Bioterrorism : crime and opportunity

The unprecedented and tragic terrorist attacks in the United States (US) have sent shock waves through national administrations that have grown accustomed to fighting expenditure wars in the health area and had relegated public health vigilance and emergency preparedness to the back burner. It was obvious from the immediate reaction to the horrors and menaces of the autumn of 2001 that, insofar as health and safety is concerned, governments continued to measure success by the degree of quietness, remoteness and uneventful normality that is achieved by those entrusted with the responsibility to protect health. The paradox of health and safety is that you are winning when you hear nothing: any publicity is bound to be bad publicity.


Bioterrorism: crime and opportunity
David Byrne, European Commission The unprecedented and tragic terrorist attacks in the United States (US) have sent shock waves through national administrations that have grown accustomed to fighting expenditure wars in the health area and had relegated public health vigilance and emergency preparedness to the back burner.It was obvious from the immediate reaction to the horrors and menaces of the autumn of 2001 that, insofar as health and safety is concerned, governments continued to measure success by the degree of quietness, remoteness and uneventful normality that is achieved by those entrusted with the responsibility to protect health.The paradox of health and safety is that you are winning when you hear nothing: any publicity is bound to be bad publicity.
In time-honoured fashion, administrations at all levels have been prompted by the sudden and massive loss of life and limb and the media attention and public pressure that was instantly generated, to reconsider how ready and able they are to prevent or mitigate the impact of threats to health and safety.Bioterrorism entered the collective psyche as food scares had done after the BSE crisis and radiation after Three Mile Island and Chernobyl.It caused a root-and-branch review by administrations of preparedness and emergency plans to face up to acts and attacks such as those that have taken place in the US, but also to other situations, as unimaginable now as anthrax spores sent through the mail or aircraft driven against buildings were before September 2001.
The paper by Bruno Coignard in this issue of Eurosurveillance paints a rather disappointing picture not so much of the bioterrorism preparedness and response in European public health institutes but of the degree of foresight and resources that were -and are -there to fight not hoaxes but real attacks.The commendable survey that the Eurosurveillance editorial board has commissioned documents both how health professionals rose to the task but also the woefully inadequate resources and arrangements that were available to cope with a real act or a credible menace.To their credit, the institutes did not conceal certain unsettling facts, such as the lack of standardised procedures, the need for syndrome-based investigation guidelines, the absence of coordination among services and across disciplines and the reluctance or hesitation to communicate with ➤ NUMÉRO SPÉCIAL SUR LE BIOTERRORISME / SPECIAL ISSUE ON BIOTERRORISM ➤ et instituts.Néanmoins, quelques leçons déjà retenues par le passé lors des efforts pour renforcer la capacité de la surveillance épidémiologique en Europe, ont été confirmées : l'utilité de partager les ressources de laboratoire, les avantages des approches intégrées, et la nécessité de consolider les systèmes de surveillance et de contrôle existants.
Les préparatifs de mise en place de ce programme, qui vise à renforcer et à améliorer les dispositions existantes, ainsi qu'à adapter les actions et la législation, sont en cours avec la création d'une Force d'Action comprenant les pays membres et les officiels de la Commission, et impliquant des partenariats avec des pays tiers et l'OMS.
Au vu de la qualité des recommandations diffusées par les articles de ce numéro d'Eurosurveillance, je pense que nous sommes sur la bonne voie pour fournir à la société le bouclier dont elle a besoin pour se débarrasser de ce fléau du 21 e siècle.s ➤ colleagues in other countries and organisations, to inform and be informed.But certain familiar lessons, well known from past efforts to boost epidemiological surveillance capacity across Europe, were once more confirmed: the usefulness of sharing laboratory resources and the benefits of using integrated approaches and building on existing surveillance and control structures.
Thinking the unthinkable and devising neat strategies to counter its occurrence and effects was the objective of D. Levy-Bruhl and N. Guérin in examining the most plausible, maximum health damage, scenario that would involve a biological agent, based on the physical history of the disease and the scarce epidemiological data that are available.Smallpox has come back to haunt us as it did our ancestors for thousand years only this time as a guest invited by miscreants and criminals and not as virus non grata with which humanity had come to cope as best as it could.The authors of this timely rejoiner have produced valuable advice on how to face a deliberate release of the once-thought dead and buried pathogen.Sensibly, they caution against sweeping measures and generalisations and recommend a tiered and targeted approach to well-guessed scenarios; whether this advice will appear convincing to decision makers or withstand knee-jerk reactions and media and societal pressures will have to be seen.
Richard Harling and his colleagues delved deeply into the bioterrorism lessons and scenarios previously considered and came up with a structured agenda for turning the present state of non-preparedness and doubt into a state of readiness and confidence.Although touching on the issue of chemical and radio-nuclear agents and stressing the serious difficulties that would arise from a covert attack in which a combination of agents are involved, the paper, coming from the communicable disease surveillance community, understandably confines itself to addressing the biological agent risks.In this area it does, however, reflect current thinking both at national and European Union level and is concordant with the action programme of cooperation on preparedness and response to biological and chemical agent attacks (health security) that the European Commission announced in its communication of November 18th, 2001 on the state of preventive alert against possible emergencies.This programme, drawn up by the Commission and the Member States following the guidelines laid down by the Health Ministers of the EU, has four objectives: • Set up a mechanism for information change, consultation and coordination for the handling of health related issues related to attacks in which biological and chemical agents might be used or have been used; • Create a EU-wide capability for the timely detection and identification of biological and chemical agents that might be used in attacks and for the rapid and reliable determination and diagnosis of relevant cases; • Create a stock of medicines and medical supplies and health services database and a stand-by facility for making medicines and health care specialists available in cases of suspected or unfolding attacks; • Drawup rules and disseminate guidance on facing up to attacks from the health point of view and coordinating the EU response and links with third countries and international organisations.
Preparations for the implementation of the programme, which will build on and improve present arrangements and will adapt measures and legislation are proceeding apace with the setting up of a Task Force comprising Member States and Commission officials and involving partnerships with third countries and the World Health Organisation (WHO).
The Commission is following up the call of the Göteborg European Council for a new centre on communicable diseases which will serve to build on and improve present arrangements -administrative and legislativewithin the Community Network on communicable diseases set up by Decision EC/2119/98 and in which public health institutes play a significant role.
The integration of the results of the Task Force within this framework will not only be crucial in the defence against terrorism from biological or chemical agents but will serve to strengthen protection of public health from disease and harm from pathogens found naturally in our environment.The role of the public health institutes in advising in this process and in the implementation of the programme will be most important.
Judging by the quality of advice already proffered by the papers in this issue of Eurosurveillance, I believe we are well on the way of delivering the shield that society needs against the scourge of the 21st century.s

Bioterrorism preparedness and response in European public health institutes
Bruno Coignard, Institut de Veille Sanitaire, Saint-Maurice, France, on behalf of the members of the Eurosurveillance editorial board.
The terrorist attacks on 11 September 2001 and the deliberate release of anthrax in the United States had consequences for public health not only there, but also in Europe.Europe's public health systems had to manage numerous postal materials possibly contaminated with anthrax.Our survey aimed to document the response of European public health institutes to recent bioterrorist events to identify the gaps that need to be addressed; 18 institutes from 16 countries participated in this Euroroundup.Bioterrorist threats in Europe were hoaxes only, and should be considered as a "preparedness exercise" from which three lessons can be drawn.Firstly, because of inadequate preparedness planning and funding arrangements, Europe was not ready in October 2001 to respond to bioterrorism.Secondly, although European institutes reacted quickly and adapted their priorities to a new type of threat, they need adequate and sustained support from national governments to main-Introduction W ithin 24 hours of the terrorist attacks on 11 September, the Cen- ters for Disease Control and Prevention (CDC) deployed epidemiologists to assess the consequences of the disaster and to reinforce surveillance for potential acts of bioterrorism (BT) (1).Less than a month later, on 4 October 2001, CDC reported a fatal case of inhalation anthrax in Florida (2).Subsequently, a total of 22 cases of anthrax have been identified in five different states; five of the patients died.All but two have been directly associated with the deliberate release of anthrax.More than 100 epidemiologists were deployed by CDC during one of its most challenging investigations, which is still in progress (3)(4)(5)(6)(7)(8)(9).
Although the terrorist events took place in the United States (US), European armed forces were put on heightened alert, and public health systems in European countries had to manage numerous letters containing powders suspected to be contaminated with Bacillus anthracis spores.Neither terrorist attacks nor anthrax cases occurred in the following weeks; all bioterrorist threats seemed to be hoaxes.The pressure on European countries, however, was high, as they quickly had to devote public health resources to face a new type of threat.
The objective of our survey was to document the role of European public health institutes in BT preparedness and response (P&R) in the year before and the month after 4 October 2001, with special emphasis on their recent response to possible bioterrorist threats.

Population and Methods
For each European public health institute, key contacts in the area of BT P&R were identified with the help of Eurosurveillance editorial board members.Seventeen institutes -in the 15 countries of the European Union, Norway, and Estonia -were included.
The survey was conducted using a self administered questionnaire, which addressed the following issues on BT P&R: description of the national public health institute, response to recent threats, P&R in the year before and the month after 4 October 2001, communication, and plans for the future.Eurosurveillance editorial board members reviewed the questionnaire, which was mailed electronically to all participants on 22 November.Participation in the survey was voluntary, and the questionnaires had to be sent back by 14     Eight institutes reported having performed in 2000 at least one communicable disease outbreak investigation, by deploying a national team to help trial investigations of an outbreak.

First actions
All institutes but one organised specific meetings on BT immediately after, or even before 4 October: two organised their first BT meeting the week before, nine one week after, and six two weeks after.Among the first actions taken by institutes, 14 reinforced communicable disease surveillance systems, and all created or updated BT related guidelines.One third reported other actions, such as increasing laboratory capacity, organising collaboration with authorities, delivering information to the public, media, or professionals, or setting up a hospital based epidemiological correspondent network.The duty system was reinforced in 14 institutes: one third had epidemiologists on call 24 hours a day and seven days a week; two had extra laboratory technicians on call.

Importance of threats according to countries
European countries experienced the first threats of contaminated letters four to 13 days after 4 October.Thirteen countries were able to provide a summary figure of these threats.They managed from 50 to 2790 threats from 4 October to 3 November; the total number of threats was 7622.The number of threats per 100 000 inhabitants ranged from 0.2/100 000 to 31.4/100 000 (median 3.6/100 000).Three countries (Denmark, Portugal, and Luxembourg) had the highest cumulative incidences of mail threats (18.9, 20.3, and 31.4,respectively) while three (Austria, Italy, and Spain) reported lower incidences ranging from 0.2 to 1.1 (figure).The proportion of mail threats that required laboratory testing ranged from 22 to 100% (median 57%).The proportion of threats that required follow up (remotely or on site) by national institutes ranged from 0 to 90% (median 17%) (table 1).Four institutes conducted on site investigations of some of the threats.
The number of people put on antibiotic prophylaxis during the same period (reported by 12 countries) ranged from 0 to 1500 (median 128); total number for reporting countries was 2237.Two countries reported false alerts of contaminated water works.

Laboratory capacity
Of 16 countries, 12 reported a national laboratory capacity for all four biological agents most likely to be involved in a deliberate release (anthrax, botulism, plague, and smallpox); all countries had capacity for anthrax and botulism, 12 for smallpox, and 14 for plague.Ten countries also reported laboratory capacity for other agents including tularaemia (eight) and viral haemorrhagic fever (five).
All countries but one used Gram stains, cultures, and polymerase chain reaction (PCR) for diagnosis of B. anthracis from human samples.Scientific methods for environmental sampling and testing were not in the public domain and rarely reported; three countries reported having tested suspected letters for agents other than B. anthracis.

Preparedness
Seven countries reported having a BT P&R plan ready in the year before 4 October; six had appointed a national BT P&R team.In the month after 4 October, all reported implementing such a plan; 12 countries had appointed a national team.Partners in this team included ministries of health in 12 countries, local health departments in nine, reference laboratories in 11, armed forces in eight, civil defence agencies in 10, ministries of internal affairs in 10, ministries of justice in four, hospitals in 12, or primary care physicians in three.➤ Tous les instituts étaient chargés du contrôle et de la surveillance des maladies transmissibles dans leurs pays.Leurs autres domaines d'expertise comprenaient la microbiologie pour 14 instituts et la santé environnementale pour 12 autres.Sept instituts déclaraient des activités complémentaires telles que la vaccinologie, les maladies chroniques et les accidents, la santé au travail ou la toxicologie.

Resources
In the year before 4 October, one institute had a specific budget for BT P&R, and two reported having a BT P&R unit or core team.A total of two full time equivalent (FTE) scientific personnel were specifically devoted to BT related activities in two European institutes during the same time period; 29 FTEs from five institutes could have been included as a "surge" capacity.One month after 4 October, seven institutes had a specific budget for BT P&R, and 11 had constituted a BT P&R unit or core team.In October 2001, a total of 33 FTEs were specifically devoted to BT related activities in nine institutes; 113 FTEs from 16 institutes could have been included as a surge capacity.Two fellows from the European Programme for Intervention Epidemiology Training (EPIET) were involved in BT related activities in the year before 4 October; six were involved one month after.

Epidemiological procedures
All European institutes created or updated guidelines and recommendations related to BT prevention and control in the month after 4 October (table 2).When writing guidelines related to specific biological agents, 14 institutes used national case definitions, 11 European case definitions, 10 CDC case definitions, and seven World Health Organization (WHO) case definitions.Five institutes shared definitions they used with other European institutes.
In the year to 4 October, four institutes reported sharing these guidelines outside their own institution.This number increased to 17 after this date: four institutes published some of them in medical journals; 14 posted them on their web site; 13 provided advice to decision makers; and 13 organised press releases or conferences.No institute organised training sessions on BT P&R in the year before 4 October, but five organised a total of nine training sessions in the month after.

Laboratory procedures
Laboratory testing of suspected letters was reorganised shortly after 4 October when countries experienced numerous threats.The year before this date, six countries reported dedicating one national or a few regional laboratories to this purpose.The month after 4 October, 12 reported dedicating one national laboratory, six several regional laboratories, and two using any laboratory available in their country.

National pharmaceutical stockpiles
European countries increased their stockpiles of pharmaceuticals shortly after 4 October 2001: 11 countries reported stocking ciprofloxacin in October.The total number of 60 day courses available in the six countries that reported this information was 87 540, that is, one course for 816 inhabitants.Nine countries reported having a smallpox vaccine stockpile in October; the total number of doses available in six countries that reported this information was 13 400 000 -one dose for 11 inhabitants.

Communication between countries for bioterrorism preparedness and response
Of 18 institutes contacted, 17 contacted other public health institutions about recent BT events in October 2001.Fifteen contacted other European institutes, 12 CDC, seven the WHO headquarters in Geneva, four the European Commission Directorate-General for Health and Consumer Protection (DG-SANCO), and three the WHO Regional Office for Europe in Copenhagen.
The objectives of these contacts were for 17 institutes to share information on BT threats in the United States or in Europe, for 11 to get epidemiological expertise, and for 10 to get laboratory expertise.Seventeen institutes received the information they requested from these institutions.
In addition to contacting public health institutions, all European institutes used other means to get information on recent BT events: all accessed the internet and browsed the web, 17 read the ProMed mailing-list, 17 reviewed the medical literature, and 15 reviewed the press.

Plans for the future
Of 18 institutes contacted, 16 plan to improve their BT P&R capacity in the next year.At the time of the survey, five institutes already had a budget for this activity in 2002.
Three institutes planned to create a specific BT P&R unit, and seven to recruit additional personnel: one to 18 (median 5) FTE personnel will be recruited next year in each of those institutes; zero to 16 (median 1) will be specifically devoted to this activity.According to this survey, a total of 47 FTE personnel will be recruited in Europe next year, of them being exclusively involved in BT related activities.Lastly, institutes planned to organise training in BT P&R in the next year.

Discussion
In October 2001, BT P&R plans were set up or updated by individual European countries.They often were classified, however, and thus prevented, at least in the beginning, effective and true discussions between European institutes.This was a major problem and we believe that such activities should be made public.We thank all respondents for the information they shared, even if individual countries could not be identified in this report.This survey is not an inventory: it is a first attempt to document the response of European public health institutes to recent BT events in order to identify the gaps that need to be addressed.We encourage national institutes to complete this picture and submit to Eurosurveillance any additional information about their recent experience.
The deliberate release of B. anthracis spores through the postal service inspired copycats, and countries had to manage numerous potentially contaminated letters.All but four countries reported the total number of mail threats they managed.It varied greatly by country and was not related to their size; such differences may be related to differences in case definitions or data collection procedures.➤ ➤ s'expliquer par des différences concernant les définitions de cas ou les procédures de recueil des données.
➤ Most European countries were not prepared to face possible bioterrorist threats: less than half reported having a BT P&R plan ready in the year before 4 October, and European institutes were not systematically a part of it.When institutes were associated, resources and funding specifically devoted to this activity were scarce.Logically, BT related efforts were rare.In the US, CDC's efforts in BT P&R began in 1998 (10).The US Department of Health and Human Services spent $158 million in 1999 for BT P&R and $230 million in 2000 (11).This budget increased in 2001 and will most likely do so again in 2002.Even if BT P&R cannot be summarised only on budget, this proves that the US administration had an early and strong commitment to public health as a response to bioterrorism.To date, most of these funds were used to improve the capacities of state and local health departments.CDC's goals are to improve public health infrastructure not only to respond to a bioterrorist event but also to any infectious disease outbreak (10).
One can argue that communicable diseases resulting from bioterrorist acts only differ from "normal" ones in the nature of their source: deliberate release as opposed to natural occurrence.Europe's public health institutes therefore have the expertise to respond to both.Adequate resources, however, are needed.We wanted to assess resources in personnel and tried to get the total number of epidemiologists working on communicable disease surveillance and control in European countries.However, we could not obtain reliable estimates, as the definition of an epidemiologist varies from one country to another.Another way to assess capacity of European public health institutes was to ask if national institutes had performed at least one outbreak investigation in 2000.Less than half reported such an activity; some institutes reported not being given a mandate to carry out outbreak investigation, or only providing remote support to local health departments.What we know for certain is that existing communicable disease surveillance and control personnel in European institutes were assigned new duties.The total number of FTE involved in BT related activities in European institutes dramatically increased in October 2001; EPIET fellows participated in this effort and would have been available for outbreak response (12).
The management of possible bioterrorist threats requires standardised procedures.As only a few countries had a BT P&R plan ready before 4 October, most of the necessary guidelines were prepared during the crisis.They first addressed priorities such as management of potential exposures to biological agents.They also addressed investigation and control of the four biological agents (anthrax, botulism, plague, and smallpox) most likely to be involved in a bioterrorist attack.Bioterrorist threats are, however, not limited to this short list and a covert release of biological agents may be difficult to recognise.Syndrome based investigation guidelines are needed, but only one third of institutes had these prepared.Regarding surveillance, most of the institutes reported having reinforced relevant communicable disease surveillance systems.Respondents did not, however, describe procedures: guidelines may have been written, but we do not know if and how surveillance systems were enhanced.
Laboratory testing also was a crucial element in the management of possible bioterrorist threats.Before 4 October, only a few countries had identified specific laboratories (national or regional) for mail testing, and only half did so for patient testing.A more centralised approach was progressively adopted after this date.The proportion of mail testing varied greatly by country.Highest proportions were observed among countries managing the lowest number of threats.In countries facing a greater number of threats, national laboratory capacities were probably exceeded, and specific, more rational testing strategies were implemented.Lastly, although all countries reported laboratory capacity for anthrax, four and two countries did not have laboratory capacity for smallpox and plague, respectively.Additional surveys will be needed to assess more precisely the capacity of European laboratories.For rare organisms that could be involved in a bioterrorist act -for example, anthrax, Francisella tularensis, or smallpox viruses -it may be better to establish good reference laboratories at the European Union level than to disperse scarce resources in multiple countries.European cooperation in BT will require sharing of laboratory resources.
Multiple partners participated in the management of possible bioterrorist threats.National public health institutes were only one element of the response, alongside local health departments, reference laboratories, ministries of health, healthcare organisations, primary care physicians, justice departments, and police and armed forces.None were involved in BT P&R teams.Local health departments and primary care physicians especially were underrepresented.These personnel may be at the forefront of an outbreak, especially in the case of a covert release, and efforts should be made to involve and train them adequately.Lastly, national BT P&R teams had very few meetings the year before 4 October.Some respondents reported issues in information sharing, action coordination, or identification of responsibilities.Those issues could have been avoided if all personnel had met previously and knew each other.
All countries that did not have a BT P&R plan implemented one immediately after 4 October.However, one can imagine that such "emergency" plans are still preliminary and will need further development.Almost all institutes added BT activity to their usual duties without additional resources, and reallocated personnel were not available for regular communicable disease control activities.Responses from institutes therefore had limits.Most of the institutes want to improve their BT P&R capacity in 2002, and reinforcing existing communicable disease surveillance and control departments seems to be the favourite, integrated approach.Some countries, however, plan to create a specific BT P&R unit.At the time of our survey, only a few institutes already had a specific budget for BT related activities in 2002.Increased and sustained support from governments will be required if European institutes want to develop their BT P&R.
Support from the European Commission may help, especially to coordinate actions and avoid duplicated efforts.Input from the Commission in the recent crisis, however, was late and respondents to the survey emphasised the need for anticipation, coordination, and support at the European level.The need for close liaison and timely communication with international agencies and other national institutes was underlined also.As a matter of fact, only a few institutes exchanged information with DG-SANCO or the WHO Regional Office for Europe in October 2001.Consequently, all institutes had similar activities: they followed events in the US, managed potentially contaminated postal materials, wrote guidelines, and provided advice to multiple partners.Only a few institutes shared the case definitions they used in guidelines; most of them were national definitions.The absence of common European BT related epidemiological procedures may be an issue in the case of an outbreak involving more than one country.Europe is currently debating the creation of a technical coordination unit (TCU) for communicable disease surveillance and outbreak response (13,14); such a unit would provide a formal structure with a high level of scientific expertise in communicable disease control.In addition to an increased investment in EPIET and related national training programmes (12), it would greatly enhance the future response capacity of Europe to bioterrorist attacks.

Conclusion
Bioterrorist threats in Europe were only hoaxes fortunately, but should be considered as a "preparedness exercise" from which lessons have to be drawn.
A recent report identified several critical control points in the European response to communicable disease outbreaks involving more than one country (15).Some of the conclusions of this report -inadequate preparedness planning and inadequate funding arrangements -are consistent with the findings of our survey.
First lesson: in October 2001, Europe was not ready to respond to bioterrorism.Nevertheless, European public health institutes quickly adapted their priorities and reallocated limited resources to manage possible bioterrorist threats.National institutes have the necessary expertise but may have lacked the resources needed to implement all the necessary procedures.
Troisième leçon : les actions bioterroristes récentes ont démontré encore une fois la nécessité d'investir davantage dans les programmes de formation à l'épidémiologie de terrain et de créer une unité de coordination technique européenne pour la surveillance et la réponse.s ➤ Lastly, anticipation, coordination, and support for communicable disease control, including BT P&R, is needed at the European level.
Third lesson: the recent bioterrorist events demonstrated again the need for increased investment in epidemiology training programmes and the establishment of a TCU for international surveillance and outbreak response in the EU.s Introduction L a dissémination délibérée d'agents biologiques contre des populations civiles est considérée depuis longtemps comme une medélibérée de spores de charbon au sein des services postaux américains et l'inquiétude croître sur la possibilité de disséminations réitérées de spores de la maladie du charbon et d'autres agents biologiques.Au vu des évènements ayant eu lieu aux Etats Unis jusqu'à présent, cet article aborde certaines des actions que les systèmes de protection sanitaire des pays européens seront amenés à entreprendre en réponse à la menace du bioterrorisme.

Deliberate releases of biological agents: initial lessons for Europe from events in the United States
Introduction T he deliberate release of biological agents against civilians has long been recognised as a potential threat (1).In the autumn of 2001, this threat became a reality, with the deliberate release of anthrax in the postal system of the United States (US) and heightened concern about the possibility of further releases of anthrax and other biological agents.In the light of events in the US so far, this article considers some Liste des répondants / List of respondents: of the actions that health protection systems in European countries will have to take to respond to the threat of bioterrorism.

Deliberate releases of anthrax in the United States
As of 31 December 2001, 22 cases of confirmed anthrax have occurred in the US as a result of deliberate releases: 11 inhalation cases have been confirmed and have resulted in five deaths, and there have been seven confirmed and a further four suspected cutaneous cases (2-7).

Deliberate release of anthrax into the US postal system
The evidence so far is convincing that anthrax spores were released through the US postal system.There seems to have been two postings of contaminated letters: the first to Florida and New York, and the second to Washington.All the letters found so far were sent from New Jersey.Two contaminated letters have been identified from the first posting.They arrived at the Hamilton Township postal facility in Trenton, New Jersey, on 18 September and were processed within three hours of each other by the same postal worker (who later developed cutaneous anthrax).They were then sent to postal facilities in New York, where anthrax spores have since been identified on sorting machines.From here they were dispatched to their destinations at media organisations.Two further letters have been identified from the second posting.These were also processed at the Hamilton Township postal facility, this time on 9 October.They were then sent through postal facilities in Washington, giving rise to five cases of inhalation anthrax.One arrived at its destination in a Senator's office and the other was subsequently discovered in mail that was sequestered as a precautionary measure when the first letter was opened.
Investigations suggest a single source for the deliberate releases.The handwriting and messages in the letters are very similar, and the strains of anthrax detected in Florida, New York, Washington, and New Jersey are indistinguishable.The perpetrator remains unidentified, and the risk of continuing deliberate releases remains high until they are captured.

Experience of false alarms and criminal hoaxes in the US and elsewhere
Complete data are not available on the number of false alarms and criminal hoaxes that have arisen following the deliberate releases in the US.A telephone survey performed by the Centers for Disease Control and Prevention (CDC) indicated that between 11 September and 17 October, 7000 reports of anthrax threats had been received.Of these, 4800 required follow up by telephone, and 1050 required testing of suspicious materials (5), a testing ratio of 15 for every 100 reports received.In comparison there were only 180 reports of anthrax threats during 1996-2000 in the USA (5).
Available evidence suggests that similar events have occurred in the United Kingdom (UK), and, according to informal reports and anecdotes, elsewhere in Europe.In the UK, the pattern of false alarms and criminal hoaxes has been similar to those reported from the US.The ratio of environmental testing of suspicious materials has been lower, only 2.3 per 100 events reported to the police, and lower still in areas where police forces have experience of assessing potential terrorist threats.Crucially, to date no environmental specimens have tested positive for B. anthracis in the UK or elsewhere in Europe.
No cases of anthrax linked to deliberate releases have so far been ascertained outside the US.B. anthracis has been identified by preliminary tests on letters and packages in the Bahamas, Brazil, Germany, Kenya, Pakistan, Venezuela, Vietnam and Chile, but not subsequently confirmed.Where anthrax spores have been detected outside the US, in Peru, Russia, and Lithuania, this has been on mail sent to US consulates and embassies abroad, and is thought to have arisen through contamination within US government postal facilities.

Implications for Europe
1. Role of the healthcare sector in surveillance and response to deliberate covert releases In the past, emergency planning for biological, chemical, and radiological threats has tended to focus on the management of large scale overt releases (10).Recent experience in the US has highlighted the need to plan ➤

La réponse pluridisciplinaire aux menaces sous la responsabilité des
services de police et de sécurité Dans la plupart des pays européens, en cas de suspicion d'une attaque terroriste biologique, les services de sécurité sont habituellement responsables de la réponse.Au Royaume-Uni, quand des colis suspects sont repérés, la police entreprend la phase d'évaluation initiale de la menace et la classe comme « crédible » ou « non crédible ».Le rôle des services sanitaires est de fournir un soutien -par exemple en décontaminant les personnes exposées et en prescrivant rapidement un traitement prophylactique lorsque la menace est considérée comme crédible.Les ser-➤ for covert releases.Mitigating the effects of covert releases requires early recognition followed by prompt activation of an effective multisector response, and health services have a crucial role.The following key elements are essential.
Surveillance for clinical syndromes.Cases of disease arising due to covert deliberate releases of any biological agent will first appear as unusual clinical syndromes (9) or unexpected patterns of occurrence of more common syndromes (11).Examples include rapid onset of severe sepsis with respiratory failure in the case of inhalation anthrax, plague or tularaemia; typical skin lesions in cutaneous anthrax; rapidly descending, afebrile, symmetrical, flaccid paralysis in botulism; and clusters of severe systemic illness with vesicular rash in smallpox (12).Clinicians must be aware of the syndromes to look out for and know how to seek expert advice and notify public health authorities in the event of their presentation.Clinical protocols are required to assist with the investigation into suspicious clinical syndromes, including appropriate history taking, while recognising that most cases will not be due to deliberate releases.
Clinical recognition must be supported by high quality laboratory diagnostic tests based on previously prepared and disseminated protocols so that deliberate releases can be rapidly confirmed or excluded with confidence if suspicious clinical syndromes arise (9).Laboratory capacity must be available to cope with large numbers of specimens if necessary.Precautions must be in place to protect laboratory staff, and to ensure safe collection and transportation of specimens.In the UK, this advice is available at: http://www.phls.co.uk/facts/deliberate_releases.htm.

Consideration of chemical and radiological agents.
Chemical and radiological agents may also be deliberately released, either alone or combined with biological agents (13,14).For this reason environmental testing of suspect materials should be undertaken only by specialised laboratories (15).There must be prepared methods of environmental sampling with agreed protocols on the respective roles of the primary diagnostic and reference laboratories.
Well developed epidemiological intelligence must be in place to allow reporting of suspected cases by clinicians to a central authority from which the public health response is coordinated (10).Rather than develop separate structures solely for dealing with deliberate releases, it is better to use (and if necessary strengthen and expand) existing public health surveillance and health protection networks.
Epidemiological support must be rapidly available to collate information about suspected cases, analyse relationships between them to establish common environmental exposures, and coordinate additional case finding.Identification of common exposures is critical to determine a potentially exposed group of people who require antibiotic prophylaxis, vaccination and / or monitoring depending on the agent.Tracing the source of covert deliberate releases requires combining data from human and environmental epidemiology with information from security services: health and criminal investigators have to work together.
A planned multisector public health response.This requires established systems for delivering testing, treatment, and prophylaxis for large numbers of people, and providing appropriate timely advice to the health community and general public.This response must be planned between national, regional, and local sectors and should be tested periodically.

Multidisciplinary response to threats -Police and security
services lead When a deliberate release is suspected, it is customary in most European countries for security services to lead the response.In the UK, when suspicious packages are identified, the police undertake the initial threat assessment and categorise the threat as "credible" and "non-credible."The role of health services is to provide support -for example, to decontaminate exposed persons and ensure rapid prescription of prophylactic treatments when the threat is considered credible.Security services may not always be used to dealing with deliberate threats and may need to gather experience quickly.
A proportionate response depends on good local, regional, and national planning between the relevant services.In the health sector there must be close interdisciplinary working between clinicians, microbiologists, toxicologists, epidemiologists, communicable disease control physicians, vices de sécurité n'ont pas toujours l'habitude de gérer les attaques biologiques et peuvent avoir besoin d'une expertise rapide.
Les réactions indésirables associées aux traitements courts par la cipro-floxacine et la doxycycline ont été décrits auparavant.Les effets indésirables potentiels lors de la prescription de traitements plus longs et à un grand nombre de personnes sont moins connus et de ce fait, devraient faire l'objet d'une surveillance particulière.Après l'incident de Floride, 19% des personnes qui avaient pris de la ciprofloxacine et qui ont répondu à un questionnaire ont ressenti des symptômes (démangeaisons, problèmes respiratoires ou gonflement du visage, du cou ou de la gorge) ou bien ont ➤ and radiation biologists and physicists.Rehearsal of possible scenarios creates an opportunity for joint working between agencies and coordination of plans.Inter-institutional tensions will arise unless their roles and responsibilities are well defined.

Surge capacity
It is essential that additional support can be provided for diagnosis and management of cases, laboratory and epidemiological investigations, and public health action in the event of an incident.This requires sharing of ideas, experience, laboratory facilities, and personnel across Europe as well as building expertise within countries.Linking laboratories into a network such as the US's national bioterrorism laboratory response network or the PHLS in the UK is helpful (2).Trainees, such as Fellows of the European Programme for Intervention Epidemiology Training (EPIET) (16), can provide vital additional support if properly supervised.

Antimicrobial prophylaxis
Experience from the US suggests that early antimicrobial prophylaxis is effective at preventing anthrax infection in those who have been exposed (5,17).No cases have arisen among people exposed but given prompt antibiotic treatment.In Washington, no cases among people in the office when the first letter was opened and who were given antibiotics, contrasts with five cases of inhalation anthrax among untreated postal staff who had handled the sealed letter previously (2).Animal studies also suggest good protective efficacy from post-exposure antibiotic treatment (18).
Antimicrobial prophylaxis for anthrax must be started early.When a deliberate anthrax release is suspected (security services assess the threat as credible), it is not possible or appropriate to wait for the results of environmental tests before making a decision about issuing treatment (7).It is safer to start a course of antibiotics, which can then be discontinued or continued for the full duration depending on laboratory results from cases and the environment.Since 8 October, some 32 000 people deemed at risk of exposure to B. anthracis in the US have started taking antimicrobial prophylaxis to prevent infection, and a full 60 day course of antibiotics has been recommended for 5000 of these (6).
Prescription of antibiotics after a suspected exposure should be highly focused and based on sound risk assessment (17).Antimicrobial prophylaxis should be restricted if possible to people who have been exposed to an air space where a suspicious material may have been aerosolised or who have shared the air space likely to be the source of a case of inhalation anthrax (7).Indiscriminate use of antibiotics is likely to induce resistance in B. anthracis and other organisms (17).
The choice of an antimicrobial agent should be based on the drug's effectiveness, the organism's susceptibility, side effects, contraindications, and cost.In the US, B. anthracis isolates have been susceptible to ciprofloxacin, doxycycline, and other agents (2-7).The strategic choice for prophylaxis against all the bacterial agents that may be used in deliberate releases is ciprofloxacin, but it is recognised that, once antimicrobial sensitivity is known, other antibiotics may be used.Ciprofloxacin has been chosen by the UK because of its broad spectrum and pharmacokinetic properties, which produce high concentrations in the lungs and cells (17).CDC recommendations are that doxycycline may be a useful alternative in order to prevent development of fluoroquinolone resistance in more common bacteria (5).Either antibiotic is an effective agent for preventing anthrax infection.
The adverse events associated with short courses of ciprofloxacin and doxycycline have been well described.The potential adverse effects when issuing longer courses to large numbers of people are less well understood, and should therefore be monitored.After the incident in Florida, 19% of the people given ciprofloxacin who responded to a questionnaire reported having experienced symptoms (including itching, breathing problems, or swelling of face, neck, or throat) or having sought medical attention for adverse events related to taking the antibiotic.Six of them discontinued the course (6).Results were similar in a larger survey of postal service employees (19).

The role of nasal swabs
Although nasal swabs may be useful to determine the extent of contamination and guide antimicrobial prophylaxis at a population level, they should not be used on an individual basis to determine who should ➤ ➤ consulté un médecin pour des effets indésirables liés à la prise d'antibiotique.Six d'entre elles ont arrêté le traitement (6).Une enquête plus importante auprès des employés des services postaux a donné des résultats similaires (19).

Conclusion
La dissémination délibérée d'agents biologiques est devenue une réalité.Même si aucune action terroriste bactériologique n'a eu lieu en Europe, celles survenues aux États-Unis ont touché l'Europe par la peur et les fausses alertes qu'elles ont engendrées.L'expérience des États-Unis offre une chance aux pays d'Europe, en collaboration avec la Commission européenne, de travailler activement à l'amélioration des plans de lutte contre les agents biologiques, chimiques et radiologiques diffusés délibérément pour nuire à la santé.La surveillance des agents biologiques reste une priorité internationale pour les gouvernements (21).Les États-Unis ont dû prendre leurs dispositions précipitamment, l'Organisation Mondiale de la Santé prépare actuellement des recommandations dans le cadre de son département Surveillance et réponse face aux maladies transmissibles, et avec le Réseau mondial d'alerte et de réponse aux épidémies (22).Il est temps pour l'Europe de coordonner sa réponse.s ➤ receive antibiotics (4).The decision about the group to be given antimicrobial prophylaxis should be made on the basis of an epidemiological and environmental assessment of the area and people exposed to anthrax spores.Everyone judged to be at risk of exposure should then receive antibiotics, regardless of whether they personally have a positive nasal swab result; failure to detect B. anthracis by nasal swab is no guarantee that the person has not inhaled spores since the nasal spaces will rapidly clear these.

Vigilance for suspicious mail
High profile individuals and organisations may be at a particularly high risk of becoming targets of deliberate releases through the post.It is important for them to develop systems to enable the prompt detection and management of suspicious items of mail so that any contamination can be minimised (20).The letter sent to the one of the media organisations in New York was postmarked 18 September and was handled on arrival at the company, leading to one cutaneous case.It remained unopened and was handled again between 12 and 15 October, leading to two further cutaneous cases.It was not opened and tested until 19 October.Earlier detection and containment of this letter may have reduced contamination of the building and prevented the later cases.

Decontamination
Firstly, there may be a need to decontaminate persons who have been exposed to a suspicious material.This involves rapid removal of clothes and showering with soap and water.It should ideally be done at the site, using mobile decontamination facilities and taking precautions to minimise the spread of contamination.If necessary, it may be possible to decontaminate clothes by autoclaving.Environmental decontamination may be required if the release of a biological agent is proven.Low levels of B. anthracis contamination may be successfully dealt with by simple cleaning with bleach solution.More heavily contaminated areas are likely to be more troublesome, as has been the case in the US, and decontamination may require fumigation with chlorine dioxide or formaldehyde.Even if decontamination of a building has been successful in a microbiological sense, there may still be psychological barriers to people living or working in it, and it may therefore lose its commercial value.

Dissemination of anthrax spores
The accepted infectious dose for inhalation anthrax is 10 000 spores, and secondary aerosolisation from surfaces once spores have settled is thought to be difficult.Some cases of inhalation anthrax among US postal workers have been attributed to aerosolisation of spores during vigorous sorting and franking of contaminated letters by an automated machine, although other cases arose in areas where only manual sorting was carried out.The mechanism of dissemination of spores and infection of inhalation cases in Florida, New York, and Connecticut is unclear (8).The most important factor has been that the material used in contaminated letters comprised particles 1-5 microns in size that can penetrate deep into the lungs.

Conclusion
Deliberate releases of biological agents are now a reality.Even though a deliberate release has not occurred in Europe, the deliberate releases in the US have affected Europe through the fear and false alarms they have precipitated.The US experience affords an opportunity for European countries, working with the European Commission, to work proactively to improve planning to cope with deliberate releases of biological, chemical, and radiological agents designed to damage health.The control of biological agents remains an international priority for states (21).The US has had to make preparations at speed, the World Health Organization is preparing guidance under its communicable disease surveillance and response branch and the global outbreak and response network (22).The time has come for a coordinated approach in Europe.s Introduction L 'éradication mondiale de la variole a été prononcée par l'Organisation mondiale de la santé en 1980 et depuis lors aucun cas nouveau n'a été enregistré.Tous les pays du monde ont abandonné, au plus tard au début des années 1980, la vaccination antivariolique.L'éventualité que du matériel viral ait pu être extrait d'un des deux laboratoires au monde autorisés à conserver des stocks de virus de la variole a renforcé, dans le contexte des évènements actuels, l'inquiétude quant à la possibilité de l'utilisation du virus de la variole comme arme biologique.
Plusieurs pays, dont la France ont conservé des stocks de vaccins anti-varioliques et une capacité de production du vaccin traditionnel.Dans le cadre de l'élaboration d'un plan de lutte contre le bioterrorisme, le ministère de la santé a demandé à l'InVS début octobre 2001 de lui rendre un avis sur la pertinence de différents scénarios de vaccination en fonction de la gravité de la menace d'une action malveillante, prenant en compte le risque épidémique et les effets secondaires du vaccin.➤ In the context of its plan to fight against bioterrorism, the French Ministry of Health asked the Institut de Veille Sanitaire to evaluate the epidemic risk from a release of the smallpox virus, and to make recommendations on potential vaccination strategies to be implemented.A benefit/risk assessment of various vaccination scenarios, including vaccination of the whole French population, was carried out to evaluate the severity of a terrorist action threat.This analysis concludes that at this stage, vaccination action does not seem to be justified.Even in the case of a real threat, the vaccination of frontline healthcare personnel, and in particular of contacts of cases, must be given priority.

Introduction
I n 1980, the World Health Organization (WHO) announced the eradication of smallpox, and since then, no new case has been reported.All countries in the world had stopped smallpox immunisation by the early 1980s at the latest.In the light of recent events, the possibility that viral material could have been extracted from one of the two laboratories in the world authorised to store the smallpox virus has revived concerns about the use of the virus as a biological weapon.
France is one of several countries that have stocks of smallpox virus and can produce the traditional vaccine.With a view to setting up a plan to fight bioterrorism, the French Ministry of Health asked the Institut de Veille Sanitaire (InVS) in early October 2001 for its conclusions on various vaccination scenarios depending on the severity of a threat from a deliberate release, taking into account the epidemic risk and the side effects of the vaccine.➤

Correspondance / Correspondence
Au / To PHLS Deliberate Release Team -incident@phls.org.uk;attention Dr Nicoll et /and Dr Morgan.

Estimation de l'impact épidémiologique d'une exposition au virus de la variole
L'ampleur d'une épidémie provoquée par une source de virus de la variole résultant d'une action terroriste en France est difficile à préciser.Elle dépend en particulier du nombre de personnes contaminées par la source initiale et de différents facteurs intervenant dans la dynamique de la transmission virale, tels que la proportion de la population susceptible, le contexte socio-démographique local et la nature et la rapidité de la mise en oeuvre de mesures de contrôle.

➤ Method
The analysis consisted of three preliminary stages: identifying conceivable vaccination strategies, defining the different risk levels, and evaluating the number and severity of side effects of the vaccine linked to the various vaccination strategies.
The strategies were identified on the basis from data on disease transmission, and on the evaluation of the epidemiological impact that the introduction of the smallpox virus would have in France.The fact that there might be other strategies to fight the disease was taken into account.

Transmission of the disease and implications in terms of control measures
Before the vaccine was introduced, the virus was widespread and highly contagious.In its major form, smallpox was a severe disease, characterised by erupting skin lesions that could kill up to 30% of non-vaccinated patients.Case fatality rates were most notable in very young or old people.
Smallpox is mainly transmitted in aerosolised form, mainly by direct contact from person to person.Transmission from cutaneous lesions has a secondary role.
Smallpox contagiousness is important but less so than that of other acute infectious diseases, such as measles.In a totally susceptible population of average density, the number of secondary cases following one case of smallpox infection was estimated to be around five, compared with 16 for measles.The disease is usually transmitted in the close environment of the patient (family contacts, relatives, or medical staff) (1).This is because transmission of the virus occurs exceptionally before the lesions erupt, which usually occurs two weeks after a patient has become infected.At this stage, patients are usually confined to bed because of their poor general condition and high fever, thus considerably limiting the number of contacts.
The number of secondary cases can be reduced by implementing control measures around the primary case.An early diagnosis, made easy by the specific clinical signs (lesions embedded in the dermis, centrifugal eruption in one 'crop'), followed by rapid and strict isolation of the patient makes it possible to limit the number of contaminated contacts.Moreover, vaccination of these contacts, if carried out within three to four days after exposure, prevents the disease or results in less severe symptoms.Close monitoring of the contacts enables physicians to detect the disease early in case of vaccination failure.It has been possible to eliminate the disease in densely populated areas, thanks to active research, isolation of cases, and vaccination of patient contacts.In these areas, the level of immunity in the general population needed to allow elimination -around 100% for the most densely populated areas alone -would have been impossible to achieve by immunisation programmes (2).

Evaluation of the epidemiological impact of an exposure to the smallpox virus
The extent of an outbreak of smallpox virus infection resulting from terrorist action in France is difficult to measure.It depends on the number of people infected from the initial source, and on various factors that influence the dynamics of viral transmission, such as the susceptible proportion of the population, the local sociodemographic context, and the nature and timeliness of control measures.
Most of France's population is probably currently susceptible to the disease.Preventive immunisation was mandatory from 1901 to 1978, and given as primary vaccination during the first two years of life, with boosters recommended at ages 11 and 21, until 1984.People who were vaccinated before 1984 are likely to have kept a degree of protection that would alleviate the severity of the disease, even though those patients would contribute to transmission.People older than 40 might still benefit from complete protection -although the proportion of the population is not known -provided they received the three doses recommended at 1, 10, and 20 years of age.medical follow up of contacts -are implemented immediately.

Frequency and severity of side effects of vaccination
The evaluation of the number of deaths and severe adverse events induced by large scale vaccination was carried out from population data of the 1999 census (source: INSEE, Institut National de la Statistique et de Etudes Economiques -National Institute of Statistics and Economic Studies), and from the estimated French population's vaccination history from statistics from INSERM (Institut National de la Santé et de la Recherche Médicale -National Institute of Health and Medical Research) (4).The rates of side effects come from two American studies carried out in 1968, a national survey and a survey carried out in 10 states (5,6).The survey protocol carried out in the 10 states was stricter, and the estimates are considered as very reliable.We have used data from this study, except where the number of vaccinated people was too low to evaluate the incidence of very rare adverse events, such as progressive vaccinia and vaccinal encephalitis.In these cases, we used the data of the national survey (table 1).
The data used on case fatality rates from side effects come from a review of the literature and appear in table 2 (2,7) .
The level of permanent neurological adverse events in patients having survived encephalitis as a result of vaccination is estimated at 25%. ➤ En cas de contamination initiale importante et inopinée dans une zone urbaine, la conjonction d'une densité de population importante et d'un niveau de susceptibilité initialement élevé pourrait induire un nombre élevé de cas In the event of important and unexpected initial contamination in an urban area, the population density and an initially high susceptibility level could lead to a considerable number of secondary cases induced by each index case, possibly reaching 10 to 20 in the first wave of cases, causing an outbreak extending on several generations of cases (1,3).But an early diagnosis may help limit the number of patients, provided response strategies -such as isolation of cases associated with vaccination and Tableau 1 / Table   (1,3).Cependant, si le diagnostic de variole était posé très rapidement, le nombre de malades pourrait rester limité à condition d'une mise en oeuvre immédiate des stratégies de réponse de type isolement des cas associée à la vaccination et au suivi médical des contacts.

Identification of different vaccination strategies
Four possible vaccination strategies have been identified.

Strategy 1: vaccination or revaccination of the entire French population
In this strategy, we considered that all the population should be vaccinated; available data on protection for more than 20 years are not conclusive about the level of protection, even in those who had been revaccinated twice.du personnel hospitalier (8).Plusieurs options de vaccination du personnel de santé peuvent être envisagées.
Des options de vaccination ciblées sur des sous-groupes à plus haut risque peuvent être également considérées : Option 1: All healthcare staff likely to be in contact with cases or contaminated equipment: private general practitioners and hospital physicians, other hospital healthcare staff, laboratory staff, hospital laundry and mortuary staff, emergency staff such as ambulance drivers, and public health professionals participating in the control of infectious diseases could be included.
Vaccination options targeting subgroups at highest risk could also be considered.
Option 2: Vaccination of teams taking care of cases in a limited number of hospital facilities (one hospital centre per district, giving priority to university and regional hospitals), including laboratory and mortuary staff.

Analyse des différentes situations
Situation 1 (correspondant à la situation à la mi-octobre 2001) : une menace potentielle existe mais aucune information n'existe sur la possession de virus par des groupes terroristes Il paraît inapproprié de proposer la vaccination ou la revaccination du personnel de soins (stratégie 2 option 1) et à plus forte raison de l'ensemble de la population française (stratégie 1), tant que le risque réel de complications graves de la vaccination ne peut être mis en balance avec le risque théorique d'exposition au virus de la variole.
La priorité, à ce stade, réside dans la planification des modalités de mise en oeuvre éventuelle de la vaccination et des mesures de contrôle autour d'un cas que nécessiterait un renforcement de la menace ou sa concrétisation (situation 2 ou au-delà).Dans ce cadre, une sensibilisation du corps médical et des acteurs de santé publique sur les caractéristiques de la maladie et les mesures à prendre devant un cas suspect ou confirmé de variole serait utile.➤ Option 3: Vaccination of all first line healthcare staff who will be in contact with the first suspected cases, before the diagnosis is confirmed: general practitioners, paediatricians, or hospital emergency staff.
If situation 4 occurred (see below), two additional strategies might be considered.

Strategy 3: vaccination of contacts of one case
Strategy 4: regional vaccination around cases

Definition of risk levels
Several situations have been studied, depending on the plausibility of a smallpox outbreak threat.
Situation 1 (this reflects the situation in mid October 2001): a potential threat exists, but there is no information on whether any terrorist groups are in possession of the virus Situation 2: information or facts make plausible terrorist action using the smallpox virus Situation 3: at least one confirmed case was diagnosed outside the national territory Situation 4: at least one confirmed case was diagnosed inside the national territory

Estimation of the number of severe side effects and deaths associated with vaccination
-Vaccination/revaccination of the whole French population Tables 3.1 and 3.2 give estimates on the number of severe side effects and deaths that one dose of vaccine given to the entire population might cause.
Vaccination and revaccination of the entire French population would result in around 315 deaths.There would be a further 89 cases with adverse events of encephalitis.
-Vaccination and revaccination of all healthcare staff, emergency and related (strategy 2, option 1) An evaluation of the number of severe side effects and deaths associated with the vaccination of healthcare and emergency staff leads to an estimate of six to eight deaths, depending on actual size of the population and their current vaccination status.

Analysis of the different situations
Situation 1 (the mid October 2001 situation): a potential threat exists, but there is no information on the possession of the virus by terrorist groups.
It seems inappropriate to suggest vaccination or revaccination of healthcare staff (strategy 2 option 1) and a fortiori the whole French population (strategy 1), as the real risk of severe complications associated with vaccination outweighs the theoretical risk of exposure to the smallpox virus.
Priority at this stage should be given to planning methods for the vaccination and control measures of a case made necessary by the intensification or realization of a threat (situation 2 or beyond).Raising awareness among the medical profession and public health professionals on the characteristics of the disease and measures to be taken when faced with a suspected or confirmed case of smallpox would be useful.
Situation 2: information or facts make plausible a terrorist attack using the smallpox virus.
Vaccination strategies for the whole population (strategy 1) and all healthcare staff (strategy 2, option 1) would remain inappropriate, even if the vaccine were available in sufficient quantity.This would expose vaccinated subjects to a disproportionately high risk of severe complications after vaccination since it would be impossible to define geographically the population likely to be affected after a terrorist attack.➤ ➤ Situation 2: il existe des informations ou des faits rendant plausible une action terroriste utilisant le virus de la variole.
➤ A favoured strategy might be selective vaccination of chosen hospital teams from the main hospitals (one hospital per district), which could be put in charge of the potential first suspected or confirmed cases of smallpox (option 2).These teams could play the part of referents, participating in raising awareness among healthcare staff.They would also be able to provide clinical expertise if necessary.
Situation 3: one or several cases of smallpox are confirmed outside the national territory.
In this situation it seems desirable to extend the preventive vaccination strategy beyond dedicated hospital teams to all first line practitioners and healthcare staff who may have to examine or be in contact with patients with smallpox, before the diagnosis is confirmed (general practitioners, paediatricians, and emergency staff) (strategy 2, options 2+3).Priority should be given to the strict planning of methods to implement response strategies around cases.That way, they will be applied without delay, in case situation 4 arises.Methods on the detection and isolation of suspected smallpox cases on entry into national territory will have to be implemented.
Situation 4: One or more smallpox cases are confirmed inside the national territory.
The vaccination strategy will depend on the situation, in particular available information on the number of subjects exposed to the source of infection and stocks of available vaccines.The following points, however, need to be emphasised.
In the case of a single attack, when the first cases are symptomatic, the source of the virus will be completely inactivated; the virus does not survive more than two days once spread in the air and exposed to light.
It is likely that a deliberate release would target urban populations first.The level of vaccine coverage necessary to prevent viral circulation would be very high and could not be reached rapidly.
People who have been vaccinated, even if a long time ago, should be assigned in priority to take care of the first cases while waiting for vaccines to be available.
Control measures around suspected or confirmed cases will affect the dynamics of the outbreak and should be implemented as soon as possible.They consist mainly of strict isolation of suspected or confirmed cases, if possible in rooms with negative pressure, and on vaccination and monitoring of body temperature of all those who had close contact with cases, since the occurrence of erupting skin lesions or, as a precautionary measure, fever (strategy 3).
A vaccination strategy for healthcare staff should be implemented as soon as possible.Depending on how many doses of vaccine are available, the number of index cases, the geographical spread of cases, decisions of public health authorities to mobilise a more or less important proportion of the medical profession in the control of the outbreak, this vaccination may or may not interest the whole personnel concerned (strategy 2, option 1) or consist of vaccinating dedicated teams, associated with the vaccination of all first line healthcare staff (strategy 2, option 2 +3).
Extension of the vaccination strategy to a geographical area where cases have been detected may be considered, provided, on the one hand, that enough vaccine is available afterwards to set up the vaccination of potential future contacts in other areas and, on the other hand, of an epidemiological context favouring a wide local circulation of the virus (strategy 4).
Only if the outbreak seems impossible to control rapidly, enough doses of vaccine are available, and all logistical, financial, legal, and ethical issues linked to vaccination are settled, a mass vaccination strategy should have to be considered on the basis of an updated analysis of benefits and risks (strategy 1).Table 4 summarises the various recommended strategies depending on the evaluation of a terrorist attack risk.
Ces conclusions, basées essentiellement sur l'expérience accumulée lors du programme renforcé d'éradication de la variole, sont en accord avec les recommandations faites en Octobre 2001 par l'OMS et plus récemment par les Centers for Diseases Control américains (10).s ➤ Discussion Our estimates of the incidence of side effects should be considered carefully, because of diverging data in the literature on the frequency of post-vaccination complications, reflection of different methods, and quality of surveys.Our evaluations, however, are based essentially on a survey whose protocol allowed for exhaustive case finding, and are likely to constitute acceptable estimates.Case fatality rates regarding primary vaccination of 6 per million vaccinated people is similar to the one evaluated in France by Martin-Bouyer et al (5.8 deaths per 1 million vaccinations) from 1968 to1977 for over four million primary vaccinations (9).Data from all surveys might have overestimated the frequency of side effects, as morbidity after vaccination by simple temporal association was not excluded.It is possible that the frequency of complications that would be observed if the old stock of vaccine currently available in France was used has been underestimated.Although regular quality controls carried out on those vaccines by the AFSSAPS (Agence Française de Sécurité Sanitaire des Produits de Santé) have ascertained their biological activity, the occurrence over time of neurotoxic products cannot be excluded.
We do not recommend preventive vaccination at the current risk level.Even in the case of a recognised threat, large scale vaccination, which is likely to be demanded, would lead to the occurrence of severe side effects in populations at no special risk of exposure.Moreover, it would raise the concern of vaccine shortage, stocks of which could be insufficient for targeted vaccination around suspected or confirmed cases, in the event of ongoing transmission.Vaccination of contacts of a case constitutes the most efficacious and efficient vaccination strategy considered, provided it is implemented rapidly.These conclusions, essentially based on the experience acquired during the reinforced programme for smallpox eradication, are in agreement with the WHO recommendations made in October, and more recently by the Centers for Disease Control in the United States (10).s du 11 septembre et la récente épidémie de maladie du charbon ont eu des conséquences pour la santé publique non seulement aux États-Unis, mais également en Europe.Les systèmes de santé publique européens ont dû traiter de nombreux envois postaux potentiellement contaminés par des spores de charbon.Notre enquête avait pour but de documenter la réponse des instituts de santé publique européens aux récents événements bioterroristes afin d'identifier les éventuelles lacunes à corriger.Dix-huit instituts de 16 pays ont participé à cette Eurosynthèse.Les menaces bioterroristes en Europe n'étaient que des canulars et peuvent être considérées comme un 'exercice de préparation' dont trois leçons sont à tirer.Tout d'abord, l'Europe n'était pas prête à répondre au bioterrorisme en octobre 2001.Ensuite, bien que les instituts européens aient réagi rapidement en adaptant leurs priorités à une nouvelle forme de menace, ils auront besoin d'un soutien adapté et pérenne de leur tutelle pour maintenir leur capacité globale.Enfin, cette crise a montré la nécessité d'investir davantage dans les programmes de formation à l'épidémiologie, et de créer une unité de coordination technique pour la surveillance et la réponse internationale aux épidémies au sein de l'Union européenne.Introduction D ans les 24 heures qui ont suivi les attaques terroristes du 11 septembre, les Centers for Disease Control and Prevention (CDC) ont déployé leurs épidémiologistes pour évaluer les conséquences de la catastrophe et renforcer la surveillance épidémiologique d'éventuels actes de bioterrorisme (BT) (1).Moins d'un mois après, le 4 octobre 2001, les CDC rapportaient un cas fatal de charbon d'inhalation en Floride Les données complètes sur le nombre de fausses alertes et de « canulars » criminels suite à ces disséminations volontaires aux États-Unis ne sont pas disponibles.Une enquête téléphonique réalisée par les Centers for Disease Control and Prevention (CDC) indique qu'entre le 11 septembre et le 17 octobre, 7 000 alertes au charbon avaient été reçues.Parmi celles-ci 4 800 ont nécessité un suivi téléphonique et 1 050 une analyse du matériel suspect (5), soit un pourcentage d'analyse de 15 % des notifications reçues.En comparaison, 180 alertes au charbon seulement ont été rapportées entre 1996 et 2000 aux États-Unis (5).

Strategy 2: vaccination of groups at risk (healthcare staff, emergency, or related)
A second preventive vaccination strategy could consist of identifying populations at particular risk from infection, in case the smallpox virus should circulate again.Healthcare staff represent a particularly exposed population.During the last two French outbreaks, 15 out of 42 patients in Marseilles in 1952 and 18 out of 74 in Brittany in 1955 were hospital staff(8).Several vaccination options for healthcare staff may be considered.