The Topic of This Month Vol. 32, No. 4 (No. 374)

Cholera, 2006-2010, Japan
(IASR 32: 95-96, April 2011)

According to WHO criteria and Japanese criteria too, cholera, an enteric infection with watery diarrhea, is defined as an infection caused by cholera toxin (CT)-producing Vibrio cholerae O1 or O139.

The amendment of the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections (Infectious Diseases Control Law) in April 2007 moved cholera from the Category II infectious disease to the Category III infectious disease.  As a consequence, admission to medical facilities is no longer recommended to cholera patients; where appropriate, only medical check and restricting certain occupational activities can be recommended for preventing spread of the pathogen.  Both symptomatic and asymptomatic carriers are notifiable.  Notification requires isolation of the bacteria and detection of CT, which is done either by detection of the toxin or the toxin-coding gene (ctx ) by PCR (accordingly, clinically suspected cases are not notifiable).  Simultaneously, the Quarantine Law was amended in June 2007 eliminating cholera from the list of quarantine infectious diseases.

Trends of cholera in Japan: Until 2007 when the Infectious Diseases Control Law was amended, there were about 50 reports annually.  After amendment of the law, however, the total number of reports was reduced to less than 30 cases per year (Table 1) and most cases were infected in abroad.  However, year 2008 experienced two suspected food-related incidents involving total 12 symptomatic and asymptomatic cases who had no history of going abroad (see IASR 30: 98-99, 2009 and p. 99 of this issue) (Fig. 1).  In domestic cases, the patients were mostly above 50 years of age (average 66.1 year for male and 66.9 year for female), and for imported cases, the age of the patients were broadly distributed from 20's to early 70's (average 50.4 years for male and 43.8 years for female) (Fig. 2).  For domestic cases, numbers of male and female patients were equal, while for imported cases there were two-fold more male cases than female cases.  The main countries suspected as place of infection were India, Philippines and Indonesia (Bali Island) (Table 2).  After the amendment of International Health Regulation (IHR2005), Japan stopped reporting number of cholera cases to WHO (from 2007 on).

Among 118 V. cholerae isolates from 2006 to 2010, all, except two belonging to serogroup O139, were of serogroup O1 biotype El Tor, and most of them were of serotype Ogawa.  There were 16 strains of serotype Inaba isolated from 2006 to 2007 (all the 16 cases were infection abroad).  Of these, 13 were derived from those who returned from India, and three of them were co-infected with serotype Ogawa (IASR 27: 233, 2006).

V. cholerae O139 is becoming minority globally except in China.  In September 2006, however, there was the first domestic infection case of V. cholerae O139 with no history of travel abroad (IASR 28: 86-88, 2007), and in June 2008 the second (IASR 30: 241-242, 2009).

Global trends of cholera epidemic: The number of cholera cases reported to WHO was in decrease from 2001 to 2004, but started to increase again in 2005, which was due to epidemic in central African region involving refugee camps.  Zimbabwe reported a large outbreak involving 100,000 estimated cases from 2008 to 2009.

Asia is considered as the second most cholera endemic area.  However, the cases reported from Asia to WHO for recording were 1,902 in 2009, and the record does not contain the data of India, Bangladesh and other regions experiencing many cases every year (see p. 100 of this issue and WER 85, No.31, 293-306, 2010).

Thailand, the third most cholera epidemic country in Asia according to WHO, experienced a large cholera outbreak in Myanmar border in 2007 and an outbreak involving more than 2,000 cases in the Southern region in 2010.  In the poor hygiene districts where refugees and laborers have immigrated from neighboring countries, poor water hygiene easily cause the cholera transmission through contamination of water and foods.  In such regions there are many asymptomatic carriers, whose excrement pollutes water causing symptomatic cholera infection among children and aged persons with decreased immunity level (see p. 102 of this issue).

Haiti experienced a huge earthquake on January 12, 2010.  The post-seism deteriorated sanitary condition led to a large-scale cholera outbreak, which started on October 21 of the same year.  Within a month, more than 60,000 infected and more than 1,400 deceased cases were reported.  PAHO reported 243,197 infected and 4,626 deceased cases (as of February 21, 2011), that exceeded the total number of cholera cases reported in the world in 2009.  The V. cholerae O1 strains that caused the epidemic were genetically closer to the strains isolated in Bangladesh during 2002 and 2008 rather than 1991 Peru epidemic strains [N. Engl. J. Med. 364(1): 33-42, 2011].

In China, V. cholerae O139 has remained the major epidemic strain since 2003 when China started reporting to WHO, and in 2006 it occupied 70% of all the reports from China.  In the countries other than China, Thailand (11 cases in 2006-2008) and United States (one case in 2009) reported V. cholerae O139.

Current epidemic strains: The current epidemic belongs to the seventh pandemic that started in 1961.  V. cholerae O1 strains involved in the first to the sixth pandemics are called biotype classical.  The current epidemic strains are called biotype El Tor.  The biotype El Tor was originally different from the biotype classical in the biological character and also in the nucleotide and amino acid sequences of CT gene (ctx ).  However, since 1993, biotype El Tor strains having classical ctx are found in Japan and other countries in the world.  Some claim that these variant El Tor strains produce larger amount of toxin and are higher in virulence (see p.99 of this issue).

Cholera vaccine: WHO recommends the oral inactivated whole bacterial vaccine with higher effectiveness and longer durability to those who are sent to cholera epidemic area in case of emergency or in conflict.  The Ground Self-Defense Force sent from Japan to Haiti for restoration received the oral vaccine.  It was the first large-scale administration in Japan.  The side effects were very few (see p.104 of this issue).

Conclusion: Laboratory confirmation of cholera is conducted according to the “Guidance on laboratory diagnosis of cholera” (Notice from Ministry of Health and Welfare, September 28, 1988; IASR 9: 219-220, 1988).  The public health institutes (PHIs) conduct confirmation of CT (ctx ).  Isolation of pathogens from cases and molecular epidemiological analysis of the isolates are important so as not to miss cholera cases and both for cholera surveillance and for investigating the contamination source (IASR 27: 8-9, 2006).  It is encouraged that whenever V. cholerae is isolated in clinical settings, the doctors send the isolates to PHIs for further investigation.

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