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Disease Eradication Kenrad Nelson, MD Johns Hopkins University Objectives Review issues related to the eradication of an infectious disease − Smallpox Polio − 3 Section A Smallpox Disease Eradication: Definitions Cockburn (1961) − …the complete extinction of the pathogen that causes infectious disease… so long as a single member of the species survives, the eradication has not been accomplished Andrews and Langmuir (1963) − The purposeful reduction of specific disease prevalence to the point of a continued absence of transmission within a specific area X Note the elements of geography, time, and implied surveillance X This is probably the “best” simple definition WHO (1980) for smallpox − …the eradication of clinical infection by variola virus… since there is no carrier state, no subclinical infection, and no animal reservoir… the absence of clinical disease implies the absence of disease transmission 5 Advantages of an Eradication Strategy Advantages of a strategy of eradication of an infectious disease 1. Once disease is truly eradicated, further control efforts can be abandoned, with savings of cost, adverse vaccine reactions, etc. 2. Cost savings continue indefinitely when disease is eradicated 3. Expenditures for eradication are temporary 6 Disadvantages of an Eradication Strategy Disadvantages of a strategy of eradication of an infectious disease 1. Rigorous surveillance and control efforts need to be continued even when disease incidence is very low 2. Competition with more important diseases for the health care resources that are needed to support successful eradication 3. Some diseases have biological characteristics inimical to eradication, for example those with environmental or animal reservoir 7 Criteria to Determine Whether a Disease Is Eradicable Biological and technical feasibility Consensus on positive costs and benefits Broad societal and political support 8 Past Efforts at Disease Eradication Yellow fever − Aedes aegypti vector elimination 1915–1977; program failed because of sylvatic YF cycle Yaws − Disease affected only remote and rural population − Program 1954–1967; failed because applied to remote and rural population and political, social, economic support faltered Malaria − Insecticide spraying 1955–1969 − Failed due to insecticide resistance and lack of support Smallpox − Vaccination, surveillance, containment strategy − 1958–1980 − Successful 9 History of Smallpox 1. The disease smallpox (variola major) probably emerged from the first agricultural human settlements about 12,000 years ago 2. Evidence of smallpox in Egyptian mummies (1580– 1350 BC) and Ramses V (1157 BC) 3. Probably carried to India by Egyptian traders 4. Variola (“spotted”) applied to the disease by Bishop Marius of Switzerland during the 6th century; later called “smallpox” to distinguish variola from “greatpox,” i.e., syphilis, in 15th century 5. 16th century—imported into the Americas with widespread epidemics among Native American populations 6. 16th–18th centuries—major epidemics in Europe; 400,000 deaths per year from smallpox at end of 18th century 10 History of Smallpox 7. Use of pustular scabs from smallpox cases introduced into skin or by nasal insufflation began in India around 10th century 8. Edward Jenner, 1796, demonstrated that cowpox virus inoculated into skin could protect against smallpox 9. Vaccination with cowpox by arm-to-arm inoculation practiced during 19th century 10. Growth of cowpox in flank of calf publicized and used, 1864 11. 1940s—freeze-dried vaccine for production of vaccine 12. 1950—PAHO began program to eliminate smallpox from the western hemisphere − By 1967 smallpox still present only in Brazil 11 History of Smallpox 13. 1958—the U.S.S.R. proposed that WHO undertake a global program to eradicate smallpox 14. The WHO global smallpox eradication program began in 1967 At that time smallpox was endemic in 31 countries. An estimated − 10 to 15 million cases per year probably occurred in these endemic countries (131,789 cases reported). 15. October 16, 1977—the last naturally occurring case of smallpox diagnosed in Merka, Somalia 16. 1980—smallpox vaccination discontinued Except for special lab workers − 17. June, 1995—the last remaining smallpox cultures to be destroyed 12 Natural History of Smallpox 13 Smallpox Photo Source: CDC PHIL 14 Smallpox Photo Source: CDC PHIL 15 India: Cases of Smallpox Deaths and case-fatality rates, by age group, 1974–1975 No. of cases Case-fatality Age group No. of deaths (% distribution by age) rate Younger than 1 yr. 1,373 (6) 597 43.5 1–4 5,867 (25) 1,436 24.5 5–9 5,875 (25) 783 13.3 10–19 5,542 (23) 432 7.8 20+ 4,889 (21) 855 17.5 Total 23,546 (100) 4,103 17.4 Notes Available 16 Complications of Smallpox Vaccination—U.S.,1968 1. Postvaccinal encephalitis 16 cases, 4 deaths 2. Progressive vaccinia 5 cases, 2 deaths 3. Eczema vaccinatum 126 cases, 1 death 4. Generalized vaccinia 143 cases 5. Accidental infection 193 cases 6. Other complications 83 cases Total complications 566 cases, 7 deaths Total estimated number of vaccinations: 14,168,000 17 Complications of Smallpox Vaccination—U.S.,1968 Number of reported cases (deaths in parentheses) Vaccination Estimated Postvaccinal Progressive Eczema Generalized Accidental status and age number of Other encephalitis vaccinia vaccinatum vaccinia infection (yrs) vaccinations Primary vaccinations <1 614,000 4 (3) – 5 43 7 10 1–4 2,733,000 6 1 31 47 91 40 5–9 1,553,000 5 (1) 1 (1) 11 20 32 8 10–19 406,000 – 1 (1) 3 5 3 1 ≥20 288,000 1 2 7 13 4 5 Unknown – – 1 3 5 2 Total 16 (4) 5,594,000 5 (2) 58 131 142 66 Revaccinations – – – – – – – <1 478,000 – – 1 – 1 1 1–4 1,643,000 – 1 (1) 4 1 3 2 5–9 2,657,000 – 1 3 – – – 10–19 3,796,000 – 4 (1) – 9 3 6 ≥20 8,574,000 – 6 (2) 8 10 7 9 Total Unvaccinated – – 60 (1) 2 44 8 contacts Total 14,168,000 16 (4) 11 (4) 126 (1) 143 193 83 Notes Available 18 Complications of Vaccinia Immunizations Complications of vaccinia immunizations per million vaccinations, 1968 Vaccination status Ten-state survey CDC national survey Complications Primary Revaccination Primary Revaccination Accidental infection 529 42 25 0.8 Generalized vaccinia 242 9 23 1.2 Erythema multiforme 165 10 – – Eczema vaccinatum 39 3 10 0.9 Encephalitis 12 2 3 0 Progressive vaccinia* 1.5 3 0.9 0.7 Other 266 39 12 1.0 *Immunocompromised hosts are at greatest risk Notes Available 19 Progressive Vaccinia Photo Source: CDC PHIL 20 Progressive Vaccinia Photo Source: CDC PHIL 21 Eczema Vaccinatum Photo Source: CDC PHIL 22 Accidental Inoculation Photo Source: CDC 23 Contraindications of Smallpox Vaccination 1. Immune disorders − Agammaglobulinemia, neoplasms, immune- suppressive drugs, etc. 2. Eczema − Including eczema in a household contact 3. Pregnancy 4. Disorders of the central nervous system 24 Factors Favoring Successful Smallpox Eradication 1. A very effective vaccine that produced long lasting immunity 2. A high proportion of the population already vaccinated 3. Single genetically stable virus 4. No animal or environmental reservoir 5. Disease only moderately contagious (contagious after onset of rash) 25 Epidemiologic Features That Favor Eradication Epidemiologic features of smallpox that favor eradication Reservoir and host Man Transmissibility Relatively low Subclinical cases Never or rare Incubation Long—12 days Public concern Very great Vaccine Efficacy >98% Logistics Practical, bifurcated needle Cost Minimal Seasonality Striking 26 Essential Principles in WHO Eradication Program Essential principles in WHO smallpox eradication program 1. Development and use of uniformly potent smallpox vaccines tested at several international laboratories 2. Provision of widespread vaccination of populations in target countries where smallpox was endemic 3. Principle outcome measure was the absence of cases of smallpox X Program relied on active surveillance X When cases were identified, their contacts were immediately vaccinated to abort further transmission 27 Bifurcated Needle Photo Source: CDC 28 Smallpox Eradication Program: Bangladesh Surveillance 1. Mobile surveillance teams visit bazaars, schools, train and bus stations, beggar colonies, bustees 2. Rewards for notification of smallpox cases—at train and bus stations, rickshaw announcers, school children, soccer games 3. Intensive search around areas of outbreaks 4. Epidemiologic investigation of every smallpox outbreak to detect source, travel of case, and travel of contacts 5. Monthly municipal area house-to-house search 6. In later stages, national house-to-house search 29 Smallpox Eradication Program: Bangladesh 1. Isolation of patient in own house 2. Front and rear house guards (with vaccine) 3. Vaccinated all household contacts and visitors 4. Line listing of all residents within half-mile of infected house, vaccinated all 5. Searched for cases within five-mile