BSL3 and BSL4 Agents -- Contents -- Acknowledgment -- Preface -- List of Contributors -- Part A Pathogens -- Part I Bacteria -- 1 Bacillus anthracis: Anthrax -- 1.1 Introduction -- 1.2 Characteristics of the Agent -- 1.3 Diagnosis -- 1.3.1 Phenotypical Identification -- 1.3.2 Growth Characteristics -- 1.3.3 Antibiotic Resistance -- 1.3.4 Phage Testing and Biochemistry -- 1.3.5 Antigen Detection -- 1.3.6 Molecular Identification -- 1.3.6.1 Virulence Plasmid pXO1 -- 1.3.6.2 Virulence Plasmid pXO2 -- 1.3.7 Chromosome -- 1.3.8 MLVA, SNR, and SNP Typing -- 1.3.9 Serological Investigations -- 1.4 Pathogenesis -- 1.4.1 Animals -- 1.4.2 Humans -- 1.5 Clinical and Pathological Findings -- 1.5.1 Oropharyngeal Anthrax -- 1.5.2 Abdominal or Intestinal Anthrax -- 1.5.3 Inhalational or Pulmonary Anthrax -- 1.6 Epidemiology -- 1.7 Conclusion -- References -- 2 Brucella Species: Brucellosis -- 2.1 Introduction -- 2.2 Characteristics of the Agent -- 2.3 Diagnosis -- 2.3.1 Immunological Approaches -- 2.3.2 Polymerase Chain Reaction Assays -- 2.4 Pathogenesis -- 2.5 Clinical and Pathological Findings -- 2.6 Epidemiology, Molecular Typing, and Control Strategies -- 2.6.1 Epidemiology -- 2.6.2 Molecular Typing Methods -- 2.6.3 Control Strategies -- 2.7 Conclusions -- References -- 3 Burkholderia mallei: Glanders -- 3.1 Introduction -- 3.2 Characteristics of the Agent -- 3.3 Diagnosis -- 3.3.1 Cultural Identification -- 3.3.2 Molecular Based Methods -- 3.3.3 Antigen Detection -- 3.3.4 Serology -- 3.4 Clinical and Pathological Findings in Humans -- 3.5 Clinical and Pathological Findings in Animals -- 3.6 Epidemiology -- 3.7 Molecular Typing -- 3.8 Conclusions -- References -- 4 Burkholderia pseudomallei: Melioidosis -- 4.1 Introduction -- 4.2 Characteristics of the Agent -- 4.3 Diagnosis -- 4.3.1 Cultural Identification -- 4.3.2 Antigen Detection.

4.3.3 Molecular Based Methods -- 4.3.4 Serology -- 4.4 Clinical and Pathological Findings in Humans -- 4.5 Clinical and Pathological Findings in Animals -- 4.6 Epidemiology -- 4.6.1 Molecular Typing -- 4.7 Conclusions -- References -- 5 Coxiella burnetii: Q Fever -- 5.1 Introduction -- 5.2 Characteristics of the Agent -- 5.3 Diagnosis -- 5.3.1 Direct Detection -- 5.3.2 C. burnetii Cultivation -- 5.3.3 Detection of C. burnetii Specific DNA -- 5.3.4 Serology -- 5.4 Pathogenesis -- 5.5 Clinical and Pathological Findings -- 5.5.1 Acute Q Fever -- 5.5.2 Chronic Q Fever -- 5.6 Epidemiology, Including Molecular Typing -- 5.6.1 Plasmid Types -- 5.6.2 RFLP -- 5.6.3 IS1111 Typing -- 5.6.4 Multispacer Sequence Typing -- 5.6.5 MLVA Typing -- 5.7 Conclusion -- References -- 6 Francisella tularensis: Tularemia -- 6.1 Introduction -- 6.2 Characteristics of the Agent -- 6.3 Diagnosis -- 6.3.1 Serology -- 6.3.2 Direct Isolation -- 6.3.3 Phenotypical Characteristics -- 6.3.4 Molecular Biology Tools for Identification -- 6.4 Pathogenesis -- 6.5 Clinical and Pathological Findings -- 6.5.1 Animals -- 6.5.2 Humans -- 6.6 Epidemiology and Molecular Typing -- 6.7 Conclusion -- References -- 7 Yersinia pestis: Plague -- 7.1 Introduction -- 7.2 Characteristics of the Agent -- 7.2.1 The Plague Bacterium: Yersinia pestis 88 -- 7.2.1.1 Yersinia pestis Microbiology -- 7.2.1.2 Yersinia pestis Virulence Markers and Pathogenesis -- 7.2.1.3 Chromosomal Virulence Genes -- 7.2.1.4 Yersinia pestis Variants -- 7.2.2 Molecular Typing -- 7.3 Pathogenesis -- 7.3.1 Clinical and Pathological Signs -- 7.3.2 Diagnosis -- 7.3.2.1 Plague Prevention and Treatment -- 7.3.3 Plague as a Biological Weapon -- 7.4 Epidemiology -- 7.4.1 Plague Distribution Today -- 7.4.2 Plague in Its Historical Perspective -- 7.4.3 An Updated Plague Cycle? -- 7.4.3.1 Flea-Borne Plague Transmission.

7.4.4 Classical Plague Cycle -- 7.5 Conclusion -- References -- 8 Rickettsia Species: Rickettsioses -- 8.1 Introduction -- 8.2 Characteristics of the Agent -- 8.3 Phylogenetic Classification of Rickettsiae -- 8.3.1 Typhus Fever Group -- 8.3.2 Spotted Fever Group -- 8.3.3 Transitional Group Rickettsiae -- 8.3.4 Ancestral Group Rickettsiae -- 8.4 Diagnosis -- 8.4.1 Clinical Diagnosis -- 8.4.2 Laboratory Diagnostics -- 8.5 Pathogenesis -- 8.5.1 Clinical and Pathological Findings -- 8.6 Epidemiology -- 8.7 Conclusions -- Acknowledgments -- References -- 9 Mycobacterium tuberculosis: Tuberculosis -- 9.1 Introduction -- 9.2 Diagnostic Microbiology of Mycobacteria -- 9.3 Staining and Microscopic Examination -- 9.4 Cultivation of Mycobacteria -- 9.5 Identification of Mycobacteria from Culture -- 9.6 Identification of Mycobacteria Directly from Clinical Specimens -- 9.7 Immunological Tests for the Diagnosis of Mycobacterium tuberculosis Infection -- 9.8 Molecular Epidemiology of Tuberculosis -- 9.9 Theoretical Principles of Typing -- 9.10 Performance Criteria Applied in Selecting the Method for Molecular Typing of Microorganisms -- 9.10.1 Reproducibility -- 9.10.2 Discriminatory Power -- 9.10.3 Typeability -- 9.11 Genetic Elements in M. tuberculosis that Contribute to DNA Polymorphism: Current Methods Applied for Genotyping of M. tuberculosis -- 9.12 IS6110-RFLP Analysis -- 9.13 Spacer Oligonucleotide Typing - Spoligotyping -- 9.14 VNTR and MIRU Analysis -- 9.15 Single Nucleotide Polymorphism -- 9.16 The Clustering Question? -- 9.17 Conclusions -- References -- Part II Viruses -- 10 Influenza Virus: Highly Pathogenic Avian Influenza -- 10.1 Introduction -- 10.2 Characteristics of the Agent -- 10.2.1 Nomenclature -- 10.2.2 Genome and Protein Structure -- 10.2.3 Viral Replication -- 10.2.4 Antigenic Drift and Antigenic Shift -- 10.3 Pathogenesis.

10.3.1 Reservoir -- 10.3.2 Low and Highly Pathogenic Influenza Viruses -- 10.3.3 Molecular Determinants of Pathogenicity -- 10.4 Clinical and Pathological Findings -- 10.4.1 HPAI (H5N1) Infection in Animals -- 10.4.2 HPAI (H5N1) Infection in Humans -- 10.5 Diagnosis -- 10.5.1 Direct Diagnosis -- 10.5.2 Indirect Diagnosis -- 10.5.3 Pathotyping -- 10.6 Evolution and Geographic Spread of HPAI (H5N1) Viruses -- 10.6.1 Chronology of H5N1 Virus -- 10.6.1.1 First Wave -- 10.6.1.2 Second Wave -- 10.6.1.3 Third Wave -- 10.6.2 Focus on Africa -- 10.7 Epidemiology of Other Influenza Subtypes -- 10.7.1 HPAI Virus Outbreaks -- 10.7.2 LPAI Virus Outbreaks -- 10.8 Conclusion -- References -- 11 Variola: Smallpox -- 11.1 Introduction -- 11.2 Variola Virus -- 11.3 Human Monkeypox -- 11.4 Vaccinia Virus -- 11.5 Cowpox Virus -- 11.6 Collection of Specimens -- 11.7 Real-Time Polymerase Chain Reaction -- 11.8 Evaluation of Real-Time PCR Assays -- 11.9 Real-Time PCR Assays with Hybridization Probes -- 11.10 Real-Time PCR Assays with 5_ Nuclease Probes -- 11.11 Other Real-Time PCR Formats -- 11.12 Conclusions -- References -- 12 Arenaviruses: Hemorrhagic Fevers -- 12.1 Characteristics -- 12.2 Epidemiology -- 12.2.1 Old World Arenaviruses -- 12.2.2 New World Arenaviruses -- 12.3 Clinical Signs -- 12.3.1 Old World Arenaviral Hemorrhagic Fevers -- 12.3.2 New World Arenaviral Hemorrhagic Fevers -- 12.4 Pathological Findings -- 12.4.1 Old World Arenaviral Hemorrhagic Fevers -- 12.4.2 New World Arenaviral Hemorrhagic Fevers -- 12.5 Pathogenesis of Old and New World Hemorrhagic Fevers -- 12.6 Diagnostics -- 12.6.1 Serological Tests -- 12.7 PCR -- 12.7.1 Virus Culture and Antigen Testing -- 12.8 Disclaimer -- References -- 13 Filoviruses: Hemorrhagic Fevers -- 13.1 Characteristics -- 13.2 Epidemiology -- 13.3 Clinical Signs -- 13.4 Pathological Findings -- 13.5 Pathogenesis.

13.6 Diagnostic Procedures -- 13.7 Disclaimer -- References -- 14 Bunyavirus: Hemorrhagic Fevers -- Introduction -- 14.1 Crimean Congo Hemorrhagic Fever Virus: an Enzootic Tick Borne Virus Causing Severe Disease in Man -- 14.1.1 Introduction -- 14.1.2 Characteristics -- 14.1.3 Epidemiology -- 14.1.4 Clinical and Pathological Findings -- 14.1.5 Pathogenesis -- 14.1.6 Diagnosis -- 14.1.6.1 Virus Isolation -- 14.1.6.2 Molecular Methods -- 14.1.6.3 Antigen Detection -- 14.1.6.4 Serology -- References -- 14.2 Rift Valley Fever Virus: a Promiscuous Vector Borne Virus -- 14.2.1 Introduction -- 14.2.2 Characteristics of the Agent -- 14.2.3 Epidemiology -- 14.2.4 Clinical and Pathological Findings in Humans -- 14.2.5 Prophylaxis and Treatment -- 14.2.6 Pathogenesis -- 14.2.7 Diagnosis and Surveillance -- 14.2.8 Conclusions -- References -- 14.3 Hantaviruses: the Most Widely Distributed Zoonotic Viruses on Earth -- 14.3.1 Introduction -- 14.3.2 Characteristics of the Agent -- 14.3.3 Epidemiology -- 14.3.4 Clinical Findings -- 14.3.4.1 HFRS -- 14.3.4.2 HCPS -- 14.3.5 Pathogenesis -- 14.3.6 Diagnosis -- 14.3.6.1 Serology -- 14.3.6.2 Virus Detection -- References -- Part B Practical Guidelines -- Part I Bacteria -- 1 Bacillus anthracis -- Recommended Respiratory Protection -- Recommended Personal Protective Equipment -- Best Disinfection -- Surface and Equipment -- Skin/Wound Disinfection -- Best Decontamination -- Prevention -- Case Reports, Ongoing Clinical Trials -- Post Exposure Prophylaxis -- Known Laboratory Accidents -- Procedure Recommended in the Case of Laboratory Spill or Other -- Type of Accident -- Treatment of Disease -- Clinical Guidelines -- 2 Brucella Species -- Recommended Respiratory Protection -- Recommended Personal Protective Equipment -- Best Disinfection -- Best Decontamination -- Prevention -- Post Exposure Prophylaxis.

Known Laboratory Accidents.