Seroprevalence of anti-mumps virus IgG antibody titer and voluntary mumps vaccination coverage in young adults in Japan

ABSTRACT

In Japan, monovalent vaccine against mumps virus (MuV) infection was shifted to a voluntary basis vaccination due to the incidences of aseptic meningitis in the past. According to an analysis of a total of 409 participants aged 18–20 years, overall vaccination coverage rate was 48%. The mean anti-MuV IgG antibody titer of participants with medical history and more than two times vaccination was significantly higher than that in those without a medical history and unvaccinated and single vaccination, respectively. Seropositivity against MuV infection was >50% regardless of the number of vaccinations. Although these results suggest that seropositivity may persist due to asymptomatic infection, it is necessary to implement either a high vaccine coverage or routine vaccination for prevention of periodic mumps epidemics.

KEYWORDS:

• Mumps
• MuV
• IgG antibody titer
• vaccination

Mumps is a viral infection caused by the mumps virus (MuV). Symptoms include swelling of the parotid glands, fever, and sore throat. In addition, it is known to cause complications such as aseptic meningitis and hearing loss. Moreover, when adults develop mumps, the disease tends to be more severe, including orchitis, ovarian inflammation, and miscarriage.¹ One of the characteristics of the MuV infection is that 30% of the cases are subclinical or asymptomatic.²

Mumps is a vaccine-preventable disease. Therefore, almost all countries schedule mumps vaccine as a routine vaccination based on a national immunization program promoted by the World Health Organization. Globally, vaccines against MuV infection are used as a trivalent live attenuated vaccine involving measles, mumps, and rubella (MMR) vaccine. The effectiveness of the two doses of the MMR vaccine against mumps has been estimated to be approximately 90%.³ In Japan, however, incidents of postvaccination aseptic meningitis were reported as soon as routine MMR vaccination was initiated in April 1989 at a rate of 1/500 to 1/900. These incidents were clarified to be caused by a live–attenuated mumps vaccine among trivalent MMR vaccines.^4,5 Subsequently, the Ministry of Health, Labor, and Welfare abolished the routine use of the MMR vaccine in April 1993. Afterward, the measles and rubella vaccine was used as a routine vaccine for the prevention of measles and rubella infection from April 2006. The mumps vaccine was excluded from the routine vaccine schedule, and the monovalent mumps vaccine alone was set as a voluntary vaccination. Therefore, mumps vaccine is generally administered only if the parent or individual requests a mumps vaccination which is free of cost. In a 2015 surveillance, >70% of the adults had no known mumps vaccination history and mumps vaccination coverage was 24% at 1 year of age, 40% at 2–3 years of age, 30% at 4–11 years of age, and 20% at ≥12 years of age.⁶ Therefore, the prevalence of anti-mumps IgG antibody varied among various age groups, and their vaccination status became uncertain as close to adulthood rather than in childhood. In addition, a nationwide serosurvey conducted in 2013 reported that seropositivity was approximately 70%, which was not enough to achieve herd immunity to control the epidemic.⁷ In countries such as Japan, where the mumps vaccine is available on a voluntary basis, it will be necessary to periodically serosurvey and to disseminate seropositivity against MuV infection. These include adolescents, especially those with ambiguous vaccine histories and those susceptible to developing severe cases of the infection.

The seroprevalence of anti–mumps virus IgG antibody titer was determined to clarify seropositivity, and mumps vaccination coverage in young adults aged 18–20 years corresponding to a generation of voluntary vaccination in Japan was explored.

Surveillance studies were conducted by obtaining samples of sera from 409 young adults aged between 18 and 20 years who were first–year students at Juntendo University (Sakura Campus, Inzai, Chiba, Japan) to assess the prevalence of specific IgG antibodies against MuV. Serum samples were obtained from January 2018 to April 2018. Simultaneously, mumps vaccine history was collected from each individual’s maternity passbook. The participants also filled out questionnaires, aimed at obtaining information about the medical history of vaccination against MuV and natural MuV infections. The collected information was used to interpret the obtained results. The Ethics Committee of the Faculty of Health and Sports Science, Juntendo University (number 30-2) approved the study protocol. Informed consent was obtained from all participants and their parents before the study.

To determine the MuV-specific serum IgG antibody titer, an enzyme immunoassay (EIA) was performed in the laboratory of BML, INC. (Tokyo, Japan) using a MuV immunoglobulin test kit (Mumps IgG-EIA manufactured by Denka Seiken Co. Ltd., Tokyo, Japan). For the EIA determinant, an anti-MuV IgG antibody titer value of ≥4.0 means seropositivity against MuV infection according to the manufacturer’s instructions.

To identify the factors that influence MuV-specific IgG antibody titers, participants were divided according to their mumps medical history, number of vaccinations, and time elapsed since the most recent vaccination. The differences in anti-MuV IgG antibody titers were evaluated using unpaired t-tests.

A total of 409 (159 females and 250 males) participants participated in serosurveillance. Mumps vaccination coverage was 42% for females and 52% for males, with an overall vaccination rate of 48%. A nationwide serosurvey of mumps vaccination history reported 20% vaccination coverage among participants of the same age group,⁶ which was more than two times higher in the participants of this study.

Table 1 summarizes an anti-MuV IgG antibody titer concerning mumps medical history, vaccination number, and elapsed period after the last vaccination. Statistical analyses revealed that the presence of medical history, more than two times mumps vaccination, and an elapsed period of <10 years after the last vaccination were required for persistence of high anti-MuV IgG antibody titers equivalent to the protection against MuV infection. However, the mean anti-MuV IgG antibody titer of participants with no previous medical history, those with no or only one dose of vaccine, and those who had been vaccinated for >10 years exhibited an antibody titer ≥4, which is defined as protective antibody titer. The overall seropositivity among the participants was 64%, which is similar to the seropositivity reported in previous national surveys (60–66%) for the same age group.⁷ The highest percentage of seropositivity (89%) was found in participants with a mumps medical history, while the lowest percentage of seropositivity (43%) was observed in those with an elapsed period of ≥10 years after the last vaccination (Table 1). Of note was the number of vaccinations, with non-vaccinated participants also showing 58% seropositivity. Concisely, participants who received two doses of vaccination showed 65% seropositivity, although the number was small, while non–vaccinated participants showed higher seropositivity than those who received one dose.

Table 1. Anti-MuV IgG antibody titer and seropositivity against MuV infection regarding medical history, vaccination number and elapsed period after last vaccination

Item	Anti-MuV IgG antibody titer (mean±standard error)	Significance	Seropositive/Total number	Seropositivity %
Total	7.7 ± 0.6	NS	261/409	64
Femal	7.7 ± 0.7		104/159	65
Male	7.7 ± 0.9		157/250	63
Medical history
Yes	10.1 ± 1.2	**	138/155	89
No	6.3 ± 0.6		123/254	48
Vaccination number^a
0	7.3 ± 0.7	**	58/100	58
1	7.1 ± 0.7		69/137	50
2	19.0 ± 7.0		11/17	65
Elapsed period after last vaccination^b
<10 year	11.9 ± 3.0	**	27/37	73
≥10 year	4.5 ± 0.3		38/89	43

^aThe participants with mumps medical history were excluded.

^bThe participants who were not received mumps vaccine or those were received mumps vaccine within one month or those with mumps medical history were excluded.

NS: Not significance

**P < 0.01

In Japan, a mumps pandemic occurs every 4–6 years, particularly in adolescents and children.⁸ After these outbreaks, the seropositivity of the population was reported to increase.^7,9 In measles and rubella, it has been reported that multiple vaccinations do not directly lead to increased antibody titers due to vaccine failure and exposure to regular epidemics, respectively.^10,11 In particular, rubella is a viral acute febrile rash infection, and congenital rubella syndrome is of particular concern; otherwise, half of the cases are unapparent and asymptomatic infection.¹² Accordingly, exposure to multiple rubella epidemics may result in persistent seroprevalence even with single rubella vaccination.¹³ Similarly, >50% of the unvaccinated participants might observe persistence of seropositivity against MuV by natural infection rather than by vaccine-induced immunity. An overall estimate of ≥90% is needed to achieve herd immunity.⁹ Furthermore, the improved mumps vaccine has been estimated to have an infinitely lower risk of vaccine-induced aseptic meningitis.¹⁴ To control mumps epidemics and outbreaks, it is necessary to observe the persistence of seropositivity in the population and to implement either a high vaccine coverage or routine vaccination.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.