The Topic of This Month Vol.23 No.1(No.263)

Tetanus in Japan as of 2001

(IASR 2002; 23: 1-2)

Clostridium tetani is an obligate anaerobic bacillus spread in soil worldwide in the form of spores highly resistant to heat and dryness. C. tetani spores enter the body through a wound and germinate and propagate under anaerobic conditions, producing tetanus toxin. Tetanus is caused by the impairment of neural stimulus-transmission due to blockade of the inhibitory neural circuit in the motor end plates, ventral horn cells, or brain stems. Various wounds may be the causes of tetanus (see p. 6 of this issue). Characteristic symptoms are stiffness of the muscle at the injury site, the jaw or the neck, trismus, canine laugh, dysphagia, dyspnea, and opisthotonus (see p. 3 of this issue). Since delayed treatment will result in a high case-fatality rate, early treatment based on accurate clinical diagnosis is extremely substantial (see p. 4 of this issue). Notification of tetanus cases became mandatory by the Communicable Diseases Prevention Law in 1947. It was classified in the category IV notifiable infectious diseases in the National Epidemiological Surveillance of Infectious Diseases (NESID) under the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law) enacted in April 1999. In a case of suspected tetanus diagnosis carrying the history of injury and clinical symptoms, the physician must notify it to the nearby health center within 7 days from the date of diagnosis. Etiological diagnosis is often difficult to make. If C. tetani is isolated from the infection site (wound) and toxin production by the isolate is proved (see p. 3 of this issue) it should be reported.

Development of tetanus symptoms after infection with C. tetani can be prevented with the toxin-neutralizing antibody. For prevention of tetanus, it is important to maintain a protective level of antitoxin titer in an individual by repeated vaccination to increase the immunity level. After 1968, for routine immunization against pertussis (P) and diphtheria (D), diphtheria-tetanus-pertussis combined (DTP) vaccine or diphtheria-tetanus combined (DT) vaccine including tetanus toxoid (T) has been utilized (see Fig. 1 and IASR, Vol. 19, No. 10 and Vol. 18, No. 5), attaining a sufficient immunization level against tetanus. In the 1994 amendment of the Preventive Vaccination Law, tetanus has been added to the target diseases of routine immunization (this came into operation in April 1995). The following schedule was recommended as a standard; for a primary series, three doses of DTP are given at 3 to 8-week intervals to infants of the age between 3 and 12 months and the fourth dose is given 12 to 18 months after the third dose. For an additional booster, DT is injected at the age of 11 to 12 years (see p. 3 of this issue).

Incidence of tetanus: The fatality rate of tetanus was 81% in 1950; the notified cases of tetanus totaled at 1,915, of which 1,558 died and the greater part of the death cases were aged under 15 years ( Cases and deaths of tetanus decreased in number after introduction of tetanus toxoid vaccine in 1953 (voluntary immunization) and the start of routine immunization with DTP vaccine in 1968 accelerated the decrease. Since the late 1980s, there have been 30-50 yearly cases with 20-60% deaths (Fig. 1). Since the enactment of the Infectious Diseases Control Law, reported cases have been on the increase, 65 (April-December 1999), 92 (January-December 2000), and 71 (January-November 2001), whereas no increase has been seen among those up to the early 30s (the age groups having received routine immunization). Of the 228 cases reported during April 1999-November 2001, 216 (95%) were aged over 35 years (the age groups seldom receiving tetanus toxoid vaccine) (Fig. 2) and 58% were males (133 males and 95 females). In 178 cases (78%), the route of infection such as from the injury has been traced; in the remaining 50, the route was unknown. In all prefectures but Shiga Prefecture, tetanus cases have been reported; in each of 17 prefectures, including Tokyo (18) and Kagoshima (13), more than six cases have been reported (Fig. 3). Tetanus cases increase in the months when the outdoor activities are high (Fig. 4).

Age-specific tetanus antitoxin prevalence: In the National Epidemiological Surveillance of Vaccine-Preventable Diseases, 1,766 healthy individuals at the ages of 0-16 years were subjected to titration of tetanus antitoxin for the first time in 1998 and 1999 with a particle agglutination test kit (Fig. 5). The positive rate of antitoxin higher than 0.01 IU/ml, the minimum level of protective immunity, increased from 0 up to 4 years. It was as high as 87-96% of those aged 3-16 years and that higher than 0.1 IU/ml, a sufficiently high level of protective immunity, was also as high as 75-93%. The proportion of those showing a high titer, 3.2 IU/ml or higher, was the highest among the age group of 3 years (39%), whose primary series of vaccination was completed. Then, it was on the decrease but again on the increase at 11-12 years, the age of the booster DT injection.

The Department of Bacterial and Blood Products, the National Institute of Infectious Diseases (NIID) surveyed all age groups for the antitoxin prevalence. The serum specimens subjected to determination were collected during 1994-1995 and totaled at 881 (Fig. 6). They included 672 samples stored at the Serum Reference Bank, NIID and other 209 samples provided by St. Marianna University Hospital. The positive rate of antitoxin higher than 0.01 IU/ml increased from 68% of 0-4 years' group to 92% of 5-9 years' group and 93% of 10-14 years' group. After that, such a high antibody titer was maintained at a high proportion, 87% at 15-19 years and 89% at 20-24 years of age. In the age group of 25-29 years, however, those showing an antitoxin titer of around 0.01 IU/ml increased and the antitoxin-positive level decreased to 53%. Therefore, the effects of booster immunization are regarded to last for approximately 10 years. Those who were over 30 years in 1994-95 when serum samples were collected had never been subjected to routine vaccination under the Preventive Vaccination Law. Of those aged 30s-70s, 6-19% had an antibody titer higher than 0.01 IU/ml (positive antibody was confirmed also by in vivo mouse protection bioassay). Since tetanus cases, if recovered, seldom produce antitoxic antibody (see p. 4 of this issue), these antibody-positive individuals must have been injected with tetanus vaccine in some occasions and many of them were confirmed for vaccination history from the questioning record.

Adult immunization: For prevention of tetanus after injury, anti-tetanus human immune globulin (TIG) and tetanus toxoid (T) is administered (see p. 4 of this issue). If primary immunization has been completed, booster injection of T may bring about elevation of antibody titer and prevention of development of tetanus symptoms can be expected even if injured unexpectedly (ex. by traffic accident). The following are the two principles of adult immunization: (1) As described above, tetanus cases often occur among those who are over 35 years, it is advisable that non-vaccinees, whether children or adults, should receive primary immunization (those who are over the target age of routine immunization should receive voluntary immunization). (2) To maintain the antibody titer of the protective level, booster immunization is necessary every 10 -15 years. It is advisable that those aged over 13 years, not receiving the booster DT injection, and those aged over 20-30 years, which whom more than 10 years have passed since receiving the booster DT injection and who are vulnerable to outdoor injury, should receive again voluntary immunization (see p. 3 of this issue).

In 1950, one third of the deaths from tetanus were 0-year infants including neonates; after 1979, only one neonatal tetanus case was reported in 1995 in Japan (see p. 9 of this issue). In 1999, about 10,000 cases of neonatal tetanus were reported in the world, the World Health Organization aims at elimination of maternal and neonatal tetanus in the Expanded Programme on Immunization. Since the case fatality rate of neonatal tetanus is very high and its treatment is difficult, vaccination of pregnant women is recommended for prevention of neonatal tetanus by transplacental passive immunity, particularly those intending to deliver at some places with poor medical facilities.

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