken concerning on high dietary selenium intake.

This study was designed to investigate the effects of excess (24.5 mg Se/kg feed) inorganic and organic dietary selenium supplementation on 3-week-old broilers. The experiments lasted 4 days. Intensity of lipid peroxidation processes (malondialdehyde, MDA) and the amount (reduced glutathione, GSH) and activity (glutathione peroxidase activity, GSHPx) of gluathione redox system were measured in blood plasma, red blood cell hemolysate and liver. Voluntary feed intake in the selenium-treated groups reduced remarkably. Elevated GSH concentration and GSHPx activity were measured in plasma and liver of both selenium-treated groups compared to the untreated control and the 'pair-fed' controls. The lipid peroxidation processes in the liver showed higher intensity than the control due to both selenium treatment. The applied dose of selenite and selenomethionine does not inhibit, but even improves the activity of glutathione redox system in the liver during the early period of selenium exposure.

The Middle East and Eastern Europe rabies Expert Bureau (MEEREB) third meeting: Lyon-France (7-8 April, 2015).

MEEREB is an inter-regional network of countries from North Africa, Europe, the Middle East and Central Asia that work together with the aim of improving rabies control and prevention at local, regional and global level. MEEREB members met for the third time in 2015 in France (Lyon) to review the current rabies situation within the network and to discuss the way forward the prospect of a One Health approach against rabies. Dogs were the main vector of transmission in all MEEREB countries except for Croatia and Serbia where foxes represented the primary source. The number of rabies animal cases reported in 2014 varied substantially between countries with Ukraine reporting the highest number of animal cases. Human cases still occur in North Africa and all Middle East and Eurasian countries while no cases of human rabies were reported in Croatia, Serbia and Romania, although cases of rabies were identified in both dogs and foxes in 2014. Participants concluded that MEEREB can act as a think-tank where countries can share data, information, experiences and best practices to jointly address challenges in rabies control and prevention. They called for elimination of dog-transmitted rabies through vaccine and rabies immunoglobulin stockpiles and implementation of a One Health approach to achieve rabies's eradication.

Differential utilization of hepatic and myocardial fatty acids during forced molt of laying hens.

Feed was totally withdrawn from laying hens (n = 30, Hy-Line Brown, 608 d of age, 2.04 +/- 0.07 kg of mean BW) to induce molting. Ten birds were slaughtered on d 0 and 12, and the hepatic and myocardial triacylglycerol (TAG) and phospholipid (PL) fatty acid composition, as well as the tissue malondialdehyde (MDA) and reduced glutathione (GSH) concentrations were determined. The liver TAG and PL contents decreased by 24.3 and 16.1%, respectively, whereas the myocardial TAG content increased by 12%, and the PL decreased by 22%. Liver TAG fraction has been found to selectively retain arachidonic and docosahexanoic acids. Hepatic PL fatty acids were markedly affected by fasting; these changes reflected an altered PL metabolism, primarily degradation. Liver TAG compensated for the absence of dietary fatty acids, because we found practically no qualitative alteration in myocardial TAG. The lipid peroxide status, as measured with MDA content was, accordingly, increased in the liver tissue only. In the myocardial PL fatty acids, preferred conservation of arachidonic acid was shown, and it was hypothesized that energy deprivation of cardiomyocytes strongly improved PL degradation in fasting laying hens and influenced PL homeostasis. Generally the physiological recovery from forced molting associated with fasting is complete; however, the use of total feed withdrawal methods should be reevaluated.

Effect of different dietary fat sources on production traits, lipid peroxide status and on the glutathione redox system in African catfish [Clarias gariepinus (Burchell)] fingerlings. Short communication.

Lipids are used to provide the energy to cover the metabolic needs and to provide essential fatty acids, which are important for membrane function [12]. Fats may contain high level of long chain polyunsaturated fatty acids, which are prone to peroxidation [8] and will interact with the antioxidant defense system [1]. There is contradiction in the literature about whether the intake of fish oil enhance [7] or deplete [4] tissue antioxidant defenses and the glutathione redox system in different organisms. The aim of the present study was to examine the effects of different dietary oils on parameters of the lipid peroxide state and the glutathione redox system in C. gariepinus fingerlings.

The Pan-African Rabies Control Network (PARACON): A unified approach to eliminating canine rabies in Africa.

Even though Africa has the highest per capita death rate from rabies of any continent, and the disease is almost entirely transmitted by the bites of rabid dogs, there has been no coordinated pan-African approach to controlling canine rabies. In order to attain an inclusive and unified network, the Pan-African Rabies Control Network (PARACON) was established in 2014. By following the 'One Health' concept, which involves close coordination between animal and human health sectors across national, regional and continental levels, PARACON will provide a platform to facilitate and promote coordinated and sustainable control strategies and programmes. Meetings will take place at regular intervals and will be centred on the involvement by key focal persons from the medical and veterinary sectors. The inaugural meeting was held in South Africa in June, 2015 and was focused around interactive discussions and workshops, whilst updating country representatives on the tools available to aid them in developing and implementing sustainable rabies intervention strategies. Experts from various global organizations, institutions and industry participated in the discussions and shared their experience and expertise. The workshops focused on the latest format of the Rabies Blueprint platform (www.rabiesblueprint.com), which in the broadest sense assists with control and elimination campaigns, including educational and advocacy drives, improvement of surveillance and diagnosis and the systematic monitoring of progress. Together with the Stepwise Approach towards Rabies Elimination, the Blueprint is a planning tool to help countries free themselves from canine-transmitted rabies.

Palisading prostate granulomas following surgery.

Fifteen cases of palisading granulomas of the prostate occurring in patients with a history of previous prostate surgery are described and illustrated. This distinctive histologic lesion strongly resembles a rheumatoid nodule, but is not associated with connective tissue disease or infection and is probably related to prior transurethral prostatectomy or needle biopsy.

Graft-versus-host disease in fully allogeneic small bowel transplantation in the rat.

Small bowel and its mesentery contain considerable amounts of lymphoid tissue that can mediate graft-versus-host disease in small bowel transplant (SBT) recipients. Present studies determined the existence of GVHD in a fully allogeneic SBT model and examined the effect of donor pretreatment with ALS in eliminating GVHD. Adult male Lewis (Lew) rats received orthotopic small bowel transplants from untreated (LewxBN)F1 (LBNF1) donors (group 1) or Brown Norway (BN) donors that were untreated (group 2) or pretreated with ALS (days -2 and -1) (group 3). All recipients were treated with cyclosporine 15 mg/kg/day i.m. on days 0-6 postoperatively. Animals were weighed and examined daily for signs of rejection and GVHD. No animals in groups 1 or 3 showed any physical signs of GVHD, but all of those in group 2 had characteristic weight loss, diarrhea, and dermatitis between 4 and 6 weeks postoperatively, from which they all recovered. Histologic examination of skin and spleen at this time confirmed the presence of GVHD. The relative spleen weight [( spleen weight/body weight] x 100) of group 2 animals was also significantly greater than that of unoperated control Lew animals. Spleen cells obtained from group 2 animals at the time of subclinical GVHD, but not cells from group 1 or 3 animals, caused enlargement of popliteal lymph nodes when they were injected into the footpads of Lew rats. This study shows that GVHD can manifest itself in recipients of a fully allogeneic small bowel transplant even when rejection is prevented by effective immunosuppression with CsA. However, combined use of recipient treatment with CsA and pretreatment of donor animals with ALS eliminates all manifestations of GVHD.

Induction of graft-versus-host disease by small intestinal allotransplantation in rats.

Adult male (LewisXBrown Norway) F1 (LBNF1) rats received heterotopic small intestinal transplants from Lewis donors. Lewis-to-Lewis and LBNF1-to-LBNF1 isografts served as controls. All of the allograft recipients died after a median survival time of 16.2 days, but all isografted rats survived indefinitely. During the period of deterioration, allografted rats developed marked cutaneous erythema and became increasingly weak and cachectic. Histological changes of the skin, spleen, and grafts were characteristic of graft-versus-host disease (GVHD). There was a marked degree of relative splenomegaly. Injection of spleen cells obtained from LBNF1 rats with clinical GVHD into the foot-pad of syngeneic LBNF1 rats resulted in significant enlargement of the ipsilateral popliteal lymph node. The degree of lymph node enlargement was comparable to that induced in LBNF1 rats by injection of normal Lewis spleen cells. These results clearly demonstrate the ability of the small intestinal allograft to cause rapid and fatal GVHD in rats that are incapable of graft rejection.

Studies in small bowel transplantation. Prevention of graft-versus-host disease with preservation of allograft function by donor pretreatment with antilymphocyte serum.

Donor pretreatment with antilymphocyte serum (ALS) effectively prevents graft-versus-host disease (GVHD) in a unidirectional (parent-to-F1 hybrid) rat small bowel transplantation model. ALS must be administered prior to or at the time of transplantation, and the intraperitoneal route is more effective than subcutaneous administration. Donor pretreatment with ALS uniformly prevents GVHD without impairing subsequent allograft function as measured by absorption of dietary energy and nitrogen, weight gain, and bowel morphology. These rodent studies suggest that ALS treatment of donors as well as recipients in small bowel transplantation may be a highly effective, simple, and easily applicable method to prevent or ameliorate GVHD in human small bowel transplantation.