School-age children and adolescents suspected of having been to be infected with pertussis in Japan
Introduction
Pertussis is a respiratory tract infection and it causes typical respiratory symptoms. Pertussis causes severe symptoms including apnea, pneumonia, and is sometimes complicated with encephalopathy in neonates. Bordetella pertussis (B. pertussis), B. parapertussis, and B. holmesii are causal pathogens of pertussis. The World Health Organization reported 139,786 pertussis cases in 2014, and estimated 89,000 deaths in 2008 [1]. Two vaccines, whole-cell pertussis (wP) vaccines and acellular pertussis (aP) vaccines, combined with diphtheria and tetanus toxoids (DTwP) vaccines or (DTaP) vaccines are used against pertussis in many countries. The aP vaccines are mainly composed of PT and FHA, and some of them include pertactin and fimbriae (Fim) 2/3. Protective immunity against pertussis is induced by 4–5 doses of DTaP vaccines, and is believed to be maintained for 3–10 years after the vaccinations [2], [3]. Tetanus toxoid with a reduced concentration of diphtheria toxoid and a pertussis vaccine components (Tdap) vaccine is used for adolescents and adults including pregnant woman, in some countries. Pertussis has been re-emerging in the latest two decades in countries where DTaP has been used [4], [5], [6], [7].
In Japan, almost 100,000 pertussis patients and 10,000 pertussis-caused deaths were reported in the early 1950s [8]. The wP vaccines were used from 1950, and wP vaccines combined with a diphtheria vaccine were used from the late 1950s. The DTwP vaccine was recommended from 1968, and suspended from 1975 to 1981. The DTaP vaccine was recommended from 1981 until 2012, and then DTaP combined with inactivated polio (DTaP-IPV) vaccine has been recommended since 2012. The number of reported pertussis cases decreased following the introduction of DTwP or DTaP, and pertussis-related deaths decreased to less than 10 cases per year in the 1980s [8]. Now, three brands of DTaP-IPV are available. Two of them consist of pertussis toxin (PT) and filamentous hemagglutinin (FHA), and the other contains PT, FHA, pertactin, and Fim 2. In Japan, children aged 3 months are vaccinated with three consecutive doses for primary immunization, and with a booster vaccine 6–12 month after the 3rd dose of primary immunization. There is no licensed Tdap vaccine in Japan.
Several pertussis outbreaks have been reported since 2007 in Japan [9], [10], [11], [12]. In these pertussis outbreaks, many patients were adults and adolescents >10 years of age [9], [13]. Kamiya et al. [14] reported that pertussis outbreaks also occurred among highly vaccinated children. The highly-vaccinated individuals were sometimes asymptomatic even when infected with B. pertussis [15], [16]. Asymptomatic pertussis infection among highly-vaccinated individuals may cause further transmission in households, offices, universities and others [15], [17].
It is not easy to clarify the burden of pertussis, including asymptomatic patients. To investigate the distribution of anti-PT IgG and anti-FHA IgG by enzyme immunoassay is useful to confirm the prevalence of pertussis infection among communities, including asymptomatic pertussis carriers and herd immunity to pertussis [18], [19], [20], [21], [22], [23], [24]. In Japan, pertussis is considered to be transmitted from school-age children because protective immunity induced by DTaP vaccine is maintained for 3–5 years [1], [24], [25], [26]. However, there is no report on herd immunity among highly vaccinated school-age children through to adolescents in Japan in the re-emerging phase of pertussis.
Section snippets
Subjects
This study was conducted from 2013 to 2015. History of pertussis and pertussis vaccination was taken by questionnaire to students of nursing schools and universities, and to the parents of elementary school and junior high school students. The candidates of the study participants consisted of 504 subjects at first grade elementary school students, 1313 subjects of junior high school students, and 200 subjects of nursing school and university students, as shown in Table 1. Among them, 502
PT antibodies in the participants who received 3 or 4 doses of DTaP
The results of PT antibodies are shown in Fig. 1. Positive rates of anti-PT IgG were 47.1% (95%CI: 40.7–53.6%) at the 1st grade of elementary school (aged 6–7 years), 60.0% (95%CI: 56.0–63.9%) at 12–13 years of age in 2014, and 73.0% (95%CI: 61.4–82.6%) at 18–19 years of age in 2013 (Fig. 1A). In 2015, those were 37.4% (95%CI: 31.2–43.9%) at 6–7 years of age, 61.3% (95%CI: 57.3–65.2%) at 12–13 years of age, and 75.7% (95%CI: 64.0–85.2%) at 18–19 years of age (Fig. 1B).
The arithmetic averages of
Discussion
The surveillance system in Japan for infectious diseases is organized based on a self-reporting system at 3000 sentinel pediatric clinics and hospitals [27]. The yearly number of reported cases of pertussis was 5208–6753 cases from 2008 to 2010, 1662 in 2013, and 2066 in 2014 [27]. The period of the present study was from 2013 to 2015, not an epidemic pertussis periods. Among the present study, 1.3–7.1% of participants who received 3–4 doses of DTaP had high levels of PT antibodies
Conclusions
Highly vaccinated school-age children and adolescents were investigated for anti-PT IgG antibodies. Approximately 60% of subjects aged 6–7 years were negative for anti-PT IgG, and the positivity and mean titers of anti-PT IgG were higher among older age groups, suggesting pertussis infection. The data suggest the additional vaccination before the entry of elementary school.
Acknowledgements
We dedicate the manuscript to the late Dr. Toshiaki Ihara in National Mie Hospital, who obtained the serum samples from students in Mie Nursing School.
Authors’ contributions
Nakayama T planned the study. Yasui Y wrote the paper. Yasui Y, Mitsui T, Nishimura T. Uchida K, Inokuchi M, Mori M, and Tokumura M collected the blood samples, and immunization history, and obtained the written informed consent. Yasui Y performed the serological and statistical analysis.
Funding
The corresponding author; TN, receives a research fund from Daiichi Sankyo pharmaceutical company, Tokyo, Japan.
Conflict of interest
None.
References (44)
Vaccine chronicle in Japan
J Infect Chemother
(2013)- et al.
Bordetella pertussis epidemiology and evolution in the light of pertussis resurgence
Infect Genet Evol
(2016) - et al.
Seroprevalence of IgG antibodies against Bordetella pertussis in healthy individuals aged 4–24 years in Turkey
Clin Microbiol Infect
(2008) - et al.
Effectiveness of acellular pertussis vaccine in a routine immunization program: a multicenter, case-control study in Japan
Vaccine
(2015) - et al.
A cross sectional survey measuring sero-incidence of pertussis infection among Japanese junior and senior high school students in 2013 and 2014
Vaccine
(2017) - et al.
First report and detailed characterization of B. pertussis isolates not expressing Pertussis Toxin or Pertactin
Vaccine
(2009) - et al.
Bordetella pertussis iron regulated proteins as potential vaccine components
Vaccine
(2013) - et al.
Protective activity of the Bordetella pertussis BrkA autotransporter in the murine lung colonization model
Vaccine
(2008) - et al.
Intrafamilial spread of pertussis
J Pediatr
(1983) - World Health Organization. Pertussis. Immunization, Vaccines and Biologicals,...