Diphtheria in the Postepidemic Period, Europe, 2000–2009
Diphtheria in the Postepidemic Period, Europe, 2000–2009
Substantial progress has been made in controlling diphtheria across Europe since the epidemic in the 1990s, but diphtheria has not disappeared as a serious public health threat. After major disruption to a mass vaccination program, recovery time is lengthy, and pockets of unvaccinated persons can remain because recovery is not necessarily homogeneous.
The protective effect of vaccination in preventing progression to severe disease is clear. However, 64 patients in Latvia recorded as fully vaccinated had classic respiratory diphtheria symptoms. Most of these patients were infected during a military outbreak in 2000 and would have been scheduled for primary vaccinations during the 1980s, when changes in vaccines, vaccination policy, medical practice, and public acceptance led to less intensive vaccination of children in the former Soviet Union. Beginning in 1980, Soviet vaccination recommendations enabled use of an alternative primary vaccination schedule against diphtheria that recommended 3 doses of a lower-potency vaccine. The classification of fully/partially vaccinated relies on specific interpretation of a country. Since the 2000 outbreak, greater attention has been given to checking vaccination records of new recruits into the Latvian military, and booster vaccinations are given where appropriate.
Lower CFRs for respiratory diphtheria in disease-endemic areas compared with those in nonendemic areas highlight how lack of familiarity with a rare disease can affect diagnosis and treatment. As the incidence of diphtheria has decreased, so has the practice of routine laboratory screening. No DIPNET member country routinely screens all throat swab specimens for corynebacteria, although sentinel screening of all throat swab specimens is conducted in Denmark, Ireland, and the United Kingdom. All other DIPNET countries (and outside sentinel screening areas) perform screening only at the request of the clinician or if the laboratory identifies particular criteria for screening from information accompanying a swab specimen (DIPNET, unpub. data). This practice has resulted in a loss of laboratory expertise and the opportunity for infections to go undetected because only clinically indicated swab specimens are tested; thus, milder cases or those with unusual manifestations may be missed.
A recent DIPNET external quality assurance evaluation of 6 simulated throat specimens found that only 6 of 34 international centers produced acceptable results for all 6 specimens; many centers could not isolate the target organism. In some poor countries, screening can be limited by cost of laboratory reagents, and problems have also occurred in obtaining Elek reagents and media. During a recent screening study across 10 countries in Europe, toxigenic organisms were isolated in Latvia and Lithuania. At least one of these cases in Lithuania would not have been correctly diagnosed in the absence of the screening study. In addition to the potential for missed or late diagnoses, in areas where diphtheria is not endemic, diphtheria antitoxin treatment is not always available, which can have serious consequences. A recent international survey highlighted global shortages of diphtheria antitoxin. Information about administration and timing of antitoxin treatment was not collected for this analysis, but studying such timing in relation to differing CFRs would be useful.
Higher incidence rates of C. diphtheriae among women in disease-endemic countries could be caused by several factors. Women more commonly work as caregivers in domestic and health care settings, consultation rates are usually higher among women, and men are more likely to have received diphtheria vaccine during military service.
Although the United Kingdom, France, and Germany regularly report isolations of toxigenic C. ulcerans, it is unlikely that this organism is present only in these countries. The ability to detect C. ulcerans could indicate the capability of a country to detect potentially toxigenic organisms and provide an indicator of good surveillance. Detection of mild diphtheria cases (any toxigenic organism) is another potential indicator of good surveillance. C. ulcerans appears to have a wide host range and has been isolated from many domestic and wild animals, including the killer whale and lion (nontoxigenic strain). During 2002 and 2003, toxigenic C. ulcerans strains isolated from domestic cats in the United Kingdom were found to have the predominant ribotypes observed among human clinical isolates, which suggests that cats could be a potential reservoir for human infection. Identical C. ulcerans strains have been isolated from diphtheria patients and dogs in France and the United Kingdom. The presence of this organism reinforces the need to maintain high vaccination levels in all countries. Higher incidence of infection among elderly women could be related to pet ownership habits, in combination with low or waning immunity.
Vaccination coverage for diphtheria is assessed annually in many countries in Europe by using a range of methods, including computerized vaccination registers, survey methods, administrative methods, or a combination. These methods will provide varying degrees of accuracy in coverage estimates, which makes countries difficult to compare. Coverage for vaccination with diphtheria-tetanus-pertussis 3 vaccine (third dose of diphtheria, tetanus, pertussis vaccine) in early childhood in 2009 was >90% for most (85%) countries in the European Region, and 66% of countries (including Latvia, Lithuania, Turkmenistan, and the Russian Federation) reported coverage >95% Coverage in Ukraine decreased from 98% in 2006 and 2007 to 90% in 2008 and 2009. Austria, Denmark, Georgia, and Moldova recorded diphtheria-tetanus-pertussis 3 vaccine coverage <90%. Azerbaijan and Malta had the lowest coverage (73% for both countries) in the European Region in 2009.
Following high-profile vaccine-scare stories in some countries in eastern Europe, such as the Russian Federation and Ukraine, anti-vaccination groups have gained strength by using television, the Internet, and other media for publicity; this activity could seriously affect vaccination coverage. Adult diphtheria immunity can be increased through scheduled booster vaccinations every 10 years (e.g., as in Austria, Belgium, Bulgaria, Cyprus, Estonia, Finland, France, Germany, Greece, Latvia, Norway, Portugal, and Romania) or as part of a combined tetanus and low-dose diphtheria vaccine given for tetanus-prone injuries. In Latvia, annual adult vaccination coverage surveys are undertaken, but in most countries adult coverage is rarely assessed. Seroprevalence studies have indicated that many adults in some countries have immunity levels below the protective threshold. Gaps in immunity in the adult population contributed to the resurgence of diphtheria in eastern Europe during the 1990s.
Trends in diphtheria cases in Europe are encouraging, but continued striving for improved vaccination coverage is essential. Diphtheria has a socioeconomic component; outbreaks are typically seen in marginalized groups. In the current economic climate, more socially deprived groups that are vulnerable to infection will emerge. The economic crisis may also threaten supplies of vaccine and antitoxin and delivery of immunization programs. Because reductions in finances can limit the capacity for surveillance, decreases in case reporting need to be interpreted with caution. Every effort must be made to maintain high diphtheria vaccination coverage.
Ms Wagner is a scientist in epidemiology at the Health Protection Agency in London, UK. Her research interests are diphtheria epidemiology and immunization and migrant health.
Discussion
Substantial progress has been made in controlling diphtheria across Europe since the epidemic in the 1990s, but diphtheria has not disappeared as a serious public health threat. After major disruption to a mass vaccination program, recovery time is lengthy, and pockets of unvaccinated persons can remain because recovery is not necessarily homogeneous.
The protective effect of vaccination in preventing progression to severe disease is clear. However, 64 patients in Latvia recorded as fully vaccinated had classic respiratory diphtheria symptoms. Most of these patients were infected during a military outbreak in 2000 and would have been scheduled for primary vaccinations during the 1980s, when changes in vaccines, vaccination policy, medical practice, and public acceptance led to less intensive vaccination of children in the former Soviet Union. Beginning in 1980, Soviet vaccination recommendations enabled use of an alternative primary vaccination schedule against diphtheria that recommended 3 doses of a lower-potency vaccine. The classification of fully/partially vaccinated relies on specific interpretation of a country. Since the 2000 outbreak, greater attention has been given to checking vaccination records of new recruits into the Latvian military, and booster vaccinations are given where appropriate.
Lower CFRs for respiratory diphtheria in disease-endemic areas compared with those in nonendemic areas highlight how lack of familiarity with a rare disease can affect diagnosis and treatment. As the incidence of diphtheria has decreased, so has the practice of routine laboratory screening. No DIPNET member country routinely screens all throat swab specimens for corynebacteria, although sentinel screening of all throat swab specimens is conducted in Denmark, Ireland, and the United Kingdom. All other DIPNET countries (and outside sentinel screening areas) perform screening only at the request of the clinician or if the laboratory identifies particular criteria for screening from information accompanying a swab specimen (DIPNET, unpub. data). This practice has resulted in a loss of laboratory expertise and the opportunity for infections to go undetected because only clinically indicated swab specimens are tested; thus, milder cases or those with unusual manifestations may be missed.
A recent DIPNET external quality assurance evaluation of 6 simulated throat specimens found that only 6 of 34 international centers produced acceptable results for all 6 specimens; many centers could not isolate the target organism. In some poor countries, screening can be limited by cost of laboratory reagents, and problems have also occurred in obtaining Elek reagents and media. During a recent screening study across 10 countries in Europe, toxigenic organisms were isolated in Latvia and Lithuania. At least one of these cases in Lithuania would not have been correctly diagnosed in the absence of the screening study. In addition to the potential for missed or late diagnoses, in areas where diphtheria is not endemic, diphtheria antitoxin treatment is not always available, which can have serious consequences. A recent international survey highlighted global shortages of diphtheria antitoxin. Information about administration and timing of antitoxin treatment was not collected for this analysis, but studying such timing in relation to differing CFRs would be useful.
Higher incidence rates of C. diphtheriae among women in disease-endemic countries could be caused by several factors. Women more commonly work as caregivers in domestic and health care settings, consultation rates are usually higher among women, and men are more likely to have received diphtheria vaccine during military service.
Although the United Kingdom, France, and Germany regularly report isolations of toxigenic C. ulcerans, it is unlikely that this organism is present only in these countries. The ability to detect C. ulcerans could indicate the capability of a country to detect potentially toxigenic organisms and provide an indicator of good surveillance. Detection of mild diphtheria cases (any toxigenic organism) is another potential indicator of good surveillance. C. ulcerans appears to have a wide host range and has been isolated from many domestic and wild animals, including the killer whale and lion (nontoxigenic strain). During 2002 and 2003, toxigenic C. ulcerans strains isolated from domestic cats in the United Kingdom were found to have the predominant ribotypes observed among human clinical isolates, which suggests that cats could be a potential reservoir for human infection. Identical C. ulcerans strains have been isolated from diphtheria patients and dogs in France and the United Kingdom. The presence of this organism reinforces the need to maintain high vaccination levels in all countries. Higher incidence of infection among elderly women could be related to pet ownership habits, in combination with low or waning immunity.
Vaccination coverage for diphtheria is assessed annually in many countries in Europe by using a range of methods, including computerized vaccination registers, survey methods, administrative methods, or a combination. These methods will provide varying degrees of accuracy in coverage estimates, which makes countries difficult to compare. Coverage for vaccination with diphtheria-tetanus-pertussis 3 vaccine (third dose of diphtheria, tetanus, pertussis vaccine) in early childhood in 2009 was >90% for most (85%) countries in the European Region, and 66% of countries (including Latvia, Lithuania, Turkmenistan, and the Russian Federation) reported coverage >95% Coverage in Ukraine decreased from 98% in 2006 and 2007 to 90% in 2008 and 2009. Austria, Denmark, Georgia, and Moldova recorded diphtheria-tetanus-pertussis 3 vaccine coverage <90%. Azerbaijan and Malta had the lowest coverage (73% for both countries) in the European Region in 2009.
Following high-profile vaccine-scare stories in some countries in eastern Europe, such as the Russian Federation and Ukraine, anti-vaccination groups have gained strength by using television, the Internet, and other media for publicity; this activity could seriously affect vaccination coverage. Adult diphtheria immunity can be increased through scheduled booster vaccinations every 10 years (e.g., as in Austria, Belgium, Bulgaria, Cyprus, Estonia, Finland, France, Germany, Greece, Latvia, Norway, Portugal, and Romania) or as part of a combined tetanus and low-dose diphtheria vaccine given for tetanus-prone injuries. In Latvia, annual adult vaccination coverage surveys are undertaken, but in most countries adult coverage is rarely assessed. Seroprevalence studies have indicated that many adults in some countries have immunity levels below the protective threshold. Gaps in immunity in the adult population contributed to the resurgence of diphtheria in eastern Europe during the 1990s.
Trends in diphtheria cases in Europe are encouraging, but continued striving for improved vaccination coverage is essential. Diphtheria has a socioeconomic component; outbreaks are typically seen in marginalized groups. In the current economic climate, more socially deprived groups that are vulnerable to infection will emerge. The economic crisis may also threaten supplies of vaccine and antitoxin and delivery of immunization programs. Because reductions in finances can limit the capacity for surveillance, decreases in case reporting need to be interpreted with caution. Every effort must be made to maintain high diphtheria vaccination coverage.
Ms Wagner is a scientist in epidemiology at the Health Protection Agency in London, UK. Her research interests are diphtheria epidemiology and immunization and migrant health.
