Historical, current and expected future occurrence of rabies in enzootic regions.

Rabies is one of the oldest recorded pathogens, with the broadest distribution of any known viral zoonosis. Antarctica is believed to be free of all lyssaviruses, but no laboratory-based surveillance has taken place to support this supposition. Re-introduction of the disease is possible in Pacific Oceania, as evidenced by a historical outbreak in Guam and the translocation of rabid bats to Hawaii. Australia is the only inhabited continent with enzootic rabies, without the presence of rabies virus. Europe and North America have broken the cycle of dog-mediated rabies, with a few remaining focal points in Latin America and the Caribbean, but wildlife rabies predominates. The greatest burden resides in the 'Old World'. The elimination of human rabies mediated via dogs by 2030 in Africa, Asia and the Middle East will not be simple, rapid or inexpensive, but it may be achievable through the use of widely available tools and the application of lessons learned during the course of the 20th century.

La rage est l'une des plus anciennes maladies infectieuses enregistrées et la zoonose virale la plus largement représentée dans le monde. On présume que l'Antarctique est indemne de tout lyssavirus mais cette hypothèse n'est étayée par aucune surveillance basée sur des analyses de laboratoire. Il existe une menace de réintroduction de la maladie en Océanie, comme l'ont révélé le foyer historique survenu à Guam ainsi que l'arrivée de chauves-souris enragées à Hawaï. L'Australie est le seul continent habité où la rage ne sévit pas à l'état enzootique, le virus de la rage y étant absent. L'Europe et l'Amérique du Nord ont mis fin au cycle de la rage transmise par les chiens, dont il ne subsiste que quelques rares foyers de propagation en Amérique latine ; en revanche, la rage sylvatique reste prépondérante dans ces régions. Le fardeau le plus lourd est supporté par l'Ancien Monde. L'élimination de la rage humaine transmise par les chiens à l'horizon 2030 en Afrique, en Asie et au Moyen-Orient ne sera pas une tâche facile, rapide ni exempte de coûts mais elle peut réussir grâce aux outils disponibles partout dans le monde et aux enseignements tirés de l'expérience acquise tout au long du xxe siècle.

La rabia, causada por uno de los patógenos más antiguos de los que hay constancia, presenta la distribución más amplia de cuantas zoonosis víricas se conocen. Se piensa que la Antártida está libre de todo tipo de lisavirus, pero no ha habido labores de vigilancia en laboratorio que prueben tal suposición. Oceanía está bajo la amenaza de reintroducción de la enfermedad, como demuestran el histórico brote registrado en Guam o el desplazamiento de murciélagos rabiosos a Hawái. Australia es el único continente habitado en el que no hay rabia enzoótica, esto es, en que el virus rábico no está presente. Europa y América del Norte han interrumpido el ciclo de la rabia transmitida por perros, de la que aún quedan contados focos en América Latina y el Caribe, aunque sigue prevaleciendo la rabia de la fauna silvestre. La carga más importante recae en el «Viejo Mundo¼. La eliminación de la rabia humana transmitida por perros para 2030 en África, Asia y el Oriente Medio no será sencilla, rápida ni barata, pero es factible si se emplean herramientas que ya están extendidas y se aplican las lecciones que hemos aprendido a lo largo del siglo XX.

Global rabies management: perspectives on regional strategies for prevention and control.

Rabies is a major neglected zoonotic disease, despite the availability of highly sensitive diagnostic tests and efficacious human and animal vaccines. Perpetuation of rabies among multiple species of bats and wild carnivores, together with the presence of diverse lyssaviruses, remains a challenge for the prevention and control of this disease. However, most of the global burden may be reduced by mass vaccination of dogs, the major reservoir. Elimination of human rabies mediated by dogs may be feasible, based upon the elicitation of herd immunity, the application of sound health economic principles for appropriate disease management and technology transfer to those developing countries where rabies is hyper-endemic. Global canine rabies elimination has clear benefits for public health, veterinary medicine and conservation biology, so these sectors must collaborate using a transdisciplinary 'One Health' approach that allows the creation of long-term regional strategies for enhanced surveillance and practical intervention.

La rage est une maladie zoonotique majeure, qui demeure négligée malgré l'existence de tests de diagnostic hautement sensibles et de vaccins efficaces chez l'homme comme chez l'animal. La persistance de la rage chez de nombreuses espèces de carnivores sauvages et de chauves-souris et la diversité des espèces de Lyssavirus continuent de poser des difficultés en termes de prévention et de lutte contre la maladie. Néanmoins, le fardeau mondial de la rage peut être considérablement réduit en pratiquant la vaccination massive des chiens, ces derniers constituant le principal réservoir. L'élimination de la rage transmise par les chiens est un objectif atteignable si l'on s'appuie sur des concepts solides en matière d'immunité à l'échelle des troupeaux, d'économie de la santé et de transfert technologique, tout en apportant des bénéfices mutuels accrus pour la santé publique, la médecine vétérinaire et la biologie de la conservation grâce à la mise en oeuvre d'une approche régionale pour la surveillance, les interventions, la certification et la collaboration pluridisciplinaire dans un contexte Une seule santé.

La rabia es una importante enfermedad zoonótica desatendida, y ello pese a que existen pruebas de diagnóstico de gran sensibilidad y vacunas de contrastada eficacia en personas y animales. La perpetuación de la rabia en múltiples especies de carnívoros silvestres y murciélagos y la presencia de diversos lisavirus siguen dificultando el trabajo de prevención y control de la enfermedad. Con todo, cabe reducir buena parte de la carga mundial que impone la rabia mediante la vacunación masiva de perros, que son su principal reservorio. Si se aplican conceptos sólidos en materia de inmunidad de rebaño, economía de la salud y transferencia de tecnología, abordando las labores de vigilancia, intervención, certificación y colaboración multidisciplinar desde una lógica regional y desde los postulados de «Una sola salud¼, la eliminación de la rabia humana transmitida por perros puede ser un objetivo factible y muy beneficioso para la salud pública, la medicina veterinaria y la biología de la conservación.

Eliminating canine rabies, the principal source of human infection: what will it take?

More than 50,000 people die of rabies each year; most are children in developing countries, and almost all have been bitten by dogs. Eliminating canine rabies throughout the world would save thousands of lives and would reduce the economic impact of the disease by dramatically reducing the requirement for postexposure prophylaxis (PEP). Lengthy experience in the industrialized countries and ongoing programs in Latin America, Africa, and Asia have shown that the elimination of rabies in dogs is an achievable goal. The presence of canine rabies in developing countries is associated with poverty, and most deaths occur in the lowest socioeconomic sectors. To be successful, national rabies control programs should share responsibility with local communities for prevention and control activities and maintaining disease-free status. Legislation should be adapted to local conditions and the realities of dog ownership. While the provision of PEP to all bite victims is affordable in many countries, it is usually beyond the capacity of impoverished nations, which deal with many other health priorities. Ministries of health should provide PEP, either free or with a charge preferably at a subsidized price, replacing the current system in many countries, in which biologics are sold by government-owned and private clinics at a cost beyond the means of bite victims. The public health sector should assume responsibility when animal control strategies are not effectively implemented or when PEP is not administered correctly or is not available. A global strategy is needed to identify gaps in surveillance and diagnosis, improve access to PEP and enhance canine immunization and population management. Such approaches based on a "One Health" model should be coordinated across regions, and should extend control efforts to other dog-related zoonoses. This article introduces a symposium in Antiviral Research on the elimination of canine rabies.

Immune surveillance of human cancer: if the cytotoxic T-lymphocytes play the music, does the tumoral system call the tune?

Accumulating evidence indicates that the innate and adaptive immune systems participate in the recognition and destruction of cancer cells by a process known as cancer immunosurveillance. Tumor antigen-specific cytotoxic T-lymphocytes (CTL) are the major effectors in the immune response against tumor cells. The identification of tumor-associated antigen (TAA) recognized primarily by CD 8(+) T-lymphocytes has led to the development of several vaccination strategies that induce or potentiate specific immune responses. However, large established tumors, which are associated with the acquisition of tumor resistance to specific lysis, are usually not fully controlled by the immune system. Recently, it has become clear that the immune system not only protects the host against tumor development but also sculpts the immunogenic phenotype of a developing tumor and can favor the emergence of resistant tumor cell variants. Moreover, it has become obvious that the evasion of immunosurveillance by tumor cells is under the control of the tumor microenvironment complexity and plasticity. In this review, we will focus on some new mechanisms associated with the acquisition of tumor resistance to specific lysis during tumor progression, involving genetic instability, structural changes in cytoskeleton, and hypoxic stress. We will also discuss the interaction between CTLs and tumor endothelial cells, a major component of tumor stroma.

Can rabies be eradicated?

Rabies, an acute progressive encephalitis, is an ancient zoonosis. Its distribution encompasses all continents, except Antarctica. Agents consist of at least 11 species orgenotypes of rhabdoviruses, in the Genus Lyssavirus. Susceptible natural hosts include all mammals. Primary reservoirs reside in the Orders Carnivora and Chiroptera. A plethora of variants, maintained by a diversity of abundant hosts, presents a challenge to a strict concept of true eradication. Globally, the domestic dog remains the most significant species for viral transmission, responsible for millions of suspect human exposures and tens of thousands of fatalities. As such, this single major target provides an ideal opportunity for focused intervention programmes in humane disease prevention and control, driven by laboratory-based surveillance and guided via modern epidemiological insights. Historically, substantial technical progress throughout the 20th century led to the development of safe, affordable and efficacious animal and human vaccines, resulting in declining disease burdens in selected developed and developing countries. Regional and local disease resurgence occurs, due in part to a combination of political and economic instability, environmental perturbations, and shifting government priorities. Society must recall that despite the recent recognition of other important emerging infectious diseases, none exceed the case fatality rate of rabies. Given the clear relevance of rabies in public health, agriculture, and conservation biology, substantive international progress must continue towards enhanced public awareness, human rabies prevention, wildlife rabies control, and canine rabies elimination, with renewed collaborative vigour.

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.

Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer.

BACKGROUND: AKT phosphorylation is a critical step in the activation of growth factor receptors and can mediate tumor resistance to anthracyclines. We evaluated the expression patterns and predictive value of phosphorylated AKT (pAKT) in breast cancer tissues. PATIENTS AND METHODS: pAKT expression was assessed by immunohistochemistry in 823 tumors from patients with early breast cancer enrolled in two randomized trials. The distribution of pAKT expression was correlated with HER2 and epidermal growth factor receptor (EGFR) expression. The predictive value of pAKT for the efficacy of adjuvant chemotherapy was determined by test for interaction. RESULTS: pAKT, EGFR, and HER2 were expressed in 119 of 781 (15%), 118 of 758 (16%), and 99 of 775 (13%) assessable tumors. Staining was positive for pAKT in 28 of 99 (28%) and 90 of 676 (13%) HER2+ and HER2- tumors (P < 0.001). pAKT was expressed in 15 of 94 (16%) and 75 of 563 (13%) HER2-/EGFR+ and HER2-/EGFR- tumors, respectively (P = 0.49). A positive staining for pAKT did not correlate with prognosis (P = 0.94), and did not predict the resistance to anthracyclines (test for interaction, P = 0.70). CONCLUSIONS: AKT phosphorylation is associated with HER2 expression but not EGFR expression in patients with early breast cancer. pAKT is not predictive for the efficacy of anthracycline-based adjuvant chemotherapy.

Efficacy of adjuvant chemotherapy according to Prion protein expression in patients with estrogen receptor-negative breast cancer.

BACKGROUND: Prion protein (PrPc) has been previously reported to be associated with resistance to proapoptotic stimuli. We evaluated whether the expression of PrPc was associated with the resistance to adjuvant chemotherapy in patients with estrogen receptor (ER) -negative breast cancer. PATIENTS AND METHODS: The expression of PrPc by primary tumors was assessed by immunohistochemistry in a series of 756 patients included in two randomized trials that compared anthracycline-based chemotherapy to no chemotherapy. The PrPc expression was correlated with ER expression and the benefit of adjuvant chemotherapy was assessed according to PrPc expression in patients with ER-negative tumors. RESULTS: Immunostaining analysis showed that PrPc was mainly expressed by myoepithelial cells in normal breast tissue. Tissue microarray analysis from 756 breast tumors showed that PrPc was associated with ER-negative breast cancer subsets (P < 0.001). Adjuvant chemotherapy was not associated with a significant risk reduction for death in patients with ER-negative/PrPc-positive disease [adjusted hazard ratio (HR) for death = 0.98, 95% confidence interval (CI) 0.45-2.1, P = 0.95], while it decreased the risk for death (HR = 0.39, 95% CI 0.2-0.74, P = 0.004) in patients with ER-negative/PrPc-negative tumors. CONCLUSION: These data indicate that ER-negative/PrPc-negative phenotype is associated with a high sensitivity to adjuvant chemotherapy.

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.

Assessing the burden of human rabies in India: results of a national multi-center epidemiological survey.

OBJECTIVE: Human rabies has been endemic in India since time immemorial, and the true incidence of the disease and nationwide epidemiological factors have never been studied. The main objectives of the present study were to estimate the annual incidence of human rabies in India based on a community survey and to describe its salient epidemiological features. METHODS: The Association for Prevention and Control of Rabies in India (APCRI) conducted a national multi-center survey with the help of 21 medical schools during the period February-August 2003. This community-based survey covered a representative population of 10.8 million in mainland India. Hospital-based data were also obtained from the 22 infectious diseases hospitals. A separate survey of the islands of Andaman, Nicobar, and Lakshadweep, reported to be free from rabies, was also undertaken. RESULTS: The annual incidence of human rabies was estimated to be 17,137 (95% CI 14,109-20,165). Based on expert group advice, an additional 20% was added to this to include paralytic/atypical forms of rabies, providing an estimate of 20,565 or about 2 per 100000 population. The majority of the victims were male, adult, from rural areas, and unvaccinated. The main animals responsible for bites were dogs (96.2%), most of which were stray. The most common bite sites were the extremities. The disease incubation period ranged from two weeks to six months. Hydrophobia was the predominant clinical feature. Many of the victims had resorted to indigenous forms of treatment following animal bite, and only about half of them had sought hospital attention. Approximately 10% of these patients had taken a partial course of either Semple or a cell culture vaccine. The islands of Andaman, Nicobar, and Lakshadweep were found to be free of rabies. CONCLUSION: Human rabies continues to be endemic in India except for the islands of Andaman, Nicobar, and Lakshadweep. Dogs continue to be the principal reservoir. The disease is taking its toll on adult men and children, the majority from rural areas, due to lack of awareness about proper post-exposure immunization. The keys to success in the further reduction of rabies in India lies in improved coverage with modern rabies vaccines, canine rabies control, and intensifying public education about the disease.

Imatinib enhances human melanoma cell susceptibility to TRAIL-induced cell death: Relationship to Bcl-2 family and caspase activation.

In order to define genetic determinants of primary and metastatic melanoma cell susceptibility to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we have applied oligonucleotide microarrays to TRAIL-sensitive primary T1 cells and TRAIL-resistant metastatic G1 cells treated or not with TRAIL. T1 and G1 cells are isogenic melanoma cell subclones. We examined 22 000 spots, 4.2% of which displayed differential expression in G1 and T1 cells. Cell susceptibility to TRAIL-mediated apoptosis was found to be correlated with gene expression signatures in this model. Some of the differentially expressed genes were identified as involved in ATP-binding and signaling pathways, based on previously published data. Further analysis provided evidences that c-kit was overexpressed in G1 cells while it was absent in T1 cells. The c-kit inhibitor, imatinib, did not restore TRAIL sensitivity, excluding a role for c-kit in TRAIL resistance in G1 cells. Surprisingly, imatinib inhibited cell proliferation and TRAIL-mediated apoptosis in melanoma cells. We investigated the possible involvement of several molecules, including c-ABL, platelet-derived growth factor receptor (PDGFR), cellular FADD-like interleukin-1 alpha-converting enzyme-like inhibitory protein (c-FLIP)(L/S), Fas-associated DD kinase, p53, p21(WAF1), proteins of B-cell leukemia/lymphoma 2 (Bcl-2) family and cytochrome c. Imatinib did not modulate the expression or activation of its own targets, such as c-ABL, PDGFRalpha and PDGFRbeta, but it did affect the expression of c-FLIP(L), BCL2-associated X protein (Bax) and Bcl-2. Moreover, c-FLIP(L) knockdown sensitized T1 cells to TRAIL-mediated apoptosis, with a sensitivity similar to that of cells previously treated with imatinib. More notably, we found that the resistance to TRAIL in G1 cells was correlated with constitutive c-FLIP(L) recruitment to the DISC and the inhibition of caspase 8, 3 and 9 processing. Moreover, c-FLIP(L) knockdown partly restored TRAIL sensitivity in G1 cells, indicating that the expression level of c-FLIP(L) and its interaction with TRAIL receptor2 play a crucial role in determining TRAIL resistance in metastatic melanoma cells. Our results also show that imatinib enhances TRAIL-induced cell death independently of BH3-interacting domain death agonist translocation, in a process involving the Bax:Bcl-X(L) ratio, Bax:Bcl-X(L)/Bcl-2 translocation, cytochrome c release and caspase activation. Our data indicate that imatinib sensitizes T1 cells by directly downregulating c-FLIP(L), with the use of an alternative pathway for antitumor activity, because PDGFRalpha is not activated in T1 cells and these cells do not express c-kit, c-ABL or PDGFRbeta. Caspase cascade activation and mitochondria also play a key role in the imatinib-mediated sensitization of melanoma cells to the proapoptotic action of TRAIL.

An epidemiological study of animal bites in India: results of a WHO sponsored national multi-centric rabies survey.

This was a WHO sponsored national multi-centric rabies survey and one of its objectives was to find out the incidence of animal bites, anti-rabies treatment practices, Pet dog population and their care. Twenty-one medical colleges chosen with geoscatter representation conducted the survey during February-August, 2003. The survey was conducted in 18 states, covering a population of 52,731 chosen randomly from 8500 households. The annual incidence of animal bites was high, 1.7% and it was more in rural areas (1.8%), children (2.6%) and poor/low income group (75%). The main biting animal was dog (91.5%), mostly stray (63%), followed by cat (4.7%). A high proportion of bite victims did not wash their wounds with soap and water (39.5%), preferred Government hospitals (59.9%) and nerve tissue vaccine (46.9%). The use of rabies immunoglobulin was low (2.1%). A single animal bite episode led to a loss of 2.2 man-days and the cost of medicines including anti-rabies vaccine was Rs.252 (US$6). The recourse to indigenous treatment (45.3%) and local application to wound (36.8%/) was quite prevalent. About 17% of households reported having a pet/domesticated dog and the pet dog: man ratio was 1: 36. Pet dog care/management practices were not satisfactory with a low veterinary consultation (35.5%) and vaccination (32.9%). The situation was slightly better in urban areas. The people also reported the presence (83%) and menace (22.8%) of stray dogs. It is recommended to initiate appropriate community awareness and dog vaccination campaigns and effective stray dog control measures.

Impact of zoonoses on human health.

By reviewing the most significant zoonotic disease outbreaks that have occurred mostly during the past ten years, the author provides a clear idea of how varied these diseases can be in regard to their aetiological agent, size and direct impact on public health. Most examples involve emerging zoonotic diseases caused by viruses and prions and transmitted to humans by a bite, close contact with affected live animals or carcasses, or through the consumption of their tissues. These outbreaks vary from very small and localised clusters of individual cases to millions of deaths, as reported during the past influenza pandemics. The author also shows that even for the larger outbreaks, the direct impact on public health measured by the morbidity and mortality of zoonoses is largely inferior to that of major communicable diseases that affect only humans, particularly human tuberculosis, malaria, HIV/AIDS. However, it is very difficult to predict the outcome on public health of these emerging zoonotic diseases since transmission patterns are not always sufficiently understood to assess this impact accurately. In addition, new modes of agent transmission may compound the initial impact on public health. Finally, the author indicates additional reasons that explain why these diseases are important by placing special emphasis on the financial losses recorded in both human and animal health and also the societal non-monetary losses these diseases can incur. Lessons learnt following major crises generated by the emergence of zoonotic diseases, such as bovine spongiform encephalopathy, severe acute respiratory syndrome and avian influenza, are provided.

Study of the dog population and the rabies control activities in the Mirigama area of Sri Lanka.

The national health authorities of Sri Lanka have adopted a combined strategy of rabies vaccination and stray dog removal to control endemic dog rabies. Despite the control efforts, an increase of animal and human rabies cases has occurred since 1994. As a consequence, a project to evaluate the national rabies control program has been started and a study focussing on the dog population and rabies control activities in a limited area of Mirigama was conducted. Information on canine abundance and the accessibility of dogs for rabies vaccination was obtained by a household survey, vaccination of dogs against rabies at several vaccination points, collar-marking, and transect line recapture. The number of unvaccinated dogs was estimated by using Bayesian methodology. The estimated number of dogs per square kilometre was 87 (95% credibility interval: 80, 93) for owned dogs and 108 (100, 116) for owned and ownerless dogs. Coverage after the immunisation campaign was 57.6% (53.3, 61.9%) if vaccination at the vaccination points was considered and 66% (60.4, 72.0%) if recently provided vaccination by private veterinarians was also taken into account. The proportion of households with at least one dog vaccinated varied between 59.1 and 94.2% within the catchment area of the different vaccination points. Unvaccinated dogs were puppies (12%), ownerless dogs (57%), and owned dogs, which were not presented for vaccination (31%). In order to improve the rabies immunisation coverage among dogs and to achieve complete elimination of rabies it was recommended that the 95% catchment area of each vaccination point be assessed, the distribution of vaccination points in the vaccination area be redefined if necessary, a system for the vaccination of dogs missing the vaccination campaign for dog owner-specific reasons be established, and an inexpensive marking system be used for vaccinated dogs.

[Brief review of the history of zoonoses]. / Brefs rappels sur l'histoire des zoonoses.

By studying the surviving documents describing surveillance and methods of control of zoonoses in the distant past, the history of the fight against these diseases can be retraced. Prior to the 20th Century, the best known zoonoses were, amongst others, rabies, anthrax, glanders, tuberculosis, plague, yellow fever, influenza, and certain zoonotic parasitic diseases. An analysis of historical events yields a number of lessons as to the positive and negative influences of past theories regarding the aetiology, contagiousness and control of these diseases. These lessons serve as a reminder, to all those involved in the fight against emerging zoonoses, of the urgent need for extensive research on the aetiology and mode of transmission of these zoonoses, in addition to the need for timely application of the findings of such research to disease control activities.

Public health implications of emerging zoonoses.

Many new, emerging and re-emerging diseases of humans are caused by pathogens which originate from animals or products of animal origin. A wide variety of animal species, both domestic and wild, act as reservoirs for these pathogens, which may be viruses, bacteria or parasites. Given the extensive distribution of the animal species affected, the effective surveillance, prevention and control of zoonotic diseases pose a significant challenge. The authors describe the direct and indirect implications for public health of emerging zoonoses. Direct implications are defined as the consequences for human health in terms of morbidity and mortality. Indirect implications are defined as the effect of the influence of emerging zoonotic disease on two groups of people, namely: health professionals and the general public. Professional assessment of the importance of these diseases influences public health practices and structures, the identification of themes for research and allocation of resources at both national and international levels. The perception of the general public regarding the risks involved considerably influences policy-making in the health field. Extensive outbreaks of zoonotic disease are not uncommon, especially as the disease is often not recognised as zoonotic at the outset and may spread undetected for some time. However, in many instances, the direct impact on health of these new, emerging or re-emerging zoonoses has been small compared to that of other infectious diseases affecting humans. To illustrate the tremendous indirect impact of emerging zoonotic diseases on public health policy and structures and on public perception of health risks, the authors provide a number of examples, including that of the Ebola virus, avian influenza, monkeypox and bovine spongiform encephalopathy. Recent epidemics of these diseases have served as a reminder of the existence of infectious diseases and of the capacity of these diseases to occur unexpectedly in new locations and animal species. The need for greater international co-operation, better local, regional and global networks for communicable disease surveillance and pandemic planning is also illustrated by these examples. These diseases have contributed to the definition of new paradigms, especially relating to food safety policies and more generally to the protection of public health. Finally, the examples described emphasise the importance of intersectorial collaboration for disease containment, and of independence of sectorial interests and transparency when managing certain health risks.