The Topic of This Month Vol. 31, No. 10 (No. 368)

Hepatitis A in Japan as of September 2010
(IASR 31: 284-285, October 2010)

Hepatitis A virus (HAV) belongs to genus Hepatovirus of Picornaviridae .  One serotype and genotypes I-VI (former genotype VII was reclassified as IIB), among which genotypes I and III are human strains, are known.  HAV spreads through fecal-oral infection.  The virus-contaminated foods and drinking water occasionally cause large outbreaks.  The improved water supply and drainage has greatly reduced the outbreaks of HAV, which is now rare in developed countries including Japan.  Nevertheless, about 200 HAV infections, including fulminant hepatitis, continued to be reported every year in Japan.

The incubation period is about one month.  Onset is usually abrupt with flu-like symptoms, such as, fever (over 38°C), extreme malaise, headache, anorexia, myalgia, abdominal pain, etc., which is followed by symptoms characteristic to hepatitis, such as, jaundice, hepatomegaly, black urine, pale stool, etc.  Importantly, HAV is shed into feces for a long time, from 1 week before the symptom onset to several months thereafter (maximum infectivity during the latter half of the incubation period).  The prognosis is generally good; it never becomes chronic though convalescence may last several months.  Therefore, socioeconomic loss is not negligible.  Many infections are asymptomatic or mild without jaundice, especially in children under five years (90% are asymptomatic).  In general, severity (fulminant type and death cases) increases with age; 90% of adult infections become symptomatic and 60% of them develop jaundice.

Hepatitis A is among the category IV infectious diseases under the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infectious Diseases (Infectious Diseases Control Law) after its amendment on November 5, 2003, requiring mandatory notification of all the diagnosed cases including asymptomatic carriers.

Cases notified under National Epidemiological Surveillance of Infectious Diseases (NESID) in Compliance with Infectious Diseases Control Law: In 2007, 2008 and 2009, relatively low number of cases were reported (157, 170 and 114 cases annually, respectively).  In 2010, however, 296 cases have been reported as of week 34.  HAV infection used to be frequent from winter to spring (January to May) (IASR 18: 231-232, 1997 & 23: 271-272, 2002) but in recent years this pattern disappeared (Fig. 1).  Most of the infections occurred in Japan, and were sporadic with exceptional occurrence of small-scale outbreaks (IASR 27: 178, & 341-342, 2006).  Cases infected abroad in 2007, 2008 and 2009 were 54, 60 and 38, respectively, occupying 33-35% of the total infections.  In 2010, 28 cases (9.5%) were infected abroad as of week 34.  During 2007-2010, the tendency of accumulation of HAV cases to specific prefectures, that was observed in 1990fs, disappeared (Fig. 2).

Infection route: During 2007-2010 (till week 34), total 737 hepatitis A cases were reported and most of them (593 cases), except 122 cases of unknown infection route, were suspected of infection through contaminated foods or water.  In addition, familial infection (16 cases), institutional infection (2 cases) and sexual infection (3 cases) were reported.  The implicated foods were mostly oysters and other seafood both for infections abroad and in Japan (oysters and other seafood including Sushi were suspected for >90% of domestic cases).  This tendency is same as in the previous years.

Age and gender: Among 737 cases reported from week 1 of 2007 to week 34 of 2010, males were 431 (58%) and females 304 (42%).  The dominance of males over females was observed among the age group of 40-65 years (Fig. 3).  In recent years, older persons tend to be affected by HAV ( (median age was 41 years in 2000, 44 years in 2004 and 46 years in 2007-2010), particularly among domestic infection cases (median age was 42 years in 2000, 46 years in 2004 and 48 years in 2007-2010).

Antibody prevalence among Japanese population: The seroepidemiology was conducted by using the sera collected in 2003 and deposited in the Serum Reference Bank, National Institute of Infectious Diseases (NIID) (Fig. 4).  88% of the samples representing all age groups and 98% of age group younger than 50 years had no HAV antibody.  The proportion of antibody positives was as high as 70% among age group older than 60 years.  The antibody positive population sharply decreased in the transition from 60 years to 40 years, and the antibody positive rate among population younger than 40 years was virtually zero (see p. 286 of this issue).

Molecular epidemiology: For the purpose of epidemiological investigation of 2010 HAV resurgence, on April 26, 2010, Ministry of Health Labour and Welfare (MHLW) issued a note requesting local governments to conduct active surveillance and collection of stool specimens for molecular epidemiological studies when they received notification of HAV infection (IASR 31: 140, 2010).  NIID, National Institute of Health Sciences and prefectural and municipal public health institutes (PHIs) jointly genotyped HAV specimens obtained from 59 cases (see p. 287 of this issue).  Among 59, 42 were genotype IA, one was IB (see p. 296 of this issue), and 16 were IIIA.  The genotype IA consisted of 2 genomic clusters, one endemic in Japan and the other that had been endemic in Philippines (see p. 291, 292 & 294 of this issue).  Genotype IIIA was related to the strain that caused large epidemic in the Republic of Korea (see p. 294 & 296 of this issue).  The resurgence of HAV in 2010 can be attributed to importation of the HAV of the latter two genotypes.

Preventive measures: As HAV is transmitted by fecal-oral infection, controls of infectious sources (patients' stools, contaminated foods, etc.) and infection routes are of prime importance.  HAV resists various disinfectants such as alcohols and phenolics.  Heat inactivation needs 85°C for 1 min.  Prevention of infection needs hygienic control such as routine hand washing, sufficient cooking, and disinfection of materials with 2% glutaraldehyde, sodium hypochlorite (greater than 5,000 ppm of free chlorine) or other disinfectants known to be effective against HAV.

As HAV has a long incubation time, it is difficult to trace back the infection to the implicated food(s) (see p. 291 of this issue).  Because the infectious period is long, in order to prevent spread of infection, immediate notification of patients and prompt countermeasures are necessary.  For this, information sharing among medical facilities, health centers, PHIs and NIID is critically important.  The information on molecular epidemiology of HAV, such as through V-Nus Net Japan (see p. 289 of this issue), will greatly facilitate the epidemiological investigation of HAV.

Passive immunization with human immunoglobulin (hIG) is effective as a post-exposure measure.  The hIG can be used also for protection of HAV infection, but the duration of immune status is short.

HAV vaccine was approved for use in Japan in 1994, and has been used for adults (older than 16 years) on a voluntary basis.  HAV vaccine has been produced 100,000 doses annually in Japan.  Three vaccine shots will give long lasting immunity.  Availability of HAV vaccination should be known to those who are at risk, such as, travelers to HAV high risk countries, medical staffs with frequent contact to HAV patients, staffs of welfare facilities, drug users among whom HAV outbreak is frequent, MSM (men who have sex with men), etc..

In addition, HAV vaccine is recommended to food handlers as the measures against foodborne HAV infection (see the notice from MHLW on November 28, 1997).

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