The Topic of This Month Vol.18 No.10(No.212)

Hepatitis A, 1987-1996, Japan

Hepatitis A virus (HAV), belonging to genus Hepatovirus of Picornaviridae, comprises a single serotype and seven genotypes, types I-VII. Human strains are mainly of genotypes I and III. HAV infection is characterized by a tendency toward severe forms among adults, although asymptomatic to mild forms are common among children. The virus is excreted before onset of symptoms, easily causing familial transmission (see IASR, Vol. 12, No. 12). Isolation of HAV in cell culture entails a great deal of difficulty, so confirmative diagnosis of hepatitis A must depend usually on detection of the IgM antibody by ELISA in the serum of the patient on the acute phase.

This has been a targeted disease of the National Epidemiological Surveillance of Infectious Diseases (NESID) since 1987 and cases have been reported monthly from about 500 sentinel hospitals in the whole country. Hepatitis A cases increase in winter and spring and decrease in summer every year (Fig. 1). The patients reported have numbered annually 353-1,881 (0.69-3.60 per sentinel hospital), and those in 1990 were the largest in number.

The annual incidence of hepatitis A in each prefecture is shown in Fig. 2. Many reports came from Fukui Prefecture (15.33 per sentinel hospital) in 1988, from Aichi (21.92) and Gunma (15.60) Prefectures in 1990, and from Tottori Prefecture (15.70) in 1991. During 1995-96, the incidence was rather low in the whole country.

The investigation undertaken during the high-incidence period with a peak in 1990 in Aichi Prefecture revealed many familial secondary infections from parents to their children and the reverse direction (see IASR Vol. 12, No. 12, 1991), although most cases were sporadic ones. Molecular epidemiological investigations performed at that time in three adjacent prefectures, Aichi, Mie, and Shizuoka, detected a variety of strains that belonged to genotype IA, subtype of I, but differed partially in the nucleotide sequence. Comparison was made between these strains and those detected in many places in the world; it was presumed that these strains had been imported from other countries (J. Gen. Virol., 73:1365-1377, 1992). In Aichi Prefecture, genotype IA has mainly been detected since then (see p. 233 of this issue).

The reports furnished to IASR revealed such other small outbreaks as the one at a nursery school (see IASR, Vol. 11, No. 7, 1990), those at welfare institutions (see IASR, Vol. 17, No. 3, 1996 and p. 233 of this issue), those involving many cases presumably due to the food contaminated during preparation at sushi bars and other restaurants (see IASR, Vol. 15, No. 5, 1994 and Vol. 16, No. 10, 1995). In European and American countries, hepatitis A infections due to blood products have been reported in addition to the infections through feces, food or drink (CDC, MMWR 45: No. 2, 29, 1996).

The age distribution of hepatitis A patients (Fig. 3) shows that those aged 5-14 years and 35-44 years accounted for a high proportion in 1987, when NESID started to collect information, whereas in 1990s, the proportion of those aged over 45 years have tended to increase.

To investigate the immune status of general populations against HAV by the age, the specimens collected in 1973, 1984, and 1994 and stored at in the Serum Reference Bank, the National Institute of Infectious Diseases were tested by ELISA for the antibody and the results were compared (Fig. 4). The prevalence curve has shifted toward higher ages in correspondence with the investigation interval in years, showing that the HAV antibody-positive rate in this country is decreasing from year to year (Jpn. J. Med. Sci. Biol., 40: 119-130, 1987 and ibid., submitted). The HAV antibody-positive rate among the population younger than 40 years was lower than 1% in 1994, but the higher the age, the higher the rate among those over 40 years. The rate was as high as 90% among the population of over 65 years. The Study Group on Refractory Liver Diseases has pointed out an increasing tendency of the incidence of fulminant hepatitis A since 1992, and future increase in severe cases accompanying the increasing tendency of patients of middle and advanced ages is anticipated.

In United States of America, the Centers for Disease Control and Prevention recommend hepatitis A vaccination of high risk groups (e.g., travelers) (MMWR 46: RR15, 1996). In this country, ganmaglobulin has been used as the only prophylaxis; domestic, inactivated vaccines (freeze-dried products containing no adjuvant or preservative) were licensed in 1994 and those over 16 years may be vaccinated on the voluntary basis. Even now, HAV is common in other countries in Asia, Near East, Africa, and South America; vaccination is recommended to travelers, particularly adults who are staying in HAV-endemic areas for more than one month. Vaccine is also an effective prophylaxis against intra-institutional infections.

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