Edited by

Mandy C. Elschner, Sally J. Cutler,

Manfred Weidmann, and

Patrick Butaye

BSL3 and BSL4 Agents

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Edited by Mandy C. Elschner, Sally J. Cutler,Manfred Weidmann, and Patrick Butaye

BSL3 and BSL4 Agents

Epidemiology, Microbiology, and Practical Guidelines

The Editors

Dr. Mandy C. ElschnerFriedrich-Loeffler-InstitutFederal Research Institute forAnimal HealthInstitute of Bacterial Infectionsand ZoonosesNaumburger Strasse 96a07743 JenaGermany

Dr. Sally J. CutlerUniversity of East LondonSchool of Health, Sports and BioscienceWater Lane, StratfordLondon E15 4LZUnited Kingdom

Dr. Manfred WeidmannUniversity Medical Center GottingenDepartment of VirologyKreuzbergring 5737075 GottingenGermany

Prof. Patrick ButayeVeterinary & Agrochemical Research Centre(VAR – CODA – CERVA)Department of Bacterial DiseasesGroeselenberg99 B-1180 BrusselsBelgium

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V

Contents

Acknowledgment XIXPreface XXIList of Contributors XXIII

Part A Pathogens 1

Part I Bacteria 3

1 Bacillus anthracis: Anthrax 5Markus Antwerpen, Paola Pilo, Pierre Wattiau, Patrick Butaye,Joachim Frey, and Dimitrios Frangoulidis

1.1 Introduction 51.2 Characteristics of the Agent 51.3 Diagnosis 61.3.1 Phenotypical Identification 61.3.2 Growth Characteristics 61.3.3 Antibiotic Resistance 71.3.4 Phage Testing and Biochemistry 81.3.5 Antigen Detection 81.3.6 Molecular Identification 81.3.6.1 Virulence Plasmid pXO1 81.3.6.2 Virulence Plasmid pXO2 101.3.7 Chromosome 101.3.8 MLVA, SNR, and SNP Typing 111.3.9 Serological Investigations 111.4 Pathogenesis 121.4.1 Animals 121.4.2 Humans 121.5 Clinical and Pathological Findings 131.5.1 Oropharyngeal Anthrax 141.5.2 Abdominal or Intestinal Anthrax 141.5.3 Inhalational or Pulmonary Anthrax 141.6 Epidemiology 15

VI Contents

1.7 Conclusion 15References 16

2 Brucella Species: Brucellosis 19Sally J. Cutler, Michel S. Zygmunt, and Bruno Garin-Bastuji

2.1 Introduction 192.2 Characteristics of the Agent 202.3 Diagnosis 222.3.1 Immunological Approaches 252.3.2 Polymerase Chain Reaction Assays 252.4 Pathogenesis 262.5 Clinical and Pathological Findings 272.6 Epidemiology, Molecular Typing, and Control

Strategies 292.6.1 Epidemiology 292.6.2 Molecular Typing Methods 292.6.3 Control Strategies 312.7 Conclusions 31

References 32

3 Burkholderia mallei: Glanders 37Lisa D. Sprague and Mandy C. Elschner

3.1 Introduction 373.2 Characteristics of the Agent 373.3 Diagnosis 383.3.1 Cultural Identification 383.3.2 Molecular Based Methods 393.3.3 Antigen Detection 393.3.4 Serology 393.4 Clinical and Pathological Findings in Humans 403.5 Clinical and Pathological Findings in Animals 413.6 Epidemiology 423.7 Molecular Typing 433.8 Conclusions 43

References 43

4 Burkholderia pseudomallei: Melioidosis 47Lisa D. Sprague and Mandy C. Elschner

4.1 Introduction 474.2 Characteristics of the Agent 474.3 Diagnosis 484.3.1 Cultural Identification 484.3.2 Antigen Detection 494.3.3 Molecular Based Methods 494.3.4 Serology 49

Contents VII

4.4 Clinical and Pathological Findings in Humans 504.5 Clinical and Pathological Findings in Animals 504.6 Epidemiology 524.6.1 Molecular Typing 524.7 Conclusions 52

References 53

5 Coxiella burnetii: Q Fever 57Matthias Hanczaruk, Sally J. Cutler, Rudolf Toman, andDimitrios Frangoulidis

5.1 Introduction 575.2 Characteristics of the Agent 585.3 Diagnosis 595.3.1 Direct Detection 595.3.2 C. burnetii Cultivation 595.3.3 Detection of C. burnetii Specific DNA 605.3.4 Serology 615.4 Pathogenesis 625.5 Clinical and Pathological Findings 635.5.1 Acute Q Fever 635.5.2 Chronic Q Fever 645.6 Epidemiology, Including Molecular Typing 645.6.1 Plasmid Types 645.6.2 RFLP 655.6.3 IS1111 Typing 655.6.4 Multispacer Sequence Typing 655.6.5 MLVA Typing 665.7 Conclusion 66

References 66

6 Francisella tularensis: Tularemia 71Anders Johansson, Herbert Tomaso, Plamen Padeshki, Anders Sjostedt,Nigel Silman, and Paola Pilo

6.1 Introduction 716.2 Characteristics of the Agent 726.3 Diagnosis 726.3.1 Serology 726.3.2 Direct Isolation 726.3.3 Phenotypical Characteristics 736.3.4 Molecular Biology Tools for Identification 736.4 Pathogenesis 736.5 Clinical and Pathological Findings 746.5.1 Animals 746.5.2 Humans 746.6 Epidemiology and Molecular Typing 77

VIII Contents

6.7 Conclusion 79References 80

7 Yersinia pestis: Plague 85Anne Laudisoit, Werner Ruppitsch, Anna Stoeger, and Ariane Pietzka

7.1 Introduction 857.2 Characteristics of the Agent 887.2.1 The Plague Bacterium: Yersinia pestis 887.2.1.1 Yersinia pestis Microbiology 897.2.1.2 Yersinia pestis Virulence Markers and Pathogenesis 897.2.1.3 Chromosomal Virulence Genes 907.2.1.4 Yersinia pestis Variants 927.2.2 Molecular Typing 927.3 Pathogenesis 937.3.1 Clinical and Pathological Signs 937.3.2 Diagnosis 957.3.2.1 Plague Prevention and Treatment 967.3.3 Plague as a Biological Weapon 977.4 Epidemiology 987.4.1 Plague Distribution Today 997.4.2 Plague in Its Historical Perspective 1007.4.3 An Updated Plague Cycle? 1027.4.3.1 Flea-Borne Plague Transmission 1037.4.4 Classical Plague Cycle 1077.5 Conclusion 109

References 110

8 Rickettsia Species: Rickettsioses 123Alice N. Maina, Stephanie Speck, Eva Spitalska, Rudolf Toman,Gerhard Dobler, and Sally J. Cutler

8.1 Introduction 1238.2 Characteristics of the Agent 1248.3 Phylogenetic Classification of Rickettsiae 1268.3.1 Typhus Fever Group 1268.3.2 Spotted Fever Group 1288.3.3 Transitional Group Rickettsiae 1298.3.4 Ancestral Group Rickettsiae 1298.4 Diagnosis 1308.4.1 Clinical Diagnosis 1308.4.2 Laboratory Diagnostics 1318.5 Pathogenesis 1348.5.1 Clinical and Pathological Findings 1368.6 Epidemiology 1388.7 Conclusions 142

Acknowledgments 142References 143

Contents IX

9 Mycobacterium tuberculosis: Tuberculosis 149Stefan Panaiotov, Massimo Amicosante, Marc Govaerts, Patrick Butaye,Elizabeta Bachiyska, Nadia Brankova, and Victoria Levterova

9.1 Introduction 1499.2 Diagnostic Microbiology of Mycobacteria 1509.3 Staining and Microscopic Examination 1519.4 Cultivation of Mycobacteria 1529.5 Identification of Mycobacteria from Culture 1539.6 Identification of Mycobacteria Directly from Clinical Specimens 1549.7 Immunological Tests for the Diagnosis of Mycobacterium tuberculosis

Infection 1559.8 Molecular Epidemiology of Tuberculosis 1579.9 Theoretical Principles of Typing 1609.10 Performance Criteria Applied in Selecting the Method for Molecular

Typing of Microorganisms 1609.10.1 Reproducibility 1609.10.2 Discriminatory Power 1609.10.3 Typeability 1619.11 Genetic Elements in M. tuberculosis that Contribute to DNA

Polymorphism: Current Methods Applied for Genotypingof M. tuberculosis 161

9.12 IS6110-RFLP Analysis 1619.13 Spacer Oligonucleotide Typing – Spoligotyping 1629.14 VNTR and MIRU Analysis 1639.15 Single Nucleotide Polymorphism 1659.16 The Clustering Question? 1669.17 Conclusions 167

References 167

Part II Viruses 173

10 Influenza Virus: Highly Pathogenic Avian Influenza 175Chantal J. Snoeck, Nancy A. Gerloff, Radu I. Tanasa, F. Xavier Abad, andClaude P. Muller

10.1 Introduction 17510.2 Characteristics of the Agent 17510.2.1 Nomenclature 17510.2.2 Genome and Protein Structure 17610.2.3 Viral Replication 17610.2.4 Antigenic Drift and Antigenic Shift 17610.3 Pathogenesis 17710.3.1 Reservoir 17710.3.2 Low and Highly Pathogenic Influenza Viruses 17710.3.3 Molecular Determinants of Pathogenicity 17810.4 Clinical and Pathological Findings 179

X Contents

10.4.1 HPAI (H5N1) Infection in Animals 17910.4.2 HPAI (H5N1) Infection in Humans 18010.5 Diagnosis 18110.5.1 Direct Diagnosis 18110.5.2 Indirect Diagnosis 18110.5.3 Pathotyping 18210.6 Evolution and Geographic Spread of HPAI (H5N1) Viruses 18210.6.1 Chronology of H5N1 Virus 18210.6.1.1 First Wave 18210.6.1.2 Second Wave 18310.6.1.3 Third Wave 18310.6.2 Focus on Africa 18510.7 Epidemiology of Other Influenza Subtypes 18710.7.1 HPAI Virus Outbreaks 18710.7.2 LPAI Virus Outbreaks 18810.8 Conclusion 188

References 189

11 Variola: Smallpox 201Andreas Nitsche and Hermann Meyer

11.1 Introduction 20111.2 Variola Virus 20111.3 Human Monkeypox 20211.4 Vaccinia Virus 20311.5 Cowpox Virus 20311.6 Collection of Specimens 20411.7 Real-Time Polymerase Chain Reaction 20411.8 Evaluation of Real-Time PCR Assays 20511.9 Real-Time PCR Assays with Hybridization Probes 20611.10 Real-Time PCR Assays with 5′ Nuclease Probes 20711.11 Other Real-Time PCR Formats 20811.12 Conclusions 209

References 209

12 Arenaviruses: Hemorrhagic Fevers 211Amy C. Shurtleff, Steven B. Bradfute, Sheli R. Radoshitzky, Peter B.Jahrling, Jens H. Kuhn, and Sina Bavari

12.1 Characteristics 21112.2 Epidemiology 21212.2.1 Old World Arenaviruses 21212.2.2 New World Arenaviruses 21312.3 Clinical Signs 21412.3.1 Old World Arenaviral Hemorrhagic Fevers 21412.3.2 New World Arenaviral Hemorrhagic Fevers 21412.4 Pathological Findings 215

Contents XI

12.4.1 Old World Arenaviral Hemorrhagic Fevers 21512.4.2 New World Arenaviral Hemorrhagic Fevers 21712.5 Pathogenesis of Old and New World Hemorrhagic Fevers 21812.6 Diagnostics 22312.6.1 Serological Tests 22312.7 PCR 22412.7.1 Virus Culture and Antigen Testing 22412.8 Disclaimer 224

References 224

13 Filoviruses: Hemorrhagic Fevers 237Victoria Wahl-Jensen, Sheli R. Radoshitzky, Sina Bavari, Peter B.Jahrling, and Jens H. Kuhn

13.1 Characteristics 23713.2 Epidemiology 23913.3 Clinical Signs 24213.4 Pathological Findings 24313.5 Pathogenesis 24513.6 Diagnostic Procedures 24613.7 Disclaimer 247

References 247

14 Bunyavirus: Hemorrhagic Fevers 253Introduction 253

14.1 Crimean Congo Hemorrhagic Fever Virus: an Enzootic Tick Borne VirusCausing Severe Disease in Man 255Ali Mirazimi

14.1.1 Introduction 25514.1.2 Characteristics 25614.1.3 Epidemiology 25614.1.4 Clinical and Pathological Findings 25714.1.5 Pathogenesis 25714.1.6 Diagnosis 25814.1.6.1 Virus Isolation 25914.1.6.2 Molecular Methods 25914.1.6.3 Antigen Detection 25914.1.6.4 Serology 259

References 259

14.2 Rift Valley Fever Virus: a Promiscuous Vector Borne Virus 263Manfred Weidmann, F. Xavier Abad, and Janusz T. Paweska

14.2.1 Introduction 26314.2.2 Characteristics of the Agent 26314.2.3 Epidemiology 264

XII Contents

14.2.4 Clinical and Pathological Findings in Humans 26514.2.5 Prophylaxis and Treatment 26514.2.6 Pathogenesis 26614.2.7 Diagnosis and Surveillance 26714.2.8 Conclusions 268

References 268

14.3 Hantaviruses: the Most Widely Distributed Zoonotic Viruses onEarth 273Jonas Klingstrom

14.3.1 Introduction 27314.3.2 Characteristics of the Agent 27414.3.3 Epidemiology 27614.3.4 Clinical Findings 27714.3.4.1 HFRS 27714.3.4.2 HCPS 27814.3.5 Pathogenesis 27914.3.6 Diagnosis 27914.3.6.1 Serology 27914.3.6.2 Virus Detection 280

References 281

Part B Practical Guidelines 291

Part I Bacteria 293

1 Bacillus anthracis 295Markus Antwerpen, Paola Pilo, Pierre Wattiau, Patrick Butaye, JoachimFrey, and Dimitrios FrangoulidisRecommended Respiratory Protection 295Recommended Personal Protective Equipment 295Best Disinfection 295Surface and Equipment 295Skin/Wound Disinfection 296Best Decontamination 296Prevention 296Case Reports, Ongoing Clinical Trials 296Post Exposure Prophylaxis 296Known Laboratory Accidents 296Procedure Recommended in the Case of Laboratory Spill or OtherType of Accident 297Treatment of Disease 297Clinical Guidelines 297

Contents XIII

2 Brucella Species 298Sally J. Cutler, Michel S. Zygmunt, and Bruno Garin-BastujiRecommended Respiratory Protection 298Recommended Personal Protective Equipment 298Best Disinfection 298Best Decontamination 299Prevention 299Post Exposure Prophylaxis 299Known Laboratory Accidents 299Procedure Recommended in Case of Laboratory Spill or Other Type ofAccident 300Treatment of Disease 300Clinical Guidelines 300

3 Burkholderia mallei: Glanders 301Lisa D. Sprague and Mandy C. ElschnerRecommended Respiratory Protection 301Recommended Personal Protective Equipment 301Best Disinfection 301Best Decontamination 301Prevention 301Case Reports, Ongoing Clinical Trials 302Post Exposure Prophylaxis 302Known Laboratory Accidents 302Procedure Recommended in Case of Laboratory Spill or Other Type ofAccident 302Treatment of Disease 302Clinical Guidelines 302References 302

4 Burkholderia pseudomallei: Melioidosis 303Lisa D. Sprague and Mandy C. ElschnerRecommended Respiratory Protection 303Recommended Personal Protective Equipment 303Best Disinfection 303Best Decontamination 303Prevention 303Post Exposure Prophylaxis 304Known Laboratory Accidents 304Procedure Recommended in Case of Laboratory Spill or Other Type ofAccident 304Treatment of Disease 304Clinical Guidelines 304References 305

XIV Contents

5 Coxiella burnetii: Q Fever 306Matthias Hanczaruk, Sally J. Cutler, Rudolf Toman, and DimitriosFrangoulidisRecommended Respiratory Protection 306Recommended Personal Protective Equipment 306Best Disinfection 306Surface and Equipment 306Skin Disinfection 307Best Decontamination 307Prevention 307Post Exposure Prophylaxis 307Known Laboratory Accidents 307Procedure Recommended in Case of Laboratory Spill or Other Type ofAccident 308Treatment of Disease 308Clinical Guidelines 308

6 Francisella tularensis: Tularemia 309Anders Johansson, Herbert Tomaso, Plamen Padeshki, Anders Sjostedt,Nigel Silman, and Paola PiloRecommended Respiratory Protection 309Recommended Personal Protective Equipment 309Best Disinfection/Decontamination 309Prevention 310Case Reports, Ongoing Clinical Trials 310Post Exposure Prophylaxis 310Known Laboratory Accidents 310Procedure Recommended in Case of Laboratory Spill or Other Type ofAccident 310Treatment of Disease 311Clinical Guidelines 311References 311

7 Yersinia pestis: Plague 312Anne Laudisoit, Werner Ruppitsch, Anna Stoeger, andAriane PietzkaRecommended Respiratory Protection 312Recommended Personal Protective Equipment 312Best Disinfection 312Surface and Equipment 312Best Decontamination 313Skin/Wound Disinfection 313Prevention 313Case Reports, Ongoing Clinical Trials 313Post Exposure Prophylaxis 314

Contents XV

Known Laboratory Accidents 314Procedure Recommended in Case of Laboratory Spill or Other Type ofAccident 314Treatment of Disease 314Prophylactic Therapy 315Clinical Guidelines 315References 316

8 Rickettsia Species: Rickettsioses 318Alice N. Maina, Stephanie Speck, Eva Spitalska, Rudolf Toman, GerhardDobler, and Sally J. CutlerRecommended Respiratory Protection 318Recommend Personal Protective Equipment 318Best Disinfection 319Best Decontamination 319Prevention 319Post Exposure Prophylaxis 319Known Laboratory Accidents 319Procedure Recommended in Case of Laboratory Spill or Other Type ofAccident 320Treatment of Disease 320Clinical Guidelines 320References 320

9 Mycobacterium tuberculosis: Tuberculosis 322Stefan Panaiotov, Massimo Amicosante, Marc Govaerts,Patrick Butaye, Elizabeta Bachiyska, Nadia Brankova, andVictoria LevterovaRecommended Respiratory Protection 322Recommended Personal Protective Equipment 322Best Disinfection 323Surface and Equipment 323Best Decontamination 323Prevention 323Ongoing Clinical Trials 323Post Exposure Prophylaxis 324Known Laboratory Accidents 324Procedure Recommended in Case of Laboratory Spill or Other Type ofAccident 324Treatment of Disease 324Clinical Guidelines 324References 325

XVI Contents

Part II Viruses 326

10 Influenza Virus: Highly Pathogenic Avian Influenza 328Chantal J. Snoeck and Claude P. MullerRecommended Respiratory Protection 328Recommended Personal Protective Equipment 328Best Disinfection 329Best Decontamination 329Prevention 329Vaccines with Marketing Authorization from the European MedicinesAgency 330Post Exposure Prophylaxis 330Procedure Recommended in Case of Laboratory Spill or Other Type ofAccident 331Treatment of Disease 331References 331

11 Variola: Smallpox 334Andreas Nitsche and Hermann MeyerRecommended Respiratory Protection 334Recommended Personal Protective Equipment 334Best Disinfection 334Best Decontamination 335Prevention 335Case Reports, Ongoing Clinical Trials 335Post Exposure 335Laboratory Accidents 336Procedure Recommended in Case of Laboratory Spill or Other Type ofAccident 336Treatment of Disease 336References 337

12 Arenaviruses: Hemorrhagic Fevers 338Amy C. Shurtleff, Steven B. Bradfute, Sheli R. Radoshitzky, Peter B.Jahrling, Jens H. Kuhn, and Sina BavariCategory 338Recommended Respiratory Protection and Personal ProtectiveEquipment 338Best Disinfection 339Best Decontamination 340Prevention 340Laboratory Accidents 341Procedure Recommended in the Case of Laboratory Spill or OtherAccident 341Treatment of Disease 342References 342

Contents XVII

13 Filoviruses: Hemorrhagic Fevers 344Victoria Wahl-Jensen, Sheli R. Radoshitzky, Sina Bavari, Peter B.Jahrling, and Jens H.Kuhn

Recommended Respiratory Protection and Particular PersonalProtective Equipment 344

Disinfection/Decontamination 344

Prevention 345

Post Exposure Prophylaxis 345

Laboratory Accidents 346

Procedure Recommended in the Case of Laboratory Spill or OtherType of Accident 346

Accident with Personnel Involvement 346

Treatment of Disease 346

References 347

14 Bunyavirus 350

14.1 Crimean Congo Hemorrhagic Fever Virus 351Ali Mirazimi

Recommended Respiratory Protection 351

Recommended Personal Protective Equipment 351

Best Disinfection 351

Best Decontamination 351

Prevention 352

Case Reports 352

Laboratory Accidents 352

Procedure Recommended in the Case of Laboratory Spill or OtherType of Accident 352

Treatment of Disease 352

Clinical Guidelines 353

14.2 Rift Valley Fever Virus: a Promiscuous Vector Borne Virus 354Manfred Weidmann, F. Xavier Abad, and Janusz T. Paweska

Recommended Respiratory Protection 354

Recommended Personal Protective Equipment 354

Best Disinfection 354

Best Decontamination 355

Prevention 355

Known Laboratory Accidents 356

Procedure Recommended in the Case of Laboratory Spill or OtherType of Accident 356

Treatment of Disease 356

References 356

XVIII Contents

14.3 Hantaviruses: the Most Widely Distributed Zoonotic Viruses onEarth 358Jonas KlingstromRecommended Respiratory Protection 358Recommended Personal Protective Equipment 358Best Disinfection 358Best Decontamination 358Prevention 359Post Exposure Prophylaxis Available? 359Laboratory Accidents 359Procedure Recommended in the Case of Laboratory Spill or OtherType of Accident 359Treatment of Disease 359Clinical Guidelines 359References 360

Index 361

XIX

Acknowledgment

This publication is supported by COST.COST – the acronym for European Cooperation in Science and Technology – is

the oldest and widest European intergovernmental network for cooperation inresearch. Established by the Ministerial Conference in November 1971, COST ispresently used by the scientific communities of 35 European countries to cooperatein common research projects supported by national funds.

The funds provided by COST – less than 1% of the total value of theprojects – support the COST cooperation networks (COST Actions) throughwhich, with ¤ 30 million/year, more than 30 000 European scientists are involvedin research having a total value which exceeds ¤ 2 billion/year. This is the financialworth of the European added value which COST achieves.

A ‘‘bottom up approach’’ (the initiative of launching a COST Action comesfrom the European scientists themselves), ‘‘a la carte participation’’ (only countriesinterested in the Action participate), ‘‘equality of access’’ (participation is openalso to the scientific communities of countries not belonging to the EuropeanUnion), and ‘‘flexible structure’’ (easy implementation and light management ofthe research initiatives) are the main characteristics of COST.

As a precursor of advanced multidisciplinary research COST has a very impor-tant role for the realization of the European Research Area (ERA) anticipatingand complementing the activities of the ‘‘Framework Programmes’’, constitutinga ‘‘bridge’’ toward the scientific communities of emerging countries, increasingthe mobility of researchers across Europe and fostering the establishment of‘‘Networks of Excellence’’ in many key scientific domains such as: Biomedicineand Molecular Biosciences, Food and Agriculture, Forests, their Products andServices, Materials, Physical and Nanosciences, Chemistry and Molecular Sci-ences and Technologies, Earth System Science and Environmental Management,Information and Communication Technologies, Transport and Urban Develop-ment, Individuals, Societies, Cultures, and Health. It covers basic and moreapplied research and also addresses issues of a pre-normative nature or of societalimportance.

Web: http://www.cost.esf.org

XX Acknowledgment

Legal Notice by the COST Office

Neither the COST Office nor any person acting on its behalf is responsible forthe use which might be made of the information contained in this publication.The COST Office is not responsible for the external websites referred to in thispublication.

XXI

Preface

This is the third book written within the framework of the European project COSTAction B28 which aims to increase knowledge on biosafety level (BSL)3 and BSL4agents, to support the development of more accurate diagnostic assays, vaccines,and therapeutics, and to better understand the epidemiology of these highlypathogenic microorganisms that can potentially be used as biological weapons.

The research initiatives and interests of COST B28 partners are organized in fiveworking packages/groups:

• WG1: Technology platform (including flow-cytometry and microarrays);• G2: Antigenicity;• WG3: Proteomics and glycomics;• WG4: Genomics;• WG5: Microbiology (bacteriology, virology, mycology).

The first book summarized knowledge on micro-array technology (WP1). Thesecond book summarized knowledge on the proteomics, glycomics, and antigenicityof the BSL3/4 agents. This book provides a summary of knowledge on the organismsthemselves.

The authors of the chapters are all involved in research concerning these agentsand have been working with them extensively. Typically the authors also haveaccess to BSL3/4 laboratories in which they can work with these agents andthus are familiar with the required precautions and legislation. Their expertisehas also been employed for the assessment of outbreaks and understanding theepidemiological factors that facilitate their spread and subsequent control.

The book is divided into two major parts, separating the viruses and bacteria.Research, epidemiology therapeutics, and the management of these infectionsare indeed quite different. All agents can cause severe disease and outbreaks aremonitored around the world. Some of the agents have been eliminated from certainparts of the world, such as Bacillus anthracis in parts of Western Europe, whileothers such as Mycobacterium tuberculosis are spreading at an ever increasing speed.Nevertheless, for most of the agents, there are regions where they remain endemicand thus the potential for reintroduction requires us to remain vigilant.

Few have actually been used for bioterroristic purposes such as B. anthracis inthe United States in 2001, or in biowarfare such as Burkholderia mallei, used in

XXII Preface

World War I to kill horses that were indispensable for warfare at the time. Othersare well known for ‘‘natural’’ expansion due to a changed epidemiological situationas was the case for Coxiella burnetii in the Netherlands or Rift Valley Fever inAfrica. To understand these differences and possibilities, this book offers thoroughinformation and should be of great value for all those involved in research dealingwith these highly pathogenic microorganisms, and for the non-expert who mightencounter these pathogens and require the background and practical supportinginformation.

To achieve this latter objective, practical guidelines are included providing ‘‘at aglance’’ information for those handling these microorganisms.

Patrick ButayeSally J. Cutler

Mandy C. ElschnerManfred Weidmann

XXIII

List of Contributors

F. Xavier AbadCentre de Recerca en SanitatAnimal (CReSA)UAB-IRTACampus de la UniversitatAutonoma de BarcelonaBellaterra08193 BarcelonaSpain

Massimo AmicosanteNational Center of Infectious andParasitic Diseases26 Yanko Sakazov Blvd1504 SofiaBulgaria

and

University of Rome ‘‘Tor Vergata’’Department of Internal MedicineVia Montpellier 1I-00133 RomeItaly

and

ProxAgen Ltd.SofiaBulgaria

Markus AntwerpenBundeswehr Institute ofMicrobiologyNeuherbergstrasse 1180937 MunichGermany

Elizabeta BachiyskaNational Center of Infectious andParasitic Diseases26 Yanko Sakazov Blvd1504 SofiaBulgaria

Sina BavariUnited States Army MedicalResearch Institute of InfectiousDiseasesFort DetrickFrederickMaryland 21702USA

Steven B. BradfuteUnited States Army MedicalResearch Institute of InfectiousDiseasesFort DetrickFrederickMaryland 21702USA

XXIV List of Contributors

Nadia BrankovaNational Center of Infectious andParasitic Diseases26 Yanko Sakazov Blvd1504 SofiaBulgaria

Patrick ButayeVeterinary & AgrochemicalResearch Centre(VAR – CODA – CERVA)Department of Bacterial DiseasesGroeselenberg99 B-1180 BrusselsBelgium

and

Faculty of Veterinary MedicineDepartment of PathologyBacteriologyand Poultry DiseasesGhent UniversitySalisburylaan 1339820 MerelbekeBelgium

Sally J. CutlerUniversity of East LondonSchool of Health, Sports andBioscienceWater Lane, StratfordLondon E15 4LZUnited Kingdom

Gerhard DoblerBundeswehr Institute ofMicrobiologyNeuherbergstrasse 1180937 MunichGermany

Mandy C. ElschnerFriedrich-Loeffler-InstitutFederal Research Institute forAnimal HealthInstitute of Bacterial Infectionsand ZoonosesNaumburger Strasse 96a07743 JenaGermany

Dimitrios FrangoulidisBundeswehr Institute ofMicrobiologyNeuherbergstrasse 1180937 MunichGermany

Joachim FreyUniversity of BernDepartment of InfectiousDiseases and PathobiologyInstitute for VeterinaryBacteriology122 Laenggassstrasse3012 BernSwitzerland

Bruno Garin-BastujiFrench Agency for Food,Occupational and EnvironmentalHealth Safety (ANSES)EU/OIE/FAO ReferenceLaboratory for BrucellosisMaisons-Alfort 94706France

Nancy A. GerloffInstitute of ImmunologyCentre de Recherche Public de laSante/LNS20A rue Auguste LumiereLuxembourg 1950Luxembourg

List of Contributors XXV

Marc GovaertsVeterinary and AgrochemicalResearch CentreGroeselenberg 991190 UccleBelgium

Matthias HanczarukBundeswehr Institute ofMicrobiologyNeuherbergstrasse 1180937 MunichGermany

Peter B. JahrlingIntegrated Research Facility atFort Detrick (IRF-Frederick)National Institute of Allergy andInfectious DiseasesNational Institutes of HealthFort DetrickFrederickMaryland 21702USA

Anders JohanssonUmea UniversityDepartment of ClinicalMicrobiologySE-901 87 UmeaSweden

Jonas KlingstromSwedish Institute forCommunicable Disease ControlDepartment of Preparedness171 82 SolnaSweden

and

Karolinska InstitutetDepartment of Microbiology,Tumor and Cell Biology (MTC)171 77 StockholmSweden

Jens H. KuhnIntegrated Research Facility atFort Detrick (IRF-Frederick)National Institute of Allergy andInfectious DiseasesNational Institutes of HealthFort DetrickFrederickMaryland 21702USA

and

Tunnell Consulting Inc.King of PrussiaPennsylvania 19406USA

Anne LaudisoitUniversity of LiverpoolEcology, Evolution and Genomicsof Infectious Disease ResearchGroupBiosciencesCrown StreetLiverpool L69 7ZBUK

and

University of AntwerpEvolutionary BiologyGroenenborgerlaan 171Antwerp 2020Belgium

XXVI List of Contributors

Victoria LevterovaNational Center of Infectious andParasitic Diseases26 Yanko Sakazov Blvd1504 SofiaBulgaria

Alice N. MainaInstitute of Tropical Medicine andInfectious DiseasesPO Box 62000-00200NairobiKenya

Hermann MeyerBundeswehr Institute ofMicrobiologyNeuherbergstrasse 1180937 MunichGermany

Ali MirazimiSwedish Institute forCommunicable Disease Control171 82 SolnaSweden

and

Karolinska InstitutetDepartment of Microbiology171 77 StockholmSweden

Claude P. MullerInstitute of ImmunologyCentre de Recherche Public de laSante/LNS20A rue Auguste Lumiere1950 LuxembourgLuxembourg

Andreas NitscheRobert Koch-Institut13353 BerlinNordufer 20Germany

Plamen PadeshkiNational Center of Infectious andParasitic DiseasesDepartment of Microbiology26 Yanko Sakazov Blvd.1504 SofiaBulgaria

Stefan PanaiotovNational Center of Infectious andParasitic Diseases26 Yanko Sakazov Blvd1504 SofiaBulgaria

Janusz T. PaweskaNational Institutefor Communicable Diseases of theNational Health Laboratory ServiceSpecial Pathogens UnitSandringhamJohannesburgSouth Africa

Ariane PietzkaAustrian Agency for Health andFood SafetyInstitute of Medical Microbiologyand HygieneSpargelfeldstrasse 1911220 ViennaAustria

List of Contributors XXVII

Paola PiloUniversity of BernInstitute for VeterinaryBacteriologyDepartment of InfectionsDiseases and PathobiologyVetsuisse FacultyLanggasstrasse 1223012 BernSwitzerland

Sheli R. RadoshitzkyUnited States Army MedicalResearch Institute of InfectionsDiseasesFort DetrickFrederickMaryland 21702USA

Werner RuppitschAustrian Agency for Health andFood SafetyInstitute of Medical Microbiologyand HygieneSpargelfeldstrasse 1911220 ViennaAustria

Amy C. ShurtleffUnited States Army MedicalResearch Institute of InfectiousDiseasesFort DetrickFrederickMaryland 21702USA

Nigel SilmanHealth Protection AgencyMicrobiology ServicesPorton DownSalisbury SP4 0JGUK

Anders SjostedtUmea UniversityDepartment of ClinicalMicrobiologySE-901 87 UmeaSweden

Chantal J. SnoeckInstitute of ImmunologyCentre de Recherche Public de laSante/LNS20A rue Auguste LumiereLuxembourg 1950Luxembourg

Lisa D. SpragueFriedrich-Loeffler-InstitutFederal Research Institute forAnimal HealthInstitute of Bacterial Infectionsand ZoonosesNaumburger Strasse 96a07743 JenaGermany

Stephanie SpeckBundeswehr Institute ofMicrobiologyNeuherbergstrasse 1180937 MunichGermany

Eva SpitalskaInstitute of VirologySAS, Dubravska Cesta 9845 05 BratislavaSlovak Republic

XXVIII List of Contributors

Anna StoegerAustrian Agency for Health andFood SafetyInstitute of Medical Microbiologyand HygieneSpargelfeldstrasse 1911220 ViennaAustria

Radu I. TanasaNational Institute of Researchand Development in Microbiologyand Immunology ‘‘Cantacuzino’’Spl. Independentei 103Sector 5Bucharest 050096Romania

Rudolf TomanLaboratory for Diagnosis andPrevention of Rickettsial andChlamydial InfectionsInstitute of VirologySlovak Academy of SciencesDubravska cesta 9845 05 Bratislava 45Slovakia

Herbert TomasoFriedrich-Loeffler-InstitutFederal Research Institute forAnimal HealthInstitute of Bacterial Infectionsand ZoonosesNaumburger Str. 96a07743 JenaDeutschland

Victoria Wahl-JensenIntegrated Research Facility atFort Detrick (IRF-Frederick)National Institute of Allergy andInfectious DiseasesNational Institutes of HealthFort DetrickFrederickMaryland 21702USA

and

Tunnell Consulting Inc.King of PrussiaPennsylvania 19406USA

Pierre WattiauVeterinary and AgrochemicalResearch CentreGroeselenberg 991180 BrusselsBelgium

Manfred WeidmannUniversity Medical CenterGottingenDepartment of VirologyKreuzbergring 5737075 GottingenGermany