Methods
Case-based diphtheria surveillance data from each of 25 Diphtheria Surveillance Network (DIPNET) member countries (Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Latvia, Lithuania, the Netherlands, Norway, Poland, Portugal, Romania, Slovenia, Spain, Sweden, Turkey, and the United Kingdom) for 2000–2007 were submitted retrospectively to the coordinating center in the United Kingdom during 2008. Data for 2008 and 2009 were obtained in August 2009 and September 2010 from the DIPNET online database, which was launched in September 2007.
We analyzed cases meeting the DIPNET case definition (isolation of a toxigenic strain or clinically compatible case with an epidemiologic link to a laboratory-confirmed case) In addition, 48 cases without laboratory confirmation and pseudomembrane (mild diphtheria/severe pharyngitis) and 5 cases with unknown manifestations were included for Latvia because these cases had been recorded in the national dataset. For most cases, toxigenicity was confirmed by using the Elek phenotypic test. However, in some cases, toxigenicity was evaluated only by detection of the toxin gene with PCR. We assumed that all cases in this dataset were toxigenic (toxin producing) because the number of cases without Elek confirmation was small and referred to symptomatic cases. Data fields collected included year; organism; biovar; and patient age, sex, clinical manifestations, vaccination status, veterinary contact, risk group, and outcome. Further strain characterization (ribotyping) was available for a limited number of isolates as part of a screening study in 10 DIPNET countries.
Cases were assigned to 5 clinical manifestation groups. These groups were classic respiratory diphtheria with pseudomembrane (the most serious form of the disease); mild diphtheria/severe pharyngitis (respiratory symptoms without the pseudomembrane); cutaneous (toxigenic organism isolated from skin lesions); other (e.g., toxigenic organism isolated from blood); and asymptomatic (carriers of toxigenic organisms, usually contacts of a confirmed case-patient).
Additional information concerning countries in the WHO European Region that are not DIPNET member countries was provided by the WHO Regional Office for Europe. Twenty-five of 53 member states of the WHO European Region are members of DIPNET. WHO European Region countries (including DIPNET members) report total cases annually to the WHO Regional Office for Europe through the WHO/United Nations Children's Fund Joint Reporting Form, which is the global annual data survey of WHO member states for vaccine-preventable diseases and immunization program indicators. In addition, 16 countries in 2003 (Figure 1) were asked to prospectively participate in monthly surveillance and provide more detailed information (e.g., pathogen biovar; patient age, sex, and outcome; and carriers among contacts). Twelve countries currently provide monthly reports to WHO Regional Office for Europe through this system. The only major source of cases that has not participated in the monthly reporting system (but does report annually) is the Russian Federation. Rates per 1 million person-years were calculated by using population estimates derived from the Population Division of Economic and Social Affairs of the United Nations Secretariat.
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Figure 1.
Diphtheria Surveillance Network (DIPNET) and World Health Organization (WHO) European Region countries. 1, Albania; 2, Andorra; 3, Armenia; 4, Austria; 5, Azerbaijan; 6, Belarus; 7, Belgium; 8, Bosnia and Herzegovina; 9, Bulgaria; 10, Croatia; 11, Cyprus; 12, Czech Republic; 13, Denmark; 14, Estonia; 15, Finland; 16, France; 17, Georgia; 18, Germany; 19, Greece; 20, Hungary; 21, Iceland; 22, Ireland; 23, Israel (neighboring countries not shown); 24, Italy, 25; Kazakhstan; 26, Kyrgyzstan; 27, Latvia; 28, Lithuania; 29, Luxembourg; 30, Malta; 31, Monaco; 32, Montenegro; 33, the Netherlands; 34, Norway; 35, Poland; 36, Portugal; 37, Republic of Moldova; 38, Romania; 39, Russian Federation; 40, San Marino; 41, Serbia; 42, Slovakia; 43, Slovenia; 44, Spain; 45, Sweden; 46, Switzerland; 47, Tajikistan; 48, Former Yugoslav Republic of Macedonia; 49, Turkey; 50, Turkmenistan; 51, Ukraine; 52, United Kingdom (Great Britain and Northern Ireland); 53, Uzbekistan.
Statistical Analyses
Proportions were compared by using χ or Fisher exact tests, as appropriate, in Stata statistical software version 7.0 (StataCorp LP, College Station, TX, USA). For assessment of a trend for variables in ordered groups (vaccinated, partially vaccinated, unvaccinated) and severity of disease (classic respiratory, mild diphtheria/severe pharyngitis, asymptomatic), the Wilcoxon test for trend in Stata. was used. This test enabled nonparametric analysis across these groups.