Measles first emerged when livestock domestication led to the adaptation of cattle rinderpest virus (Rinderpest morbillivirus) to humans, and the growth of both human and cattle populations supported the circulation of the virus [1]. The time of divergence is suggested to be in the range from 10,000 [2] years before to VII–XII [3] century, according to the different published evolution models. The etiologic agent of measles named Measles morbillivirus belongs to Paramyxoviridae [2]. This RNA virus is genetically stable, and a common ancestor of the modern measles strain suggested to have emerged in 1908–1943 year [4].

The most dangerous feature of measles is the high basic reproduction number (R₀), i.e., the average number of secondary infection cases arising from a sick person in a totally susceptible population. In the case of measles, R₀ varies from 12 to 20 [5]. The disease commonly presents with mild symptoms but can proceed in life-threatening form in younger children. Till anti-measles immunisation is initiated, the measles incidence rate reached 120-300 cases per 100,000 population million per year [6, 7]. The progress towards measles elimination is not persistent and the return of the disease in the USA after 2000 when no further measles cases were registered. United Kingdom, Albania, the Czech Republic, and Greece also eliminated measles but lost this status [9].

Currently, new measles cases are registered in all parts of the world, and morbidity increases are periodically reported, for example in 2000 when the measles frequency in the world reached 853,479 confirmed cases (i.e. 145.3 per 100,000 of the population) or in 2019 (873,022 confirmed cases, 119.5 cases per 100,000 of the population) [10].

In Russia, measles is endemic, and in 2012–2014, the outbreak of measles incidence occurred. The morbidity reached 3.3 cases per 100,000 in 2014 [11]. In Northwestern Russia, the epidemiological situation is more prosperous, and the measles incidence in the previous decade fluctuated from 0 cases per 100,000 in 2016 to 1.1 per 100,000 in 2014 and 0.96 per 100,000 in 2019 [12].

Vaccination is the most effective way to control measles incidence [13]. John E. Enders developed the first measles vaccine after the initial isolation of the virus in 1954 [14]. In 1968, Maurice Hilleman produced a more attenuated measles-containing vaccine (MCV) derived from the virus isolated by John Enders in 1962 [15]. In the USSR, the vaccine strain Leningrad-16 (L-16) was isolated in Leningrad Pasteur Institute of Epidemiology and Microbiology. Observation of L-16 vaccinated children demonstrated more than 10-fold risk of disease reduction [16]. With the onset of the COVID-19 pandemic, the management of global measles in epidemiological situations weakened. The global level of MCV immunisation decreased from 86 to 81%, and the global measles burden grew by 67% [10]. Despite the lack of published data, there is reason to believe that the in Russia the same trend occurs.

The published data for the actual anti-measles seroprevalence in North-Western Russia are limited. In the group 386 volunteers of the maternity hospital staff, the seroprevalence reached 87.5% in 2018, but in other groups, like 1,399 employees at the Military Medical Academy clinics, the level of seropositivity was lower and reached only 81.6% [17]. A more massive seroprevalence study was published in 2019 and demonstrated 78.5% seropositivity in 5,303 subjects recruited from North-Western State Medical University named after I.I. Mechnikov students and staff [18]. Meanwhile, all these data were received in narrow groups with high medical competence. At the same time, according to the results of sociologic studies, there is a growing decrease in vaccination compliance in Russia [19].

The main aim of the present study is to analyse the data of twelve-year (from 2012 to 2023) surveillance dynamics of the anti-measles IgG levels in the Northwestern Russia population to fill the missing data for the actual seroprevalence status and retrospectively estimate its dynamic in this long-time period Taking into account, that there was no publicly available data for the immunisation coverage, we could only consider the impact of changes in National vaccination schedule on the studied parameters. So, we also analysed the seroprevalence in groups based on the coverage by the particular vaccination programs.

Herd immunity means that not every member of a population must be immune to prevent large-scale outbreaks [24]. Suggested, that the seroprevalence level, which is necessary to prevent the measles spread, is 93–95% [2, 13]. In our study, we reveal that actual seroprevalence in Northwestern Russia is near 75%. The seroprevalence levels observed in the present study could not protect the population from outbreaks, which registered in Russia in the past decade [12]. Measles incidence in Northwestern Russia is lower than the national average. Nevertheless, Saint Petersburg, Leningrad region, and Kaliningrad region, which were studied in the present surveillance, are the most affected regions in this territory [24]. In 2012–2014 and 2018–2020, the increase in measles incidence from 0.02 cases per 100,000 to 0.9–1.1 cases per 100,000 was recognised [12, 24]. Our data covers the period from 2012 to 2023, so we compare the mean IgG levels and seroprevalence in the population in different years. As the study’s aim is to estimate the dynamics of immune protection, we identified significant growth of mean IgG levels in 2014 and 2018–2021 years and a decrease in 2022–2023. The possible reasons are the decline of an immune layer in the population because [25] the natural reduction of the number of people who were born before vaccination initiation and had high-level post-infection immunity, accompanied by reducing vaccine coverage [26] that was worsened by the COVID-19 pandemic [20]. The last factor seems to be less significant because of vast majority of studied subjects were adults and were vaccinated before the COVID-19 pandemic. However, both of these processes do not explain the abrupt decrease of seroprevalence in the post-COVID period and some hidden causes may be input in the identified tendency.

In the present study, in the youngest subjects, the IgG levels are the lowest in the population, despite the method of IgG evaluation (i.e., ELISA or CLIA). Previous literature reported a similar trend for the general population [11, 12, 27] or specific groups like medical staff [28, 29]. The oldest group of patients (i.e. those born before 1967) had a higher number of subjects who had previously suffered the measles, which resulted in the tendency for the growth of anti-measles IgG antibody levels. Considering that measles had affected up to 90% of the population until 15 years old [30], the percentage of subjects who suffered the natural infection in the patients born before 1967 is substantial. Also, previous studies have identified lower antibody levels in late post-vaccination serum samples compared to serum from subjects who previously had a natural infection [31]. Meanwhile, we demonstrate IgG levels decreasing not only in people born in 1966-1990 (Groups 2 and 3), which were covered by the first vaccination programs in 1960–1970s but also in younger participants from Group 1 (i.e. subjects who were born at the beginning of 1960s). This trend may reflect the protective effect achieved by beginning immune interlayer formation in younger children.

When seroprevalence in different groups was compared, the downward trend was identified in younger participants. In subjects, who were born before the initiation of vaccination, over 90% are seropositive for measles, but in the age group partially covered by immunisation seroprevalence level is only 79.17–82.76% (depending on immunologic test). In the population that received only MCV1 in childhood, the seroprevalence is only 66,88%. Similarly, in countries in other parts of the world, including Guinea, where over 28,5% of the population aged 19–40 years was seronegative [27]. Also, in Thailand and Columbia, in adult subjects who received only MCV1 in childhood only 70% [32] and 64.7% [33] have protective level of anti-measles IgG, respectively.

Then we compare the youngest group of participants, that suggested to be mandatory vaccinated by MCV1 and MCV2, with other age groups. Despite the indefinite vaccination status, this group demonstrated a near 10% gain in seroprevalence loss compared to subjects covered by mandatory MCV1 vaccination. On the other hand, the previous study of measles epidemiology features in Saint Petersburg demonstrated, that the mean age of infected subjects in 2017–2019 was 33.4 years old [12], i.e. they correspond to Group 3 rather the Group 4 in our study. This supports the idea that the two-times-vaccinated younger group is better protected than the population that received only a single MCV immunisation. The decreased seroprevalence was identified in adolescents in several studies, for example in Canada [34] or South Korea [35], where the declined IgG positivity in younger age may reflect the failure of vaccination [34] or lack of boosting by the natural virus [35]. Altogether, the current data for the IgG levels and seroprevalence in the contingent that received MCV2 seems to be controversial. In some populations, a higher seroprevalence in children and adolescents compared to young adults or middle-aged adults was identified. For example, this trend was represented in Poland [36].

There were some limitations to the present study. First, we have no access neither to the information about the actual participants' vaccination status nor to the data for the vaccination coverage in the region. Despite this limitation, the obtained data is in line with the trends described in the literature. Second, the analysed data were acquired retrospectively, and the seroprevalence was estimated by different methods in unmatched groups, which are difficult to compare with another one. Meanwhile, the comparable trends in groups examined by the CLIA or ELISA additionally support the validity of identified population serological characteristics. Additionally, we identified a significant gender imbalance between age groups and insufficient data for several years at the beginning of surveillance. These limitations are insuperable, but despite these constraints, our results seem to be in common trend with published data, as discussed above.

Also, the protective immunity against measles is not determined solely by IgG levels. Strong T-cell-mediated immunity also may protect the subject against the measles infection despite the low activity of humoral immunity. So, screening T-cell immunity, for example, by the ELISPOT assay, may improve understanding actual herd immunity status [37]. The study aggregates the data for the population of several districts, but all these regions are characterised by similar social tendencies in common and possible differences are not the aims of the study.

The present study identified certain tendencies in anti-measles IgG levels and seroprevalence dynamics in the Northwestern Russian population in the past decade. We have revealed a significant decrease in anti-measles IgG levels in the Northwestern Russian population in the past decade, accompanied by a trend of seropositivity decline. The mandatory MCV1 vaccination, which was started in the USSR in 1972 year, decreased the measles incidence and provided the immune layer in the population. It appears that there is controversy surrounding the effect of including MCV2 in the National Vaccination Schedule. There was no increase in seroprevalence observed in the population that received MCV2 according to this schedule. Measles outbreaks are still being registered in schoolchildren and students in Northwestern Russia, in line with this trend. The possible reason is the low population compliance with preventive measures and refusal of vaccination. The COVID-19 pandemic disrupted the preventive medicine work, which also affected herd immunity, especially in younger subjects, who did not receive vaccination in time. However, this effect can only be evaluated in the future. Currently, a debate is being held about what will be the next global pandemic after COVID-19. The present data demonstrates that the success achieved by measles immunisation is not resistant. So, for now measles is on the one line with new influenza, coronaviruses, or “Disease X”. The lack of commitment to the control of this disease may cause measles to re-emerge with a massive infection spread.