Genetic monitoring of endemic measles virus circulation in European countries

Анотація

Introduction. The measles virus is still one of the main causes of morbidity and mortality in children and adults and is a threat of infectious outbreaks in many countries around the world. The World Health Organization (WHO), at the 2015 meeting in Europe, set out to eliminate measles infection. To control the elimination of this disease requires the accumulation of genotyping data of the detected measles virus to interrupt the situation of endemic spread. All six WHO regions have set a target for combating measles. In order to monitor and evaluate the degree of endemic circulation of measles virus (MV), the transmission chains of the epidemiologically relevant variants of MV identified in Central and Western Europe are analyzed. More systematic molecular monitoring and recording of MV transmission data between many countries can help to create a meaningful picture of the process of eliminating the problem of the occurrence and spread of measles infection. Goal. To study whether molecular surveillance meets the challenge of eliminating measles infection with the assurance of molecular data quality, continuity and intensity of molecular monitoring and analysis of transmission chains in different geographical regions.  Material & methods. Published articles, molecular program for external WHO quality assessment, WHO EUR central infectious disease information system, and WHO measles surveillance database.  Results & discussion. According to the WHO standardized nomenclature using the nucleotide (nt) sequences of the N and H variable genes, wild-type measles viruses are currently divided into 24 genotypes. The most variable is the 450-nt variable coding sequence of the C-terminal portion of the N protein (N-450 region) and is used to differentiate detected MV for observation. Antigenic differences between measles virus strains - representatives of different genotypes are minimal, all known genotypes of the virus belong to one serotype. Since the beginning of molecular surveillance in Europe in the early 1990s, only two genotypes of MV (C2 and D6) have been identified, which have been spread throughout the region and are therefore called indigenous European genotypes. Molecular observation has shown that, over the years, the endemic genotypes C2 (IR / Kempten.DEU / 23.00) and D6 (IR / Berlin.DEU / 47.00) have changed rapidly with the circulating D7 genotype (IR / Mainz.DEU / 06.00) to the beginning of 2003. The imported measles virus of genotypes B3, D4, D5, D6, D8, D9, H1 appeared in Germany from 2005 to 2009 - 2010. Most cases were related to the measles virus of genotype D4, and its several sub-variants. According to the monitoring data, genotypes D8, B3, H1, D9, D4 have been circulating in the world in recent years (from August 2017 to July 2018).  Of the 179 measles deaths reported in European countries during 2009-2018, 114 (64%) occurred during 2017-2018, including 93 (82%) in four countries: Romania (46), Ukraine ( 20), Serbia (15) and Italy (12). EU countries report 17587 measles virus sequences to the WHO global measles surveillance database. The most common measles virus genotypes were D4 (21% overall, 66% in 2009-2012), D8 (45% overall, 76% in 2013-2016) and B3 (33% overall, 58% in 2017- 2018). Conclusion. Our research illustrates the long-term transmission of MV in Europe. Which probably happens because of the unvaccinated people in the various hard-to-reach groups that transmit the infection to the general population. This situation is, of course, inconsistent with the purpose of the WHO and UNESCO (WHO-UNICEF, 2002) measles elimination program already achieved in America and Australia. In order to address the global problem of measles infection worldwide, additional efforts are needed to identify deficiencies in immunization among the population. As the elimination of MV should be a problem for all EUR countries, similar research to ours should be expanded to obtain comprehensive information on the circulation of MV strains in different regions across Europe.

DOI: 10.5281/zenodo.3885184