Smallpox and its Eradication

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Cover Smallpox and its Eradication Jan 1989, 9241561106 Contents Foreword Preface Acknowledgements 1. The Clinical Features of Smallpox Introduction Varieties of smallpox The classification of clinical types of variola major Ordinary-type smallpox The incubation period Symptoms of the pre-eruptive stage The eruptive stage Clinical course Grades of severity Modified-type smallpox Variola sine eruptione Subclinical infection with variola major virus Evidence from viral isolations Evidence from serological studies Flat-type smallpox The rash Clinical course Haemorrhagic-type smallpox General features Early haemorrhagic-type smallpox Late haemorrhagic-type smallpox Variola minor Clinical course Variola sine eruptione and subclinical infection Smallpox acquired by unusual routes of infection Inoculation variola and variolation Congenital smallpox Effects of vaccination on the clinical course of smallpox Effects of vaccination on toxaemia Effects of vaccination on the number of lesions Effects of vaccination on the character and evolution of the rash Effects of vaccination in variola minor Laboratory findings Virological observations Serological observations Haematological observations Complications The skin Ocular system Joints and bones Respiratory system Gastrointestinal system Genitourinary system Central nervous system Sequelae Pockmarks Blindness Limb deformities Prognosis of variola major Calculation of case-fatality rates Effects of immunity Effects of age Effects of pregnancy Clinical type of disease Differential diagnosis Ordinary- and flat-type smallpox Haemorrhagic-type smallpox Effects of prior vaccination on symptomatology Alternative diagnoses Laboratory confirmation of smallpox diagnosis Treatment : prophylactic and curative Vaccination during the incubation period Immunoprophylaxis and immunotherapy Chemoprophylaxis and chemotherapy Symptomatic treatment 2. Variola Virus and Other Orthopoxviruses Introduction Classification and nomenclature Development of knowledge of the structure of poxvirions The nucleic acid of poxviruses Classification of poxviruses Chordopoxvirinae: the poxviruses of vertebrates The genus Orthopoxvirus Recognized species of Orthopoxvirus Characteristics shared by all species of Orthopoxvirus Morphology of the virion Antigenic structure Composition and structure of the viral DNA Non-genetic reactivation Characterization of orthopoxviruses by biological tests Lesions in rabbit skin Pocks on the chorioallantoic membrane Ceiling temperature Lethality for mice and chick embryos Growth in cultured cells Inclusion bodies Comparison of biological characteristics of different species Viral replication Adsorption, penetration and uncoating Assembly and maturation Release Cellular changes Characterization of orthopoxviruses by chemical methods Comparison of viral DNAs Comparison of viral polypeptides Summary: distinctions between orthopoxviruses Variola virus Isolation from natural sources Variola major and variola minor Laboratory investigations with variola virus Pathogenicity for laboratory animals Growth in cultured cells Laboratory tests for virulence Differences in the virulence of strains of variola major virus Comparison of the DNAs of strains of variola virus Differences between the DNAs of variola and monkeypox viruses Genetic studies Species diagnosis Vaccinia virus Isolation from natural sources The variability of strains and their pathogenicity Variation within a strain Genetic studies Species diagnosis Cowpox virus Cowpox and horsepox in Europe Genetic studies Species diagnosis Laboratory confirmation of smallpox diagnosis Preparation of a guide for laboratory diagnosis Methods of laboratory diagnosis Comparison of different laboratory diagnostic methods Tests for species-specific viral antibodies Resistance to physical and chemical agents Vaccinia virus Variola virus Speculations about the origins of variola virus The diversity and specificity of viruses of man Requirements for human-to-human transmission Possible derivation of variola virus from another Orthopoxvirus Variola virus as the descendant of an Orthopoxvirus of early man Conclusions 3. The Pathogenesis, Pathology and Immunology of Smallpox and Vaccinia Introduction The portal of entry of variola virus The respiratory tract Inoculation smallpox The conjunctiva Congenital infection The spread of infection through the body Mousepox Rabbitpox Monkeypox Variola virus infection in non-human primates Smallpox in human subjects The dissemination of virus through the body The rash Toxaemia Pathological anatomy and histology of smallpox General observations The skin lesions Lesions of the mucous membranes of the respiratory and digestive tracts Effects on other organs The histopathology of vaccinia and vaccinia1 complications Normal vaccination Postvaccinial encephalitis Viral persistence and reactivation Persistence of variola virus in human patients Persistence of orthopoxviruses in animals Epidemiological significance The immune response in smallpox and after vaccination Protection against reinfection Humoral and cellular responses in orthopoxvirus infections Methods for measuring antibodies to orthopoxviruses The humoral response in relation to pathogenesis Methods for measuring cell-mediated immunity Cell-mediated immunity in relation to pathogenesis The immune response in smallpox The immune response after vaccination Cells involved in immunological memory Reducing the risks of vaccination Inactivated virus vaccines Non-specific mechanisms involved in host defence Body temperature Nutrition Age Hormonal effects Interferon Genetic aspects of resistance to smallpox Natural selection for resistance to smallpox Summary : the pathogenesis of smallpox Viral entry and infection Spread through the body The immune response Death or recovery 4. The Epidemiology of Smallpox Introduction The morbidity and mortality of smallpox in the 20th century Secular changes in the global occurrence of smallpox Smallpox incidence and incidence rates The effect of vaccination on the incidence of smallpox Case-fatality rates in smallpox Smallpox epidemics in endemic countries Seasonal variations in incidence Infection and infectivity Routes of exit and entry of virus Shedding of variola virus Routes of infection The infectious dose of variola virus The incubation period of smallpox The infectivity of cases of smallpox The infectivity of case contacts not exhibiting disease Transmission Contact infection Indirect transmission Factors affecting the spread of smallpox Individual susceptibility Social factors Demographic factors Political and economic factors Variolation and laboratory-associated smallpox Patterns of spread in populations Spatial distribution The rate of spread within small groups Spread in institutions Dispersal by travellers Illustrative case studies in rural areas Illustrative case studies in urban areas Summary 5. The History of Smallpox and Its Spread Around the World Introduction Smallpox before AD 1000 Egypt India South-western Asia Europe China and Japan Summary: the spread of smallpox from antiquity until AD 1000 Smallpox in southern Asia between 1000 and 1900 The Indian subcontinent Burma, Siam and Indochina South-western Asia Smallpox in eastern Asia between 1000 and 1900 China and Korea Japan Indonesia and the Philippines Smallpox in Europe between 1000 and 1900 The spread of smallpox by European explorers and colonists Smallpox in Africa between 1000 and 1900 Smallpox in the Americas between 1507 and 1900 The Spanish and Portuguese colonies North America Smallpox in Oceania between 1789 and 1900 Australia New Zealand Papua New Guinea Other Pacific islands The appearance and spread of variola minor Summary: smallpox from antiquity to the end of the 19th century 6. Early Efforts at Control: Variolation, Vaccination, and Isolation and Quarantine Introduction Variolation Variolation and vaccination performed with different viruses Variolation in China Variolation in India and south-western Asia Introduction of variolation into Europe Introduction of variolation into the Americas Variolation in Africa The discovery of vaccination Jenner's observations and experiments The world-wide acceptance of vaccination Early problems with vaccination Evidence for the efficacy of vaccination Control by isolation and quarantine Quarantine for shipping Isolation of cases The establishment of smallpox hospitals 7. Developments in Vaccination and Control Between 1900 and 1966 Introduction Vaccine production and quality control before 1967 Production of vaccine lymph Preparation of liquid vaccine Preparation of dried vaccine Quality control Vaccination techniques before 1967 Vaccination site Methods of vaccination Age for primary vaccination Interpretation of the results of vaccination Complications of vaccination Types of complication Frequency of complications Contraindications to vaccination Prevention and treatment of complications Reconsideration of vaccination policies in non-endemic countries Complications : the overall picture Programmes for vaccination and revaccination Vaccination and revaccination of the general public Simultaneous vaccination with several antigens Vaccination of international travellers 8. The Incidence and Control of Smallpox Between 1900 and 1958 Introduction Variations in the incidence of variola major and variola minor The elimination of smallpox from Europe by 1953 United Kingdom Russia and the Union of Soviet Socialist Republics Germany France Portugal and Spain Scandinavia The elimination of smallpox from North America, Central America and Panama by 1951 Central America and Panama United States of America Canada Mexico Smallpox in South America, 1900-1958 Brazil Other countries Smallpox in Asia, 1900-1958 Eastern Asia China Japan Korea Indonesia Philippines Malaysia Burma Thailand Indochina The Indian subcontinent and Afghanistan India Pakistan and Bangladesh Afghanistan Sri Lanka South-western Asia Smallpox in Africa, 1900-1958 North Africa Western, central and eastern Africa Western Africa Central Africa Eastern Africa Southern Africa Angola and Mozambique Malawi, Zambia and Zimbabwe South Africa and adjacent countries Madagascar Smallpox in Oceania during the 20th century Australia New Zealand Hawaii Summary: the global incidence of smallpox, 1900-1958 9. Development of the Global Smallpox Eradication Programme, 1958-1966 The commitment to global smallpox eradication, 1958-1959 History of the concept of eradication Introduction Eradication of animal diseases The first eradication programmes for human diseases - hookworm and yellow fever Aedes aegypti eradication Eradication of another mosquito vector - Anopheles gambiae Programmes for the eradication of malaria, yaws and other human diseases WHO smallpox control and eradication activities, 1946-1958 Introduction Smallpox eradication in the Region of the Americas An abortive attempt to launch a global smallpox eradication programme, 1953 The smallpox eradication programme, 1959-1966 Introduction Status of smallpox, 1959 The global eradication programme begins, 1959 Budgetary provision for the programme Programme activities, 1959-1962 Proposed provision of support through the WHO regular budget, 1963 Voluntary contributions The first WHO Expert Committee on Smallpox, 1964 The Seventeenth World Health Assembly, 1964 A retrospective view of progress in smallpox eradication, 1959-1964 Events leading to the introduction of an intensified global programme, 1965 The Eighteenth World Health Assembly, 1965 A special budget for smallpox eradication, 1966 The Director-General’s report to the Nineteenth World Health Assembly The discussions at the Executive Board (January 1966) and at the Nineteenth World Health Assembly (May 1966) Preparations for initiating the Intensified Programme, 1966 Summary 10. The Intensified Smallpox Eradication Programme, 1967-1980 Introduction The strategic plan The World Health Organization The Members and governing bodies of WHO Role of the Director-General WHO programme management in Geneva The Smallpox Eradication unit in Geneva WHO regional offices WHO representatives in countries Smallpox eradication programme staff Obtaining national agreements to undertake programmes Sustaining government interest and commitment Role of the World Health Assembly Surveillance reports Interregional and intercountry meetings of smallpox eradication staff Use of the mass media International support in cash and in kind The WHO regular budget Other types of assistance to programmes Supply of vaccine and vaccination instruments Vaccine requirements Support for production laboratories in endemic countries Vaccine donations Development of vaccination devices Vaccine practices and complications Surveillance and notification of smallpox cases The concept of surveillance The routine systematic collection of data Changes in the international data collection system International surveillance reports Research A natural reservoir of smallpox Epidemiological observations Vaccination practices Vaccine production and testing Characterization of the orthopoxviruses Summary Strategies and tactics in the execution of national programmes Introduction Mass vaccination campaigns The surveillance-containment strategy Surveillance and containment measures after September 1973 Conclusions A chronology of progress, 1967-1980 Introduction The situation at the start of the Intensified Programme, 1967 The situation in 1968 The situation in 1969 The situation in 1970 The situation in 1971 The situation in 1972 The situation in 1973 The situation in 1974 The situation in 1975 The achievement of global eradication, 1976-1977 The certification and formal declaration of global eradication, 1978-1980 11. Smallpox Vaccine and Vaccination in the Intensified Smallpox Eradication Programme Introduction Vaccine requirements for the Intensified Smallpox Eradication Programme Providing the finance Shortfalls in vaccines-quality and quantity WHO survey of vaccine producers Methods of vaccine production Strains of vaccinia virus Number of doses per container Initial potency Heat stability Bacterial count Establishment of the WHO reference centres for smallpox vaccine Development of improved vaccines Meeting of experts (March 1968) Production of freeze-dried vaccine Continuing quality control of smallpox vaccine Testing samples of vaccine Visits by consultants Reference vaccine Seed lots of vaccine Evaluation of testing methods Improvements in vaccine quality Vaccine production in endemic countries Donations of vaccine and their distribution New vaccination techniques The bifurcated needle Jet injectors Modification to vaccination procedures Preparation of skin Neonatal vaccination The search for new vaccines Selection of vaccinia virus strains of low pathogenicity Attenuated strains Inactivated vaccines Production of vaccine in eggs and tissue culture Silicone ointment vaccine Efficacy of vaccination 12. South America Introduction Regional strategy and allocation of resources The programme in Brazil Development of the Brazilian national programme, 1966 The beginning of the vaccination campaign, 1966-1967 The outbreak in Branquinhas The repercussions of the Branquinhas outbreak The vaccination campaign gains momentum, 1968 The beginning of an effective surveillance programme, 1969 Conclusion of the vaccination campaign, 1970 The last known cases of smallpox in Brazil Expansion of the reporting network, 1970-1971 Numbers of reported cases and deaths, 1968-1969 Resources employed Smallpox vaccine production Conclusions 13. Indonesia Introduction The decision to begin the programme Demography and geography of Indonesia and its history of smallpox control Smallpox incidence, 1963-1967 Organization of the programme, January-June 1968 The early stages of the programme, June 1968 July 1969 The strategy changes, July 1969 Tjirebon regency Bandung regency Bogor regency Factors affecting transmission The surveillance-containment strategy becomes fully established Strengthening of programmes in the outer islands, 1970 Indonesia's last outbreak, 1971 Morbidity and mortality patterns Conclusions 14. Afghanistan and Pakistan Introduction Afghanistan Smallpox control before 1963 Commencement of a WHO-assisted vaccination campaign, 1963 Changes in the strategy and structure of the eradication programme, January 1969 Progress in the vaccination campaign The elimination of smallpox : epidemiological patterns, 1969 The final outbreaks Conclusion of the programme Epidemiological data The problem of variolation Pakistan Smallpox before 1967 Programme strategy Studies of smallpox in West Pakistan, 1966-1967 Beginning of the mass vaccination campaign, 1968-1969 One programme becomes six, July 1970 The fourth year of the programme, 1971 Commencement of country-wide activities, 1972 Variolation in Pakistan Conclusions 15. India and the Himalayan Area Introduction India Background Smallpox in India before 1962 India's national smallpox eradication programme, 1962 The Intensified Smallpox Eradication Programme begins, 1967 Assessment of the programme in India, October 1967 Progress achieved in the programme, 1968-1970 The foundations are laid for the intensified national campaign, 1971-1973 The Intensified Programme in India, June-December 1973 The darkest months of the programme, January-June 1974 A redoubled effort, June-December 1974 “Operation Smallpox Zero”, January 1975 The last case in India, May 1975 India celebrates Independence Day and freedom from smallpox, August 1975 Morbidity and mortality data Nepal Introduction The country: geographical and socio-cultural considerations A smallpox control pilot project begins, 1962 The programme extends beyond the Kathmandu valley, 1968 The programme strategy changes, 1971 Cost of the programme Sikkim and Bhutan Sikkim Bhutan Summary Conclusions 16. Bangladesh Introduction Background Smallpox and its control before 1968 The WHO-supported eradication programme begins, 1968 Initiation of surveillance-containment and the interruption of transmission, 1970-1971 The refugee camps and the reintroduction of smallpox, December 1971-May 1972 The programme is re-established, June 1972-September 1973 Reorganization of the health services, October 1973 An emergency plan for smallpox control, April 1974-January 1975 National mobilization for smallpox eradication, February 1975 Special search programmes The final chapter The last outbreak Morbidity and mortality data Conclusions 17. Western and Central Africa Introduction The region of western and central Africa Origins of the regional programme, 1961-1965 The addition of smallpox eradication as an objective Government agreements and organization of the programme Preparation for the campaign, January-December 1966 Characteristics of western and central Africa Plans for the programme Execution of the programme Coordination with international organizations Changing roles of the CDC office and the Lagos regional office Surveillance and containment activities National programmes Nigeria Dahomey and Togo Mali, Niger and Upper Volta Guinea and Sierra Leone Cote d'Ivoire, Ghana and Liberia The Gambia, Mauritania, and Senegal The OCEAC countries: Cameroon, Central African Republic, Chad, the Congo and Gabon Conclusions 18. Zaire and Sudan Introduction Zaire Background Smallpox before 1967 The eradication programme begins, 1967-1968 The restructuring of the programme, September 1968 The vaccination campaign becomes fully established, 1970 The problem of surveillance The discovery of a case of monkeypox in a human being The creation of a surveillance programme, 1971 Sudan Background Population movements Smallpox in the Sudan before 1968 The decision to undertake an eradication programme, 1967 Smallpox is reintroduced into the Sudan The national mass vaccination campaign is launched, 1969 Recurrent epidemic smallpox, December 1968 Major epidemics begin, 1970 The initiation of an effective surveillance-containment programme, 1971 Conclusion 19. Eastern Africa: Kenya, Uganda, United Republic of Tanzania, Rwanda and Burundi Introduction Smallpox control activities before 1969 Agreements to undertake eradication programmes Provision of freeze-dried vaccine The vaccination campaigns Kenya Uganda Tanzania Rwanda and Burundi Smallpox occurrence, 1969-1970 Importations into Uganda Importations into Kenya Conclusion 20. Southern Africa Introduction Zambia Malawi, Mozambique and Southern Rhodesia Background Vaccination campaigns The smallpox situation Age distribution of cases South Africa, Botswana, Lesotho, Namibia and Swaziland Background Lesotho, Namibia and Swaziland South Africa Botswana Angola Conclusion 21. Ethiopia, Yemen and Democratic Yemen Introduction Yemen Democratic Yemen Ethiopia Background Delays in launching an eradication programme The programme begins, 1971 The second year, 1972 A year of hope, 1973 A year of turmoil, 1974 The final phase, 1975-1976 Morbidity and mortality data Exportation of cases Conclusions 22. Somalia and Djibouti Introduction Background Population movements and health facilities Smallpox and its control before 1969 The commencement of the smallpox eradication programme, 1969 The smallpox outbreak in Mogadishu, September 1976 Initial containment measures First coordination meeting, March 1977 Epidemic smallpox in Somalia, March 1977 The emergency programme, May 1977 The epidemic, March to October 1977 Surveillance among nomads in adjacent areas of Ethiopia The last smallpox outbreak, October 1977 Morbidity and mortality data, 1977 Conclusions 23. Smallpox in Non-endemic Countries Introduction Criteria for defining non-endemic countries The significance of smallpox in non-endemic countries Actions taken by the non-endemic countries Actions taken by WHO Smallpox in Europe, 1959-1978 Sources of importations Nature of index cases Delays in notification Transmission from imported cases Case studies of importations into Europe Importations into North America after 1959 Importations into Japan Importations into recently endemic countries, 1959-1976 Africa South America Southern Asia The 1970-1972 outbreak in south-western Asia and Europe Iran Iraq Syrian Arab Republic Yugoslavia Laboratory-associated outbreaks in the United Kingdom The London outbreak, 1973 The Birmingham outbreak, 1978 Outbreak of variola minor in the Midlands and Wales, 1966 Conclusions 24. The Certification of Eradication : Concepts, Strategy and Tactics Introduction Historical development of the concept of certification Eradication : definition and criteria Definition in terms of vaccination programmes (1962) Definition in terms of the interruption of transmission (1968-1980) Development of strategies for certification South America Indonesia Western Africa Coordination of certification activities National preparations for certification Effectiveness of the routine reporting system Active searches for unreported cases Pockmark surveys Chickenpox surveillance Rumour register Specimens for laboratory diagnosis Publicity campaigns and rewards Documentation Operation of international commissions Membership Mode of operation Procedures for global certification Consultation on the Worldwide Certification of Smallpox Eradication Establishment and responsibilities of the Global Commission Chronology of certification Declaration of the global eradication of smallpox Annex 24.1. Membership of international commissions for the certification of smallpox eradication Annex 24.2. Participants in the Consultation on the Worldwide Certification of Smallpox Eradication and members of the Global Commission 25. Certification by International Commissions: 1973-1977 Introduction Certification in South America Recent history of smallpox Precertification activities Visit of the International Commission Certification in Indonesia Recent history of smallpox Precertification activities Visit of the International Commission Certification in Africa south of the Sahara Western Africa Recent history of smallpox Preparations for certification Visit of the International Commission Central Africa Recent history of smallpox Preparations for certification Visit of the International Commission Certification in Afghanistan and Pakistan Afghanistan Precertification activities Visit of the International Commission Pakistan Precertification activities Visit of the International Commission Certification in the rest of the Indian subcontinent and Burma India, Nepal and Bhutan India Nepal Bhutan Visit of the International Commission Burma and Bangladesh Burma Bangladesh Visit of the International Commission Conclusions 26. Certification of 29 Countries in Africa and Asia: 1978-1979 Introduction Southern Africa Logistics Malawi, Mozambique, United Republic of Tanzania, and Zambia Botswana, Lesotho and Swaziland South Africa Namibia Southern Rhodesia (Zimbabwe) Angola Madagascar Uganda and the Sudan Uganda Sudan South-western Asia Yemen Democratic Yemen Arab countries of the Gulf area: Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates Iran Iraq Syrian Arab Republic South-eastern Asia Lao People’s Democratic Republic and Viet Nam Democratic Kampuchea Thailand Conclusions 27. The Completion of Global Certification: The Horn of Africa and China Introduction Preparations for the certification of smallpox eradication in the Horn of Africa Coordination of arrangements for certification Precertification activities in Ethiopia Precertification activities in Somalia Precertification activities in Kenya Precertification activities in Djibouti Smallpox surveillance among Muslim pilgrims from the Horn of Africa Certification of smallpox eradication in the Horn of Africa Preliminary visits to Ethiopia Visits by the international commissions Joint meeting in Nairobi Certification of smallpox eradication in China Lack of information on smallpox eradication Development of effective contacts with China Smallpox in Yunnan Province Smallpox in Xizang Autonomous Region (Tibet) Province of Taiwan Variolation in China after 1950 Variola virus stocks Review by the Global Commission Conclusions 28. Post-eradication Operations: Implementation of the Recommendations of the Global Commission Introduction Vaccination policy Routine vaccination programmes Vaccination certificates for international travel Reserve stocks of vaccine WHO reserve stocks of vaccine National stocks of vaccine Seed lots of vaccinia virus Vaccine production laboratories Investigation of suspected smallpox cases Guidelines for the management of suspected cases of smallpox The international rumour register Laboratories retaining variola virus stocks Reduction in number Inspection Human monkeypox Epidemiological surveillance in Zaire Review of monkeypox, March 1986 Laboratory investigations Laboratory diagnosis of suspected smallpox and monkeypox Continuing research on orthopoxviruses Other studies of variola and “whitepox” viruses Documentation of the smallpox eradication programme Publications The smallpox eradication programme archives WHO Headquarters staff Staff arrangements at WHO Headquarters Committee on Orthopoxvirus Infections Use of vaccinia virus as a vector for foreign genes 29. Human Monkeypox and Other Poxvirus Infections of Man Introduction Monkeypox in captive primates The properties of monkeypox virus Pathogenicity for laboratory animals Comparison of DNA maps of strains of monkeypox virus Genetic studies Species diagnosis Serological diagnosis of past monkeypox infection Human monkeypox Discovery of human infections Organization of laboratory research Organization of field research Incidence and distribution Clinical features Epidemiology Ecological studies Monkeypox: the overall picture Other Orthopoxvirus infections of man Vaccinia Cowpox Camelpox Parapoxvirus infections Molluscum contagiosum Tanapox virus infections General comment 30. Potential Sources for a Return of Smallpox Introduction Is there an animal reservoir of variola virus? The example of yellow fever Smallpox in apes and monkeys Monkeypox “Whitepox” virus isolations Conclusion: There is no animal reservoir of variola virus Material stored by variolators Laboratory stocks of variola virus Changes in attitude towards work with variola virus Safety regulations in laboratories holding and handling variola virus Justification for the retention and use of variola virus Reduction in the number of laboratories retaining variola virus Deliberate release Reactivation and excretion of virus in humans Viral persistence in the environment “Transformation” as a source of variola virus General conclusions 31. Lessons and Benefits Introduction Principles and lessons Political commitment, coordination and implementation The importance of a special programme Definition of objectives and goals Quality control Programme management Research Certification Costs and benefits The cost to the developing countries The cost to the industrialized countries Expenditure Implications for the future Eradication of other diseases Conclusion References Index of Names Subject Index