Diphtheria in the Postepidemic Period, Europe, 2000–2009

Karen S. Wagner

, Joanne M. White, Irina Lucenko, David Mercer, Natasha S. Crowcroft, Shona Neal, Androulla Efstratiou, and on behalf of the Diphtheria Surveillance Network

Author affiliations: Health Protection Agency, London, UK (K.S. Wagner, J.M. White, N.S. Crowcroft, S. Neal, A. Efstratiou); State Agency Infectology Center of Latvia, Riga, Latvia (I. Lucenko); World Health Organization Regional Office for Europe, Copenhagen, Denmark (D. Mercer); Public Health Ontario, Toronto, Ontario, Canada (N.S. Crowcroft); University of Toronto Dalla Lana School of Public Health, Toronto (N.S. Crowcroft)

Abstract

Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000–2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae infections.

In 1994, following success of widespread vaccination programs earlier in the century, diphtheria was proposed as a candidate for elimination in the World Health Organization (WHO) European Region; the goal was for elimination of indigenous diphtheria by 2000 (1). However, during the 1990s, when this goal seemed within sight, several factors caused a resurgence of diphtheria to epidemic proportions in the newly independent states of the former Soviet Union. There were a large number of unnecessary contraindications to vaccination in guidance for these countries at that time, which led to reductions in adequate vaccination coverage in children. This problem was exacerbated by mistrust in vaccinations among health professionals and the public and by use of low-dose formulation vaccine for primary vaccinations. Waning immunity in the adult population, large-scale population movements caused by breakup of the former Soviet Union, disruptions in health services, and lack of adequate supplies of vaccine and antitoxin for prevention and treatment in most affected countries provided conditions under which diphtheria could spread (2,3). At the peak of the epidemic in 1995, there were >50,000 cases reported in the WHO European Region (2). Intensive vaccination strategies brought the disease under control in most countries, but some endemic transmission still continues.
Clinical diphtheria is caused by toxin-producing corynebacteria. Three species (Corynebacterium diphtheriae, C. ulcerans, and C. pseudotuberculosis) can potentially produce diphtheria toxin. C. diphtheriae is the most common of potentially toxigenic species and is associated with epidemic diphtheria and person-to-person spread. The organism has 4 biovars (gravis, mitis, intermedius, and belfanti). C. ulcerans is historically associated with cattle or raw dairy products, and, although it is rarely reported, its incidence has increased slightly in some countries in western Europe and in the United States in recent years (4–6). C. pseudotuberculosis rarely infects humans and is typically associated with farm animals (7). Currently, no direct evidence has been found of person-to-person spread of C. ulcerans or C. pseudotuberculosis.
Classical respiratory diphtheria is characterized by formation of a gray-white pseudomembrane in the throat that is firmly adherent (8). A swollen, bull-neck appearance caused by inflammation and edema of soft tissues surrounding lymph nodes is associated with severe illness and higher death rates (8). In progressive disease, the toxin can bind to cardiac and nerve receptors and cause systemic complications. Milder respiratory disease may manifest as a sore throat, most commonly seen in patients who are fully or partially vaccinated. In some tropical areas, cutaneous symptoms, characterized by rolled-edge ulcers, are more common. Patients may have both cutaneous and respiratory disease. The purpose of this study was to analyze diphtheria data for Europe during 2000–2009.