The Topic of This Month Vol. 29, No. 2 (No. 336)

Botulism in Japan as of January 2008
(IASR 29: 35-36, February 2008)

Botulism is a disease with neuroparalytic symptoms caused by botulinum toxin produced by Clostridium botulinum and some other related organisms.  C. botulinum is an anaerobe, forming heat-stable spores that can be detected in soil samples throughout the world.  When C. botulinum spores are placed under anaerobic conditions, germination of spores and outgrowth of organisms will occur and be producing toxin.  Botulinum toxin comprises seven immunologically distinct types, types A through G.  Human botulism is caused principally by type A, B or E toxin and rarely by type F toxin.  Botulinum toxin inhibits acetylchorine release at the peripheral nerve endings, resulting in blockade of parasympathetic and motor nerves (see p. 37 of this issue).  Botulism is classified into four types; foodborne, infant, wound, and adult intestinal colonization botulism. 

Infant botulism was classified into the category IV notifiable infectious diseases in the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (the Infectious Diseases Control Law) enacted in April 1999.  By the amendment of the Law in November 2003, infant botulism was expanded to botulism involving all kinds of diseases due to Clostridium botulinum and related organisms.  Physicians must notify botulism cases to the nearby health center promptly after diagnosis (for the criteria for reporting, see http://www.mhlw.go.jp/bunya/kenkou/kekkaku-kansenshou11/01-04-32.html).  When food is involved in the occurrence, immediate notification of food poisoning in compliance with the Food Sanitation Law is also necessary. 

Foodborne botulism: This is so-called botulinum food poisoning and is caused by ingestion of food contaminated with botulinum toxin.  Most cases complain abnormal vision, such as impaired vision, mydriasis, diplopia, blepharoptosis, and loss of light reflex.  They may show such signs as dried mouth, hoarse voice, abdominal distention, nausea, vomiting, ataxia, dysphagia, constipation, and hypomyotonia of the whole body.  In severe cases, respiratory failure occurs due to paralysis of respiratory muscles resulting in fatality.  The time from consumption of botulogenic food to onset of symptoms depends on the dosage of the toxin consumed and the toxin type, ranging from a few hours to approximately two days.  Since it is caused by very potent toxin, the case-fatality rate (10-20%) is considerably higher than that of other food poisoning. 

Infant botulism: When an infant younger than one year ingests botulinum spores perorally, germination of spores and outgrowth of C. botulinum may sometimes occur intraintestinally and the toxin produced may cause botulism of an infection type.  The reason why the infant younger than one year old develops the disease is thought to be that the intestinal floras of infants are different from those of adults and have a predisposing factor of colonization and growth of C. botulinum .  The symptoms start from a trend towards constipation, followed by depressed myodinamia of the whole body.  Weak cry and slowed feeding may develop and the head can not be supported due to relaxation of cervical muscles.  Facial flaccidity develops and such symptoms resembling those of foodborne botulism as dilated pupils, blepharoptosis and depressed light reflex may develop.  Respiratory failure may develop and severe cases may sometimes result in death.  The case fatality rate of infant botulism is low, being approximately 2%, as compared with that of foodborne botulism. 

Wound botulism: C. botulinum spores germinate at wounds and the toxin produced causes botulinum symptoms.  In the United States, drug addicts having acquired infection with C. botulinum at traces of injection have often been reported (MMWR 52(37): 885-886, 2003). 

Adult intestinal colonization botulism: Like infant botulism, colonization and proliferation of C. botulinum may occur in the child (≥1 year) and adult intestines causing botulism.  Symptoms may develop only when the microbial flora is destroyed or microbial alteration is caused, by surgical operation or administration of antibiotics. 

Incidence: The first Japanese episode of foodborne botulism due to eating homemade "izushi" was reported in Hokkaido in 1951.  Since then, several incidents due to izushi or similar kinds of fermented fish products were reported every year until the early half of 1980fs principally in northern Japan such as Hokkaido and Aomori Prefecture.  Then, foodborne botulism has become sporadic (IASR 21: 49-50, 2000).  No report was published after 2000 until April 2007, when an episode due to homemade "ayu" (sweetfish)-izushi occurred in Iwate Prefecture (a single case) (see p. 38 of this issue).  Izushi-borne botulism has been caused by type E only.  Incriminated foodstuffs other than izushi have been imported bottled imitation caviar (1969, Miyazaki, type B, 23 cases of which three died), vacuum-packaged deep-fried mustard-stuffed lotus root (1984, in 14 different prefectures, type A, 36 cases of which 11 died), imported bottled green olives in brine (1998, Tokyo, type B, 18 cases), and vacuum-packaged (not pressure-cooked) hashed beef sauce (1999, Chiba, type A, one case).  These outbreaks commonly involved types A or B toxin (IASR 21: 49-50, 2000). 

There have been 24 reports of infant botulism after the first episode occurring in Chiba Prefecture in 1986 (Table 1).  Infant botulism is a low incidence disease in Japan; seven cases have been reported since the enactment of the Infectious Diseases Control Law.  After 2005, two cases have been reported every year.  Before 1990, most cases occurred after feeding bee honey.  Since risk of feeding honey to infants was publicized to the protectors of infants, recent cases have no history of feeding honey (see p. 38 of this issue).  The causes identified were homemade vegetable soup due to C. butyricum producing type E botulinum toxin in Tokyo in 2004 (Table 1, No. 18) and water of a well for private use of the case's house in Miyagi Prefecture in 2006 (Table 1, No. 22).  One of the present problems involved in infant botulism is that infectious sources of most cases remain unclear.  When infant botulism has occurred, active epidemiological investigation of the living environment of the case should be made, including microbial examination of house dust, to identify the cause and to prevent further cases.  The toxin types responsible for infant botulism are mainly types A and B.  Spores of these types may possibly be brought in through attaching on imported food materials from other countries where type A and B are prevalent in soil. 

No case of wound botulism or adult intestinal colonization botulism has been reported in Japan. 

As described above, botulism is a rare disease in Japan, while in USA, about 100 cases of botulism have been reported annually and approximately 70% of them are infant botulism (http://www.emergency.cdc.gov/agent/botulism/clinicians/epidemiology.asp).  Table 2 shows reported infant botulism cases in countries where statistical data are available. 

Diagnosis and treatment: Diagnosis of botulism is confirmed by detection of the toxin or organisms in patient's vomits or feces or incriminated foodstuffs (see p. 39 of this issue).  Toxin is detected also in serum, however, not often in infant botulism. 

For regular treatment, symptomatic treatments under aggressive respiratory care and administration of equine botulinum antitoxin are performed (see p. 45 of this issue).  Early diagnosis of food poisoning cases promotes early antitoxin therapy lowering case-fatality rate.  In infant botulism, antitoxic serum is usually not administered because the fatality rate is usually low and the benefit or the risk to infants is not established.  In USA, human-derived botulism immune globulin approved in 2003 has been applied to treat infants and a certain effect on shortening the hospitalization period has been reported.  Antibiotics are sometimes administered, however, since the toxin released from the killed cells may worsen the symptoms; care must be taken especially to infant.  Feces of infant botulism cases contain many organisms and a large amount of toxin and it takes often two or three months after onset of symptoms until their disappearance.  Therefore, to prevent secondary infection, medical personnel and nursing personnel must treat patient's feces as infectious wastes (see p. 38 of this issue). 

A reference center network has been constructed between the National Institute of Infectious Diseases and prefectural and municipal public health institutes and has been accomplished smooth response for executing laboratory tests and sharing intelligence (see p. 42 of this issue). 

Restriction on C. botulinum and botulinum toxin under the Infectious Diseases Control Law: By the amendment of the Infectious Diseases Control Law in June 2007, C. botulinum and botulinum toxin have been classified in the group 2 pathogens and like substances and severe restrictions and regulations are posed on its possession, use and transportation (IASR 28: 185-188, 2007).  If the organisms are isolated and identified by examination, notification within one day, disinfection, destruction and disposal within three days, or transfer to other facilities will be necessary.  To possess the isolates, a special permission by the Minister of Health, Labour and Welfare (see p. 42 of this issue) will be necessary which requires special biosafety facilities and safekeeping measures. 

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