국가필수예방접종 프로그램이 유행성 이하선염 발생에 미친 영향: 국가 감염병 감시체계 자료 연구

Abstract

Objective: Mumps is a highly communicable disease characterized by painful swelling of parotid glands. There have been growing reports which indicate increase of mumps globally including the Republic of Korea. The mumps vaccines have proven to be very effective in decreasing the overall incidence and prevalence of disease. However, different vaccination policy and strains of mumps vaccine virus strains have shown differences in levels of protection. This study was to identify the temporal trend of incidences of the mumps in Korea and the changes after the introduction of the 2-doses of measles-mumps-rubella vaccination program in the public sector. The objectives are as follows:

First, evaluate the epidemiology of measles, mumps and rubella, and to share a baseline evidence for the future routine and outbreak-response immunization policy.

Second, to analyses the effect of birth cohort exposed to Rubini strain on recent increase of mumps, conduct an age-period-cohort (APC) analysis of gender-specific mumps incidence in Korea from 2001 to 2015.

Third, identify spatial patterns in mumps incidence to give an indication to the geographical risk of the disease in the settings with high MMR vaccination coverage.

Methods: (1) The data were stored centrally at the National Notifiable Disease Surveillance System (NNDSS), which is operated by Korean Center for Disease Control (KCDC). The NNDSS data was used to calculate the crude incidence of mumps in Korea during 1955-2012, and to explore the changes in epidemiology of mumps between 2001 and 2015. An age-specific incidence per 100,000 population using population data from Korea Statistical Information Service. From internal database acquired from KCDC and Korea Ministry of Food and Drug Safety (MFDS), the major vaccine strains used in Korea in each year were identified. (2) Incidence of measles, mumps, and rubella cases for birth cohorts were calculated according to vaccination policy as follows: pre catch-up, 1976-1984

catch-up, 1985-1993

keep-up (early), 1994-2002

and keep-up (late), 2003-2011. Pre catch-up (1976-1984) cohort was those who were with limited vaccination coverage of MMR with only one dose provided by the public. Catch-up (1985-1993) cohort was those who were with limited MMR vaccination coverage, but were given the Measles-Rubella (MR) vaccine during the 2001 catch-up campaign. Early keep-up (1994-2002) cohort was those who were candidates for the keep-up program in the first 8 years (2002-2008), and the late keep-up (2003-2011) were the candidates for the next 8 years (2009-2016). (3) Age-specific incidence according to gender was calculated for periods and birth cohorts in 3-year blocks to find difference in incidence between the cohorts affected by the Rubini strain. The Poisson age-period-cohort (APC) model was used to estimate the age, period, and cohort effects on secular trend of mumps from 2001-2015. (4) A geographic weighted regression (GWR) analysis was performed to find demographic predictors of mumps incidence according to district level. The population, density, childhood percentage, and the timely vaccination coverage rate data was derived from the National Statistics database.

Results: (1) Of the 209,817 cases of mumps reported in Korea between 1955 and 2015, 109,850 (52.4%) were reported between 2001 and 2015. The secular trend of mumps incidence was characterized by a cyclical pattern of spikes at intervals of 5-10 years. Before the introduction of MMR into National Immunization Program in 1980, the average incidence was 11.1 (range 1.7-31.0) cases per 100,000 populations per year for period 1955-1979. (2) Between 1995 and 1999, the average numbers of measles and mumps cases were 46 (range: 2-88) and 1,601 (range: 254-2,626), respectively. In 2000 and 2001, an outbreak of measles resulted in a total of 55,707 cases. Following the MR catch-up campaign, the annual reported cases of measles decreased, although there were outbreaks in 2007, 2010, 2013, and 2014 that resulted around 100 cases each year. Between 2001 and 2015, there was constant increase in the number of reported cases of mumps from 1,668 cases to 23,446 cases. (3) The period effects displayed a similar pattern for both genders, with an upward shift since 2008 with a significantly elevated risk by 2014. In general, the risk of mumps has increased according to birth cohorts in both genders. From 2001-2015, the overall net drifts were 27.67/100,000 (95% CI: 27.5.47-29.90) for males and 27.25/100,000 (95% CI: 24.91-29.65) for females. There were statistically significant cohort and period relative risks and net drifts in both genders. (4) During low endemic periods, the clusters were mostly confined to Seoul-Incheon-Gyeonggi and Gangwon regions. During high endemic period of 2013-2015, most of the Gwangju-Jeolla regions were with clusters. These regions showed the core cold spot clusters consistently during 2004-2006, 2007-2009, and 2010-2012. The result of GWR model to detect demographic predictor of mumps incidence is summarized in Table 3. The un-timely vaccination coverage was a significant predictor of mumps incidence during 2010-2012 period (β: 0.66, P = 0.002). The proportion of children population was a predictor during high endemic period of 2013-2015 (β: 2.68, P = 0.001).

Conclusions: (1) The first study was to address the increasing trend of incidence of mumps in the Republic of Korea for the last decade. The study describes the change in mumps incidence in Korea, which was resulted from different vaccine strains used during past 30 years. The description of age-specific and cohort-specific risk of acquiring mumps has identified the need to strengthen its surveillance in adolescents as well as in younger aged children group. The dynamic in population susceptibility of mumps the study described in this report may provide guidance for the future MMR immunization program. (2) The second study demonstrates the first result of longitudinal study on the difference in incidence between the three infectious diseases that are combined to form a single vial of vaccine: measles, mumps, and rubella. The key messages of this study are that the incidence of the three diseases could show differential trend according to the choice of vaccine that was used during catch-up vaccination campaign. The study reports a population study of measles, mumps, and rubella in Korea, which was resulted from MR catch-up vaccination campaign and MMR2 keep-up program used during past 15 years. The description of age-specific and cohort-specific risk of acquiring mumps has identified the need to strengthen its surveillance in adolescents as well as in younger aged children group. For preschool aged children, a timely second dose MMR vaccination should be emphasized, whereas for adolescents and young adults, unvaccinated individuals or those without certain vaccination history should be considered for the catch-up vaccination. The dynamic in population susceptibility of mumps this study described may provide guidance for the future MMR vaccination program. (3) The third study was to explore the impact of the age, period, and cohort effect on the individual risk of mumps transmission. The study describes a cohort and period-specific risk of acquiring mumps in Korea, and have identified the need to strengthen surveillance in adolescents as well as in younger aged children group. The dynamic in population susceptibility of mumps we described in this report may provide guidance for the future MMR immunization program and the mumps elimination strategies. (4) In the last study, the intent was to demonstrate the transmission pattern of mumps by space in Republic of Korea during the past 15 years that might inform public health planning and future vaccination strategies. The study indicates that the rate of mumps incidence according to geographic regions vary by population proportion and neighboring regions, and timeliness of MMR vaccination, suggesting the importance of community-level surveillance and strengthening of vaccination program. Further researches are needed to determine if population structure and non-timely coverage rate are associated with the temporal and spatial variation in other vaccine-preventable disease epidemiology.