Sabine Santibanez

Global Distribution of Measles Genotypes and Measles Molecular Epidemiology

A critical component of laboratory surveillance for measles is the genetic characterization of circulating wild-type viruses. The World Health Organization (WHO) Measles and Rubella Laboratory Network (LabNet), provides for standardized testing in 183 countries and supports genetic characterization of currently circulating strains of measles viruses. The goal of this report is to describe the lessons learned from nearly 20 years of virologic surveillance for measles, to describe the global databases for measles sequences, and to provide regional updates about measles genotypes detected by recent surveillance activities. Virologic surveillance for measles is now well established in all of the WHO regions, and most countries have conducted at least some baseline surveillance. The WHO Global Genotype Database contains >7000 genotype reports, and the Measles Nucleotide Surveillance (MeaNS) contains >4000 entries. This sequence information has proven to be extremely useful for tracking global transmission patterns and for documenting the interruption of transmission in some countries. The future challenges will be to develop quality control programs for molecular methods and to continue to expand virologic surveillance activities in all regions.

Rapid replacement of endemic measles virus genotypes

Although vaccination campaigns have significantly reduced the number of measles cases worldwide, endemic transmission of measles virus (MV) continues to occur in several continents, including Europe. To obtain current information on measles incidence and molecular data on circulating MVs in Germany, a nationwide measles sentinel was established. Phylogenetic analysis based on the variable part of the N gene from 80 MVs isolated between November 1999 and October 2001 revealed the presence of at least six distinct MV genotypes: B3, C2, D4, D6, G2 and a new variant of D7. Both the incidence and the pattern of MV genotypes differed markedly between the former East and West Germany. In the eastern part, few measles cases, mainly caused by genotypes originating from other countries (B3, D4, G2), were detected. In the western and southern parts, genotypes C2, D6 and D7 were associated with endemic transmission. Surprisingly, the indigenous genotypes predominant during the 1990s - C2 and D6 - disappeared simultaneously over the period of observation coinciding with the emergence and the wide spread of D7 viruses. While the incidence of measles remained constant, all MVs isolated in 2001 were assigned to D7. We note that the haemagglutinin (H) sequence of D7 viruses shows distinct exchanges of certain amino acids in the stem and propeller domain compared to C2, D6 and the MV vaccine strains used. This raises the possibility of a selective advantage of D7 viruses transmitted in the presence of H-specific antibodies.

Further efforts needed to achieve measles elimination in Germany: results of an outbreak investigation

OBJECTIVE To determine morbidity and costs related to a large measles outbreak in Germany and to identify ways to improve the countrys national measles elimination strategy. METHODS We investigated a large outbreak of measles in the federal state of North Rhine-Westphalia (NRW) that occurred in 2006 after 2 years of low measles incidence (< 1 case per 100,000). WHOs clinical case definition was used, and surveillance data from 2006 and 2001 were compared. All cases notified in Duisburg, the most severely affected city, were contacted and interviewed or sent a questionnaire. Health-care provider costs were calculated using information on complications, hospitalization and physician consultations. FINDINGS In NRW, 1749 cases were notified over a 48-week period. Compared with 2001, the distribution of cases shifted to older age groups (especially the 10-14 year group). Most cases (n = 614) occurred in Duisburg. Of these, 81% were interviewed; 15% were hospitalized and two died. Of the 464 for whom information was available, 80% were reported as unvaccinated. Common reasons for non-vaccination were parents either forgetting (36%) or rejecting (28%) vaccination. The average cost per measles case was estimated at 373 euros. CONCLUSION An accumulation of non-immune individuals led to this outbreak. The shift in age distribution has implications for the effectiveness of measles control and the elimination strategy in place. Immediate nationwide school-based catch-up vaccination campaigns targeting older age groups are needed to close critical immunity gaps. Otherwise, the elimination of measles in Germany and thus in Europe by 2010 will not be feasible.

Large measles outbreak at a German public school, 2006.

Background: In 2006, a large measles outbreak (n = 614) occurred in Duisburg city, Germany, with 54% of cases aged >9 years. An investigation was launched to determine reasons for the resurgence of measles, assess vaccination coverage and vaccine effectiveness (VE). Methods: A retrospective cohort-study was undertaken at a Duisburg public school affected early in the outbreak. We distributed questionnaires to all 1250 students aged 10–21 years and abstracted vaccination records. Cases were identified according to a standard clinical case definition. Results: Questionnaires were returned by 1098 (88%) students. Vaccination records were abstracted from 859 students, of whom 820 (95.4%) had received at least one, 605 (70.4%) 2, and 39 (4.5%) no dose(s) of measles-containing vaccine (MCV). Coverage with 2 doses was higher in younger students. We identified 53 cases (attack rate = 5%). Measles-virus sequencing revealed genotype D6. After excluding students vaccinated in 2006 and those with a history of measles, the attack rate was 53% in unvaccinated students, 1.0% in students with one, and 0.4% in those with 2 MCV-doses. VE was 98.1% (95% CI: 92–100%) in students with one and 99.4% (95% CI: 97–100%) with 2 MCV-doses. Based on observed attack rates in vaccinated and unvaccinated students with vaccination records and in students without vaccination records, one-dose-coverage among all participating students was estimated at 91%. Conclusions: VE was high. Vaccination coverage was, however, insufficient to prevent the outbreak. Immunization gaps were found especially in older students. To prevent further outbreaks and to achieve the goal of measles elimination in Germany, vaccination coverage must be increased.

High Genetic Diversity of Measles Virus, World Health Organization European Region, 2005–2006

Importation of viruses from other continents caused prolonged circulation and large outbreaks in the WHO European Region.

Spread of Measles Virus D4-Hamburg, Europe, 2008–2011

TOC Summary: More than 24,300 cases were identified in 22 countries.

Genotyping of measles virus isolates from central Europe and Russia.

Sequence analysis of 285 nucleotides located on the variable part of the N gene was undertaken on measles virus (MV) samples collected from acutely infected patients in Germany, the Czech Republic, Denmark, Poland, and Russia. Two distinct genotypes (C2 and D6) have circulated in Germany between 1993 and 1996. Isolates of genotype C2 were related to strains reported in Germany before 1993. This genotype was also found in the Czech Republic in 1992 and in Denmark in 1997. The occurrence of genotype D6 in Germany is described below for the first time. In 1998, this genotype was identified in Poland. Genotypes C2 and D6 were also reported in Spain and in the United Kingdom between 1992 and 1996. Therefore, it is concluded that these genotypes are widely distributed over Europe. The analysis of the isolates from Russia revealed that genotype A was present in 1988 in the European part of the country and in 1996 in Siberia. An isolate identified in 1997 in Siberia belonged to genotype D6, which had never been found previously in Russia. We also analysed MV obtained from a case of subacute sclerosing panencephalitis (SSPE) in 1995 in Turkey. A comparison of this sequence with published sequences implied that this SSPE case was associated with a new genetic lineage of MV. J. Med. Virol. 58:313–320, 1999.

Progress toward Measles Elimination in Germany

While the former East Germany (FEG) achieved a reduction of measles incidence to <1 case per 100,000 population before reunification in 1990, the former West Germany (FWG) experienced significant measles morbidity. In 2001, according to statutory surveillance data, the incidence of measles was still higher in FWG than in FEG (8.7 vs. 0.7 cases/100,000 population). This article describes the development of the vaccination strategies in FEG and FWG, vaccination coverage, results of seroprevalence studies, measles surveillance in Germany, the epidemiology of a recent outbreak, and the role of laboratory diagnosis for measles control in Germany. Recent establishment of comprehensive nationwide surveillance and prevention programs to attain higher vaccine coverage have led to a decrease in measles incidence. However, further improvement of age-appropriate vaccine coverage and closure of immunity gaps in school-age children are necessary to eliminate measles in Germany.

Closer to the Goal: Efforts in Measles Elimination in Germany 2010

Increasing 2-dose vaccination coverage has led to an interruption of endemic measles virus circulation in Germany. However, outbreaks after virus importation still occur and contribute to international transmission chains. Between 2003 and 2009, annual measles incidence ranged between 0.2 and 2.8 per 100,000 population. Immunization gaps have been identified especially in secondary-school students and young adults, which is also reflected by a shift in age distribution of reported measles cases toward older age groups. Stronger political commitment and standardized guidelines for outbreak containment were put in place in Germany in the past years, but the last step toward measles elimination cannot be made until the number of susceptible individuals has been further reduced. In addition to routine childhood vaccination, supplementary immunization activities are needed targeting school students and young adults to close critical immunization gaps. Intensification of public awareness and sound information on vaccinations are necessary to convince skeptics and remind the forgetful.

Measles outbreak linked to a minority group in Austria, 2008

We report on a measles outbreak originating in an anthroposophic community in Austria, 2008. A total of 394 (94.9%) cases fulfilled the outbreak case definition including 168 cases affiliated to the anthroposophic community. The source case was a school pupil from Switzerland. The Austrian outbreak strain was genotype D5, indistinguishable from the Swiss outbreak strain. A school-based retrospective cohort study in the anthroposophic school demonstrated a vaccine effectiveness of 97.3% in pupils who had received a single dose of measles-containing vaccine and 100% in those who had received two doses. The vaccination coverage of the cases in the anthroposophic community was 0.6%. Of the 226 outbreak cases not belonging to the anthroposophic community, the 10-24 years age group was the most affected. Our findings underline the epidemiological significance of suboptimal vaccination coverage in anthroposophic communities and in older age groups of the general population in facilitating measles virus circulation. The findings of this outbreak investigation suggest that the WHO European Region is unlikely to achieve its 2010 target for measles and rubella elimination.