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Diphtheria is a contagious upper respiratory illness that was a major cause of childhood mortality in the prevaccine era. In the early twentieth century, an effective toxoid vaccine was developed. Implementation of childhood vaccination virtually eliminated diphtheria from developed countries after the Second World War and implementation of the Expanded Program on Immunization in developing countries led to rapid declines in diphtheria globally in the 1980s. However, in the 1990s, a massive epidemic of diphtheria spread throughout the countries of the former Soviet Union. Unlike the prevaccine era, most cases of severe disease and deaths were reported among adults. Multiple factors contributed to the epidemic, including increased susceptibility among both adults and children; suboptimal socioeconomic conditions; high population movement; and delay in implementing appropriate control measures. Mass immunization was the key element in the epidemic control strategy developed and implemented in a well-coordinated response by an international public health coalition. This strategy focused on rapidly raising population immunity of both adults and children; the immunization of more than 140,000,000 adults and adolescents and millions of children successfully controlled the epidemic. While improved coverage of children in developing countries with diphtheria toxoid has led to progressive decreases in diphtheria; eradication is unlikely in the foreseeable future and gaps in immunity among adult population exist or are developing in many other countries. Routine childhood immunization with diphtheria toxoid is the key to controlling diphtheria while the role of routine adult reimmunization is less established; mass immunization will remain an important control measure for widespread diphtheria outbreaks. [ABSTRACT FROM AUTHOR]