The Topic of This Month Vol.26 No.3(No.301)

Pertussis, Japan, 1997-2004

(IASR 2005; 26 : 61-62)

Bordetella pertussis is a gram-negative aerobic short rod, producing such virulence factors as pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) and adenylate cyclase toxin (ACT). It is transmitted through droplets of upper respiratory secretions and highly infectious. In Japan, diphtheria-tetanus-acellular pertussis (DTaP) combined vaccine containing purified antigen (the main principles are detoxified PT and FHA) has been introduced since 1981. Mass immunization used to be practiced to children >= 2 years of age in principle, whereas it has been changed since April 1995 to individual immunization to infants over 3 months after birth by the 1994 amendment of the Preventive Vaccination Law. Vaccines produced by some manufacturers contained a small amount of gelatin, which was found to induce anti-gelatin IgE antibody (Sakaguchi M. & Inouye S., Jpn. J. Infect. Dis. 53:189-195, 2000), and DTaP vaccines of all Japanese manufacturers were improved to "gelatin-free" before 2000.

Incidence of pertussis cases: Pertussis, a Category V infectious disease under the National Epidemiological Surveillance of Infectious Diseases (NESID) based on the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law), is reported every week by about 3,000 pediatric sentinel clinics nationwide. During 1950-70, pertussis epidemics occurred every 4 years, then gradually became smaller in scale afterward until only small increases in number of cases were recognized in 1982-83, 1986, and 1990-91 (see IASR 18:101-102, 1997). Since 1997, distinct peaks indicating epidemics have disappeared (Fig. 1).

Looking at incidence by prefecture during 2000-2004, 11 prefectures reported two or more cases per sentinel in 2000, while in 2001 and later, only Yamagata, Tokushima, and Tochigi Prefectures did so (Fig. 2). From these facts, pertussis epidemics spreading over prefectures may already have disappeared. In Fig. 3, reports of yearly pertussis cases by age group (per sentinel) during 1982-2004 are shown. After introduction of DTaP vaccine, cases aged 1-4 years, which used to account for about 40% of all cases, decreased markedly. Cases aged 0 year also decreased, although a 4- year-epidemic cycle still exists. In 2004, the number of cases per sentinel increased slightly in all age groups. Since 2000, 0-year cases have outnumbered 1-4 year ones. The increases in rates of younger cases have also been observed in other diseases (see IASR 25:318-320, 2004). One of the reasons is that sentinels have been changed to principally pediatric clinics and hospitals after enactment of the Infectious Diseases Control Law in 1999.

Pertussis antibody prevalence: By the National Epidemiological Surveillance of Vaccine-Preventable Diseases in 2003, healthy population was surveyed for pertussis ELISA antibody prevalence (in 2003, the survey covered for the first time all age groups including not only infants but also adults). FHA and PT, the major components of the vaccine, possess independent antigenicities, and antibodies against FHA and PT are considered protective against symptomatic and asymptomatic infection. From the lowest titers of convalescent sera of pediatric pertussis cases, an antibody titer of 10 EU/ml was determined to be the protective against infection. Therefore, the prevalence rate of antibodies higher than 10 EU/ml against FHA and PT will be considered here. In the survey for antibody prevalence by age group, the anti-PT antibody prevalence of age groups of 45-49 years was the lowest at 28%. Although, the prevalence in other age groups ranged between 41-60%, no significant difference by specific age groups was seen (Fig. 4). On the other hand, prevalence of anti-FHA antibody was somewhat low in the age group of 25-44 years (51-57%), whereas in other age groups antibody prevalence was high, being 71-91%. The age group of 25-29 years reflects the temporary interruption of vaccination in 1975 and the low vaccine coverage period until introduction of DTaP vaccine in 1981. The 30 to mid-40 age groups reflect the vaccination period of whole-cell vaccine.

The antibody prevalence by vaccination history indicates that the prevalence of both anti-PT and anti-FHA antibodies at 10 EU/ml or higher was not affected by booster immunization (Fig. 5). In non-vaccinees, both anti-PT and anti-FHA antibody prevalence increased with age, indicating that B. pertussis is circulating in the community and infection of unvaccinated children occurs even at present when cases have markedly decreased. Since both anti-PT and anti-FHA antibody prevalence among 1-16 year children is nearly constant and no difference has been seen since 1995 (Fig. 6), no change in the quality of the current vaccine is likely to have occurred.

Current problems: Although pertussis epidemics have already disappeared in Japan, small outbreaks (nosocomial infection) in maternity and children's wards (see p. 64 of this issue) and some familial infections (see p. 64 & 66 of this issue) still occur. It is considered that adolescents and adults who lack typical symptoms are not diagnosed as pertussis and are likely to make infection sources. Because the rate of B. pertussis isolation (necessary for confirmatory diagnosis) is low, and a large amount of time is required for antibody detection, diagnosis is based on symptoms in the clinical setting. Molecular diagnosis by PCR assay is also carried out at the research laboratory level, although neither specificity nor sensitivity is sufficient. In reality, there may be many hidden sporadic cases and outbreaks that are neither diagnosed nor reported. From now on, development of rapid and easy molecular diagnosis methods seems necessary.

Since the lowering of the age of vaccine administration due to the amendment of the Preventive Vaccination Law in 1995, cases aged 1-4 years have decreased. However, cases of 0 year of age have recently not decreased, therefore giving vaccination soon after turning 3 months of age are desirable. This is supported by the relationship between vaccination history and incidence (see p. 67 of this issue). In the US, where high vaccination coverage is maintained, increases in case counts have been observed, thereby characterizing pertussis as a re-emerging disease (see p. 69 of this issue). The cause of the re-emergence of pertussis in foreign countries is not clear, although genetic diversity of circulating strains (see p. 63 of his issue) and increase in cases among adolescents has been recognized (see p. 66 of this issue). In the US, the emergence of macrolide-resistant B. pertussis strains has been confirmed (see p. 68 of this issue).

Presently, at a time when pertussis cases have markedly decreased, sentinel surveillance is difficult to detect local outbreaks in each area where there is no sentinel. In order to accurately grasp trends in case incidence, it will be necessary to develop a surveillance system incorporating pertussis as a nationally notifiable desease. Possible increases in pertussis cases, due to such factors as the emergence of drug-resistant strains or infection of adults with decreased antibody levels against B. pertussis , can not be ruled out in Japan. It will be necessary to strengthen infectious agents' surveillance for active pathogen isolation and analysis of B. pertussis .

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