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Contents

Notice

Committee on the Assessment of Future Needs for Variola (Smallpox) Virus

Board on Global Health

Preface

Acknowledgments

Executive Summary

PART I. INTRODUCTION

1 Introduction

Background
Contemporary Context
Scope
Scientific Needs for Variola Virus
Organization of This Report

PART II. SMALLPOX AND ITS CONTROL

2 Variola Virus and Other Orthopoxviruses

General Attributes of Orthopoxviruses
Poxvirus Replication
Properties of Specific Orthopoxviruses

3 Clinical Features of Smallpox

Entry and Infection
Dissemination
The Rash
Lesions of the Mucous Membranes
Effects on Other Organs
Immune Response
Immunity Against Smallpox

4 Epidemiology

Characteristics of Historical Outbreaks
Likely Characteristics of Future Smallpox Outbreaks
Control Strategies

5 Variola Virus Stocks Following Eradication of Smallpox

Establishment of International Repositories
Decision by the World Health Assembly to Destroy Variola Virus Stocks
U.S. Research on Smallpox
Research at CDC and USAMRIID

PART III. SCIENTIFIC NEEDS FOR VARIOLA VIRUS

6 Development of Antiviral Agents

In Vitro Assays
Animal Models

7 Development of Vaccines

Current Status of Vaccinia Vaccine Preparations
Evaluation of Vaccinia Vaccine Derived from Tissue Culture
Evaluation of Novel Vaccines

8 Detection and Diagnosis

Environmental Detection
Diagnosis of Infection
Alternatives to Live Virus

9 Bioinformatics

Variability of Variola Virus
Potential Developments

10 Understanding of the Biology of Variola Virus

Virus-Cell Interactions
Virus-Host Interactions

11 Research on the Expressed Protein Products of Variola

Synthesis of Variola Proteins
Potential Utility of Variola Proteins

PART IV. FINDINGS

12 Summary and Conclusions

The Broader Context
Scientific Needs for Live Variola Virus
Overall Conclusions

References

APPENDIXES

A Glossary

B Acronyms

C Committee and Staff Biographies