The Topic of This Month Vol. 30, No. 3 (No. 349)

Tetanus in Japan as of December 2008
(IASR 30: 65-66, March 2009)

Clostridium tetani is an obligate anaerobic gram-positive bacillus forming a terminal spore.  While C. tetani in the vegetative form is sensitive to heat and oxygen, its spore is resistant to heat, oxygen and most antiseptics.  The spores are found widely in soil or in the animalsf intestines and feces.  The spores, once entering the body tissues through a wound, germinate and grow under anaerobic conditions producing tetanus toxin (see p. 68 of this issue). The toxin is circulated in the blood stream and reaches central nervous system, such as ventral horn or brain stem. Once the toxin is fixed to the endplate of motor neuron, inhibitory neural circuit is blocked. The consequence is the typical manifestation of tetanus infection.  The incubation period for tetanus is usually 3-21 days.  However, longer incubation period exceeding one month has been reported.  Characteristic symptoms are contraction of the muscle at the injury site, trismus, risus sardonicus (a rigid smile), dysphagia, dyspnea, and opisthotonus.  If the treatment is delayed, case-fatality rate is high.

Depending upon the cause and patient profile, tetanus is categorized into two following forms.

1. Wound tetanus: It is most common in adults.  Infection usually occurs through deep puncture wounds or cuts or even through tiny breaks of skin such as pinprick or scratch (IASR 28: 47-49, 2007).  C. tetani infections through pyorrheal legions or through self-administration of insulin or self-sampling of blood among diabetic patients have been reported.  In the United States and in the United Kingdom, tetanus cases among injection-drug abusers have been reported, indicating possible infection through spore-contaminated drugs, solutions, needles or syringes (see p. 70 of this issue).

2. Neonatal tetanus: Tetanus infection occurs in newborns at the time of delivery and during the postnatal period in unhygienic circumstances.  After 1-2 weeks of incubation, early symptoms appear, for example, babyfs sucking power weakens.  Once tetanus symptoms become manifest, 60-90% of newborns will die within 10 days.  In developing countries, tetanus is a major cause of neonatal deaths.  According to the WHOfs estimate, neonatal tetanus killed about 128,000 babies in the world in 2004 (see p. 70 of this issue).  In Japan, a neonatal tetanus case occurred in 2006 after an 11-year absence (IASR 29: 50-51, 2008).

Incidence of tetanus: Tetanus is classified as a category V notifiable infectious disease under the Infectious Diseases Control Law and physicians must notify the case to the nearby health center within 7 days after diagnosis (for reporting guidelines, refer to http://www.mhlw.go.jp/bunya/kenkou/kekkaku-kansenshou11/01-05-12.html).

Since the enactment of the Infectious Diseases Control Law, the number of reported cases, which is about 100 cases per year, remained unchanged (Table 1 and additional data on p. 67 of this issue).  Tetanus cases tend to increase from May to October when the outdoor activities are high (Fig. 1).  Of 546 cases reported during 2004-2008, 513 patients (94%) were older than forty, and the proportion of those in their 60s-70s became higher than in 1999-2003 (Fig. 2). The male cases dominated the female cases in number, but among patients older than 80-year-old individuals, there were more females than males (Fig. 3).  Tetanus cases were reported in all prefectures.  According to the Vital Statistics in Japan (Table 1), there were 35 deaths in 2004-2008, meanwhile, during the same period, number of fatal cases reported at the time of notification or additionally later was only ten, far less than the figures appearing in the Vital Statistics.  When the notified cases died or when laboratory diagnosis was obtained after the notification, such information should be sent to the health center in compliance with the National Epidemiological Surveillance of Infectious Diseases (NESID).

Age-specific tetanus antitoxin prevalence: According to the provisional report of the National Epidemiological Surveillance of Vaccine-Preventable Diseases in 2008 (1,078 samples from healthy individuals, as of February 19, 2009), the rate of antitoxin positives (those with antitoxin titer higher than 0.01 IU/ml which is the minimum level of protective immunity to tetanus) was 92% among 0-year-old infants, 99% among 1-4 year-olds, and as high as ≥92% among individuals up to 35-39 years (Fig. 4).  Among the 45-49 to 55-59 year-old individuals, the positive rate was 25%, and for those older than 60 years it was as low as 11%.  By comparing the present survey data in 2008 with the previous one in 2003 (the first anti-tetanus serosurvey of adult population in Japan), it was found that the age groups with high incidence of high antitoxin titers (U ≥ 0.1 IU/ml giving a sufficiently high level of protective immunity) expanded to older ages by five years (Fig. 5).  It indicates that the immunity was maintained for five years even among adult populations.  This could be confirmed further by the next survey planned for 2013.

Diagnosis and treatment: The diagnosis is usually made clinically by the characteristic symptoms of tetanus, i.e., unopposed muscle contraction and spasm.  Isolation of C. tetani from infection site and detection of tetanus toxin produced by the isolates will confirm the diagnosis (see p. 69 of this issue).  If tetanus was suspected from symptoms, the treatment, through debridement of wounds and administration of anti-tetanus human immune globulin (TIG) should begin without delay.  Antibiotics are used when necessary. To treat spasms, anticonvulsants are used.  Suspected tetanus cases should be transported to the hospital equipped with emergency intensive care unit in early stage since many cases need respiratory control (the Japan Medical Association, Diagnosis and Treatment Guidelines for Infectious Diseases, 2004).

For injuries that may be associated with tetanus infection, TIG and tetanus toxoid vaccine (T) should be administered in addition to cleaning and disinfection of the wound.  If primary immunization has been completed, even when one encounters unexpected traffic accident, injection of T may boost antibody titer and prevent clinical manifestation of tetanus.

Immunization to adults: The case-fatality rate of tetanus was 81% in 1950; the notified cases of tetanus totaled up to 1,915, of which 1,558 died and the greater part of the death cases were aged under 15 years (IASR 23: 1-2, 2002).  Cases and deaths of tetanus decreased in number after introduction of T in 1953 (voluntary immunization) and the start of routine immunization of diphtheria-tetanus-pertussis combined vaccine (DTP) in 1968 accelerated the decrease.  Majority of recent tetanus cases were born before the introduction of DTP routine immunization, ≥40 years, and their tetanus antibody positive rate is low, meanwhile among those born after the start of DTP routine immunization, <40 years, tetanus antibody positive rate is high and tetanus cases are fewer.  It could be stated that the immunity against tetanus obtained through vaccination is effective enough to prevent clinical manifestation of tetanus.  To reduce tetanus cases, it is necessary to immunize the generation aged ≥40 years.  Those who have no vaccination history of DTP, DT or T should receive two doses of T within a year first and then another in the next year to obtain the basic immunization status (see p. 71 of this issue).

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