Laboratory case confirmation and MV genotyping have increased significantly since the establishment of a global laboratory network for measles and rubella in 2000 (16). During 2005–2006, MV genotypes were identified in 25 of the 53 member states of the WHO European Region (Appendix Table). Most epidemics and sustained transmissions were associated with genotypes D6, D4, and B3 viruses (Appendix Figure 1). All strains were genotyped by sequencing the 450 nt that code for the C-terminus of the MV N protein (hypervariable region [HVR]), as recommended by WHO (17). Sequencing was performed in different laboratories of the WHO laboratory network for measles and rubella.

All 53 member states of the WHO European Region except 1 have implemented a routine vaccination program against measles, resulting in an overall regional coverage of 94% for the first dose of measles-containing vaccine. In 2006, 45% of the member states had reached an incidence of <1/1,000,000 population (Appendix Table), the threshold to declare measles elimination. To achieve regional elimination of measles by 2010, enhanced vaccination strategies are required, especially in countries with a persistently high measles incidence.

Molecular epidemiology, an essential component of measles surveillance, helps to distinguish between endemic transmission and importation of the virus. It enables identification of regions with continued MV circulation, which reflect suboptimal herd immunity. During 2005–2006, 9 of the 17 active MV genotypes (27) were found in the WHO European Region. The major epidemics were caused by different variants of genotypes D4, D6, and B3. The largest outbreaks occurred in the Ukraine (genotype D6, >45,000 as of June 2007), Romania (D4, >8,000 cases as of June 2007), Germany (North Rhine Westphalia, D6, ≈1,700 cases), and the Russian Federation (D6, >1,100 cases). Epidemics involving 100–500 cases were reported from the UK (B3, originated in a traveler community), Spain (B3, D4), Germany (D4, D6, B3), Italy (D4), Belarus (D6), and Greece (D6, D4). Smaller epidemics and sporadic cases were caused by either the above-mentioned genotypes or others (B2, D5, D8, D9, H1, G3).

Since the early 1990s, genotype D6 has been continuously detected in Europe (4–12). During 2005–2006, D6 strains were reported from 17 European countries and were mostly related to the large outbreak in the Ukraine (Appendix Table). The overall genetic diversity of the recent D6 strains was, however, much lower than that found during the 1990s and early 2000s, and recent D6 strains were most similar to those found during 2000–2004 mainly in the Russian Federation and Turkey (Figure 1). The low genetic diversity of D6 strains suggests that enhanced vaccination has largely reduced the cocirculation of highly diverse D6 variants in Europe. Moreover, genotypes C2 and D7, which were frequently identified in Europe until 2004 (4–8,10–12), were no longer found during the past 2 years, despite greatly improved virologic surveillance. Genotype C2 had been continuously identified in the European Region since the early 1970s, and genotype D7 had partially replaced genotypes C2 and D6 in Germany during 2000–2004 (6). Thus, the transmission of several indigenous MV strains from Europe has probably been interrupted by enhanced control programs.

In contrast, the prevalence of imported genotype D4 and B3 strains considerably increased during 2005–2006. Genotype D4 strains have a vast geographic distribution, and measles outbreaks associated with this genotype have been reported from all continents (5). D4 viruses are still endemic on the Indian subcontinent as well as in East and South Africa (5,27). Although some outbreaks and sporadic cases associated with genotype D4 had been reported from Europe, the corresponding viruses were mostly imported from other continents and differed considerably from the more recent strains (6,11,30). In 2005–2006, genotype D4 was found in 16 of the 27 countries in which MV has been genotyped; most of the corresponding viruses were related to the outbreak in Romania. Roma and Sinti, communities which had mostly low vaccination levels, were involved in the transmission of the Romanian D4 viruses to at least 10 other countries in Europe. The remaining genotype D4–associated cases from Europe (2005–2006) were often epidemiologically linked to the Indian Subcontinent, East Africa, and the Middle East. The high genetic diversity of the corresponding MV variants is characteristic of multiple importation events. The increased frequency of genotype D4 detection during recent years can be explained by the interruption of transmission of most of the indigenous strains, as well the introduction of genotype D4 strains into highly mobile and hard-to-reach populations with low vaccination levels.

Genotype B3 is the endemic genotype in sub-Saharan Africa; a large diversity of genotype B3 viruses continues to circulate in many countries of West and Central Africa (31–37). Before 2005, genotype B3 viruses had only been reported sporadically from Europe (6,11). The genetic diversity of the multiple B3 variants detected in Europe during 2005–2006 suggests that each one was directly or indirectly imported from sub-Saharan Africa. All of them belonged to subgroup B3.1 of genotype B3, a finding that suggests a high prevalence of B3.1 strains in Africa during 2005–2006.

Several other imported genotypes (B2, D5, D8, D9, G2, and H1), which usually do not occur in Europe, were also sporadically detected during 2005–2006. Sequence analysis confirmed or identified suspected sources of importation for most of these.

While some countries reported outbreaks caused by a single strain, other countries experienced epidemics that were caused by multiple importations of unrelated strains. As an example, the isolation of different genetic variants (D4, B3, D6–2000, D6–2005) from the 4 major epidemics in Germany (2005–2006) shows that these cases were not epidemiologically linked. The identification of multiple genotypes in Spain, Switzerland, and the UK also demonstrates multiple origins of the different outbreaks and sporadic cases. Cocirculation of different genotypes during what seemed to be 1 outbreak has been identified in Greece, Italy, and Germany. In Italy (Lazio region, 2006) and Greece (2006), viruses obtained toward the end of an epidemic (genotype B3 and D4) belonged to genotypes different from those found in the early phase (D4 and D6). In Germany very different variants of genotype D4 were found in distinct parts of the country simultaneous with the epidemic in North Rhine Westphalia. In Denmark (2006), the detection of genotypes B3 and D5 and 2 D4 variants occurred in close geographic and temporal proximity (38). The identification of genotype D4 in Poland did not corroborate the putative epidemiologic link between the outbreaks in Poland and the Ukraine (genotype D6) (39). The presence of both genotypes D4 and D6 in Poland can, however, not be excluded because no viruses were characterized from the early phase of what seemed to be 1 epidemic. The corresponding examples from Germany, Italy, Greece, Denmark, and Poland thus highlight the importance of MV genotyping during different phases of a presumably single protracted outbreak. On the other hand, MV genotyping alone may not always be sufficient to distinguish linked and unlinked outbreaks caused by multiple importations. Epidemiologic investigations in Belarus showed multiple importations from the Ukraine that caused different, unrelated outbreaks and sporadic cases in which highly similar or identical D6 variants were found.

In conclusion, the absence of previously circulating genotypes (C2 and D7) and the low genetic diversity of D6 strains during 2005–2006 suggest an interruption of several MV transmission chains in the WHO European Region attributable to enhanced vaccination. However, the virus continues to be imported from other continents where measles remains highly endemic. Moreover, prolonged circulation and spread of imported strains, mostly after introduction into unvaccinated and highly mobile communities, continue to cause a high incidence of measles disease in Europe. Some countries did not report measles genotypes despite large numbers of cases (Appendix Table). As a consequence, to achieve measles elimination by 2010, measles surveillance and control need to be further optimized, and specific emphasis must be given to the vaccination of hard-to-reach populations.